[Federal Register Volume 68, Number 50 (Friday, March 14, 2003)]
[Proposed Rules]
[Pages 12500-12534]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-5205]



[[Page 12499]]

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Part III





Department of Health and Human Services





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Food and Drug Administration



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21 CFR Parts 201, 606, and 610



Bar Code Label for Human Drug Products and Blood; Proposed Rule

  Federal Register / Vol. 68, No. 50 / Friday, March 14, 2003 / 
Proposed Rule  

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 201, 606, and 610

[Docket No. 02N-0204]
RIN 0910-AC26


Bar Code Label Requirement For Human Drug Products and Blood

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Proposed rule.

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SUMMARY:  The Food and Drug Administration (FDA) is proposing a new 
rule that would require certain human drug product labels and 
biological product labels to have bar codes. The bar code for human 
drug products and biological products (other than blood and blood 
components) would contain the National Drug Code (NDC) number in a 
linear bar code. The proposed rule would help reduce the number of 
medication errors in hospitals and other health care settings by 
allowing health care professionals to use bar code scanning equipment 
to verify that the right drug (in the right dose and right route of 
administration) is being given to the right patient at the right time. 
The proposed rule would also require the use of machine-readable 
information on blood and blood component container labels to help 
reduce medication errors.

DATES: Submit written or electronic comments on this proposed rule by 
June 12, 2003. Submit written comments on the information collection 
requirements by April 14, 2003.

ADDRESSES: Fax written comments to the Dockets Management Branch (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Fax electronic comments to http://www.fda.gov/dockets/ecomments. Submit written comments on the information 
collection provisions to the Office of Information and Regulatory 
Affairs, Office of Management and Budget (OMB), Attn: Stuart Shapiro, 
Fax: (202) 395-6974.

FOR FURTHER INFORMATION CONTACT:  Philip L. Chao, Office of Policy, 
Planning, and Legislation (HF-23), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-3380.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Introduction
    A. What Actions Led to This Rulemaking?
    B. What Are Medication Errors?
    C. How Frequently Do Medication Errors Occur? What Is Their 
Impact?
    D. How Would Bar Coding Help Prevent Medical Errors?
    E. Can Bar Code Use Reduce the Incidence of Medication Errors?
    F. Is There Support for Putting Bar Codes on Drug Products?
II. Description of the Proposed Rule
    A. Who Would Be Subject to the Bar Code Requirement? (Proposed 
Sec.  201.25(a))
    B. What Products Would Have to Have a Bar Code? (Proposed Sec.  
201.25(b))
    C. What Would the Bar Code Contain? (Proposed Sec.  
201.25(c)(1))
    D. Would the Rule Require a Specific Type of Bar Code? (Proposed 
Sec.  201.25(c)(1))
    E. Where on the Label Would the Bar Code Appear? (Proposed Sec.  
201.25(c)(2))
    F. What Would Happen if a Bar Code Could Not Be Put on a 
Product?
    G. What Is the Proposed Implementation Plan?
    H. How Does This Rule Apply to Blood and Blood Components? 
(Proposed Sec.  606.121(c)(13))
    I. What Bar Code Requirement Would Apply to Biological Products? 
(Proposed Sec.  610.67)
III. Legal Authority
IV. Environmental Impact
V. Paperwork Reduction Act of 1995
VI. Executive Order 13132: Federalism
VII. Analysis of Impacts
    A. Introduction
    B. Objective of the Proposed Rule
    C. Estimate of Risk/Risk Assessment
    D. The Proposed Rule
    E. Description of Affected Sectors
    F. Regulatory Costs of the Proposed Rule
    G. Other Anticipated Expenditures
    H. Reduction in Preventable Adverse Drug Events
    I. Value of Avoided ADEs
    J. Aggregate Benefit of Avoiding ADEs
    K. Other Benefits of Bar Code Technology
    L. Distributional Effects of Bar Code Technology
    M. Comparison of Costs, Expenditures, and Benefits
    N. Uncertainty and Sensitivity
    O. Small Business Analysis and Discussion of Alternatives
    P. Conclusion
VIII. Request For Comments
IX. References
Appendix--Additional Information on Various Studies Identifying 
Different Types of Medication Errors

I. Introduction

A. What Actions Led to This Rulemaking?

    In 1999, the Institute of Medicine (IOM) issued a report entitled 
``To Err Is Human: Building a Safer Health System'' (Ref. 1). (The IOM 
is a private, nonprofit organization that provides health policy advice 
under a congressional charter granted to the National Academy of 
Sciences.) The IOM report cited studies and articles to estimate that 
between 44,000 and 98,000 Americans may die each year due to a range of 
medical mistakes made by health care professionals. The IOM report 
estimated that, in 1993 alone, an estimated 7,000 deaths were 
attributable to medication errors (Ref. 1 at p. 27) and that:
    [sbull] Medication errors account for 1 out of every 131 outpatient 
deaths, and 1 out of every 854 inpatient deaths (Ref. 1 at p. 27); and
    [sbull] The death rate attributable to medication errors may be 
increasing. The IOM report cited a study that examined death 
certificates from 1983 to 1993. The study found that, in 1983, 2,876 
deaths were due to medication errors (which the authors defined as 
accidental poisoning by drugs, medicaments, and biological products 
resulting from acknowledged errors by patients or health care 
professionals) (Ref. 1 at p. 32, Ref. A-14 of the Appendix to this 
document). In 1993, 7,391 deaths were attributed to medication errors, 
a 2.57-fold increase in the death rate (Ref. 1 at p. 32). Moreover, a 
comparison of outpatient death rates suggested nearly an 8-fold 
increase in medication error death rates (Ref. 1 at pp. 32 and 33).
    The IOM report stated that deaths due to medication errors are 
often preventable and cited bar codes as one way to prevent them (Ref. 
1 at pp. 37, 175, 188, 189, 195-196).
    The IOM report generated considerable controversy. Some felt that 
the IOM's figures were exaggerated (Ref. 2), while others felt the 
figures might have been too low (Ref. 3). Some felt that the term 
``medical errors'' was, itself, misleading (Ref. 4). Others, including 
FDA, suggested that the IOM report's basic message--that medical errors 
are a serious public health problem--should not be lost regardless of 
whether the annual mortality was 10,000 or 100,000 (Ref. 5)
    The IOM report led to new efforts to improve patient safety. For 
example:
    [sbull] In December 1999, President Clinton directed the HealthCare 
Quality Task Force to analyze the IOM report and to report back on 
recommendations to

[[Page 12501]]

protect patients and to promote safety. In February, 2000, he announced 
a plan to reduce preventable medical errors by 50 percent within 5 
years.
    [sbull] In February 2000, the Quality Interagency Coordination 
(QuIC) Task Force (a group composed of the Department of Health and 
Human Services (DHHS) and other Federal agencies) issued an action plan 
that highlighted steps for Federal agencies to take to reduce medical 
errors and to improve patient care.
    [sbull] In March 2001, the Agency for HealthCare Research and 
Quality (AHRQ) issued a report entitled ``Reducing and Preventing 
Adverse Drug Events to Decrease Hospital Costs.'' The report stated 
that more than 770,000 people are injured or die each year in hospitals 
from adverse drug events and that studies had suggested that 28 to 95 
percent of adverse drug events could be prevented by reducing 
medication errors through the use of computerized monitoring systems, 
especially computerized medication ordering systems (Ref. 6).
    [sbull] In April 2001, the Secretary of Health and Human Services, 
Tommy G. Thompson (Secretary Thompson), announced the establishment of 
a new Patient Safety Task Force within DHHS. Secretary Thompson named 
FDA as one of the Federal agencies leading this new effort (Ref. 7).
    Congress also focused its attention on patient safety by holding 
hearings in 2000 and 2001 on patient safety and medical errors. On May 
24, 2001, Secretary Thompson appeared before the Senate Committee on 
Health, Education, Labor, and Pensions' Subcommittee on Patient Health 
and stated that new technology, such as bar coding, could help save 
lives and money. Secretary Thompson noted that other industries used 
bar coding and that the same technology could be used to track drug 
dispensing and use and to prevent medication errors (Ref. 8).
    Shortly thereafter, the American Society for Health-System 
Pharmacists (ASHP) wrote to Secretary Thompson to urge that FDA 
``develop regulations that mandate that drug manufacturers provide a 
standardized machine-readable code (bar coding) on all drug product 
containers, including single unit containers, which are essential for 
hospital unit dose drug distribution systems'' (Ref. 9). ASHP mentioned 
a June 26, 2001, recommendation by the National Coordinating Council 
for Medication Error Reporting and Prevention (NCCMERP) urging FDA and 
the United States Pharmacopeia (USP) to establish and implement a 
uniform bar coding program for drugs (Ref. 9 at pp. 1 and 2). Secretary 
Thompson later asked FDA to begin working on a bar coding proposal, 
thereby putting in motion the events that led to this proposed rule.

B. What Are Medication Errors?

    NCCMERP \1\ defines a medication error as:
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    \1\ NCCMERP is composed of over 20 national organizations 
(including FDA) whose objectives are to increase the reporting, 
understanding, and prevention of medication errors and to recommend 
strategies relative to systems modifications, practice standards, 
and guidelines, and changes in packaging, labeling, and product 
identity.
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    * * * any preventable event that may cause or lead to 
inappropriate medication use or patient harm while the medication is 
in the control of the healthcare professional, patient, or consumer. 
Such events may be related to professional practice; healthcare 
products, procedures, and systems, including prescribing; order 
communication; product labeling, packaging, and nomenclature; 
compounding; dispensing; distribution; administration; education; 
monitoring; and use. (Ref. 10)
For purposes of this preamble, we will adopt the same definition of 
``medication error.''
    Medication errors are a part of the overall ``medical errors'' 
problem because medical errors include surgical errors, device 
failures, and medication errors. Medication errors can occur at several 
points from the time the physician selects the drug to prescribe to a 
patient to the time when the patient receives the drug. For example, 
the physician may write a prescription for the right drug, but in the 
wrong dose. The pharmacist might misread the prescription and provide 
the wrong drug, or read the prescription correctly and dispense the 
wrong drug. The health care professional administering the drug might 
give it to the wrong patient or give it to the right patient, but at 
the wrong time or in the wrong dose.
    Articles discussing medication errors can be found dating back 
several decades, and refer to such errors under various names, 
including ``preventable adverse events,'' ``drug misadventuring,'' and 
``iatrogenic illness'' or ``iatrogenic injury.'' (The word 
``iatrogenic'' refers to ``any adverse condition in a patient occurring 
as the result of treatment by a physician or surgeon'' (see Dorland's 
Illustrated Medical Dictionary, 26th ed., at p. 647).) The articles 
often identify the following types of medication errors:
    [sbull] Administering the wrong dose,
    [sbull] Administering a drug to a patient who is known to be 
allergic,
    [sbull] Administering the wrong drug to a patient or administering 
a drug to the wrong patient,
    [sbull] Administering the drug incorrectly,
    [sbull] Administering the drug at the wrong time or missing doses.
    (See the Appendix elsewhere in this document for a description of 
various studies identifying different types of medication errors.)

C. How Frequently Do Medication Errors Occur? What Is Their Impact?

    Studies differ as to how frequently medication errors occur. Some 
studies suggest that the medication error rate is under 7 percent, 
whereas others suggest a medication error rate at or above 20 percent. 
The differences may be due, in part, to different definitions of 
``medication error'' or different research methodology that focused on 
fatalities, injuries, or medication orders. (See the appendix for a 
summary of medication error rates reported in several studies.)
    Although most medication errors do not result in harm to patients, 
medication errors can result and have resulted in serious injury or 
death (Ref. 11).
    Medication errors also represent a significant economic cost to the 
United States. In an article published in 1995, Johnson and Bootman 
estimated the direct cost of preventable drug-related mortality and 
morbidity to be $76.6 billion annually, with drug-related hospital 
admissions accounting for much of the cost (Ref. 12). The authors 
suggested that indirect costs, such as those relating to lost 
productivity, might be two to three times greater than the direct 
costs, making the total cost of all preventable, drug-related mortality 
and morbidity range from $138 to $182 billion. A study by Ernst and 
Grizzle published in 2001 used updated figures and revised the direct 
cost estimate to $177.4 billion (Ref. 13). Another article estimated 
the cost of preventable adverse drug events in hospitalized patients to 
be $5,857 for each adverse drug event and the estimated annual costs 
for preventable adverse drug events for a 700-bed hospital to be $2.8 
million (Ref. 14).

D. How Would Bar Coding Help Prevent Medication Errors?

    Bar codes would be part of a system, along with bar code scanners 
and computerized databases, that would enable health care professionals 
to check whether they are giving the right drug via the right dose and 
right route of administration to the right patient at the right time. 
Under this model, the system could work as follows:
    [sbull] A patient would have his or her drug regimen information 
entered into a computerized database.

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    [sbull] Each drug would have a bar code. The bar code would provide 
unique, identifying information about the drug that is to be dispensed 
to the patient.
    [sbull] In hospitals, health-care professionals, such as 
pharmacists and nurses, would use bar code scanners (also called bar 
code readers) to read the bar code on the drug before dispensing the 
drug to the patient and use bar code scanners to read a bar coded wrist 
band on the patient before giving the drug to the patient. In an 
outpatient setting, the health care professional (such as a pharmacist) 
could scan the bar code on the drug and compare the scanned information 
against the patient's electronic prescription information before giving 
the drug to the patient.
    [sbull] The bar code scanner's information would go to the computer 
where it would be compared against the patient's drug regimen 
information to check whether the right patient is receiving the right 
drug (including the right dose of that drug in the right route of 
administration). The system could also be designed to check whether the 
patient is receiving the drug at the right time.
    [sbull] If the identity of the health care professional 
administering the drug was desired, each health care professional could 
also have a bar code. The health care professional would scan his or 
her own bar code before giving the drug to the patient.
    Bar codes could also complement other efforts to reduce medication 
errors.
    [sbull] In computer physician order entry (CPOE) systems, a 
physician enters orders into a computer instead of writing them on 
paper. The order can be checked against the patient's records for 
possible drug interactions, overdoses, and patient allergies (Ref. 26).
    [sbull] The retail pharmacy community is beginning to use a bar-
coded NDC number to verify that a consumer's prescription is being 
dispensed with the correct drug. These pharmacy-based systems compare a 
bar code that the pharmacy's computer prints on the consumer's 
prescription against the bar code on the drug's label. If the computer 
detects an error, the computer alerts the pharmacist to the problem.
    In addition, bar codes could make it easier to enter medication 
order entries into a patient's electronic medical records, help in 
inventory control and billing, and help conserve hospital or health 
care staff resources or free those resources so that they can be 
devoted to patient care.

E. Can Bar Code Use Reduce the Incidence of Medication Errors?

    Published articles and other information submitted to FDA suggest 
that bar coding can reduce medication error rates significantly.
    [sbull] One New Hampshire hospital reduced its medication error 
rate by 80 percent after it adopted a bar coding program (Ref. 15).
    [sbull] A medical center in Colorado lowered its medication error 
rate by 71 percent between 1992 and 1994 (Ref. 16).
    [sbull] A Department of Veterans Affairs (VA) hospital in Kansas 
had no medication errors when its computerized, bar coding system was 
used properly; the hospital estimated that the system prevented over 
378,000 medication errors in a 5-year period (Ref. 17).
    [sbull] Other published articles have discussed how bar coding can 
reduce medication errors, including missed doses, or increase drug 
dispensing accuracy (Refs. 18 through 23).
    At a public meeting that we (FDA) held on July 26, 2002 (67 FR 
41360, June 18, 2002), the VA gave a presentation on its use of bar 
codes at the VA Medical Center in Topeka, Kansas. The VA stated that a 
comparison of medication error data from 1993, the last year before the 
VA implemented the bar code system, to data for 2001 showed that the 
Topeka medical center reduced its reported medication error rate by 
86.2 percent (Ref. 24). The improvements included:
    [sbull] 75.5 percent improvement in errors caused by the wrong 
medication being administered to a patient;
    [sbull] 93.5 percent improvement in errors caused by the incorrect 
dose being administered to a patient;
    [sbull] 87.4 percent improvement in wrong patient errors; and
    [sbull] 70.3 percent improvement in errors caused when medications 
scheduled for administration were not given.
(Ref. 24 at p. 14).
    One comment submitted in response to the public meeting indicated 
that a bar code scanning system, in conjunction with a robotic system 
for pharmaceutical distribution, reduced dispensing errors at the 
University of Wisconsin from 1.43 percent to 0.13 percent and that the 
university realized a return on its investment in 2 years (Ref. 25). 
The comment also stated that there was an 89 percent reduction in 
medication administration errors due to point-of-care bar code scanning 
(Ref. 25 at p. 6).
    We discuss the public meeting in greater detail in section II of 
this document.

F. Is There Support for Putting Bar Codes on Drug Products?

    In recent years, many organizations have either commented favorably 
on or recommended the adoption of bar coding to reduce medication 
errors. These organizations include the QuIC Task Force, NCCMERP, ASHP, 
and Premier, Inc., an alliance of not-for-profit hospital and health 
care systems (Refs. 27 through 29).
    We also saw considerable support for bar coding at the July 26, 
2002, public meeting we held to discuss a possible rule to require bar 
code labeling. Nearly 400 individuals attended the meeting, and they 
represented a broad range of interests, including:
    [sbull] Nurses, including the American Academy of Nursing;
    [sbull] Pharmacists, including the American Society of Health-
System Pharmacists;
    [sbull] Physicians, including the American Medical Association;
    [sbull] Hospitals, including the American Hospital Association, the 
VA, which already has a bar code program in place for drugs used in VA 
hospitals, and the Hospital Corporation of America, Inc., which intends 
to have bar coding technology in place in its hospitals by the end of 
2005;
    [sbull] Pharmaceutical manufacturers, including the Pharmaceutical 
Research and Manufacturers of America (PhRMA) and the Generic 
Pharmaceutical Association (GPhA);
    [sbull] Over-the-counter (OTC) drug manufacturers, including the 
Consumer HealthCare Products Association (CHPA);
    [sbull] Medical device manufacturers, including the Advanced 
Medical Technology Association (also known as AdvaMed);
    [sbull] Blood centers and blood organizations, including the 
American Association of Blood Banks, America's Blood Centers, and the 
American Red Cross;
    [sbull] The Vaccine Identification Standards Initiative (VISI), a 
collaborative effort between public health agencies and private 
organizations involved in immunization practices and whose purpose is 
to establish voluntary, uniform guidelines for vaccine packaging and 
labeling and recording identifying information;
    [sbull] Bar coding and other ``automatic identifier'' interests, 
including the Uniform Code Council and the Health Industry Business 
Communications Council (two standards development organizations that 
have established bar code standards);
    [sbull] Health or medical product distributors, including McKesson

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Corporation, the HealthCare Distribution Management Association, and 
Cardinal Health; and
    [sbull] The USP.
    In addition, in response to requests to discuss bar code issues in 
greater detail, we met separately with PhRMA on August 19, 2002, with 
CHPA, GPhA, and others on September 17, 2002, and with the National 
Alliance for Health Information Technology on October 9, 2002.
    In general, almost all individuals, companies, and organizations 
attending or commenting on the public meeting strongly supported the 
use of bar codes on human drug products to help reduce medication 
errors, but differed in their opinions as to the information that 
should go into the bar code and whether certain products, such as over-
the-counter (OTC) drugs and medical devices, should have a bar code. We 
discuss various aspects of the public meeting throughout the remainder 
of this preamble to show how information from the public meeting helped 
shape this proposal.

II. Description of the Proposed Rule

    The proposal would create a new Sec.  201.25 entitled ``Bar Code 
Label Requirements.'' The proposal would address:
    [sbull] Who is subject to these bar code requirements?
    [sbull] What drugs are subject to these bar code requirements?
    [sbull] What does the bar code look like?
    [sbull] Where does the bar code go?
    The proposed bar code requirement would also apply to biological 
products (other than blood and blood components). We cross-reference 
this requirement in the biologics regulations at new Sec.  610.67.
    For blood and blood components, the proposal would amend part 606 
(21 CFR part 606) in Sec.  606.121(c)(13) which currently allows, but 
does not require, the use of machine-readable symbols, approved by the 
Director of the Center for Biologics Evaluation and Research (CBER), on 
blood and blood component container labels. The proposal would require 
the use of encoded, machine-readable information approved by the CBER 
Director on blood and blood component labels.

A. Who Would Be Subject to the Bar Code Requirement? (Proposed Sec.  
201.25(a))

    In brief, under proposed Sec.  201.25(a), manufacturers, repackers, 
relabelers, and private label distributors of human prescription drug 
products and OTC drug products regulated under the Federal Food, Drug, 
and Cosmetic Act (the act) or the Public Health Service Act would be 
subject to the bar code requirement unless they are exempt from the 
establishment registration and drug listing requirements in section 510 
of the act (21 U.S.C. 360(g)(1)). In practice, this means that 
pharmacies which are exempt under section 510(g) of the act are not 
required to put bar codes on drugs they are dispensing. (The 
requirements in proposed Sec.  201.25 would apply to biological 
products (other than blood and blood components) and would include a 
cross-reference at proposed Sec.  610.67. For convenience, this 
preamble will refer only to proposed Sec.  201.25 alone without 
repeated cross-references to proposed Sec.  610.67 (see section II.I of 
this document).) For purposes of this proposal:
    [sbull] ``Manufacturer'' means a person or persons who owns or 
operates an establishment engaged in the manufacture, preparation, 
propagation, compounding, or processing of a drug by chemical, 
physical, biological, or other manipulations of the drug. These 
activities include repackaging or otherwise changing the container, 
wrapper, or labeling of any drug package in furtherance of the drug's 
distribution from the original place of manufacture to the person who 
makes final delivery or sale to the ultimate consumer or user.
    [sbull] ``Repacker'' means a person or persons who owns or operates 
an establishment that repackages and relabels a drug and does not 
engage in any other activities performed by a manufacturer.
    [sbull] ``Relabeler'' means a person or persons who owns or 
operates an establishment that affixes or changes labels on a drug and 
does not engage in any other activities performed by a manufacturer.
    [sbull] ``Private label distributor'' means a person or persons who 
owns or operates an establishment that commercially distributes, under 
its own label or trade name, any drug manufactured, prepared, 
propagated, compounded, or processed by a manufacturer, repacker, or 
relabeler.
For example, if you make a prescription drug product, you would be 
subject to the bar coding requirement. However, if you are a pharmacy 
operating in conformance with applicable local laws regulating the 
practice of pharmacy and are regularly engaged in dispensing 
prescription drugs upon prescriptions of practitioners licensed to 
administer such drugs to patients, and do not manufacture, prepare, 
propagate, compound, or process drugs for sale other than in the 
regular course of business of dispensing such drugs at retail, you 
would not be subject to the bar code requirements. Your pharmacy would 
be exempt because section 510(g)(1) of the act does not require you to 
comply with the establishment registration and listing requirements.
    We recognize that some hospitals themselves place bar codes on 
drugs and have reduced their medication error rates significantly. 
Requiring persons who manufacture, repackage, or relabel human drug 
products to bar code their own products should be more efficient and 
result in better quality bar codes. Manufacturers, repackers, and 
relabelers generally have sophisticated manufacturing processes and 
labeling machinery, and quality control systems that hospitals cannot 
afford. Bar coding by third parties (such as hospitals) would be more 
costly for the facility and would not achieve the economies of scale 
that larger entities could realize. Having many small entities affix 
bar codes could increase the possibility of a label error through the 
attachment of the wrong bar code and could lead to inconsistent bar 
code quality. For example, one comment from the public meeting stated 
that an institution administering 2.5 million doses per year, even if 
operating at 99.9 percent effectiveness at applying its own bar codes, 
would introduce seven new errors per day from repackaging. Another 
comment, submitted by an entity familiar with ``automatic 
identification'' methods, stated that ``on demand'' bar code printing, 
as used in hospitals and clinics, will have a higher error rate 
compared to bar code printing by manufacturers and that the ``use and 
maintenance of this type of bar code printing is historically haphazard 
at best.'' Another comment from a bar code standards organization 
estimated the error rate in hospital labeling to be approximately 17 
percent nationwide.
    More importantly, requiring persons who manufacture, repackage, or 
relabel human drug products and private label distributors to bar code 
their own products and to use the same bar coding standard should 
result in a more uniform bar coding system that can be used regardless 
of a patient's or hospital's location in the United States (Ref. 15). 
Uniformity should also make it easier for health care professionals to 
train themselves on bar coding procedures and technique and make it 
easier and less expensive for hospitals to buy bar coding equipment. 
Uniformity should also make it easier for manufacturers, repackers, 
relabelers, and private label distributors to put bar codes on 
products, because they would not have to customize their symbols or

[[Page 12504]]

bar codes to meet individual needs. (We discuss issues relating to the 
choice of a bar code symbology, standard, or other machine-readable 
format, and the potential impact on innovation, in detail in section 
II.D of this document.)

B. What Products Would Have to Have a Bar Code? (Proposed Sec.  
201.25(b))

1. What Did We Hear at the Public Meeting?
    In the June 18, 2002, Federal Register notice (67 FR 41360 at 
41361) announcing the public meeting on bar coding, we asked which 
medical products should have a bar code. We specifically invited 
comment on whether all prescription and OTC drugs should be bar coded, 
and we asked about blood products, vaccines, and medical devices (id.). 
We wanted our request for comments to help us decide which products 
should be covered by the proposal. For example, we sought information 
about OTC drugs because we did not know the costs and benefits of 
requiring all OTC drugs to have a bar code. For blood, we knew that an 
international bar coding standard (ISBT 128) existed, but did not know 
whether a rule requiring blood to have a bar code was necessary given 
that international standard. For vaccines, we were concerned that bar 
coding costs could have an adverse impact on vaccine manufacturers and 
vaccine supplies. For devices, our request for information was prompted 
by several letters to Secretary of DHHS Thompson, asking him to include 
devices in any bar coding rule (Refs. 31, 32, and 33).
    The public comments we received reflected a variety of different 
positions. For example, almost all comments agreed that prescription 
drugs should have a bar code and that the bar code should extend to 
products at the unit dose level. However, comments from the 
pharmaceutical industry indicated that some products, such as samples, 
should not fall within a bar code regulation or that we should allow 
for exemptions. The USP also supported an exemption for certain 
containers, such as ampules or vials under 5 milliliters (mL).
    For OTC drugs, many health care professionals supported bar codes 
on all OTC drugs, but other comments, including a comment from a trade 
association representing the OTC drug industry, disagreed, stating most 
OTC drugs are used in consumer settings where bar codes would not add 
value. The trade association also stated that all OTC drug products 
intended for retail sale have the universal product code (UPC) on the 
outer container and that there could be ``significant potential 
negative impact'' if we modified the UPC bar code system on OTC drug 
products. In contrast, one manufacturer of OTC drugs supported 
requiring bar codes on the outer container, but did not favor requiring 
bar codes for certain categories of products that carry little or no 
risk of causing adverse drug events in an institutional setting. CHPA 
and other companies repeated their concerns about bar codes for OTC 
drug products during a meeting with FDA on September 17, 2002, and 
emphasized the potential adverse impact on retailers if we required the 
UPC code to contain the NDC number. Some comments supported bar codes 
on OTC drugs used in hospitals or in ``institutional settings'' or OTC 
drugs packaged and sold for use in institutions.
    A split between health care professionals and industry also existed 
for vaccines. For example, the Centers for Disease Control and 
Prevention, which coordinates the VISI program, recommended that 
vaccines have bar codes so that information on vaccines could be 
readily captured into medical records and other forms, thereby 
enhancing the monitoring of immunization programs and surveillance of 
adverse effects. Vaccine manufacturers, including VISI members, 
expressed a different view, stating that even small bar codes may be 
difficult to place on vaccines. One industry comment added that 
requiring bar codes on vaccines would ``increase the potential for 
disrupting vaccine production lines, particularly if there is a need 
for in-line printing'' and that ``[g]iven the fragile nature of vaccine 
supply and recent shortages of a number of vaccines, there is concern 
that any additional disruptions could exacerbate this situation.''
    For blood, the comments generally agreed that we should require bar 
codes. Most comments acknowledged that an internationally standardized 
bar code symbology (ISBT 128) for blood exists and that the bar codes 
describe the blood's identification number, blood group and Rh type, 
product number, expiration date and time, and special testing results. 
However, while some comments recommended that we require blood 
containers to have bar codes using the ISBT 128 symbology, one comment, 
representing thousands of blood collection centers, blood banks, and 
transfusion services, opposed requiring the use of ISBT 128 through a 
regulation. Instead, the comment wanted us to require adoption of a 
United States Industry Consensus Standard for the Uniform Labeling of 
Blood and Blood Components or ``focus on requiring electronic data 
interchange and the definition and use of standard data structures.''
     For devices, the comments suggested another split between health 
care professionals and the regulated industry. Many health care 
professionals and hospital groups supported requiring bar codes on 
devices, although some would defer action on medical devices so that 
progress on a rule to require bar codes on drugs would not be slowed 
down. Others would defer action on medical devices because different 
device classes present different levels of risk. Device manufacturers 
generally opposed the inclusion of medical devices in a bar coding 
proposal. The device industry noted, as we did in our June 18, 2002, 
Federal Register notice (67 FR 41360) announcing the public meeting, 
that medical devices present different issues compared to drugs, 
biological products, and blood. For example, there are different 
classes of medical devices, and each class represents a different 
degree of risk, so, for a low-risk device (such as a bandage), a bar 
code might not have an impact on patient safety (67 FR 41360 at 41361). 
As another example, some medical devices may be reconditioned by 
parties other than the original manufacturer; in such situations, the 
original manufacturer might want to ensure that its bar code is removed 
or eliminated if the device is reconditioned, because the device no 
longer comes directly from the original manufacturer. Comments from 
device industry interests recommended further study and a separate 
rulemaking for devices or the voluntary use of ``automatic 
identifiers.'' However, one device manufacturer indicated that it 
already uses bar codes on its devices, but it uses the bar code for 
reimbursement purposes and for logistical reasons rather than for 
safety concerns. The manufacturer also recommended that, if we wanted 
bar codes on devices, we should issue guidelines instead of a rule.
2. What Products Would the Rule Cover?
    After careful consideration of the comments, we propose to require 
the following products to carry a bar code:
    [sbull] All prescription drug products, including biological 
products (including vaccines), but excluding physician samples; and
    [sbull] Over-the-counter (OTC) drugs that are dispensed pursuant to 
an order and are commonly used in hospitals; and
    For blood and blood components, the proposal would require the use 
of machine-readable information.

[[Page 12505]]

    a. Why Cover Prescription Drug Products, Including Vaccines, But 
Not Physician Samples? The comments from the public meeting agreed that 
prescription drug products should have a bar code, although a small 
number of comments suggested that only prescription drug products used 
in institutions should be subject to a bar code requirement and that 
prescription drug samples should not be included.
    We decided to cover all prescription drug products, rather than 
limit the rule to prescription drug products used in institutions, 
because we are unaware of any prescription drug products that are not 
used in hospitals. Our primary focus is to help reduce the number of 
medication errors occurring in hospitals, and, as we consider 
``prescription drugs used in institutions'' as being the same as 
``prescription drugs'' generally, the proposal refers to ``prescription 
drugs.''
    However, with regard to prescription drug samples, we decided to 
omit prescription drug samples from a proposed bar code requirement 
because most samples are given to patients at physicians' offices, and 
we do not believe that physicians or patients would have or be inclined 
to buy bar code scanners for their own use in the immediate future. We 
recognize that an argument could be made for including samples. We know 
that some samples are donated to charitable organizations, such as free 
clinics, for distribution to patients without charge (Ref. 34). These 
samples could be subject to the same medication errors as marketed 
prescription drugs, and those medication errors could be prevented 
through the use of bar codes. In addition, Congress and FDA have been 
concerned about illegal sales of prescription drug samples, the 
potential diversion of samples to illegal drug trafficking, and the 
entry of counterfeit drugs into the wholesale distribution system. 
Requiring bar codes on samples could help identify diverted or 
counterfeit drug products that enter distribution through illegal 
channels, and this could result in benefits that are not directly 
related to the prevention of medication errors.
    We recognize that the vast majority of prescription drug samples 
are usually given to patients at physicians' offices and are not 
administered in hospitals. Because we have no evidence to suggest that 
physicians' offices are likely to be equipped with bar code scanners in 
the immediate future, the benefits associated with preventing 
medication errors through bar codes on prescription drug samples are 
unlikely to be realized in this health care setting. We also recognize 
that it is unlikely that charitable institutions, such as free clinics, 
would have the resources to buy bar code scanners to prevent medication 
errors. As a result, we have decided to omit prescription drug samples 
from the rule at this time. We do, however, invite comment on whether 
to require bar codes on prescription drug samples. Comments should 
address the costs and benefits associated with requiring bar codes on 
prescription drug samples.
    The proposal would apply to vaccines. The National Childhood 
Vaccine Injury Act of 1986 (Public Law 99-660) (42 U.S.C. 300aa-25(a)) 
requires each health care provider who administers a vaccine set forth 
in the Vaccine Injury Table to any person to record, in that person's 
permanent medical record or in a permanent office log or file, the date 
of administration of the vaccine, the vaccine manufacturer, the 
vaccine's lot number, and other information. A bar code on vaccines 
could help ensure the accuracy of those records insofar as 
identification of the vaccine, its manufacturer, and date of 
administration are concerned, and, for those vaccines administered in 
health care facilities, help ensure that the right vaccine is 
administered to the right patient at the right time. However, we are 
sensitive to the vaccine manufacturers' concerns, particularly as they 
relate to possible adverse impacts on vaccine production or 
availability, and we invite comment on the risks and benefits of 
including vaccines in a bar code rule.
    As for those comments that suggested an exemption for certain 
products or small containers, we decline to create an exemption 
mechanism and explain our reasons in section II.F of this document.
    b. Why Cover OTC Drugs That Are Dispensed Under an Order and 
Commonly Used in Hospitals? The public meeting notice asked whether we 
should require bar codes on all OTC drugs. After reviewing the 
comments, we decided against requiring all OTC drugs to carry a bar 
code because it is unlikely that putting bar codes on all OTC drugs 
would have a significant impact on reducing medication errors and 
offset the large costs associated with requiring bar codes on all OTC 
drugs. Most OTC drugs are used outside hospitals and other health care 
facilities and are used by consumers who purchase the OTC drugs at 
retail. At this point, it is unlikely that individual consumers would 
buy, use, or have access to bar code scanners or use such scanners 
before taking an OTC drug.
    We recognize, however, that some OTC drugs are administered to 
patients in hospitals and that bar codes would enable health care 
professionals to check whether they are giving the right OTC drug in 
the right dose and right route of administration to the right patient 
at the right time. In addition, we recognize that OTC drugs could 
interact with prescription drugs administered at that hospital or 
affect another drug's performance. Thus, we propose to require bar 
codes on OTC drugs that are dispensed pursuant to an order and are 
commonly used in health care facilities. For example, the bar code on 
an OTC drug dispensed pursuant to an order and commonly used in a 
hospital may allow a hospital's database to identify any potential 
interactions between the OTC drug and any prescription drugs prescribed 
for the patient, or may alert a health care professional to the 
patient's allergies relative to the OTC drug's ingredients. The 
proposal would apply to any manufacturer, repacker, relabeler, or 
private label distributor who sells a specific package of an OTC drug 
product to hospitals. It would not apply to all packages of a specific 
OTC drug product. An example of a specific package of an OTC drug 
product sold to hospitals would be an individual product, such as an 
aspirin tablet, packaged in a unit-of-use container.
    We would interpret ``commonly used in hospitals'' to include OTC 
drugs that are sold to hospitals, packaged for institutional use, 
labeled for institutional use, or marketed, promoted, or sold to 
hospitals through drug purchasing contracts or catalogues. For example, 
if an OTC drug product manufacturer sends its catalogues to hospitals 
to solicit orders from them, the OTC drug products described in the 
catalogue would be ``commonly used in hospitals'' because the 
manufacturer is marketing its OTC drugs to hospitals. If a distributor 
relabeled an OTC drug ``for institutional use,'' then that OTC drug 
would be ``commonly used in hospitals'' because it is intended for 
hospital use.
    We expect that manufacturers, repackers, relabelers, and private 
label distributors would know which of their products meet the 
definition of OTC drug products commonly used in hospitals. For 
example, we believe that when manufacturers, repackers, relabelers, and 
private label distributors label or package their OTC drugs for 
institutional use, they know that the products will likely be sold to 
hospitals. Manufacturers also know that their OTC drug products will be 
sold to hospitals when they market or promote those OTC drugs to 
hospital staff through detailing the products or other means, enter 
into hospital purchasing contracts, or sell to hospitals through 
catalogues.

[[Page 12506]]

    We recognize that it is possible for a manufacturer to sell an OTC 
drug to a wholesaler or retailer who then re-sells the product, without 
making any changes to the product, directly to a hospital without the 
manufacturer's knowledge. We believe that, in most cases, the 
manufacturer would know that the product may be sold to a hospital 
(e.g., because of the product's labeling, packaging). However, there 
may be rare instances when the manufacturer may not have had reason to 
believe that its product would be sold to a hospital. Therefore, if the 
OTC drug is not packaged, labeled, marketed, promoted, or sold to a 
hospital as described above, we would not expect the OTC drug's 
manufacturer to comply with the bar code requirement.
    Proposed Sec.  201.25(b) would also include the phrase ``dispensed 
pursuant to an order'' with regard to OTC drugs. Some products in 
hospitals that are traditional types of OTC drugs, such as aspirin or 
acetominophen, are dispensed pursuant to a physician's order. Other 
products that are regulated as OTC drugs are not dispensed pursuant to 
a physician's order. For example, a hospital might provide fluoride 
toothpaste or mouth rinses to a patient without a physician's order. 
Because these products are not likely to contribute to medication 
errors, the proposal would focus only on those OTC drugs used in 
hospitals that are dispensed pursuant to an order.
    We recognize that there may be other ways to describe the types of 
OTC drugs that should have a bar code. For example, we considered 
requiring bar codes for OTC drugs ``sold directly to hospitals.'' If 
the proposal pertained to OTC drugs sold directly to hospitals, most 
manufacturers, repackers, relabelers, and private label distributors 
who sold their products directly to hospitals would be subject to the 
rule, but the bar code requirement could be avoided by selling the OTC 
drugs to distributors or other third parties for re-sale to hospitals. 
We considered applying the bar code requirement to OTC drugs that are 
labeled for use in an institutional setting. This alternative is 
equally difficult to administer because it is easily circumvented by 
relabeling the drug. We considered requiring bar codes on OTC drugs 
commonly used in health care facilities (rather than hospitals), but 
could not determine whether clinics, nursing homes, and other 
facilities would invest in bar code scanning equipment.
    We specifically invite comment on the terms we should use to 
describe OTC drugs that should be subject to the bar code requirement. 
Comments should also consider the following issues:
    [sbull] Who should be required to apply the bar code on the OTC 
drugs that are subject to a bar code requirement? If the proposal 
refers to OTC drugs ``commonly used in hospitals,'' will manufacturers, 
repackers, and relabelers know which products require a bar code?
    [sbull] Do the terms ``dispensed pursuant to an order'' 
sufficiently distinguish between those OTC drugs that are likely to be 
involved in medication errors from those that are not?
    c. Which Blood Products Are Covered? Current FDA regulations state 
that the container label on blood and blood products ``may bear encoded 
information in the form of machine-readable symbols approved for use by 
the Director, Center for Biologics Evaluation and Research'' (see 21 
CFR 606.121(c)(13)), but they do not require the use of such symbols 
nor do they specify a particular symbol. Correct identification of 
blood is essential because transfusion errors or use of contaminated 
blood can have serious adverse health consequences for a patient. For 
example, one comment submitted in response to the public meeting stated 
that transfusion errors cause as many as two dozen patient deaths 
annually and that the number may be under reported. Consequently, we 
propose to require that blood and blood component container labels bear 
``encoded information that is machine-readable'' and approved for use 
by the Director of CBER. We address this specific requirement at 
proposed Sec.  606.121(c)(13), which we discuss more fully in section 
II.H of this document.
    d. Why Did We Omit Medical Devices From the Rule? At this time, we 
are omitting medical devices from this rulemaking. We recognize that 
different issues arise for devices than for drugs, so further 
consideration is needed regarding the need for putting bar codes on 
medical devices. We will continue to study whether to develop a 
proposed rule to require bar codes on medical devices to prevent or 
reduce medication errors.

C. What Would the Bar Code Contain? (Proposed Sec.  201.25(c)(1))

1. What Is the National Drug Code Number, and Why Would It Be Helpful?
    Proposed Sec.  201.25(c)(1) would require the bar code to contain, 
at a minimum, the drug's NDC number. The NDC number identifies each 
drug product that is listed under section 510 of the act. Most persons 
attending the public meeting agreed that a bar code should, at a 
minimum, contain the drug's NDC number.
    To complement this proposed requirement, we intend to revise our 
drug establishment registration and listing regulations to redefine the 
NDC number and to make the NDC number unique and more useful to 
informational databases, whether those databases are created for 
purposes of preventing medication errors, obtaining the latest 
information about a specific drug, or tracking drug use or 
distribution. We hope to publish a proposed drug establishment 
registration and listing rule in the Federal Register soon.
    Please note that proposed Sec.  201.25(c)(1) would require the bar 
code to contain, at a minimum, the NDC number. Several comments 
submitted in response to the public meeting indicated that some drug 
manufacturers already place bar codes on their products, but that the 
bar code contains a numerical identifier that contains, but is not 
identical to, the NDC number. For example, some comments suggested that 
the bar code contain the International Article Number (EAN) or the 
Global Trade Item Number (GTIN). We are aware that some drug companies 
already use a bar code containing the:
    [sbull] Universal Product Code number (UPC). The UPC is usually a 
12-digit number that may or may not contain the NDC number within it. 
For example, if the drug's NDC number were 1234567890, the UPC number 
might be 312345678906, where the first digit (3) signifies that the 
product is a drug, and the last digit is a ``check digit'' that helps 
confirm that the bar code was read correctly. However, some drugs, 
particularly OTC drugs, may have a UPC number that does not contain the 
NDC number;
    [sbull] International Article Number (EAN). The EAN is a 13-digit 
number and also contains the NDC number within it; or
    [sbull] Global Trade Item Number (GTIN). The GTIN is a 14-digit 
number that contains the NDC number in conjunction with a code that 
identifies the product's packing level. In the GTIN, the first digit 
signifies the packaging level.
Thus, under the proposal, the bar code could contain the NDC number 
alone or the UPC number, EAN number, or GTIN number, as long as the NDC 
number is present. By making the NDC number the minimum bar code 
information requirement, firms could continue using various numbering 
systems (such as the UPC, if the UPC number contains the NDC number, 
EAN, or GTIN numbers) in their bar codes, thus minimizing or 
eliminating the need for companies to redesign or generate new bar 
codes and

[[Page 12507]]

minimizing any disruptions to the companies' international markets.
    We recognize that some comments supported the use of a unique 
identifying number rather than the NDC number. One comment explained 
that the UPC code that goes on the product label does not always use 
the NDC number, so if we required the bar code to contain the NDC 
number, important label changes could go unnoticed if health care 
professionals relied on the bar codes instead of product labels. The 
comment suggested that if distributors establish the unique identifying 
codes and revise those codes when they make label changes, the revised 
code could then trigger a need for a health care professional 
administering the drug to read the label and to update its database 
accordingly. Another comment described the NDC number as a ``dumb 
number'' in OTC drugs and suggested following UCC/EAN guidelines 
instead to identify the product. Another comment stated that OTC drugs 
should use the UPC number instead of the NDC number because changing 
UPC bar codes to include the NDC number would result in great expense 
without a discernable benefit. Additionally, during a meeting with CHPA 
and others, the industry representatives stated that UPC codes do not 
always contain NDC numbers, and retailers rely on the UPC codes, so 
requiring the use of NDC numbers would be disruptive to the industry 
and retailers. The industry representatives suggested using a unique 
identifier other than the NDC number.
    We decline to require the use of unique identifying numbers other 
than the NDC number. Through the proposed drug establishment 
registration and listing rule, the NDC number would become a unique 
identifying number for listed drugs and correspond to a particular 
listed drug. If we allowed distributors to assign unique identifying 
numbers and did not coordinate the assignment of such numbers to drugs, 
the result could be extremely confusing as distributors could use 
different identification schemes (such as a mixture of letters, 
numbers, or other characters). Moreover, creating and maintaining 
databases on drug products for medication error purposes would become 
more difficult because identifying information would have to come from 
multiple sources. For example, the Federal Government might be the 
source for NDC number information, but firms who created unique, non-
NDC identifying numbers would have to provide information on those 
numbers to the databases themselves if the databases are to be complete 
and useful. Multiple information sources would increase the likelihood 
that some information and databases might not be updated as frequently 
as others, that some information might be unavailable, or that the 
information would be presented in different or incompatible ways. While 
we understand the OTC drug industry's reservations about changing UPC 
codes to include NDC numbers because of a possible impact on retailers, 
proposed Sec.  201.25(b) would only require bar codes on OTC drugs that 
are dispensed pursuant to an order and are commonly used in hospitals, 
so most OTC drugs should not be affected.
2. Would the Bar Code Be Required to Contain the Lot Number and 
Expiration Date?
    Many organizations and individuals have recommended that the bar 
code contain information regarding the drug's lot number and expiration 
date, and others have recommended phasing-in a requirement to have the 
bar code contain the lot number and expiration date.
    We decline to require lot number and expiration date information in 
the bar code at this time. In general, while lot number and expiration 
date information would make it easier to identify drugs that had been 
recalled or were expired, we neither found nor received data to show 
that the benefits of bar coding lot number and expiration date 
information would exceed the costs of putting that information in the 
bar code. There is, however, limited information on the extent to which 
patient safety is affected by and medication errors occur as a result 
of taking expired or recalled drugs. We reviewed data from our adverse 
event reporting system (containing 71,546 cases) and found 90 cases 
where patients received an expired drug and 21 cases where patients 
received a recalled drug. Expired drugs may become subpotent and might 
not have the intended therapeutic effect. They also may contain 
degradation products associated with aging. Products may be recalled 
for a variety of reasons including no active ingredient present in the 
product or contamination of the product that could lead to infection.
    We also tabulated data from the Office of Compliance, Center for 
Drug Evaluation and Research, on the reasons for and the extent to 
which drug products have been recalled from the market. From fiscal 
year 1997 through fiscal year 2002, there were 1,230 recalls, of which 
97 were Class I (reasonable probability that the use or exposure to the 
violative product will cause serious adverse health consequences or 
death) and 1,133 were Class II (use or exposure of the violative 
product may cause temporary or medically reversible adverse health 
consequences or where the probability of serious adverse health 
consequences is remote). Despite this number of recalls for safety and 
health reasons, we received few reports of adverse events associated 
with the administration of a recalled drug, and we do not have reliable 
data that show how often these products were administered to patients.
    Thus, based on the data available to us, we cannot determine the 
magnitude of the public health problem associated with administering 
expired or recalled products, and we cannot quantify the patient safety 
benefit associated with requiring lot number and expiration date 
information in a bar code.
    Some comments suggested that requiring lot number and expiration 
date information in a bar code could have benefits outside the 
medication error context by making it easier to track or trace products 
and to identify counterfeit products.
    We agree that bar codes may be useful outside the medication error 
context, but our rule focuses on the use of bar codes to prevent 
medication errors.
    Industry comments indicated that adding lot number and expiration 
date information to the bar code would adversely affect production line 
speed. One comment from a drug company predicted that encoding lot 
number and expiration date information would reduce packaging line 
speed by 40 percent and cost more than $4.8 million for its product 
lines. Another drug industry comment indicated that a requirement to 
encode lot number and expiration date information could cause companies 
to reconsider their packaging choices, or require companies to alter 
their printing methods.
    We also note that inclusion of lot number and expiration date 
information might require the use of a different machine-readable 
format, such as a two-dimensional symbology, in addition to or as a 
substitute for a linear bar code, and that could affect a hospital's 
equipment purchasing decision. Use of nonlinear bar code formats could 
require the purchase of a different scanning or reading device and also 
increase a hospital's equipment costs.
    Based on the evidence we had and our obligation under Executive 
Order 12866 to choose regulatory approaches that maximize net benefits, 
the potential burden of encoding lot number and expiration date 
information appeared to outweigh the potential benefit at this time. 
Consequently, the proposed rule

[[Page 12508]]

would not require lot number and expiration date information in the bar 
code. We will continue to study the issue and invite comments and, more 
importantly, data on costs and benefits associated with requiring lot 
number and expiration date information in the bar code. If comments 
provide information and data to support requiring lot number and 
expiration date information, we may consider requiring that information 
with the bar coded NDC number as part of a final rule.
    Although the proposed rule would not require the drug's lot number 
and expiration date to appear in the bar code, the proposed rule would 
not prohibit the inclusion of such information. In other words, FDA 
will not object if a manufacturer, repacker, relabeler, or private 
label distributor were to add the lot number and expiration date to its 
bar code or add such information in a machine-readable format provided 
that the lot number and expiration date information is accurate. In a 
meeting with PhRMA on August 19, 2002, the industry representatives 
suggested to us that they might add machine-readable lot number and 
expiration date information if a demand existed for it. (We have placed 
a memorandum of this meeting in the docket for this rule, along with 
memoranda of meeting for other meetings we attended.) We do not know 
how much more such drugs would cost (compared to drugs that only had 
the NDC number encoded in the bar code) or whether hospitals and other 
health care facilities would be willing to pay more for drugs that have 
the NDC number, lot number, and expiration date in a bar code or 
machine-readable code, but the meeting raises the possibility that 
market forces could lead to the inclusion of lot numbers and expiration 
dates in bar codes or other machine-readable formats.

D. Would the Rule Require a Specific Type of Bar Code? (Proposed Sec.  
201.25(c)(1))

1. What Did We Hear from the Public Meeting?
    In the public meeting notice, we asked whether we should require 
the use of a specific bar code symbology, such as reduced space 
symbology (RSS), adopt one symbology over another, or allow for 
``machine readable'' formats (67 FR 41360 at 41361). We also asked for 
the ``pros and cons'' of each approach (id.). We had identified RSS as 
a possible symbology because we knew about industry-conducted pilot 
studies that used RSS bar codes on small vials (Ref. 35). Our reasoning 
was that if RSS symbology could be used on small containers, it could 
be used on larger containers, too.
    The comments we received reflected an array of differing opinions, 
ranging from the adoption of a specific, non-bar code technology to 
prescribing no specific symbology or standard at all in order to 
promote innovation. Two principal, yet contradictory, themes emerged. 
One view advocated requiring a specific symbology or standard to 
promote uniformity and to create the conditions whereby hospitals could 
invest confidently in bar code scanning equipment, without having to 
buy different pieces of equipment to read different bar codes or other 
machine readable formats or without having to fear that any equipment 
purchases would soon become obsolete. Another comment declared that the 
bar code symbology adopted by FDA should be compatible with current 
scanning devices used by health care organizations. However, if the 
rule adopted a single symbology or standard, the rule could affect 
future innovation in this field, and we would have to engage in new 
rulemaking to adopt any newer symbology or standard.
    The other view stated that we should not select any specific 
symbology or even require linear bar codes at all; instead, these 
comments said the rule should require the use of machine-readable or 
automatic identifier technology, thus creating the conditions under 
which newer, and perhaps better, technologies could be used in the 
future. However, the comments and our own analysis suggested that if 
the rule allowed for multiple symbol types or technologies, hospitals 
might be confronted with incompatible technologies and decide against 
buying multiple pieces of equipment. For example, if one drug used an 
RSS bar code, another used a radio frequency identification format, and 
a third used a unique, patented, automatic identification technology, a 
hospital would have to decide whether to buy a bar code scanner, a 
device to detect the radio frequency information, and a device to 
detect the patented identifier, or some combination of the three 
devices. If those costs were too great, the hospital could decide 
against making any equipment investments altogether, and the benefits 
from bar coding would not be realized.
    Other comments suggested that we require the use of machine-
readable codes capable of being read by ``machines currently deployed'' 
and ``economically available'' or use symbology that is ``compatible'' 
with ``current scanners.''
    Some comments suggested that we conduct research to develop time 
lines for adopting specific bar code symbologies, that we have USP 
provide bar code standards, or adopt a standard or family of 
symbologies. Other comments said we should form a group involving 
various interests to study issues further or create an ``automatic 
identification coordinating council'' to ensure that minimum 
information requirements are met and that the best technology is used.
    Deciding whether to require a specific symbology, standard, or an 
unspecified ``machine-readable'' symbol was a very difficult decision 
because of the comments' competing and sometimes incompatible 
positions. For guidance, we examined how another Federal agency reached 
a decision when confronted with an analogous problem of whether to 
require a particular action to accomplish a specific goal or to let 
market forces decide the outcome. We examined how the Federal 
Communications Commission (FCC) decided to adopt an order to require 
all television receivers to include digital television (DTV) reception 
capability in order to move towards a 2006 target date for a transition 
to digital television. Congress had imposed a December 31, 2006, target 
date for the return of the spectrum used by broadcasters for analog 
channels unless 85 percent of homes in a market could not receive local 
digital broadcast television signals. The FCC faced a problem; the 
public was reluctant to buy DTV receivers until there were DTV stations 
offering attractive DTV programs, but broadcasters lacked the incentive 
to provide such DTV programming in the absence of an audience that 
would attract advertisers (Ref. 36 at p. 13). Moreover, because analog 
televisions were still being sold, each sale of an analog television 
set put the FCC farther from reaching the 85 percent DTV reception goal 
(Refs. 37 and 38). The FCC ultimately decided to adopt a plan to 
require DTV tuners on almost all new television sets by 2007 and 
established a 5-year rollout schedule to minimize costs to television 
manufacturers and consumers. It recognized that requiring the 
manufacture of DTV receivers would address ``the root cause of the 
problem, namely the lack of television receivers capable of receiving 
DTV signals'' (Ref. 36 at p. 13). The FCC also recognized that, without 
its intervention, the transition to DTV might remain stalled. The FCC's 
decision to require all television receivers to include digital 
television (DTV) reception capability is

[[Page 12509]]

even more noteworthy because some FCC Commissioners did not favor 
significant regulatory intervention in the market (Ref. 38 at p. 1).
    Our case is similar to the FCC's in the sense that we have an 
objective (reduction of medication errors) that can be achieved through 
bar codes, but hospitals are reluctant to invest in equipment because 
of the lack of bar coded products, and manufacturers, repackers, 
relabelers, and private label distributors are reluctant to invest in 
such bar codes or other technologies in the absence of a demand by 
hospitals or a requirement for such bar codes. If we fail to specify a 
particular measure, such as a symbology or standard, progress towards 
medication error reduction through bar codes could remain stalled; 
hospitals might still be reluctant to invest in equipment because of 
uncertainties in the marks, symbols, or technologies used on the drug 
or a limited amount of resources to buy different types of equipment to 
read the various marks, symbols, or other technologies. Likewise, 
manufacturers, repackers, relabelers, and private label distributors 
might not invest in bar codes or other technologies because no demand 
would exist or because their investments in such bar codes would be 
wasted if hospitals declined to buy the necessary equipment to take 
advantage of those bar codes or other technologies.
    Consequently, proposed Sec.  201.25(c)(1) would require the bar 
code for drugs and biological products (other than blood and blood 
products) to be any linear bar code in the UCC/EAN standard. This means 
that the bar code can be any linear bar code symbology, such as UCC/
EAN-128, RSS, or UPC (if the UPC contains the NDC number), within the 
UCC/EAN standard. Adopting a linear bar code in the UCC/EAN standard, 
as opposed to a specific bar code symbology, should give firms some 
flexibility in selecting the bar code symbology that best fits their 
needs and should also give the rule some flexibility as linear bar code 
symbologies change, are added, or are phased out. For example, we know 
that the UCC has announced a ``sunrise'' date of 2005 for a new EAN-13 
code because the commonly-used UPC code is running out of new company 
prefixes for that 12-digit code (Ref. 39). So, as new linear bar codes 
are added to the UCC/EAN standard, those new codes would be acceptable 
under the proposed rule as long as those new codes include the NDC 
number.
    The UCC/EAN standard also has the advantage of being a widely used 
global standard. One comment submitted on behalf of the International 
Working Group on Barcoding of Pharmaceuticals advocated the use of the 
UCC/EAN standard because it represents a ``validated, testable global 
standard.'' The comment also suggested that regulatory authorities from 
Europe, Japan, and Canada are actively pursuing a bar code standard for 
pharmaceuticals and ``are watching to see what the FDA decides.'' 
Comments from the UCC, EAN, and some pharmaceutical interests also 
mentioned the global applicability of the UCC/EAN standard.
    We recognize that other bar code standards exist, notably those 
advanced by the Health Industry Business Communication Council (HIBCC). 
HIBCC bar code symbologies include code 39 and code 128. (The UCC/EAN 
system also has a UCC/EAN-128 symbology that is similar, but not 
identical, to the HIBCC code 128.) HIBCC also has the Universal Product 
Number (UPN) system which is used for medical and surgical products. 
Comments from drug and biological product companies, however, usually 
referred to UCC/EAN standards if they identified any standard at all, 
so we presume that the use of UCC/EAN standards would be less 
disruptive to those industries compared to requiring the use of a 
different bar code standard. However, a comment from HIBCC suggested 
that some drugs may use HIBCC bar codes, that medical devices, in 
particular, are ``uniquely identified by the UPN number,'' and that the 
Department of Defense, Veterans Administration, and other organizations 
use the UPN numbering system. Therefore, we cannot preclude the 
possibility that some drug firms and organizations may use or prefer to 
use HIBCC bar codes, so we invite comment as to whether the rule should 
refer instead to linear bar codes without mentioning any particular 
standard or refer to UCC/EAN and HIBCC standards.
    Our position presumes that, by the time any final bar code rule 
becomes effective (assuming that we do issue a final rule), bar code 
scanners will be able to read different UCC/EAN linear bar code 
symbologies reliably and efficiently. This is a critical consideration 
because the proposed rule's benefits are realized only if hospitals 
invest in bar code scanners, and we reiterate that their willingness to 
make that investment may depend on the number of different bar code 
symbologies that will be used and the ability of bar code scanners 
(particularly those scanners already in use at the hospitals) to read 
different symbologies. Comments from the public meeting disagreed on 
what capabilities different bar code scanning technology had to read 
different symbologies. Some comments suggested that new bar code 
scanners can read different linear bar code symbologies, particularly 
those in the UCC/EAN standard. In contrast, others suggested that bar 
code scanners may be unable to read newer bar code symbologies or that 
older scanners cannot read new symbologies or composite codes. Our 
understanding is that scanner capability depends on how the scanner is 
programmed (because scanners are programmed to read individual 
symbologies) and whether scanners can be upgraded or modified to read 
new symbologies. For example, some bar code scanners might be 
programmed to read the most commonly used linear bar codes and might 
not be able to read the RSS symbology. Some scanner manufacturers may 
be able to upgrade or modify an existing scanner to read newer 
symbologies, while other scanners, due to their age or the manner in 
which they were made, might not be capable of being upgraded. We invite 
further comment on this point.
    As for non-bar code technologies, we know that other technologies 
exist or are under development, but we decline to specify the use of 
DataMatrix or other nonlinear bar code formats or technologies, such as 
radio frequency identification (RFID). We realize that other 
technologies may be able to encode more data or be more versatile 
compared to linear bar codes. For example, in a meeting with the 
National Alliance for Health Information Technology, we heard how RFID 
could be used to facilitate inventory control and to track individual 
items because each RFID tag would have its own unique ``electronic 
product code'' (EPC) consisting of a header code, an ``EPC manager'' 
that would probably identify the product's manufacturer, an ``object 
class'' that would refer to the product type, and a ``serial 
identifier'' that would be unique to each individual item. RFID's 
ability to track individual items could help drug companies and public 
health agencies identify and eliminate counterfeit drug products. 
However, the costs associated with RFID tags and readers could be 
significant; literature provided by the Auto-ID Center conceded that 
current RFID tags are ``fairly expensive'' and that a firm might have 
to purchase more than one reader if multiple RFID frequencies exist 
(Ref. 40). A representative from the Auto-ID Center stated that the 
``target cost'' is five cents per RFID tag, so the technology could 
become more available and less expensive in the future.
    Nevertheless, we find that linear bar codes are sufficient for 
encoding NDC

[[Page 12510]]

numbers, and hospitals that already have or intend to buy linear bar 
code scanners might not have to upgrade those scanners or purchase new 
devices if the proposed rule would require the use of linear bar codes 
only. In contrast, if we were to allow for other technologies such as 
RFID or even two-dimensional symbols such as DataMatrix, hospitals 
might have to buy RFID readers, optical scanning equipment, or other 
equipment because linear bar code scanners may be incapable of reading 
other technologies and, depending on the particular scanner, may be 
incapable of being upgraded. However, we invite comment on whether the 
rule should adopt a different format (whether that format is a 
symbology, standard, or other technology), and recommend that any 
comments advocating the use of a different model consider and discuss 
the following issues:
    [sbull] What other symbol, standard, or technology should we 
consider, either in place of a linear bar code or in addition to it? 
How accepted is that symbol, standard, or technology among firms that 
would have to affix or use that symbol, standard, or technology? For 
example, we know that RFID technology has great potential for encoding 
a lot of data and for identifying individual products, but the 
technology is not yet widely accepted in the pharmaceutical industry 
due to its novelty and costs.
    [sbull] Will hospitals be able to read or use the symbol, standard, 
or technology, either with existing equipment or equipment under 
development? We reiterate that hospitals might not have the financial 
resources to buy multiple pieces of equipment to read multiple, 
incompatible formats, so hospitals must be able to make equipment 
purchasing decisions confidently, knowing that they will recapture 
their investment costs.
    Insofar as drug products are concerned, we also decline to have the 
proposal refer to the use of machine-readable codes or symbologies that 
can be read by machines ``currently'' used. Although a reference to 
``machine-readable'' symbols or to ``current'' technology might seem to 
make a rule more accommodating to future technological developments, 
words such as ``machine-readable'' and ``current,'' when used in a 
regulation, can create several practical difficulties. For example, in 
the absence of an accepted standard or process, disputes could arise as 
to how we or any other person or group determines what is ``current.'' 
A manufacturer who wants to use a novel bar code or symbol could get 
different answers depending on whom it consulted; a hospital using 
linear bar code readers might find the novel code incapable of being 
read by its ``current'' scanners, whereas the firm marketing a new 
machine to read the novel code would argue that the novel code is 
``machine-readable'' by ``current'' machines. Similarly, if only a 
fraction of the machines used in hospitals can read a new code, a 
hospital might argue that the new code cannot be read by ``current'' 
machines, yet, if machines were or could be upgraded or modified, a 
firm that marketed the machines or upgrade service might argue that the 
new code can, indeed, be read by current machines, provided that 
upgrades or modifications are made. These and other potential problems 
associated with a reference to ``current'' machines or ``machine-
readable'' technology lead us to avoid using such terms in this 
proposal. (Different considerations apply for blood and blood products, 
and we discuss the proposed requirement for machine-readable symbols 
for blood and blood product containers at section II. H of this 
document.)
    Furthermore, we decline to establish committees or other bodies to 
study the issue further or to decide technological issues. Given the 
comments we have received thus far, we have no assurance that a 
committee or other body would arrive at a consensus.
    Nevertheless, if a group comprised of the affected industries and 
persons who would use the bar code could agree on a standard, 
symbology, or technology, we would be interested in learning about such 
standard, symbology, or technology and its costs and benefits. We would 
carefully review the information and consider the information when 
drafting a final rule.
2. Are There Any Specific Requirements for the Bar Code?
    Proposed Sec.  201.25(c)(1)(i) and (c)(1)(ii) would require the bar 
code to be surrounded by sufficient blank space so that the bar code 
can be scanned correctly and to remain intact under normal conditions 
of use. These requirements would help ensure that the bar code can be 
read easily and accurately so that its safety benefits may be realized. 
We note that today some manufacturers have bar codes at locations where 
the bar codes are destroyed, damaged, or otherwise rendered useless. 
For example, some manufacturers have put bar codes on individual foil-
wrapped packets, but the bar code overlaps the folds or perforations 
that separate the foil-wrapped packets. When one packet is separated 
from the others, the bar code is split into pieces, and the resulting 
bar code fragments can provide misleading or nonsensical information to 
the bar code scanner or might not be read at all by the scanner. So, 
the proposed rule would require the bar code to be placed in a manner 
so that it remains intact during normal conditions of use. For the 
foil-wrapped packet example, this would mean that the bar code would be 
placed away from folds or perforations so that each packet, when 
separated from the others, has its own intact and easily scanned bar 
code.
    Note, too, that the proposal would include the phrase ``under 
normal conditions of use.'' Depending on the packaging and container 
used, the ``normal conditions of use'' may or may not require the bar 
code to remain intact at all times. For example, assume that you have a 
tablet in a blister package and that the bar code is printed on the 
flat side of the blister package. If the bar code is scanned before the 
tablet is pushed through the flat side, the bar code would not remain 
``intact'' after the tablet has been dispensed, and this would be 
acceptable because, under ``normal conditions of use,'' the bar code 
would have already served its purpose by being scanned before the drug 
was dispensed. In contrast, assume that you have a bottle that contains 
multiple tablets. The bar code on the bottle, under proposed Sec.  
201.25(c)(1)(ii), would have to remain intact throughout the bottle's 
use so that the bar code could be scanned each time a tablet is 
dispensed from that bottle.
    One comment said we should audit bar code quality, help industry 
build a bar code information infrastructure, publish our results, and 
support mandatory testing and verification of bar codes.
    We decline to adopt the comment's suggestions. The bar code would 
be part of the drug's label, so issues concerning its quality and 
verification would be subject to current good manufacturing practices 
(GMP's). In general, persons who would be subject to the bar code 
requirement would be responsible for having written procedures for the 
receipt, identification, storage, handling, sampling, examination, and/
or testing of labeling and packaging materials, for exercising control 
over labeling materials and label operations, and for ensuring that 
correct labels are used (see 21 CFR 211.122, 211.125, 211.130). Failure 
to meet GMP's will cause a drug to be considered adulterated under 
section 502(a)(2)(B) of the act.
    We also note that there are various standards relating to bar codes 
already. For example, the American Society for

[[Page 12511]]

Testing and Materials has a standard procedure for bar code 
verification (Ref. 41). The International Organization for 
Standardization has various standards for automatic identification and 
data capture techniques, and several deal with bar code quality and 
symbologies. The UCC has guidelines on bar code placement and other 
documents on specific symbologies or quality matters. Given these 
standards and other documents, as well as the comparatively greater 
expertise of standards organizations in this area, we do not intend to 
develop our own guidance documents regarding bar code details such as 
quality, verification, or testing.
    The bar code can also be used to access the medication information 
found in the professional labeling of a specific drug product. We are 
currently working on a collaborative initiative with the National 
Library of Medicine and the Department of Veterans Affairs to create a 
collection of up to date, computer readable electronic labels for 
marketed drug products called the ``DailyMed.'' By linking the NDC to 
the appropriate label in the DailyMed, people will be able to use 
computer systems to access important medication information simply by 
scanning the bar code found on the drug package. This could help locate 
proper dosage instructions, identify drug interactions, and find other 
information necessary for the safe use of medications.

E. Where on the Label Would the Bar Code Appear? (Proposed Sec.  
201.25(c)(2))

    In the public meeting notice, we asked where the bar code should be 
placed. We asked if there were benefits to placing bar codes on 
immediate containers and if there was a way to distinguish whether 
certain containers with a bar code would have a more significant effect 
on preventing medication errors than other containers (67 FR 41360 at 
41361).
    Some comments suggested that the bar code go on every package level 
down to the unit-of-use or unit dose. Other comments recommended 
placing the bar code on the ``immediate container'' or unit dose or 
unit-of-use package only.
    In contrast, one comment expressed surprise that we would even 
consider putting bar codes on unit dose or unit-of-use packages because 
of the potential impact on manufacturers.
    Several comments also disagreed as to whether we should specify 
where a bar code should appear on a particular package. For example, 
one comment recommended that we draft guidelines for bar code 
placement; the guidelines would consider ergonomics, scanner types, 
symbologies, and packaging. Another comment would require the bar code 
to be placed where ``the typical user of the scanning device can 
reliably and consistently scan it.''
    In contrast, other comments stated that we should not restrict the 
bar code's placement on a package because differences relating to 
package size, shape, and material demand flexibility as to the bar 
code's placement.
    Proposed Sec.  201.25(c)(2) would require the bar code to appear on 
the drug's label. Section 201(k) of the act defines ``label'' as ``a 
display of written, printed, or graphic matter upon the immediate 
container of any article; and a requirement made by or under authority 
of this act that any word, statement, or other information appear on 
the label shall not be considered to be complied with unless such word, 
statement, or other information also appears on the outside container 
or wrapper, if any there be, of the retail package of such article, or 
is easily legible through the outside container or wrapper.'' Thus, by 
requiring the bar code to be on the drug's label, proposed Sec.  
201.25(c)(2) would result in bar codes on the drug's immediate 
container label as well as the outside container or wrapper, unless the 
bar code is easily legible and machine-readable through the outside 
container or wrapper.
    We decline to adopt the comments' positions to require bar codes on 
all packages or only on immediate containers because that would either 
result in too many products being bar coded or too few. For example, if 
we required every package to bear a bar code, then arguably a shipping 
container of drugs would have a bar code, even though no hospital would 
dispense a drug directly from a shipping container to a patient, and a 
bar code on the shipping container would have no impact on medication 
errors. (The bar code could help with inventory control and tracking, 
but such matters are outside the scope of this proposed rule.) If we 
required only the immediate container (which is the container that is 
in direct contact with the drug at all times) to have a bar code, then 
patients receiving multiple-unit containers (such as a box holding 
blister packed tablets) would be vulnerable to medication errors 
because the multiple-unit container would not have a bar code.
    As the previous paragraph suggests, there may be more than one bar 
code on a product depending on the package and whether it has a unique 
NDC number. For example, assume that you make drug tablets that are 
individually packaged in a plastic blister pack and then boxed in a 
cardboard container. If the individually packaged tablets have a unique 
NDC number, then each individual blister pack would have a bar code. 
The cardboard container holding the blister pack would have to have a 
bar code, too, because the cardboard container would be an ``outer 
container'' within the statutory definition of ``label.''
    Although proposed Sec.  201.25(c)(2) would not require the bar code 
to appear at a specific location on a product, proposed Sec.  
201.25(c)(1)(ii) would require the bar code to remain intact under 
normal conditions of use. The latter requirement may influence the bar 
code's location.

F. What Would Happen if a Bar Code Could Not Be Put on a Product?

    The proposed rule would not contain an exemption provision. We are 
aware of industry-conducted pilot studies that have placed RSS bar 
codes on small vials (Ref. 35). These pilot studies suggest that almost 
all products are capable of bearing a bar code. However, some comments 
from the public meeting suggested that small products might not be 
capable of bearing a bar code and recommended that we allow for 
exemptions.
    We decline to create an exemption provision because we believe that 
almost all products are capable of bearing a bar code. In addition, 
exemption provisions sometimes create unintended administrative 
problems and consume agency resources as some individuals or firms may 
be tempted to submit exemption requests notwithstanding their ability 
to comply with a particular regulatory requirement. For example, if we 
were to create a general exemption provision, a firm whose drug product 
was packaged in a small vial might seek an exemption even though it 
could use a RSS linear bar code on that vial. If we tried to impose a 
limitation on the exemption, such as allowing for possible exemptions 
if it would not be technologically feasible to affix a bar code on the 
label, a firm might argue over whether economic or other considerations 
determined whether a bar code was technologically feasible. In the end, 
we could be obliged to devote resources to reviewing, deciding, and 
perhaps re-examining exemption requests, and we can avoid that 
potential drain on FDA resources by not creating an exemption 
provision. We invite comment as to whether any specific product or 
class of products should be exempt from a bar code requirement and the 
reasons why such an exemption is considered to be necessary. We also 
invite comment on

[[Page 12512]]

how we might create a waiver provision that would minimize the 
potential for misuse of the waiver. We will consider whether to 
incorporate specific exemptions into the rule.

G. What Is the Proposed Implementation Plan?

    If we issue a final rule to require bar coding, we would require 
bar codes on human prescription drugs and OTC drugs dispensed under an 
order and commonly used in hospitals within three years after we 
publish the final rule in the Federal Register. The 3-year period would 
give affected parties time to obtain NDC numbers, if necessary, exhaust 
supplies of existing labels, and make new labels that contain the bar 
code or machine-readable information.
    Additionally, because the bar code's addition to a label would be a 
ministerial act that would not require us to exercise any judgment as 
to the information being presented, we intend to have firms whose drug 
products are already approved or marketed notify us about the addition 
of the bar code to their product labels through an annual report (see 
Sec.  314.81(b)(2)(iii) (21 CFR 314.81(b)(2)(iii) and 601.12(d)). For 
marketed OTC drugs, there is no comparable, routine reporting 
requirement if the drug is not the subject of an approved new drug 
application, and we do not intend to impose any reporting obligation 
relating to bar codes on OTC drugs.
    We recognize that the bar codes' ability to prevent medication 
errors depends on many external factors outside this rule, such as the 
availability of bar code scanners, computer software that can process 
the bar code information and compare it against patient information, 
training health care professionals to use scanning equipment, and the 
willingness of hospitals to invest in bar code scanning equipment. 
However, requiring bar coding on human drugs is a necessary ``first 
step'' for promoting the use of technology to combat medication errors 
(Ref. 42).
    We also acknowledge the various comments from the public meeting 
suggested different implementation periods for this rule. In general, 
some comments suggested short implementation dates measured in months 
whereas other comments suggested implementation dates measured in 
years. A few comments suggested different implementation dates for 
different products or would have the implementation date depend on the 
product's potential for harm. Several comments recommended requiring 
bar codes to contain the NDC number first, and require the lot number 
and expiration date at some future date.
    We decided on the 3-year implementation date to give affected firms 
time to redesign their labels and exhaust pre-existing label stocks and 
to give hospitals time to decide which scanning devices or systems to 
develop or purchase. Additionally, as we suggested earlier, we want to 
give hospitals more time to decide whether they would be willing to 
work with pharmaceutical firms to have other information (such as lot 
number and expiration date) encoded. While we believe the 3-year 
implementation date is appropriate, we invite comment on whether the 
implementation period can and should be shortened.
    We decline to create a ``phased-in'' implementation system whereby 
we would require the NDC number first, and then require inclusion of 
lot numbers and expiration dates at a future time. As we explained 
earlier in section II.C.2 of this document, we lack data that would 
support requiring lot numbers and expiration dates on bar codes at this 
time. While we will not object if firms volunteer to encode such 
information (assuming that they encode the correct information), we 
will not require or specify any implementation period for the encoding 
of lot number and expiration date information.

H. How Does This Rule Apply to Blood and Blood Components? (Proposed 
Sec.  606.121(c)(13))

    Like medication errors, errors involving blood transfusions can 
result in serious injury or death. For example, one study examined 
reported transfusion errors occurring between January 1, 1990, and 
December 31, 1999, from approximately 256 transfusion services in New 
York (Ref. 43). The study focused on reports involving the 
administration of a unit of blood to someone other than the intended 
patient or the issuance of incorrect blood because of a blood bank or 
phlebotomy error. During the study period, nine million red blood cell 
and whole-blood units were transfused, and 659 cases of erroneous 
administration were observed, for a frequency of 1 error per 14,000 
transfusions. Five cases resulted in fatalities, at a rate of 1 per 
1,800,000 units. In cases where the patient received an incompatible 
unit, nearly half (47 percent) suffered no ill effects, but 41 percent 
of the cases resulted in an acute hemolytic reaction, and 2 percent 
resulted in fatalities (id.) The most common error outside blood banks 
was administering properly labeled blood to a patient other than the 
one for whom the unit was intended (37 percent). In blood banks, the 
study identified issuance of the wrong unit (4 percent) and testing 
errors (7 percent) as some common errors (id.).
    Current FDA regulations, at 21 CFR 606.121(c)(13), state that the 
container label for blood and blood components ``may bear encoded 
information in the form of machine-readable symbols approved for use by 
the Director, Center for Biologics Evaluation and Research.'' The 
reference to ``machine-readable symbols'' in Sec.  606.121(c)(13) was 
intended to be flexible and accommodate changes in machine-readable 
technologies. For example, FDA recognized the use of Codabar (a 
specific bar code symbology) in 1985, and, in 2000, approved the use of 
ISBT 128, version 1.2.0 (Ref. 44).
    Unlike the situation for other prescription drugs, there is already 
substantial use of bar codes for blood and blood products. Most blood 
establishments currently use machine-readable symbols or ``ABC 
Codabar'' on their blood and blood component labels. In August, 1989, 
the International Society for Blood Transfusion (ISBT), an organization 
established to promote and maintain a high level of ethical, medical, 
and scientific standards in blood transfusion medicine and science 
throughout the world, recognized that ABC Codabar, the first bar coding 
system adopted by the health care industry, was becoming outdated and 
initiated the design of a new system using the bar code symbology which 
eventually became known as ISBT 128.
    In December, 1996, the International Council for Commonality in 
Blood Bank Automation (ICCBBA) held an ISBT 128 Consensus Conference in 
Washington, DC, to provide an opportunity for dialogue among the 
affected industry groups and FDA. Although there was a consensus for 
use of ISBT 128, some participants expressed concerns regarding 
implementation time frames and costs of implementation to hospital 
transfusion services. However, ISBT 128 has numerous advantages over 
the ABC Codabar. For example, ISBT 128 is more secure, allows more 
flexibility in coding highly variable information, uses double-density 
coding to allow more information to be encoded in a limited space, and 
can be interpreted by the same bar code readers used with ABC Codabar.
    The ISBT 128 bar code system established by ISBT is similar, but 
not identical to, Code 128. ISBT 128 is a copyrighted symbology. The 
ability to read, store, interpret, transfer, print, or otherwise 
manipulate ISBT 128 data structures requires registration with the 
ICCBBA and payment of an annual

[[Page 12513]]

licensing fee, and the ICCBBA uses the fees to revise, enhance, extend, 
and maintain the ISBT 128 system and associated databases (Ref. 45). 
The ISBT Council accepted an application specification for ISBT 128 in 
July, 1994, and approved a resolution that all bar coded blood products 
collected after July 4, 1998, be labeled using ISBT 128. However, the 
use of ISBT 128 in the United States has been slow, and the ISBT 128 
system has not been implemented in accordance with the ISBT Council's 
resolution.
    Despite the international convention and guidance document, 
comments submitted in response to the public meeting suggest that Sec.  
606.121(c)(13) has not resulted in a uniform, international bar coding 
system for blood in the United States. While some comments described 
ISBT 128 in favorable terms, stating, for example, that it allows more 
information to be encoded or is more accurate than Codabar or that ISBT 
128 represents an internationally-accepted standard for blood, at least 
one comment indicated that licensing fees associated with ISBT 128 may 
deter hospitals from using the ICCBBA system. Comments were also 
divided as to whether to require the use of ISBT 128 or simply require 
the use of ``machine readable'' symbols.
    We considered whether the proposal should specify the use of ABC 
Codabar, ISBT 128, a different symbology or standard, or simply require 
the use of ``machine-readable information'' approved by the CBER 
Director. Each approach has its advantages and disadvantages. For 
example, requiring the use of ISBT 128 would help ensure a uniform bar 
coding standard for blood and blood components and be consistent with 
the international standard, but requiring ISBT 128 would mean that we 
would have to institute new rulemaking if a new symbology, standard, or 
technology was adopted. Requiring ``machine-readable'' information 
approved by the Director of CBER would allow CBER to consider new 
technologies in the future, but could result in some blood 
establishments adopting one system and others using a different system, 
thereby defeating the goal of creating a uniform system for identifying 
blood and blood components. Therefore, we invite comment as to whether 
we should require the use of ISBT 128, require the use of a symbology 
consistent with that required for drugs in proposed Sec.  201.25, or 
require ``machine-readable information'' as approved by the Director of 
CBER or some other standard or symbology.
    In developing this proposal, we recognize that the blood industry 
currently uses a machine-readable code that does not meet UCC/EAN 
standards. Some comments at the public meeting stated that the scanners 
are capable of reading multiple systems (e.g., UCC/EAN and ISBT). Based 
on our understanding of the state of the industry and the ability of 
scanners to read more than one symbology, we decided to propose a rule 
that would permit the existing coding to continue. We invite comments 
on whether this proposal is feasible or whether we should require the 
use of UCC/EAN standards for blood and blood components.
    The proposal would require that the machine-readable information 
meet certain minimum requirements and be approved by the Director of 
CBER. These minimum requirements would move us closer to the goal of 
increasing patient safety. We anticipate that the industry will 
standardize encoded machine-readable information and readers, using our 
minimum requirements to minimize, to the greatest extent possible, the 
need for ``country-specific'' software and the high cost associated 
with software development and maintenance.
    Thus, we propose to amend Sec.  606.121(c)(13) to require the use 
of ``machine-readable information'' approved by the Director of CBER. 
The Director will review the machine-readable information technology to 
ensure that the minimum requirements are met regarding the accuracy of 
the required labeling information, spacing, and conditions of use.
    Proposed Sec.  606.121(c)(13) also would:
    [sbull] Explain that all blood establishments that manufacture, 
process, repackage, or relabel blood or blood components intended for 
transfusion and regulated under the act or the Public Health Service 
Act are subject to the machine-readable information requirement. This 
would be consistent with the pre-existing requirement at Sec.  
606.121(a) and (b).
    [sbull] State that blood and blood components intended for 
transfusion are subject to the machine-readable information 
requirement. This would be consistent with the pre-existing requirement 
at Sec.  606.121(a) that describes the purpose behind container label 
requirements.
    [sbull] Describe the minimum contents of the machine-readable 
information as a unique facility identifier, lot number relating to the 
donor, product code, and the donor's ABO blood group and Rh type. This 
would reflect the pre-existing requirement at Sec.  606.121(c)(1), 
(c)(2), (c)(3), (c)(10), and (c)(12).
    [sbull] Specify that the machine-readable information must be 
unique to the blood or blood component, be surrounded by sufficient 
blank space so that the machine-readable information can be read 
correctly, and remain intact under normal conditions of use. This would 
be consistent with the pre-existing requirement at Sec.  606.120(c) 
that requires labeling to be clear and legible.
    [sbull] State that the machine-readable information must appear on 
the label of the blood or blood component which is or can be transfused 
to a patient or from which the blood or blood component can be taken 
and transfused to a patient. The proposal would not specify where the 
machine-readable information must appear on the label. To illustrate 
how this would work, the proposal's reference to any blood or blood 
component would include a unit of whole blood, packed red blood cells, 
plasma, platelets, and cryoprecipitate AHF. The unit of blood or blood 
component label would contain the machine-readable information if the 
blood or blood component has any possibility of being transfused to a 
patient, whether or not the unit is actually transfused. Additionally, 
the phrase, ``from which the blood or blood component can be taken and 
transfused to a patient'' would include the circumstance where blood or 
a blood component is extracted or aspirated with a syringe from the 
container of blood or blood component in order to transfuse to a 
patient. This technique might be used when transfusing neonates or 
under other medically necessitated circumstances. In this case, the 
blood or blood component from which the aspirate is taken must have 
affixed to it a label containing the required machine-readable 
information. This would be consistent with the pre-existing requirement 
at Sec.  606.121(c)(8)(iii) that requires specific statements if a 
product is intended for transfusion.
    We also invite comment on how the proposed rule might affect 
hospitals where patients receive blood or blood components. 
Specifically, we want to hear how the proposal might affect a 
hospital's decision to purchase a machine reader (e.g., scanner) that 
properly identifies the intended recipient of the blood or blood 
component. To prevent medical errors, this machine reader would need to 
be compatible with the machine readable information encoded on the 
blood or blood component label, yet a hospital's purchasing decision 
might also be influenced by the bar codes appearing

[[Page 12514]]

on drugs and OTC drugs that are dispensed pursuant to an order and 
commonly used in the hospital.
    We intend to make a machine-readable information requirement 
effective for blood and blood components 3 years after we publish a 
final rule in the Federal Register. Changes to existing blood and blood 
component labels would require the submission of an annual report as 
described in 21 CFR 601.12(f)(3).

I. What Bar Code Requirement Would Apply to Biological Products? 
(Proposed Sec.  610.67)

    The proposal would create a new Sec.  610.67 that describes a new 
labeling requirement for biological products (other than blood and 
blood products, which would be covered by proposed Sec.  
606.121(c)(13)). Proposed Sec.  610.67 would simply state that 
biological products must be labeled in accordance with the bar code 
requirements at Sec.  201.25. In addition to the separate authority 
provided by section 351(j) of the Public Health Service Act, the 
Federal Food, Drug, and Cosmetic Act also applies to a biological 
product that is regulated under section 351 of the Public Health 
Service Act.
    The proposal would not apply to biological products that are 
regulated as devices for the reasons we stated earlier in section 
II.B.2.d of this document.

III. Legal Authority

    We believe we have the authority to impose a bar coding requirement 
for the efficient enforcement of various sections of the act. These 
include sections 201(n), 201(p), 501, 502, 503, 505, and 701(a)) (21 
U.S.C. 321(n), 321(p), 351, 352, 353, 355, and 371(a)) of the act, and 
sections 351 and 361 of the Public Health Services Act.
    A bar coding requirement for drugs would permit the efficient 
enforcement of the misbranding provisions in section 502(a) and (f) of 
the act, as well as the safety and effectiveness provisions of sections 
201(p) and 505 of the act. Bar coding is expected to significantly 
advance: (1) The provision of adequate directions for use to persons 
prescribing, dispensing, and administering the drug; (2) the provision 
of adequate warnings against use by patients where a drug's use may be 
dangerous to health; and (3) the prevention of unsafe use of 
prescription drugs.
    Section 502(a) of the act prohibits false or misleading labeling of 
drugs. This prohibition includes, under section 201(n) of the act, 
failure to reveal material facts relating to potential consequences 
under customary conditions of use. Information in a database that could 
be readily accessed through the use of a bar code, such as the drug 
strength, dosage form, route of administration, and active ingredient 
and drug interactions is material with respect to consequences which 
might result from use of the drug under such conditions of use. Because 
all the drugs (prescription drugs and the subset of covered OTC drugs) 
covered by this proposal may be used in the hospital setting, such use 
in hospitals can be considered the ``conditions of use as are customary 
or usual.'' As is made clear in section I of this document, bar coding 
can be expected to reduce the incidence of the following types of 
medication errors:
    [sbull] Administering the wrong dose to a patient;
    [sbull] Administering a drug to a patient who is known to be 
allergic;
    [sbull] Administering the wrong drug to a patient or administering 
a drug to the wrong patient;
    [sbull] Administering the drug incorrectly;
    [sbull] Administering the drug at the wrong time; and
    [sbull] Missing or duplicating doses.
    Because information accessed through use of the bar code will 
reveal material facts relating to potential consequences under 
customary conditions of use, the bar code requirements are justified 
under section 502(a) of the act.
    Section 502(f) of the act requires drug labeling to have adequate 
directions for use, adequate warnings against use by patients where its 
use may be dangerous to health, as well as adequate warnings against 
unsafe dosage or methods or duration of administration, in such manner 
and form, as necessary to protect users. The bar code would make it 
easier for the person administering the drug to have full access to all 
of the drug's labeling information, including directions for use, 
warnings and contraindications. Moreover, because the bar code's 
information would go to the computer where it could be compared against 
the patient's drug regimen and medical record, the person administering 
the drug will be able to determine whether the right patient is 
receiving the right drug (including the right dose of that drug in the 
right route of administration) at the right time. The person 
administering the drug will also be able to avoid giving products to a 
patient who might be allergic to, or otherwise unable to take, a 
particular drug. Because the bar code will facilitate access to 
information including adequate directions for use and adequate 
warnings, the bar code requirements are justified under section 502(f) 
of the act.
    In addition to the misbranding provisions, the premarket approval 
provisions of the act authorize FDA to require that prescription drug 
labeling provide the practitioner with adequate information to permit 
safe and effective use of the drug product. Under section 505 of the 
act, we will approve a new drug application (NDA) only if the drug is 
shown to be safe and effective for its intended use under the 
conditions set forth in the drug's labeling. Bar coding will ensure the 
safe and effective use of drugs by reducing the number of medication 
errors in hospitals and other health care settings. Such coding would 
allow health care professionals to use bar code scanning equipment to 
verify that the right drug (in the right dose and right route of 
administration) is given to the right patient at the right time.
    Section 505(b)(1)(D) of the act requires a new drug application to 
contain a full description of the methods used in, and the facilities 
and controls used for, the manufacture, processing, and packing of such 
drug. The same requirement exists for abbreviated new drug applications 
(see section 505(j)(2)(A)(vi) of the act) and for biological products 
(see section 351(a)(2)(B)(i)(II) of the Public Health Service Act). 
Information in the bar code would reflect the facilities and controls 
used to manufacture the product. As described in section II.C.1 of this 
document, the NDC number would identify the manufacturer, product, and 
package.
    A bar coding requirement also would permit the efficient 
enforcement of the adulteration provisions of the act. A regulation 
requiring the bar coding of products should avert unintentional mix up 
and mislabeling of drugs during labeling, packaging, relabeling, and 
repackaging. A bar coding requirement therefore prevents adulteration 
under section 501(a)(2)(B) of the act. It is a manufacturing method or 
control necessary to ensure that a drug product has the identity and 
strength its labeling represents it to have, and meets the quality and 
purity characteristics which the drug purports or is represented to 
possess.
    Requiring that the bar code be surrounded by sufficient blank 
space, and remain intact under normal conditions of use, would also 
further the efficient enforcement of section 502(c) of the act. Section 
502(c) of the act provides that a drug product is misbranded if: Any 
word, statement, or other information required by or under authority of 
this Act to appear on the label or labeling is not prominently placed 
thereon with such conspicuousness (as compared with

[[Page 12515]]

other labeling) and in such terms as to render it likely to be read and 
understood by the ordinary individual under customary conditions of 
purchase and use. The requirement that the bar code be surrounded by 
sufficient blank space and remain intact under normal conditions of use 
would help ensure that the bar code can be read easily and accurately 
so that its safety benefits may be realized.
    Because biological products, including blood, are also prescription 
drug products, the sections of the act discussed elsewhere in this 
legal authority section provide ample legal authority for promulgating 
a regulation requiring bar coding for such biological products. There 
is, however, additional legal authority for the rule's requirements as 
to biological products. Section 351 of the Public Health Service Act 
authorizes the imposition of restrictions through regulations 
``designed to insure the continued safety, purity, and potency'' 
(including effectiveness) of the products. Biological product licenses 
are to be ``issued, suspended, and revoked as prescribed by 
regulations'' (42 U.S.C. 262(d)(1); see Sec. Sec.  601.4 through 
601.6). The bar code requirement for biological drugs, and the machine-
readable information requirement for blood and blood products, is 
designed to insure the continued safe and effective use of licensed 
biological products. Therefore, if this rule were finalized, we may 
refuse to approve biologics license applications (BLAs), or may revoke 
already approved licenses, for biological drug products that do not 
have such codes.
    Additionally, section 361 of the Public Health Service Act 
authorizes regulations necessary to prevent the introduction, 
transmission, or spread of communicable diseases. With specific regard 
to blood and blood products, the requirement for machine readable 
information will aid in the recall, quarantine and retrieval of units 
that are at risk of spreading communicable diseases.
    After the effective date of any final rule, if a product required 
by the final rule to bear a bar code does not have such a bar code, the 
product may be considered adulterated or misbranded under the act and 
would be subject to regulatory action. Our enforcement actions under 
the act include seizure, injunction, and prosecution, and violation may 
result in withdrawal of an NDA or BLA.

IV. Environmental Impact

    We have determined under 21 CFR 25.30(h) and 25.30(k) that this 
action is of a type that does not individually or cumulatively have a 
significant effect on the human environment. Therefore, neither an 
environmental assessment nor an environmental impact statement is 
required.

V. Paperwork Reduction Act of 1995

    This proposed rule contains information collection requirements 
that are subject to public comment and review by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
(44 U.S.C. 3501-3520). We describe the provisions in this section of 
the document with an estimate of the annual reporting burden. Our 
estimate includes the time for reviewing instructions, searching 
existing data sources, gathering and maintaining the data needed, and 
completing and reviewing each collection of information.
    We invite comments on: (1) Whether the collection of information is 
necessary for the proper performance of FDA's functions, including 
whether the information will have practical utility; (2) the accuracy 
of FDA's estimate of the burden of the proposed collection of 
information, including the validity of the methodology and assumptions 
used; (3) ways to enhance the quality, utility, and clarity of the 
information to be collected; and (4) ways to minimize the burden of the 
collection of information on respondents, including through the use of 
automated collection techniques, when appropriate, and other forms of 
information technology.
    Title: Bar Code Label Requirement for Human Drug Products and 
Blood.
    Description: We are proposing a new rule that would require human 
drug product and biological product labels to have bar codes. The 
proposed rule would require bar codes on human prescription drug 
products and OTC drug products that are dispensed pursuant to an order 
and commonly used in hospitals and would require machine-readable 
information on blood and blood components. For human prescription drug 
products and OTC drug products that are dispensed pursuant to an order 
and commonly used in hospitals, the bar code would contain the National 
Drug Code for the product. For blood and blood components, the proposed 
rule would specify the minimum contents of the machine-readable 
information approved by the Director of the Center for Biologics 
Evaluation and Research as blood centers have generally agreed upon the 
information to be encoded on the label. The proposed rule would help 
reduce the number of medication errors in hospitals and other health 
care settings by allowing health care professionals to use bar code 
scanning equipment to verify that the right drug (in the right dose and 
right route of administration) is being given to the right patient at 
the right time.
    Because the Center for Drug Evaluation and Research would have bar 
code information for drugs subject to a new drug application or 
abbreviated new drug application to be reported through an annual 
report, this proposed rule affects the reporting burden associated with 
Sec.  314.81(b)(2)(iii) (21 CFR 314.81(b)(2)(iii)). Section 
314.81(b)(2)(iii) requires the submission of an annual report 
containing a representative sample of package labels and a summary of 
labeling changes (or, if no changes have been made, a statement to that 
effect) since the previous report. Here, the bar code would result in a 
labeling change. We have previously estimated the reporting burden for 
submitting labels as currently required under Sec.  314.81(b)(2)(iii), 
and OMB has approved the collection of information until March 31, 2005 
under OMB control number 0910-0001. We are not re-estimating these 
approved burdens in this rulemaking; we are only estimating the 
additional reporting burdens associated with the submission of label 
changes under Sec.  314.81(b)(2)(iii).
    Minor label changes for blood and blood products may be reported as 
part of an annual report, as described in 21 CFR 601.12(f)(3), and we 
would consider the machine-readable information on blood and blood 
product labels to be a minor change. We have previously estimated the 
reporting burden for submitting labels as currently required under 
Sec.  601.12(f)(3), and OMB has approved the collection of information 
until August 31, 2005 under OMB control number 0910-3338. We are not 
re-estimating these approved burdens in this rulemaking; we are only 
estimating the additional reporting burdens associated with the 
submission of label changes under Sec.  601.12(f)(3).
    Description of Respondents: Persons who manufacture, repackage, or 
relabel prescription drug products or OTC drugs that are dispensed 
pursuant to an order and commonly used in hospitals, and blood 
establishments.
    We estimate the burden of this collection of information as 
follows:

[[Page 12516]]



                                 Table 1.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
                    No. of        Frequency of      Total Annual
21 CFR Section    Respondents      Responses          Responses      Hours per Response        Total Hours
----------------------------------------------------------------------------------------------------------------
Sec.   201.25,      1,447               31.1                45,000             24 hrs.        1,080,000
 Sec.   610.67
Sec.                1,447                5.9                 8,576           10.5 min.            1,497
 314.81(b)(2)(
 iii)
Sec.                  211                1                     211              1 min.                3.5
 601.12(f)(3)
Sec.                  981           42,507.7          41.7 million              1 min.          695,000
 606.121(c)(13
 )
Total           ..............  ...............  ..................  ..................       1,776,590.5
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    Our estimates are based on the following assumptions.
    [sbull] For prescription drugs (including prescription biologics 
and vaccines) and OTC drugs subject to the bar code requirement, 
information from our own records indicates that there are 1,447 
establishments that would be affected by a bar code requirement, and 
there are approximately 89,800 separate, identifiable product packages 
subject to this proposed rule. We expect that half of the packages 
(45,000) would need redesigned labels to comply with a bar code 
requirement because they do not currently use coded NDC numbers. This 
means that the annual frequency of reports, under proposed Sec.  201.25 
(and proposed Sec.  610.67 for biological products not regulated as 
devices), would be 31.1 (45,000 package labels requiring a bar code/
1,447 establishments = 31.09 packages per establishment, which we have 
rounded up to 31.1). Consultations with industry sources suggest that 
the number of hours per response to redesign a package label to include 
bar coded information to comply with this regulation is approximately 
24 hours. Therefore, the total burden hours for proposed Sec.  201.25 
and Sec.  610.67 would be 1,080,000 hours (45,000 packages x 24 hours 
per package label = 1,080,000 hours).
    [sbull] For prescription drugs whose label changes would be 
reported in an annual report under Sec.  314.81 or under Sec.  
601.12(f)(3) for biological products), there are approximately 1,447 
registered establishments that would be reporting. Information on 
listed drugs indicates there are 89,800 separate, identifiable product 
packages that will comply with the proposed bar code requirement. These 
packages account for 8,576 separate and distinct products (each product 
is marketed in an average of 10.47 packaging variations). This means 
that the annual frequency of reports would be 5.9 (8,576 products 
subject to annual reports/1,453 registered establishments = 5.92 
products per registered establishment, which we have rounded down to 
5.9). Section 314.81(b)(2)(iii) requires firms to submit an annual 
report that includes a summary of any changes in labeling since the 
last annual report. Similarly, Sec.  601.12(f)(3)(I)(A) requires 
manufacturers of biologics to include in their annual reports editorial 
or similar minor labeling changes. We expect that the addition of a bar 
code to a label would necessitate a simple statement in the annual 
report declaring that the bar code has been added, so we have assigned 
an estimate of one minute for such statements per label. Each product's 
annual report would include labels for all packaging variations. Thus, 
the total reporting burden would be 1,496.67 hours ((8,576 reports x 
10.47 labels (or one label per packaging variation) per report x 1 
minute per report)/60 minutes per hour = 1,496.67 hours), which we have 
rounded up to 1,497 hours.
    [sbull] For minor labeling changes for blood and blood components 
included in an annual report under Sec.  601.12(f)(3)(i)(A), FDA's 
database indicates there are 211 licensed blood and blood component 
manufacturers. We expect that the addition of machine-readable 
information to the label of blood and blood components would 
necessitate a simple statement in the annual report declaring that the 
machine-readable information has been added, so we have assigned an 
estimate of one minute for such statements. Thus, the total reporting 
burden would be 3.5 hours ((211 reports x 1 minute per report)/60 
minutes per hour = 3.516 hours), which we have rounded down to 3.5 
hours.
    [sbull] For the requirement in proposed Sec.  601.121(c)(13) to 
include machine-readable information on blood and blood components, 
FDA's registration database indicates there are 981 blood and plasma 
establishments. The American Association of Blood Banks estimates that 
approximately 13.9 million blood donations are collected annually. We 
estimate that each blood donation yields approximately three blood 
components. This means that the frequency of responses is approximately 
41.7 million occurrences (13.9 million blood donations x three blood 
components per donation) divided by 981 establishments or 42,507.645 
occurrences per establishment, which we have rounded up to 42,507.7. We 
estimate that it takes 1 minute to apply a machine-readable code 
manually; if a blood collection facility uses an on-demand printer, the 
time would range between 15 to 30 seconds. For purposes of this 
estimate, we adopt the larger time estimate of 1 minute per machine-
readable information for blood, thus resulting in an annual reporting 
burden of 695,000 hours ((41.7 million reports x one minute per report) 
/60 minutes per hour = 695,000 hours). However, we reiterate that 
facilities using on-demand printers would face lower burdens. In 
addition, blood collection centers are currently allowed and encouraged 
to apply machine readable information to collections. This burden 
estimate accounts for requiring an activity that is currently voluntary 
and does not reflect an additional activity.
    In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C. 
3507(d)), we have submitted the information collection requirements of 
this rule to OMB for review. Interested persons are requested to fax 
comments regarding information collection by April 14, 2003, to the 
Office of Information and Regulatory Affairs, OMB (see ADDRESSES).

VI. Executive Order 13132: Federalism

    We have analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. We have determined that 
the rule does not contain policies that have substantial direct effects 
on the States, on the relationship between National Government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government. Accordingly, we have concluded that the 
rule does not contain policies that have federalism implications as 
defined in the order and, consequently, a federalism summary impact 
statement is not required.

[[Page 12517]]

VII. Analysis of Impacts

A. Introduction

    We have examined the proposed rule under Executive Order 12866, the 
Regulatory Flexibility Act as amended by the Small Business Regulatory 
Enforcement Fairness Act, the Unfunded Mandates Reform Act, and the 
Congressional Review Act. Executive Order 12866 directs agencies to 
assess all costs and benefits of available regulatory alternatives and, 
when regulation is necessary, to select regulatory approaches that 
maximize net benefits (including potential economic, environmental, 
public health and safety, distributive impacts and equity). Under the 
Regulatory Flexibility Act (as amended by the Small Business Regulatory 
Enforcement Fairness Act), if a regulation has a significant economic 
impact on a substantial number of small entities, we must analyze 
regulatory options that would minimize the impact on small entities. 
Section 202(a) of the Unfunded Mandates Reform Act requires that 
agencies prepare a written statement of anticipated costs and benefits 
before proposing any regulation that may result in expenditure by 
State, local, and tribal governments, or by the private sector of $100 
million in any one year (adjusted annually for inflation). Currently, 
such a statement is required if costs exceed about $110 million for any 
one year. The Congressional Review Act requires that regulations 
determined to be major must be submitted to Congress before taking 
effect.
    The proposed rule is consistent with the principles set forth in 
Executive Order 12866 and the three statutes. We have identified the 
proposed rule as an economically significant regulatory action, as 
defined in Executive Order 12866. We believe the proposed rule is 
unlikely to have a significant impact on a substantial number of small 
entities. The expected cost of this proposed rule is greater than $110 
million in a single year and therefore is considered a major regulatory 
action as defined by the Unfunded Mandates Reform Act. The Office of 
Information and Regulatory Affairs (OIRA) in the Office of Management 
and Budget (OMB) has determined this proposed rule to be major under 
the Congressional Review Act.
    We contracted with the Eastern Research Group, Inc. (ERG), to 
collect data, interview industry experts, and analyze the costs and 
benefits of the proposed rule. The detailed analyses and references in 
support of the impacts summarized in Table 2 are included in the docket 
as Reference 46.

                    Table 2.--Estimated Impacts of the Proposed Rule (in Millions of Dollars)
                                (Over 20-Year Period at 7-Percent Discount Rate)
----------------------------------------------------------------------------------------------------------------
                                     Anticipated                                                  Net Benefits
     Impacts        Regulatory        Hospital          Societal         Potential Hospital      (benefits minus
                       Costs          Costs\1\         Benefits\2\         Efficiencies\3\          costs)\4\
----------------------------------------------------------------------------------------------------------------
Present Value         $53.1            $7,204.3         $41,381.3           $4,783.3-$7,643.0       $34,123.9
Annualized             $5.1              $680.0          $3,906.1               $451.5-$721.5        $3,221.0
----------------------------------------------------------------------------------------------------------------
\1\ Costs due to voluntary accelerated purchase and utilization of bar coding systems.
\2\ Benefits to public health due to avoidance of adverse drug events.
\3\ Potential efficiencies in reports, records, inventory, and other hospital activities.
\4\ Net benefits include only public health benefits of increased patient safety.

    Table 2 presents the total expected regulatory costs to 
manufacturers, repackers, relabelers, retail outlets, and FDA. Most of 
these costs will occur during the first several years after 
implementation. Table 2 also shows the estimated opportunity costs of 
the expected accelerated investment in bar coding systems by the health 
care sector. These investment expenditures are necessary to achieve the 
societal benefits expected from the proposed rule. Table 2 also shows 
our estimated range of possible efficiencies in hospital activities 
associated with accelerated adoption of technology. Both anticipated 
hospital costs and societal benefits would occur after hospitals 
purchase and install the necessary equipment to take advantage of bar 
codes. The net benefit figure is the societal benefit minus the induced 
expenditures minus the regulatory costs. This estimate, however, 
accounts for neither potential hospital efficiencies, nor income 
transfers to hospitals following fewer awards for medical malpractice.

B. Objective of the Proposed Rule

    The objective of the proposed rule is to enable the health care 
sector to utilize technological solutions to reduce preventable adverse 
drug events (ADEs)\2\ associated with medication errors\3\ in 
hospitals.\4\
---------------------------------------------------------------------------

    \2\ For this analysis, an adverse drug event (ADE) is an injury 
from a medicine (or a lack of an intended medicine). (source: 
American Society of Hospital Pharmacists, 1998)
    \3\ For this analysis, a medication error is a preventable event 
that may cause or lead to inappropriate medication use or patient 
harm while the medication is in the control of the health care 
professional, patient, or consumer. (source: NCCMERP, 2002)
    \4\ For this analysis, a hospital is a facility that provides 
medical, diagnostic, and treatment services that include physician, 
nursing, and other health services to inpatients and the specialized 
accommodation services required by inpatients. (source: NAICS, 2002)
---------------------------------------------------------------------------

C. Estimate of Risk/Risk Assessment

    In 1999, the Institute of Medicine (IOM) issued a report that drew 
public attention to the number of deaths that occur each year in the 
United States from preventable medication errors in hospitals. A 
significant proportion of the reported deaths, as well as the 
additional illnesses and morbidities, were associated with errors 
involving FDA-regulated products, especially medications. This section 
briefly describes the agency's efforts to estimate the current number 
of preventable ADEs.
    The public health literature includes many attempts to determine 
the rate of preventable ADEs in United States hospitals, although these 
studies typically employed varying methodologies and definitions. Our 
methodology begins by multiplying estimated hospital admissions by 
reported rates of ADEs per admission. We combined the resulting number 
of ADEs per hospital per year with the reported ratio of preventable to 
total ADEs to estimate the number of preventable ADEs per hospital per 
year. We first developed these calculations for various hospital size 
classes and then aggregated the data to present national estimates. We 
relied on published literature to derive ADE rates for each major stage 
of the medication process in hospitals.
    ERG identified four comparable published studies that reported 
rates of ADEs per hospital admissions (Bates et al., 1995, Classen et 
al., 1997, Jha et al.,

[[Page 12518]]

1998, and Senst et al., 2001). The reported incidence rates of hospital 
admissions with ADEs ranged from 2.4 percent to 6.5 percent with a mean 
rate of 4.3 percent. According to AHRQ, there were 29.1 million 
nonobstetric hospital admissions during 2000. We multiplied these 
admissions by 0.043 and found that approximately 1.25 million ADEs 
occur annually in United States hospitals. The same four studies 
reported that between 15 percent and 49 percent of all ADEs are 
preventable. We used the mean of these studies to estimate that about 
372,400 (30 percent) of these ADEs were preventable. Based on published 
reports (Bates et al., 1998, and Leape et al., 1998), we also estimated 
that 1,046,000 potential ADEs\5\ are either intercepted before reaching 
the patient or do not cause an injury. According to projected increases 
in hospital expenditures and population demographics that imply future 
increases in hospital admissions, the annual number of ADEs could 
triple within 20 years.
---------------------------------------------------------------------------

    \5\ A potential ADE is a medication error that could have caused 
an ADE, but did not. Potential ADEs include medication errors that 
were intercepted before reaching the patient. Potential ADEs include 
any errors that do not involve patients.
---------------------------------------------------------------------------

    ERG searched the public health literature to identify stages in the 
hospital medication process in which errors occur and concluded that 
the medication stages of prescribing, transcribing, dispensing, and 
administration provide a useful analytic structure. The most common 
reported ADE symptom was cardiac arrhythmia followed by itching and/or 
nausea. Relatively few fatalities have been documented as preventable 
ADEs, but several published studies conclude that as many as 2.8 
percent of all preventable ADEs probably result in fatalities. Another 
study has asserted that as many as 2.7 percent of all ``negligent'' (as 
defined in the study) ADEs have resulted in permanent disability. We 
used these estimates in our analysis.

D. The Proposed Rule

    We propose to require machine-readable information on all 
prescription drug and biological products (including vaccines), all OTC 
drug products dispensed pursuant to an order and commonly used in 
hospitals, and all human blood products. This information would include 
the NDC number identifying the dosage, strength, nature, and form of 
each administered product and would be portrayed in a standardized 
linear bar code\6\ and include product-specific and package-specific 
NDC numbers. We would maintain a database of all unique NDC numbers and 
ensure these data are available for use in commercial computerized 
systems that can provide bedside bar code identification. The bar code 
requirement would, if finalized, be effective within 3 years after we 
have published a final rule.
---------------------------------------------------------------------------

    \6\ A bar code is a graphic representation, in the form of bars 
and spaces of varying width, of numeric or alphanumeric data.
---------------------------------------------------------------------------

    We are proposing this regulation because private markets have 
failed to establish the standardized bar codes that are needed to 
motivate hospitals to adopt an important health-saving technology. In 
particular, we believe that the private market's failure to develop 
standardized bar codes has impeded the growth of the technological 
investment necessary to reduce the number of ADEs in the nation's 
hospitals. We find that a regulatory intervention to establish a 
standardized system of bar codes is needed to address this market 
failure.
    The proposed rule would increase costs to the manufacturers, 
marketers, and packagers of the affected products by requiring changes 
in manufacturing, packaging, and labeling processes. It would also 
increase costs to some hospitals by requiring a change in some bar code 
readers associated with these products. The proposed rule would also 
require FDA resources to ensure industry compliance with the bar coding 
requirement and additional resources to maintain a computerized 
database of NDC numbers. Once bar codes are standardized, the proposed 
rule would enable hospitals to take advantage of the coded information 
that would permit hospitals to reduce ADEs, while achieving other 
operational cost efficiencies. The proposed rule would also enable 
other sectors to use machine-readable technology in ways that would 
benefit public health (for example, accessing up to date labeling 
information from home computers).

E. Description of Affected Sectors

1. Current Machine-Readable Technologies
    Before developing the proposed rule, we contracted with ERG to 
examine the current machine-readable technologies available for use by 
the health care sector and report on trends. The resulting report is 
included in the docket (Ref. 47) and summarized here.
    Bar coding is currently the most widely used machine-readable 
technology and is also the technology most likely to see increased 
acceptance in the near future. Healthcare companies have sponsored two 
organizations that have each developed different bar code 
symbologies;\7\ the Uniform Code Council's Universal Product Code (UPC) 
and the Health Industry Bar Code Council's Health Industry Bar Code 
(HIBCC). UPC codes are more widely used in retail stores while HIBCC is 
specially designed to safeguard against errors. However, although the 
HIBCC code has been more effectively used by medical device 
manufacturers, it has not won wide acceptance within the pharmaceutical 
markets. Within these symbologies, the groups have defined acceptable 
linear (or one-dimensional) codes, two-dimensional codes, and composite 
codes (a combination of one- and two-dimensional symbology). The 
advantage of two-dimensional and composite codes is that they can 
include additional information in the same area. Potential 
disadvantages of two-dimensional and composite symbologies are the 
higher costs for readers and scanners and the additional risk of 
uncertain data recovery by misinterpreting coded information.
---------------------------------------------------------------------------

    \7\ A symbology refers to a distinct technological, machine-
readable language.
---------------------------------------------------------------------------

    While these organizations' bar codes are widely used, their use for 
the prevention of ADEs remains limited. Most pharmaceutical and OTC 
manufacturers use bar codes to move shipping cases through their 
distribution chain, but relatively few pharmaceuticals are sold with 
the specific bar codes that would be required by this proposed rule. 
Some hospitals use computer-controlled technology to add their own bar 
codes to incoming products.
    Bar code systems require printers, scanners, and software to ensure 
that correct information is communicated. According to discussions with 
consultants, pharmaceutical manufacturers prefer to label products as 
late as possible in the manufacturing process in order to maximize 
their flexibility. Printing technology advancements have allowed more 
printing options to be available. Manufacturers currently use contract 
label printers or packagers along with in-house operations. Contract 
printers are commonly used for preprinted labels that do not carry 
customized data. Currently, ink jet and thermal printers may be 
appropriate for production line printing of bar codes, although ink jet 
printers may cause difficulties in media compatibility, print speed, 
and resolution. Water-based inks can streak or blur, but nonwater 
soluble inks produce a shine that reflects to the scanner and affect 
how the bar code is read. Laser printers are subject to toner

[[Page 12519]]

flaking, which makes them unreliable for long-term bar code printing. 
Production line speeds may also create problems for bar code resolution 
levels.
    The complexities of bar code scanners have evolved as the codes 
have become more data intensive. Most scanners in current use are 
laser-based systems designed to read linear bar codes. In health care 
settings, scanners are routinely programmed to discriminate among the 
symbologies they are likely to encounter. Some laser scanners can also 
read composite or two-dimensional codes, if properly programmed. These 
scanners are more costly, and some consultants have cautioned that 
multiple data systems may introduce potential misreading at hospital 
bedsides. Moreover, in certain situations, health care scanners may not 
need to use all of the available information. For example, scanners at 
bedside point of care may only need to capture limited identifying 
information while the central dispensing pharmacies may require full 
database capabilities. At this time, the scanning industry is confident 
that linear standards\8\ will be readily accessible, whereas other 
standards may require additional market research. We believe that 
scanners will work in conjunction with hand-held personal digital 
assistants (PDAs) in wards due to their portability and multi-
functional characteristics.
---------------------------------------------------------------------------

    \8\ A standard refers to a general description of a system of 
machine-readable languages.
---------------------------------------------------------------------------

2. Manufacturers and Packagers of Affected Products
    Discussions with staff at two large Veteran Health Administration 
Comprehensive Mail Order Pharmacies indicate that the large majority of 
exterior pharmaceutical packages include the NDC number in a bar code. 
The proposed rule, however, would require this bar coded information on 
both exterior and interior packaging. In addition, some prescription 
and OTC drug products are sold in blister packs, where individual pills 
or capsules are enclosed in a bubble. Prescription products are often 
repackaged into blister cards for more convenient use in hospitals. 
While some blister cards may now be labeled with bar codes for 
specified concerns, many are not. OTC drug products rarely include bar 
coded information on blisters. Moreover, many bar coded exterior 
packages cannot be read by hospital or retail scanners, because 
manufacturers use bar codes for sales promotions and other special 
offers that have separate and distinct NDC numbers that do not appear 
in all customer databases.
    There are currently approximately 1,218 establishments in the 
Pharmaceutical and Biologic Preparation industries (NAICS 325412 and 
325414). Based on the size distribution of industry establishments, we 
estimate a total of approximately 3,728 in-house packaging production 
lines. In addition, an estimated 229 establishments in the Packaging 
and Labeling Services industry (NAICS 561910) are dedicated to serving 
the pharmaceutical industry, accounting for an additional 501 packaging 
lines. Overall, we estimate that 4,229 packaging lines are used in 
1,447 establishments for these products.
    In addition, we estimate there are 981 blood collection centers in 
the United States (NAICS 621991). Each of these collection centers acts 
as a separate packaging line. Consultants have estimated that about 25 
percent of these blood collection centers are included in published 
industry counts. We added blood collection centers to the industry 
packaging lines for a total of 4,995 affected packaging lines in 2,428 
separate establishments.
    The number of separate trade and generic named products has 
increased by over 500 percent since 1990, and now encompasses about 
17,000 names. Each of these named products may be marketed in varying 
strengths or dosage forms. Overall, we estimate there are 78,000 
separate prescription unit-of-sale packages, 98,000 OTC drug packages, 
and 2,000 blood/vaccine packages. Over time, the number of distinct 
packaging units is expected to continue to increase. The OTC drug 
industry has suggested that fewer than 10 percent of OTC packages 
(9,800 packages) are commonly used in hospital settings and would be 
subject to the proposed rule. For example, OTC analgesics that may be 
dispensed to a patient pursuant to an order would be subject to the 
proposed rule, but mouth rinses or toothpastes that may be provided 
would not. We are collecting data to confirm the proportion of affected 
OTC drug products. The Consumer Healthcare Products Association (CHPA) 
estimated that as many as 10 percent of their members' products were 
regularly dispensed from hospital pharmacies or packaged specifically 
for sale to hospitals. Other responses include a report from a hospital 
that only 200 OTC drug products are routinely dispensed. For purposes 
of this analysis, we have assumed that 10 percent of all OTC drug 
products would be required to provide bar coded information. We are 
trying to collect better information for these products. Overall, 
89,800 separate unit-of-sale packages are expected to be subject to the 
proposed rule.
    OTC drug manufacturers frequently redesign labels. Based on 
discussions with manufacturers, we believe that the majority of OTC 
labels are redesigned within a 6-year cycle for marketing reasons. Many 
products have redesigned labels every 2 or 3 years. Prescription drug 
product labels may be redesigned less frequently, but there is evidence 
that numerous labeling changes occur. While marketing of prescription 
products may not be as sensitive to labeling graphics and package 
design as OTC products, there are many other reasons why manufacturers 
change their labels. Although we examined NDA files and found that 
changes to prescription product labels occur an average of more than 
once per year, for this analysis we have nevertheless assumed that the 
proposed rule would require significant involuntary actions by the 
affected industry.
3. Retail Outlets
    Retail pharmacies currently have the capacity to read linear 
standardized bar codes at their in-house scanners. However, if we had 
selected an alternative to the proposed rule that would have required 
reduced space symbology (RSS), the current stock of scanners may have 
required upgrades or replacement. These upgrades would not have been 
directly mandated by the alternative, but would have been necessary for 
these entities to continue with bar coded activity. The retail sector 
currently relies on UPC or other symbologies, and a single standard 
would not require scanner replacements or upgrades. Only OTC drug 
products dispensed pursuant to an order and commonly used in hospitals 
would be affected by the proposed rule. Although small vials or bottles 
may require specific RSS symbology, these items are available to 
consumers in larger packages that accommodate current standards for 
retail outlets. According to the National Association of Chain Drug 
Stores, there are 55,000 community and chain pharmacies (NAICS 446110), 
and pharmacies in supermarkets and mass merchandisers (NAICS 445110) 
that utilize over 515,000 scanners. The expected useful life of a 
retail scanner is 5 years. The proposed rule is not expected to impact 
this sector, but we have considered alternatives that would affect 
retail outlets.
4. Hospitals
    The proposed rule would not require hospitals to introduce the new 
automated technologies, but the development of consistent bar codes on

[[Page 12520]]

pharmaceutical and blood products would greatly encourage hospitals to 
implement bar code based systems to reduce ADEs associated with 
medication errors. Moreover, unit-dose blister packs and other vials 
and small bottles might necessitate the use of RSS symbology. In order 
to scan these products properly, hospitals that currently have 
installed bar code readers may need to upgrade or replace some 
scanners. According to the most recent census, there are 6,591 
hospitals in the United States (NAICS 622) with a total of over 1.25 
million beds. Estimates of personnel in these hospitals include 97,500 
pharmacists, 75,500 pharmacy assistants, and almost 1.2 million nurses. 
Overall, a nurse is responsible for 4.5 beds per shift. An average 
hospital includes 191 beds and employs approximately 15 pharmacists, 11 
pharmacy assistants, and 182 nurses.
    Hospitals are currently adopting bar code technology to better 
control the entire medication process and improve the delivery of care 
to patients. Virtually all hospital pharmacies use bar code scanners 
for inventory and stock keeping activities, but only approximately one 
percent of all hospitals have installed bedside, point-of-care systems 
that use bar coded information. An additional three percent of 
hospitals use some form of computerized system in the medication 
process, but not all use bar codes. Overall, an estimated two percent 
of all hospitals (131 hospitals) currently use bar codes in everyday 
operations. Even in the absence of the proposed rule, we expect the 
remaining 6,460 hospitals to gradually implement computerized tracking 
systems. Discussions with industry consultants and the American 
Hospital Association (AHA), however, suggest that without 
standardization, it would take 20 years for all hospitals to adopt and 
use systems with bar code readers and utilize in-house overpackaging 
and self-generation of bar code identifiers. ERG discussed with several 
consultants whether 20 years is a realistic horizon for acceptance of 
this technology. While they recognized the uncertainty of future 
projections in this area, these industry experts felt that 20 years was 
a reasonable expectation. We examined the impact of alternative 
acceptance streams as a sensitivity analysis.
    We requested comments on the potential uses of bar coded 
information on drug products at a public meeting held on July 26, 2002. 
These comments indicated that while patient safety reasons were the 
primary goals for installation of scanning systems, there are other 
potential uses. Industry groups and individual hospitals noted that 
installation of scanning systems may lead to more efficient inventory 
control, purchasing and supply utilization, and other potential risk 
management activities. Other groups noted that an integrated 
computerized network would assist billing and laboratory systems as 
well. The AHA stated that bar codes would improve patient care and 
safety, increase workforce productivity and satisfaction, streamline 
payment, billing, and administrative systems, lead to efficient 
management of assets and resources, and meet consumer expectations for 
service and access to information. We believe these comments indicate 
that internal investment decisions concerning the acquisition of 
computerized systems entail additional returns that are in addition to 
ADE avoidance. While some of these returns to hospitals (such as 
reduced liability awards and malpractice liability insurance premiums) 
may be transfers, we believe additional efficiencies are likely.
5. FDA Oversight and Responsibilities
    We would be affected in two areas. For successful bar code use, 
hospitals need access to the unique NDC numbers that identify specific 
active ingredients, packages, dosage forms, and units. We would 
maintain the database containing these unique identifiers and arrange 
access to it for the private sector.
    The second area in which our activities would be impacted by the 
proposed rule is our use of compliance resources. The proposed rule 
would require the affected products to have bar coded information. 
Although the exact impact on our compliance resources is not 
quantified, we recognize that the creation of new regulatory 
requirements would require additional resources to ensure compliance.

F. Regulatory Costs of the Proposed Rule

1. Introduction
    We estimated costs for a 20-year evaluation period to reflect the 
time that hospitals are expected to take to invest in bar code 
technology in the absence of the regulation. This summary describes 
these costs and presents both the present value (PV) and the annualized 
value of the cost streams. We analyzed costs in the affected sectors 
over the entire evaluation period using a seven percent annual discount 
rate. We assume that costs accrue at the beginning of any period. The 
detailed calculations and references that support the following 
analysis are available in Reference 46.
2. Costs to Manufacturers and Packagers of Affected Products
    The pharmaceutical industry would face compliance costs from this 
proposed rule because we would require manufacturers, repackers, 
relabelers, and private label distributors to include NDC numbers in 
bar code format, using linear standardized symbology, down to the unit-
dose level. The proposed rule would require this information within 3 
years of the implementation date of the final regulation. The proposed 
rule would also affect the production processes of the pharmaceutical 
and biological product industries. Although manufacturers appear to 
initiate labeling changes fairly often for internal purposes, the 
proposed rule would necessitate large-scale production line alterations 
that could affect a manufacturer's entire product line.
    a. Prescription Drugs. Based on ERG's analysis, we expect the 
overall investment costs to the prescription drug industry to total 
$26.3 million over the first 3 years of the evaluation period. Most 
costs ($17.6 million) accrue for modifications to unit-dose interior 
packaging to include a unique NDC number in a linear standardized 
format for every product. Exterior packaging modifications that include 
NDC information would cost $4.1 million over the 3-year period. Because 
the capital equipment installed for these packaging modifications would 
require upgrading and replacement after an average 10-years of 
productive life, the industry would invest an additional $3.8 million 
over the 11th, 12th, and 13th evaluation year for this replacement and 
upgrade. In addition, the packaging production process would require 
additional annual operating and maintenance costs reaching $0.4 million 
by the third evaluation year. In total, we estimate that the PV of the 
costs incurred by prescription drug manufacturers, repackers, and 
relabelers to comply with the proposed rule over the 20-year period is 
$30.4 million and the annualized cost is $2.9 million.
    b. Over-the-Counter Drugs. The OTC drug industry has estimated that 
fewer than 10 percent of its products are commonly used in hospitals 
(CHPA, 2002). We are currently collecting data on the size of this 
market share. For this analysis, we assume that 10 percent of all OTC 
drug products would be subject to the regulation and will include bar 
coded NDC numbers. The industry would either assign internal production 
processes that allow labeling differentiation for these products, or 
repackers and relabelers would provide the required labeling. We 
believe that

[[Page 12521]]

the magnitude of packaging changes required to install bar coding 
equipment would result in manufacturer decisions to bar code entire 
product lines rather than incremental, specific products. We estimate 
that the initial investment for OTC drug manufacturers, repackers, and 
relabelers would total $1.7 million over 3 years, with additional 
capital investments of $0.1 million during the 11th evaluation year. 
The estimated annual operating costs to provide bar codes to the 
affected proportion of the OTC drug market are negligible (less than 
$0.05 million by the third year). Overall, the PV of these costs over 
the 20-year evaluation period to the OTC drug industry is $2.1 million 
and the estimated annualized costs are $0.2 million.
    c. Blood and Blood Products. Manufacturers of blood and blood 
products would also be affected by the proposed rule. Although most 
blood and blood product manufacturers have voluntarily applied bar 
coded information, this requirement would add to their costs by 
requiring specific machine-readable information in a consistent format. 
These costs would equal approximately $0.4 million over the first 3 
years, with additional capital expenditures of $0.1 million over the 
following 20-year evaluation period for replacement or upgrade of 
equipment installed in response to the proposed rule. The annual 
operating costs to blood manufacturers of maintaining the equipment 
would be negligible (less than $0.05 million by the third year). We 
estimate that the PV of these compliance costs to blood and blood 
product manufacturers for using machine-readable information in a 
consistent machine-readable format over the 20-year period is $0.7 
million and that the annualized costs are $0.1 million.
    d. Total Cost to Manufacturers, Repackers, and Relabelers. The 
estimated PV of regulatory costs to manufacturers, repackers, and 
relabelers of prescription drug products, OTC drug products, blood, and 
blood products is $33.2 million. The average annualized costs to these 
industries are $3.2 million.
3. Costs to Retailers and Distributors
    We do not expect increased costs to retailers, wholesalers, and 
distributors. Currently installed scanners and readers are able to read 
the linear bar codes described in the proposed rule. However, if we had 
selected an alternative that would have required RSS symbology, 
independent community pharmacies, chain pharmacies, and pharmacies in 
chain merchandisers or supermarkets would have had to upgrade scanners 
in order to take advantage of the proposed standardized information. 
Given the widespread reliance on bar code information in the retail 
sector, the currently installed stock of bar code scanners would not be 
affected by the proposed rule.
4. Costs to Hospitals
    The proposed rule would require NDA numbers in linear bar codes on 
the immediate containers of affected products and machine-readable 
information on blood and blood products. However, because 
manufacturers, repackers, and relabelers are expected to find it 
necessary to use RSS symbology on small unit-dose packages or vials and 
bottles, their scanners and readers must have the ability to capture 
this information in a RSS format. As a result, in order for hospitals 
that have currently installed bar code reading systems to maintain 
current operating practice, their scanners may need to be replaced with 
scanners that are capable of reading RSS symbologies. Replacement of 
these scanners would not be a voluntary hospital investment, but would 
be necessary to maintain current operations.
    These costs are somewhat mitigated for the approximately 2 percent 
of all hospitals (131 hospitals) that currently use bar codes in 
everyday practice by repackaging medications in unit-dose form and 
applying internally printed and generated bar codes. According to 
published reports and discussions with industry experts, ERG estimated 
that such hospitals now incur costs to apply bar codes on nearly 28 
percent of dispensed medications. These 131 hospitals would avoid these 
expenditures under the proposed rule.
    The proposed rule would result in the premature replacement of 
scanners used in hospital pharmacies and treatment wards. ERG has 
estimated that the PV of the incremental initial cost of accelerated 
scanner replacement or upgrade to read RSS symbologies, based on the 
expected remaining useful life of current equipment, is approximately 
$13.7 million. The average annualized costs to hospitals of early 
replacement is $1.3 million.
    According to reports in the literature, it costs as much as $0.03 
per unit-dose to apply a bar code in hospital pharmacies. Avoidance of 
this activity will reduce costs by approximately $0.7 million per year. 
The PV of this cost reduction is $7.6 million.
    Overall, we estimate the PV of regulatory costs, less the cost 
savings to hospitals of the proposed rule, to be $6.1 million, and the 
average annualized costs are $0.6 million.
5. Costs to the Food and Drug Administration
    According to a recent study, the number of available pharmaceutical 
products has increased by 500 percent in 10 years and now totals over 
17,000 separate trade and generic names. With the multitude of dose 
strengths and packages, the total number of unique packaging units is 
now 178,000 separate identifiable products. Of this total, we expect 
89,800 of these packaging units would need bar coded NDC numbers 
because we estimate that only 10 percent of all OTC drug products will 
be affected. Even if the recent growth rate in new products were halved 
(so that the number of available products increased by 500 percent in 
20 years), there would be 449,000 new NDC codes over 20 years, or 
22,500 per year for the evaluation period.
    We expect that the requirement for notification of unique NDC 
numbers would require the development and maintenance of an accessible 
agency database. We have assumed 0.5 hours per notification to 
represent the cost to input and encode a specific NDC number and to 
maintain an accessible data base containing all NDC numbers. This 
implies an annual resource requirement of 11,250 hours, or 
approximately 5.6 full-time equivalents (FTEs). These direct resources 
require supervision, administration, and support. To account for these 
indirect resources, we multiplied direct resources by two, resulting in 
11.2 annual FTEs. The most recent FDA budget documents have used a 
value of approximately $120,000 per FTE. Therefore, we expect the 
annual costs of maintaining a system of unique NDC numbers to be $1.3 
million with a PV of $13.8 million. Although additional regulatory 
requirements, such as requiring readable bar code information on 
product labels, would increase our compliance burden, we have not 
quantified that impact at this time.
6. Total Regulatory Costs
    The estimated PV of the total direct regulatory costs of the 
proposed rule over the 20-year period is $53.1 million, which is 
equivalent to an annualized cost of $5.1 million. Table 3 illustrates 
the timing of the stream of investments and increased annual operating 
and maintenance costs expected from the proposed rule.

[[Page 12522]]



                                Table 3.--Regulatory Costs (in Millions) by Year
----------------------------------------------------------------------------------------------------------------
   Evaluation Year               Investment During Year                    Operating and Maintenance Cost
----------------------------------------------------------------------------------------------------------------
1                                         $23.2                                          $0.9
2                                          $9.5                                          $1.0
3                                          $9.5                                          $1.1
4                                           0                                            $1.1
5                                           0                                            $1.1
6                                           0                                            $1.1
7                                           0                                            $1.1
8                                           0                                            $1.1
9                                           0                                            $1.1
10                                          0                                            $1.1
11                                         $1.4                                          $1.1
12                                         $1.4                                          $1.1
13                                         $1.4                                          $1.1
14                                          0                                            $1.1
15                                          0                                            $1.1
16                                          0                                            $1.1
17                                          0                                            $1.1
18                                          0                                            $1.1
19                                          0                                            $1.1
20                                          0                                            $1.1
----------------------------------------------------------------------------------------------------------------

G. Other Anticipated Expenditures

    We anticipate that the proposed rule would affect all facilities 
defined as hospitals and included in NAICS 622, including general 
medical and surgical hospitals, psychiatric and substance abuse 
hospitals, and other specialty hospitals. We did not quantify impacts 
on nursing and residential care facilities (NAICS 623). The proposed 
rule would impact hospitals by encouraging them to accelerate the 
efficient use of bar code reading technology in hospital bedside point 
of care settings. The expected increased investment would lead to a 
significant reduction in the number of ADEs among hospital patients. We 
assume that investments by the health care sector are made at the 
beginning of each period.
    The hospital sector has long considered the application of bar code 
reading technology for its facilities. According to the AHA, almost 
half of the hospitals in the United States have explored the 
possibility of independently installing this technology. A few (about 
four percent of all hospitals) are currently using some form of 
computerized systems in their medication processes, and half of them 
use bar codes in everyday practice. However, because hospitals 
currently have no standardized bar coded information for all 
therapeutic products, each hospital must generate and internally affix 
bar codes that are only applicable within that specific facility. In 
some cases, hospitals overpackage drug products in order to make 
current scanning systems usable. This extra effort reduces the expected 
efficiency of the bar code reading systems and has been a barrier to 
the general acceptance of readable technology. Standardized universal 
codes would remove this impediment and encourage health care facilities 
to invest and use technology to reduce patient ADEs.
    Hospital facilities will face significant capital investments and 
significant process changes in order to implement bar code reading and 
scanning technology. ERG estimated that the average initial cost to a 
typical hospital for installation of scanners, readers, software, 
initial training etc. is $377,000.\9\ In addition, although there is 
considerable uncertainty, ERG contacted hospital industry executives 
and consultants who agreed that negative productivity effects were 
likely after installation of a bar code reading system. The contacts 
noted that using the scanners could result in reductions in patient 
ward productivity because current scanners and administration 
procedures would have to be revised to accommodate this technology. 
Difficulties could arise, for example, when multiple doses of 
medication are required at the same time for different patients and 
when current administrative practices, such as pre-preparing certain 
medication, could not be accommodated with the bar code reading 
systems. Also, moving the scanner and reader from room to room, not 
adequately reading the bar code on one swipe, and other procedural 
changes might result in operational inefficiencies. It is possible (and 
hopeful) that long-term process changes would moderate or eliminate 
these potential inefficiencies, but our analysis assumes that hospital 
ward productivity levels would fall by three percent annually over the 
evaluation period. The annual opportunity costs of these productivity 
losses, together with the operation and maintenance expenses, amount to 
$320,000 per year for the average sized hospital. Some of these 
expected productivity losses would be mitigated by efficiency gains in 
other hospital procedures and are discussed later.
---------------------------------------------------------------------------

    \9\ Per hospital expenditures and benefits are based on an 
average sized hospital based on bed capacity. The average United 
States hospital has 191 beds (ASHP, 1999).
---------------------------------------------------------------------------

    Despite these costs, interviews with consultants in the field of 
health care technology indicate that hospitals are gradually making 
this commitment. Experts have predicted that in the absence of this 
proposed rule, the hospital sector would likely install bar code 
readable technology within 20 years. Therefore, we believe that, while 
approximately 131 hospitals currently use bar codes in everyday 
operations, the remaining 6,460 hospitals would ultimately invest in 
this technology. The experts have also predicted that if standardized 
bar code information on medications were available to allow scanning 
systems to capture information without requiring in-facility labeling 
systems, many hospitals would make these investments much earlier. For 
example, ERG estimated that if in-hospital pharmacy operations were no 
longer required to repackage and relabel products because of the 
proposed rule, the annual operating and maintenance costs of a bar code 
scanning system would fall from $377,000 to $314.800. Thus, we believe 
that the proposed rule would effectively prompt facilities to 
accelerate these investments.

[[Page 12523]]

    Based on ERG's discussions with industry consultants, we predict 
that the rule could double the rate of hospital investment in this 
technology, thereby achieving the installation of complete systems 
within 10 years. For example, for those hospitals that now expect to 
acquire bar code systems within 10 years, we assume the availability of 
standardized bar codes on medications would accelerate the purchase to 
within 5 years. The cost to the hospital of this accelerated investment 
expenditure would be the opportunity cost of the investment capital for 
5 years (the difference between making the investment in year 5 as 
opposed to year 10) as well as the five additional years of maintenance 
expenses and productivity losses. In addition, industry experts suggest 
that systems of bar code readers and scanners would require software 
and equipment upgrades within 10 years of installation. For the example 
facility, the installed system would require upgrades during the 15th 
project year under the accelerated investment, whereas upgrades would 
not occur until the 20th year in the absence of a regulation. We 
acknowledge that precise estimates of the rate of acceleration of 
technology acceptance are highly uncertain, but industry experts have 
indicated that doubling the rate of technology acceptance is a 
reasonable assumption. Alternative rates of acceptance were analyzed 
and discussed as a sensitivity exercise. We specifically invite public 
comment on the feasibility of this assumption.
    ERG used a Probit function to estimate the annual rate of 
acceptance. This function assumes a normal density distribution for the 
selected period and has been used to describe rates of technology 
acceptance for other new products. Consequently, over the 20-year 
period, FDA estimates the PV of the costs of the accelerated investment 
in bar coding technology by hospitals, including the annual operating 
expenses and productivity losses, to be $7.2 billion. The estimated 
annualized cost is $680.0 million. Table 4 shows the expected annual 
incremental expenditures by year for adopting hospitals under the 
proposed rule.

 Table 4.--Expected Incremental Hospital Expenditures (in Millions) Per
                                 Year\1\
------------------------------------------------------------------------
                                          Incremental Cost to Hospitals
            Evaluation Year                   Adopting Bar Codes\1\
------------------------------------------------------------------------
1                                       $1.2
2                                       $18.9
3                                       $129.8
4                                       $506.9
5                                       $1,187.4
6                                       $1,823.6
7                                       $2,062.7
8                                       $1,934.0
9                                       $1,617.8
10                                      $1,226.8
11                                      $834.3
12                                      $499.2
13                                      $254.5
14                                      $102.4
15                                      ($15.3)\2\
16                                      ($29.4)
17                                      ($34.5)
18                                      ($35.6)
19                                      ($36.0)
20                                      ($36.0)
------------------------------------------------------------------------
\1\ Reflects both negative and direct positive fixed productivity
  changes. Hospitals expected to install bar code systems without the
  proposed rule would not achieve productivity gains associated with
  internal repackaging. Therefore, given the different expected rates of
  technology adoption with the proposed rule, the hospital sector would
  have net productivity gains beginning in the 15th evaluation year.
\2\ Numbers in parentheses indicate cost reductions from baseline.

H. Reduction in Preventable Adverse Drug Events

    The benefits of the proposed rule are focused on the reductions in 
ADEs that would follow the earlier use of bar code reading technology 
and bar coded drug products. We have not quantified all of the other 
institutional benefits of computerized systems and medical informatics, 
but have estimated a potential range of efficiency gains. Any ADEs 
avoided during a period are analyzed as if they occur at the end of the 
period.
    ERG determined that, under current conditions, about 1.25 million 
ADEs occur each year in the United States, of which 372,400 are 
preventable. As discussed above, the proposed rule would substantially 
reduce the number of ADEs caused by errors originating in the 
dispensing and administration of pharmaceutical or blood products in 
hospitals. Studies of medication errors in hospitals that have 
installed bedside bar coding and use internally applied labels show 
error interception rates of from 70 percent to 85 percent (Malcolm et 
al., 1999; Yang et al., 2001; Brown, 2002; Rough, 2002; and Churchill, 
2002). Other industry experts, however, suggest that those published 
interception rates would not be as high if the technology were widely 
dispersed, because of the likelihood of events such as lost wristbands, 
erroneous bar codes, or intentional system bypasses. Therefore, FDA and 
ERG have assumed that bar code system use would produce no reduction in 
prescribing and transcribing errors, but that its use would intercept 
one-half of 45.1 percent of all preventable ADEs that now originate in 
the dispensing and administration stages of the medication process. 
Thus, ERG assumed that if all hospitals adopted bar code systems, the 
number of preventable ADEs would fall by 22.6 percent (45.1 times 0.5), 
which would prevent about 84,200 ADEs per year (372,400 times 0.226). 
This equals a reduction of 12.8 preventable ADEs per year for an 
average hospital. We believe the assumption that bar code readers could 
intercept one-half of both dispensing and administration errors is 
reasonable and conservative, but we specifically invite comment on 
alternative interception rates. This assumption is tested as a 
sensitivity analysis.
    We estimate that the proposed rule, by stimulating earlier hospital 
investment in bar code scanning systems, would produce a corresponding 
increase in the number of avoided ADEs. To project the aggregate number 
of ADEs avoided due to the proposed rule, ERG calculated the number of 
ADEs per hospital that would be avoided by bar coding systems and 
multiplied that number by the additional number of hospitals that would 
use bar coding reading systems during each year of the evaluation 
period. For example, during the 10th evaluation year, our model 
predicts that 3,295 more hospitals would have installed bar code 
reading systems than would have installed them in the absence of the 
rule. The additional hospitals using bar codes would intercept an 
estimated 42,182 errors (12.8 ADEs per hospital times 3,295 hospitals) 
that would otherwise have resulted in ADEs during that year. Over the 
entire evaluation period, this methodology predicts that the 
accelerated investment would avoid over 413,000 ADEs.

I. Value of Avoided ADEs

    FDA and ERG estimated two values of avoided preventable ADEs. 
First, ERG estimated the avoided direct hospital

[[Page 12524]]

costs needed to cover additional tests, longer patient stays, and other 
direct expenses. Based on published studies, the estimated average 
direct cost of an ADE not attributable to prescribing error is $2,257 
(Classen et al., 1997; Bates et al., 1997; and Senst et al., 2001). 
This figure represents a weighted average of direct hospital costs over 
all degrees of ADE severity and does not include patient pain and 
suffering or liability. Second, ERG and FDA estimated the monetized 
value of avoiding decreases in quality-adjusted life years (QALYs) due 
to ADEs. This latter approach attempts to value a patient's subjective 
ADE experience, including inconvenience, pain and suffering, foregone 
earnings, and other out-of-pocket costs.
    ERG examined the literature to determine the probability 
distribution of specific symptoms associated with ADEs. These reported 
symptoms range from rashes and itching to cardiac arrhythmia, renal 
failure, and mortality. The duration of each symptom (additional length 
of hospital stays) ranged from about 0.7 days to 5.5 days (except for 
mortality). ERG then examined reported preference scores from the 
Harvard Center for Risk Analysis' (HCRA) Catalog of Preference Scores, 
which includes a survey of the health economics literature and presents 
published estimates of preferences for defined symptoms. The preference 
scores ranged from 0.95 (for significant but not serious ADEs) to 0.00 
for death. Typical symptoms encountered with serious ADEs had a 
preference score of 0.8, while life-threatening ADEs had a derived 
preference score of 0.6. We note that the reported preference scores 
vary widely by definition and methodology and must be interpreted with 
great caution.
    ERG calculated the change in QALYs expected from an avoided ADE as 
one minus the preference score multiplied by the duration of the event. 
For example, minor drug toxicity (such as a rash) has a derived 
preference score of 0.95 and a reported duration of 2 days (0.005 
years). The change in QALYs expected for such an event is 0.05 (one 
minus 0.95) times 0.005, or 0.0003 QALYs. There are no precise means of 
valuing QALYs. One approach is to derive the value from studies that 
estimate the willingness-to-pay to avoid a statistical death. For 
example, values derived from occupational wage-premiums to accept 
measurable work-place risk suggest a figure of about $5 million per 
statistical death avoided. Apportioning this value over the remaining 
life expectancy of the average workforce member and adjusting for 
future disability implies (at a 7-percent discount rate) a value per 
QALY of about $373,000. Thus, in the example above, the value of the 
decease in QALYs due to minor drug toxicity would be $102.
    ERG examined the literature and found that by combining several 
published accounts, 36.1 percent of the outcomes associated with 
preventable ADEs were deemed significant, 41.7 percent were deemed 
serious, 19.4 percent were deemed life threatening (of which 10 percent 
(or 1.9 percent of the total) result in permanent conditions), and 2.8 
percent resulted in fatalities. Overall, these assumptions indicate 
that the weighted average preference value for each avoided preventable 
ADE is $181,600. We note that this value is very sensitive to the 
number of fatal preventable ADEs.

J. Aggregate Benefit of Avoiding ADEs

    FDA and ERG estimated the benefit of avoiding ADEs due to the use 
of bar code reading systems by multiplying the value of each avoided 
preventable ADE by the expected number of ADEs avoided. As stated 
earlier, an average hospital is expected to have 12.8 fewer preventable 
ADEs each year after installing bar code reading technology. The direct 
cost savings by avoiding treatment ($2,257 per ADE) and the weighted 
preference value ($181,600 per ADE) indicate a societal value of 
$183,900 per average ADE avoided, and a societal benefit of about $2.35 
million per facility per year. We multiplied this derived value per 
hospital by the expected difference in the number of hospitals with 
installed bar code technology under the proposed rule. For example, 
during the 10th evaluation year, an estimated 3,245 additional 
hospitals would have installed bar code reading systems due to the 
proposed rule. We would expect the increased use of these systems to 
result in 42,182 fewer ADEs. The estimated PV of avoiding these ADEs is 
$7.7 billion. The PV of the societal benefits that would result from 
reductions in ADEs over the entire 20- evaluation period is $41.4 
billion. The annualized societal benefit of the reduced number of ADEs 
is $3.9 billion. Table 5 illustrates the expected reduction in ADEs for 
the entire evaluation period.

  Table 5.--Expected Reduction in ADEs by Year with Bar Code (Societal
                          Benefits in Millions)
------------------------------------------------------------------------
  Evaluation                                 Societal Benefit of Avoided
     Year         Additional ADEs Avoided                ADEs
------------------------------------------------------------------------
1                           38                           $7.0
2                          627                         $113.7
3                        4,314                         $781.9
4                       16,845                       $3,053.5
5                       39,462                       $7,153.4
6                       60,634                      $10,991.1
7                       68,646                      $12,443.6
8                       64,486                      $11,689.5
9                       54,144                       $9,814.7
10                      41,344                       $7,494.5
11                      28,493                       $5,164.9
12                      17,523                       $3,176.5
13                       9,510                       $1,724.0
14                       4,531                         $821.4
15                       1,882                         $341.1
16                         678                         $123.0
17                         218                          $39.4
18                          51                           $9.3
19                          13                           $2.3
20                           0                            0
------------------------------------------------------------------------


[[Page 12525]]

K. Other Benefits of Bar Code Technology

    The availability of standardized bar codes would result in 
additional benefits to patients and the health care sector. As bar 
codes are an enabling technology, their adoption for hospital patient 
care would foster their use in other hospital and nonhospital settings. 
With automated systems, hospitals would no longer need to repackage and 
self-generate bar codes. Hospital pharmacies and wards would likewise 
take advantage of the availability of bar coded products to generate 
new production efficiencies for activities such as reporting, record 
keeping, purchasing, and inventory controls. For example, integrated 
scanning systems may allow for electronic versions of daily Medication 
Administration Records (MARs) and pharmacy reconciliation reports. 
According to industry experts, if these activities could be avoided by 
automatically generating the records, an average sized hospital could 
save as many as 592 hours of pharmacist resources and 4,233 hours of 
nursing resources each year. The estimated annual efficiency savings of 
avoiding these opportunity costs equals $167,000. Moreover, ERG and FDA 
believe the identified potential gains from electronic MAR and 
reconciliation reports may account for only between 50 and 80 percent 
of the potential gains in these areas. If so, the total estimated 
annual efficiency gains to an average hospital would range from 
$209,000 to $334,000 from use of bar code scanners in pharmacies and 
patient care wards. These new operation efficiencies would continue 
beyond the evaluation period. If such gains were obtainable, the PV of 
these gains for the sector as a whole would be between $4.8 billion and 
$7.6 billion. The average annualized gains of these potential 
efficiencies are between $451.5 million and $721.5 million.
    The proposed rule could also increase the use of medical 
informatics in locations other than hospitals. Other health care 
facilities, such as physician offices and home health delivery systems, 
would be more likely to adopt bar coding and scanning systems to 
safeguard the use of patient medications and achieve additional 
efficiencies. We could not quantify the value of all of these expected 
additional uses of bar coding, but note that they are realistic and 
practical future uses of the technology.

L. Distributional Effects of Bar Code Technology

    Bar code usage would likely result in distributional transfers 
between sectors of society. For example, bar code use could reduce 
hospital payments due to punitive damage awards from potential 
lawsuits. According to legal data bases (JVR, 2002), there were 
approximately 35,000 personal injury and malpractice claims per year 
between 1995 and 2000 in the health care sector. Approximately half of 
these claims involved pregnancies with the remainder including surgical 
claims, misdiagnosis, and medication errors. If these claims are 
distributed equally by type and sector (inpatient and outpatient), we 
estimate that approximately 600 legal claims per year are potentially 
associated with preventable ADEs in hospitals. This implies that only 
0.2 percent of all preventable ADEs are likely subject to legal claims 
(600 divided by 372,400). The average jury award for damages from 
medication errors was $636,800 in 2000, although only 40 percent of the 
cases were decided for plaintiffs. Estimated pre-trial settlements for 
malpractice claims in 2000 averaged $318,400. We do not have data on 
the proportion of settlements, but have assumed that 80 percent of 
claims are settled before trial. If so, the average likely award per 
preventable ADE is $532. Bar code systems are expected to avoid 12.8 
ADEs per year in an average hospital. This implies an average reduction 
in annual legal awards of $6,800 per hospital and $43.9 million for all 
hospitals. Fewer awards would also result in lower malpractice 
insurance premiums, which would reduce other hospital expenditures. The 
General Accounting Office (GAO, 1995) reported hospital malpractice 
insurance rates ranging between $511 and $7,734 per bed, depending on 
location. Recent reports have suggested that annual premiums have 
increased to approximately $1,250 to $18,800 per bed. Although we were 
unable to quantify average hospital malpractice premiums or precise 
reductions in hospital liability insurance premiums due to the use of 
bar codes, the potential exists for industry savings. While reductions 
in legal settlements or liability insurance premiums represent 
transfers between hospitals, third-party payers, attorneys, and 
patients, and are not opportunity gains or losses, such reductions 
could increase the efficient allocation of resources by sector.
    Bar code systems may also increase hospital revenues by improving 
the ``cost capture rate.'' One published study (Lee et al., 1992) 
reported the cost capture rate (the ratio of billed uncontrolled 
pharmaceuticals to all pharmaceuticals used) increased from 63 percent 
to 97 percent after installation of computerized systems in nursing 
wards. According to the authors, this would imply an increase in 
revenues of approximately $65,000 per year for an average hospital. 
While such accounting improvements are transfers from patients and 
third-party payers to hospitals rather than reduced opportunity costs, 
this practice illustrates the potential use of bar code scanning 
systems in increasing the efficient allocation of resources by sector. 
Other potential transfers may include avoidance of certain billing 
errors or increased timeliness of payment.
    Although reduced lawsuits and liability insurance and increased 
cost capture represent transfers, they are also critical in determining 
whether and at what rate hospitals will adopt bar code technology. 
Combined with the efficiency gains explained previously, these 
transfers should allow hospitals to cover a significant portion of 
their bar code technology investment.

M. Comparison of Costs, Expenditures, and Benefits

    The annualized costs of the proposed rule to the manufacturing, 
packaging, and labeling sectors totals $3.2 million. Hospitals would 
incur an annualized cost of $0.6 million to continue current operating 
practices. FDA resource costs to support the regulation equal an 
estimated $1.3 million per year. Thus, we estimate the annualized 
regulatory cost of the proposed rule to be $5.1 million. In addition, 
we expect the proposed rule to spur earlier investment by hospitals in 
bedside point-of-care systems that read bar coded labels. The 
annualized opportunity cost of this accelerated investment in 
technology is $680.0 million for the entire industry. Table 6 presents, 
by sector, the present value of the estimated regulatory costs, the 
annual costs expected at the end of the 20-year evaluation period, and 
the annualized costs over the entire evaluation period. The estimated 
reduction in hospital operating expenses results from the assumption 
that hospitals could eliminate in-house labeling operations.

[[Page 12526]]



  Table 6.--Costs and Other Expected Expenditures of Proposed Rule (in
Millions of Dollars; 20-Year Evaluation Period; 7-Percent Discount Rate)
------------------------------------------------------------------------
                                              Annual
                      Present Value of   Operating Costs    Annualized
  Industry Sector           Costs           at End of          Costs
                                              Period
------------------------------------------------------------------------
Prescription Drugs           $30.4                 $0.4        $2.9
OTC Drugs                     $2.1                  \1\        $0.2
Blood Products                $0.7                  \1\        $0.1
Sub-Total                    $33.2                 $0.5        $3.2
 Manufacturers
Hospital Regulatory           $6.1           (-$0.7)\2\        $0.6
Sub-Total Private            $39.8              (-$0.2)        $3.8
 Sector Regulatory
 Costs
FDA Oversight                $13.8                 $1.3        $1.3
Total Regulatory             $53.1                 $1.1        $5.1
 Costs
Expected                  $7,204.3         (-$348.8)\2\      $680.0
 Expenditures From
 Healthcare Sector
------------------------------------------------------------------------
\1\ Less than $0.05 million
\2\ Hospital operating costs decrease due to fewer in-house packaging
  and bar coding operations.

    As discussed above, we estimate the annualized public health 
benefit to be $3.9 billion. This estimate includes the societal value 
of the avoided ADEs as well as the reduced hospital stays expected due 
to the earlier use of bar code reading technology. Other indirect 
potential benefits, such as efficient inventory control, patient 
tracking, electronic generation of daily reconciliation and medication 
reports, or other administrative gains were estimated to contribute an 
annualized amount of between $451.5 and $721.5 million in efficiency 
gains to hospitals. The likely distributional effects of revenue 
enhancement, other cost capture measures, or reduced legal costs are 
not completely quantified, but are likely.
    If all costs and expenditures are combined, the annualized outlays 
total $685.1 million. The expected annualized public health benefit of 
over $3.9 billion far outweighs these outlays. Thus, the annual net 
benefits for the entire evaluation period are greater than $3.2 
billion. Moreover, this calculation does not account for the potential 
efficiency gains as described above.

N. Uncertainty and Sensitivity

    We recognize that the expected impacts of the proposed rule are 
based on a large number of uncertain assumptions. We attempted to 
account for this uncertainty by examining the key assumptions in the 
analysis.
1. Voluntary Share of Labeling Costs
    The costs attributable to the proposed rule are the incremental 
costs above what the industry would incur in the normal course of 
business. As briefly discussed earlier, many drug products change 
labels, on average, as often as once a year for marketing or design 
reasons. The ERG estimate, however, assumes that 30 percent of the 
required labeling costs would be attributable to the regulation, due to 
the production process changes that would be required to use bar coding 
equipment. In addition, we believe that market driven label changes are 
not completely comparable to regulation required changes. We reviewed 
the sensitivity of this assumption by examining the impact that would 
occur if no required re-labeling costs were attributable to the 
regulation, 75 percent were attributable to the regulation, or all re-
labeling costs were attributable to the regulation. These scenarios 
altered the current estimate of $3.2 million in annualized costs for 
manufacturers, repackers, and relabelers to a range of from $2.7 
million (if all costs are considered voluntary) to $4.2 million (if no 
additional labeling costs are considered voluntary).
2. Packaging Decisions
    We are sensitive to industry packaging decisions and asked our 
contractor to specifically assess the impact of the proposal on the 
future of unit-dose packaging (e.g. blister packs) trends. The concern 
was whether bar code printing would reduce the use of unit-dose 
packaging because it would add more to its cost than to other formats. 
In general, ERG found that although the overall demand for the product 
is inelastic, the demand for a particular package type is more elastic 
in that it is affected by relative prices to a greater degree. Industry 
contacts, however, noted that this impact is moderated because 
consumers of some OTC drug product are accustomed to blister packs, and 
manufacturers could lose market share if they abandon this format. 
Also, many hospitals require drug purchases to be in unit-dose form.
    ERG concluded that although a bar code requirement would increase 
the relative cost of the unit-dose version of a product, the cost 
increment would not be great enough to significantly impact the market. 
In fact, ERG found that the expected reduction in hospital over-
packaging could increase market demand for unit-dose products despite 
the cost difference. Thus, we expect that the proposed rule would not 
have a significant impact on product packaging choices.
3. Mortality Associated with ADEs
    FDA's contractor estimated that 2.8 percent of preventable ADEs are 
fatal. This was derived by averaging results from several medical 
studies. These studies relied on relatively small samples and varying 
methodologies. Due to the uncertainty attached to this estimate and the 
major impact this assumption has on valuing public health benefits, we 
tested two additional mortality rates: one percent and 0.1 percent. 
These rates reduce the expected value of an avoided ADE from $183,900 
to $91,500 and $46,400, respectively, by changing the probability 
distribution of the expected outcomes of ADEs. The impact on the 
expected annualized benefits of ADE avoidance fall from $3.9 billion to 
$2.0 billion and $1.0 billion respectively. These estimated benefits 
continue to exceed the costs.
4. Value per QALY
    There is no precise measure of value for quality-adjusted life-
year. We have used published estimates of society's implied value of a 
statistical life (VSL) of $5 million derived from wage premiums 
required to attract employment to higher risk occupations. The life 
expectancy of a 35 year-old blue-collar male employee (the typical 
characteristics of the population for most of the wage premium studies) 
was adjusted for expected future bed and nonbed disability. When the 
implied VSL is amortized over the 41.3 years of adjusted life-
expectancy, using a 7-percent discount rate, the resulting value 
($373,000) may suggest a societal willingness-to-pay for a QALY. Cost-

[[Page 12527]]

effectiveness studies in the health economics literature have often 
relied on lower values, such as $100,000, to represent the monetary 
value of a QALY. In addition, the $5 million VSL is based on research 
conducted in the early 1990's and relies on relative risk and relative 
wages. Other typical estimates of the VSL have ranged from as low as $2 
million to as high as $8 million.
    We analyzed the societal benefit of the proposed rule using 
$100,000 as the QALY value for preventing a nonfatal ADE and the low 
VSL estimate of $2 million as the willingness-to-pay to avoid a 
fatality. The willingness-to-pay to avoid an average ADE decreased from 
$183,900 to $70,800 using these parameters. Overall, the estimated 
annualized benefit of the proposed rule fell from $3.9 billion to $1.5 
billion, which would still exceed the estimated annualized costs.
5. Hospital Response Rates
    The expected benefits rely on a faster rate of hospital acceptance 
of bar code technology than the rate expected in the absence of the 
regulation. The current estimate of public health benefits is based on 
all hospitals acquiring bar coding systems within 10 years as compared 
to 20 years without the proposed rule. However, because we are not 
requiring hospitals to make this investment, we examined the impact of 
different diffusion rates. ERG examined two additional scenarios: one 
in which the technology is accepted within 20 years with a rule as 
compared to 30 years without a rule, and one in which technology is 
accepted within 15 years, as compared to 20 years with a rule. Both 
cases decrease costs and benefits. The first case reduced expected net 
annualized net benefits from $3.2 billion to $2.0 billion. Annualized 
hospital expenditures declined from $680 million to $408 million, and 
benefits decreased from $3.9 billion to $1.8 billion. The second case 
reduced annualized net benefits to $1.5 billion. Annualized hospital 
expenditures declined from $680 million to $303 million, and benefits 
decreased from $3.9 billion to $1.8 billion. The public health benefits 
of the proposed rule would still exceed costs and expenditures with 
these slower diffusion rates.
6. Hospital Intercept Rates with Machine-Readable Technology
    The expected benefit of avoidance of patient ADEs is dependent on 
the expected rate of error interception. For this analysis, ERG found 
that about 45 percent of the errors that lead to preventable ADEs 
originate in the dispensing and administration stages of the medication 
process and that the use of bar coded information and installed systems 
would intercept about 50 percent of these errors. Because of the direct 
relationship between expected interception rates and avoided ADEs, we 
tested the impact of the assumed rates. Although the literature has 
implied that interception rates as high as 85 percent are obtainable, 
ERG assumed a 50 percent rate to account for potential nonoptimal use 
of technology. If the true increase in interception rates were between 
80 percent and 20 percent, the total number of avoided ADEs would be 
between 660,400 and 165,000. The monetized annualized value of these 
avoided ADEs would vary from the current estimate of $3.9 billion to 
the lower and higher values of $1.6 billion (with a 20 percent 
improvement in interception rates) or $6.2 billion (with an 80 percent 
improvement in interception rates). From a societal perspective, 
therefore, the accelerated technology investment appears reasonable 
even with significantly lower interception rates.
7. Productivity Losses in Hospital Wards
    The decision by hospitals to make significant investments in bar 
code reading technology is highly dependent on expected productivity 
changes in the delivery of bedside care by nurses. Our current analysis 
assumes a 3-percent productivity loss of ward nurses due to the use of 
this new technology. We examined the sensitivity of this estimate and 
found that if long-term productivity loss approximated only 1 percent 
of the current workload, the average annualized cost of accelerated 
hospital investments would decrease from $680.0 million to $246.7 
million. However, if the productivity loss of nursing resources was as 
great as 5 percent, the annualized expenditures by hospitals would 
increase to $1.2 billion. In order for the productivity losses to 
outweigh the expected benefits, however, there would have to be an 
almost 700-percent estimated productivity loss. We recognize the 
extreme uncertainty of this projection and particularly invite public 
comment in this area.
8. Minimum Hospital Response
    The expected benefits rely on a faster rate of hospital acceptance 
of bar code technology than the rate expected in the absence of a rule. 
The current estimate of public health benefits is based on all 
hospitals acquiring bar code systems within 10 years as compared to 20 
years without the proposed rule. However, because we are not requiring 
hospitals to make this investment, we examined the minimum number of 
hospitals needed to install systems in order to be confident that 
benefits exceed costs. The ratio of costs to benefits implies that if 
only 0.05 percent of all hospitals in the United States (three 
facilities) make this investment 10 years earlier, the rule would 
generate sufficient public health benefits to justify costs. This 
estimate is based on average hospital size. We tested this assumption 
by assuming that only very small (fewer than 50 bed capacity) hospitals 
would adopt the technology. In this case, 22 hospitals would be 
required to adopt the technology (0.3 percent of all hospitals and 1.9 
percent of all small capacity hospitals) in order for the expected 
benefits to exceed the costs.
9. Investments by Hospital Size
    The internal decision to acquire and use new bar code reading 
technology could be affected by the size of the purchasing hospital. 
Hospitals that have already installed this equipment are, for the most 
part, fairly large or part of a large network of hospitals. Because the 
benefits of error interception are dependent on the number of annual 
admissions, we were concerned about the likelihood of technology 
adoption by small hospitals.
    According to the most recent census, there are 1,117 hospitals in 
the United States with capacities fewer than 50 beds. These hospitals 
account for only about 3 percent of the estimated annualized 
opportunity cost of investment from this proposed rule, because the 
potential productivity losses are not as great as for larger hospitals. 
The annualized opportunity costs per facility with fewer than 50 beds 
is approximately $57,100. However, because of the fewer admissions to 
hospitals of this size, we estimate that the interception rate of the 
bar code technology is expected to result in an average of 1.7 avoided 
ADEs per year per facility. The estimated societal benefit of avoiding 
1.7 ADEs is $303,800. If these small hospitals adopt technology at the 
same accelerated rate as all hospitals, the annualized benefit per 
hospital is $86,900, or more than the investment.
    We are aware that the estimated direct annual hospital cost savings 
of avoiding ADEs alone ($2,257 per avoided ADE) may not cover the costs 
of the expected earlier investment pattern. For example, the average 
facility with fewer than 50 beds would experience direct annual cost 
savings of $3,837 (1.7 ADEs avoided x $2,257) and annualized costs

[[Page 12528]]

of $57,100. As noted, the investment decision to install bar code 
reading technology is voluntary and would include consideration of 
patient safety and other cost-savings. We have estimated that potential 
reductions in resources needed to generate reports and to keep track of 
records may likely vary between $27,400 and $43,700 per year for a 
small hospital. Other institutional gains, including transfers such as 
increased revenue capture rates and reduced malpractice awards, may 
also affect internal decisions. Many industry representatives have 
indicated their willingness to invest in this technology. Nonetheless, 
even if some hospitals choose to delay or not to invest, this rule 
would still produce substantial societal benefits.

O. Small Business Analysis and Discussion of Alternatives

    We believe the proposed rule is unlikely have a significant impact 
on a substantial number of small entities. Despite this, we have 
prepared an initial Regulatory Flexibility Analysis (IRFA) and invite 
comment from affected entities. In addition, the regulation is 
considered a significant economic impact under UMRA and alternatives 
are examined and briefly discussed here.
1. Affected Sectors and Nature of Impacts
    We described the affected industry sectors earlier in this section. 
The proposal would directly affect manufacturers of pharmaceutical and 
biological products (NAICS 325412 and NAICS 325414), packaging services 
(NAICS 561910), and blood and organ banks (NAICS 621991), and 
indirectly affect hospitals (NAICS 622). We accessed data on these 
industries from the 1997 Economic Censuses and estimated revenues per 
establishment. Although other economic measures, such as profitability, 
may be preferable alternatives to revenues in estimating the 
significance of regulatory impacts in some cases, any reasonable 
estimate of profits would not change the results of this analysis. 
These revenues were updated to 2000 values by using the Consumer or 
Producer Price Index as appropriate.
    a. Pharmaceutical Manufacturers (NAICS 325412). The Small Business 
Administration (SBA) has defined as small any entity in this industry 
with fewer than 750 employees. According to census data, 84 percent of 
the industry is considered small. The average annual revenue for these 
small entities is $26.6 million per entity. Small manufacturers of 
prescription and OTC drug products dispensed under an order and 
commonly used in hospitals would be required to generate and label 
products with bar coded information. We estimate the annualized 
compliance costs for small entities in this industry at $1,800 per 
entity. This is less than 0.1 percent of their annual revenues. We 
believe this does not constitute a significant impact on a substantial 
number of small entities in this industry.
    b. Biological Product Manufacturers (NAICS 325414). The SBA has 
defined as small any entity in this industry with fewer than 500 
employees. According to census data, 68 percent of the industry is 
considered small. The average annual revenue for these small entities 
is $4.7 million per entity. Small manufacturers of biological products 
would be required to use standardized bar code information on their 
products. We estimate the annualized compliance costs for small 
entities in this industry at $600 per entity. This is less than 0.1 
percent of their annual revenues. We believe this does not constitute a 
significant impact on a substantial number of small entities in this 
industry.
    c. Packagers (NAICS 5619190). The SBA has defined as small any 
entity in this industry that has less than $6 million in annual 
revenues. On this basis, almost 75 percent of the industry is 
considered small. The average annual revenue for small entities is $1.7 
million per entity. Small packagers would be required to apply bar 
coded information to all affected products. This would require printing 
and process improvements to packaging operations. We estimated the 
annualized compliance cost for small entities in this industry at $240 
per entity. This is less than 0.1 percent of their annual revenues. We 
believe this does not constitute a significant impact on a substantial 
number of small entities in this industry.
    d. Blood and Organ Banks (NAICS 621991). The SBA has defined as 
small any entity in this industry with less that $8.5 million in annual 
revenues. On this basis, 40 percent of the industry is considered 
small. The average annual revenue for small entities is $1.4 million 
per entity. Small blood banks and collection centers would be required 
to apply standardized bar coded information on all blood products. This 
would require printing and process improvements to blood handling 
operations. We estimated the annual compliance cost for small entities 
in this industry at $100 per entity. This is less than 0.1 percent of 
their annual revenues. We believe this does not constitute a 
significant impact on a substantial number of small entities in this 
industry.
    e. Hospitals (NAICS 622). The SBA has defined as small any entity 
in this industry with less than $29.0 million in annual revenues. 
According to census data, 35 percent of the industry is considered 
small. The average annual revenue for small entities is $12.6 million 
per entity. There is no specific regulatory requirement for hospitals 
to respond to this proposed rule. We anticipate that the rule would 
make the investment in bar code technology more attractive to 
hospitals, but the rule would not require such investments. Hospitals 
that have already installed bar code reading systems and internally 
affix self-generated information might need to prematurely upgrade or 
replace currently installed scanners in order to capture bar coded 
information on small vials or bottles. These hospitals would also 
achieve productivity gains by avoiding the resources now used to self-
generate bar code readable information. The total annual net cost of 
the proposed rule is estimated at $3,300 per facility, which is equal 
to less than 0.1 percent of annual revenues. We believe this does not 
constitute a significant impact on a substantial number of small 
entities in this industry.
2. Alternatives
    We considered several alternatives to the proposed rule. Each is 
discussed below. We invite comments and suggestions for additional 
potential alternatives.
    a. Do Nothing. This alternative would not result in any change in 
current labeling or packaging practices. We believe that, in the 
absence of agency action, hospitals would gradually purchase and 
utilize independent bar code reading systems, but that it would take 20 
years before they were installed in all facilities. We rejected this 
alternative because of the expected positive net benefits of the 
proposal. Also, we believe that standardizing bar codes would generate 
additional health and production efficiencies for a variety of 
different health care sectors.
    b. Requiring Variable Information. We considered requiring 
additional information in bar codes, such as expiration dates and lot 
numbers. The incremental benefit of this data would include improved 
inventory control and ease of recalls. In addition, we are aware that 
some firms are voluntarily applying this information. However, we were 
unable to quantify potential public health benefits for this additional 
information, and the estimated additional annualized cost of this

[[Page 12529]]

alternative was $46.0 million. We did not select this alternative 
because we could not demonstrate that the added benefits would exceed 
the added costs.
    c. Covering All OTC Drug Products. We considered requiring all OTC 
drug products to include bar coded information. This alternative is 
currently rejected (although we invite comments on the OTC drugs to be 
covered) because the additional costs do not appear to be justified by 
the expected benefits. At this time, most noninstitutional settings are 
unlikely to have access to bar code reading systems. Therefore, we 
could not identify any significant reductions in ADEs due to this 
alternative. Including all OTC drug products would create estimated 
additional annualized costs to the manufacturing sector of $1.9 
million. The expected annualized costs of the regulation therefore 
would increase from $5.1 million to $7.0 million with no additional 
quantifiable benefit.
    d. Exemption for Small Entities. We considered exempting small 
entities, but rejected the alternative due to the modest projected 
impact of this initiative on small businesses and the lack of label 
standardization that would result.
     e. FDA Selecting a Specific Symbology. We considered requiring bar 
coded information with a specific symbology. The rationale for 
considering this option was to minimize uncertainty to hospitals in 
selecting systems that would be able to confidently read the specific 
language. We decided, however, that identifying a specific symbology 
might adversely impact future innovations in other machine-readable 
technologies. The selected alternative would allow individual 
facilities and suppliers to devise systems that would maximize their 
own internal efficiencies, as long as the standardized information 
could be accessed. The lack of consistent universal standards has been 
a major impediment to the use of this technology. As long as 
symbologies could be read within a single standard, however, the 
identified market failure would be overcome. In addition, the expected 
costs of this proposal would be much greater than the selected 
alternative. Annualized costs to manufacturers would increase to $8.3 
million and significant costs would occur to the retail sector due to 
the need for accelerated upgrade or replacement of currently installed 
scanners. Retail pharmacies would incur annualized costs of $14.4 
million. Consequently, we rejected the alternative of identifying a 
specific symbology.
3. Outreach
    We held a public meeting on July 26, 2002 to solicit comments from 
the affected sectors. Interested parties from the health care sector, 
manufacturing sector, retail sector, and equipment suppliers provided 
comment and insight to the agency. In addition, we met with various 
industry groups in order to ensure viewpoints were appropriately 
considered. These insights affected the regulatory considerations, and 
additional outreach is planned during the regulatory process.

P. Conclusion

    We have examined the proposed rule and find that the expected 
benefits outweigh the costs and that the regulation would improve 
public health. The detailed analysis that provides references and 
support for the summary that appears in this section is available in 
the docket as Ref. 46.

VIII. Request for Comments

    In addition to requesting general comments on the proposal, and the 
specific requests on assumptions contained in the economic analysis, we 
are seeking comment on the following specific issues identified in the 
description of the proposed rule (presented here for the convenience of 
the reader):
    1. Whether we should require bar codes on prescription drug 
samples, and the costs and benefits associated with such bar codes (see 
section II.B.2.a of this document).
    2. The risks and benefits of including vaccines in a bar code rule 
(see section II.B.2.a of this document).
    3. What terms we should use to describe OTC drugs that should be 
subject to the bar code requirement (see section II.B.2.b of this 
document).
    4. Information on the costs and benefits associated with putting 
lot number and expiration date information in the bar code (see section 
II.C.2 of this document).
    5. Whether the rule should refer instead to linear bar codes 
without mentioning any particular standard or refer to UCC/EAN and 
HIBCC standards (see section II.D.1 of this document).
    6. Additional information regarding bar code scanning technology 
and the ability of bar code scanners to read different symbologies (see 
section II.D.1 of this document).
    7. Whether the rule should adopt a different format (whether that 
format is a symbology, standard, or other technology), considering the 
following issues:
    [sbull] What other symbol, standard, or technology should we 
consider, either in place of a linear bar code or in addition to it?
    [sbull] How accepted is that symbol, standard, or technology among 
firms that would have to affix or use that symbol, standard, or 
technology?
    [sbull] Will hospitals be able to read or use the symbol, standard, 
or technology, either with existing equipment or equipment under 
development? (see section II.D.1 of this document).
    8. Whether any specific product or class of products should be 
exempt from a bar code requirement and the reasons why an exemption is 
considered to be necessary (see section II.F of this document). In 
addition, how could we create a waiver provision that would minimize 
the potential for misusing the waiver?
    9. Whether the implementation period for a final rule can and 
should be shortened from 3 years to some other specific time period 
(see section II.G of this document).
    10. Whether we should require the use of ISBT 128 for blood 
products, a specific symbology that is consistent with that required 
for drugs in proposed Sec.  201.25, or ``machine-readable symbols'' as 
approved by the Director of CBER (see section II.H of this document).
    11. How the proposed rule might affect hospitals where patients 
receive blood or blood components, particularly with respect to a 
hospital's decision to purchase a machine reader (e.g., scanner) that 
can properly identify the intended recipient of the blood or blood 
component, the machine readable information encoded on the blood or 
blood component label, and perhaps the linear bar codes appearing on 
drugs and OTC drugs that are dispensed pursuant to an order and 
commonly used in the hospital (see section II.H of this document).
    12. Whether any of the alternatives discussed in the economic 
analysis have merit (see section VII.O of this document).
    Interested persons may submit to the Dockets Management Branch (see 
ADDRESSES) written or electronic comments regarding this document. 
Submit a single copy of electronic comments to http://www.fda.gov/dockets/ecomments or two hard copies of any mailed comments, except 
that individuals may submit one hard copy. Comments are to be 
identified with the docket number found in brackets in the heading of 
this document. Received comments may be seen in the Dockets Management 
Branch between 9 a.m. and 4 p.m., Monday through Friday.

[[Page 12530]]

IX. References

    The following references have been placed on display in the Dockets 
Management Branch (see ADDRESSES) and may be seen by interested persons 
between 9 am. and 4 p.m., Monday through Friday.
    1. Institute of Medicine, ``To Err Is Human: Building a Safer 
Health System,'' 1999.
    2. McDonald, C. J., M. Winer, and S. L. Hui, ``Deaths Due to 
Medical Errors Are Exaggerated in Institute of Medicine Report,'' 
Journal of the American Medical Association, 284:93-95, July 5, 
2000.
    3. Leape, L. L., ``Institute of Medicine Medical Error Figures 
Are Not Exaggerated,'' Journal of the American Medical Association, 
284:95-97, July 5, 2000.
    4. Brennan, T. A., ``The Institute of Medicine Report on Medical 
Errors--Could It Do Harm?'' New England Journal of Medicine, 342: 
1123-1125, April 13, 2000.
    5. Honig, P., J. Phillips, and J. Woodcock, letter to the 
editor, ``How Many Deaths Are Due to Medical Errors?,'' Journal of 
the American Medical Association, 284: 2187-2188, November 1, 2000.
    6. Agency for Healthcare Research and Quality, ``Reducing and 
Preventing Adverse Drug Events to Decrease Hospital Costs'' at pages 
4 to 6.
    7. Department of Health and Human Services, ``HHS News: 
`Secretary Thompson Announces HHS Patient Safety Task Force','' 
April 23, 2001.
    8. Testimony of Tommy G. Thompson, Secretary of Health and Human 
Services, before the Senate Committee on Health, Education, Labor, 
and Pensions' Subcommittee on Patient Health, May 24, 2001.
    9. Letter from Henri R. Manasse, Jr., Executive Vice President 
and Chief Executive Officer, ASHP, to the Honorable Tommy G. 
Thompson, Secretary of Health and Human Services, dated July 10, 
2001, at p. 1.
    10. National Coordinating Council for Medication Error Reporting 
and Prevention, ``What is a Medication Error?'' (Undated).
    11. Phillips, J. et al., ``Retrospective Analysis of Mortalities 
Associated with Medication Errors,'' American Journal of Health-
System Pharmacy, 58: 1835-1841, October 1, 2001.
    12. Johnson, J. A. and J. L. Bootman, ``Drug-Related Morbidity 
and Mortality: A Cost-of-Illness Model,'' Archives of Internal 
Medicine, 1949-1956, 1995.
    13. Ernst, F. R. and A. J. Grizzle, ``Drug-Related Morbidity and 
Mortality: Updating the Cost-of-Illness Model,'' Journal American 
Pharmaceutical Association, 41: 192-199, March/April 2001.
    14. Bates, D. W. et al., ``The Cost of Adverse Drug Events in 
Hospitalized Patients,'' Journal of the American Medical 
Association, 277: 307-311, January 22/29, 1997.
    15. Bates, D. W., ``Using Information Technology to Reduce Rates 
of Medication Errors in Hospitals,'' British Medical Journal, 320: 
788-791, March 18, 2000.
    16. Puckett, F., ``Medication-Management Component of a Point-
of-Care Information System,'' American Journal of Health-System 
Pharmacy, 52: 1305-1309, June 15, 1995.
    17. Malcolm, B., R. A. Carlson, C. L. Tucker, and C. Willette, 
``Veterans Affairs: Eliminating Medication Errors Through Point-of-
Care Devices,'' Technical paper for 2000 Annual HIMSS Conference, 
November 30, 1999.
    18. Hokanson, J. A. et al., ``Potential Use of Bar Codes to 
Implement Automated Dispensing Quality Assurance Programs,'' 
Hospital Pharmacy, 20: 327-337, May 1985.
    19. Dinklage, K. C., S. J. White, J. C. Lenhart, and H. N. 
Godwin, ``Accuracy and Time Requirements of a Bar-Code Inventory 
System for Controlled Substances,'' American Journal of Hospital 
Pharmacy, 46: 2304-2307, November 1989.
    20. Davis, N. M., ``Detection and Prevention of Ambulatory Care 
Pharmacy Dispensing Errors,'' Hospital Pharmacy, 25: 18-28, January 
1990.
    21. Meyer, G. E. et al., ``Use of Bar Codes in Inpatient Drug 
Distribution,'' American Journal of Hospital Pharmacy, 48: 953-966, 
May 1991.
    22. Hynniman, C. E., ``Drug Product Distribution Systems and 
Departmental Operations,'' American Journal of Hospital Pharmacy, 
48: S22-S35, October 1991 (Supplement 1).
    23. Carmenates, J. and M. R. Keith, ``Impact of Automation on 
Pharmacist Interventions and Medication Errors in a Correctional 
Health Care System,'' American Journal of Health System Pharmacy, 
58(9): 779-783, May 1, 2001.
    24. Transcript from ``Public Hearing: Bar Coding--A Regulatory 
Initiative,'' at pages 13-14 (remarks of Kay Willis, Chief of 
Pharmacy, VA Medical Center, Chicago, IL).
    25. Comment from McKesson Corp., dated July 26, 2002, at page 5; 
this comment is in FDA docket number 02N-0204 as EMC 15.
    26. The Leapfrog Group, ``Fact Sheet: Computer Physician Order 
Entry (CPOE),'' dated November 2000.
    27. Quality Interagency Coordination Task Force, ``Doing What 
Counts for Patient Safety: Federal Actions to Reduce Medical Errors 
and Their Impact--Report of the Quality Interagency Coordination 
Task Force (QuIC) to the President,'' at page 74 (February 2000).
    28. National Coordinating Council for Medication Error Reporting 
and Prevention, ``Promoting and Standardizing Bar Coding on 
Medication Packaging: Reducing Errors and Improving Care,'' adopted 
June 27, 2001.
    29. American Society of Health-System Pharmacists, House of 
Delegates Session-2001, Policy Recommendation F, ``Machine-Readable 
Coding,'' dated June 4 and 6, 2001.
    30. Testimony of Albert Patterson, Vice-President for 
Contracting, Premier, Inc., before the Senate Subcommittee on 
Science, Technology, and Space, dated July 23, 2001.
    31. Letter from Robert A. Hankin, President and CEO, Health 
Industry Business Communications Council (HIBCC), to the Honorable 
Tommy G. Thompson, Secretary of Health and Human Services, dated 
January 3, 2002.
    32. Letter from Herb Kuhn, Corporate Vice-President, Premier, 
Inc., and others, to the Honorable Tommy G. Thompson, Secretary of 
Health and Human Services, dated January 24, 2002.
    33. Letter from Joe Pleasant, Chair of Board, Premier, Inc., and 
others for the Coalition for Healthcare eStandards, to the Honorable 
Tommy G. Thompson, Secretary of Health and Human Services, dated 
March 19, 2002.
    34. Food and Drug Administration, ``Guidance for Industry: 
Prescription Drug Marketing Act Regulations for Donation of 
Prescription Drug Samples to Free Clinics'' (draft), June, 2002.
    35. Uniform Code Council, ``Case Study: Alcon Laboratories, 
Reduced Space Symbology on Small Healthcare Items from Print to 
Beside'' (sample GTIN applied using RSS on 3 mL and 5 mL bottles).
    36. Federal Communications Commission, ``In the Matter of Review 
of the Commission's Rules and Policies Affecting the Conversion to 
Digital Television,'' MM Docket No. 00-39, adopted August 8, 2002, 
at page 13.
    37. Federal Communications Commission, ``In the Matter of Review 
of the Commission's Rules and Policies Affecting the Conversion to 
Digital Television,'' MM Docket No. 00-39, adopted August 8, 2002, 
``Separate Statement of Commissioner Michael J. Copps.''
    38. Federal Communications Commission, ``In the Matter of Review 
of the Commission's Rules and Policies Affecting the Conversion to 
Digital Television,'' MM Docket No. 00-39, adopted August 8, 2002, 
``Separate Statement of Commissioner Kathleen Q. Abernathy.''
    39. Uniform Code Council, ``UCC Establishes Sunrise Date of 2005 
for Expansion of U.P.C. to EAN-13,'' dated June 9, 1997.
    40. Auto-ID Center, Massachusetts Institute of Technology, 
``Technology Guide'' at page 4.
    41. ASTM, ``F1851-98: Standard Practice for Bar Code 
Verification'' (1998).
    42. Davis, N.M., ``Initiatives for Reducing Medication Errors: 
The Time is Now,'' American Journal of Health-System Pharmacy, 57: 
1487-1492, August 15, 2000.
    43. Linden, J.V. et al., ``Transfusion Errors in New York State: 
An Analysis of 10 Years' Experience,'' Transfusion, 40: 1207-1213 
(October 2000).
    44. FDA, ``Guidance for Industry: Recognition and Use of a 
Standard for the Uniform Labeling of Blood and Blood Components,'' 
June 2000, at page 1.
    45. Food and Drug Administration, ``Guidance for Industry: 
United States Industry Consensus Standard for the Uniform Labeling 
of Blood and Blood Components Using ISBT 128,'' November 1999, at 
section 1, page 2.
    46. Eastern Research Group, ``Impact of Proposed Barcode 
Regulations for Drug and Biological Products,'' Contract Number 223-
98-8002, Task Order Number 21, December 2, 2002.
    47. Eastern Research Group, ``Profile of Machine-Readable 
Technologies for Medical Applications,'' Contract Number 223-94-
8031, In partial fulfillment of Task Order Number 8, December 2, 
2002.

Appendix

Additional Information on Various Studies Identifying Different Types 
of Medication Errors

[[Page 12531]]

    This appendix includes summaries of several articles that identify 
different types of medication errors, a table illustrating varied 
medication error rates among studies, and a list of references cited in 
the appendix.

I. Types of Medication Errors Administering the Wrong Dose

    Folli et al. examined errant chart orders in two large pediatric 
hospitals (Ref. A-1). The study defined an errant chart order as a 
potentially lethal error if certain consequences (such as 
cardiopulmonary arrest if administered at the dose ordered) resulted. 
The authors found that incorrect doses and missed doses were the most 
prevalent errors. Overdoses accounted for 55 percent of the dosing 
errors, while underdoses led to 26.9 percent of all errors.
    In a study of adverse events in hospitalized patients, Leape et al. 
reviewed 30,195 randomly selected hospital records and identified 1,133 
patients whose disabling injuries were caused by medical treatment 
(Ref. A-2). Errors in dose or method of use accounted for 42 percent of 
all errors.
    In a study of two urban teaching hospitals, Kaushal et al. found 
dosing errors to be the most frequent medication error (which the 
authors defined as errors in drug ordering, transcribing, dispensing, 
administering, or monitoring) and the most frequent preventable adverse 
drug event (Ref. A-3).
    Lesar et al. conducted a study of prescribing errors at a teaching 
hospital (Ref. A-4). The authors' review of 289,411 medication orders 
revealed 905 prescribing errors that were detected and averted, and 
overdoses and underdoses accounted for 28.7 and 17.8 percent of total 
errors respectively.
    McCarthy, Kelly, and Reed studied the medication administration 
practices of school nurses (Ref. A-5). The authors found that 48.5 
percent of school nurses surveyed reported medication errors, and 
overdoses or double doses were the third most commonly reported error 
(22.9 percent of medication errors).
Administering a Drug to a Patient Who Is Known to Be Allergic 
    In the Lesar review of medication orders, 6.7 percent of all 
medication order errors that were detected and averted involved 
prescribing a drug to a patient who is allergic to the prescribed drug 
(Ref. A-4).
    In an article by Classen et al. involving a case control study of 
all patients admitted to a hospital in a 3-year period, medication 
errors due to known drug allergies represented 1.5 percent of all 
adverse drug events, and all were preventable (Ref. A-6).
Administering the Wrong Drug to a Patient or Administering a Drug to 
the Wrong Patient
    A study by Thur et al. observed how nurses in two surgical units 
prepared to administer parenteral admixtures (which the authors defined 
as including only fluids to which one or more drugs were added directly 
into a single or primary bottle) (Ref. A-7). The authors defined 
``medication error'' as including the administration of the wrong drug 
or solution, the wrong dosage of a drug or solution volume, an 
unordered or discontinued drug, or two or more pharmaceutically 
incompatible drugs in the same admixture. The study involved 100 
observations where 331 parenteral admixtures were prepared; unordered 
drugs accounted for 3 percent of the errors that were observed. In one 
instance, the drug was administered two times per day for 4 days, even 
though the order for the drug had been discontinued earlier.
    In the Classen et al. article that involved a case control study, 
of 905 prescribing errors that were detected and averted, 1.1 percent 
of all errors involved prescribing a drug to the wrong patient (Ref. A-
6).
Administering the Drug Incorrectly
    In the study by Kaushal et al. that examined 10,778 medication 
orders at two urban teaching hospitals, errors involving the drug's 
route of administration were the second most common form of medication 
error and accounted for 18 percent of the medication errors (Ref. A-3). 
These medication errors also accounted for the third-most common form 
(14 percent) of potential adverse drug events, which the authors 
defined as a medication error having a significant potential for 
injuring a patient.
Administering the Drug at the Wrong Time or Missing Doses 
    In a study of two pediatric critical care units by Tisdale, ``wrong 
time'' errors, which were defined as medications administered 30 
minutes before or after the scheduled administration time, were the 
most prevalent error and accounted for a 16 percent error rate (Ref. A-
8).
    In McCarthy, Kelly, and Reed's study of school nurses, of the 315 
school nurses who reported a medication error, 251 cited missed doses 
as the most common medication error (Ref. A-5).
    In their study of the relationship between medication errors and 
adverse drug events, Bates, Boyle, et al. found that 53 percent of the 
medication errors surveyed involved at least one missing dose of 
medication (Ref. A-9).
    A recently published study by Barker et al. examined 36 
institutions in Colorado and Georgia and found that 19 percent of the 
doses administered were in error and that the most prevalent error (at 
8 percent of the medication errors) was ``wrong time'' medication 
errors (Ref. A-10). The authors defined ``wrong time'' as 
administration of a dose more than 60 minutes before or after the 
scheduled administration time, or a 30 minute window for medications 
that were ordered before, with, or after a meal. However, the ``wrong 
time'' medication error rate ranged between zero percent for some 
nonaccredited hospitals in Georgia to 26.2 percent for a nonaccredited 
hospital in Colorado.

II. Frequency of Medication Errors

    Table 1 illustrates the variation in medication error rates among 
several studies. Some studies suggest a medication error rate of under 
7 percent, whereas others suggest a rate at or above 20 percent. The 
differences may be due, in part, to different definitions of medication 
error or different research methodology that focused on fatalities, 
injuries, or medication orders.

      Table 1.--Medication Error Rates Reported in Various Studies
------------------------------------------------------------------------
                         Definition of Medication
         Study                  Error Used         Medication Error Rate
------------------------------------------------------------------------
Observation of nurses   ``Medication error''       21%.
 in two surgical units   defined as wrong drug or
 by Thur (Ref. A-7).     solution; wrong dosage
                         of a drug or solution
                         volume; an unordered or
                         discontinued drug; or
                         two or more
                         pharmaceutically
                         incompatible drugs in
                         the same admixture.

[[Page 12532]]

 
Review of 101,022       ``Errant medication        Medication order
 medication orders at    order'' considered to be   error rate was
 2 pediatric hospitals   an order that was not in   between 4.9 and 4.5
 by Folli et al. (Ref.   accordance with standard   errors per 1,000
 A-1).                   pediatric references,      orders.
                         current published
                         literature, or dosing
                         guidelines approved by
                         the hospital's pharmacy
                         and therapeutics
                         committees.
Review of 289,411       Not defined.               Prescribing errors
 medication orders                                  were detected at a
 written during a 1-                                rate of 3.13 errors
 year period by Lesar                               per 1,000 orders.
 (Ref. A-4).
Survey of 26,462        ``Suspected adverse        0.02% fatality rate
 patients in 7           reactions'' defined as     (6 deaths were
 countries; 24 were      any undesired or           considered
 considered to have      unintended effect of a     preventable).
 died as a result of a   drug.
 drug or group of
 drugs, by Porter and
 Jick (Ref. A-11).
Review of 30,195        ``Adverse event'' defined   Of the adverse
 randomly selected       as an unintended injury    events due to drug
 hospital records by     caused by medical          treatment, 18%
 Leape et al. (Ref. A-   management and resulted    resulted from
 2).                     in measurable              negligence, although
                         disability. The            the authors also
                         reviewers considered an    explain that
                         adverse event to be due    negligence occurs
                         to ``negligence'' if       not merely when
                         they felt there was a      there is error, but
                         deviation from accepted    when the degree of
                         norms of treatment and     error exceeds an
                         after they considered      accepted norm.
                         other factors (such as
                         potential consequences,
                         frequency of risk,
                         degree of emergency, and
                         complexity of the case).
                         The authors defined
                         ``negligence'' as
                         failure to meet the
                         standard of care
                         reasonably expected of
                         an average physician
                         qualified to take care
                         of the patient in
                         question.
Study of 18,262         Not defined.               Medication order
 medication and                                     error rate ranged
 intravenous fluid                                  between 2.6 to 8.5
 orders given in a 3-                               per 1,000 orders.
 month period at a                                  Verbal medication
 children's hospital                                orders had the
 by West et al. (Ref.                               lowest error rate,
 A-12).                                             followed by computer-
                                                    entered orders (6.3
                                                    per 1,000) and
                                                    handwritten orders.
Study of 4,031 adult    ``Adverse drug event''     28% of adverse drug
 admissions of 11        defined as an injury       events are
 medical and surgical    resulting from medical     preventable, and
 units in 2 hospitals    intervention related to    there were 7.3
 by Bates, Cullen et     a drug.                    preventable adverse
 al. (Ref. A-13).                                   drug events per
                                                    every 100
                                                    admissions.
Review of 10,070        ``Medication error''       5.3%.
 medication orders to    defined as errors in the
 identify medication     process of ordering or
 errors by Bates,        delivering medication,
 Boyle et al. (Ref. A-   regardless of whether an
 9).                     injury occurred or the
                         potential for injury was
                         present.

[[Page 12533]]

 
Matched case-control    ``Adverse drug event''     1% of all adverse
 study of all patients   defined as an event that   drug events, but the
 admitted to a           is ``noxious and           authors also state
 hospital in a 3-year    unintended and occurs at   that almost 50% of
 period by Classen et    doses used in humans for   all adverse drug
 al. (Ref. A-6).         prophylaxis, diagnosis,    events are
                         therapy, or modification   potentially
                         of physiologic             preventable.
                         functions'' but excludes
                         therapeutic failures,
                         poisonings, and
                         intentional overdoses.
Review of 10,778        ``Medication errors''      5.7%, with adult
 medication orders at    defined as errors in       patients cared for
 2 urban teaching        drug ordering,             in a pediatric
 hospitals by Kaushal    transcribing,              setting experiencing
 et al. (Ref. A-3).      dispensing,                the most medication
                         administering, or          errors.
                         monitoring.
Prospective cohort      ``Medication error''       19%, or nearly 2
 study in 36             defined as a dose          errors every day for
 institutions by         administered differently   a typical patient
 Barker et al. (Ref. A-  than as ordered on the     receiving 10 doses
 10).                    patient's medical          per day, or, for a
                         records.                   facility with 300
                                                    patients, almost 40
                                                    potential adverse
                                                    drug events in a
                                                    facility. The
                                                    percentage of
                                                    potentially harmful
                                                    errors was 7% or
                                                    more than 40 per day
                                                    per 300 inpatients.
Examination of all      ``Medication errors are    Medication error rate
 U.S. death              ``accidental poisonings    rose from 1 out of
 certificates between    by drugs, medicaments,     every 439 outpatient
 1983 and 1993 by        and biologicals'' and      deaths and 1 out of
 Phillips et al. (Ref.   have resulted from         every 1, 622
 A-14).                  ``acknowledged errors,     inpatient deaths in
                         by patients or medical     1983 to 1 out of
                         personnel.                 every 131 outpatient
                                                    deaths and 1 out of
                                                    every 854 inpatient
                                                    deaths in 1993. The
                                                    authors suggest the
                                                    increase may be due
                                                    to an increasing
                                                    willingness to
                                                    attribute error
                                                    deaths that were
                                                    previously ascribed
                                                    to natural causes.
------------------------------------------------------------------------

III. References in the Appendix

    The following references have been placed on display in the Dockets 
Management Branch (see ADDRESSES) and may be seen by interested persons 
between 9 am. and 4 p.m., Monday through Friday.
    A-1. Folli, H. L., R. L. Poole, W. E. Benitz, et al., 
``Medication Error Prevention by Clinical Pharmacists in Two 
Children's Hospitals,'' Pediatrics, 79:718-722, 1987.
    A-2. Leape, L. L. et al., ``The Nature of Adverse Events in 
Hospitalized Patients,'' New England Journal of Medicine, 324:377-
384, 1991.
    A-3. Kaushal, R. et al., ``Medication Errors and Adverse Drug 
Events in Pediatric Inpatients,'' Journal of the American Medical 
Association 285:2114-2120, 2001.
    A-4. Lesar, T. S. et al., ``Medication Prescribing Errors in a 
Teaching Hospital,'' Journal of the American Medical Association 
263:2329-2334, 1990.
    A-5. McCarthy, A. M., M. W. Kelly, and D. Reed, ``Medication 
Administration Practices of School Nurses,'' Journal of School 
Health, 70:371-376, 2000.
    A-6. Classen, D.C. et al., ``Adverse Drug Events in Hospitalized 
Patients,'' Journal of the American Medical Association, 277:301-
306, 1997.
    A-7. Thur, M. P., ``Medication Errors in a Nurse-Controlled 
Parenteral Admixture Program,'' Journal of Hospital Pharmacy, 
29:298-304, 1972.
    A-8. Tisdale, J. E., ``Justifying a Pediatric Critical-Care 
Satellite Pharmacy by Medication-Error Reporting,'' American Journal 
of Hospital Pharmacy, 43:368-371, 1986.
    A-9. Bates, D.W., D. L. Boyle, M. B. Vander Vliet, et al., 
``Relationship Between Medication Errors and Adverse Drug Events,'' 
Journal of General Internal Medicine, 10:199-205, 1995.
    A-10. Barker, K. N. et al., ``Medication Errors Observed in 36 
Health Care Facilities,'' Archives of Internal Medicine, 162:1897-
1903, 2002.
    A-11. Porter, J., and H. Jick, ``Drug-Related Deaths Among 
Medical Inpatients,'' Journal of the American Medical Association, 
237:879-881, 1977.
    A-12. West, D. W., S. Levine, G. Magram, et al., ``Pediatric 
Medication Order Error Rates Related to the Mode of Order 
Transmission,'' Archives of Pediatric and Adolescent Medicine, 
148:1322-1326, 1994.
    A-13. Bates, D. W., D. J. Cullen, N. Laird, et al., ``Incidence 
of Adverse Drug Events and Potential Adverse Drug Events,'' Journal 
of the American Medical Association 274:29-34, 1995.
    A-14. Phillips, D. P., N. Christenfeld, and L. M. Glynn, 
``Increase in US Medication-Error Deaths Between 1983 and 1993,'' 
Lancet, 351: 643-644, 1998.

List of Subjects

21 CFR Part 201

    Drugs, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 606

    Blood, Labeling, Laboratories, Reporting and recordkeeping 
requirements.

21 CFR Part 610

    Biologics, Labeling, Reporting and recordkeeping requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that parts 201, 606, and 610 be amended as follows:

PART 201--LABELING

    1. The authority citation for 21 CFR Part 201 continues to read as 
follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 353, 355, 358, 360, 
360b, 360gg-360ss, 371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.
    2. Section 201.25 is added to read as follows:

[[Page 12534]]

Sec.  201.25  Bar code label requirements.

    (a) Who is subject to these bar code requirements? Manufacturers, 
repackers, relabelers, and private label distributors of a human 
prescription drug product or an OTC drug product that is regulated 
under the Federal Food, Drug, and Cosmetic Act or the Public Health 
Service Act are subject to the bar code requirements in this section 
unless they are exempt from the registration and drug listing 
requirements in section 510 of the act.
    (b) What drugs are subject to these bar code requirements? The 
following drug products are subject to the bar code label requirements: 
Prescription drug products (excluding samples), biological products, 
and over-the-counter drug products that are dispensed under an order 
and are commonly used in hospitals. For purposes of this section, an 
over-the-counter drug product is ``commonly used in hospitals'' if it 
is packaged for institutional use, labeled for institutional use, or 
marketed, promoted, or sold to hospitals.
    (c) What does the bar code look like, and where does the bar code 
go?
    (1) Each drug product described in paragraph (b) in this section 
must have a bar code that contains, at a minimum, the appropriate 
National Drug Code (NDC) number in a linear bar code that meets Uniform 
Code Council (UCC/EAN) standards. Additionally, the bar code must:
    (i) Be surrounded by sufficient blank space so that the bar code 
can be scanned correctly; and
    (ii) Remain intact under normal conditions of use.
    (2) The bar code must appear on the drug's label as defined by 
section 201(k) of the act.

PART 606--CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD 
COMPONENTS

    3. The authority citation for part 606 continues to read as 
follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 355, 360, 360j, 371, 
374; 42 U.S.C. 216, 262, 263a, 264.
    4. Section 606.121 is amended by revising paragraph (c)(13) to read 
as follows:


Sec.  606.121  Container label.

* * * * *
    (c) * * *
    (13) The container label must bear encoded information that is 
machine-readable and approved for use by the Director, Center for 
Biologics Evaluation and Research.
    (i) Who is subject to this machine-readable requirement? All blood 
establishments that manufacture, process, repackage, or relabel blood 
or blood components intended for transfusion and regulated under the 
Federal Food, Drug, and Cosmetic Act or the Public Health Service Act.
    (ii) What blood products are subject to this machine-readable 
requirement? All blood and blood components intended for transfusion 
are subject to the machine-readable information label requirement in 
this section.
    (iii) What information must be machine-readable? Each label must 
have machine-readable information that contains, at a minimum:
    (A) A unique facility identifier,
    (B) Lot number relating to the donor,
    (C) Product code, and
    (D) ABO and Rh of the donor.
    (iv) How must the machine-readable information appear? The machine-
readable information must:
    (A) Be unique to the blood or blood component;
    (B) Be surrounded by sufficient blank space so that the machine-
readable information can be scanned correctly; and
    (C) Remain intact under normal conditions of use.
    (v) Where does the machine-readable information go? The machine-
readable information must appear on the label of any blood or blood 
component which is or can be transfused to a patient or from which the 
blood or blood component can be taken and transfused to a patient.
* * * * *

PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS

    5. The authority citation for part 610 continues to read as 
follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c, 
360d, 360h, 360i, 371, 372, 374, 381; 42 U.S.C. 216, 262, 263, 263a, 
264.
    6. Section 610.67 is added to read as follows:


Sec.  610.67  Bar code label requirements.

    Unless it is regulated as a device, a biological product must 
comply with the bar code requirements at Sec.  201.25 of this chapter.

    Dated: January 24, 2003.
Mark B. McClellan,
Commissioner of Food and Drugs.

    Dated: February 6, 2003.
Tommy G. Thompson,
Secretary of Health and Human Services.
[FR Doc. 03-5205 Filed 3-13-03; 8:45 am]
BILLING CODE 4160-01-S