[Federal Register Volume 80, Number 178 (Tuesday, September 15, 2015)]
[Notices]
[Pages 55364-55371]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-23203]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-D-0609]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Guidance for Industry 
on Drug Supply Chain Security Act Implementation: Identification of 
Suspect Product and Notification

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995 (the PRA).

DATES: Fax written comments on the collection of information by October 
15, 2015.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-7285, or emailed to [email protected]. All 
comments should be identified with the

[[Page 55365]]

OMB Control number 0910-NEW and title ``Guidance for Industry on Drug 
Supply Chain Security Act Implementation: Identification of Suspect 
Product and Notification.'' Also include the FDA docket number found in 
brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver 
Spring, MD 20993-0002, [email protected].

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Guidance for Industry on Drug Supply Chain Security Act Implementation: 
Identification of Suspect Product and Notification (OMB Control Number 
0910--NEW)

    In the Federal Register of June 11, 2014 (79 FR 33564), FDA 
announced the availability of a draft guidance for industry entitled 
``Drug Supply Chain Security Act Implementation: Identification of 
Suspect Product and Notification.'' The draft guidance addressed new 
provisions in the Federal Food, Drug, and Cosmetic Act (the FD&C Act), 
as amended by the Drug Supply Chain Security Act (DSCSA). Section 202 
of the DSCSA adds section 582(h)(2) (21 U.S.C. 360eee-1(h)(2)) to the 
FD&C Act, which requires FDA to issue guidance to aid certain trading 
partners (manufacturers, repackagers, wholesale distributors, and 
dispensers) in identifying a suspect product and terminating 
notifications. The draft of this guidance identified specific scenarios 
that could significantly increase the risk of a suspect product 
entering the pharmaceutical distribution supply chain and provided 
recommendations on how trading partners can identify the product and 
determine whether the product is a suspect product as soon as 
practicable.
    Beginning January 1, 2015, section 582 of the FD&C Act requires 
trading partners, upon determining that a product in their possession 
or control is illegitimate, to notify (1) FDA and (2) all immediate 
trading partners that they have reason to believe may have received the 
illegitimate product, not later than 24 hours after making the 
determination. Manufacturers are additionally required under section 
582(b)(4)(B)(ii)(II) of the FD&C Act to notify FDA, and any immediate 
trading partners that the manufacturer has reason to believe may 
possess a product manufactured by or purported to be manufactured by 
the manufacturer, not later than 24 hours after the manufacturer 
determines or is notified by FDA or a trading partner that there is a 
high risk that a product is illegitimate. The draft guidance addressed 
how trading partners should notify FDA using Form FDA 3911. In 
addition, in accordance with section 582(h)(2) of the FD&C Act, the 
draft guidance sets forth the process by which trading partners must 
terminate the notifications using Form FDA 3911, in consultation with 
FDA, regarding illegitimate product and, for a manufacturer, a product 
with a high risk of illegitimacy, under section 582(b)(4)(B), 
(c)(4)(B), (d)(4)(B), and (e)(4)(B).
    Burden Estimates: Under section 202 of the DSCSA, manufacturers, 
repackagers, wholesale distributors, and dispensers (e.g., pharmacies) 
must: (1) Notify FDA when they have determined that a product in their 
possession or control is illegitimate (and, for manufacturers, when 
they have determined or been notified by FDA or a trading partner that 
a product has a high risk of illegitimacy); (2) notify immediate 
trading partners about an illegitimate product that they may have 
received (and, for manufacturers, a product with a high risk of 
illegitimacy); (3) terminate notifications regarding illegitimate 
products (and, for manufacturers, products with a high risk of 
illegitimacy), in consultation with FDA when the notifications are no 
longer necessary; and (4) notify immediate trading partners when the 
notifications are terminated.

1. Notifications to FDA

    Under section 582(b)(4)(B)(ii)(I), (c)(4)(B)(ii), (d)(4)(B)(ii), 
and (e)(4)(B)(ii) of the FD&C Act, and beginning not later than January 
1, 2015, a manufacturer, repackager, wholesale distributor, or 
dispenser who determines that a product in its possession or control is 
illegitimate, must notify FDA of that determination not later than 24 
hours after the determination is made. In addition, section 
582(b)(4)(B)(ii)(II) of the FD&C Act requires manufacturers to notify 
FDA when a manufacturer determines that a product poses a high risk of 
illegitimacy.
    FDA originally estimated that a total of approximately 5,000 
notifications per year would be made by all manufacturers, repackagers, 
wholesale distributors, and dispensers. This estimate included the 
notifications by trading partners who have determined that illegitimate 
product is in their possession or control, as well as notifications by 
manufacturers that have determined a product poses a high risk of 
illegitimacy. As discussed in the June 11, 2014, Federal Register 
notice, this estimate was based on FDA's experience with FARs (Form FDA 
3331) required to be submitted by holders of approved drug applications 
for certain drug quality issues (Sec.  314.81(b)(1) (21 CFR 
314.81(b)(1))), and with reports of the falsification of drug sample 
records, diversion, loss, and known theft of prescription drug samples 
as currently required under Sec.  203.37 (21 CFR 203.37). In response 
to the Federal Register notice, FDA received a comment from a trade 
association representing a primary stakeholder stating that the 
estimate of 5,000 notifications was too high based on experience of its 
members. In response to the comment, FDA reexamined the estimate of 
5,000 notifications. We determined that the 5,000 FARs and 5,000 sample 
reports under Sec.  203.37 received each year included initial, 
followup and final reports. While FDA does not know the exact number of 
notifications that will be submitted, we lowered the estimate to 1,000 
notifications in response to the comment and our reexamination of the 
data, and adjusted the PRA accordingly.
    FDA is combining the estimates for manufacturers and repackagers 
because FDA's establishment and drug product listing database indicates 
that many companies perform activities of both manufacturers and 
repackagers. While the DSCSA specifically defines dispensers, for 
estimation purposes, FDA is using estimates for pharmacies in general 
terms based on those that must comply with the new requirements under 
section 582(d) of the FD&C Act.
    Because, collectively, manufacturers, repackagers, and wholesale 
distributors are responsible for prescription drugs from the point of 
manufacturing through distribution in the drug supply chain, in the 
June 11, 2014, Federal Register notice, FDA assumed that most 
notifications of illegitimate products would be made by these three 
trading partners. FDA received a comment from a major stakeholder group 
stating that they believed that the number of notifications estimated 
for wholesale distributors was too high based on their past experience. 
The commenter speculated that most notifications would be made by 
manufacturers. In addition, manufacturers are the only stakeholder 
group required to submit notifications of high risk of illegitimacy. 
FDA originally estimated that approximately 50 percent of the 
notifications will be made by manufacturers and repackagers, 45

[[Page 55366]]

percent by wholesaler distributors, and 5 percent by pharmacies. In 
response to the comment and the fact that only manufacturers submit 
notifications of high risk of illegitimacy, FDA is changing the 
proportion that will be made by manufacturers and repackagers to 80 
percent (800), 16 percent by wholesale distributors (160), and 4 
percent by pharmacies (40).
    FDA estimates that the number of annual notifications will vary 
from 0-2 for manufacturers/repackagers, wholesale distributors, and 
pharmacies, with the vast majority of companies making no 
notifications. While the FDA establishment and drug product listing 
database currently contains registrations for approximately 6,500 
manufacturers and repackagers, we estimate that approximately 800 
manufacturers/repackagers will notify FDA of illegitimate product or a 
product with a high risk of illegitimacy an average of one time per 
year. While FDA estimates approximately 69,000 pharmacy sites in the 
United States, based on data from the National Association of Chain 
Drug Stores, the National Community Pharmacists Association, and the 
American Hospital Association, we estimate that approximately 40 
pharmacies will notify FDA of illegitimate product an average of one 
time per year. Because, according to Healthcare Distribution Management 
Association, approximately 30 wholesale distributors are responsible 
for over 90 percent of drug distributions, based on sales, and because 
FDA is estimating that over 2,200 small wholesale distributors might be 
responsible for the remaining 10 percent of drug sales, we estimate 
that distributors will be responsible for making an estimated 160 
notifications FDA will receive regarding illegitimate product.
    FDA intends to make Form FDA 3911 available on its Web page for 
trading partners to use to notify FDA. Each notification should include 
information about the person or entity initiating the notification, the 
product determined to be illegitimate, or to have a high risk of 
illegitimacy, and a description of the circumstances surrounding the 
event that prompted the notification. FDA estimates that each 
notification will take about 1 hour. The estimated total annual burden 
hours for making notifications to FDA is approximately 1,000 hours 
annually (table 1).

2. Notifications to Trading Partners of an Illegitimate Product or 
Product With a High Risk of Illegitimacy

    Under section 582(b)(4)(B)(ii)(I), (c)(4)(B)(ii), (d)(4)(B)(ii), 
and (e)(4)(B)(ii) of the FD&C Act, a trading partner who determines 
that a product in its possession is illegitimate must also notify all 
immediate trading partners that the trading partner has reason to 
believe may have received such illegitimate product of that 
determination not later than 24 hours after the determination is made. 
In addition, a manufacturer is required, under section 
582(b)(4)(B)(ii)(II) of the FD&C Act, to notify all immediate trading 
partners that the manufacturer has reason to believe may possess a 
product manufactured by or purported to be manufactured by the 
manufacturer not later than 24 hours after the manufacturer has 
determined or been notified by FDA or a trading partner that the 
product has a high risk of illegitimacy.
    Because the extent of distribution of any illegitimate product is 
likely to vary from one situation to another, FDA assumed a wide 
distribution of each illegitimate product. FDA estimates that for each 
notification made by a manufacturer or repackager to FDA, approximately 
30 trading partners (based on the number of distributors) will also be 
notified. This results in approximately 24,000 notifications annually 
to trading partners of manufacturers/repackagers. This estimate 
includes the notifications by manufacturers and repackagers who have 
determined that illegitimate product is in their possession or control, 
as well as notifications by manufacturers that have determined that a 
product poses a high risk of illegitimacy.
    FDA estimates that a large wholesale distributor may have up to 
4,500 trading partners, but a small wholesale distributor may have 200 
trading partners, for an average of approximately 2,350. FDA originally 
estimated that a wholesale distributor would notify all 2,350 trading 
partners for each of the illegitimate products identified. However, 
comments received from a trade association indicated that they believed 
this number was too high based on past experience. FDA has reduced the 
number of trading partners that a wholesale distributor would notify to 
50 percent resulting in the notification of 1,175 trading partners for 
each of the 160 notifications resulting in a total of 188,000 
notifications to trading partners.
    FDA estimates that a pharmacy purchases prescription drugs from an 
average of two wholesale distributors. Therefore, a pharmacy would 
notify 2 trading partners for each of the 40 illegitimate products 
identified, resulting in approximately 80 notifications annually to 
pharmacy trading partners.
    Manufacturers/repackagers, wholesale distributors, and pharmacies 
may notify their trading partners using existing systems and processes 
used for similar types of communications, which might include, but is 
not limited to, posting of notifications on a company Web site, 
telephoning, sending an email, or mailing or faxing a letter or 
notification. The information contained in the notification to the 
immediate trading partner should be the same as or based on the 
notification that was already submitted to FDA. FDA estimates that for 
all trading partners, each notification of immediate trading partners 
will take approximately 0.2 hours. The estimated total burden hours of 
making notifications to trading partners is approximately 42,416 hours 
annually (table 2).

3. Consultation With FDA and Termination of Notification

    Section 582(b)(4)(B)(iv), (c)(4)(B)(iv), (d)(4)(B)(iv), and 
(e)(4)(B)(iv) of the FD&C Act require that a trading partner, who 
determines in consultation with FDA that a notification made under 
section 582(b)(4)(B)(ii), (c)(4)(B)(ii), (d)(4)(B)(ii), or 
(e)(4)(B)(ii) is no longer necessary, must terminate the notification. 
The guidance sets forth the process by which trading partners must 
consult with FDA to terminate notifications that are no longer 
necessary.
    FDA is making Form FDA 3911 available to trading partners on its 
Web page to request a termination of notification. Each request for 
termination of notification must include information about the person 
or entity initiating the request for termination, the illegitimate 
product or product with a high risk of illegitimacy, the notification 
that was issued, and an explanation about what actions have taken place 
or what information has become available that make the notification no 
longer necessary. Trading partners should also include the FDA-assigned 
incident number associated with the initial notification on the request 
for termination. The request for a termination will be viewed as a 
request for consultation with FDA. FDA estimates that the same amount 
of time will be required to provide the information necessary to 
request termination as is required to make the notification. The time 
required to investigate and resolve an illegitimate product 
notification will vary, but FDA assumes that each notification will 
eventually be terminated at some point. FDA assumes that the number of

[[Page 55367]]

requests for termination of a notification per year will be the same as 
the original number of notifications for a given year. The estimated 
total burden hours of making requests for termination of notifications 
to FDA is approximately 1,000 hours annually (table 3).

4. Notifications to Trading Partners That a Notification Has Been 
Terminated

    Section 582(b)(4)(B)(iv), (c)(4)(B)(iv), (d)(4)(B)(iv), and 
(e)(4)(B)(iv) of the FD&C Act require that a trading partner who, in 
consultation with FDA, terminates a notification made under section 
582(b)(4)(B)(ii)(I) or (II), (c)(4)(B)(ii), (d)(4)(B)(ii), or 
(e)(4)(B)(ii) must also promptly inform previously-notified immediate 
trading partners that the notification has been terminated. FDA 
estimates that the burden for notifying trading partners of an 
illegitimate product and the number of trading partners notified will 
be the same as the estimates for notification of termination. The 
estimated total burden of notifying trading partners that the 
notification is terminated is approximately 42,416 hours annually 
(table 4).
    The total burden of drug notifications for all stakeholders is 
86,832 hours.
    In the Federal Register of June 11, 2014 (79 FR 33564), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received comments on the draft guidance 
from 20 different organizations, companies, and individuals. The draft 
guidance provided scenarios that could increase the risk of a suspect 
product entering the supply chain and recommendations on how trading 
partners may identify products that may be suspect. The draft guidance 
also provided the process for notifying FDA and immediate trading 
partners when a trading partner has determined that a product is an 
illegitimate product or a manufacturer has determined that a product 
has a high risk of illegitimacy and the process for terminating those 
notifications in consultation with FDA. Many of the comments requested 
information about parts of the DSCSA that were not specifically covered 
by, nor intended to be covered by, the draft guidance, such as cleared 
product notifications, suspect product investigation, illegitimate 
product determinations, quarantine, and verifications, which FDA 
intends to address in other guidance or by other public means.
    Several commenters raised issues pertaining to the information 
collection provisions in the draft guidance and Form FDA 3911. FDA has 
clarified the process for making notifications and requests for 
termination to FDA in the final guidance. FDA also clarified several 
fields on Form FDA 3911 and the instructions for using Form FDA 3911 in 
response to comments received to the draft guidance. The issues raised 
by the commenters are addressed further in this document.
Scope-Related Issues
    Issue 1: Several comments were received requesting clarification 
about the scope of what is considered to be an illegitimate product or 
what constitutes a high risk of illegitimacy. For example, commenters 
requested clarification that a product may be determined to be 
illegitimate only as a result of fraud and not due solely to quality 
issues. Commenters also asked for a definition of high risk of 
illegitimacy.
    FDA Response to Issue 1: The purpose of this guidance is to provide 
a process for trading partners to submit notifications to FDA and 
immediate trading partners after the determination of illegitimacy or 
high risk of illegitimacy has been made and to submit requests for 
consultation to FDA to terminate a notification. To determine the scope 
of illegitimate products, trading partners should refer to the 
definition of illegitimate product in section 581(8) of the FD&C Act 
(21 U.S.C. 360eee(8)), which does not exempt quality issues. The 
current guidance has been amended to add scenarios to help 
manufacturers determine if a product has a high risk of illegitimacy. 
Please refer to Issue 14 for more information on ``high risk of 
illegitimacy.''
    Issue 2: Is it necessary to send a notification to FDA when an 
illegitimate product or product with high risk of illegitimacy can be 
dispositioned or contained quickly?
    FDA Response to Issue 2: Yes. Provisions of the DSCSA require 
trading partners to notify FDA when a determination has been made that 
a product is illegitimate, or for manufacturers, that a product has a 
high risk of illegitimacy. The amount of time it takes for a firm to 
control the product or manage the situation is not a factor in 
determining when a notification to FDA and other trading partners is 
required, i.e. not later than 24 hours after the determination is made 
that a product is illegitimate or has a high risk of illegitimacy.
    Issue 3: Many commenters asked if FDA was going to make either Form 
FDA 3911 or information about the notifications public.
    FDA Response to Issue 3: The notifications and requests for 
termination will be handled according to Agency regulations, the 
Freedom of Information Act, and other applicable disclosure law. In 
some cases, FDA may coordinate with the notifying person or entity and 
issue Agency public health alerts to protect the public health based on 
information received through drug notifications received under section 
582(b)(4)(B)(ii), (c)(4)(B)(ii), (d)(4)(B)(ii), and (e)(4)(B)(ii) of 
the FD&C Act.
Form FDA 3911 and Instruction-Related Issues
    Several commenters requested clarification of the instructions for 
filling out existing fields on Form FDA 3911 or requested additional 
information be added to Form FDA 3911 including additional fields.
    Issue 4: Commenters requested clarification about the fields on 
Form FDA 3911 to describe the product that is the subject of the 
notification. Specifically, commenters wanted clarification about the 
terms ``generic'' and ``trade'' names.
    FDA Response to Issue 4: FDA has clarified the names of these 
fields on Form FDA 3911 and the associated instructions. The field 
called ``Generic Name'' was changed to ``Name of Product as it appears 
on the label''. The field called ``Trade Name (if applicable)'' was 
changed to ``Primary Ingredients'' and the instructions were amended to 
request that the notifying person or entity list the active 
pharmaceutical or biological ingredients, if known, and if the 
information is not already listed in the ``Name of Product as it 
appears on the label'' field. These changes will clarify how the 
notifying person or entity should describe the product that is the 
subject of the notification.
    Issue 5: Several commenters wanted clarification about the fields 
on Form FDA 3911 for identification of company versus the reporter.
    FDA Response to Issue 5: FDA modified Form FDA 3911 to make it 
clearer that we want information about the company who is responsible 
for making the notification. The ``reporter'' is the person whom the 
FDA may contact for additional information about the notification. FDA 
considers the company with the illegitimate product in its possession 
or control, or a manufacturer that has made a determination that a 
product has a high risk of illegitimacy, to be the company that is 
responsible for making and terminating the notification, even if that 
company contracts with another person or entity to submit the 
notification on its behalf.

[[Page 55368]]

    Issue 6: Commenters asked about the term ``unique facility 
identifier'' since the D-U-N-S number is a corporate identifier not a 
facility identifier. The commenter requested that FDA clarify that it 
is asking for the unique ``Corporate'' and not ``Facility'' identifier.
    FDA Response to Issue 6: FDA uses a site specific identifier called 
the unique facility identifier (UFI) as a useful resource in 
identifying and confirming certain business information for the company 
responsible for making the notification. FDA currently prefers the D-U-
N-S number as the UFI. Since the commenters were confused about the 
term ``facility'', we clarified in the instructions to Form FDA 3911 
that the UFI for the company making the notification is the number 
being requested.
    Issue 7: Several commenters requested a notification reference 
number for identification purposes.
    FDA Response to Issue 7: FDA agrees with the commenters and has 
added a field for an incident number. FDA plans to assign an incident 
number when the initial notification is received. FDA will send the 
incident number in the response that confirms the receipt of the 
initial notification to the notifying person or entity. This incident 
number should be used in all future correspondence about the specific 
incident/event that is the subject of the initial notification, 
including any request for termination. The form, instructions, and 
process in the guidance have been amended to include the incident 
number. There is no additional burden to the company making the 
notification to include this number on any additional correspondence 
with FDA including the request for termination.
    Issue 8: Commenters requested the addition of an FDA contact be 
added to Form FDA 3911 for questions about the form.
    FDA Response to Issue 8: FDA has added a contact telephone number 
in addition to the email address previously provided on the Drug 
Notification Web page referenced in the guidance.
    Issue 9: Commenters requested a field to indicate that the company 
making the notification (wholesale distributor, repackager, or 
dispenser) has consulted with the manufacturer when determining whether 
a product is illegitimate.
    FDA Response to Issue 9: The DSCSA, section 582(c)(4)(B), 
(d)(4)(B), and (e)(4)(B), requires that wholesale drug distributors, 
dispensers, and repackagers coordinate with the manufacturer when 
determining whether a product is illegitimate. Form FDA 3911 should be 
used to submit a notification after the determination that a product is 
illegitimate is made. A separate field was not designated for this 
topic because the company making the notification may identify the 
manufacturer they coordinated within the ``For Notification, 
Description of Event/Issue'' Field. This option has been added to the 
instructions.
    Issue 10: Commenters requested a field on Form FDA 3911 to list all 
trading partners that they believe may possess the illegitimate 
product.
    FDA Response to Issue 10: FDA did not add a specific field to Form 
FDA 3911 for companies to list the names of trading partners that may 
have illegitimate product. While not required, a company may identify 
all trading partners that they believe may possess the illegitimate 
product in the ``Description of Event/Issue'' Field. Under the DSCSA, 
trading partners are responsible for making notifications to all 
immediate trading partners that they have reason to believe may have 
received such product.
    Issue 11: Commenters requested a space or field to list a case or 
report number associated with a Medwatch report or other report 
submitted to FDA.
    FDA Response to Issue 11: FDA agrees with commenters that it may be 
useful to know the report or case number for other required or 
voluntary submissions made to FDA about the same issue. This 
information may be included in the ``For Notification: Description of 
Event/Issue'' or ``For Request for Termination of Notification: 
Description of Why Notification is No Longer Necessary'' fields. FDA 
amended the instructions on Form FDA 3911 for notifying parties to 
provide this information if known.
    Issue 12: Commenters requested a check box to indicate that testing 
of the drug product was completed.
    FDA Response to Issue 12: FDA did not add a check box to indicate 
if testing was completed. However, the company making the notification 
or request for termination should provide this type of information in 
the fields, ``For Notification, Description of Event/Issue'' or ``For 
Request for Termination of Notification: Description of Why 
Notification is No Longer Necessary.''
    Issue 13: Commenters asked for clarification about the purpose of 
the ``drug use'' and ``drug description'' fields.
    FDA Response to Issue 13: The DSCSA applies to prescription drugs 
for human use. Including these fields helps FDA confirm that the DSCSA 
requirement applies to the product(s) subject to the notification. The 
fields also provide flexibility for future use of this form in other 
contexts. FDA included an ``other'' option under the ``drug use'' field 
to choose if a drug has multiple approvals for use. An instruction to 
explain ``other'' when selected by a notifying person or entity was 
added. We have also included more choices under the ``drug 
description'' field to help FDA distinguish between products regulated 
by the Center for Drug Evaluation and Research and the Center for 
Biologics Evaluation and Research.
High Risk of Illegitimacy-Related Issues
    Issue 14: Several manufacturers requested clarification and 
specific information about how to document that a notification is for a 
product with ``a high risk of illegitimacy.'' Commenters also requested 
clarification on FDA's interpretation of ``high risk of illegitimacy.''
    FDA Response to Issue 14: In the draft guidance, FDA did not 
distinguish between illegitimate product notifications and high risk of 
illegitimacy notifications because the timing and process for these 
submissions is the same. However, because we received several comments, 
FDA has revised the guidance to specify the process for notifications 
for products with a ``high risk of illegitimacy'' that are required by 
the DSCSA to be submitted by manufacturers. The guidance provides 
direction for manufacturers on how to submit notifications for products 
with a high risk of illegitimacy. It also clarifies when products may 
have a high risk of illegitimacy. These clarifications do not affect 
our expected numbers of notifications or terminations, since the PRA 
estimates in the draft guidance already included products with a high 
risk of illegitimacy. FDA also amended the instructions for Form FDA 
3911 to indicate that manufacturers document a notification for product 
with a ``high risk of Illegitimacy'' in the ``For Notification, 
Description of Event/Issue'' field. FDA clarified the instructions for 
several other fields on Form FDA 3911 to indicate more clearly that 
they apply to both notifications for illegitimate products and for 
products with a high risk of illegitimacy.
Timing-Related Issues
    Issue 15: Commenters asked for clarification regarding the 
requirement to submit a notification within 24 hours of making the 
determination that a product is illegitimate or has a high risk of 
illegitimacy.
    FDA Response to Issue 15: The DSCSA specifies that notifications 
are to

[[Page 55369]]

be submitted no later than 24 hours after making the determination that 
a product in the possession or control of the trading partner is 
illegitimate. This same timeframe also applies to manufacturers 
notifying FDA and other trading partners when they determine that a 
product has a high risk of illegitimacy. This timeframe will help 
prevent or limit illegitimate product or product with a high risk of 
illegitimacy from entering or being further distributed in the U.S. 
supply chain.
    Issue 16: Several commenters indicated that a 10-day timeframe for 
FDA to provide a consultation in response to a request for termination 
is too long and could result in drug shortages. Commenters stated that 
the process for requesting expedited consultation was unclear.
    FDA Response to Issue 16: FDA will review and consult with 
notifying parties regarding requests for termination as soon as 
possible. The timing of FDA's review and consultation will depend on 
the number of requests and the circumstances surrounding the requests 
for termination that are received. Since notifications under the DSCSA 
are submitted to FDA when it has been determined by trading partners 
that a product is illegitimate or by manufacturers that a product has a 
high risk of illegitimacy, in many cases, these products would be 
counterfeit, intentionally adulterated, diverted, stolen, or otherwise 
unfit for further distribution and would likely not be further 
distributed. As FDA indicated in the draft guidance, FDA will consider 
requests for expedited review when included with a request for 
termination. We have clarified the process for requesting expedited 
review by adding an instruction to Form FDA 3911 directing the company 
that is requesting termination to also request and justify the need for 
expedited review when explaining why the notification is no longer 
necessary.
Duplication of Submission-Related Issues
    Issue 17: Comments were received requesting an explanation of why 
the development of Form FDA 3911 was necessary instead of using the 
standard FAR for notifications under the DSCSA.
    FDA Response to Issue 17: The FAR is a required postmarketing 
report made by an application holder (new drug or generic drug) when 
there is a problem, generally a quality problem, associated with a drug 
as outlined in Sec.  314.81(b)(1). FDA developed Form FDA 3911 because 
the FAR form was inadequate for making notifications required under the 
DSCSA for a product that is illegitimate or has a high risk of 
illegitimacy for a reason not necessarily related to product quality or 
otherwise described in Sec.  314.81(b)(1) (e.g., diverted, stolen, 
etc.). In addition, only applicant holders are required to submit the 
FAR to FDA. Illegitimate product notifications are required to be sent 
to FDA by manufacturers, repackagers, distributors, and dispensers. 
Notifications of products with a high risk of illegitimacy are also 
required to be submitted by manufacturers. It is not known how 
frequently the same incident will generate submission of a FAR and Form 
FDA 3911 notifications. FDA is collecting information on FDA Form 3911 
that will enable us to quantify duplication of submissions.
    Issue 18: Commenters requested clarification about whether every 
trading partner should submit a separate notification to FDA about the 
same illegitimate product.
    FDA Response to Issue 18: The DSCSA (section 582(b)(4)(B)(ii), 
(c)(4)(B)(ii), (d)(4)(B)(ii), and (e)(4)(B)(ii)) requires that certain 
trading partners (manufacturers, repackagers, wholesale distributors, 
and dispensers) with illegitimate product in their possession or 
control submit a notification. Trading partners should submit 
notifications as required by the relevant statutory provisions.
    Issue 19: Commenters requested clarification about whether they are 
required to submit a notification to FDA if they are notified of a 
suspect or illegitimate product by FDA and determine that they have it 
in their possession or control.
    FDA Response to Issue 19: The DSCSA (section 582(b)(4)(B)(ii), 
(c)(4)(B)(ii), (d)(4)(B)(ii), and (e)(4)(B)(ii)) requires certain 
trading partners (manufacturers, repackagers, wholesale distributors, 
and dispensers) to submit an illegitimate product notification to FDA 
if a trading partner determines that it has illegitimate product in its 
possession or control.
Notifying Trading Partners-Related Issues
    Issue 20: Several comments asked for clarification about the 
process for notifying trading partners of an illegitimate product. 
Commenters stated that FDA should clarify that existing systems and 
processes can be used to make notifications to trading partners as well 
as informing them of terminations of such notifications.
    FDA Response to Issue 20: In the draft guidance, FDA specified that 
existing processes and systems can be used to inform trading partners 
that a notification has been terminated. FDA agrees with the comments 
received and has added to the final guidance that trading partners can 
use existing systems and processes to provide notification to trading 
partners that they believe may have received the illegitimate product 
or a product with high risk of illegitimacy.
    Issue 21: A commenter requested that FDA develop a system that 
would allow for notification of FDA and other trading partners at the 
same time.
    FDA Response to Issue 21: Manufacturers, repackagers, wholesale 
distributors, and dispensers with illegitimate product or manufacturers 
that determine that a product has a high risk of illegitimacy are 
responsible for notifying their trading partners in addition to FDA. 
FDA developed a process for trading partners to use to notify FDA using 
Form FDA 3911. As clarified in the guidance and Issue 20, the notifying 
person or entity can use its existing systems and processes to provide 
the necessary notification to trading partners. If preferred, the 
notifying person or entity may provide a copy of Form FDA 3911 to other 
trading partners in addition to FDA to meet that requirement.
    Issue 22: A commenter asked for clarification if dispensers' 
immediate trading partners include other pharmacies in the same group 
of chain pharmacies as well as the wholesale distributor or 
manufacturer from whom the dispenser purchased drug.
    FDA Response to Issue 22: The intent of the notification provisions 
in the DSCSA is to prevent illegitimate product entering or being 
further distributed into the supply chain to protect public health. FDA 
expects that a dispenser that has illegitimate product in its 
possession or control would let the other trading partners know about 
such illegitimate product if the dispenser has reason to believe that 
they might have possession or control of the same product. This 
analysis will be situation-specific. FDA refers the commenter to the 
definition of ``trading partner'' in section 581(23) of the FD&C Act 
and the definition of ``dispenser'' in section 581(3) of the FD&C Act.
Termination Process-Related Issues
    Issue 23: One commenter stated that FDA should publish guidance on 
criteria to terminate a notification so that the FDA does not have to 
play ``gatekeeper'' for the termination of a notification.
    FDA Response to Issue 23: The DSCSA (section 582(b)(4)(B)(iv), 
(c)(4)(B)(iv), (d)(4)(B)(iv), and (e)(4)(B)(iv) of FD&C Act) requires 
that a notification be terminated in

[[Page 55370]]

consultation with FDA. This guidance addresses the process by which 
trading partners should use Form FDA 3911 to make requests for 
termination, and the form will serve as a request to consult with FDA.
    Issue 24: Comments were received asking for clarification about 
which entities could request to terminate a notification. Several 
commenters thought that FDA should be able to self-initiate a 
termination. Other commenters suggested that the request for 
termination could be made by any involved trading partner and not 
limited to the trading partner making the initial notification.
    FDA Response to Issue 24: FDA believes that the trading partner 
making the notification should be responsible for making the request 
for termination because it knows if the illegitimate product in its 
possession or control has been satisfactorily dispositioned and if the 
notification is no longer necessary. The process in the guidance has 
been amended to clarify this point. The guidance does not specify a 
process for trading partners to terminate notifications submitted by 
other trading partners.
PRA Analysis Related Issues
    Issue 25: One commenter stated that the estimates in the PRA 
analysis did not take into account the time it takes to investigate and 
make the determination that a product is illegitimate. It only included 
the time to fill out the form and notify trading partners.
    FDA Response to Issue 25: While the commenter's assessment is 
correct, the PRA analysis in this guidance was calculated for the 
process for making and terminating notifications to FDA and notifying 
immediate trading partners who are believed to have the drug. This 
guidance assumes that the determination has already been made that the 
drug is illegitimate or has a high risk of illegitimacy. FDA intends to 
publish additional guidance that will address the investigation of 
suspect product to determine whether the product is illegitimate. The 
PRA analysis for those activities will be covered at that time.
    Issue 26: One commenter stated that, based on its experience, FDA 
estimates for notifications are high.
    FDA Response to Issue 26: FDA reexamined the estimate of 
notifications in response to this comment. FDA originally estimated 
that a total of approximately 5,000 notifications per year would be 
made by all manufacturers, repackagers, wholesale distributors, and 
dispensers based on FDA's experience with FARs (Form FDA 3331) required 
to be submitted by holders of approved drug applications for certain 
issues specified by Sec.  314.81(b)(1), and with reports of the 
falsification of drug sample records, diversion, loss, and known theft 
of prescription drug samples as currently required under Sec.  203.37. 
We determined that the 5,000 FARs and 5,000 sample reporting under 
Sec.  203.37 received each year included initial, followup, and final 
reports. While FDA does not know the exact number of notifications that 
will be submitted, we lowered the estimate to 1,000 notifications in 
response to the comment and our reexamination of the data and adjusted 
the PRA analysis accordingly.
    Issue 27: Commenters stated that the FDA estimated number of 
trading partners that would likely have the illegitimate product and 
have to be notified was high.
    FDA Response to Issue 27: FDA recognizes that not every trading 
partner will possess illegitimate product. However, until serialization 
is required and implemented, the initial notifying person or entity may 
not be able to identify which specific immediate trading partners may 
possess or control illegitimate product. FDA assumed that the initial 
notifying person or entity would notify all trading partners and we 
have chosen not to amend the number of trading partners that are 
notified at this time.
    Issue 28: A major stakeholder association stated that it did not 
believe, based on past experience, that wholesale distributors would be 
making as many notifications as FDA estimated both to FDA and to 
trading partners.
    FDA Response to Issue 28: In the original estimates, FDA assumed 
that most notifications will be made by three trading partners, 
manufacturers, repackagers, and wholesale distributors. FDA reexamined 
the proportion of notification expected from each of the regulated 
groups. The commenter had speculated that it believed that 
manufacturers would be making most notifications. In addition, 
manufacturers are required to submit notifications of high risk of 
illegitimacy. In response to the comment and the fact that only 
manufacturers submit notifications of high risk of illegitimacy, FDA is 
changing the proportion of notifications that will be made by 
manufacturers and repackagers from 50 percent to 80 percent (800), from 
45 percent to 16 percent by wholesale distributors (160), and 5 percent 
to 4 percent by pharmacies (40). FDA had also originally assumed that 
wholesale distributors would have to notify an average of 2,350 trading 
partners for each notification. We agree with the commenters that this 
was an overestimation and have lowered the number of trading partners 
to be notified by wholesale distributors to 1,175 (50 percent) for each 
notification.
    Description of Respondents: Respondents are drug manufacturers, 
repackagers, wholesale distributors, and dispensers and might include 
small businesses in these categories.

                                 Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
      Notifications to FDA           Number of     responses per   Total annual     burden per      Total hours
                                    respondents     respondent       responses       response
----------------------------------------------------------------------------------------------------------------
Manufacturers and Repackagers...             800               1             800               1             800
Wholesale Distributors..........             160               1             160               1             160
Dispensers......................              40               1              40               1              40
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............           1,000
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


[[Page 55371]]


                           Table 2--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
   Notifications to trading                        Number of
 partners of an illegitimate      Number of     disclosures per   Total annual    Average burden    Total hours
           product               respondents      respondent       disclosures    per disclosure
----------------------------------------------------------------------------------------------------------------
Manufacturers and Repackagers             800                30          24,000  0.20 (12                   4800
                                                                                  minutes).
Wholesale Distributors.......             160             1,175         188,000  0.20 (12                 37,600
                                                                                  minutes).
Dispensers...................              40                 2              80  0.20 (12                     16
                                                                                  minutes).
                              ----------------------------------------------------------------------------------
    Total....................  ..............  ................  ..............  ...............          42,416
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


                                 Table 3--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
    Consultation with FDA and        Number of     responses per   Total annual     burden per      Total hours
   termination of notification      respondents     respondent       responses       response
----------------------------------------------------------------------------------------------------------------
Manufacturers and Repackagers...             800               1             800               1             800
Wholesale Distributors..........             160               1             160               1             160
Dispensers......................              40               1              40               1              40
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............           1,000
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


                           Table 4--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
   Notifications to trading                        Number of
 partners of an illegitimate      Number of     disclosures per   Total annual    Average burden    Total hours
     product termination         respondents      respondent       disclosures    per disclosure
----------------------------------------------------------------------------------------------------------------
Manufacturers and Repackagers             800                30          24,000  0.20 (12                   4800
                                                                                  minutes).
Wholesale Distributors.......             160             1,175         188,000  0.20 (12                 37,600
                                                                                  minutes).
Dispensers...................              40                 2              80  0.20 (12                     16
                                                                                  minutes).
                              ----------------------------------------------------------------------------------
    Total....................  ..............  ................  ..............  ...............          42,416
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


    Dated: September 10, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-23203 Filed 9-14-15; 8:45 am]
BILLING CODE 4164-01-P