[Federal Register Volume 71, Number 220 (Wednesday, November 15, 2006)]
[Rules and Regulations]
[Pages 66448-66450]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 06-9211]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 203 and 205

[Docket Nos. 1992N-0297 (Formerly 92N-0297), 1988N-0258 (Formerly 88N-
0258), 2006D-0226]


Prescription Drug Marketing Act Pedigree Requirements under 21 
CFR Part 203 Compliance Policy Guide and Guidance for Industry: 
Prescription Drug Marketing Act Pedigree Requirements Questions and 
Answers; Notice of Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability of guidances.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a final Compliance Policy Guide (CPG) 160.900 entitled 
``Prescription Drug Marketing Act--Pedigree Requirements under 21 CFR 
Part 203'' (PDMA CPG). This CPG describes how the agency intends to 
prioritize its enforcement efforts in the first year after the December 
1, 2006, effective date of 21 CFR Sec. Sec.  203.3(u) and 203.50. In 
addition, the FDA is announcing the availability of ``Guidance for 
Industry: Prescription Drug Marketing Act (PDMA) Pedigree

[[Page 66449]]

Requirements Questions and Answers'' (PDMA Q & A). The PDMA Q & A 
guidance is issued in response to the many questions received regarding 
the Prescription Drug Marketing Act (PDMA) pedigree requirements. The 
two guidance documents explain FDA's current thinking on issues related 
to the pedigree requirements of the PDMA.

DATES: The effective date for the PDMA CPG is December 1, 2006. The 
PDMA CPG expires December 1, 2007. The PDMA Q & A guidance is effective 
November 15, 2006. Submit written or electronic comments on the PDMA Q 
& A guidance or the PDMA CPG at any time.

ADDRESSES: Submit written comments on the PDMA Q & A guidance or the 
PDMA CPG identified by the docket numbers found in the heading of this 
document by any of the following methods:
Electronic Submissions
    Submit electronic comments in the following ways:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
     Agency Web site: http://www.fda.gov/dockets/ecomments. 
Follow the instructions for submitting comments on the agency Web site.
Written Submissions
    Submit written submissions in the following ways:
     FAX: 301-827-6870.
     Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    To ensure more timely processing of comments, FDA is no longer 
accepting comments submitted to the agency by e-mail. FDA encourages 
you to continue to submit electronic comments by using the Federal 
eRulemaking Portal or the agency Web site, as described in the 
Electronic Submissions portion of this paragraph.
    Instructions: All submissions received must include the agency name 
and docket numbers for this rulemaking. All comments received may be 
posted without change to http://www.fda.gov/ohrms/dockets/default.htm, 
including any personal information provided. For additional information 
on submitting comments, see the ``Comments'' heading of the 
SUPPLEMENTARY INFORMATION section of this document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.fda.gov/ohrms/dockets/default.htm 
and insert the docket numbers, found in brackets in the heading of this 
document, into the ``Search'' box and follow the prompts and/or go to 
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Ilisa Bernstein, Office of the 
Commissioner, Office of Policy (HF-11), Food and Drug Administration, 
5600 Fishers Lane, Rockville, MD 20857, 301-827-3360, or by e-mail 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

A. Implementation of 21 CFR Sec. Sec.  203.3(u) and 203.50

    The PDMA, as modified by the Prescription Drug Amendments of 1992, 
amended sections 301, 303, 503, and 801 of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 331, 333, 353, and 381) to establish, 
among other things, requirements related to the wholesale distribution 
of prescription drugs. A primary purpose of the PDMA is to increase 
safeguards to prevent the introduction and retail sale of substandard, 
ineffective, and counterfeit drugs in the U.S. drug supply chain.
    Section 503(e)(1)(A) of the Federal Food, Drug, and Cosmetic Act 
(act) establishes the so-called ``pedigree'' requirement for 
prescription drugs. A drug pedigree is a statement of origin that 
identifies each prior sale, purchase, or trade of a drug, including the 
dates of those transactions and the names and addresses of all parties 
to them. Under the pedigree requirement, each person who is engaged in 
the wholesale distribution of a prescription drug in interstate 
commerce, who is not the manufacturer or an authorized distributor of 
record for that drug, must provide a pedigree for that drug to the 
person who receives the drug. The PDMA states that an authorized 
distributor of record is a wholesaler that has an ``ongoing 
relationship'' with a manufacturer to distribute that manufacturer's 
drug. However, the PDMA does not define ``ongoing relationship.''
    In 1999, FDA published final regulations related to the PDMA (part 
203 (21 CFR part 203)). The regulations were to take effect in December 
2000. After publication of the 1999 final rule, the agency received 
comments objecting to the provisions in Sec. Sec.  203.3(u) and 203.50. 
Section 203.3(u) defines ``ongoing relationship'' to include a written 
agreement between a manufacturer and a distributor. Section 203.50 
specifies the fields of information that must be included in the drug 
pedigree, and states that the information must be traceable back to the 
first sale by the manufacturer. Based on concerns raised by various 
stakeholders, the agency delayed the effective date of Sec. Sec.  
203.3(u) and 203.50 several times.
    Most recently, in February 2004, FDA delayed the effective date of 
Sec. Sec.  203.3(u) and 203.50 until December 1, 2006, in part because 
we were informed by stakeholders in the U.S. drug supply chain that the 
industry would voluntarily implement electronic track and trace 
technology by 2007. If widely adopted, this technology could create a 
de facto electronic pedigree (e-pedigree) documenting the sale of a 
drug product from its place of manufacture through the U.S. drug supply 
chain to the final dispenser. If properly implemented, an electronic 
record could thus meet the pedigree requirements in section 
503(e)(1)(A) of the act. Based on a recent fact-finding effort by FDA 
to assess the use of e-pedigree across the supply chain, however, it 
appears that industry will not fully implement track and trace 
technology by 2007.
    As a result of this fact finding, FDA published a notice in the 
Federal Register on June 14, 2006 (71 FR 34249), announcing that it 
does not intend to delay the effective date of Sec. Sec.  203.3(u) and 
203.50 beyond December 1, 2006. Thus, these provisions defining 
``ongoing relationship'' and setting forth requirements regarding the 
information that must appear in pedigrees will go into effect as of 
December 1, 2006. As part of its June 14, 2006, announcement, FDA also 
issued and requested comment on draft Compliance Policy Guide 160.900 
entitled ``Prescription Drug Marketing Act Pedigree Requirements under 
21 CFR Part 203.''

B. PDMA Compliance Policy Guide

    We are issuing the final PDMA CPG, which describes how we plan to 
prioritize our enforcement efforts during the first year in which 
Sec. Sec.  203.3(u) and 203.50 are effective. This PDMA CPG lists 
factors that FDA field personnel are expected to consider in 
prioritizing FDA's pedigree related enforcement efforts. Consistent 
with our risk-based approach to the regulation of pharmaceuticals, 
utilizing these factors will focus our efforts on drug products that 
are most vulnerable to counterfeiting and diversion or that are 
otherwise involved in illegal activity.
    The priorities described in the PDMA CPG reflect a phased-in type 
approach to the enforcement of the previously stayed pedigree 
provisions. The PDMA CPG will expire December 1, 2007. By providing 
guidance on the types of drugs that are currently of greatest

[[Page 66450]]

concern to FDA, we believe that wholesale distributors will have a 
better idea of where and how to focus their initial energies as they 
implement systems and approaches to come into complete compliance with 
21 CFR part 203.
    FDA is issuing this PDMA CPG as a level 1 guidance consistent with 
FDA's good guidance practices (21 CFR Sec.  10.115).
    We note that guidance documents are not binding on FDA or industry, 
and, under appropriate circumstances, the agency may initiate 
regulatory action, including criminal prosecution, for violations of 
the pedigree requirements.

C. Guidance for Industry: Prescription Drug Marketing Act Pedigree 
Requirements Questions and Answers

    We are also issuing the PDMA Q & A, which represents FDA's current 
thinking on several issues regarding the PDMA pedigree requirements. It 
addresses numerous questions that FDA received as comments to the PDMA 
CPG docket, as well as through e-mail and other communications, 
regarding the PDMA pedigree requirements. The questions and answers in 
the guidance address issues pertaining to manufacturers, wholesale 
distributors, pharmacies, and other entities affected by the PDMA 
pedigree requirements.
    FDA is issuing the PDMA Q & A as a level 1 guidance consistent with 
FDA's good guidance practices (21 CFR Sec.  10.115). Given that the 
relevant PDMA pedigree provisions will go into effect as of December 1, 
2006, FDA is implementing the PDMA Q&A immediately, in accordance with 
Sec.  10.115(g)(2) (21 CFR 10.115(g)(2)), because the agency has 
determined that prior public input is not feasible or appropriate. As 
noted, the pedigree requirements set forth in Sec. Sec.  203.3(u) and 
203.50, which had been stayed on several occasions, will apply to 
prescription drug products as of December 1, 2006. Promptly clarifying 
FDA's current thinking on the questions in the guidance should 
facilitate industry's compliance with the PDMA pedigree requirements.
    Under Sec.  10.115(g), FDA is opening a docket on the PDMA Q & A, 
and we invite interested persons to submit comments and questions. FDA 
intends to review the comments and questions and to revise the PDMA Q & 
A when appropriate, using the question and answer format in the PDMA Q 
& A guidance. For purposes of transparency, efficiency, and clarity, 
the agency believes that, at the present time, it is important to 
maintain FDA's written responses to the significant questions 
concerning the PDMA pedigree requirements in a single guidance document 
that is periodically updated as the agency receives and responds to 
additional questions. We also intend to use the following four 
indicators to help users of the guidance identify future additions or 
revisions: (1) The updated guidance will be identified as a revision of 
the previously issued document, (2) the revision date of the guidance 
will appear on its cover, (3) the edition number of the guidance will 
be included in its title, and (4) questions and answers that have been 
added to the guidance, or prior answers that have been in any way 
modified, will be identified as such in the body of the guidance.
    The PDMA CPG and PDMA Q & A guidance represent the agency's current 
thinking on issues related to the PDMA pedigree requirements. The 
guidances do not create or confer any rights for or on any person and 
do not operate to bind FDA or the public. An alternative approach may 
be used if such approach satisfies the requirements of the applicable 
statutes and regulations.

II. Electronic Access

    An electronic version of the PDMA CPG is available on the Internet 
at http://www.fda.gov/ora under ``Compliance Reference''. An electronic 
version of the PDMA Q & A guidance is available at http://www.fda.gov/pdma.

III. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding the PDMA Q & A 
guidance or PDMA CPG at any time. Submit a single copy of electronic 
comments or two paper copies of any mailed comments, except that 
individuals may submit one paper copy. Comments are to be identified 
with the docket number found in brackets in the heading of this 
document. Received comments and the guidance may be seen in the 
Division of Dockets management between 9 a.m. and 4 p.m., Monday 
through Friday.

    Dated: November 8, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 06-9211 Filed 11-13-06; 8:45 am]
BILLING CODE 4160-01-S