06-9211. 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.

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 §§ 203.3(u) and 203.50. In addition, the FDA is announcing the availability of “Guidance for Industry: Prescription Drug Marketing Act (PDMA) Pedigree 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: [phone].
• 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 [e-mail].

SUPPLEMENTARY INFORMATION:

I. Background

A. Implementation of 21 CFR §§ 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 §§ 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 §§ 203.3(u) and 203.50 several times.

Most recently, in February 2004, FDA delayed the effective date of §§ 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 §§ 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 §§ 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 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 § 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 § 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 § 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 §§ 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 § 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.