FDA has published updated guidelines on Pedigree Drugs for ADR wholesalers (Authorized Distributors of Record) that carry out the sale of drugs. Under the rules, ADRs are exempt from having to supply a pedigree. Pedigree documentation are required for tracing any 3^rd party that handles a drug from the time the drug leaves the manufacturers' facility. A drug pedigree is a statement of origin that identifies each prior sale, purchase, or trade of a drug, including the date of those transactions and the names and addresses of all third parties. This pedigree may be in paper (hard copy) or electronic form and must include the addresses and lot numbers of the drug.

(NOTE! The current law does NOT apply to wholesalers (ADRs) designated as authorized distributors of record by the manufacturer. The law is focused on manufacturers, re-handling agents and middle party resellers)

On November 13, 2006, FDA released its Questions and Answers Guidance (Q&A) and a final Compliance Policy Guide 160.900 (CPG) to clarify pedigree requirements contained in its regulations implementing the Prescription Drug Marketing Act (PDMA). Enforcement of pedigree requirements begins December 1, 2006. The CPG set forth the FDA's intentions for enforcement of the PDMA.

The PDMA requires wholesale distributors of prescription drugs provide information identifying each prior sale, purchase and trade of a drug. Manufacturers and authorized distributors of record (ADRs) are excluded from the requirement to provide pedigrees. The PDMA sets forth "an ADR is a wholesaler that has an ongoing relationship with a manufacturer to distribute that manufacturer's drug."

The PDMA regulations:

• Define "ongoing relationship" to include a written agreement between manufacturer and wholesaler;
• Specify the information to be included in the drug pedigree; and
• Require that the information be traceable back to the first sale by the manufacturer.

1. The proprietary and established name of the drug;
2. Dosage;
3. Container size;
4. Number of containers;
5. The drug's lot or control number(s);
6. The business name and address of all parties to each prior transaction involving the drug, starting with the manufacturer; and
7. The date of each previous transaction.

ADR Status

ADR status is determined by the drug manufacturer and requires a written agreement; invoices are not sufficient to establish ADR status. The manufacturer and the wholesale distributor must both maintain records of the written agreement that establishes the wholesale distributor as ADR. These records must be kept for at least three (3) years. The written agreement must list the specific products and the period of time or number of shipments for which the wholesale distributor is granted ADR status.

Manufacturer's List of ADRs

The manufacturer must maintain its list of ADRs on a continuing basis, and the list must be available at the manufacturer's corporate offices. FDA also encourages manufacturers to post their updated ADR lists on their website so that the lists are easily accessible to the public.

Who is required to pass a pedigree?

Non-ADRs are required to pass pedigrees. If an ADR obtains a drug with a pedigree from a non-ADR, then the ADR must pass the pedigree and maintain records for three (3) years. The FDA strongly encourages manufacturers, ADRs, and all others in the prescription drug supply chain to cooperate by providing pedigrees to trading partners and customers. Intra-company sales and transfers, as well as drugs acquired through a merger, acquisition or buyout, are excluded from pedigree requirements because they are fall outside the definition of wholesale distribution.

Existing Inventory

A pedigree is required for prescription drug products sold, purchased or traded by a non-ADR after December 1, 2006. Although it believes wholesale distributors have had six months to comply with pedigree requirements, FDA will exercise enforcement discretion of pedigree requirements until April 1, 2007 if wholesalers can show:

1. Documentation, including bills of sale or invoices, that the drugs were purchased prior to December 1, 2006; and
2. It had purchased the same type of drugs from the manufacturer on at least two prior occasions in the previous 24 months.

Medical Convenience Kits

Repackaging Agents

Unless they are an ADR, a repackaging agent must provide pedigrees.

Authentication of Pedigree

FDA does not require specific authentication or verification methods.

Recordkeeping Requirements

Pedigree records must be kept for at least three (3) years. Although a pharmacy that does not engage in further wholesale distribution of drugs is not required to maintain pedigrees, FDA encourages them to retain records for three years in case there are questions about the source or history of the drugs.

Scope of Pedigree Requirements

PDMA applies to all human prescription drugs, including those sold to veterinarians. PDMA also applies to bulk drug substances. Pedigree requirements do not apply to drug samples.

Shipping/Delivery Arrangements

A pedigree is required if either a manufacturer or an ADR drop ships on behalf of a non-ADR directly to the pharmacy or customer. A third party logistics provider (3PL) must also provide pedigree unless the 3PL has ADR status.

Returns

A pedigree is required for returns from a non-ADR pharmacy or physician office. However, FDA will exercise enforcement discretion to allow pharmacies and physicians' offices to return drugs that are expired, damaged, recalled, or in another non-saleable condition without requiring a pedigree if a pharmacy or physician office: (1) returns the drugs to the wholesaler or manufacturer from which they purchased the drugs, or to a licensed reverse distributor for destruction; and (2) maintains documentation of each return and original purchase for three (3) years. If the returned drugs are in saleable condition and may be resold, then a pedigree is required for non-ADRs. FDA will monitor drug distribution for abuse of its enforcement discretion. Returns by hospitals, health care entities, and charitable institutions are excluded from the definition of wholesale distribution and therefore do not have to meet pedigree requirements.

Electronic v. Paper Pedigrees

Both paper and electronic documents may be used to meet pedigree requirements. FDA has not adopted any specific electronic standards or technology.

Compliance and Enforcement

Criminal activity related to drug pedigree should be reported to FDA's Office of Criminal Investigations at rxdrugcops@oci.fda.gov. FDA urges wholesale distributors to practice due diligence in accepting pedigrees.

Compliance Policy Guide

The FDA's final CPG is very similar to the draft CPG that was released in June, with minor changes. The CPG lists suggested enforcement targets for FDA field personnel:

1. High value in the U.S. market
2. Prior history of counterfeiting or diversion
3. Reasonable probability for new drugs

The CPG also states that the FDA will enforce other violations of law related to the manufacture or distribution of counterfeit drugs. The CPG expires December 1, 2007.

Resources

The FDA has created a new web site to provide complete background on PDMA, including the Q&A and CPG documents, as well as legislative and regulatory history. The web site is: http://www.fda.gov/cder/regulatory/PDMA/default.htm.