Doc. Ref: US/MRA/EMEAv1.0

 United States - EC Mutual Recognition Agreement

FINAL

Status

Article 20 of the U.S.-EC MRA Pharmaceutical Good Manufacturing Practices Annex (hereinafter referred to as "the Annex") requires that an alert system be developed and maintained. The intention of the alert system is to promptly notify authorities of quality defects, recalls, counterfeiting and other problems concerning quality which could necessitate additional actions or suspension of the distribution of pharmaceutical/medicinal products.

Appendix 5 of the Annex indicates a number of elements to be considered in developing this alert system. The elements include documentation, a crisis management system, enforcement procedures, a quality assurance system, and contact points. The MRA Framework states that the U.S. and the EU "will maintain, to the extent required under its laws, the confidentiality of information exchanged under this Agreement."

It is the responsibility of the Competent Authority of each EU Member State and the FDA in the United States to assist the recalling firm in the recall process, as appropriate, and to monitor its effectiveness. It is also the responsibility of the Competent Authority/FDA to ensure that information concerning a recall of pharmaceutical products is notified to other Member States and MRA-Partners, if the nature of the defect presents a risk to public health.

By joint collaboration and agreement this document establishes the procedures for US-EU exchanges of certain product recall information in partial implementation of Article 20 of the U.S.-EC MRA, Pharmaceutical GMPs Annex. In the future, additional information exchanges or procedures will be established to fully implement Article 20.

The purpose of this procedure is to share information in a timely and effective manner so as to minimize the risk to the affected public and maintain confidence in the system. It includes the transmission of information relating to the quality of pharmaceutical products under recall.

The goals expected to be achieved by this procedure are:

• To protect U.S. and EU Member State consumers from potential health risks arising from the use of human/animal pharmaceutical products.
• To facilitate the recall from the market of human/animal pharmaceuticals which pose a risk to public health.
• To promote collaboration between regulatory authorities on emerging product quality problems.
• To ensure the U.S. public is adequately notified of recalls that pose a risk to public health.

This recall notification standard operating procedure is intended to cover the same human/animal pharmaceutical products covered by the Annex, as stated below:

• Human medicinal products including prescription and nonprescription drugs;
• Human biologicals including vaccines and immunologicals;
• Veterinary pharmaceuticals, including prescription and nonprescription drugs, with the exclusion of veterinary immunologicals;
• Premixes for the preparation of veterinary medicated feeds (EC), Type A medicated articles for the preparation of veterinary medicated feeds (United States);
• Intermediate products and active pharmaceutical ingredients or bulk pharmaceuticals (United States)/starting materials (EC).

Parties agree to exchange product recall information with the designated contacts in a timely manner. Parties will exchange all Class I and Class II recalls of pharmaceutical products, as defined by the respective party, if the recalled product or a component in the product that causes the product to be in violation of the law or is considered to be defective was distributed to the jurisdiction of the other party (i.e., any EU Member State or the USA) or originated from the jurisdiction of the other party (i.e., any EU Member State or the USA). Whenever feasible, parties will make an effort to exchange information about emerging Class I recalls prior to their official classification.

Specifically, only the following information about each recall is to be exchanged:

• Name of intended recipient (regulatory authority official(s)) of recall notification;
• Product recall classification (indicate either I or II);
• Recall number assigned by sender (if available);
• Product name, trade or brand and generic or INN;
• Dosage form and strength;
• Packaging information;
• Batch or lot number(s) and expiration date (if any);
• Date and method of recall (e.g., by letter, fax/phone, press release, etc.);
• Reason for recall (a brief description of the problem or defect);
• Recalling firm's name, address, and contact information;
• Product manufacturer's name and address (if different from recalling firm).
• Name of sender (regulatory authority official);

Attachment A, Notice of Recall is the standard form to be used in this exchange. Shaded areas are not required in the information to be exchanged.

For a batch manufactured in an EU Member State, or a batch manufactured in a third country and imported into the EU, which is the subject of a national or decentralized marketing authorization, it is the responsibility of the Competent Authority of that State to issue the Notice of Recall. Normally this is the State in which the defect was first identified.

In the case of a centralized authorization, it is the responsibility of EMEA to issue the Notice of Recall and to co-ordinate subsequent action.

For a batch manufactured in the United States, it is the responsibility of the FDA to issue the Notice of Recall.

Both parties will endeavor to exchange the Notice of Recall (described in II. A. above and Attachment A) in the English language and transmit by fax and/or electronic mail to the EU Member State/EMEA/FDA contacts identified in Attachment B. The EMEA will facilitate clarification of any document received by the FDA under this SOP.

U.S. FDA:

• Title 21, Code of Federal Regulations, Part 7, Enforcement Policy - Recalls (Including Product Corrections) - Guidelines on Policy, Procedures, and Industry Responsibilities
• Regulatory Procedures Manual, Ch. 7, Recall and Emergency Procedures http://www.fda.gov/ora/inspect_ref/iom/IOMCoverPg.html
• FDA publishes all classified recalls in the weekly Enforcement Report, which is posted on FDA's website at http://www.fda.gov/opacom/enforce.html.

EU:

• Council Directive 75/319/EEC, Ch. V and VI, for Human Medicinal Products
• Council Directive 81/851/EEC, Ch. V and VI, for Veterinary Medicinal Products
• Compilation of Community Procedures on Administrative Collaboration and Harmonization of Inspections (Rapid Alert System).

This SOP is for immediate implementation and will be reevaluated after being in effect for a time period of six (6) months.

The U.S. FDA contact points are:

• Human Drugs: Michael J. Verdi, Recall Coordinator, Office of Compliance (HFD-301), MPNI, 7520 Standish Place, Rockville, MD 20855-2737, phone: 301-594-2456, fax: 301-594-2114; email: CDERRECALLS@cder.fda.gov.
• Biologics: Beatrice Greenberg, Recall Coordinator, Office of Compliance and Biologics Quality (HFM-650), 1401 Rockville Pike, Rockville, MD 20852-1448, phone: 301-827-6201, fax: 301-594-9040; email: CBERRECALLS@cber.fda.gov.
• Veterinary Drugs: Barbara Rodgers, Recall Coordinator, Office of Surveillance and Compliance (HFV-236), MPNII, 7500 Standish Place, Rockville, MD 20855-2773, phone: 301-827-0356, fax: 301-594-1812; email: brodgers@cvm.fda.gov.

The EU Member State/EMEA contact points (at the request of the EU/EMEA, the designated contact list is not being posted at this time).