Chapter 3: Mutual Recognition Agreements

Mutual Recognition Agreements

Mutual recognition agreements (MRA) are international agreements that specify the conditions under which the participating countries will accept or recognize one another’s conformity assessments, and that identify how the parties will cooperate on other activities, as specified. The primary objective of MRA is to provide effective and efficient market access throughout the territories of the MRA parties.

MRA Established by the European Union and Partner Countries

The European Union (EU), Australia, Canada, New Zealand, and Switzerland are referred to as MRA partner countries, whereas other countries outside the European Economic Area (EEA) are referred to as third countries. Each agreement has slight differences in coverage; however, the broad general purpose of each MRA is fourfold:

• Facilitate market access while safeguarding consumer health

• Grant mutual acceptance of reports, certificates, and authorizations issued by the regulated authorities of the signatories, and provide certification of conformity to the requirements

• Exchange information concerning procedures used to ensure that the conformity bodies comply with the general principles of designation

• Encourage greater international harmonization

The premise of the MRA is that the MRA partner country and EU member states mutually recognize relevant manufacturing authorizations granted by the competent authorities of the other party, conclusions of inspections of manufacturers carried out by the relevant inspection services of the other party, and manufacturers’ certification of the conformity of each batch to its specifications by the respective party without recontrol at import.

The scope of the agreements covers medicinal products that have undergone one or a series of manufacturing operations in the MRA partner country and/or the EU. For the purposes of these agreements, manufacturing operations include manufacturing, labeling, testing, and wholesaling activities.

Key Elements of Mutual Recognition Agreements

Issuance of Certificate of GMP Compliance of Manufacturers. The purpose of the certificate is to confirm that the manufacturer or laboratory is authorized to carry out activities and is regularly inspected and complies with national good manufacturing practices (GMP) requirements that are deemed equivalent to EU GMP. Authorities responsible for supervision of the entity issue the certificate. A manufacturer can request an inspection by the local competent authority to obtain a certificate.

Batch Certification. Each batch being transferred between MRA countries must be accompanied by a batch certificate issued by the manufacturer in the exporting country. The importer of the batch needs to receive and to maintain this certificate that attests that the batch has been manufactured in accordance with the requirements of the marketing authorization of the importing country and that it meets specifications. The certificate includes a statement that batch processing and packaging records have been reviewed and comply with GMP. The content of the batch certificate has been harmonized and agreed on by MRA partners.

Responsibilities of the Qualified Person. The qualified person (QP) may rely on the written confirmation of the manufacturer’s batch certificate without further testing. Responsibilities of the various parties should, however, be clearly defined in a written agreement.

Pharmaceutical Inspection Cooperation Scheme

The Pharmaceutical Inspection Convention and the Pharmaceutical Inspection Co-operation Scheme (jointly referred to as PIC/S) provide a means for international cooperation in the field of GMP. PIC/S is a cooperation scheme. Membership, however, does not mean that an MRA exists. PIC/S’s mission is to lead the international development, implementation, and maintenance of harmonized GMP standards and quality systems of inspectorates in the field of medicinal products. The purpose of the PIC/S scheme is to:

• Pursue and strengthen the cooperation established between the participating authorities in the field of inspection and related areas with a view to maintaining mutual confidence and promoting quality assurance of inspections

• Provide the framework for all necessary exchange of information and experience

• Coordinate mutual training for inspectors and for other technical experts in related fields

• Continue common efforts toward the improvement and harmonization of technical standards and procedures regarding the inspection of the manufacture of medicinal products and the testing of medicinal products by official control laboratories

• Continue common efforts for the development, harmonization, and maintenance of GMP

• Extend cooperation to other competent authorities having the national arrangements necessary to apply equivalent standards and procedures with a view to contributing to global harmonization.

Currently there are 44 member countries, including all EEA countries, Argentina, Australia, Canada, Israel, Malaysia, Singapore, South Africa, and Switzerland. The United States Food and Drug Administration (FDA) is also a participating authority.

Before a regulatory authority can become a member of the PIC/S, a detailed assessment is undertaken to determine whether the authority has the arrangements and competence necessary to apply an inspection system comparable to that of current PIC/S members. This assessment involves an examination of the authority’s inspection and licensing system, quality system, legislative requirements, inspector training, and so on, and is followed by a visit from a PIC/S delegation to observe inspectors carrying out actual GMP inspections.