by Robert M. Tribe

Background
As explained in the November/December 2004 edition of Regulatory Review, the Pharmaceutical Inspection Cooperation Scheme (PIC/S) is a cooperative arrangement between regulatory authorities that enables active and constructive cooperation and sharing of information in the field of GMP¹. This number increased to 28 regulatory authorities in July, when the Czech Veterinary Institute became a member².

Before a regulatory authority can become a member of PIC/S, a detailed assessment is undertaken to determine whether the authority has the arrangements and competence necessary to apply a GMP inspection system comparable to that of current PIC/S members. This assessment involves an examination of the authority's GMP inspection and licensing system, structure and organization of the inspectorate, quality system, legislative requirements, inspector training, etc. Following this, a PIC/S delegation visits the regulatory authority to observe inspectors carrying out actual GMP inspections.

Membership may take several years to achieve, during which time various changes and improvements may be recommended by PIC/S. If necessary, a PIC/S delegation may conduct follow-up visits to verify the suitability of corrective actions.

The regulatory authorities of the following countries are currently undergoing assessment for membership in PIC/S²:

	Argentina			Poland
	Estonia			Russia
	Israel			South Africa
	Lithuania			Ukraine
	Oman			UNICEF 

The regulatory authorities of the following countries have expressed interest in becoming members of PIC/S:

	Brazil			Philippines
	Chinese Taipei		Slovenia
	Cyprus			Thailand
	Indonesia			U.S. (FDA)

The U.S. FDA indicated its decision to seek membership in PIC/S in an FDA News release issued on 29 September 2004³. The FDA is expected to make its application in the latter part of 2005.

Steps to Accession
The steps to becoming a member of PIC/S are as follows:

1. The regulatory authority is expected to show an interest in PIC/S activities; for example, by participating in PIC/S training seminars for GMP inspectors. This provides the interested regulatory authority with an understanding of how PIC/S operates and the benefits that would be realized from becoming a member of PIC/S. It also gives PIC/S members the opportunity to become acquainted with the potential new applicant.
2. A written application for membership is lodged with the Secretary of PIC/S. This application comprises an application form, a completed questionnaire, a copy of the inspectorate's quality system, description of key operating procedures, and a description of key legislation utilized by the regulatory authority for undertaking the inspection and authorization of manufacturers.
3. The PIC/S Committee (comprising one senior representative from each member authority, responsible for the operation of PIC/S)⁴ considers the application and appoints a rapporteur to carry out an assessment of the submitted application. The rapporteur usually liaises directly with the applicant authority to seek clarification of specific issues, to request additional documentation, etc.
4. The report of the rapporteur's assessment, containing recommendations on the next steps in the accession process, is provided to the PIC/S committee for its consideration. The applicant is invited to attend the PIC/S committee meeting during the discussion of the rapporteur's assessment report in order to answer any questions that Committee members may have.
5. Once the PIC/S Committee is satisfied that the applicant has a system of regulatory controls in place that are generally equivalent to the controls operated by PIC/S member authorities, a delegation of senior PIC/S inspectors is selected to accompany the Rapporteur to visit the country to undertake an on-site assessment. However, it may take several years before the Committee will agree to an on-site assessment, particularly if there is a need for the applicant to take remedial actions to bring its systems, controls, legislation, etc. into line with PIC/S requirements.
6. The PIC/S delegation undertakes its on-site assessment of the applicant's quality system, operating procedures, staff training, etc., and also observes three or four typical GMP inspections being conducted. It is usual for different types of manufacturers to be selected for these observed inspections, e.g. a manufacturer of sterile products, a manufacturer of solid dosage forms and a small manufacturer of some other dosage form. An assessment visit usually lasts one week.
7. The delegation issues a report of its on-site assessment, which is submitted to the PIC/S Committee for its consideration. This report provides a recommendation on whether or not the applicant has the necessary controls, systems and competence to become a member of PIC/S. It may take several on-site assessment visits before a positive recommendation can be made, with a range of remedial actions undertaken by the applicant between each visit.
8. The total time-frame for the application process is not permitted to exceed six years. Any application which exceeds this limit (e.g. because the applicant is slow to introduce appropriate legislative changes in order to comply with PIC/S requirements) is rejected and a fresh application must be made.
9. Once the PIC/S Committee is satisfied that the regulatory authority has a system of GMP inspection and controls in place that are equivalent to existing PIC/S member authorities, the Committee will advise the applicant that its membership in PIC/S will commence from a specific date.

Existing members of PIC/S are re-assessed at regular intervals in order to help ensure that the systems, controls and competence of all member authorities, particularly the older members of PIC/S, are maintained at a consistent level.

Benefits of PIC/S Membership
The benefits of PIC/S membership for regulatory authorities include the following:

• More effective use of inspection resources through the sharing of the results of GMP inspections, resulting in cost savings.
• Training of inspectors through participation in PIC/S Seminars, Expert Circle meetings and the PIC/S Joint Visits Program.
• Promotion of the harmonisation of GMP inspections.
• Improvements in the inspection systems and procedures of authorities seeking to join PIC/S, including the implementation of a quality system for the inspectorate.
• Involvement in the development of internationally harmonized GMP standards and guidelines.
• Sharing of information and experiences amongst inspectors.

There are also benefits to industry when relevant regulatory authorities become members of PIC/S. These benefits may include the following:

• Reduced duplication of inspections.
• Cost savings.
• Export facilitation.
• Enhanced market access.

References

1. Pharmaceutical Engineering, November/December 2004; page 110.
2. PIC/S Web site (www.picscheme.org ), Press Release, PIC/S Committee Meeting, Geneva, Switzerland, 14 February 2005.
3. FDA News, PO4-93, September 29, 2004. www.fda.gov/bbs/topics/news/2004/NEW01120.html
4. PIC/S Web site (www.picscheme.org ), Roles and Functions of PIC/S, Pharmaceutical Inspection Cooperation Scheme, Geneva - 12 November 2003, PIC/S 1/95 (Rev 3).

About the Author
Bob Tribe is ISPE’s Regulatory Affairs Advisor for the Asia Pacific, based in Canberra, Australia. He joined ISPE from the Therapeutic Goods Administration (TGA) in Australia, where he served as Chief GMP Auditor for 23 years. During that time, he not only enhanced the TGA’s reputation as a leading GMP regulator internationally but also held leadership positions with the Pharmaceutical Inspection Cooperation Scheme (PIC/S), serving as vice chairman in 1998-1999 and chairman in 2000-2001. Recently, Tribe founded a company to provide consulting to GMP regulatory authorities around the world.