Inside PIC/S: The Importance of PIC/S in a Globalized World

The Pharmaceutical Inspection Cooperation Scheme (PIC/S) celebrated its 40th anniversary in Geneva this past May. PIC/S has been a pioneer organization in the field of pharmaceutical inspections and GMP. The Pharmaceutical Inspection Convention (PIC) entered into force in May 1971, as the first ever mutual recognition agreement (MRA) in the field of GMP inspections.

Tor Graberg

Changing times

Today, the organization has grown from 10 original European country members to 39 participating authorities from five continents. An additional nine authorities from countries such as Brazil and Indonesia, are in the process of becoming members. Paradoxically, the growth of the organization has been made possible by moving from a legally-binding MRA (PIC) to an informal arrangement between regulatory authorities that better facilitates cross-border trade of pharmaceuticals while ensuring the safety of patients.

Members exchange GMP information such as inspection reports, recall alerts, and other relevant data on a voluntary basis. PIC/S has adopted other goals as well, including the development and harmonization of GMP standards and guidance documents, the training of competent authorities, in particular inspectors, the assessment (and reassessment) of inspectorates, and the facilitation of cooperation and networking for competent authorities and international organizations in view of promoting mutual confidence.

The expansion of the PIC/S mission illustrates how successfully the organization has been able to adapt to a constantly changing environment—in particular, globalization. The increasing globalization of public-health issues and the multiplication of actors involved (both in industry and among regulatory authorities) has made it necessary to increase harmonization efforts in setting regulatory requirements, inspecting and evaluating GMP compliance, licensing manufacturing sites, recalling defective batches, and the exchange of information. The philosophy of PIC/S is based on cooperation, communication, and trust. Because information-sharing within PIC/S is voluntary, it is up to the receiver of the information to decide how to use it (e.g., a participating authority can use the outcome of an inspection conducted by another PIC/S authority to avoid duplicating an inspection).

FDA's membership

FDA has acknowledged PIC/S' efforts. The agency applied for PIC/S membership a few years ago and became an offical member in January 2011. PIC/S invited FDA Commissioner Margaret Hamburg, MD, to deliver a kenote address at the May 2011 anniversary celebration (1). In this address, Hamburg called upon all regulatory authorities to cooperate more closely and to share information on GMP inspections.

Due to the globalization of the supply chain, a growing part of finished products and APIs are imported. Globalization represents not only new opportunities for manufacturers but also considerable challenges for regulators. As Hamburg asserted, "...no one country is capable of inspecting the world on its own, nor can we assure quality with inspections alone" (1).

All PIC/S members, including FDA, need to think about how to best pool resources and work together to protect public health. For FDA, PIC/S represents a key way to avoid the duplication of efforts and ensure the global security of the supply chain. Hamburg concluded her speech by saying, "Today, PIC/S is more important than ever, given the realities of globalization" (1).

The FDA Commissioner's speech is remarkable on at least two counts:

• As Hamburg underlined—and this is also valid for other countries, "In the US, a stunning 80% of the active pharmaceutical ingredients in our drugs come from outside our borders and about 40% of the finished drugs themselves" (1). Because neither the US nor any other regulatory authorities can inspect all imported medicinal products (including APIs), cooperation with other authorities is vital to get the most possible amount of information that a single regulatory agency's inspectors cannot gather.

• FDA is willing to use PIC/S as a tool to better safeguard the health of Americans. Following the heparin crisis of 2009 and 2010, the soundness of regulatory action, within the national borders and without foreign cooperation, has been seriously questioned. A repeat must be avoided at all costs. Said Hamburg, "We must continue to work together in a proactive, rather than reactive, manner in dealing with potential threats" (1). In addition, the international financial crisis will affect budgets and limit the amount of money that governments will spend on healthcare. As a result, cooperation with other regulatory authorities in the framework of PIC/S has become a strategic and financial priority for FDA.

Transforming PIC/S

Today, PIC/S is set to become a major player on the international GMP scene. However, there are two limitations: the first is that not all important regulatory authorities are members, in particular countries such as China, India, and Japan. Second, PIC/S is competent in GMP (i.e., control at the manufacturing level) but not for controlling the entire supply chain. For example, the PIC/S mandate does not cover good distribution practice (GDP).

To address the issue of membership, the organization recently revised its accession procedure to include a pre-accession phase. This phase includes a gap analysis, thereby offering a safe option to future applicants who may not be able to meet all PIC/S requirements immediately. Among the 160 guests who came to the PIC/S 40th anniversary symposium, several nonmembers attended, including representatives from Bulgaria, China, Croatia, Georgia, Hong Kong SAR, Hungary (Vet), Japan, Nigeria, Russia, Saudi Arabia, South Korea, Turkey, and Uganda. Some of these nonmembers have since expressed interest in joining PIC/S. The organization has also proposed establishing a Memorandum of Understanding with authorities that are unable to apply for membership. Russia signed a memorandum with PIC/S in 2010. Such agreements make it possible to include nonmembers into the PIC/S network and further facilitate global harmonization.

PIC/S is also considering extending its mandate to include GDP. The growth of the industry and the effects of counterfeiting have led to a need to strengthen overall pharmaceutical supply-chain control. Little work is being done in other fora to coordinate and harmonize GDP inspections (except in the European Union). An initiative by PIC/S could fill a gap in the control system of medicines.

Tor Gråberg is chairman of the PIC/S.

Reference

1. M. Hamburg, "The Importance of PIC/S in Our Globalized World," presented at the 40th Anniversary of PIC/S (Geneva, May 31, 2011), www.fda.gov/NewsEvents/Speeches/ucm257974.htm.