Why the FDA Joined PIC/S

Regulatory authorities worldwide undertake various initiatives to ensure the quality and safety of pharmaceuticals. Among these efforts, one particularly noteworthy development was the accession of the U.S. Food and Drug Administration (FDA) to the “Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S)” in 2011. This article explores the background and reasons behind FDA’s decision to join PIC/S, as well as the impact of this accession.

The Origins of GMP and the International Development of PIC/S

GMP (Good Manufacturing Practice) is a standard for pharmaceutical manufacturing quality control first established by the FDA in 1963, prompted by the thalidomide incident that occurred in 1961. The thalidomide tragedy involved a sedative-hypnotic drug that, when administered to pregnant women, caused severe congenital malformations in their fetuses. In response to this catastrophic pharmaceutical disaster, the need for comprehensive regulations to ensure drug safety and efficacy was recognized, and GMP was born as a crucial framework for ensuring quality in the pharmaceutical manufacturing process.

Subsequently, in 1970, the “Pharmaceutical Inspection Convention (PIC)” was established, primarily among European countries. PIC initially aimed to promote mutual recognition of pharmaceutical GMP between member states of the European Economic Community (EEC) and the European Free Trade Association (EFTA). In 1995, to foster broader international cooperation, PIC evolved into the “Pharmaceutical Inspection Co-operation Scheme (PIC/S).” This transformation made it an open organization that non-European countries could join, with Australia, Canada, Singapore, and others becoming early members. This evolution represents the process by which a framework aimed at international harmonization of GMP standards in pharmaceutical manufacturing and mutual recognition of inspection results among member countries developed into a more extensive international cooperation mechanism.

FDA cGMP (current GMP) and PIC/S GMP each have different approaches and focuses, yet they share the common goal of ensuring pharmaceutical quality and safety, and both play important roles in international pharmaceutical regulation. As of 2025, regulatory authorities from 58 countries and regions worldwide are members of PIC/S, contributing significantly to harmonizing national GMP standards, ensuring pharmaceutical quality, and facilitating smooth international trade. What began as a European initiative has now become a vital framework for global pharmaceutical quality assurance.

Background to FDA’s Accession to PIC/S

1. Role as the World’s Largest Pharmaceutical Market and International Regulatory Harmonization

The United States is the world’s leading pharmaceutical consumer, and ensuring quality standards in this enormous market is critically important. The FDA was required to maintain high quality standards while promoting international harmonization of quality criteria. As international pharmaceutical trade increased, cooperation among regulatory authorities and harmonization of standards became essential for efficient regulatory oversight.

Entering the 2000s, pharmaceutical manufacturing globalization accelerated rapidly. Many pharmaceuticals and pharmaceutical raw materials distributed in the U.S. market came to be manufactured overseas, and the number of foreign manufacturing facilities that the FDA needed to oversee increased year by year. By 2010, the number of overseas pharmaceutical manufacturing facilities requiring FDA oversight exceeded 3,000, making it an urgent challenge to conduct effective surveillance with limited resources.

Furthermore, PIC/S, which initially began as a European initiative, was establishing itself as a truly international cooperation framework through the accession of major non-European countries such as Australia, Canada, Singapore, and South Africa—a development that warranted the FDA’s attention. As major U.S. trading partners successively joined PIC/S, the importance of participating in this international pharmaceutical regulatory cooperation system grew increasingly apparent.

2. Participation in International Rule-Making and Regulatory Efficiency

The FDA recognized the significance of participating in PIC/S’s decision-making processes to play an active role in the development of international pharmaceutical regulation. As a pioneer in pharmaceutical regulation, maintaining influence in international standard-setting was an important objective for the FDA. By participating in PIC/S committee activities and guideline development processes, the FDA believed it could reflect its extensive regulatory experience and expertise in the formation of international standards.

Additionally, the FDA aimed to utilize resources efficiently through international sharing of inspection information. Cooperation with regulatory authorities in other countries was essential for monitoring pharmaceutical manufacturing facilities worldwide, and joining PIC/S was positioned as a means to strengthen such international cooperation frameworks. Access to inspection results and quality issue information conducted by member countries through PIC/S’s information sharing system was expected to significantly improve the efficiency of FDA’s oversight activities.

3. Optimization of Inspection Resources

The FDA needed to monitor pharmaceutical manufacturing facilities worldwide with limited resources. In the late 2000s, the FDA had approximately 600 inspectors while the number of domestic and foreign manufacturing facilities requiring oversight numbered in the thousands. Inspecting overseas facilities in particular required considerable time and cost, making it practically difficult to inspect all facilities regularly.

Through joining PIC/S, the FDA determined it could establish an efficient oversight system by sharing inspection information with regulatory authorities in other countries. By mutually recognizing inspection results conducted by trusted regulatory authorities, it was believed possible to reduce duplicate inspections and concentrate inspection resources on higher-risk facilities.

4. Recovery of International Regulatory Leadership

As the originator of GMP and the regulatory authority overseeing the world’s largest pharmaceutical market, the FDA recognized the need to re-engage proactively in shaping the international regulatory environment. During the 2000s, with the European Medicines Agency (EMA) and other European regulatory authorities becoming increasingly active, along with activities within the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), there were concerns that the FDA was not maintaining sufficient presence in international regulatory harmonization discussions.

Joining PIC/S was also a strategic decision to regain the leadership position in international GMP regulation that was being lost and to re-establish its position as a regulatory leader. By participating in the already established international platform of PIC/S, the FDA determined it could strengthen dialogue with regulatory authorities worldwide and play an active role in promoting international regulatory harmonization.

The Process of FDA’s Accession to PIC/S

As the originator of GMP, the FDA’s accession process to PIC/S followed the same standard accession procedures as other member countries. PIC/S allows up to six years from application to assessment, during which time accession requirements must be met. Accession requirements include establishing a legal framework for GMP regulation, establishing an inspection system, inspector qualification requirements and training programs, and systems for responding to quality defects.

The FDA formally applied to join PIC/S in 2006 and subsequently underwent detailed review by PIC/S evaluation teams. The evaluation process included comprehensive document reviews of the FDA’s regulatory system, inspection processes, organizational structure, legal authority, and two on-site evaluation visits. The evaluation team visited not only FDA headquarters but also regional offices that actually conduct inspections, conducting interviews with inspectors and observing the inspection process in the field.

During this evaluation process, the FDA reviewed its own regulatory system against PIC/S standards and implemented several improvements. For example, strengthening inspector training programs, standardizing inspection report formats, and introducing quality risk management approaches were undertaken. After an evaluation period of approximately five and a half years, on July 1, 2011, the FDA formally achieved accession to PIC/S.

This process—whereby the FDA, the regulatory authority that first established GMP, joined the subsequently developed PIC/S framework and underwent the same review as other member countries—was a significant event in the history of international pharmaceutical regulation. Dr. Margaret A. Hamburg, FDA Commissioner at the time, evaluated that this process provided the FDA with a valuable opportunity to review and improve its own regulatory processes. Dr. Hamburg stated that “joining PIC/S provided the FDA with an opportunity to learn from other regulatory authorities and share best practices.”

This experience demonstrated the reality that international regulatory frameworks develop through mutual understanding and cooperation among regulatory authorities in various countries and regions. While respected internationally as the originator of GMP, the FDA determined that participation in the international cooperation framework of PIC/S was important in the globalizing pharmaceutical regulatory environment. This attitude demonstrates the importance of regulatory authorities building more effective regulatory systems through continuous learning and improvement.

Specific Reasons for Accession

1. Harmonization of International GMP Standards and Promotion of Mutual Understanding

The FDA recognized that there were many commonalities between PIC/S Guidelines and FDA cGMP. Both define similar requirements for fundamental elements of pharmaceutical manufacturing, including quality management systems, document control, manufacturing process control, facility and equipment requirements, personnel training, and quality assurance. However, due to differences in historical backgrounds and legal frameworks, subtle differences existed in specific interpretations and implementation methods.

Through accession, the FDA determined that mutual understanding between the two would advance and international standard harmonization would be promoted. By participating in various PIC/S committee activities, the FDA believed it could promote convergence between FDA cGMP and PIC/S GMP Guidelines, reducing the burden on pharmaceutical companies when complying with multiple regulatory systems. Dialogue and cooperation between organizations with different regulatory approaches held significant importance for the development of global pharmaceutical quality standards.

2. Effective Resource Utilization Through Sharing of Inspection Information

Among PIC/S member countries, active information sharing regarding inspection results and quality issues takes place. PIC/S operates a “Rapid Alert System,” through which member countries have an established mechanism to promptly share information with other member countries when serious quality issues or manufacturing deficiencies are discovered. Additionally, regular PIC/S meetings provide opportunities for exchanging insights gained from inspections and information about emerging quality risks.

The FDA determined it could allocate limited inspection resources more efficiently by utilizing this system. This sharing framework was expected to provide significant advantages particularly in monitoring overseas manufacturing facilities. For example, for facilities recently inspected by European regulatory authorities, the FDA could adjust inspection priorities by referring to that information, making it possible to concentrate inspection resources on facilities that had not been inspected for longer periods or on higher-risk facilities.

Furthermore, PIC/S also implements a “Joint Audit Programme,” providing opportunities for multiple regulatory authorities to conduct joint inspections. This not only improves inspection efficiency but also creates opportunities for inspectors from different regulatory authorities to learn from one another.

3. Improving Safety and Building International Cooperation Frameworks

For the United States, which imports pharmaceuticals from around the world, harmonization of international quality standards is essential to protecting public health. In the early 2010s, approximately 80% of active pharmaceutical ingredients (APIs) and approximately 40% of finished pharmaceutical products (drug products) used in the United States were manufactured overseas. These figures were increasing annually, and the globalization of pharmaceutical supply chains had become an irreversible trend.

Joining PIC/S became an important step not only in improving the safety of pharmaceuticals distributed in the U.S. market but also in strengthening international cooperation frameworks among regulatory authorities. Through the PIC/S network, the FDA became able to work closely with regulatory authorities worldwide to effectively implement early detection and response to quality issues, prevention of international distribution of substandard pharmaceuticals, and counterfeit medicine countermeasures.

PIC/S also contributes to capacity building in regulatory authorities in emerging countries. Regulatory authorities in countries seeking to join must strengthen their regulatory systems to meet PIC/S standards, which contributes to raising global pharmaceutical quality standards. By participating in PIC/S, the FDA was considered able to contribute to such international capacity-building efforts.

4. Training and Knowledge Sharing Opportunities

PIC/S conducts regular training and seminars for inspectors from member regulatory authorities. These include training ranging from GMP inspection fundamentals to specialized training on specific manufacturing technologies (e.g., biopharmaceutical manufacturing, continuous manufacturing, sterile manufacturing), and seminars on data integrity.

The FDA determined that through these activities, it could share the latest inspection techniques and knowledge. Enhancing the expertise of regulatory authority staff was an important element forming the foundation for effective regulatory oversight. Additionally, by participating in PIC/S training programs, FDA inspectors gained opportunities to interact directly with inspectors from other countries and learn about different regulatory approaches and inspection techniques.

Furthermore, the FDA could also provide its extensive experience and expertise to PIC/S training programs. This represents bidirectional knowledge sharing, and for the FDA, sharing its practices with regulatory authorities in other countries and receiving feedback provides opportunities for continuous improvement.

Impact of Accession

1. Progress in International Regulatory Harmonization

FDA’s accession to PIC/S significantly promoted harmonization of GMP regulations between the United States and other PIC/S member countries. Through the FDA’s active participation in PIC/S committee activities and contributions to guideline development, consistency between FDA cGMP and PIC/S GMP Guidelines improved. For example, common understanding and practices advanced in areas such as quality risk management, computerized system validation, and data integrity.

This enabled pharmaceutical companies to streamline regulatory compliance across multiple countries and regions, resulting in expectations for cost reductions in pharmaceutical development and accelerated market entry. Improved regulatory predictability and transparency hold significant importance in international pharmaceutical development. By complying with a single GMP standard, pharmaceutical companies gained easier access to markets in multiple countries and regions, facilitating the formulation of global manufacturing strategies.

Additionally, FDA’s accession to PIC/S influenced other major regulatory authorities. In 2012, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) joined PIC/S, and in 2014, China’s National Medical Products Administration (NMPA, then CFDA) began participating as an observer, accelerating the trend of regulatory authorities from major pharmaceutical markets worldwide gathering within PIC/S.

2. Improved Inspection Efficiency

Mutual recognition of inspection results among member countries enabled the reduction of duplicate inspections. The FDA became able to adjust inspection priorities for facilities by referring to inspection results recently conducted by trusted regulatory authorities. This led to FDA resource savings while also reducing the inspection response burden on pharmaceutical companies.

For pharmaceutical companies, repeatedly undergoing inspections from multiple regulatory authorities within short periods had been a significant operational burden. Preparing for inspections, responding to inspections, and implementing corrective actions required considerable resources and could sometimes impact manufacturing schedules. The reduction in inspection duplication through the PIC/S framework enabled companies to allocate more of these resources toward quality improvement and technological innovation.

The ability to utilize limited regulatory resources more effectively also contributes to improving the quality of regulatory oversight. By concentrating inspections on high-risk facilities, the FDA became able to implement more effective risk-based oversight. Additionally, through PIC/S information sharing, early recognition of emerging quality risks and manufacturing issues became possible, enabling appropriate responses.

3. Improved Pharmaceutical Quality and Safety

Application of internationally harmonized GMP standards improved quality control levels at manufacturing facilities worldwide. Regulatory authorities in countries seeking to join PIC/S must strengthen their national regulatory systems to meet PIC/S standards, which leads to enhanced oversight of manufacturing facilities. Additionally, undergoing inspections by PIC/S member country regulatory authorities provides manufacturing facilities with opportunities to improve their quality systems.

This ultimately contributes to improving the quality and safety of pharmaceuticals reaching patients. The international dissemination of high quality standards contributes to fulfilling regulatory authorities’ most important mission of protecting patient safety. Ensuring that pharmaceuticals manufactured anywhere in the world maintain a certain level of quality or higher provides significant reassurance to patients.

The establishment of international standards regarding data integrity was a particularly important development. From the mid-2010s onward, problems related to data falsification and inappropriate data management were discovered in succession around the world, being recognized as serious challenges in pharmaceutical quality assurance. In 2016, PIC/S issued “Guidance on Good Data and Records Management Practices,” establishing international standards regarding data integrity. The FDA actively contributed to creating this guidance and also implements regulatory oversight in accordance with these standards.

4. Strengthened Global Supply Chain Oversight

Through PIC/S membership, the FDA became able to monitor pharmaceutical global supply chains more effectively through the international network. Through PIC/S’s rapid alert system, information about quality issues and manufacturing deficiencies discovered in one country is promptly shared, enabling other countries to take necessary responses. This contributes to reducing risks from counterfeit and substandard pharmaceuticals.

International cooperation frameworks are essential to respond to the increasing complexity of pharmaceutical supply chains in recent years. It is not uncommon for multiple countries’ API manufacturers, intermediate manufacturers, drug product manufacturers, and packaging companies to be involved in manufacturing a single pharmaceutical. To ensure quality in such complex supply chains, it is extremely important for regulatory authorities in each country to work closely together and share information.

Additionally, the COVID-19 pandemic highlighted the vulnerability of pharmaceutical supply chains and the importance of global cooperation. During the pandemic period, the PIC/S network played an important role in cooperation among regulatory authorities to ensure supply of essential medicines. For example, coordination of emergency inspection methods, implementation of remote inspections, and information sharing regarding COVID-19 vaccine quality assurance were conducted. The FDA’s membership in PIC/S enabled effective participation in these international initiatives.

Future Prospects and Challenges

More than ten years have passed since FDA’s accession to PIC/S, and its effects are clearly evident. However, the environment surrounding pharmaceutical regulation is constantly changing, and new challenges are emerging.

First, there is the matter of regulatory response to advances in pharmaceutical manufacturing technology. Innovative manufacturing technologies such as continuous manufacturing, 3D printing, and artificial intelligence (AI)-utilized manufacturing control are emerging, requiring establishment of appropriate regulatory approaches for these technologies. PIC/S is working on modernizing regulations through creating guidance on such new technologies and updating inspector training programs.

Next is the utilization of digital technology. Beyond ensuring data integrity, digital technology has the potential to bring significant transformation to pharmaceutical regulation, including improving supply chain traceability using blockchain technology and enhancing risk assessment through big data analysis. PIC/S is also expected to lead international discussions on the utilization of such technologies.

Continued improvement of regulatory capacity in emerging countries is also an important challenge. Many emerging countries are seeking to join PIC/S, and PIC/S implements support programs for candidate countries. To improve global pharmaceutical quality, it is important to continue these efforts and support more countries in achieving high regulatory standards.

Conclusion

FDA’s accession to PIC/S was an important turning point in the development of international pharmaceutical regulation. The FDA’s choice to participate in an international cooperation framework, as the originator of GMP, demonstrates recognition of the reality that in the globalizing pharmaceutical industry, no regulatory authority can conduct effective oversight alone.

Through joining PIC/S, the FDA was able to gain many benefits including promoting international regulatory harmonization, improving inspection resource efficiency, and strengthening global supply chain oversight. Simultaneously, the FDA has provided its extensive experience and expertise to PIC/S, contributing to improving international pharmaceutical quality standards.

The environment surrounding pharmaceutical regulation will continue to change in the future. Various challenges will need to be addressed, including new manufacturing technologies, infectious disease pandemics, and supply chain complexity. The importance of international cooperation frameworks like PIC/S is expected to increase further going forward. It will become increasingly important for regulatory authorities worldwide, including the FDA, to collaborate toward the common goal of patient safety and public health improvement based on mutual trust and cooperation.