Global Pharmaceutical Regulatory Harmonization: An Overview

Resources to dive deep into current regulatory harmonization efforts and issues.

While the FDA looms large in the US pharmaceutical industry, a global perspective is also important. A new editorial has ignited discussion of global regulatory harmonization for pharma. Read on to learn more about current arguments and existing harmonization efforts.

A recent editorial in Science Translational Medicine promoted global regulatory harmonization as a public health solution that would benefit all stakeholders in the pharmaceutical industry. The piece’s authors, former NIH director Elias Zerhouni and former FDA commissioner Margaret Hamburg, argue that globalization has blurred the line between foreign and domestic  pharmaceutical products. Manufacturing, R&D and supply chains are now global, and many drugmakers rely on a high proportion of imported products. As the nature of the industry changes, a global view of regulatory oversight becomes necessary.

Zerhouni and Hamburg argue that nation-by-nation regulatory oversight creates “unnecessary barriers,” whereas greater harmonization could meet the world’s growing public health needs by increasing efficiencies, reducing costs, enhancing R&D, and benefitting patients by improving safety, innovation and access. There are inherent challenges to this process, of course, and untangling the existing web of nation-by-nation bureaucracy would be a complicated feat. The authors acknowledge that individual nations have their own approaches to legal and regulatory frameworks. Each country weighs differently key factors such as risks and benefits, disease burden, vulnerable populations, privacy concerns and social and economic costs. Many regulators are also overburdened and underresourced.

Despite these challenges, however, the authors argue that drug regulatory harmonization is both highly necessary and very possible. The key to sweeping change will be leadership by senior government officials who recognize the advantages of harmonization and who are willing to collaborate.

The editorial sets out an ambitious agenda, and certainly an international collaboration to create efficient, effective regulatory standards for the pharmaceutical industry would be a game-changing development for all involved. As it stands, though, what work is being done? Who is leading the charge for greater harmonization?

A number of global harmonization efforts are already underway. Here is a quick reference to existing organizations and initiatives.

Global Regulatory Harmonization Organizations and Initiatives

• The International Coalition of Medicines Regulatory Authorities (ICMRA) is a “voluntary, executive-level, strategic coordinating, advocacy and leadership entity of regulatory authorities.” The coalition’s membership includes 23 national and regional regulatory authorities. Strategic initiatives include GMP, generics, capacity building, mapping, supply chain integrity, pharmacovigilance and crisis management.

• The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) “is unique in bringing together the regulatory authorities and the pharmaceutical industry to discuss scientific and technical aspects of drug registration.”  The council’s mission is greater worldwide harmonization. Membership is comprised of regulatory bodies, pharmaceutical industry associations and observers.

• The Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) “are two international instruments between countries and pharmaceutical inspection authorities, which provide together an active and constructive co-operation in the field of GMP.” The organization’s mission is harmonized GMP (good manufacturing practice) standards. 48 participating authorities comprise the current membership.

• The International Medical Device Regulators Forum (IMDRF) is a “voluntary group of medical device regulators from around the world” who build on the work begun by the WHO’s Global Harmonization Task Force (GHTF) on medical devices in order “to accelerate international medical device regulatory harmonization and convergence.” The IMDRF’s main page lists current members, official observers and affiliates. Current work items include standards, adverse event terminology, good regulatory review practices, patient registries (click here to learn more about patient access), software as a medical device, NCAR system review and regulated product submission.

• IFPMA (International Federation of Pharmaceutical Manufacturers and Associations) has published a statement in support of harmonization efforts, noting that the organization plays a “facilitating role” by providing positions and sharing information and platforms.

• WHO sponsors International Conference of Drug Regulatory Authorities (ICDRA) conferences that “provide drug regulatory authorities of WHO Member States with a forum to meet and discuss ways to strengthen collaboration.” The conferences have been held since 1980 and help WHO members and other stakeholders to identify “priorities for action in national and international regulation of medicines, vaccines, biomedicines and herbals.” Documents from the most recent conference, held in Brazil in 2014, can be found here. The current edition of WHO Drug Information discusses ICDRAs and regional harmonization efforts

FDA Initiatives and Resources on Globalization and Harmonization

• The FDA Office of International Programs (OIP) oversees food and medical products imported into the US. OIP obtains foreign scientific and regulatory information, participates in trade negotiations and advises other FDA offices regarding FDA activities in an international context.

• FDA Globalization, which is part of the OIP, provides information and resources about the FDA’s “multifaceted approach to globalization,” including a number of reports on global regulatory issues and international activities relating to drugs and devices.

• The Office of Global Regulatory Operations and Policy (GO) is comprised of the Office of Regulatory Affairs and the Office of International Programs. The GO’s Deputy Commissioner provides executive oversight, leadership and policy direction on a number of international issues, including global collaboration and harmonization and development of standards. The GO page includes links to various testimonies and blog posts about globalization and international efforts.

• FDA maintains a page of International Council on Harmonisation documents and guidances.

• The Vaccines, Blood & Biologics division of the FDA maintains a Regulatory Harmonization and Covergence page listing current harmonization activities and initiatives involving the Center for Biologics Evaluation and Research (CBER).

• FDA hosted a recent regional public consultation of the ICH.

• FDA’s Pharmaceutical cGMPs for the 21^st Century include a GMP Harmonization Analysis.
• A 2012 global engagement report (prepared during Margaret Hamburg’s tenure as FDA Commissioner) includes sections on harmonizing standards, global surveillance and advancing regulatory science.

Conclusion

Global regulatory harmonization is likely to remain a key issue in the years to come, as we see burgeoning harmonization efforts worldwide, increasing attention to the need for international coordination, and growing awareness of the truly global nature of the pharmaceutical marketplace. Globalization is inevitable, meaning the regulatory challenges will be inescapable.  As Zerhouni and Hamburg point out, though, regulation “can either grease the wheels of progress or throw a wrench in the works.” With any luck, harmonization efforts will prove effective and benefit patients and stakeholders worldwide.