OGD Global Affairs Program, One Year Progress Report of Generic Drug Cluster

Dr. Sarah Ibrahim

Through a rigorous scientific and regulatory process, CDER’s Office of Generic Drugs (OGD) helps to ensure Americans have access to safe, effective, and high-quality generic drugs. The role of the Global Generic Drug Affairs Program is to lead, coordinate, and manage OGD’s international activities in collaboration with other offices in CDER offices and throughout the FDA to advance the overall mission of OGD and FDA. In an increasingly globalized pharmaceutical market, collaboration among drug regulators is critical. Actions one country or territory takes can affect others.

The Global Generic Drug Affairs Program has been exploring what administrative, scientific, and technical avenues FDA can take for further harmonization of generic drug standards globally by engaging with international standard-setting organizations, and through dialogue with the world’s leading regulatory authorities.

As one important example, in June 2021, OGD established a multi-country forum, the Generic Drug Cluster, to achieve a common understanding of each member agency’s generic drug regulatory requirements and to help increase scientific alignment. Regulatory requirements and scientific approaches to developing and assessing generic drugs can vary from country to country, which can add complexity to the development and approval process for generic drug developers.

In this CDER Conversation, we reflect on the first-year progress of the Generic Drug Cluster with OGD’s Sarah Ibrahim PhD., associate director for Global Generic Drug Affairs.

Sarah, what is the Generic Drug Cluster, and what is the significance of the Cluster?

We know the importance of generic drugs to the public. Ninety percent of patients’ prescriptions in our country are now filled with generics – many of these are critically needed, life-saving drugs – that may provide enormous cost savings. Generic drugs play an important role in helping to address rising health care costs and in promoting access to medicines across the world.

To enhance our knowledge and view of the global generic drug landscape, we initiated and launched (in less than a year) the Generic Drug Cluster (the Cluster), a forum that provides OGD and the agency access to information from partner regulatory agencies. Currently, the Cluster includes FDA, European Medicines Agency, Health Canada, Medicines and Healthcare products Regulatory Agency (United Kingdom), Swissmedic, and the Israeli Ministry of Health.

The Cluster offers a confidential forum for the world’s leading regulatory agencies to develop a common understanding of each agency’s regulatory requirements for approval as well as their current thinking on topics related to generic drug development. The Cluster is unique among international generic drug discussion groups in that it focuses on early communication to establish alignment on scientific perspectives where possible. This alignment can help lead to convergence: a pre-harmonization process through which technical recommendations from countries become more aligned over time, ultimately leading to greater harmonization. The International Council for Harmonisation (ICH) is an organization that reviews relevant scientific and technical standards for drugs focusing on harmonization and consensus guidelines used for the development of drugs. The ICH follows the same process of convergence.

And to speak to the significance of bringing together global stakeholders in the forum created by the Cluster - we know that variations in regulatory approaches around the world can result in increased cost in the generic drug development and approval process. For example, it is common for countries to require different manufacturing specifications and different tests to support approval, which can add complexities for generic drug developers filing applications for approval in different markets for a generic drug. Regulatory agencies also often deal with complex drug safety issues at the same time. Greater information sharing through the Cluster can improve the quality of information an agency has to consider in reaching decisions on issues such as generic drug safety and shortages.

This regulatory cooperation can help streamline industry interactions with individual agencies and allow industry submission pathways that are more efficient - which can lead to lower costs for drug applicants and patients and help facilitate timelier patient access to generic drugs.

Basically, we see this forum as providing an opportunity to discuss policies under development (including draft guidances for industry) and the scientific bases for those policy decisions; to discuss specific targeted drug development issues and drug/class-related scientific review issues; to seek alignment in our scientific evaluation of drugs; and to address long-term safety issues to ensure a global safety net for generic drugs through confidential sharing of related reports.

Any major accomplishments to highlight from the Cluster’s first year?

During its inaugural year, FDA and the other Cluster agencies conducted a series of meetings at which they collaborated on a variety of regulatory topics, many of which focused on comparing and evaluating regulatory approaches, identifying similarities, and assessing differences.

Specifically, Cluster meetings led to an agreement about gathering and assessing data from participating agencies concerning both an oncology treatment and bioequivalence for a mental health treatment. The assessment by the agencies of combined data could lead to a faster approval pathway for both a critically needed cancer treatment and treatment for mental health disorders.

Cluster participants also agreed to share data on human testing of certain drugs for which different testing populations are used (i.e., patients vs. healthy volunteers). The assessment of the combined data could support regulatory agencies developing similar recommendations on testing populations. Finding no statistically significant difference in patient vs. healthy volunteer populations means the door is open for a wider pool of people from which to find testing participants for these classes of drugs. A more plentiful pool of potential testing populations means test volunteers could be available more quickly, which could help expedite time to approval of some drugs.

The Cluster is currently establishing a process for sharing data integrity concerns pertaining to bioequivalence and pharmacokinetic data - both critical components of generic drug applications. Data integrity, which refers to the completeness, consistency, accuracy, and quality of data, is fundamental for approving generic drugs that are equivalent to the brand product. The sharing of data integrity concerns and findings within the Cluster’s structured and confidential information-sharing environment can help agencies establish protective measures to ensure effective responses to threats as they arise.

How will future Cluster efforts support FDA’s mission?

All of the Cluster’s efforts support FDA’s public health mission of assuring the safety, efficacy, and quality of FDA-regulated drugs for the American public.

By easing the barriers to global entry for generic firms, FDA can help encourage increased investment in this sector. And we can promote more generic drug competition – and therefore lower drug prices – for American consumers.

Information exchange and discussion at the Generic Drug Cluster meetings support FDA efforts to reach scientific consensus on recommendations for the development of drugs, including complex drugs. The goal of the Cluster is to collaborate early in the regulatory process so that participating agencies can facilitate the development and approval of generic drugs in a more efficient way, and with similar standards. This will ultimately give patients around the world access to high-quality generic drugs in a cost-effective manner and improve patient outcomes.

The Cluster foresees regulatory authorities from other countries and regions participating in Cluster activities.

Again, we believe that early alignment and harmonizing of scientific and technical standards for generic drugs will help us advance a robust generic drug market that drives generic drug competition, lowers drug prices, and increases patient access to high-quality drugs worldwide. We will continue to work with our international regulatory partners to advance policies that will help us continue to accelerate generic drug development in order to provide high quality generic drug products while increasing drug competition.