Title:Current Regulatory Framework and Challenges for the Approval of Complex
Generics in the US and the EU
Volume: 2
Author(s): Sharvari Patil, Sandeep Kumar*, Dasari Mallikarjuna Rao*Kishore Rewatkar*
Affiliation:
- Department of Regulatory Affairs, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, 500037, India
- Department of Regulatory Affairs, Dr. Reddy’s Laboratories Ltd., Hyderabad, Telangana, 500090, India
- Department of Regulatory Affairs, Dr. Reddy’s Laboratories Ltd., Hyderabad, Telangana, 500090, India
Keywords:
Complex drugs, Complex generics, Harmonization, Follow-on generics, Regulatory framework, Low molecular weight heparins.
Abstract:
The pharmaceutical industry is witnessing a growing demand for complex generic products, which are generic versions of drugs that possess
complex formulations, delivery systems, or active ingredients. However, the approval process for these complex generic products poses unique
challenges compared to traditional generics. There is no specific regulatory procedure available for the approval of complex generics, unlike smallmolecule
generics and biosimilars. This led to controversial arguments in the past about the scientific evidence needed for applications, which led
to lengthy approval processes. The regulatory frameworks that are currently being used for complex generics are debatable and unclear.
Complexity in the molecular structure, mechanism of action, route of delivery, and complex manufacturing process makes proving bioequivalence
and pharmaceutical equivalence difficult. There is a need for harmonization of the regulatory framework by the agencies to help the generic
manufacturers by providing scientific advice, defining the submission requirements for complex products, and fastening the approval process.
This review begins by discussing the regulatory landscape surrounding complex generic products in various regions, including the United States
and Europe. It examines the specific guidelines and requirements set forth by regulatory authorities to ensure the safety, efficacy, and quality of
these products. Additionally, the review explores the differences in terminology and definitions used to classify complex generics across different
jurisdictions. Furthermore, it delves into the challenges faced by both regulatory agencies and pharmaceutical companies in evaluating and
approving complex generic products. These challenges include establishing appropriate bioequivalence criteria, determining interchangeability
with the reference product, addressing patent and exclusivity issues, and ensuring consistent quality throughout the product lifecycle. The impact of
these challenges on market entry and competition is also discussed. The review highlights the need for harmonization and streamlining of
regulations for complex generic products worldwide. It emphasizes the importance of clear and consistent guidelines to enable timely approvals,
foster innovation, and facilitate patient access to affordable alternatives.
