P225: Global Regulatory Landscape of Complex Generics
Victor Samuel Pribluda
Senior Manager International Regulatory Intelligence
U.S. Pharmacopeia United States
The two main objectives of this research were to assess the regulatory landscape and availability of complex generic products belonging to US FDA’s categories of Complex Products, in ten countries, as their complexity is not explicitly recognized in their countries’ guidelines.
For this study, information was gathered in 2022 through primary research at regulatory agency websites, other publicly available regulatory and pharmaceutical market databases, national and regional pharmacopeias, and personal interviews with relevant stakeholders.
Argentina, Brazil, China, Egypt, Germany, India, Japan, Mexico, South Korea, and Turkey were chosen for evaluation. Complex products belonging to four or five of the five categories of complex products defined by US Federal and Drug Administration (FDA) are marketed in these countries, and in most of them there are quality and/or general bioequivalence guidelines that could apply to many of these categories.
Drug products containing twelve specific Active Pharmaceutical Ingredients (APIs) that were selected based on a variety of criteria were assessed in seven of the ten countries. Complex and non-complex products containing seven of these APIs were identified in most countries, while no complex products were found for five of them. Complex products containing two of these APIs were identified in all seven countries. For the seven APIs for which there are complex products, most countries have products belonging to three or four of US FDA’s five categories.
The largest number of non-complex and complex products containing these APIs were identified in India and Turkey, and the largest number of pharmacopeial standards for these APIs were also identified in India (National Pharmacopeia) and in Turkey (regional European Pharmacopeia).
US FDA and the European Medicines Agency (EMA) recognize that due to the complexity of certain products, the development of generics require specific guidance to ensure therapeutic equivalence with the reference listed drug. For that purpose, they introduced the categories of Complex Generics (US FDA) and Hybrid Medicines (EMA), through which they provide specific paths for registration and guidance to manufacturers to facilitate the development of generic versions of these complex products. None of the ten countries assessed in this research had a definition for these types of products nor specific guidelines to address their complexity; however multiple products belonging to the categories of complex products as defined by US FDA were identified, as well as general guidelines under which those products may have been registered in the countries. In these countries, non-complex and complex products containing selected active pharmaceutical ingredients were identified, but most national pharmacopeias have no standards for the drug substance and/or the drug product. The lack of specific regulatory information for assessing these types of products, as well as the lack of standards to assess their quality, uncovers the potential risks in their quality, safety, and efficacy. As more complex generics enter the market in the US and Europe, it is warranted to advocate for convergence in other countries, to facilitate their registration and ensure the access to patients of quality-assured, efficacious, and safe generic medicines.