2006-06-08-世界卫生组织-WHO_Informal_Consultation_on_International_Nonproprietary_Names_INN_Policy_for_Biosimilar_Products_12页_78kb

Summary of WHO Informal Consultation on INN Policy for Biosimilar Products (Geneva, 4-5 September 2006)

Core Content

The document outlines the findings and recommendations from a WHO informal consultation on the naming of biosimilar products using International Nonproprietary Names (INNs). The consultation aimed to address the challenges of naming biosimilars in a global regulatory context and to ensure that the INN system remains consistent, scientifically based, and free from commercial influence.

Main Participants

• Professor Derek Calam – Chairman, WHO INN Expert Group
• Dr Nick Gate – Human Unit Pre-Authorisation, EMEA
• Dr Elwyn Griffiths – Associate Director General, Health Canada
• Dr Toru Kawanishi – Head, Division of Drugs, Japan NIS
• Ms Yun Hee Lee – Drug Evaluation Department, KFDA
• Dr Patrick G. Swann – FDA, USA
• Professor Jean-Hugues Trouvin – EMEA, UK
• Ms Julienne Vaillancourt – FDA, USA

Key Recommendations

To the WHO INN Expert Group

1. INN Assignment for Biosimilars
   INNs for biosimilars should follow the same standard process as for stand-alone biologicals, based on molecular characteristics and pharmacological class. No special designation should be introduced to indicate biosimilarity.

2. Review of Current INN Policy
   An in-depth review of the current INN policy for biologicals is recommended to ensure consistency and identify anomalies. Any new policy should not be applied retrospectively.

3. Exploration of New Nomenclature Approaches
   Consideration should be given to new nomenclature systems that can better accommodate future biological products. One proposed approach involves using simplified naming based on amino acid sequence and post-translational modifications (e.g., glycosylation). Another proposal is to publish the full amino acid sequence along with any modifications to unambiguously define the product.

4. Timing of INN Applications
   The timing of INN application submissions for biologicals should be reconsidered. The current practice of applying early in product development may limit the availability of sufficient data for accurate naming decisions.

5. Clarification of INN Purpose and Limitations
   The WHO INN Expert Group should develop a clear message explaining the purpose and limitations of the INN system for biologicals. INNs should not be used to imply interchangeability or as the sole means of product identification, especially in pharmacovigilance and regulatory contexts.

Key Points on Biosimilar Naming

• Biosimilars vs. Generics: Biosimilars are not true generics because they are not chemically identical but are highly similar in structure and function to the innovator biological product. This distinction is crucial for regulatory and nomenclature purposes.
• Regulatory vs. Scientific Naming: The term "biosimilar" is regulatory in nature, while INNs are based on scientific characterization. Therefore, the INN system should remain independent of regulatory processes.
• Glycosylation and Naming: Differences in glycosylation patterns can affect the safety and efficacy of biological products. Currently, INNs for glycosylated proteins use Greek letters to distinguish variants, but this approach is not applied to monoclonal antibodies.
• Need for Standardization: There is a call for standardization of biological nomenclature, especially for glycosylated proteins. The current system has anomalies that need to be addressed.
• Pharmacovigilance and Traceability: While INNs are useful for global pharmacovigilance, additional identifiers such as manufacturer name, lot number, and host cell type should be included to ensure traceability and safety monitoring.

Views from Regulatory Authorities

• Health Canada: Emphasized that biosimilars are not true generics and that interchangeability decisions should be made by national regulatory authorities based on scientific and clinical data. They are developing a regulatory framework for subsequent-entry biologics.
• European Medicines Agency (EMA): Has established a regulatory framework for biosimilars, including simplified dossier requirements and a centralized licensing procedure. INNs should not be used to differentiate biosimilars from innovator products.
• Japan: Prefers the term "follow-on biologics" or "biosimilars" to distinguish them from generic pharmaceuticals. They support the idea of using host cell information in INN designations and are considering changes to better reflect product differences.
• Korea: Is in the process of developing its regulatory pathway for biosimilars and has adopted INNs for biosimilars as per the innovator product. However, inconsistencies in naming schemes exist, particularly for glycoproteins.
• Australia: Unable to attend, but submitted written views. Advocated for distinguishing glycosylation differences in INN designations and suggested including host cell information in the naming process.

Conclusion

The consultation highlighted the complexity of naming biosimilar biological products and the need to maintain the scientific integrity of the INN system. While there is general agreement that INNs should be based on scientific criteria and not regulatory pathways, the discussion underscored the importance of clarity in nomenclature for ensuring safety, efficacy, and traceability. The WHO INN Expert Group is encouraged to revisit the naming policy for biologicals and consider new approaches that can better address the evolving landscape of biosimilar products.