2015-08-08-世界卫生组织-INN_60th_Executive_Summary_15页_212kb

60th Consultation on International Nonproprietary Names for Pharmaceutical Substances

Executive Summary

• Meeting Period: Geneva, 13-15 April 2015.
• Attendees: Representatives from WHO, academia, industry, regulators, funding agencies, and non-governmental organizations.

Key Topics Discussed

1. Biological Qualifier (BQ):

   • Core Debate: Proposal to assign a unique 4-letter code to the Marketing Authorization Holder (MAH) for biological substances, supplementing the INN.
   • Arguments For: Potential to link biological products per their drug substance, aid pharmacovigilance, address counterfeit medicines, and provide a consistent global identifier.
   • Arguments Against: Concerns over impracticality (long-term needs, code memorability/ transcription errors, checksum viability), potential negative impact on biosimilar uptake (due to linkage to MAH outside biosimilar nomenclature), confusion with existing identifiers (company names, 2D barcodes, etc.), and legal hurdles for retrospective implementation.
   • Proposed Format: Kept 4-letter code format for now. MAH as the qualifier assignee. Code independent of manufacturing site or jurisdiction. Emphasis that BQ supplements, not replaces, the INN.
   • Stakeholder Views: Broad support for BQ concept in principle; disagreements on details (scope, code format, implementation, data sharing). Further development needed, with a planned Stakeholder Forum (June 2015) and refinement based on feedback before the 61st Consultation.
   • Committee Decision: Willing to develop the BQ scheme temporally but stressed the importance of a robust framework before focusing on fine details. Recommended code backward compatibility to preserve INN integrity.

2. Requirement for BQ:

   • Various suggestions regarding BQ format were proposed, with the 4-letter code recommended but acknowledged limitations regarding memorability and potential transcription errors.

3. Cell Therapy (CT) Nomenclature:

   • Four options considered:
     • (i) Re-engineer INN/USAN system for CTs (flexible, concise names).
     • (ii) Adapt USAN system (omit -T, -L, -X suffixes).
     • (iii) Maintain current system (retrospectively). (Chosen).
     • (iv) No INN for CTs.
   • Chosen Approach: Maintain the current system within the existing INN/USAN framework, agreeing in principle to a final decision later.
   • Key Points:
     • Preliminary Conclusion: Keeping the current system.
     • Challenges with current system: Long, complex names often leading to transcription errors.
     • US Alignment: Need for coordination with the US FDA (CBER) regarding alignment with their scheme (USAN contribution). Initial technical discussion with US side was requested.
     • Combined Systems (ISBT 128/INN): Interest in complementary use, possibly linking INN 5-digit reference numbers with ISBT descriptors for unique identification.

4. Greek Letters for Glycoproteins:

   • Current Practice: Used to distinguish proteins with identical amino acid sequences but different glycosylation; not applicable to Monoclonal Antibodies (mAbs).
   • Limitations in IS: Stated by experts advising against adding Greek letters to mAbs, feeling it complicates mAb side of development (though perhaps necessary).
   • Recommendation: Publishing the rule clearly (e.g., on WHO website). Provided more flexibility for future INN mAb assignment. Leave final decision on mAbs to the Expert Group citing WHO/IUIS.

5. Other Relevant Issues:

   • PEGylation: Proposed INN reforms: PEG size should not be part of the code (use of circumflex). Differences only due to PEG mass should not imply a new INN.
   • Conjugated Compounds (e.g., drug-toxin conjugates): Discussed transcription errors due to falling off the second name component. Proposed to use a single word prefix when beneficial (PEGylation), but wider issue unresolved.
   • MAbs: Specialist subgroup meeting confirmed using amino acid sequence, not engineering method, to define 'humanised'/'chimeric'; agreed to pursue alignment with key databases (IMGT, etc.).
   • Conjugated Small Molecules: Need to clarify naming rules to prevent confusing salts/esters with INNs.

Committee Action & Future Work

• Expert Group: To formulate a draft INN BioNomenclature with clear description rules. To be finalized by a small working group before the next meeting. Also to re-examine the use/acceptability of Greek letters for mAbs.
• MAH Focus: Maintained that the BQ applicant must report changes relevant to the BQ back to the INN Secretariat.
• Future Meeting: 61st Consultation, October 13-16, 2015.
• Stakeholder Forum: To be held June 16, 2015, to discuss the BQ proposal.
• Open Session: Originally 'Open' but function focused predominantly on BQ feedback.