New Excipient Evaluation Procedure: An IPEC Proposal

1
New Excipient Evaluation Procedure An IPEC
Proposal

• Jay Goldring, Ph.D.
• IPEC Regulatory Affairs Committee
• Wyeth Consumer Healthcare
• Jan. 26, 2006

2
Current Evaluation Procedures for New Excipients

• US New excipients evaluated only in the context
  of NDA
• No independent evaluation procedure
• Entire NDA could be rejected if excipient is
  unacceptable
• Similar situation in other countries
• Barrier to innovation
• New drug product manufacturers reluctant to
  jeopardize approval with new excipient

3
New Excipient Evaluation Guidelines

• 2005 FDA Guidance for Industry Nonclinical
  Studies for the Safety Evaluation of
  Pharmaceutical Excipients
• Extensive safety testing requirements dependent
  on dose/treatment duration
• ICH guidance
• No specific excipient guidance
• Assumption of requirements similar to drugs
• No guidance identified in other countries

4
Inactive Ingredient Guide (IIG)

• Online list of excipients in approved drug
  products (US)
• Maximum dose and dosage form specified
• Assumption that all listed materials approvable
  in drug products up to specified dose
• May not be current
• No similar list in other countries

5
Questions

• Degree of newness
• When should completed safety testing or safety
  surveillance results for related materials be
  considered applicable?
• Role of other regulatory approvals
• GRAS/Food Additive
• Cosmetics
• Other countries (food/cosmetics/drugs)

6
More questions

• Regulatory status in other countries
• Food ingredient, cosmetic, drug
• Format for data submission
• US DMF system not adequate
• IPEC proposal Excipient Master File format
  consistent with CTD
• Consistent format will reduce review times
• When is an excipient package complete?

7
Independent Evaluation the IPEC Proposal

• Excipient manufacturers submit dossiers to IPEC
  committee, who evaluates
• Newness
• Safety data
• FDA/global health authority agrees to consider
  results of IPEC committee evaluation
• Retain authority to approve final drug product
• Positive appraisal limits risk of rejection based
  on excipient
• Could encourage innovation

8
Proposed Excipient Review Committee Objectives

• Evaluation limited to safety
• Use FDA criteria (US) and/or ICH Safety
  Evaluation Criteria (ex-US)
• Include impurity profile in evaluation
• CMC issues other than impurities evaluated
  separately (e.g. IPEC/GMP audit)
• Companies or other entities can submit petitions

9
Proposed Committee Structure

• Managed as an independent entity under auspices
  of IPEC Safety Committee
• Committee members chosen by Safety Committee
• Safety Committee maintains roster of committee
  members and their expertise
• Minimum of three independent well-known experts
  chosen for each application
• Committee will be financially self-sustaining
• Application fees
• Membership fees

10
Evaluation conclusions

• Meets or does not meet safety criteria
• Petitioners can re-submit if necessary
• FDA/global health authorities agree to consider
  conclusion
• Results are confidential
• Released at the discretion of the petitioner

11
Expected outcome

• Encourage innovation
• Marketing tool for excipient manufacturers
• Drug manufacturers encouraged to use new
  excipients
• Shorter review times
• Some work already done for FDA/global health
  authorities

12
IPEC Proposal Current Status

• Draft proposal presented to FDA Aug. 2005
• Detailed proposal submitted by IPEC Safety
  Committee Nov. 2005
• FDA reaction/comments to be discussed at this
  meeting