ITFG/IPAC TECHNICAL TEAM: CMC SPECIFICATIONS Presented by: Bo Olsson, PhD 26 April 2000 Rockville, MD

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ITFG/IPAC TECHNICAL TEAM CMC SPECIFICATIONSPre
sented by Bo Olsson, PhD26 April
2000Rockville, MD
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CMC SPECIFICATIONS TECHNICAL TEAM

• Focus on
• Dose Content Uniformity (DCU)
• Particle Size Distribution (PSD)

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ICH HARMONISATION

• OINDP are amenable to the principles set forth by
  the International Conference on Harmonisation of
  Technical Requirements for Registration of
  Pharmaceuticals for Human Use (ICH).
• The ICH Harmonised Tripartite Guideline on
  "Specifications Test Procedures and Acceptance
  Criteria for New Drug Substances and New Drug
  Products Chemical Substances" (Q6A) provides a
  process for establishing specifications.

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ICH Q6A SPECIFICATIONS

• The justification of specifications should
  refer to relevant development data,
  pharmacopoeial standards, test data for drug
  substances and drug products used in toxicology
  and clinical studies, and results from
  accelerated and long term stability studies, as
  appropriate.
• Additionally, a reasonable range of expected
  analytical and manufacturing variability should
  be considered.
• It is important to consider all of this
  information.
• (62 Fed Reg 62892)

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DCU

• Hypothesis
• The current state of OINDP technology may not
  allow general compliance with the DCU
  specifications in the draft FDA CMC Guidances.
• To date, more than 12 companies have initiated
  the process to collect a world-wide blinded
  database of more than 45 products to examine
  actual DCU capability of OINDP
• Initial assessment by July 31

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DCU

• ITFG/IPAC position
• The specifications in the draft Guidances should
  be based upon sound statistical practices such
  that they can be translated into a quality
  requirements.
• Investigate, using database, alternate DCU
  specifications
• ICH Q4 (Pharmacopoeial Harmonisation) draft
  proposal
• Dr. Walter Hauck's Approach
• ISO 2859-1 Approach
• Other Approaches

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PSD

• To date, more than 12 companies have initiated a
  process to collect a world-wide blinded database
  of more than 40 products to examine actual PSD
  capability of OINDP
• Initial assessment by July 31
• Purpose of PSD survey
• Examine the relevancy of the mass balance
  requirement as a product specification versus
  system suitability requirement.
• Investigate if fewer than 3-4 stage groupings can
  provide equivalent control.