ITFG/IPAC TECHNICAL TEAM: CMC LEACHABLES AND EXTRACTABLES Presented by: Kaushik J. Dave, R.Ph, PhD 26 April 2000 Rockville, MD

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ITFG/IPAC TECHNICAL TEAM CMC LEACHABLES AND
EXTRACTABLESPresented by Kaushik J. Dave,
R.Ph, PhD26 April 2000Rockville, MD
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LEACHABLES AND EXTRACTABLES TECHNICAL TEAM
The Team recognizes that control of extractables
and leachables is important for ensuring the
safety and quality of inhalation drug products
CMC Leachables and Extractables Technical Team
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DEFINITIONS
Extractables Compounds that can be extracted
from the elastomeric or plastic components, or
coatings of the container closure system when in
contact with appropriate solvent(s).
Leachables Compounds that leach into the
formulation from the elastomeric or plastic
components, or coatings of the container and
closure system as a result of direct contact with
the formulation.
CMC Leachables and Extractables Technical Team
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TEAMS FOCUS

• The Team has identified four key areas of the
  draft CMC guidances for clarification and/or
  further investigation
• Analytical Characterization of Extractables
  (Control Extraction Studies)
• Analytical Characterization of Leachables
• Safety Qualification of Leachables
• Routine Extractables Testing

CMC Leachables and Extractables Technical Team
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TEAMS TOPICS FOR STUDY
1. Analytical Characterization of Extractables
(Control Extraction Studies) The Team requests
clarification and will propose alternate language
with respect to the specific requirements for
control extraction studies (e.g., determination
of which critical components are required for
extractables analysis )
CMC Leachables and Extractables Technical Team
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TEAMS TOPICS FOR STUDY

• 2. Analytical Characterization of Leachables
• How is a correlation with extractables
  established?
• The Team will prepare a review of available
  leachables data and examine it for correlation
  with the corresponding extractables data . A
  working definition of correlation will be
  proposed based on an examination of the data.

CMC Leachables and Extractables Technical Team
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TEAMS TOPICS FOR STUDY
3. Safety Qualification of Leachables What are
current industry practices for establishing
safety of leachables? The Teams Working Group
on Toxicology will survey current industry
practices and will propose a strategy for safety
qualification of leachables based on best
practices (e.g., What are the qualification
criteria? Does ICH apply?)
CMC Leachables and Extractables Technical Team
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TEAMS TOPICS FOR STUDY
4. Routine Extractables Testing Is
quantitative testing of extractables appropriate
for control of composition of all
components? The Leachables and Extractables
Team, in collaboration with Supplier QC Team,
will propose a control strategy combining
appropriate scientific practices, cGMP controls
and supplier qualification systems for ensuring
the relevant performance and safety
characteristics of critical components
CMC Leachables and Extractables Technical Team
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TEAMS APPROACH AND COMMITMENT
The Team is committed to offer data-based
technical reports and recommendations to the
Agency and the OINDP Subcommittee within 3-4
months. The Team is available to evaluate any
extractable and leachable issue which the Agency
and the OINDP Subcommittee request.
CMC Leachables and Extractables Technical Team