Transcript Document 7517543

ICH Q4B
Regulatory Acceptance of Analytical
Procedures and/or Acceptance Criteria
(RAAPAC)
Overview and Update
Robert H. King, Sr.
Office of Pharmaceutical Science, CDER, FDA
Advisory Committee for Pharmaceutical Science (ACPS)
October 5, 2006
Presentation Outline
• History and Overview
• Q4B Process
• Current Activities for the Q4B Expert
Working Group (EWG)
• Implementation Considerations
ACPS – October 5, 2006
Background
• The harmonization of specific compendial test chapters has
been considered as critical by the ICH Steering Committee to
attaining full utility of the ICH Q6A guideline.
• Industry asks ICH SC to create an EWG to address regulatory
acceptance (3 regions) of harmonized pharmacopeial
methods from EP/JP/USP (PDG) – July 2003
• ICH SC establishes Q4 EWG with a scope to address 11
General Test Chapters discussed during development of ICH
Q6A Guideline - November 2003
• SC approves Q4B Work Plan – April 2004
ACPS – October 5, 2006
Background (Continued)
• SC approves development of an ICH Guideline – June 2004
• Q4B EWG begins evaluating PDG harmonized text –
November 2004
• Step 2 ICH Q4B Guideline approved by SC – June 2006
• 1st Annex (Residue on Ignition/Sulphated Ash) approved June
2006
• FDA Draft Guidances printed in FR August 2006 (60-day
comment period)
ACPS – October 5, 2006
Q6A-related General Chapters
•
Dissolution
•
*Uniformity of Content
•
Extractable Volume
Particulate Matter
•
Sterility
Microbiological Quality
• Bacterial Endotoxins
Disintegration
*Uniformity of Mass
ROI/Sulphated Ash
• Colour and Clarity
(per ICH SC, work will just be on "Colour")
______
* Harmonized to Uniformity of Dosage Units
ACPS – October 5, 2006
What is PDG?
• Pharmacopeial Discussion Group (PDG)
comprised of representatives of the United States
Pharmacopeia (USP), Japanese Pharmacopoeia
(JP), and the European Pharmacopoeia (Ph.Eur.
or EP)
• Multi-step process to harmonize selected general
test methods and monographs
• May result in some residual or local differences
that may pose issues for regulators – Q4B/PDG
interaction to resolve issues
ACPS – October 5, 2006
PDG Process Results in Harmonized Text
Individual Pharmacopeial Approval & Official Printing Process
JP Version
____________
____________
____________
____________
____________
____________
____________
____________
____________
____________
USP Version
____________
____________
____________
____________
____________
____________
EP Version
____________
____________
____________
____________
____________
____________
____________
____________
____________
Do differences impact on the ability to achieve same result
with same accept/reject capability?
ACPS – October 5, 2006
Q4B Process Steps
FOR EACH TOPIC:
• PDG provides to Q4B Expert Working Group:
– PDG-harmonized text
– JP/EP/USP draft version of how harmonized text will
be implemented in their compendia
– Briefing note to delineate any local differences or
potential issues
– Printing timeline to move each pharmacopeia to
official status
• Q4B member parties bring the documents back
to their constituents for independent evaluation
ACPS – October 5, 2006
Q4B Process (continued)
• Q4B EWG reviews the evaluations
• Issues discussed within Q4B EWG for
possible resolution
• Evaluation results and possible resolution
mechanisms conveyed back to and/or
discussed with PDG
• Once issues are resolved, Q4B EWG
recommends approval (ICH Step 2) to the
ICH SC – start of Annex process
ACPS – October 5, 2006
Topic Specific Annex Process
PDG Process
PDG Document
Submission
ICH Process
Step 1: Q4B EWG assessment and annex
development
Step 2: ICH Sign off on draft Q4B annex
Regional
pharmacopoeial
implementation
Step 3: Regulatory Consultation on annex
Step 4: Annex adopted by ICH Steering
Committee
Step 5: Regional regulatory implementation
Inter-regional
Acceptance
ACPS – October 5, 2006
What Q4B Activity Is
•
Effective way to raise and resolve issues that might impact
both industry and regulators.
•
For FDA, interchangeability means the possible use of the
harmonized methods of JP and EP, where deemed
appropriate and based on our scientific review, to be
considered as equivalent to the USP method.
•
A savings in time and effort:
– More so to industry to globally unify testing strategies
[for applications and other regulatory (compliance)
needs] – one test rather than three
– To possibly reduce or eliminate the need to go through a
justification procedure as to the use of other compendial
methods (done one time to eliminate repetitive
justifications)
ACPS – October 5, 2006
What Q4B Activity Is
(continued)
• Given the unified approach and strength of working
directly with the three regulatory regions, it is an effective
way to partner in the pharmacopeial process to effect
change, where single, independent efforts might not be
as successful.
• Maintains FDA's review authority
• In case of any question, the local regional method
prevails.
• Establishes a process for multi-center input into scientific
review for determining the interchangeability.
ACPS – October 5, 2006
What Q4B Activity Is Not
•
It will not be a mechanism to supplant FDA's CMC
review processes and mandate. It will be up to the
CMC reviewer and the sponsor to establish what are
the best methods and acceptance criteria to ensure a
safe and efficacious product
•
It will not reinvent the compendial revision cycle that
resulted in the PDG harmonized text -- Industry and
regulators have their input during the individual
revision processes
•
It will not establish acceptance criteria outside of
normal processes
ACPS – October 5, 2006
Q4B Activity for Chicago Meeting
• Work continuing to move Q4B Guideline and 1st Annex to
ICH Step 4/5
• Finalize 2nd Annex for “Extractable Volume” to ICH Step
2 and move to regulatory consultant (ICH Step 3)
• Work continuing on evaluation of other PDG harmonized
text submissions:
– Sterility Test
– Particulate Matter
– Dissolution
– Other general test chapters to come
ACPS – October 5, 2006
Implementation Considerations
• Each completed topic moved to FDA Guidance for
Industry
• Transparency for industry and regulators
• FDA stakeholder Work Group formed for
awareness and training relative to the Q4B
process. Representation from:
–
–
–
–
CDER (ONDQA, OGD, OBP, OTR, Office of Compliance)
CBER
CVM
ORA
ACPS – October 5, 2006
Acknowledgements
My thanks to:
• Cindy Buhse
• Jon Clark
ACPS – October 5, 2006