Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as...
Transcript of Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as...
![Page 2: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/2.jpg)
2
•Overview
•Pre-Clinical
•Early clinical trials (IND)
•API, reference standards
•ASAP and QbD
•ASAP in NDA (sNDA) submissions
•ASAP in ANDA submissions
•Post-approval change
Outline
[email protected] 2018
![Page 3: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/3.jpg)
[email protected] 2018 3
Overview• ASAPprime® has been successfully used as
part of regulatory documents• ASAP replaces/supplements standard
methods for meeting regulatory obligations• FreeThink can help
• Key references• “Talking points”• Responses to queries• Meetings with regulatory authorities
![Page 4: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/4.jpg)
[email protected] 2018 4
Agency Awareness
• Presentations made to many country agencies• Specific countries we are aware that
presentations have been made:• US• Canada• UK• Brazil• China• Czech Republic
![Page 5: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/5.jpg)
[email protected] 2018 5
Pre-Clinical
• ASAP estimation of degradant level at end of shelf-life used to guide what specification limit to request with authorities• Allows regulatory groups to
determine what to request• Supports requested levels
![Page 6: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/6.jpg)
[email protected] 2018 6
API and Reference Standards
• ASAP-only used to set 1-year retest period• No reported regulatory issues in US• Expect acceptance world-wide• Note that patient safety is not at risk since
the drug product will get tested—stability testing is part of product control and understanding
![Page 7: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/7.jpg)
[email protected] 2018 7
Early Clinical Trials—IND’s, Generics
• ASAP only using prototype formulations to justify 12-month use-period
• Date clinical supplies for 12-months (if >95% probability of passing under storage conditions)
• Place clinical material on standard ICH stability protocol• Only analyze if queried
![Page 8: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/8.jpg)
[email protected] 2018 8
Early Clinical Trials—IND’s, generics
• >10 Companies have employed this strategy• Pfizer, AZ and Janssen (Johnson & Johnson) have
discussed this publically• Regulatory authorities in each case have the
following options:• Make no comment—no further data required• Query the approach—need an explanation, more
data• Reject and request traditional
![Page 9: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/9.jpg)
ASAP Regulatory Experience (Clinical)
From F. Qiu presentation “Science of Stability Conference” Boston 2018
[email protected] 2018 9
![Page 10: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/10.jpg)
ASAP Regulatory Experience (Clinical) by Country
From F. Qiu presentation “Science of Stability Conference” Boston 2018
[email protected] 2018 10
![Page 11: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/11.jpg)
[email protected] 2018 11
ASAP under Quality Systems
• FreeThink SOP’s/practice• Set-up of ASAP study including
• Chambers• Salt solutions• Use of monitors• Sample handling pre and post stressing until
testing• Calibration of monitors• Chambers• Analytical methods• Data handling
• Empower III output as input to ASAPprime®• Algorithmic point/condition removal
![Page 12: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/12.jpg)
[email protected] 2018 12
ASAP under Quality Systems• GMP and use of ASAP
• Most companies do not conduct ASAP studies under GMP for IND’s
• Many companies use some part GMP for NDAs/post approval applications• Most only have GMP for analytical• Some outsource to FreeThink for regulatory
filings
• ASAPprime® Validation• ASAPprime® fully validated and CFR11 compliant• Validation documentation available on request
(no charge)• Starting 2019, IQ/OQ service will be available
![Page 13: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/13.jpg)
[email protected] 2018 13
ASAP and QbD
• Quality by Design (QbD) for stability requires understanding factors that influence stability• T, RH impact• Packaging impact• Lot-to-lot consistency
• API lots• Excipient variability• Process variability
![Page 14: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/14.jpg)
[email protected] 2018 14
ASAP and QbD
• Can use ASAP to examine range of factors• May not be able to scope all variables• Quality by Testing (QbT) using ASAP may de-
risk future changes• Run ASAP on product after changes to
test impact• Establish change as minor change and
therefore not needing full stability program
![Page 15: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/15.jpg)
[email protected] 2018 15
ASAP in NDA Submissions• ASAP used in registration packages world-wide• No ASAP-only NDAs• ASAP used to bridge clinical to commercial changes
ASAP demonstrating validity of model against ICH data for clinical
ASAP demonstrating equivalence after change
![Page 16: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/16.jpg)
[email protected] 2018 16
ASAP in NDA Submissions
• ASAP plus 3 month ICH data successfully used to justify 3-year shelf-life at launch (EU)!• Note: commitment to ongoing monitoring of
commercial material
• ASAP used to justify specification limit change successful in EU
![Page 17: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/17.jpg)
[email protected] 2018 17
ASAP in ANDA Submissions
• Show generic product in its packaging is at least as stable as originator in its packaging• Easier to show statistical equivalence with
ASAP• Especially helpful when specification limits
not known
![Page 18: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/18.jpg)
[email protected] 2018 18
Post-Approval
• Companies have successfully used ASAP-only submissions for reduced-protection packaging without other (new) data• US only (so far)
• Justification for acceptance after shipping excursions
![Page 19: Use of ASAPprime® in Regulatory Filings · Overview •ASAPprime® has been successfully used as part of regulatory documents •ASAP replaces/supplements standard methods for meeting](https://reader033.fdocuments.in/reader033/viewer/2022050421/5f90df700724d041c6677323/html5/thumbnails/19.jpg)
[email protected] 2018 19
Summary
• ASAP can play a significant role in meeting regulatory obligations
• ASAP provides understanding which improves filings
• In some cases, ASAP can replace ICH stability studies
• When ICH stability studies needed, they can be minimized (confirmation only)