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Extractables and Leachablesfor Cell and Gene TherapyBPSA 2018 International Single-Use SummitPaul G. CummingsGeneral ManagerSmithers Rapra Analytical Services10 July 2018www.smithersrapra.com www.smitherspira.comCONFIDENTIAL
CGT E&L Subcommittee Develop a white paper covering the specifics of E&Las they apply to CGT. It is not complete yet. Yes, it is late.www.smithersrapra.com www.smitherspira.comCONFIDENTIAL
A (very) Brief History of E&L Started with the Metered Dose Inhaler Rapidly evolved to include parenteral drug productswww.smithersrapra.com www.smitherspira.comCONFIDENTIAL
A (very) Brief History of E&L USP has multiple chapters PQRI developed recommendations in 2007– Reflux extract components– Test extracts against a defined threshold– Perform a toxicological evaluation of observed extractables– Develop and validate analytical methods– Perform long term leachables studies– Still significant variation between different drug productswww.smithersrapra.com www.smitherspira.comCONFIDENTIAL
Cell and Gene Therapy A whole new thingVery sophisticated, leading edge therapeuticsEssentially all Single Use TechnologiesMore variety in materials of construction used in processingVirtually every drug product is uniqueRequire more nuanced E&L studieswww.smithersrapra.com www.smitherspira.comCONFIDENTIAL
CGT vs Traditional Packaging The “standard” approach to E&L testing for packagingjust does not apply. Exposure times to components are significantlyshorter:– Days/Hours/Minutes, not yearswww.smithersrapra.com www.smitherspira.comCONFIDENTIAL
CGT vs Traditional Packaging Significantly tighter control over conditions ofexposure.www.smithersrapra.com www.smitherspira.comCONFIDENTIAL
CGT vs Traditional Packaging Strong scientific justification for less vigorousextraction conditions. Many materials cannot tolerate vigorous extractionwww.smithersrapra.com www.smitherspira.comCONFIDENTIAL
CGT vs Traditional Packaging Time-based leachables studies are not really relevant. Simulation studies have emerged as the best practicefor leachables in CGT. But they cannot be “drug product” specific. Simulated matrices are used under expectedconditions of use.– Worst case when possible.www.smithersrapra.com www.smitherspira.comCONFIDENTIAL
CGT vs Traditional Packaging Some things remain the same.– Component treatment (washing, sterilization)– How long is the course of treatment?– How many doses per day?– How large a dose?www.smithersrapra.com www.smitherspira.comCONFIDENTIAL
Delivering to the Patient CGT is highly innovative science Developing therapeutics not even dreamed in the nottoo distant pastHowever Still have to be manufactured Still have to be stored, even for short periods of time Still have to get the treatment to the patientwww.smithersrapra.com www.smitherspira.comCONFIDENTIAL
Conclusions There is no single “Right Way” of doing an E&L study forCGT components. Extractables can be more universal. Leachables will require custom study design in many cases. Multiples factors must be considered in study design. As in “traditional” E&L Industry groups are involved. BPSA BPOG Regulators recognize the role and value of industry groups.www.smithersrapra.com www.smitherspira.comCONFIDENTIAL12
USP has multiple chapters PQRI developed recommendations in 2007 -Reflux extract components -Test extracts against a defined threshold -Perform a toxicological evaluation of observed extractables -Develop and validate analytical methods -Perform long term leachables studies -Still significant variation between different drug .
