Module 9 2021

19/03/2021

TSE & virus RA-life cycle of product

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Full Release of MCB/WCB for Ph I/II MCB/WCB TSE & virus RA

Full Release of MCB/WCB for Ph III and IVCA studies

Pre-MCB Transfer and Testing

Pre-MCBTSE & virus RA

MCB/WCB Transfer for Commercial Mfg

Manufacture Phase II/III material

Manufacture Commercial material

Manufacture GLP Tox material

Manufacture Phase I material

Manufacturing TSE & virus RA

Manufacturing TSE & virus RA

Manufacturing TSE & virus RA

IND/IMPD Submission prior to Phase I study

BLA/MAA/JNDA Submission

IND/IMPD Submission prior to Phase II /III study

Candidate Selection

File and Launch

Life Cycle Management

Preclinical

Phase I

Phase II

Phase III

• Pre-MCB, MCB/WCB and Manufacturing raw and starting materials assessed for TSE and virus risk from use of animal derived materials which informs MCB/IVCA virus testing strategy and TSE risk assessment. • Virus Clearance Validation carried out to support Phase I/II and Phase III and MAA/BLA submissions

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Conclusion

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 Biopharmaceuticals and Biologicals are produced from cells which have the potential to become infected with viruses  Virus (and TSE) risk assessments need to be in place and risk managed holistically to ensure patient safety, facility, personnel safety and Regulatory acceptance by a combination of: ● Raw materials sourcing and use of well characterized cell lines ● Testing of pre-MCB, MCB, WCB and intermediates according to ICH Q5A and Q5D ● Virus clearance validation (<1 virus like particle per 10^6 doses) ● Personnel Gowning procedures and facility cleaning, closed systems and airflows- use of disinfectants provides anti-viral assurance  TSE and Virus risk can be carried for the life-time of the product (from Research cell lines) and evidence of clear mitigation of risk must be demonstrated to the Regulatory Agencies within the relevant Dossiers

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