Biosafety in upstream bioprocessing. Erik Kakes, Sales & Marke;ng director Applikon Biotechnology

Transcription

1 Biosafety in upstream bioprocessing Erik Kakes, Sales & Marke;ng director Applikon Biotechnology

2 About Erik Kakes Studied Biochemistry Ac;ve in bioreactor design since 1988 Project manager Product development Marke;ng & Sales Co-owner of Applikon Biotechnology since 2008

3 Applikon Biotechnology One of the largest privately owned bioreactor companies Started in 1974 by Jan van Burg Keywords: Reliable New technologies Long term customer rela;on Micro scale to produc;on scale systems Local experts for sales, service and support Jan van Burg Bioreactor systems only Daughter companies in Netherlands, UK, USA, China

4 Applikon history in vaccine produc;on 1970 s: Bilthoven units Dr. van Hemert & Ir. van Wezel 1989 Applikon and Contact Flow merger 1990 s: China Vaccine Project RIVM, DHV, Applikon Last 30 years Mul;ple large scale vaccine projects

5 Laboratory bioreactors

6 Produc0on systems

7 Applikon Inside! Single Use systems

8 Vaccine Development Discovery Preclinical Phase 1 Phase 2 Phase 3 Product Licensure Phase 4 Lead Development Process & Assay Development, Scale-up Animal models Clinical & Regulatory Pilot manufacturing, QC & QA Techtransfer Facility development (See next detail slide) Pharmacovigilance QA / QP oversight including CMOs, CROs CMC Project management

9 Facility Development Phase 3 Product Licensure Phase 4 Techtransfer Plant design & engineering Project management, Project QA and compliance management Procurement Facility Construc0on Equipment Delivery Quality Systems development Comple0on and commissioning Recruitment & training Qualifica0on Tech transfer and valida0on Factory Licencing Commercial Manufacturing, QC & QA

10 Biosafety vs GMP Biosafety Protect the operator GMP Protect the consumer Keep them in Keep them out

11 Biosafety Responsibility of supplier & customer Customer: Provide safe environment for personnel Inform supplier of poten;al risks Supplier: Intrinsic safety as a design criterium Understand and minimize the process risks Communica;on is key

12 Project communica;on: Website Open informa;on exchange 24/7 accessible Up-to-date informa;on Documented communica;on Documented decisions Everybody works with the same documents No surprises

13 Recap: Bioreactor Gas Out Hea;ng/cooling medium: FROM JACKET =Risk Area Hea;ng/cooling medium: TO JACKET Sampling Down Stream

14

15 Biosafety: Single-Use or Re-Usable Single-Use Short lead ;me Lower ini;al investment More flexibility More manual labor so more procedures required Re-Usable Longer lead ;me Higher ini;al investment Less flexibility More automa;on

16 Biosafety: Single-Use bioreactors Report April 2016, Dutch Commission for Gene;c Modifica;on Integrity test of bag not standardized Biggest risk is during installa;on where manual manipula;on is the highest risk No reliable integrity test possible afer installa;on Increased risk for operator Con;nuous training programs are needed

17 Biosafety: Re-Usable bioreactors Benefits of process automa;on Less manual manipula;on Automated test procedures Automated documenta;on Interlocks for increased safety Verified automated transfer between units Con;nuous feedback loops

18 Recap: Bioreactor Biosafety No virus to exit No virus to exit No virus to exit Hea;ng/cooling medium: FROM JACKET No virus to exit Gas Out No virus to exit No virus to exit =Risk Area Hea;ng/cooling medium: TO JACKET Sampling No virus to exit uncontrolled No virus to exit uncontrolled Down Stream

19 Recap: Bioreactor GMP =Risk Area No contaminant to enter No contaminant to enter No contaminant to enter Reproducible & Controlled conditions Gas Out No organisms to enter or exit uncontrolled Hea;ng/cooling medium: FROM JACKET Well defined materials No contaminant to enter Hea;ng/cooling medium: TO JACKET Homogeneous mixing Defined gas supply No organisms to enter or exit uncontrolled Sampling Down No organisms to enter or Stream exit uncontrolled

20 Off-gas Incinerator Gas Filters

21 0.2 micrometer pore size Membrane filter Integrity test points Exhaust gas filter Test integrity before and afer process

22 Exhaust gas incinerator Temperature measurement & Control Time & heat kill, con;nuous monitoring 200 C, Up to 200 l/min

23 Agitator sealing Magne;c coupling No direct contact between inside and outside of reactor Minimal maintenance Up to 40 Nm torque Cell culture up to 3000 liter volume Microbial up to 500 liter volume

24 Equipment risk management Focus on the interfaces!!! Different suppliers Building, upstream and downstream equipment Different equipment Liquid flow path, connec;on types, temperatures, flows Different sofware solu;ons Handshakes between devices, communica;on and data integra;on, valida;on, unified operator interfaces Use as many standard building blocks as possible Proven performance

25

26 What is Hazop? Hazop study Hazard and operability study a structured and systema;c examina;on of a complex planned or exis;ng process or opera;on in order to iden;fy and evaluate problems that may represent risks to personnel or equipment

27

28

29

30 Hazop study report

31 Hazop ra;ng

32 Hazop ac;onlist

33

34

35 Resuming Biosafety is a shared responsibility Advanced automa;on improves safety Build intrinsic safety into design Hazop analysis iden;fies problems and solu;ons Hazop can be done on old and new installa;ons

36 Thank you!