PIC/S Guide to GMP PE009-13 Key Changes to Annex 2 Manufacture of - - PowerPoint PPT Presentation

PIC/S Guide to GMP PE009-13

Key Changes to Annex 2 – Manufacture of Biological Medicinal Substances and Products for Human Use

June 2018

Francesco Cicirello GMP Inspector Manufacturing Quality Branch

Key changes to Annex 2:

M ajor re-write to provide clarification on existing GM Ps and new technologies Guidance for application of GM P to starting materials Emphasis on controlling adventitious agents, TSE and zoonotic diseases Part A: General Guidance Part B: Specific guidance for selected product types

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Scope of Annex 2

Table 1. Illustrative guide to manufacturing activities within the scope of Annex 2

Type and source of material Example product Application of this guide to manufacturing steps shown in grey

• 1. Animal or

plant sources: non- transgenic Heparins, insulin, enzymes, proteins, allergen extract, ATMPs immunosera Collection of plant, organ, tissue or fluid

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Cutting, mixing, and /

• r initial

processing Isolation and purification Formulation, filling

• 2. Virus or

bacteria / fermentation / cell culture Viral or bacterial vaccines; enzymes, proteins Establishment & maintenance of MCB4, WCB, MVS, WVS Cell culture and/or fermentation Inactivation when applicable, isolation and purification Formulation, filling 3. Biotechnolog y fermentation/ cell culture Recombinant products, MAb, allergens, vaccines Gene Therapy (viral and non-viral vectors, plasmids) Establishment & maintenance of MCB and WCB, MSL, WSL Cell culture and /or fermentation Isolation, purification, modification Formulation, filling

• 4. Animal

sources: transgenic Recombinant proteins, ATMPs Master and working transgenic bank Collection, cutting, mixing, and/or initial processing Isolation, purification and modification Formulation, filling

• Clarification of the application of GM P to

biological substances and products

• M aster Cell Banks, Working Cell Banks,

etc.

• Collection of plant, tissue or fluid
• GM P applies to all steps in grey
• Sponsors – refer to TGA website for

evidence requirements

• M anufacturers – should hold

evidence of GM P for the materials you source

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• 5. Plant

sources: transgenic Recombinant proteins, vaccines, allergen Master and working transgenic bank Growing, harvesting5 Initial extraction, isolation, purification, modification Formulation, filling

• 6. Human

sources Urine derived enzymes, hormones Collection of fluid6 Mixing, and/or initial processing Isolation and purification Formulation, filling

• 7. Human

and/or animal sources Gene therapy: genetically modified cells Donation, procurement and testing of starting tissue / cells8 Manufacture vector7 and cell purification and processing, Ex-vivo genetic modification of cells, Establish MCB, WCB or primary cell lot Formulation, filling Somatic cell therapy Donation, procurement and testing of starting tissue / cells8 Establish MCB, WCB or primary cell lot

• r cell pool

Cell isolation, culture purification, combination with non- cellular components Formulation, combination, fill Tissue engineered products Donation, procurement and testing of starting tissue / cells8 Initial processing, isolation and purification, establish MCB, WCB, primary cell lot

• r cell pool

Cell isolation, culture, purification, combination with non- cellular components Formulation, combination, fill

3 See section B1 for the extent to which GMP principles apply. 4 See section on ‘Seed lot and cell bank system’ for the extent to which GMP applies. 5 In the EEA: HMPC guideline on Good Agricultural and Collection Practice - EMEA/HMPC/246816/2005 may be applied to growing, harvesting and initial processing in open fields. 6 For principles of GMP apply, see explanatory text in ‘Scope’. 7 Where these are viral vectors, the main controls are as for virus manufacture (row 2). 8 In the EEA, human tissues and cells must comply with Directive

Currently regulated with the Australian code of GM P (2013)

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Heads up: PIC/S Annex 2 Revision

• Working Group established to revise the Annex 2 (M anufacture of biological

medicinal products for human use) of the Guide to Good M anufacturing Practice of M edicinal Products PE 009-13 (Annexes)

• TGA (chair), WHO and EM A amongst participants
• Objectives:
• The revision of the requirements for ATM Ps will remain an integral part to the existing GM P guidelines and will not

be a standalone guide

• The WG will draft a separate Annex specific to ATM P and align the existing Annex 2 to the EU for remaining

products

• Efforts will be made, with the aim at maintaining as close harmonisation as possible, to use the language of the

“Guidelines on Good M anufacturing Practice (GM P) specific to Advanced Therapy M edicinal Products (ATM P)” where possible. PIC/ S and WG represented stakeholder’s concerns will guide the final language.

• Efforts will be made to accommodate language that address challenges such as “diffuse manufacturing”
• Efforts will be made to accommodate language that will permit the standard to facilitate cross border movement
• f ATM P. The standard will aim to be bridging across the expectations for these products through all jurisdictions,

even the ones that will not formally adopt it

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PIC/S Guide to GMP PE009-13

Key Changes to Annex 11– Computerised Systems

Francesco Cicirello GM P Inspector M anufacturing Quality Branch June 2018

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Annex 11: What’s new?

Scope

Applies to all forms of computerized systems (CS) in GM P environment. software applications validated and IT infrastructure qualified. Focus on QRM CS lifecycle management. Roles and Responsibilities

Suppliers and Service Providers

Quality/ technical Agreements Audits of service suppliers visible Review and approval of supplied documentation

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Annex 11: What’s new?

Validation

Life-cycle approach System inventory list URS for each system - traceability matrix System parameter limits, data limits and error handling Periodic Review Change Control

Data Integrity

Data accuracy, audit trails, and security Data migration controls Electronic Signatures Checks on back-up

IT support

Back-up and archiving Incident management – RCA & CAPA Business continuity

Validation

Retrospective validation not permitted Parallel testing not required

Annex 11: What’s gone?

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• Retrospective Validation

– Annex 11 originated in 1992 – Retrospective validation allowed manufacturers to validate existing systems – All systems in use today should be validated

• Parallel testing

– Not widely adopted – Allows increased focus of resources on new system