Updating the Manufacturing Principles Adoption of Updates to the - PowerPoint PPT Presentation

Updating the Manufacturing Principles Adoption of Updates to the PIC/S Guide to GMP PE009 Matt Davis Senior GMP Inspector Manufacturing Quality Branch 26 June 2018

Overview • Why adopt updates to GMP? • Update Processes: – EMA process – PIC/S process – TGA process • Future Revisions – PE009-14 – PE009-?? Updating the Manufacturing Principles - GMP Forum 2018 1

Why adopt the latest PIC/S Guide to GMP? • Australia is highly respected and regarded on an international level due to our involvement and innovation with respect to GMP • GMPs are routinely updated in response to identified risks: – Risks to patient health – Ambiguity leading to misinterpretation and compliance risks • Relevant to our Mutual Recognition Agreements • Provides assurance of equivalence to international markets • GMP, science and innovation never stands still. Updating the Manufacturing Principles - GMP Forum 2018 2

EC/EMA GMP Update Process Final draft submitted by EM A / PIC/ S Draft Consultation Consolidated Update Consultation EM A GM DP Concept Guidance (Participating comments to identified (General) IWG – Paper Document Authorities) PIC/ S / EM A approval by EC Updating the Manufacturing Principles - GMP Forum 2018 3

PIC/S GMP Update Process Draft Comments Draft paper Update document TGA consults considered and Document Draft released to identified submitted to with TIWGG on final draft approved and document in participating - EC PIC/ S draft PIC/ S provided to published with PIC/ S format authorities for Committee for document PIC/ S effective date - SC-H comments adoption. Committee TIWGG M embers: Accord Australia New Zealand Industrial Gas Association (ANZIGA) Active Pharmaceutical Ingredient M anufacturer's Association of Australia (APIM AA) Australian Self M edication Industry (ASM I) Complementary M edicines Australia (CM A) 4 Generic and Biosimilar M edicines Association (GBM A) M edicines Australia (M A).

TGA GMP Update Process TGA consults Comments Regulatory External Adoption of Establish with TIWGG on considered and Develop gap Impact communications new internal project draft Gap final Gap Statement strategy M anufacturing analysis team Analysis Analysis (OBPR) developed Principles document endorsed Updating the Manufacturing Principles - GMP Forum 2018 5

Gap Analysis PE 009-13 PE 009-08 Nature of impact Estimated significance of impact Nil 1. ORGANISING AND PLANNING FOR QUALIFICATION AND VALIDATION New clause, but equivalent requirements provided in PE009-8 Annex Clarification of 15§2. existing requirements, no 1.1 All qualification and validation activities should be planned and take the life cycle change to of facilities, equipment, utilities, process and product into consideration. PLANNING FOR VALIDATION interpretation. 2. All validation activities should be planned. The key elements of a validation programme should be clearly defined and documented in a validation master plan (VMP) or equivalent documents. Expanded planning section in PE009-13 However, this section provides additional clarification to that included within PE009-8: 5.21 A process validation protocol should be prepared which defines the critical New clause, but equivalent requirements provided in PE009-8 Annex Introduction of new Nil for some process parameters (CPP), critical quality attributes (CQA) and the associated 15§6. terminology (CPP manufacturer acceptance criteria which should be based on development data or documented and CQA) into s; minor for validation systems. some. This clause introduces the terms CPP and CQA in line with ICH Q11 process knowledge. terminology. While the terminology may be more prescriptive, the process of identifying critical steps (that directly influence the critical attributes of the product) and acceptance criteria remain very similar to existing methods and expectations. (Note that these concepts already exist for API manufacturers) 6. A written protocol should be established that specifies how qualification and validation will be conducted. The protocol should be reviewed and approved. The protocol should specify critical steps and acceptance criteria. Updating the Manufacturing Principles - GMP Forum 2018 6

Adoption Plan – Examples PIC/ S GM P Requirement Between 1 J anuary and 30 J une 2018 Between 1 J uly 2018 and 31 December 2018 From 1 J anuary 2019 Part I, Chapter 1 Clause 1.6 M anagement Reviews Approved policy Initial management review meetings held. Full implementation Documented assessment of which data will be M echanisms for resolving issues formalised and collated and reported. implemented Commenced amending and drafting procedures Schedule for management reviews finalised. Commenced training staff in M anagement Reviews Part I, Chapter 7 Outsourced activities Approved policy Approved procedures Full implementation M edium Risk Item Commenced drafting procedures Commenced amending/ drafting new contracts All outsourced activities approved and covered by an appropriate contract. Risk assess/ Determine list of all service providers implicated. Develop priority list for evaluation and approval of providers. • Refer TGA website for guidance for deficiency reporting during the period 7

MQB Adoption Timeline for PE009-13 September 2017 1 January 2018 31 June 2018 1 January 2019 Ongoing November 2017 • 1 st notification for • Adopt New GMP Guide • 2 nd notification for industry industry • Publish Q&A for GMP • APVMA notification • Main changes table • Adoption strategy • Deficiency reporting 12m Transition Period Assess & establish Implement Full Compliance Updating the Manufacturing Principles - GMP Forum 2018 8

Future Revisions of PE009 Future 1 July 2018 • 1 Jan 2017 revisions PE009- PE009- PE009- Chapters 3, 5 • Chapter 1, Chapter 4 & 8 13 14 ?? 2, 6 & 7 (Part Annexes 1, 2, I) Annex 17 11, 13, 16, 21 9

PE009-14 Chapter 3 – Premises and Equipment • Additional guidance on Cross-contamination • Quality Risk Management principles should be used to assess and control the risks. • Dedicated facilities are required when: – the risk cannot be adequately controlled by operational and/ or technical measures , – scientific data from the toxicological evaluation does not support a controllable risk (e.g. allergenic potential from highly sensitising materials such as beta- lactams) or – relevant residue limits , derived from the toxicological evaluation , cannot be satisfactorily determined by a validated analytical method. Updating the Manufacturing Principles - GMP Forum 2018 10

PE009-14 Chapter 5 – Production – Cross Contamination (1) • Quality Risk Management process… should be used to assess and control the cross-contamination risks presented by the products manufactured. • Technical Measures: – Dedicated processes, equipment and facilities; – Use of closed systems, barrier, isolator, single-use technologies; – Dust extraction, air-locks, pressure cascades; – Clean-in-place, ease of cleaning considered in process/equipment design • Organisational Measures: – Campaign operation, campaign washing, cleaning verification; – Gown management, waste management, spill management; – Detailed cleaning records and instructions, continued oversight of compliance. Updating the Manufacturing Principles - GMP Forum 2018 11

PE009-14 Chapter 5 – Production – Starting Materials • Selection, qualification, approval and maintenance of suppliers of starting materials, together with their purchase and acceptance , should be documented as part of the pharmaceutical quality system. • Staff involved in these activities should have a current knowledge of the suppliers, the supply chain and the associated risks involved. • Active Substances – Supply chain traceability established and associated risks formally assessed and periodically verified. – Audits should be carried out at the manufacturers and distributors of active substances…audits should be of an appropriate duration and scope to ensure that a full and clear assessment of GMP is made. – The holder of the manufacturing authorisation shall verify such compliance either by himself/herself or through an entity acting on his/her behalf under a contract. • Excipients – formalised quality risk assessment (PI 045-1) 12 Updating the Manufacturing Principles - GMP Forum 2018

PE009-14 Chapter 8 – Complaints & Product Recall • Defined requirements for Personnel and Organisation within the PQS • Procedures for handling and investigating complaints including possible quality defects • Investigation and decision making • Root cause analysis and CAPA • Product Recalls and risk-reducing actions • Reflects URPTG requirements Updating the Manufacturing Principles - GMP Forum 2018 13