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 November 2019

Overview Why adopt updates to GMP? Adoption of PE009-14 Changes in version 14 Future updates to the PIC/S GMPs Updating the Manufacturing Principles - GMP Forum 2019 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 2019 2

MQB adoption timeline for PE009-14 April 2019 - 3 Months DD MMM 2020 +6 months + 12 months Ongoing •Gap Analysis •Notification for industry •Adopt New GMP TIWGG Guide •Main changes table •Publish Q&A for GMP •Adoption strategy •Deficiency reporting 12m Transition Period TIWGG Members: Assess & Implement Full Compliance Accord establish Australia New Zealand Industrial Gas Association (ANZIGA) Active Pharmaceutical Ingredient Manufacturer's Association of Australia (APIMAA) Complementary Medicines Australia (CMA) Consumer Healthcare Products Australia (formerly ASMI) Generic and Biosimilar Medicines Association (GBMA) 3 Medicines Australia (MA).

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 2019 4

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 2019 5

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 6 Updating the Manufacturing Principles - GMP Forum 2019 – formalised quality risk assessment (PI 045-1)

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 2019 7

PE009-14 Annex 17– RTRT & parametric release • Real Time Release Testing (RTRT) (ICH Q8 Q&A) • Control of critical parameters and relevant material attributes are authorised as an alternative to routine end-product testing of active substances and/or finished products. • RTRT may apply to any stage in the manufacturing process and to any type of finished products or active substances, including their intermediates. • Real time measurement of CPP(s) as a predictor of compliance with CQA . • Thorough understanding of critical material attributes . • Well defined control strategy: QRM, validation, change control, training, etc Updating the Manufacturing Principles - GMP Forum 2019 8

PE009-14 Annex 17– RTRT & parametric release • Parametric Release – terminally sterilised products • Updates to text providing clarification of existing requirements. • Detailed guidance regarding the scope of the sterility assurance program . • Additional emphasis on Quality Risk Management . • Guidance for pre-sterilisation bioburden testing and controls , and consideration of heat-resistant organisms . • Well defined control strategy: QRM, validation, change control, training, etc Updating the Manufacturing Principles - GMP Forum 2019 9

Future PIC/S GMP updates • Annex 1 – Sterile Medicinal Products • Annex 13 – Investigational Medicinal Products • Annex 2A/2B - Advanced Therapy Medicinal • Annex 16 - Certification by the Authorised Person and Products & Biological substances and products Batch Release • Annex 11 Computerised Systems & Chapter 4 • Annex 21 – Importation 10

Summary • TGA Guidance documents available on TGA website • TGA has commenced reviews of PE009-14 and will continue to work with industry on adoption of future changes • Several changes in the pipeline • Get involved! – EMA/EC Feedback – TGA/TIWGG Feedback 11