presentation: updating the manufacturing principles · pe009-14 chapter 5 – production –...

Updating the Manufacturing PrinciplesAdoption of updates to the PIC/S Guide to GMP PE009

Matt DavisSenior GMP InspectorManufacturing Quality Branch

November 2019

Overview

Updating the Manufacturing Principles - GMP Forum 2019 1

Why adopt updates to GMP?

Adoption of PE009-14

Changes in version 14

Future updates to the PIC/S GMPs

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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

TIWGG Members:AccordAustralia 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)Medicines Australia (MA).

MQB adoption timeline for PE009-14

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- 3 Months•Notification for industry•Main changes table•Adoption strategy•Deficiency reporting

DD MMM 2020•Adopt New GMP Guide

•Publish Q&A for GMP

+6 months + 12 months Ongoing

Assess & establish

12m Transition Period

Implement Full Compliance

April 2019 •Gap Analysis TIWGG

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.

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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.5Updating the Manufacturing Principles - GMP Forum 2019

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)


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


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


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


Future PIC/S GMP updates

• Annex 1 – Sterile Medicinal Products• Annex 2A/2B - Advanced Therapy Medicinal

Products & Biological substances and products • Annex 11 Computerised Systems & Chapter 4

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• Annex 13 – Investigational Medicinal Products• Annex 16 - Certification by the Authorised Person and

Batch Release• Annex 21 – Importation

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

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presentation: updating the manufacturing principles · pe009-14 chapter 5 – production –...

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