Presentation on updates to TGA guidance, adoption of PE009-14, changes in version 14 and future updates to the PIC/S GMPs

1. Updates to Good Manufacturing Practices
Recent, current and future changes
Matt Davis
Senior Inspector
Manufacturing Quality Branch
August 2019

2. Overview
Updates to TGA Guidance
Adoption of PE009-14
Changes in version 14
Future updates to the PIC/S GMPs
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3. Updates to TGA Guidance
• PE009-13, the PIC/S guide to GMP for medicinal products: TGA interpretation and
expectations for demonstrating compliance
• Release for supply of medicines
General GMP Guidance
• Ongoing stability testing for listed and complementary medicines
• Process validation for listed and complementary medicines
• Product Quality Reviews (PQRs) for listed and complementary medicines
• Sampling and testing for listed and complementary medicines
• Supplier assessment, approval and qualification for listed and complementary
medicines
Listed & Complementary Medicines
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4. Updates to TGA Guidance
• Sunscreen manufacturing: demonstrating compliance with the PIC/S Guide to
GMP PE009-13
• Manufacture of sterile radiopharmaceuticals labelled with fluorine-18
• Manufacture of medicinal cannabis for supply under 'approved access' provisions
• Medicinal gases and good manufacturing practice (GMP)
Specific Dosage forms
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5. MQB Adoption Timeline for PE009-14
TIWGG Members:
Accord
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)
Medicines Australia (MA).
- 3 Months
•Notification for industry
•Main changes table
•Adoption strategy
•Deficiency reporting
DD MMM 202?
•Adopt New GMP
Guide
•Publish Q&A for GMP
+6 months + 12 months Ongoing
Assess &
establish
Implement Full Compliance
12m Transition Period
April 2019
•Gap Analysis
TIWGG
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6. 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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7. 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.
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8. 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)
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9. 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
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10. 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
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11. 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
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12. 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
Annex 13 –
Investigational Medicinal
Products
Annex 16 - Certification
by the Authorised Person
and Batch Release
Annex 21 – Importation
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13. 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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