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PE009-13, the PIC/S guide to GMP for medicinal products

TGA interpretation and expectations for demonstrating compliance

2 January 2018

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About PE009-13

The TGA is adopting version PE009-13 of the PIC/S Guide to Good Manufacturing Practice for Medicinal Products (PIC/S Guide to GMP), excluding Annexes 4, 5 and 14, as the manufacturing principles for:

  • medicines and active pharmaceutical ingredients
  • biologicals that comprise or contain live animal cells, tissues or organs

PE009-13 is available from the PIC/S website, and will take effect on 1 January 2018 as communicated on the 13 September 2017. TGA have published a notice about the transition to new GMP requirements for medicinal products.

PE009-13 does not apply to:

  • medical devices
  • biologicals that comprise, contain or are derived from human cells or human tissues

This guidance

This guidance explains the TGA's interpretation and expectations for compliance with specific sections of the PIC/S Guide to Good Manufacturing Practice for Medicinal Products, PE009-13. The content is based on questions and feedback received from industry stakeholders and replaces the questions and answers on GMP previously published by the TGA.

This guidance is not mandatory or enforceable under law. It is not intended to be restrictive. It describes a way that a manufacturer may operate to demonstrate compliance with the PIC/S Guide to GMP.

This information is provided for guidance only and has been developed on the basis of current knowledge of the subject matter. It should not be relied upon to address every aspect of the relevant legislation.

For legislative requirements, refer to:

For technical requirements, refer to:

For more TGA guidance:

Further questions

If you have further questions, or you require further clarification of a particular requirement, you can email your questions to the Manufacturing Quality Branch.

Australian legislation and the manufacturing principles

For medicines and other therapeutic goods that are not medical devices, section 36 of the Therapeutic Goods Act 1989 applies.

Section 36(1): The Minister may, from time to time, determine written principles to be observed in the manufacture of therapeutic goods for use in humans.

The manufacturing principles are determined in a therapeutic goods (manufacturing principles) determination.

Periodic changes

Good Manufacturing Practice requirements change over time due to various reasons, such as to:

  • provide guidance for the management of new technologies
  • address gaps or clarify existing compliance requirements
  • manage risks identified through inspections and regulation
  • facilitate continuous improvements in the way medicines are manufactured

The TGA uses internationally harmonised manufacturing standards to allow manufacturers to operate in an international environment. The TGA maintains its GMP standards in line with updates issued through PIC/S. Regular updates are necessary to:

  • maintain mutual confidence with international regulators
  • promote quality assurance of inspections
  • promote harmonisation of technical standards and procedures with international inspection standards for the production and testing of medicinal products

Australian manufacturers benefit from reduced regulatory burden where the TGA is able to adopt harmonised international standards and establish mutual recognition agreements and cooperation arrangements with comparable international assessment bodies.

Adoption of PE009-13

PIC/S guide to GMP is mandatory

Under provisions of section 36, Therapeutic Goods Act 1989 the PIC/S Guide to GMP PE009-13 will be adopted as the mandatory standard for the manufacture of medicinal products, replacing PE009-08. This means that the requirements outlined in the PIC/S Guide to Good Manufacturing Practice PE009-13 will be legally enforceable following adoption.

Timing of adoption

PE009-13 is to be adopted on 1 January 2018 with a transition period up to 1 January 2019, and will replace PE009-08 as the manufacturing principles. TGA commences inspecting against the requirements of PE009-13 from 1 January 2018. However, there will be a transitionary period and expectations for compliance are outlined in the transition plan. Compliance with all elements of the PIC/S GMP guide is mandatory from 1 January 2019.

Implication for imported products

The adoption of PE009-13 has no impact on imported products cleared by GMP certificates and other evidence of GMP compliance as outlined in the GMP Clearance Guidance. Following introduction of the PE009-13, the TGA will conduct its overseas inspections according to the new standard.

The main changes introduced by PE009-13

The changes between the PE009-08 and PE009-13 PIC/S Guide to GMP are clarifications of existing expectations. Some of these changes may require manufacturers to revise or modify their approach to compliance.

The main differences between the PE009-8 and PE009-13 are:

  1. clarified requirements for the pharmaceutical quality system used to manage the manufacture and/or testing of medicinal products including:
    • inclusion of changes aligned with ICH Q10 principles Pharmaceutical Quality System
    • clearer definition of the scope and design of the quality system
    • the introduction of the need to perform management reviews
    • requirements for the manufacturer to develop a quality policy
  2. clearer expectations for the evaluation of supply chains used for active pharmaceutical ingredients as part of Product Quality Reviews (PQRs)
  3. clarification of the application of quality risk management principles
  4. specifying the roles and responsibilities for senior management involved in the operation and management of manufacturing sites
  5. clearer expectations for the management of all outsourced activities that have the potential to affect product quality
  6. clarification on existing GMPs and new technologies used in the manufacture of biological medicinal substances and products for human use (Annex 2)
  7. updates to Annex 3, regarding the manufacture of radiopharmaceuticals, specifically in relation to the application of GMP and clarification of the requirements for sterile products
  8. updates to the Annex 11, regarding computerised systems, to align with current expectations regarding system validation and management
  9. several modifications to requirements for the manufacture of investigational medicinal products in Annex 13
  10. modifications to Annex 15, regarding qualification and validation, including modification of requirements for process and cleaning validation and clarification of requirements for validation of transportation methods

For more information, refer to:

Implications of PE009-13 adoption for current TGA guidance

TGA will be working with industry representatives and manufacturers to update all technical guidance documents to reflect any modified or clarified requirements as a result of the adoption. These documents will be completed and available during the transition phase (i.e. prior to 1 January 2019).

In the interim period, TGA inspectors will accept compliance with existing guidance documentation published on the TGA website. However, manufacturers are expected to:

  • review the requirements of PE009-13
  • assess the required modifications to their Pharmaceutical Quality Systems
  • implement changes in line with the transition plan

Application of PE009-13

Sections of PE009-13 that apply

The sections of the PIC/S Guide (PE009-13) that apply will be determined by the nature of your operations and the types of products or dosage forms you manufacture. In general:

  • Manufacturers of finished dosage forms should follow the principles of Part I of PE009-13, and in addition, all annexes relevant to their operations and dosage forms. Generally speaking, these manufacturers should meet the requirements of Annex 1 (for sterile API/product manufacturers), Annex 8 (sampling), Annex 11 (computerised systems), Annex 15 (qualification and validation) and Annex 19 (reference and retention samples)
  • Manufacturers of active pharmaceutical ingredients (APIs) should follow the principles of Part II of PE009-13, and in addition, all annexes relevant to their operations, (e.g. annexes 1, 2, 3, 7, 12, 14). Note that annexes 6, 8, 9, 10, 11 and 15 do not directly apply to the manufacture of APIs as specific guidance for APIs is provided within Part II of the guide; these annexes may however, be used as supplementary guidance without introducing additional requirements.
  • Guidance within annexes for specific dosage forms or product types should be read in conjunction with the relevant part of PE009-13 (Part I or II), e.g.:
    • a manufacturer of herbal liquid products should meet the requirements of Part I and annexes 8, 9, 11, 15 and 19
    • a manufacturer of sterile injectable products should meet the requirements of Part I and annexes 1, 8, 9, 11, 15, 17 and 19

Data management and data integrity

TGA has specific guidance relating to data management and data integrity. Refer to:

TGA inspections of veterinary medicines

The Australian Pesticides and Veterinary Medicines Authority (APVMA) will continue to accept TGA inspections of veterinary manufacturers. The TGA and the Australian Pesticides and Veterinary Medicines Authority (APVMA) have a Memorandum of Understanding (MoU) for cooperation on medicinal products manufactured in Australia for veterinary use.

For information about APVMA-TGA cooperation, refer to:

Requests for inspections of veterinary medicinal products in addition to human medicinal products must be conveyed to the APVMA by the manufacturer.

For inspections of veterinary medicines manufacturers that also hold a TGA licence to manufacture, inspections are restricted to the equipment and facilities used for the common production of human and veterinary medicines. Areas used solely for the manufacture of veterinary medicines, and that are not for the purpose of exporting to EU under the MRA, are outside the scope of the TGA inspection. However, if there are concerns about the impact of these areas on the manufacture of human therapeutic goods, these areas may be reviewed.

PIC/S GMP Annexes 4 and 5 have not been adopted by the TGA. However, if a domestic veterinary manufacturer is inspected by the TGA under the European Community - Australia Mutual Recognition Agreement, the TGA will use the relevant parts and annexes of PE009-13, including Annex 4 and Annex 5.

GMP for specific medicine types

Sunscreens

Sunscreens with a Sun Protection Factor (SPF) claim of 4 or more are required to be manufactured in compliance with GMP and so will be required to be compliant with PE009-13. More details are in the Australian Regulatory Guidelines for Sunscreens.

The technical GMP guidance for listed complementary medicines are baseline documents, elements of which can also be applied to other listed medicines (such as sunscreens) if justified.

Medicinal gases

The implications of the adoption of PE009-13 for medicinal gas manufacturers are similar to those for other medicines manufacturers.

Technical Guidance for manufacturers of medicinal gases can be found within the Guide to interpretation of the PIC/S Guide to GMP – 15 January 2009; applicable to the manufacture of medicinal gases. This guidance will be revised to reflect PE009-13. However, in the interim period, the TGA will accept compliance with the principles in the current TGA guidance.

Export-only medicines

For medicines listed in the ARTG as 'export only':

  • Medicines that would require registration on the ARTG for domestic supply (i.e. contain substances, quantities of substances or labels without mandatory warning statements required for supply in Australia) should be manufactured in accordance with the GMP applicable to registered medicines
  • Medicines that can be listed in the ARTG (i.e. contain substances that are included in the Catalogue of permitted ingredients for use in listed medicines) should be manufactured in accordance with the GMP applicable to listed medicines, with consideration to any TGA GMP guidance relevant to the manufacture of listed medicines

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