You are here

Evidence of GMP for prescription medicines

Guidance for sponsors

15 December 2019

This guidance is for sponsors and applicants preparing applications to:

GMP compliance

Good Manufacturing Practice (GMP) compliance is required for all steps in the manufacture of medicines regulated as prescription medicines, unless there is an exemption outlined in the Therapeutic Goods Regulations 1990.

To demonstrate the manufacture of medicinal products supplied in Australia complies with principles of GMP, please refer to Manufacturing principles for medicinal products.

The Sponsor is responsible for therapeutic goods to be sold in Australia. If the manufacturer and manufacturing step is required to be recorded on the ARTG, then you need to provide us with valid evidence of GMP and keep this evidence current while that medicine remains registered.

Refer to Sponsor responsibilities related to GMP clearance and certification for further information.

What is considered 'Evidence of GMP'

For a manufacturer performing steps of manufacture that are required to be recorded on the ARTG, evidence of GMP may vary depending on the location of the manufacturing site:

For Australian-based manufacturers:

  • Evidence of GMP is a reference to the relevant manufacturing licence for the required manufacturing step(s)

For overseas manufacturers:

  • Evidence of GMP is a reference to the active GMP Clearance for the required manufacturing step(s)

For further information on how to obtain the required evidence, please refer to:

When to submit evidence

Evidence of GMP can be provided at different stages of the registration process depending on the type of submission being made:

For new product registration and major variation (Category 1) applications

Submit valid evidence of GMP with your product application. If you do not have valid evidence of GMP at the time of your submission, you should provide the GMP Clearance (CL), Certification (CE) or licence (LI) application tracking number.

Ensure the timeframes for obtaining the required evidence of GMP are achievable prior to submitting your product application.

Evidence provided on submission should not change or expire during the evaluation process.

Final approval of your product application cannot be granted until valid evidence of GMP is provided. If this is not provided, your registration application may be rejected or approval may be significantly delayed.

For minor variations applications

Valid evidence of GMP is required prior to submitting a minor variation application that involves a manufacturer change.

We will not accept your minor variation application for a manufacturer change if your GMP applications are still being processed.

Further information is available in the Minor variations to prescription medicines guidance.

Manufacturing steps required on the ARTG

The manufacture of a prescription medicine can typically consist of separate or continuous processes for the manufacture of Active Pharmaceutical Ingredient (API - also known as drug substance) and finished product (also known as drug product).

Evidence of GMP is required for both API and finished product manufacture.

Use the tables below to determine the manufacturing steps that require evidence of GMP. These are the steps and manufacturers that need to be recorded on the ARTG.

Important - Where the manufacturing steps are not required to be recorded on the ARTG as per the tables below, compliance with GMP or other relevant standards is still mandatory and evidence may be requested.

Sponsors should ensure that responsibility of GMP compliance for these steps are clearly identified within the relevant quality/technical agreements and made available to the Authorised Person (AP) performing Release for supply.

Chemically derived medicines

Please refer to the TGA glossary for a definition of chemically derived medicine.

API/drug substances - chemically derived manufacturing step(s) Recorded on ARTG

Active Material Manufacture♣♦ including sites performing:

  • principal manufacture of the crude
  • Purification of the API
  • blending or mixing with excipients (in certain circumstances, i.e. for stability or safety reasons)
Yes
Manufacture of intermediate API No
Milling or micronisation No
Chemical and Physical, biological or microbiological testing No
Packaging No
Release for further processing No
Storage No
Distribution No

♣: Exceptions are common inorganic salts and simple organic compounds. For more information see 11.2 What substances require a drug master file in TGA guidance on drug master files (active substance master files).

♦: For chemical entities derived from fermentation, you may also need to provide us with GMP evidence for certain steps prior to the principal manufacturing site; these steps will be recorded on the ARTG.

Finished/drug products - chemically derived manufacturing step(s) Recorded on ARTG

Manufacture of dosage form including sites performing:

  • blending or mixing with excipients (for reasons other than stability or safety)
  • manufacture of intermediate products
Yes
Manufacture of Diluent Yes
Primary Packaging and labelling Yes

Secondary packaging including sites performing:

  • assembly of kits and composite packs
Yes
Chemical and Physical testing required for release for supply Yes
Microbiological testing required for release for supply (including Endotoxin and Sterility testing) Yes
Biological testing required for release for supply Yes
Storage of product prior to release for supply (where this is separate from a site performing manufacture) Yes
Release for supply Yes
Distribution and storage after release for supply No#

#: Compliance with other standards may apply

Biological medicines

Please refer to the TGA glossary for a definition of Biological medicines

APIs/drug substances - biological medicines manufacturing step(s) Recorded on ARTG
Master cell bank manufacture, storage and maintenance No♥
Working cell bank manufacture, storage and maintenance Yes
Manufacture of intermediates from higher risk starting material (e.g. sourced from animals, bacteria, viruses, recombinant material) Yes
Active Material Manufacture Yes
Chemical and Physical, biological or microbiological testing that is later used to inform release for supply of the finished product Yes*
In-process control testing No
Packaging No
Storage of drug substance No♥
Release for further processing No

♥: While this may be 'No', it needs to be clear who takes responsibility for GMP compliance

*: For Biological Medicines, evidence of GMP is required for all crucial quality and safety tests performed on the API/drug substance that is not repeated on the finished dosage form (i.e. potency, content and purity).

Excipients

Submit evidence of GMP for the manufacture of higher risk excipients, such as those of human or animal origin for steps of:

  • production
  • quality control and release testing

The sponsor is responsible for ensuring the safety of higher risk excipients. However, responsibility for providing us with evidence of safety resides with the drug substance or drug product manufacturer who first uses the higher risk excipients.

Plasma master files

Plasma master files (PMFs) record the quality aspects of human plasma as a raw material for the manufacture of therapeutic goods. Submit evidence of GMP for plasma master files for:

  • storage facilities
  • viral safety testing on:
    • individual samples
    • mini-pools
    • manufacturing pool (the manufacturer of plasma for fractionation is also considered responsible for the safety testing on the manufacturing pool)
Finished/drug products - biological medicines manufacturing step(s) Recorded on ARTG

Manufacture of dosage form including sites performing:

  • manufacture of intermediate products
Yes
Manufacture of diluent Yes
Primary Packaging and labelling Yes

Secondary packaging including sites performing:

  • assembly of kits and composite packs
Yes
Chemical and Physical testing required for release for supply Yes
Microbiological testing required for release for supply (including Endotoxin and Sterility testing) Yes
Biological testing required for release for supply Yes
Storage of product prior to release for supply (where this is separate from a site performing manufacture) Yes
Release for supply Yes
Distribution & storage after release for supply No#

#: Compliance with other standards may apply

Sterilisation

Sterilisation requirements apply equally to both chemically derived medicines and biological medicines for API, finished products and containers.

API and finished products

Manufacturing step Recorded on ARTG
Sterilisation of API when the API is labelled as sterile Yes
Sterilisation of API, excipients and intermediates of finished product, when there is no later sterilisation of the finished products (i.e. Aseptic manufacturing processes) Yes
Sterilisation of finished products Yes
Sterilisation of API/drug substance, excipients and intermediates of finished product when there is later sterilisation of the finished products No

Containers

Use the table below to determine the steps for which you need to send us evidence of GMP. These are the steps that need to be recorded on the ARTG.

Where the steps are not required to be recorded on the ARTG, compliance with GMP or other relevant standards is still mandatory

Manufacturing step Recorded on ARTG
Sterilisation of containers for sterile products by the finished product manufacturer (the whole container and any product contact component) Yes
Sterilisation of containers manufactured by a supplier when there is later sterilisation of the finished products No*
Sterilisation of containers manufactured by a supplier when there is no later sterilisation of the finished products No*

*: The relevant ISO standards apply and may be requested as required

Version history

Version Description of change Author Effective date
V1.0 Original publication Scientific Evaluation Branch, Regulatory Guidance Team November 2015
V2.0 Clarification of original guidance Manufacturing Quality Branch, Scientific Evaluation Branch, Regulatory Guidance Team December 2019