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This guidance is for sponsors and applicants preparing applications to:
register a medicine regulated as a prescription medicine
OR
- vary the registration of a prescription medicine, when the variation involves the manufacturing steps recorded on the Australian Register of Therapeutic Goods (ARTG)
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.
Sponsor responsibilities
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:
- The Australian manufacturing licences and overseas GMP certification guidance for domestic and overseas TGA on-site inspections
- The GMP clearance guidance for desk-top assessment pathways
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:
| 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:
| Yes |
| Manufacture of Diluent | Yes |
| Primary Packaging and labelling | Yes |
Secondary packaging including sites performing:
| 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:
| Yes |
| Manufacture of diluent | Yes |
| Primary Packaging and labelling | Yes |
Secondary packaging including sites performing:
| 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 |