Before signing the release for supply certification, it is the responsibility of the RFS authorised person to ensure all manufacturing stages comply with the GMP requirements. We have presented a list of stages to help clarify the RFS requirements.
The stages presented are not in a specified order.
For completeness, information has been included to cover:
- all medicines, which refers to medicines that need to comply with RFS (as described in this document)
- additional requirements for those medicines on the ARTG
- additional requirements for complex supply chains where manufacturing occurs at multiple sites
For all medicines that need to comply with RFS, obtain and review the information described below and any other relevant information.
GMP of manufacturer(s)
For all medicines check that the manufacturer:
- holds a current TGA-licence or GMP-clearance
- all relevant manufacturing steps are covered
For a medicine on the ARTG, check:
- that the manufacturer of the batch is included in the ARTG entry
- if the medicine is also manufactured at multiple manufacturing sites, check each manufacturer and partial manufacturer are included in the ARTG entry
For a medicine manufactured at multiple manufacturing sites, check:
- all manufacturers (and partial manufacturers) of the batch hold a current TGA-licence or GMP-clearance
- all relevant manufacturing steps are covered by the appropriate licence or clearance
GMP agreements
For all medicines check that valid GMP agreements are established in accordance with PIC/S Guide to GMP between the sponsor (market authorisation holder) and manufacturer, where they are different entities.
For a medicine manufactured at multiple manufacturing sites, check that a valid GMP agreement is in place for all manufacturers and partial manufacturers, in accordance with PIC/S Guide to GMP.
Acceptability of PQS
Where manufacturing occurs at multiple sites:
- check that an appropriate PQS describes all manufacturing steps - you might do this by accepting the PQS through the supplier qualification program
- ensure that you have ongoing assurance that your reliance on their PQS is well founded
- check that the GMP internal audits and supplier audit systems of the manufacturers are operational
Validating processes
For all medicines, check that the principal manufacturing and release testing processes (as per finished product specifications) have been validated taking into account actual production conditions, manufacturing and test records.
Batch records
RFS involves verification of all production and quality control testing records of a batch.
Batch production and testing
For all medicines:
- Check that all the necessary checks and tests have been performed, including any additional sampling, inspections, tests or checks initiated because of deviations or planned changes.
- Check all production and quality control documentation has been completed and endorsed by staff authorised to do so, including out-of-specification (OOS) investigations for quality control documentation.
- Take into account any transport data that are available.
- Take into account any other factors that you are aware of relevant to the quality of the batch.
- Check both production and controls for each batch comply with:
- the TGA-adopted version of the PIC/S Guide to GMP (TGA-licensed manufacturers)
- manufacturing standards at least equivalent to the PIC/S Guide to GMP (overseas manufacturers)
For medicines on the ARTG:
- Check both production and controls for each batch comply with the market authorisation, where applicable.
Traceability
For all medicines, ensure traceability of each batch:
- Make sure that it is easy to identify all products in a batch, so that if there is a quality defect in the batch it will be possible to recall all affected products without delay.
- Check that the following information is easy to find in the batch documentation:
- the RFS site
- the name of the RFS authorised person
Deviations and changes
For all medicines:
- Check that any significant deviations or planned changes in production or quality control have been authorised by the persons responsible in accordance with a defined system.
- Check that the TGA has authorised any changes requiring variation to the:
- marketing authorisation, for medicines in the ARTG
- manufacturing licence, for TGA-licensed manufacturers
- GMP clearance, for overseas manufacturers
Product quality review and stability testing
For all medicines:
- Consider whether all relevant issues raised in the PQR have been adequately addressed for the batch being released.
- Check that the shelf life is consistent with the available stability data.
Signature
For all medicines:
- Certify release for supply with a legally valid signature of the RFS authorised person.
- Make sure the signature is dated.