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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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Quality control (Chapter 6)

Sampling and testing complementary medicines

A separate guidance document is available for the sampling and testing of complementary medicines.

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

Although the principles in this guidance are still applicable, this guidance will be revised where necessary, in consultation with industry, to clarify the requirements in the PE009-13 version of the PIC/S Guide to GMP.

Conducting on-going stability studies

Principles for conducting on-going stability studies

In general, on-going stability studies should be based on the principles of ICH Q1.

Use of on-going stability program results in release for supply

The results of the on-going stability program are expected to be available to the Authorised Person who should consider the results before releasing a batch for supply.

On-going stability studies for listed complementary medicines

The TGA's expectations for on-going stability studies for listed complementary medicines are similar to those for other medicines. A separate guidance document is available for the on-going stability testing for listed complementary medicines.

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

Although the principles in this guidance are still applicable, this guidance will be revised where necessary, in consultation with industry, to clarify the requirements in the PE009-13 version of the PIC/S Guide to GMP.

On-going stability studies in a GMP certified laboratory

Ongoing stability testing does not need to be conducted in a GMP certified laboratory, because ongoing stability testing is not considered to be a step in manufacture, as defined by the Therapeutic Goods Act 1989.

However, the results from these studies are required to be reliable and meaningful. It is the responsibility of the contract giver to ensure that any laboratories used for ongoing stability testing is appropriate. For that reason, other certification may be used in lieu of a GMP certification, such as a licence issued by a regulatory authority acceptable to the TGA or a current ISO 17025 accreditation certificate. Stability test methods used by the laboratory should be appropriately validated and documented according to the requirements of the PIC/S Guide to GMP (PE009-13).

The results from the on-going stability monitoring studies must be considered as part of release for supply, which is the final step in manufacturing.

Responsibility for ongoing stability studies of imported medicines

In the case of imported medicines, the responsibility to conduct an on-going stability monitoring program is with both the manufacturer and the sponsor.

  • The manufacturer who carries out release for supply needs to ensure that the batch meets its marketing authorisation, and that an on-going stability monitoring program is conducted and data is available to support the expiry date.
  • The sponsor is responsible for the marketing authorisation, ensures an on-going stability testing program is performed and has access to the stability results.

In the contract manufacturing agreement, the responsibility for on-going stability may be contracted out to the manufacturer or other parties.

Bulk medicine on-going stability studies

Where bulk medicines are imported into Australia to be packaged by a domestic manufacturer, the domestic manufacturer cannot use the on-going stability program of the bulk manufacturer to support the packed product stability.

On-going stability is required to be performed in the packaging material in which the product is marketed in Australia. The overseas bulk manufacturer will use different packaging equipment and processes although the packaging materials might be the same.

Grouping for the purposes of stability testing

Grouping (also known as bracketing or matrixing) could be acceptable, if scientifically justified. This will be assessed during inspections on a case-by-case basis.

Review of on-going stability data during inspections

During inspections, the operation of an appropriate on-going stability program is normally reviewed, including the results of on-going stability studies, where appropriate. If there are any concerns, the inspector can refer the evaluation to the area of the TGA responsible for regulating the product ARTG entry.

Notifying TGA of on-going stability issues

Although it is acknowledged that some normal variability in the results of on-going stability studies can be expected, all statistically significant departures from established stability profiles must be notified to the area of the TGA responsible for regulating the product ARTG entry. In general, 'significant change' for a medicinal product is defined as:

  • a 5% change in assay from its initial value; or failure to meet the acceptance criteria for potency when using biological or immunological procedures
  • any degradation products exceeding its acceptance criterion
  • failure to meet the acceptance criteria for appearance, physical attributes, and functionality test (e.g. colour, phase separation, re-suspendibility, caking, hardness, dose delivery per actuation); however, some changes in physical attributes (e.g. softening of suppositories, melting of creams) may be expected under accelerated conditions
  • OR, as appropriate for the dosage form:
    • failure to meet the acceptance criterion for pH
    • OR
    • failure to meet the acceptance criteria for dissolution for 12 dosage units

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