Preparing and submitting Type I Plasma Master Files

A Type I PMF is a document submitted to support applications for new ARTG entries or requests to vary existing ARTG entries (for example, where a new plasma fractionator or albumin supplier is proposed).

A Type I PMF details the quality aspects of human plasma used as a raw material for the manufacture of therapeutic derivatives, including clotting factors, immunoglobulins, and albumin.

The PMF remains a stand-alone document that is separate from the registration or variation dossier. We then evaluate the PMF alongside other product clinical and quality data.

A new Type I PMF should be submitted to the Prescription Medicines Authorisation Branch via electronic submission, alongside the related Category 1 application for the registration of a new product that contains or is produced from human plasma onto the ARTG.

A PMF may also be required when applying to vary an existing ARTG entry. For example:

• If a manufacturer of a therapeutic good including human albumin, changes the supplier of the albumin to a different manufacturer, the variation application must include a PMF for the new albumin manufacturer as part of the Module 3 data. 
• If a manufacturer of a plasma-derived medicine proposes to use a fractionation intermediate from an alternative manufacturer, the Module 3 data for the variation application must include the PMF from the alternative manufacturer.
• If the relevant PMF has already been submitted to and is held by us the sponsor may provide a letter of access instead of resubmitting the PMF. 
• The letter must be provided by the PMF holder and authorise us to assess and evaluate the PMF for the application. 
• The letter should confirm whether the PMF complies with the applicable requirements of TGO 108 and TGO 102.
• If compliance with either standard relies on Section 14/14A consent, the sponsor must apply for the relevant Section 14/14A consent for their product and provide evidence with the submission.
• For further information please refer to our website - Consent to import, supply or export therapeutic goods that do not comply with standards - information for industry.

The data and format of the PMF should comply with both:

• Annex 1 to Guideline on the scientific data requirements for a plasma master file (PMF) Revision 1 (EMEA/CHMP/BWP/3794/03 Rev 1)
• Guideline on epidemiological data on blood transmissible infections (EMA/CHMP/BWP/548524/2008 rev 1)

The PMF should describe all activities from donor recruitment and selection through to the manufacture of the first homogeneous plasma pool including collection, testing, processing, storage, transport and traceability. We evaluate these activities as part of the assessment of the PMF.

Sponsors must include:

• the source of the plasma
• the location(s) where the plasma was collected
• the screening process for donors including eligibility assessment and exclusion criteria
• a description of the tests used to screen donated blood and plasma including test methods, testing sites, assay validation and acceptance criteria
• traceability from donation to plasma pool
• plasma quarantine, storage, transport and hold times
• manufacturing plasma pool size and pooling controls
• epidemiological data for relevant blood-transmissible infections.

Sponsors must demonstrate compliance with applicable Australian standards, including TGO 102, TGO 108 and, where relevant, TGO 111. Sponsors should ensure that the information provided is current, accurate, clearly presented and supported by appropriate evidence.

The PMF should:

• follow our General dossier requirements for formatting and presentation
• use the Common Technical Document (CTD) format
• be clearly organised and easy to navigate
• include sufficient detail to support all claims made
• identify applicable standards and guidelines
• include relevant supporting data and validation evidence
• include a table of contents and appropriate cross-referencing.

Once a product containing a plasma derivative is included on the ARTG, or a variation application is approved, a condition of registration may be that the sponsor is required to submit annual PMF updates to us.

We review each PMF annual update to ensure the ongoing quality and safety of the plasma used in the manufacture of plasma derivatives.

An annual PMF update should include updated epidemiology data and information about changes to plasma collection and screening that have occurred since the previous update.

Sponsors should provide a covering letter with each annual update that includes:

• the sponsor's name
• the plasma source(s) covered by the PMF that are relevant to the Australian product
• the product(s) covered by the PMF, including the ARTG number(s)
• the period covered by the PMF.

A Type I PMF annual update may be submitted to us as either a standalone submission or bundled with a Category 3 variation application (for each product entered on the ARTG covered by the PMF).

Once we have approved a PMF, any changes to plasma collection or testing represent changes to quality information that may affect product quality and safety.

We group Type I PMF variations into two categories, depending on the nature and potential impact of the change.

Variations that require data to be submitted 

These are changes that have the significant potential to affect product quality, safety or compliance. Sponsors must obtain our approval before implementing these changes. The PMF holder must not introduce these changes for the first time through an annual PMF update.

The types of changes that are required to be reported as a Category 3 variation application, include but are not limited to the:

• country of origin of plasma
• addition of a new organisation acting as a supplier of plasma (the addition of a new collection site within an organisation may be reported in the next PMF annual update)
• test or site for viral testing of the manufacturing plasma pool
• manufacturing pool size or number of donations per pool
• plasma hold times
• donor selection/exclusion criteria
• donation quarantine period.

The data requirements for these applications are described in our guidance: Variations to prescription medicines - excluding variations requiring evaluation of clinical or bioequivalence data, Appendix 2: Variation types - biological medicines.

Sponsors should include approved changes in the next annual PMF (Type I) update and reference the previous relevant approval date and submission number.

Variations that can be reported in a Type I Plasma Master File annual update

These are changes that are not expected to affect product quality, safety or compliance. PMF holders should document these changes through their quality management system and document them in the next annual PMF update.

Changes that may be reported for the first time in an annual PMF update include, but are not limited to:

• addition or removal of collection centres for an approved collection organisation
• changes to sites used for testing individual donations
• changes to tests used for testing individual donations, provided the type and principle of the test remain unchanged.

Sponsors should submit Type I PMFs and related updates as follows:

• initial Type I PMFs electronically to the Prescription Medicines Authorisation Branch via electronic submission. 
  • The evaluation time frame for a new Type I PMF matches the regulatory timeframe for the associated Category 1 submission.
• Type I PMF Annual updates bundled with a Category 3 variation, for each ARTG registered product included in the PMF, to the Prescription Medicines Authorisation Branch via electronic submission
  • The evaluation time frame for annual updates bundled with a Category 3 application matches the regulatory timeframe for the associated Category 3 submission
• a standalone Type I PMF Annual update electronically to the Biological Sciences Section via electronic submission
  • Our target timeframe for review and acknowledgement of a standalone Type I PMF annual update is 90 working days.

Sponsors are responsible for ensuring that organisational and personnel contact details held by us remains current.

If you have any questions, please contact us at bloodandtissues@health.gov.au or 1800 678 799.