Plasma Master File PMF

Plasma Master File


Plasma Master File (PMF)
For marketing authorization of a plasma-derived medicinal product, the so called PMF has to be submitted to regulatory authorities. The PMF is a compilation of all the required scientific data on the quality and safety of human plasma relevant to the medicines, medical devices and investigational products that use human plasma in their manufacture. These data cover all aspects of the use of plasma, from collection to plasma pool – such as:

  • Selection of donors: Selection of donors is regulated by European law. Criteria that shall ensure safety of the donation’s recipient are divided into permanent and temporary deferral criteria.
  • Blood/plasma donation: Plasma for the manufacture of plasma-derived medicinal products can be sourced from whole blood donation (recovered plasma) or by plasmapheresis (source plasma). During plasmapheresis, a needle is inserted as it is done for blood donation.  By centrifugation and filtration the blood is separated into blood cells and plasma components. While the plasma is collected in a container, the blood cells are returned to the donor by the extraction tube immediately.
  • Recovered plasma is collected through whole blood donation in which plasma is separated from its cellular components by filtration, centrifugation and separation. Resulting from this, the plasma may be shock frozen and used for fractionation of plasma-derived medicinal products (Fresh Frozen Plasma) and the cellular components (red blood cell concentrate) is used for transfusion.
  • Screening of donations: Donations from first time donors are screened by licensed test kits/systems to ensure quality and safety. Not until the same donor turns up for a second donation which as well turns out to be of adequate quality and safety, the first donation is released for further production/use. Screening is performed for HIV, HBV, HCV and other infectious agents. Donations revealing a positive screening result are discarded.
  • Epidemiological data on blood transmissible infections: By collecting and reporting these data, information on the infection risk in a specific donor population shall be obtained to ensure that donations do not come from donors with a high probability of being infected with blood transmissible agents. Data on prevalence and incidence of transfusion transmissible infectious markers in donors and the estimated risk of infectious donations entering the plasma supply have to be presented and discussed on a yearly basis.
  • Screening of plasma pools:  At the manufacturing site the frozen single plasma units are unpacked, pooled, and thawed under stirring. Plasma pool samples are drawn for screening to ensure quality and safety. Screening is performed using licensed test kits/systems. Screening of pool samples is not only performed by the manufacturer, but also by an EU competent authority (see Plasma pool testing by Official Medicines Control Laboratory).
  • Look-back system: Traceability has to be ensured from the plasma pool to the individual donation and vice versa.
  • Blood collection sites, testing laboratories, transport organizations, plasma storage sites (EU and third countries): All these sites have to be listed by name, address and last inspection by an EEA competent authority.

 

In 2004 a special EU-wide authorization process for the PMF data-package was implemented. This special procedure is called “PMF certification” and is coordinated by EMA (European Medicines Agency). Following a positive evaluation, the PMF data-package is certified by EMA and thus licensed throughout the EU. A PMF certificate is valid for one year. Every year the whole data-package has to be updated by the PMF-Holder and re-evaluated by EMA (“PMF Annual Update procedure”). To date, 14 PMFs have been certified using this EU certification procedure.
BASG/AGES is one of the PMF Coordinators significantly involved in this PMF-EU certification procedure by evaluating the scientific data as well as by performing the relevant inspections of collection sites, testing labs, transport organizations and storage sites within Austria and third countries (mostly USA). Last but not least the OMCL (Official Medicines Control Laboratory) of BASG/AGES performs Plasma pool testing as described below.

Plasma pool testing by Official Medicines Control Laboratory (OMCL)

Plasma pool testing by Official Medicines Control Laboratory (OMCL)
Samples for screening are drawn from the first homogenous plasma pool.
For Human Plasma for Fractionation laboratory tests are carried out to detect antibodies against HIV 1 and 2 (human immunodeficiency virus), HBsAg (hepatitis B surface antigen) and HCV (hepatitis C virus) RNA by NAT (nucleic amplification technique).
On manufacturing pools for Human Plasma Pooled and Treated for Virus Inactivation additionally Parvovirus B19, HAV (hepatitis A virus) RNA and HEV (hepatitis E virus) RNA are determined.
Manufacturing pools for Human anti-D Immunoglobulin are screened in the same way as Human Plasma for Fractionation but also including determination of Parvovirus B19.
In case that all specifications are met, the OMCL approves the respective plasma pool and hence enables the manufacturer to release this plasma for manufacture.

Created: 18.07.2012 | Page last modified: 09.03.2017

© Austrian Federal Office for Safety in Health Care
to top