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Collaborative study to establish a new biological reference preparation for prekallikrein activator
C Longstaff1, M-E Behr-Gross, A Daas
1National Institute for Biological Standards and Control, Division of Haematology, South Mimms, Potters Bar, Herts, EN6 3QG United Kingdom.
Pharmeuropa Bio
|December 13, 2005
Summary
A new international standard for Prekallikrein Activator (PKA) in albumin was established, showing stability and suitability for long-term storage. This replacement standard ensures accurate PKA measurements for quality control in pharmaceutical products.
Area of Science:
- Biochemistry and Pharmaceutical Sciences
- Quality Control and Standardization
Background:
- The current World Health Organization (WHO) International Standard (IS) for Prekallikrein Activator (PKA) is nearing depletion, necessitating a replacement.
- A European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for PKA is required for the Official Control Authority Batch Release (OCABR) of Human Albumin.
- The existing IS (82/530) is a 5% albumin solution, but a replacement using 20% albumin is preferred due to higher PKA levels often found in concentrated solutions.
Purpose of the Study:
- To establish a new WHO IS and Ph. Eur. BRP for PKA.
- To calibrate suitable materials for use as the new IS and BRP.
- To investigate the impact of prekallikrein substrate (PKS) variability on PKA determination.
Main Methods:
- An international collaborative study involving 31 laboratories from 17 countries.
- Calibration of candidate materials (NIBSC ampouled material 02/168 and EDQM vialed material Batch 1) against the current IS (82/530).
- Assays were performed using both a provided commercial substrate and laboratories' in-house substrates to assess PKS influence.
Main Results:
- Candidate materials B (NIBSC) and C (EDQM) were found to have equivalent PKA levels of 29 IU/ampoule.
- No significant difference in PKA determination was observed between the commercial and in-house substrates.
- The PKA in the candidate reference materials (samples B and C) demonstrated excellent stability, suitable for long-term storage.
Conclusions:
- The collaborative study successfully identified and calibrated new reference materials for PKA, suitable for replacing the current WHO IS and serving as a Ph. Eur. BRP.
- The study confirmed the stability of PKA in 20% albumin preparations, making them appropriate for use as reference standards.
- Variability in in-house prekallikrein substrates does not significantly impact PKA determination in albumin solutions.