New methods of plasma fractionation – a presentation of the ‘mini‐pool’ fractionation procedure developed in Egypt

Abstract

Background Availability of safe and affordable human plasma‐derived products (factor VIII, prothrombin complex concentrate/FIX, albumin and intravenous immunoglobulin) is a main concern of healthcare providers, particularly in resource‐limited countries. Several mechanisms may be used at national levels to secure the supply of these products, including import of finished products, contract fractionation and/or domestic fractionation. Contract fractionation may be considered only when there is a sufficient and steady amount of plasma (typically well over 10 000 l/year) complying with the international quality and regulatory requirements for fractionation, prepared following good manufacturing practice (GMP) principles, and ideally generated by a nationally coordinated blood transfusion organization. Fractionated products obtained by contract fractionation are not necessarily cheaper than imported ones. A domestic fractionation facility requires the guarantee to have access to a larger volume of plasma (typically over 100 000–200 000 l/year) that should also strictly comply with international quality and regulatory requirements. This option implies the construction, qualification and validation of a very high cost GMP pharmaceutical fractionation facility, use of state‐of‐the‐art technologies, and availability and training of highly qualified staff. The local market should have the capacity to use at least three out of the main four products to ensure the financial viability of the project. Due to these constraints, both contract fractionation and domestic fractionation may not currently be feasible for a number of resource‐limited countries. Objectives As an initial alternative to the conventional approaches to secure the supply of plasma products, our group started in 2003 to develop a new concept for the preparation of plasma protein components at a ‘mini‐pool’ fractionation scale (MPFS). Methods The main feature relies on the application of a single‐use sterile bag system process that can be implemented by blood establishments or a national service centre. The technology is straightforward and uses equipment that is largely available at blood establishments. The current pool size of 5–10 l of plasma can be largely processed, in an enclosed single‐use bag system, without the need of expensive fixed large‐scale equipment. A validated universal virus inactivation technology (solvent‐detergent) has been successfully integrated into this MPFS process, using such single‐use disposable bags. Results Mini‐pool, in‐bag, virus inactivation of cryoprecipitate, fresh‐frozen plasma and cryo‐poor plasma have been successfully developed and the medical device will soon be marketed. A factor VIII‐enriched preparation, also containing von Willebrand factor, has been obtained at a yield of about 300 IU/l, a concentration of 20–25 IU/ml, and a specific activity of 5–10 IU/mg. A chromatographic separation process of a PCC component from cryo‐poor plasma at a yield of 300 IU factor IX/l, containing factors II, VII and X was also developed. Work on separation of albumin‐ and Intravenous immunoglobulin‐enriched preparations is in progress. Conclusion This MPFS offers numerous advantages, among which is avoiding the need of an expensive GMP facility. The plasma mini‐pool size (5–10 l) gives flexibility of production of different combination of plasma component fractions. The concept that should be applied following GMP represents a gateway for resource‐limited countries to make use of their domestic plasma to improve the supply of plasma protein fractions and the standard of care of patients. The technology can also be used for preparation of safe plasma products for rare bleeding disorders.