Blood Plasma : Understanding and its Usage
Plasma is the liquid portion of blood. Of the usual 500 ml of blood collected from a donor, about 230 ml of plasma is generated into a separate plasma bag. This is often referred to as ‘fresh frozen plasma’ when it is frozen for transfusion purposes, and if it is sent to fractionation plants, it is referred to as ‘recovered plasma’ or ‘plasma for further manufacture.’ Plasma may also be collected directly from donors by apheresis.
Human blood plasma contains more than 1000 proteins, and more than 250 of these have been well characterized. There are more than 100 licensed assays to identify these proteins and numerous international standards and reference preparations.
More than 30 commercial preparations of blood protein concentrates are available as medicinal products; most are expensive, and some are in short supply. New candidate therapeutics are identified almost every year. Several of these plasma protein concentrates have been identified as essential medicines by the World Health Organization (WHO).
These include clotting factor concentrates on treating hemophilia and gamma globulin preparations. Therefore, to treat immuno-deficiencies and several specific infectious exposures such as tetanus and rabies, or anti-Rho (D) for the prevention of hemolytic disease in newborns (1). Unmet needs In LMIC economies, new plasma for fractionation is needed to generate essential plasma-derived medicines (clotting factors and immunoglobulins).
National and Global sufficiency of blood plasma
National and global sufficiency in plasma products can be achieved only by reducing wastage of non-transfused plasma. Approximately 21.6 million Liters of plasma can be recovered from whole blood collections each year. Of this volume, an estimated 4.2 million units are transfused, and an estimated 8.1 million units are sent for fractionation.
This leaves an estimated 9.3 million liters that are discarded annually. The majority of patients in LMIC with clotting disorders, immuno-deficiencies, and autoimmune disorders do not currently have adequate access to treatment. Well documented data from the World Federation of Haemophilia indicate that patients with hemophilia in these countries are undertreated, many are untreated, and many more areas yet undiagnosed. To some extent, definitive diagnoses are not even pursued because specific treatment is not available.
The numbers of untreated or undertreated patients with immunodeficiencies are not as well documented, but the unmet need is unquestioned. Furthermore, new treatments (e.g., transplant, protein deficiencies) that require plasma protein therapy are being identified each year. World use and need for both clotting factors and immunoglobulins have been increasing almost exponentially; there is every indication that use will increase into the foreseeable future, limited only by the availability of plasma for fractionation.
The unmet need in red blood cells for transfusion in LMIC will increase the number of whole blood donations, generating more plasma that could be used for fractionation, but which, under present conditions, would be discarded.
Blood Plasma and World
In many low-income economies, fewer than five units of blood are collected per 1000 inhabitants each year. Even in middle-income 11 countries (MIC), fewer than ten units per 1000 inhabitants are collected. In high-income countries (HIC), the number is 30 units per thousand population. No one knows the ideal number of red cells per capita, but to satisfy an essential need for red cells (for anemia related to malaria, to prevent women in childbirth from fatal hemorrhage and for managing trauma) some 15 units per thousand inhabitants is estimated to be the basic number that needs to be collected.
It is certain that the number of blood collections will rise in LMIC, mirroring increases in the developed world. In the United States, red cell collections increased 40% between 1994 and 2008, the last year for which complete data are available.
Lack of appropriate technology for blood plasma
The lack of appropriate technology means that in LMIC, far more blood is transfused as whole blood than in HICs. If a higher proportion of the blood collected in LMIC were separated into components, millions of additional plasma units would be generated, which under current conditions are discarded. This is a human tragedy, an economic misfortune, and since these biological materials are often inadequately destroyed, an environmental calamity.
Conserving recovered blood plasma If recovered plasma is to be conserved in LMIC, manufacturing practices and quality systems have to be improved along the entire manufacturing process, from the initial selection of the donor to the final shipment of the plasma to fractionators.
A big percentage of the plasma collected in developing countries as wasted and destroyed. This wastage occurs because of the lack of appropriate technology, regulatory controls, quality systems, and good manufacturing practices, thereby rendering the plasma unsuitable for conversion into fractionated medicinal products.
Facilitation of blood plasma for everyone
The facilitation of collaboration between various types of countries, namely developing and developed countries with regulations and technology transfer, is an important part of a global approach.
Blood should be seen as a manufactured product. Implementation of GMP is critical and requires that blood establishments separate medical functions from manufacturing activities (e.g., plasma for fractionation). Current GMP addresses these activities (collection, testing, storage, processing, labeling, and distribution) of the blood establishment. Testing of the blood plasma alone is not enough. Such testing does not address emerging infectious agents, variations in the existing agents like human immuno-deficiency virus HIV, HBV and HCV, that are not detected by current assays, and variations in the quality of the proteins in the plasma.
The process should be controlled from start to finish, as is required for the manufacture of other medicines.
Why does WHO focus on recovered blood plasma?
WHO does not collect, prepare, or distribute plasma. The organization has a responsibility to assist countries in making the best use of recovered plasma to generate essential medicines. It is established that the principle of nationally supported, managed, and coordinated blood systems, a series of WHO initiatives (including the responsibility for developing standards for therapeutic proteins and for in vitro diagnostic tests (IVD)) have been promulgated.
The initiatives aim to improve public health through the development of a safe donor pool and high-quality blood establishments complying with GMP, increasing the supply of high-quality plasma, increasing the supply of essential medicines derived from plasma, and assistance in the development of government bodies, such as inspectorates and regulatory agencies to improve blood quality.
WHO wants to improve the availability of safe blood products for patients, raise the quality standards in blood establishments, reduce the risk of transmission of infectious diseases, and enforce implementation of blood products regulations. WHO has produced technical documents that address plasma fractionation and implementation of GMP in blood establishments through the WHO Expert Committee on Biological Standardization and has established a Blood Regulators Network (BRN) to support the organization in enhancing NRAs in the blood area.
WHO makes available guidelines and physical standards to improve biological products derived from blood. WHO is well positioned and should be adequately resourced to assist developing countries as they strive to make optimum use of recovered plasma and provide access to essential medicines. Furthermore, GMP-compliant blood facilities are ideally positioned to generate both products and data to advance public health in these countries further.
Plasma product demand in the world is increasing and will expand significantly in the coming decades as will the need for related essential medicines. The availability of plasma protein therapeutics in developing countries is currently inadequate, and much of the blood collected is either not processed to generate blood plasma or the plasma generated is of low quality as to make it unusable for fractionation and production of biological medicines. This plasma is currently discarded as a human tragedy, and an economic calamity.
LMIC will collect increasing volumes of whole blood and recovered plasma. Strengthening GMP should conserve discarded plasma, supply therapeutics, and improve blood safety. Adequate treatment of hemophilia, immuno-deficiencies, and an increasing number of diseases will require additional raw material.