Status – approved; marketed

Organizations involved:

Baxter Healthcare Corp.. – Manuf.; Intl. mark.

Talecris Biotherapeutics Inc. – Manuf.; USA mark.

Instituto Grifols, S.A. – Parent

NPS Pharmaceuticals Inc – Former

Bayer Schering Pharma AG – Intl mark.

Bayer Corp. – Former

Description: Plasma Protein Fraction is a mixture of albumin and immune globulin obtained by standard commercial (Cohn-Oncley cold ethanol) fractionation of pooled human plasma (or mixed fractions/products). This product is apparently primarily used for further manufacture of more refined products [Plasma and plasma-derivatives, and Albumin (Human)], and for sale to other licensed blood products manufacturers for further use. According to the Code of Federal Regulations, Title 21, Section 640.90, “The product is defined as a sterile solution of protein composed of albumin and globulin, derived from human blood. (b) Source material. The source material of Plasma Protein Fraction (Human) shall be blood, plasma, or serum from human donors determined at the time of donation to have been free from disease-causative agents.”

An example product, Plasma Protein Fraction (Human) 5% or Plasmanate from Talecris (originally Bayer) consists of approximately 88% normal human albumin, 12% alpha and beta globulins, and not more than 1% gamma globulin (immune globulin), as determined by electrophoresis). The concentration of these proteins is isotonic with normal human plasma. Each 100 ml of Plasmanate contains 5 grams of selected plasma proteins buffered with sodium carbonate and stabilized with 0.004 sodium caprylate and 0.004 acetyltryptophan.

Nomenclature: Plasma Protein Fraction [BIO]; Plasma Protein Fraction (Human) [FDA]; PPF [SY]; Plasmanate [TR for product from Talacris]

History: Companies previously licensed to manufacture Plasma Protein Fraction (Human): Abbott Labs. (April. 1971-Aug. 1978); Oesterreichisches Institut fuer Haemoderivate GmbH (June 1960-Jan. 1980); and Seralc Corp. (March 1982-May 1983). Alpha Therapeutic Corp., now Grifols Biologicals, and V.I. Technologies, later Precision Pharma Services, Inc. (now Talecris Biotherapeutics) were licensed until sometime in 2003.

Companies.: Two manufacturers currently (4/2006) hold licenses for manufacture – Talecris Biotherapeutics, Inc. (formerly Bayer Corp., FDA CBER est. no. 1716; and Baxter Hyland Immuno, FDA CBER est. no. 0140. Plasmanate from Bayer was formerly marketed by Bayer Corp. in the U.S., and internationally by Bayer AG affiliates. In April 2005, Talecris Biotherapeutics Inc., a subsidiary of NPS Pharmaceuticals Inc., acquired the plasma products business of Bayer AG, including manufacturing and U.S marketing, with Bayer AG, now Bayer Schering Pharma AG, retaining international marketing. Baxter Hyland Immuno markets its product worldwide.

In Feb. 2011, Grifols S.A./Instituto Grifols acquired Talecris Biotherapeutics.

FDA class: Biologic PLA

CBER class: Blood And Blood Derivatives

Approvals: Date =19581002; first approval for this product, granted to Bayer Corp.

Indications: [from recent product insert/labeling for Plas-manate from Bayer Corp.]:

for treatment of shock due to burns, crushing injuries, abdominal emergencies and any other cause where there is predominant loss of plasma fluids and not red blood cells. It is also effective in the emergency management of shock due to hemorrhage. In infants and small children, Plasmanate has been shown to be very useful in the initial therapy of shock due to dehydration and infection.

Status: Only two companies are currently FDA-approved for manufacture of Plasma Protein Fraction – Talecris Biotherapeutics Inc. (formerly Bayer) and Baxter Hyland Immuno.

In early 1999 (or late 1998), CBER/FDA sent a letter to U.S. physicians indicating that use of Albumin and plasma protein fraction (PPF) outside of rigorous clinical trials “warrants serious consideration” and physicians should “exercise discretion” using these products. The FDA encouraged additional clinical trials with both products. See Code of Federal Regulations, [Title 21, Volume 7, Part 640.9 (21CFR640.90) for information about Plasma Protein Fraction (Human).

Market: The 2007 Average Wholesale Price (AWP) for Plasmanate is $21.12/50 mL and $42.24/250 mL (Red Book, 2007).