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CPG Sec. 230.100 Blood and Blood Products - Definitions

 

BACKGROUND:

Out of necessity, the Center for *Biologics Evaluation and Research (CBER)* and the industry have established terminology used to designate specific blood products. Although these products may be mentioned in the regulations, they often are not fully defined. The intent of this guide is to define and clarify that terminology about which confusion has been expressed.

POLICY:

Recovered [] Plasma

Recovered [] Plasma is derived from single units of Whole Blood, or * * Plasma, or as a by-product in the preparation of blood components from whole blood collection. It is an unlicensed raw material intended for use in the manufacture of both licensed and unlicensed products, such as licensed fractionation products for injection, licensed diagnostic products; and diagnostic products not subject to license, including clinical chemistry controls. A license is not required to manufacture, distribute, relabel, pool, or repack Recovered [] Plasma.

When Recovered [] Plasma is to be used in licensed products, it must be shipped in full compliance with the provisions of 21 CFR 601.22 (Short Supply) by the short supplier (the initial manufacturer) or an authorized agent (the licensed manufacturer's agent) solely to the manufacturer under whose license the short supplier or an authorized agent is on file. Recovered [] Plasma for use in manufacturing licensed products may be pooled by the short supplier if complete records, including donor numbers for each unit pooled, are maintained. Any product manipulated by an authorized agent cannot be shipped under the short supply provisions.

Recovered [] Plasma pooled by other than the short supplier or manufacturer may be sold for use only in manufacturing unlicensed products, including clinical chemistry controls, and must be labeled, inter alia, "Not for use in products subject to license under Section 351 of the Public Health Service Act".

* See attached chart. [LOCATED AT END OF CHAPTER]

All firms that manufacture, relabel, pool, or repack recovered human plasma are required to register and follow appropriate GMP's for blood and blood products. Dealers who act only as authorized agents and do not take physical custody of the product are exempted from the registration requirements.

Salvaged [] Plasma

Salvaged [] Plasma is the name give to plasma originally collected as Source Plasma [], but because of: 1) its exposure to storage temperatures in excess of 10o C; or 2) its collection during a period of noncompliance (usually, material in inventory at the time of license suspension due to deviations which occurred during the manufacturing of those units, and which affect or may affect the safety, purity, or potency of the plasma,) is not permitted to be used as a licensed product. It is restricted to use in the manufacture of products not subject to license under Section 351 of the Public Health Service Act.

Short Supply

The concept of "Short Supply" as it pertains to blood products recognizes that: 1) there are only a limited number of persons who can serve as donors of blood which contains high concentrations of antibodies needed for the preparation of special blood typing serums and immune globulins; and 2) Recovered [] Plasma is a valuable resource for fractionation products. In order to have access to these source materials throughout the country, licensed manufacturers are permitted to use other persons or firms, not a part of their own establishment, to collect blood and plasma and to perform the initial and partial manufacturing steps required to prepare these intermediate products for shipment to the licensed manufacturer.

To utilize the short supply provisions (21 CFR 601.22), the manufacturer holding a license to prepare the finished biological product must establish with his suppliers, those procedures, inspections, tests or other arrangements necessary to assure full compliance with the applicable regulations. A list of suppliers with whom the licensed manufacturer has a short supply agreement must be on file at the *CBER*. No products can be obtained under short supply until proper agreements have been entered into by the licensed manufacturer of the final product and the person or firm actually collecting the source material. No source material collected prior to the completion of such agreements, or subsequent to their terminations, may be shipped to or utilized by the licensed manufacturer.

When utilizing the short supply provisions, the supplier must ship the short supply product directly to the licensed manufacturer, or, under certain circumstances, to an authorized agent under contract with the licensed manufacturer. The supplier must maintain physical and property control over the product at all times until it is shipped to the licensed manufacturer of the final product. **

Short supply provisions also apply to a few other non-blood products.

Licensed Blood Bank Reagents and Diagnostic Products

Licensed blood bank reagents (e.g., blood grouping sera, HBsAg test kits) are under the jurisdiction of the *CBER.*

Therapeutic Exchange Plasma (TEP)

Therapeutic Exchange Plasma is the plasma obtained from therapeutic plasmapheresis. In this procedure, a patient's plasma is incrementally removed and replaced with electrolyte and/or protein solutions or plasma. The procedure is intended to remove harmful elements from the patient's circulation.

Patients undergoing therapeutic plasma exchange may suffer from a wide variety of disorders, such as autoimmune or paraproteinemic conditions, idiopathic thrombocytopenic purpura and kidney disease, and other disorders that may be associated with transmissible etiologic agents. Antibodies derived from TEP may be used only to manufacture special in-vitro diagnostic reagents which are not available from any other source.

TEP intended for further manufacture is a biolgocial product subject to the licensing provisions of section 351(a) of the Public Health Service Act.

Any firm intending to collect and ship TEP in interstate commerce for sale, barter or exchange must first obtain a U.S. license. Licensed manufacturers of Source Plasma * * must obtain a separate license for TEP, which is a different product.

It is emphasized that therapeutic plasmapheresis of a patient is a medical procedure which is used at the discretion of physicians and consequently is not within the purview of FDA. However, a firm must obtain a U.S. license when the plasma collected from the therapeutic procedure is intended or offered for sale, barter or exchange in interstate commerce for further manufacture.

*Material between asterisks is new or revised*

[] Indicates material has been deleted

Issued: 4/10/78 as 7134.14
Revised: 10/5/79, 6/18/80, 10/1/80, 11/1/83, 3/95