Sec. 230.110 Registration of Blood Banks and Other Firms Collecting, Manufacturing, Preparing or Processing Human Blood or Blood Products (CPG 7134.01)

INTRODUCTION:

This compliance guidance document is an update to the Compliance Policy Guides Manual (August 1996 edition). It is a revised CPG and will be included in the next printing of the Compliance Policy Guides Manual. It is intended for FDA personnel and is available electronically to the public. This guidance document represents the Agency's current thinking on registration of blood banks and other firms collecting, manufacturing, preparing, or processing human blood or blood products. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternate approach may be used if such approach satisfies the requirements of the applicable statute, regulation, or both.

BACKGROUND:

Section 510 of the Federal Food, Drug, and Cosmetic Act (the Act) requires drug and device manufacturers, including manufacturers of biological products, to register with FDA. Title 21, Code of Federal Regulations, Part 607 spells out the registration requirements for manufacturers of human blood and blood products. The Center for Biologics Evaluation and Research (CBER), Office of Blood Research and Review (OBRR), Division of Blood Applications, administratively processes the registration and listing information for human blood and blood products, including licensed in-vitro diagnostic products and biological products such as albumin, clotting factors, and immune globulin.

The Food and Drug Administration Modernization Act of 1997 (FDAMA) amended the registration provision of Section 510, at 510(i), to require that all foreign manufacturers of drugs and devices, including biological products, imported or offered for import into the United States register with FDA. The Agency is in the process of promulgating regulations that will amend the registration provisions of Part 607 to reflect this provision.

Unless exempt, as described below, any establishment that manufacturers human blood or blood products by chemical, physical, biological, or other means must register. This includes the following operations:

o Manipulation, sampling, testing, or utilization of control procedures, whether applied to the final product or to any other part of the manufacturing process;

o Repackaging or otherwise changing the containers, wrapper or labeling of any blood or blood products package in furtherance of distribution of the product from the original place of manufacture to the person who makes the final delivery to the ultimate consumer;

o Processing and any other work that is performed on human blood or blood products; and

o Testing, such as blood grouping and compatibility testing, when performed by a non-Medicare approved establishment in conjunction with transfusion of blood or blood components.

Currently, Part 607 exempts from registration transfusion services and clinical laboratories approved by the Health Care Financing Administration (HCFA) for reimbursement under its Medicare program.

Transfusion Service - a hospital facility or portion thereof engaged in compatibility testing and transfusion of blood and blood products but that do not (1) routinely collect blood or blood products; (2) routinely process blood or blood products, except red blood cells; or (3) routinely process blood and blood components for further distribution to other facilities. ("Routinely" means functions are performed on a regular basis.)

Transfusion Services may perform any of the following activities and remain exempt from registration:

o Compatibility testing

o Transfusion of blood and blood components

o Collection of blood in emergency situations or for therapeutic procedures

o Processing of Whole Blood into plasma products, e.g., recovered plasma intended solely for further manufacture

o Preparation of packed Red Blood Cells from Whole Blood

o Pooling of products, such as platelets, for in-house transfusion

o Removing leukocytes via bedside filtration

A Facility that operates primarily as a transfusion service is required to register if it:

o Routinely collects blood, including autologous units.

o Freezes, deglycerolizes, washes, rejuvenates, irradiates, or removes leukocytes from red blood cells and/or platelets.

Clinical Laboratories - those facilities that test donor blood or plasma for infectious disease agents in support of the preparation of the blood products by other establishments. Clinical laboratories that are engaged in the testing of blood products in support of registered blood establishments are exempt from registration if they are approved for Medicare reimbursement. If a blood establishment utilizes a clinical laboratory that is not approved for Medicare reimbursement, the laboratory is required to register with FDA.

The Agency recently published a proposed rule that would revoke the current exemption from registration for clinical laboratories that are approved for Medicare reimbursement (64 FR 45340 at 45353, August 19, 1999). If this change is implemented, all clinical laboratories that perform testing for blood establishments will be required to register with FDA. This CPG will be revised at that time to reflect any changes that are made to the regulations.

POLICY:

Blood banks and other human blood or blood product establishments required to register under Section 510 of the FD&C Act and 21 CFR Part 607 include:

o Blood banks and other establishments that collect, manufacture, relabel, or prepare human blood, blood components, or products including establishments that prepare components from blood or blood products received from other blood banks or sources. Some examples include: 
   o Community blood banks
   o Hospital blood banks that collect or prepare components (except red blood cells not otherwise manipulated by freezing, rejuvenating, etc.)
   o Brokers that perform manufacturing steps on the blood, blood components, or blood products.
   o Manufacturers of albumin, blood grouping sera, immune globulin, clotting factors, thrombin, and other blood diagnostic products.

o Establishments that collect or prepare blood cells, serums, or plasma for further manufacture into a drug or device. This includes establishments that collect blood or blood components to be used in the manufacture of laboratory reagents or controls such as in-house drawing facilities for diagnostic manufacturers and non-Medicare approved establishments that supply outdated pooled plasma to manufacturers of fractionation products or laboratory control reagents.

o All plasmapheresis establishments, regardless of whether the plasma is to be used for fractionation, unlicensed laboratory control reagents, licensed blood grouping serums, other licensed biological products, or any other diagnostic reagents made from plasma.

o Hospital transfusion services engaged in compatibility testing that neither routinely collect or prepare blood or blood products, but that are not approved for a Medicare reimbursement, such as VA, military, and certain PHS hospitals.

o Testing laboratories that are not approved for a Medicare reimbursement program.

The following establishments are not required to register:

o Establishments that are solely Medicare approved testing laboratories or hospital transfusion services.

o Establishments that only store and distribute blood or blood products, unless the establishment also performs an activity that would be considered manufacturing. An example of a storage facility that would be required to register is a facility that holds product under quarantine and culls out unsuitable units under the direction of the manufacturer. Other manufacturing activities that would require a storage facility to register include pooling, relabeling, reworking, or repackaging blood or blood components.

o Establishments that collect and manufacture products solely for research use only.

REGULATORY ACTION GUIDANCE

Districts are authorized to issue Warning Letters in accordance with Chapter 4, Regulatory Procedures Manual, when the following conditions are met:

o The firm is required to register, as documented by the current inspection. This documentation should include records to show what manufacturing steps the firm performs and documentary sample(s).

o The establishment file documents that management has been advised of the firm's responsibility to register and the firm has failed to do so.

o The district has contacted the Division of Blood Applications, Office of Blood Research and Review, CBER, HFM-370, to confirm that CBER has not received a registration form from the firm.

The warning letters should require the firm to complete the registration form and return it to the district within 15 days. Districts should forward completed Form FD-2830s to HFM-370 for processing. If, after issuance of the warning letter, the firm fails to comply with the registration requirements within ten (10) calendar days after the response period expires, districts should prepare and forward a complaint for injunction (usually a preliminary injunction citing 301(p)) to CBER, Office of Compliance and Biologics Quality, Division of Case Management, HFM-610.

Copies of all Warning Letters issued and responses should be forwarded to the Division of Case Management within 30 days.

Issued: 6/17/74
Revised: 10/1/81, 11/1/81, 12/1/82, 3/95, 8/17/2000