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Analysis of October 2008 Final Rule on Exemptions to PDMA for Blood Establishments that Qualify as Health Care Entities

Clarification of the federal regulations that restrict the sale, purchase and trade of prescription drugs for registered blood establishments and comprehensive hemophilia diagnostic treatment centers that are also health care entities were provided in a final rule, Distribution of Certain Drug Products by Registered Blood Establishments and Comprehensive Hemophilia Diagnostic Treatment Centers That Qualify as Health Care Entities; Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; Policies, Requirements and Administrative Procedures, which takes effect Nov. 10, 2008.

Blood establishments have maintained that Congress, in implementing the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), did not intend to prohibit them from distributing drug products used in transfusion medicine and cellular and related biological therapies that are not blood derivatives and that this should have been included in the exclusions to 21 CFR 203. This position was addressed in comments to the docket for the February 2006 proposed rule and at the May 2006 Advisory Committee on Blood Safety and Availability:

 

AABB, ABC, ARC, and BCA believe that the Proposed Rule only partially addresses a problem with FDA’s original regulations implementing the Prescription Drug Marketing Act. We applaud FDA’s decision in the Proposed Rule to allow certain registered blood establishments that qualify as health care entities to distribute blood derivatives. However, to be faithful to Congress’s intent in enacting PDMA, and to avoid disrupting the current ability of FDA-licensed blood establishments to perform their core blood-related mission, the exclusion in 21 C.F.R. § 203.22 should be broadened to read as follows: “The sale, purchase, or trade of, or the offer to sell, purchase, or trade any transfusion medicine and cellular and related biological therapy product by a registered blood establishment that qualifies as a health care entity, so long as any health care services that it provides are predominantly related to its activities as a registered blood establishment.

 

The final rule modified the 2006 proposed exclusions in several areas:

 

Exclusion applies to a registered blood establishment that qualifies as a health care entity, as long as all of the health care services that the establishment provides are related to its activities as a registered blood establishment or the health care services consist of collecting, processing, storing, or administering human hematopoietic stem/ progenitor cells or performing diagnostic testing of specimens provided that these specimens are tested together with routine donor testing.

 

Exclusion applies to the sale, purchase, or trade of, or the offer to sell, purchase, or trade any: (1) Drug indicated for a bleeding or clotting disorder, or anemia;(2) blood collection container approved under section 505 of the act; or (3) drug that is a blood derivative (or a recombinant or synthetic form of a blood derivative).

 

Exclusion applies to the sale, purchase, or trade of, or the offer to sell, purchase, or trade, by a comprehensive hemophilia diagnostic treatment center that is receiving a grant under section 501(a)(2)of the Social Security Act and that qualifies as a health care entity, any drug indicated for a bleeding or clotting disorder, or anemia, or any drug that is a blood derivative (or a recombinant or synthetic form of a blood derivative).

 

In the preamble to the final rule, FDA responded to a request that the exclusion should extend to any distribution of drug products used in cellular and related biological therapies by noting their interpretation that this would go beyond the scope of the proposed rule and declined to incorporate these products into the exclusions as part of this final rule.

 

Further clarifications found in Section II. Comments on the February 2006 Proposal

FDA recognized that flexibility is needed to provide for the potential future development of drugs, such as blood substitutes, that would be used to treat bleeding disorders, such as hemoglobin-based oxygen carriers, which may partially or transitionally replace the function of blood elements. “Our intent is that the exclusions in Sec. 203.22(h) and (i) could apply to a blood substitute product that might be licensed or approved in the future.”

 

The final rule allows for a comprehensive hemophilia diagnostic treatment center that is also a registered blood establishment to utilize the exclusion in Sec. 203.22(i).

 

Erythropoiesis-stimulating agents used to treat anemia fall within the scope of the exclusions delineated in the rule.

     

In addressing a list of drugs other than blood derivatives that were noted to be distributed by some blood centers, FDA stated the following: 

 

The manufacturer of TRASYLOL (aprotinin) is removing the drug from the U.S. market due to safety concerns and therefore at this time access to TRASYLOL is limited to investigational use of the drug according to the procedures described in a special treatment protocol.

 

Desmopressin acetate injection is indicated for treatment of certain types of blood disorders such as Hemophilia A and von Willebrand's disease (Type I). It is therefore included in the Sec. 203.22(h) exclusion for any drug indicated for a bleeding or clotting disorder, or anemia. Desmopressin acetate nasal spray, however, is not indicated for a bleeding or clotting disorder, or anemia, and it is not a blood derivative (or a recombinant or synthetic form of a blood derivative), and therefore is not included within the exclusion in Sec. 203.22(h).

 

Tetanus and diphtheria (Td) vaccine and rabies vaccines are not included within the exclusion in Sec. 203.22(h) because they are not indicated for a bleeding or clotting disorder, or anemia, and they are not blood derivatives (or recombinant or synthetic forms of blood derivatives). Therefore, the further distribution by a registered blood establishment of Td vaccine and rabies vaccines is prohibited by Sec.  203.20.

 

In responding to comments suggesting that the exclusion in Sec. 203.22 should be broadened to include registered blood establishments that qualify as health care entities as long as any health care services they provide are predominantly related to their activities as a registered blood establishment, FDA noted:

   

Substitution of the word “predominantly” for “all” in the phrase referring to the health care services that a registered blood establishment provides would make the provision too broad and would not provide the protections intended in the PDMA. However, we recognize that certain blood establishments, due to their specialized medical expertise, routinely collect, store and administer human hematopoietic stem/progenitor cells and conduct diagnostic testing of specimens concurrently with specimens undergoing routine donor testing. Our intent is to not interfere with the current practice of blood establishments to provide these specialized health care services. Therefore, instead of replacing “all” with “predominantly,” we extended the exclusion in Sec. 203.22(h) to those registered blood establishments that collect, process, store, or administer human hematopoietic stem/progenitor cells or perform diagnostic testing of specimens provided that these specimens are tested together with specimens undergoing routine donor testing.

 

               

Examples of health care services that are related to registered blood establishments’ activities and that would therefore allow these establishments to utilize the exclusion in Sec.  203.22(h) include: therapeutic hemapheresis, therapeutic phlebotomies, plasma exchange, transfusion services, and ordinary donor screening activities for donor suitability (e.g., measuring a donor's temperature, blood pressure, and hematocrit or hemoglobin). Also included was preventive health care services intended to maintain a healthy donor population, such as administering influenza virus vaccines and testing the levels of prostate specific antigen and cholesterol in potential donors, to be related activities.

 

Background

 

Under a December 1999 final rule, a blood establishment or a hemophilia treatment center could not generally resell blood derivatives to entities other than consumers or patients and simultaneously provide health care, such as medical services associated with those products. Examples of blood derivatives that are prescription drugs include, but are not limited to, albumin, antihemophilic factor, Coagulation Factor IX, alpha-1 proteinase inhibitor, and immune globulin. The provisions of this final rule threatened to disrupt basic interactions between blood centers and their hospital customers as many blood centers performed services such as therapeutic phlebotomy, therapeutic plasma exchange, stem cell and cord blood collection and processing and distributed certain blood-related products.  The distributed products include anti-hemophilic factor, IVIG, and albumin as well as recombinant erythropoietin (not blood-derived), and blood bags containing anti-coagulants that qualify as drugs. 

 

FDA several times delayed implementation of the 1999 final rule — the last extension was until Dec. 1, 2008 — while trying to address the various concerns.  A February 2006 proposed rule addressed some of the issues and would have allowed certain registered blood establishments that qualify as health care entities to distribute blood derivatives. The proposed rule also sought information about the functions of registered blood establishments in order to determine whether further modification of the December 1999 final rule would be warranted, including whether the proposal should be expanded to allow registered blood establishments that also provide health care services to distribute drugs other than blood derivatives that might be used to treat blood disorders. In addition, FDA requested comment on whether hemophilia treatment centers should be included within the scope of the exclusion.