WASHINGTON_The FDA on Thursday released adocument to give manufacturers of transgenictherapeutics insight on what the Center for BiologicsEvaluation and Research (CBER) considers to be keyissues in the manufacture and testing of these products."We hope the document will provide manufacturers withappropriate benchmarks without being proscriptive," saidPhilip Noguchi, director of CBER's Division of Cellularand Gene Therapy. "This document signals that we areprepared to deal with manufacturers who are developingthese new therapeutic approaches and is anotherindication that we are serious about the regulation oftransgenic materials used to produce biologics andpotential xenograft materials," Noguchi told BioWorldToday.CBER will hold manufacturers of transgenic products tothe same standard of safety and efficacy used to measureother biologicals. According to the CBER document, theagency seeks to "ensure that biological products fromtransgenic animals are as safe and effective as biologicsproduced from other methods."CBER said the document should be considered bymanufacturers in the preparation of applications forinvestigational and new drugs; for product andestablishment licensing submissions; and "to determinewhat scientific data should be submitted in support ofthese applications."Biotech manufacturers should see the document as an"extension of the principles applied to the production ofbiotech materials, such as protein purification," Noguchisaid. The document, "Points to Consider in theManufacture and Testing of Therapeutic Products forHuman Use Derived from Transgenic Animals," does nothave the clout of a formal regulation and will be updated.Genzyme Transgenics, located in Framingham, Mass.,immediately hailed the CBER document. President andCEO James Geraghty called it "a major step in thegrowing acceptance of transgenic production as amainstream alternative."Geraghty told BioWorld Today some biotech firms wereconcerned the agency would "introduce new hurdles orraise existing standards for makers of transgenictherapeutics. But he said "the CBER statement does notraise additional hurdles but sets high quality standardsthat we are confident Genzyme Transgenics can meet."

Genzyme Transgenics operates a commercial facility toproduce recombinant therapeutic and diagnostic productsin milk from dairy goats. (See BioWorld Today, Feb. 13,1995, p. 1).Xenotransplant Guidelines Next

Noguchi sees the document on transgenic animals as"complementary" to planned FDA guidelines onxenotransplantation of animal organs and tissues intohumans. (See BioWorld Today, July 17, 1995, p. 1)."While the document released today focuses on thecharacteristics of animals and proteins produced byanimals, the xenotransplantation guidelines will cover theentirety of issues involved, including patient selection,public health concerns, and privacy issues," he said in aninterview with BioWorld Today.Drafting the document presented the FDA with anopportunity to wrestle with several unique issues, saidNoguchi. For example, officials from several FDACenters, including FDA veterinarians and officials fromthe U.S. Department of Agriculture, hammered out howto determine if carcasses from pigs used to producehuman blood should be allowed into the food supply.The majority of products derived from transgenic animalswill be regulated by CBER, but those not regulated asbiologics will be controlled by the Center for DrugEvaluation and Research or the Center for Devices andRadiological Health. In addition, the FDA's Center forVeterinary Medicine and Center for Food Safety andApplied Nutrition and the Department of Agriculture areresponsible for veterinary and food safety issuesassociated with the use of transgenic animals.Animal Breeding Discussed

Because transgenic animals are necessarily inbred toproduce the requisite characteristics, the FDA consideredwhat was the best way for manufacturers to assure the"purity and reproducibility" of the stock animal. CBERexpects that manufacturers will establish criteria foracceptance of transgenic animals into a production herd"to ensure that animals reliably produce a product ofreasonable quality and safety for the anticipated lifetimeof the product."In addition, CBER's "points to consider" stated, "Thesecriteria should be established for each new transgenicstrain derived from a particular founder animal and themating pool of transgenic animals."Calling on manufacturers to use a system similar to thatused in cell production schemes, the document urgesfirms to "develop approaches to ensure that a desiredproduct from a useful transgenic founder animal remainsavailable for an extended period of time. This approachshould take into account the possibility that genes fromtransgenic animals may interact with different geneticbackgrounds in the breeding partner, potentially affectingthe quantity, quality and purity of the product produced ineach offspring."The CBER document makes clear manufacturers mustaddress the possibility of endogenous and adventitiousagents in the transgenic animal. "The rigor of infectioncontrol in the animal host and validation and eliminationof adventitious agents from the product will depend onseveral factors including the intended use of the product;the tissue from which the product is derived; how theproduct is collected; the purification process and theanimal husbandry practices used during production of thefounder and production animals," CBER stated.In xenotransplantation the spread of animal viruses tohumans also is a major issue. FDA's recent decision toapprove the transplantation of baboon bone marrow into ahuman involved a number of concerns about thetransmitability of diseases endogenous to the baboon.

FDA was recently notified by physicians planning toconduct the baboon bone marrow transplant at aUniversity of California at San Francisco hospital thatthey had located a baboon free of foamy virus, aretrovirus that has unknown contagion to humans."Investigators found the suitable baboon after screeningtwo other baboons found to have endogenous disease,"Noguchi told BioWorld Today. n

-- Michele L. Robinson Washington Editor

(c) 1997 American Health Consultants. All rights reserved.