WASHINGTON _ The FDA has published an additionalset of draft guidelines aimed at harmonizing U.S.regulation of drugs with standards set by Japan andEuropean nations. (See BioWorld Today, July 27, 1995,p.1).

To reduce the differences in technical requirements fordrug development and approval, the FDA has participatedin a number of conferences organized by the InternationalConference on Harmonization (ICH).

The six ICH sponsors are the European Commission, theEuropean Federation of Pharmaceutical IndustriesAssociations, the Japanese Ministry of Health andWelfare, the Japanese Pharmaceutical ManufacturersAssociation, the FDA's Center for Drug Evaluation andResearch and Center for Biologics Evaluation andResearch, and the Pharmaceutical ResearchManufacturers of America (PhRMA).

"As an ICH sponsor, PhRMA supports the developmentof the guidelines," said John Siegfried, PhRMA associatevice president of medical affairs. "U.S. drug makers andthe FDA worked together to come up with a documentthat meets our needs," he told BioWorld Today.

However, ICH sponsors did encounter some problemstrying to "collate regulatory practices from different partsof the world," Siegfried said. "While Japan was willing toaccept to Good Clinical Practice document, the Europeannations pressed for acceptance of language that wasresisted by the U.S. participants."

"To accommodate the concerns of the Europeannegotiators, the Good Clinical Practices guidelines permitmanufacturers the flexibility to meet either requirementsproscribed by the national regulatory agency or locallaw," Siegfried said.

Publication of the draft guidelines means the ICH is morethan halfway through final development of 35 documentsthat address quality, efficacy and safety issues raised byharmonization of regulatory requirements, said JanetShowalter, FDA's ICH coordinator.

"We hope to obtain final comments on six draftguidelines that will be published in the Federal Registerthis month to take with us to the next ICH conference inYokohama, Japan, at the end of October," Showalter toldBioWorld Today.

The Good Clinical Practices draft guideline, published inthe August 17, 1995, Federal Register, provides a unifiedstandard for designing, conducting and reporting clinicaltrials that involve human subjects. Assurances are soughtto protect patient rights and confidentiality. Theguidelines will govern clinical trials in the U.S., EuropeanUnion, Japan, Australia, Canada, the Nordic nations andthe World Health Organization, according to the FDA.

"Analysis of the Expression Construct in Cells Derivedfor Production of rDNA Derived Protein Products,"published in the August 21, 1995, Federal Register, isanother one of the set of international regulatoryharmonization guidelines. It "presents guidance regardingthe characterization of the expression construct for theproduction of rDNA protein product in eukaryotic andprokaryotic cells . . . and describes the types ofinformation that are considered valuable in assessing thestructure of the expression construct used to produce"rDNA-derived proteins, according to the draft guideline.

A second biotech draft guideline, also published in theAugust 21, 1995, Federal Register, specifies the type ofstability studies that should be provided by manufacturersin support of applications for approval. "Quality ofBiotechnological Products: Stability Testing ofBiotechnological/Biological Products," supplements aprevious ICH guideline, "Stability Testing of New DrugSubstances and Products."

FDA says the ICH added the additional requirements forbiotechnology drugs and biologicals because theseproducts "have distinguishing characteristics to whichconsideration should be given in any well-defined testingprogram designed to confirm their stability during theintended storage period."

Draft guidelines on "Technical Requirements forRegistration of Pharmaceuticals for Human Use" definewhen carcinogenicity studies are to be conducted. Thisdocument also "provides guidance to avoid theunnecessary use of animals in testing and to provideconsistency in worldwide assessment of applications," thedocument said.

"The objectives of carcinogenicity studies are to identifya tumorigenic potential in animals and to understand thepotential for such risk in humans. Any cause for concernderived from laboratory investigations, animal toxicitystudies, and data in humans may lead to a need forcarcinogenicity studies," according to the guideline, alsopublished in the August 21, 1995, Federal Register.

Fundamental considerations in deciding to conduct acarcinogenicty study were defined by the FDA as "anyperceived cause for concern arising from otherinvestigations and the maximum duration of patienttreatment" as well as "appropriate study design, timing ofstudy performance relative to clinical development, theintended patient population, prior assessment ofcarcinogenic potential, the extent of systemic exposure"or the similarity or dissimilarity to endogenoussubstances.

Also published in the August 21, 1995, Federal Register,were principles for reproductive toxicity testingconcerning male fertility. The "Detection of Toxicity toReproduction: Addendum on Toxicity in Male Fertility"is related to an earlier ICH guideline on reproductivetoxicity published in 1994. n

-- Michele L. Robinson Washington Editor

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

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