WASHINGTON _ The FDA gathered more than 1,000pharmaceutical industry experts here this week to helprewrite the rules governing biotechnology products, aneffort that may become the most sweeping change in theregulation of biologicals in half a century.
FDA's Center for Biologics Evaluation and Research(CBER) announced the planned change in November at aWhite House press conference, billing the revision asperhaps the most significant aspect of the Clintonadministration's push to "reinvent" the way governmentworks.
The new rules will eliminate strictures on facilitylicensing and lot-by-lot release. They also will shrinkproduct marketing applications from 21 forms to one _similar to those used by the Center for Drug Evaluationand Research _ thus streamlining the FDA's approvalprocess and giving firms with "well-characterized"biotech products the same flexibility as manufacturers ofother types of drugs.
In the meeting's final sessions today, participants willoffer the FDA recommendations to consider when theagency drafts its revised guidelines. The draft guidelinesare scheduled to be released in early 1996 and finalizedlater in the year.
Kathryn Zoon, CBER director, said, "This is the biggestchange in the regulation of biologic products since 1944."
The three-day meeting on "Characterization ofBiotechnology Pharmaceutical Products," which beganMonday, was called to give the FDA and industry expertsan opportunity to decide what the term well-characterizedmeans, and what tests will be required to satisfy the newstandard.
These are not simple questions, and no one has any easyanswers, said Paul Vik, director of regulatory affairs atPro-Neuron Inc., of Rockville, Md. "It's been the blindleading the blind, so far," Vik said mid-way through thefirst session. "The agency is clearly looking for help."
The outcome of the discussion could have far-reachingimplications for biotech firms, large and small. Some mayhave to buy costly new measurement devices _ highperformance liquid chromatography equipment, forinstance, may cost anywhere from $100,000 to $400,000_ or carry out labor-intensive lab work to satisfy the newdefinition.
Zoon told BioWorld Today that the FDA hopes todevelop "decision trees" to simplify the analysis of well-characterized biotech products.
"If you don't have a well-characterized product, it doesn'tmean you won't get approved," she said. "You'll justhave to go through the old framework."
Vern Reinhold, a microbiologist at Boston University,said it's difficult to characterize a biotech product _"especially a big one" _ totally.
"There are just too many parameters to pursue," he said."And you don't want to chase a lot of details that couldturn out to be meaningless." Thus, he said, a paramountaim of the FDA session involves figuring out "what isappropriate and how much you should do."
Not surprisingly, many of the firms present sent smalldelegations of employees responsible for different aspectsof the drug development process to add their input to thedebate.
"People are worried," said Stephen Berenzenko, head ofprocess development for Delta Biotechnology Ltd., aprivately held firm based in Nottingham, U.K.
Some tests under discussion, Berenzenko said, such asthose that assess the strength of the disulfide bondsbuttressing certain molecules, could actually alter themake-up of the products they are intended to characterize.
Berenzenko said the measurements are not impossible but"could create a lot of difficulties" for firms required touse disulfide bonds as evidence of a product's stability.
Much of the first day's discussion focused on similar, andequally technical, questions relating to the ways biotechfirms might assess a product's amino-acid sequence;measure the way its secondary and tertiary structure foldsaround this amino-acid backbone; and characterize theimportance of a molecule's glycosylation, or sugaryappendages.
Raymond Dwek, director of the Oxford BiotechnologyInstitute, at Oxford University in the U.K., said obtaining"sugar prints" would be an invaluable way to characterizebioactive molecules. "If you can get sugar prints," Dweksaid, "you own the molecule."
Dwek said glycoforms could prove an invaluable way ofdistinguishing one drug from another. And because theconfiguration of a molecule's sugars are an indication of"what's going on inside a cell," he said, the tests couldalso be a useful tool for quality control.
But the example also demonstrates how complex achallenge this will be. So far, Dwek said, no one hasdeveloped an automated way to determine a molecule'sglycosylation characteristics that is both rapid andaccurate.
Reinhold, of Boston University, said investing in newtechnology is unavoidable. "Technology clearly isimproving all the time and we will have to keep chasingit," he told participants.
Among the other techniques discussed were circulardichroism, which involves measuring changes in theorientation of polarized light beamed through a columncontaining a protein solution, and using high performanceliquid chromatography to determine a molecule's weight.
In breakout sessions on Monday, the participantsconsidered using these tests and others to determine aproduct's antigenic potential; to assess its potency; and todetect and analyze impurities. They also discussed waysto evaluate DNA/plasmid products. They explored waysto evaluate multi-antigen peptides; polysaccharideconjugates used in vaccines; monoclonal antibodies andhighly purified proteins from natural sources. n
-- Steve Sternberg Special To BioWorld Today
(c) 1997 American Health Consultants. All rights reserved.