WASHINGTON _ As promised at last November's White Houseceremony, the FDA has published on schedule proposed rules tomake the regulation of biotechnology products comparable tosynthetic drugs.
Published in the Jan. 29, 1996, Federal Register are proposedregulations to eliminate the establishment license application (ELA)and a proposed definition of well-characterized biotech drugs. TheFDA held a workshop on the issue of how to describe well-characterized products last December. (See BioWorld Today, Dec.14, 1995, p. 1.)
Standardizing the regulation of biotech drugs by characterizing theirattributes may have several intended and unintended consequences.Bruce Mackler, a partner in the Washington office of Fenwick &West, a Palo Alto, Calif. law firm, said the proposed rule will firstmake some changes in how research and development is conducted.The definition will force manufacturers to characterize a productearlier in the research and development phase. "This will be aproblem for small companies that have not yet invested incharacterizing their product," he said.
But Mackler said the change would benefit biotech companies in thelong run. "If the product is well characterized up front, then the betterthe argument the manufacturer can make that the product is the sameafter manufacturing changes are made."
"Previously the FDA required a bridging study to show the productwas the same after a change was made in the manufacturing process.Now the agency will rely on physicochemical studies and potencymodels to demonstrate the product is the same despite certainchanges," said Mackler.
Mackler predicted that those companies that fail to invest incharacterization of each biotech product will encounter moreproblems getting the drug approved by the FDA. He expected that theagency will demand that the manufacturer have characterizationcomplete by the end of Phase III studies.
Standardization of biotech drugs by applying the definition couldhave an unintended consequence: generic biotech drugs. Macklerpointed to the example of one company that used different butcomparable cell lines in clinical trials and in the approval procedure."It would have been hearsay a couple of years ago to suggest thatdifferent cell lines were the same product. But that is what well-characterization is leading to," said Mackler.
Carl Feldbaum, president of the Biotechnology Industry Organization(BIO), said he prefers a broader definition of a well-characterizedbiotech product. "All recombinant DNA and monoclonal antibodyproducts should be considered well-characterized unless the FDA canidentify some specific reason why they do not meet the criteria of awell-characterized product," he said.
"At this point in the evolution of biotech products, the burden ofproof has shifted to the agency," said Feldbaum.
Manufacturing Inspections To Change
Feldbaum praised the ELA changes as facilitating corporatemanufacturing agreements signed by biotech companies. "In the newproduct license application, the company only has to list themanufacturing sites since the ELA is no longer required," he stated.
Elimination of the ELA moves biotech drugs significantly closer tobeing regulated like synthetic drugs, said Mackler. "This fits in nicelywith the shift of emphasis at the Center for Biologics Evaluation andResearch [CBER] to delegate inspection from the national office tothe field where inspectors who are experienced in inspectingsynthetic drug makers will now add biotech firms to their complianceschedule."
"The downside to this equation is that it calls into question whetherwe need CBER and its separate regulation of biotech products," saidMackler. n
-- Michele L. Robinson Washington Editor
(c) 1997 American Health Consultants. All rights reserved.