WASHINGTON - The Clinton Administration Thursday unveiled itsplan to reinvent the FDA saying that it will speed review of drugs andmedical devices while "maintaining critical public health protectionsthat American people expect and deserve."
Most of the plan's changes will be made administratively except forchanges in export rules and the enactment of medical device userfees, which will require legislative action.
The White House said its plan, developed in cooperation with FDACommissioner David Kessler, was based on the principle of usingperformance standards, rather than command and controlsregulations, whenever possible. The administration also sought toexpedite product reviews, eliminate unnecessary requirements anduse modern automated technology to streamline agency management.
Kessler stressed that he could not buy into all of industry's suggestedreforms because they would compromise the independence of theagency.
At the second of a two-day Senate Labor and Human ResourcesCommittee hearing on FDA reform, Kessler rejected "radical inroadsinto the independence of the agency, ranging from requiring it to useadvisory committees with industry experts who have conflicts ofinterest, to wholesale delegation of critical functions to private thirdparties, to requiring it to hire industry employees who would reviewdrug and device applications."
Biotechnology Industry Organization (BIO) President Carl Feldbaumsaid he was "disappointed" by what he called "limited steps by theadministration."
"The FDA plan is silent on a number of issues that need to beaddressed, including dealing better with export issues, expandingpatient access to medical information, deregulation of Phase I clinicaltrials and refocusing FDA reviews," Feldbaum said.
Feldbaum added that BIO had also hoped for new safety guidelinesfor the use of human tissue, removal of the requirement that theagency inspect every production lot of a biological drug andprivatization of certain FDA functions.
The planned FDA reforms will:
* Allow manufacturers of drugs and biologics to change the way theymanufacture an approved drug without FDA pre-approval if the riskis negligible, enabling the FDA to focus its resources on more criticalproduct reviews.
* Permit manufacturers of biologics to get licenses for pilot facilitiesinstead of building full-scale manufacturing plants, lowering start-upcosts and speeding production. Manufacturers still will have to showthey meet safety, purity and potency standards.
* Permit greater flexibility to allow distributors' names to appear onbiological containers, packages and labeling.
* Regulate insulin and antibiotics the same way other drugs areregulated.
* Exclude drug and biologics manufacturers from mostenvironmental assessments.
* Clarify the effectiveness standard for new drugs to speed reviews.
* Harmonize international standards for review of drugs and medicaldevices to end duplicative testing needed to meet differing standardsof other countries.
* Expand and standardize computer technologies to reduce reviewtimes and to allow imported products in the U.S. marketplace faster.
Trimming Rules On Manufacturing Changes
The FDA will immediately issue a guidance document to implementits three categories of reporting requirements that biologicsmanufacturers will submit prior to making manufacturing changes.The document will identify the types of manufacturing changesexempt from approval. Within nine months, the FDA will amend itsregulations further to reduce the instances requiring its approvalbefore products may be marketed. The agency also will review itspolicy on lot release of biologics to determine how to ease thoseregulatory burdens as well.
The planned regulatory categories for reporting changes in biologicsmanufacturing are:
Category 1: Changes where no supplemental submission will berequired. The sponsor will generate and retain all relevant datadefining and validating, if necessary, changes being made. Voluntarynotification of changes and dates of implementation.
Category II: Sponsors will submit standard supplements unless theFDA objects. Examples include expansion of existing manufacturingsystems; modification of approved manufacturing areas which do notadversely affect safety, purity or potency, and replacement ofequipment that is similar but not identical in design.
Category III: Changes requiring FDA approval include change inprocessing conditions, change in dosage forms, extension of datingperiod and use of previously unapproved manufacturing area orfacility.
To give the biologics industry flexibility, the FDA will issue productand establishment licenses on the basis of demonstrated safety, purityand potency of the product manufactured in pilot or small-scalefacilities. Before moving to a large manufacturing plant, the makerswill only have to file a supplement to previous applications. Detailson the small-scale and pilot plant licenses will be available from theFDA within three months. For the 2,000 pending applications for newdrugs and biologics, the proposal to permit use of small-scale andpilot facilities during development of biologics may convince themnot to launch construction of new facilities. The FDA estimates that itcosts $25 million to construct a biologics manufacturing facility andabout $15 million a year to operate it.
Labeling Requirements Eased
Many biotech companies will be permitted to have their names ondrugs manufactured by another company under the FDA's plan toallow both the names of the distributors and selling agents to bedisplayed prominently on biological product containers, packagelabels, and labeling. New labeling regulations will be publishedwithin six months.
Drug companies will be able to export their products to the 21countries now specified in law, even if they do not haveinvestigational new drug (IND) exemption in the U.S. Currently amanufacturer must have an approved IND and the drug must beapproved for use in the importing country.
Responding to manufacturers' complaints that the FDA's regulatoryrequirements for demonstrating efficacy present unreasonablebarriers to developing new therapies and bringing them to market, theFDA plans to issue a public statement to address those concernswithin three months.
The statement will outline the agency's rationale for weighing thedemonstrated effectiveness of the product against its risks, todetermine whether the benefits outweigh the risks. That weighingprocess also takes into account information such as the seriousnessand outcome of the disease, the presence and adequacy of existingtreatments, and adverse reaction data.
The FDA will not drop its requirement for multiple studies.Manufacturers must be able to replicate effectiveness data toadequately demonstrate effectiveness of a new product.
"While a second study may well be needed to replicate resultsdemonstrated in a first study, in some instances it is possible toreplicate results within one large, well-designed, multi-center study.It should be emphasized that this approach can be successful onlywhen results are strong," such as in the cases of Pulmozyme andtimolol, according to the FDA.
The FDA will work with the European Union, Japan and its NorthAmerican Free Trade Agreement partners to harmonize producttesting and development standards with those of the U.S. Building onefforts already under way, the FDA will issue guidelines forharmonized standards; accelerate work on harmonizing GoodManufacturing Practices, Good Clinical Practices and GoodLaboratory Practices standards and inspections. The FDA said itdoesn't expect those trade initiatives to be completed for two to threeyears. n
-- Michele L. Robinson Washington Editor
(c) 1997 American Health Consultants. All rights reserved.