About the Accelerated Approval Regulations

Under Subpart H, approval may be based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity ("Surrogate") [21 CFR 314.510], or a product may be approved with restrictions to assure safe use ("Restricted" ) [21 CFR 314.520].

          [21 CFR 314.510]   Surrogate - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity.

FDA may grant marketing approval for a new drug product on the basis of adequate and well-controlled clinical trials establishing that the drug product has an effect on a surrogate endpoint that is reasonably likely, based on epidemiologic, therapeutic, pathophysiologic, or other evidence, to predict clinical benefit or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity.   Approval under this section will be subject to the requirement that the applicant study the drug further, to verify and describe its clinical benefit, where there is uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical benefit to ultimate outcome.  Postmarketing studies would usually be studies already underway.  When required to be conducted, such studies must also be adequate and well-controlled.  The applicant shall carry out any such studies with due diligence.

[21 CFR 314.520]   Restricted - Approval with restrictions to assure safe use.

   (a)  If FDA concludes that a drug product shown to be effective can be safely used only if distribution or use is restricted, FDA will require such postmarketing restrictions as are needed to assure safe use of the drug product, such as:

(1)  Distribution restricted to certain facilities or physicians with special training or experience; or
(2)  Distribution conditioned on the performance of specified medical procedures.
(3)  The limitations imposed will be commensurate with the specific safety concerns presented by the drug product.

Under Subpart E, approval may be based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity ("Surrogate") [21 CFR 601.41], or a product may be approved with restrictions to assure safe use ("Restricted") [21 CFR 601.42]. (See Table below)

[21 CFR 601.41] Surrogate - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity.

FDA may grant marketing approval for a biological product on the basis of adequate and well-controlled clinical trials establishing that the biological product has an effect on a surrogate endpoint that is reasonably likely, based on epidemiologic, therapeutic, pathophysiologic, or other evidence, to predict clinical benefits or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity.  Approval under this section will be subject to the requirement that the applicant study the biological product further, to verify and describe its clinical benefit, where there is uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical benefit to ultimate outcome.  Postmarketing studies would usually be studies already underway.  When required to be conducted, such studies must also be adequate and well-controlled.  The applicant shall carry out any such studies with due diligence.

[21 CFR 601.42] Restricted - Approval with restrictions to assure safe use.

(a) If  FDA concludes that a biological product shown to be effective can be safely used only if distribution or use is restricted, FDA will require such postmarketing restrictions as are needed to assure safe use of the biological product, such as:

(1) Distribution restricted to certain facilities or physicians with special training or experience; or
(2) Distribution conditioned on the performance of specified medical procedures.
(3) The limitations imposed will be commensurate with the specific safety concerns presented by the biological product.