§ 601.26 - Reclassification procedures to determine that licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested conditions of use.

Link to an amendment published at 81 FR 7446, Feb. 12, 2016.

This regulation establishes procedures for the reclassification of all biological products that have been classified into Category IIIA. A Category IIIA biological product is one for which an advisory review panel has recommended under §601.25(e)(3), the Commissioner of Food and Drugs (Commissioner) has proposed under §601.25(f)(3), or the Commissioner has finally decided under §601.25(g) that available data are insufficient to determine whether the product license should be revoked or affirmed and which may be marketed pending the completion of further testing. All of these Category IIIA products will either be reclassified into Category I (safe, effective, and not misbranded) or Category II (unsafe, ineffective, or misbranded) in accordance with the procedures set forth below.

(a) Advisory review panels. The Commissioner will appoint advisory review panels and use existing advisory review panels to (1) evaluate the safety and effectiveness of all Category IIIA biological products; (2) review the labeling of such products; and (3) advise the Commissioner on which Category IIIA biological products are safe, effective, and not misbranded. These advisory review panels will be established in accordance with procedures set forth in §601.25(a).

(b) Deliberations of advisory review panels. The deliberations of advisory review panels will be conducted in accordance with §601.25(d).

(c) Advisory review panel report to the Commissioner. An advisory review panel shall submit to the Commissioner a report containing the panel's conclusions and recommendations with respect to the biological products falling within the category of products reviewed by the panel. The panel report shall include:

(1) A statement designating the biological products in the category under review in accordance with either §601.25(e)(1) or §601.25(e)(2).

(2) A statement identifying those biological products designated under §601.25(e)(2) that the panel recommends should be designated as safe and presumptively effective and should remain on the market pending completion of further testing because there is a compelling medical need and no suitable alternative therapeutic, prophylactic, or diagnostic agent that is available in sufficient quantities to meet current medical needs. For the products or categories of products so recommended, the report shall include:

(i) A description and evaluation of the available evidence concerning effectiveness and an explanation why the evidence shows that the product has any benefit; and

(ii) A description of the alternative therapeutic, prophylactic, or diagnostic agents considered and a statement of why such alternatives are not suitable. In making this recommendation the panel shall also take into account the seriousness of the condition intended to be treated, prevented, or diagnosed by the product, the risks involved in the continued use of the product, and the likelihood that, based upon existing data, the effectiveness of the product can eventually be established by further testing and new test development. The report shall also recommend with as much specificity as possible the type of further testing required and the time period within which it might reasonably be concluded.

(d) Proposed order. After reviewing the conclusions and recommendations of the advisory review panels, the Commissioner shall publish in the Federal Register a proposed order containing:

(1) A statement designating the biological products in the category under review in accordance with either §601.25(e)(1) or 601.25(e)(2);

(2) A notice of availability of the full panel report or reports. The full panel report or reports shall be made publicly available at the time of publication of the proposed order.

(3) A proposal to accept or reject the findings of the advisory review panel required by §601.26(c)(2)(i) and (ii).

(4) A statement identifying those biological products that the Commissioner proposes should be designated as safe and presumptively effective under §601.26(c)(2) and should be permitted to remain on the market pending completion of further testing because there is a compelling medical need and no suitable alternative therapeutic, prophylactic, or diagnostic agent for the product that is available in sufficient quantities to meet current medical needs. In making this proposal, the Commissioner shall take into account the seriousness of the condition to be treated, prevented, or diagnosed by the product, the risks involved in the continued use of the product, and the likelihood that, based upon existing data, the effectiveness of the product can eventually be established by further testing.

(e) Final order. After reviewing the comments on the proposed order, the Commissioner shall publish in the Federal Register a final order on the matters covered in the proposed order. Where the Commissioner determines that there is a compelling medical need and no suitable alternative therapeutic, prophylactic, or diagnostic agent for any biological product that is available in sufficient quantities to meet current medical needs, the final order shall provide that the biologics license application for that biological product will not be revoked, but will remain in effect on an interim basis while the data necessary to support its continued marketing are being obtained for evaluation by the Food and Drug Administration. The final order shall describe the tests necessary to resolve whatever effectiveness questions exist.

(f) Additional studies and labeling. (1) Within 60 days following publication of the final order, each licensed manufacturer for a biological product designated as requiring further study to justify continued marketing on an interim basis, under paragraph (e) of this section, shall submit to the Commissioner a written statement intended to show that studies adequate and appropriate to resolve the questions raised about the product have been undertaken. The Federal Government may undertake the studies. Any study involving a clinical investigation that involves human subjects shall be conducted in compliance with the requirements for informed consent under part 50 of this chapter. Such a study is also subject to the requirements for institutional review under part 56 of this chapter unless exempt under §56.104 or §56.105. The Commissioner may extend this 60-day period if necessary, either to review and act on proposed protocols or upon indication from the licensed manufacturer that the studies will commence at a specified reasonable time. If no such commitment is made, or adequate and appropriate studies are not undertaken, the biologics license or licenses shall be revoked.

(2) A progress report shall be filed on the studies by January 1 and July 1 until completion. If the progress report is inadequate or if the Commissioner concludes that the studies are not being pursued promptly and diligently, or if interim results indicate the product is not a medical necessity, the biologics license or licenses shall be revoked.

(3) Promptly upon completion of the studies undertaken on the product, the Commissioner will review all available data and will either retain or revoke the biologics license or licenses involved. In making this review the Commissioner may again consult the advisory review panel which prepared the report on the product, or other advisory committees, professional organizations, or experts. The Commissioner shall take such action by notice published in the Federal Register.

(4) Labeling and promotional material for those biological products requiring additional studies shall bear a box statement in the following format:

Based on a review by the (insert name of appropriate advisory review panel) and other information, the Food and Drug Administration has directed that further investigation be conducted before this product is conclusively determined to be effective for labeled indication(s).

(5) A written informed consent shall be obtained from participants in any additional studies required under paragraph (f)(1) of this section, explaining the nature of the product and the investigation. The explanation shall consist of such disclosure and be made so that intelligent and informed consent be given and that a clear opportunity to refuse is presented.

(g) Court appeal. The final order(s) published pursuant to paragraph (e) of this section constitute final agency action from which appeal lies to the courts. The Food and Drug Administration will request consolidation of all appeals in a single court. Upon court appeal, the Commissioner of Food and Drugs may, at the Commissioner's discretion, stay the effective date for part or all of the final order or notice, pending appeal and final court adjudication.

(h) [Reserved]

(i) Institutional review and informed consent. Information and data submitted under this section after July 27, 1981, shall include statements regarding each clinical investigation involving human subjects, that it was conducted in compliance with the requirements for informed consent under part 50 of this chapter. Such a study is also subject to the requirements for institutional review under part 56 of this chapter, unless exempt under §56.104 or §56.105.

[47 FR 44071, Oct. 5, 1982, as amended at 64 FR 56452, Oct. 20, 1999]