Regulatory Focus™ > News Articles > Industry Weighs in on Expanded Access Guidance, Says Additional Clarity is Needed

Industry Weighs in on Expanded Access Guidance, Says Additional Clarity is Needed

Posted 18 July 2013 | By Alexander Gaffney, RAC

A draft guidance recently released by the US Food and Drug Administration (FDA) that clarifies ways that sponsors of investigational drugs may voluntarily expand access to the therapy to permit exceptionally ill patients to obtain treatment is winning general praise from some of the life science industry's biggest names, according to comments published to FDA's Federal Register docket.


In May 2013, FDA released two draft guidance documents meant to clarify the process of granting access to trials on a "compassionate use" basis. The main draft guidance, Expanded Access to Investigational Drugs for Treatment Use - Q&As, is meant to clarify many aspects of an existing guidance on the expanded access program.

For example, the document explains how to obtain clearance for expanded use, the information that must be contained in a protocol amendment, the various sub-categories of expanded access, who can request expanded access, the role of the patient and his/her physician in the process, reasons FDA might deny an expanded access request, the involvement of an IRB in the process, how to ensure expanded access doesn't interfere with an existing trial protocol, and the involvement of FDA and the sponsor in the process.

A second draft guidance, Charging for Investigational Drugs under an Investigational New Drug Application, is meant to define when it is acceptable to obtain compensation for expanded access, and is closely related to the first guidance.

Industry Comments

The former guidance document has won strong praise from several industry groups, including the Association of Clinical Research Professionals (ACRP), the American Society of Clinical Oncology (ASCO) and the Biotechnology Industry Organization (BIO), but both BIO and ASCO said they had ideas on how to improve upon the existing language.

In comments submitted on 8 July 2013, BIO wrote that, "In general, the draft guidance is well written and provides very useful clarification of the implementation of FDA's regulations on expanded access to investigational drugs for treatment use under an investigational new drug application (IND)."

However, BIO said the guidance failed to offer "adequate information on the appropriate design of an expanded access protocol," leaving several areas without sufficient clarity. For example, the term "intermediate-sized population" goes undefined in the guidance, as does the specific information required in an access IND to assess safety risks when no other IND is currently in effect.

Further, the various types of INDs are not well-defined, BIO said, noting that some patients would appear to meet multiple definitions, and that a treatment protocol may expand over time, altering their definition under the section. Further clarity was requested from FDA.

BIO also highlighted lines 78-85 of the guidance, which it said used language that differed from that in the regulation on which the guidance is formulated. The regulation, BIO said, refers to treatment protocols, while FDA refers to them as access protocols. Consistent terminology would prevent potential confusion, BIO wrote, and recommended the terms be changed.

ASCO also weighed in on the guidance, arguing that the language used in the guidance was relatively advanced given that many patients and physicians would be likely to reference the document. Ordinarily, guidance documents are most referenced by life science industry professionals, and typically those in the manufacturing or clinical trials sector. "The use of regulatory language only serves to further confusion surrounding this topic," ASCO wrote, noting a separate document for patients might prove useful. The logical flow of the document was also seen as in need of improvement.

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