The FDA finalized guidance on its special protocol assessment (SPA) program that offers sponsors an advanced declaration from the agency that their trial designs, clinical endpoints and statistical analyses are acceptable.

The guidance finalizing the agency’s May 2016 draft details the procedures for submitting an SPA request, the content necessary to make such a request, the FDA’s assessment process, what happens if the FDA and the sponsor do not agree on trial protocols and when changes can be made to SPA agreements.

The guidance outlines the options for sponsors who receive a “No Agreement” letter from the agency. Such sponsors can initiate the trials without an SPA agreement, hold off on the trial to address the non-agreement in writing or request a Type A or biological product development Type 1 meeting to discuss the non-agreement.

The FDA also has the option to rescind an SPA agreement, although this is very rare and has occurred in fewer than one percent of the more than 1,000 SPA agreements the agency has issued since 1997. It can occur when division directors or senior management identify a substantial scientific safety or efficacy safety after the trial has begun. This could include:

• Identification of data calling the relevance of agreed-upon efficacy endpoints into question
• Identification of safety concerns for either the product or its pharmacological class
• The discovery of false or mistaken information or data in the SPA materials submitted by the sponsor.

Five main protocols are eligible for SPA approval, including: protocols for animal carcinogenity; drug substance and drug product stability; trials that aim to form the primary basis of an efficacy claim; and clinical studies necessary to prove interchangeability or biosimilarity; as well as animal efficacy protocols for studies intended to prove primary evidence of effectiveness required for approval or licensure.