FDA Finalizes Special Protocol Assessment Guidance for Industry

The FDA has finalized its guidance on the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research special protocol assessments (SPAs). SPA is a process in which product sponsors may ask to meet with FDA to reach an agreement on the design and size of clinical trials and clinical or animal studies to determine whether they adequately address the scientific and regulatory requirements to support eventual marketing approval.

An SPA agreement indicates that the FDA concurs with the adequacy and acceptability of the overall protocol design, though it does not guarantee that the FDA will accept a New Drug Application or a Biologics License Application for the resulting proposed product, or that a marketing application will be approved.

The protocols that are eligible for SPA request are animal carcinogenicity protocols, drug substance and drug product stability protocols, animal efficacy protocols, protocols for trials intended to form the primary basis of an efficacy claim, and protocols needed for clinical studies to demonstrate biosimilarity or interchangeability of proposed biosimilar.

For proposed biosimilar products, protocols will only qualify for the SPA program if the sponsor has conducted a biosimilar biological product development (BPD) type 2 or type 3 meeting with the agency. The FDA says that “These detailed discussions are especially important if the development plan will include trial elements with which there is little past experience.”

If the product sponsor receives a letter indicating that no agreement with the agency has been reached, the sponsor can choose to initiate the trial without an agreement, respond in writing to the FDA to address the nonagreement letter without initiating the trial, or request a meeting to discuss the nonagreement letter.

An SPA agreement can be modified after testing begins if the FDA and the sponsor agree to a change in writing, and, in some cases, the FDA can rescind an SPA agreement (though the guidance notes that fewer than 1% of all SPA agreements have ever been rescinded).