The Food and Drug Administration (FDA) released a draft guidance on the Special Protocol Assessment (SPA) in May 2016, updating the original SPA guidance issued in 2002. SPAs are meant to give Sponsors and FDA a framework to meet, discuss, and agree upon certain clinical trial designs before the initiation of a study. This guidance discusses several key considerations for Sponsors who are contemplating the submission of a SPA. First, it is necessary to understand what type of protocols are eligible for a SPA. Animal carcinogenicity or efficacy protocols, drug substance or drug product stability protocols, biosimilarity or interchangeability protocols, and human efficacy protocols all qualify for a SPA request. It should be noted that only human efficacy protocols are only eligible if they are intended to be relied on as the primary basis for an efficacy claim. Additionally, the Sponsor should meet with the FDA prior to the submission of a request. The meeting type varies based on the product being developed, but can include an End of Phase 2 (EOP2) meeting or a Type 2 biological product development meeting.
In the guidance Sponsors are given criteria required to be included in a SPA submission. Those materials are:
- Information regarding the role the trial will have in product development;
- Reflection of the study and disease population;
- Justification for the design of the trial, including but not limited to: dosing, endpoints, controls, and statistical plan.
Sponsors must give the Agency adequate information to thoroughly critique the SPA and decide if it addresses the key scientific concerns. Therefore, any potentially problematic features of the study protocol should be addressed with sufficient information for the FDA to come to a consensus.
Despite the provided justification, the FDA does not always agree that the submitted protocol will satisfy all questions. Subsequently, a nonagreement letter can be issued. When a nonagreement letter is reached, the Sponsor has three general options. They can initiate the clinical trial without an agreed upon SPA, send a written response to the FDA regarding the nonagreement letter, or request a meeting to discuss the nonagreement letter. To ensure the most effective utilization of resources, reaching an agreed upon SPA is recommended before initiating the clinical trial. Depending on how many outstanding protocol issues are presented, a meeting or written response may be preferred.
