This guidance finalizes a draft version of the same name issued in May 2016, and replaces guidance of the same name issued in May 2002. “Changes were made from the 2016 draft guidance to improve clarity and readability,” FDA said. Background According to FDA, SPA is a process by which sponsors may request to meet with FDA to reach agreement on certain trials to determine if they adequately address scientific and regulatory requirements. “After completing the SPA review, FDA issues a letter including comments from the review team, agreement or nonagreement with the proposed protocol, and answers to the sponsor’s relevant questions,” the agency said. Per the Food, Drug & Cosmetic Act, as well as prescription drug and biosimilar user fee goals, FDA said the following protocols are eligible for SPA: “(1) animal carcinogenicity protocols; (2) drug substance and drug product stability protocols; (3) animal efficacy protocols for studies intended to provide primary evidence of effectiveness required for approval or for licensure for products developed under the animal rule; (4) protocols for trials intended to form the primary basis of an efficacy claim; and (5) clinical studies necessary to prove biosimilarity and/or interchangeability.” Guidance The 30-page guidance highlights the procedures for submitting an SPA request, the content necessary to make such a request, FDA’s assessment process, what happens if FDA and the sponsor do not agree on trial protocols and when changes can be made to SPA agreements. “Sponsors should note that, despite additional communications in writing and/or additional Type A or BPD Type 1 meetings, sponsors and FDA may not reach agreement on all aspects of the protocols and specific questions posed,” the guidance explains. The following options are available to sponsors after receiving what’s called a “Special Protocol Assessment — No Agreement letter”: ● Initiate Trial Without SPA Agreement — “Sponsors can initiate trials after receipt of Special Protocol Assessment — No Agreement letters. FDA agreement is not required before proceeding with trials intended to form primary evidence of effectiveness, and FDA reviews marketing applications on the basis of submitted data, regardless of whether FDA previously agreed with protocol designs in SPA agreements. If the results from a trial are submitted in a marketing application, FDA will review the results and determine whether they support the approval of the application. Applications that meet the statutory standards will result in approval. ● Do Not Initiate Trial and Respond in Writing to Address Nonagreement — “Sponsors can respond in writing to amend protocols or provide additional supporting information to address the reasons for the nonagreement expressed by FDA. This amendment and response will be considered an SPA resubmission, not a new SPA submission under PDUFA and BsUFA performance goals, and FDA will make every effort to complete the subsequent review within 45 days.” ● Request a Type A or BPD Type 1 Meeting to Discuss Nonagreement — “Sponsors can request Type A or BPD Type 1 meetings with the divisions to discuss nonagreement issues. If FDA believes that meeting with a sponsor is the best way to resolve outstanding issues regarding an SPA, FDA can suggest in the Special Protocol Assessment — No Agreement letter that the sponsor request such a meeting.” More Information On RAPS