Background

Advanced manufacturing technologies can help to expedite and accelerate scale manufacturing capacities, offer new solutions to address drug shortages, and increase supply chain resilience.

The program is required by Sec. 3213 of the Food and Drug Omnibus Reform Act (FDORA) of the “Consolidated Appropriations Act, 2023.” FDA’s new draft guidance is intended to promote advanced manufacturing, which it defines as “an innovative pharmaceutical manufacturing technology or approach that has the potential to improve the reliability and robustness of the manufacturing process and supply chain and increase timely access to quality medicines for the American public.”

The new guidance builds on FDA’s Emerging Technology Program (ETP), established in 2014 to help pharmaceutical companies seeking to resolve novel technical and regulatory issues related to the development and implementation of new technology prior to filing a regulatory submission. Despite the agency’s work on ETP and the mandate from FDORA, in a report issued in March 2023, the Government Accountability Office called for the agency to do more to support the real-world uptake of AMTs. The GAO report cited interviews with key industry stakeholders to conclude that regulatory uncertainty remained the primary obstacle for manufacturers deciding whether to invest in new manufacturing technology. The report noted that the agency had only approved 16 drug applications using an advanced manufacturing technology since 2015.

What methods are AMT eligible?

The AMT designation applies to manufacturing methods that incorporate a novel technology or use an established technique or technology in a novel way that will substantially improve the manufacturing process for a drug while maintaining equivalent, or providing superior, drug quality. Improvement could include:

• Reducing development time for a drug using the designated manufacturing method; or
• Increasing or maintaining the supply of a drug that is life-supporting, life-sustaining, or of critical importance to providing health care, or a drug that is on the drug shortage list.

FDA considers a “novel technology” to be one “that has not been used in a previously approved application and for which FDA therefore has limited assessment or inspectional experience.” Similarly, an established technique or technology would be novel if it is used in a way that has not been described in a previously approved application. However, the novel technology or use must not play a “limited role in the development or manufacture of a particular drug” for its incorporation to qualify the method of manufacturing for AMT designation. Commonly cited examples of AMT are 3D printing or continuous manufacturing platforms.

Who is eligible for AMT designation?

The draft guidance doesn’t place limitations on the types of entities that can submit a request for AMT designation. Although the potential benefits of the program are perhaps most relevant for drug and biological product sponsors, contract manufacturers and technology developers can request the designation. As discussed below, non-applicants who do not directly reap application-related benefits of the program may still benefit from an AMT designation for a particular technology.

Benefits of an AMT designation

An AMT designation allows early and frequency interaction with the agency through written correspondence and meetings. In addition, “FDA expects to prioritize applicant interactions that are intended to discuss the use of a designated AMT in drug development or commercial manufacturing, with higher priority being given to drug development activities and applications using a designated AMT with the potential to significantly improve product quality, address known quality issues for a drug or class of drugs, or increase or maintain the supply of drugs that are currently in shortage or imminently at risk of being in shortage.”

Even for non-applicants – for example, contract manufacturers or technology developers – AMT designation offers tangible benefits. Typically, non-applicant entities don’t have designated communication channels with the agency (e.g., controlled correspondence, meetings) that are available under user fee programs; however, an AMT designation offers a new opportunity for interaction with the agency to discuss, for example, building a new facility with an AMT or retrofitting an existing manufacturing area with an AMT. It might also be possible for a non-applicant entity with an AMT designation to market to applicant-customers the potential for increased engagement with FDA. As an example, an ANDA applicant for a non-complex generic drug that uses a CMO with a method of manufacturing that is designated as an AMT would be entitled to request meetings that are typically limited to ANDA applicants with complex generic drugs.

Next steps – AMT submissions

AMT designation requests are made independently of application submissions, which means there is no predetermined stage of product development or specific application assessment cycle during which AMT designation requests can be submitted to FDA. Requestors should submit their request when they have sufficient knowledge to support justification for AMT designation. However, we note that it may be difficult for an applicant to determine whether the technology has been used in a previously approved application because this information may not have been disclosed, and we hope that FDA will provide greater clarity on the eligibility criteria in the final guidance. FDA “strongly recommends” early engagement with the Center for Drug Evaluation and Research (CDER) Emerging Technology Team (ETT) or the Center for Biologicals Evaluation and Research (CBER) Advanced Technologies Team (CATT).