The FDA is seeking industry feedback by mid-February on a new program to facilitate innovation in pharmaceutical manufacturing and related technologies to improve the reliability and robustness of manufacturing processes and the supply chain. What does the proposed new program entail?

The US Food and Drug Administration (FDA) issued draft guidance last month (December 2023) detailing its new advanced manufacturing technologies (AMT) designation program by providing guidance on submitting designation requests, agency communications, and interaction with designation holders. FDA says that the benefit of the program will be early interaction with manufacturers and expediting the development and assessment of applications receiving the designation.

The FDA defines “advanced manufacturing” 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 medicines. Advanced manufacturing can integrate novel technological approaches, use established techniques in an innovative way, or apply production methods in a new domain where there are no defined best practices or experience. Advanced manufacturing can potentially be used for new or currently marketed small molecule drugs or biological products.

“FDA encourages the early adoption of advanced manufacturing technologies (AMTs) that have the potential to benefit patients by improving manufacturing and supply dependability and optimizing development time of drug and biological products,” said the agency in its draft guidance. “These technologies can be integral to ensuring quality and supporting a robust supply of drugs that are life-supporting, life-sustaining, of critical importance to providing health care, or in shortage. AMTs can directly improve product quality (e.g., through better manufacturing controls and fewer human interventions).”

The draft guidance provides recommendations to persons and organizations interested in participating in FDA’s Advanced Manufacturing Technologies Designation Program, which is intended to facilitate the development of drugs, including biological products, manufactured using an AMT that has been designated as such under the program. The guidance outlines the eligibility criteria for AMT designation, the submission and assessment process for requests, and the benefits of receiving an AMT designation and includes a questions and answers section to cover additional details about key concepts important for program utilization.

Specifically, the draft guidance specifies the following:

• The process for submitting an AMT designation request, including a description of eligibility criteria and the data and other information to be included.

• When and how FDA will communicate receipt of and provide advice on an AMT designation request.

• When and how FDA will assess AMT designation requests.

• The process by which FDA will engage with holders of designated AMTs and applicants for drugs  manufactured using, referencing, or relying upon a designated AMT,

• Potential benefits related to drug development and application assessment.

AMT submission process
In its draft guidance, the FDA says that an AMT designation request must include data or information demonstrating that the method of manufacturing meets the statutory criteria in a particular context of use. In addition, the request must demonstrate the ability of the proposed AMT to substantially improve the manufacturing process for a drug while maintaining or improving upon its quality, including by reducing drug development time or increasing or maintaining the supply of a drug that is life-supporting, life-sustaining, of critical importance to providing health care, or in shortage. The robustness of the data and information should be commensurate with the level of risk inherent to the process and potential product, such that the data and information can be later leveraged in a marketing  application.

Specifically, an AMT designation request should include the following information as outlined below.

• A brief description of the method of manufacturing or combination of methods and why it should be considered for AMT designation, including a brief explanation of how the method, in part or in whole, incorporates a novel technology or uses an established technique or technology in a novel way.

• A detailed description of how the method of manufacturing or combination of methods meets the eligibility criteria in a particular context of use. This description should include: (1) an outline of the steps of the proposed AMT, including information about where in the overall manufacturing process the proposed AMT is intended to be used; (2) a description of proposed process controls, quality information, and, if applicable, proposed controls of critical steps, intended to ensure equivalent or superior drug quality; and (3) developmental data and information for the proposed AMT that evaluates and justifies the context of use.

• The context of use under which the proposed AMT will be used in drug development, including information (e.g., dosage form, class of drug) about a model (i.e., representative) drug used to generate data submitted in the request.

• Perceived regulatory, technical, or other challenges to implementation of the proposed AMT.

• The timeline, as applicable and if known at the time of the AMT designation request, for drug- development activities that incorporate the proposed AMT, including the planned submission of any applications that would use, reference, or rely upon data and information about the proposed AMT in the same context of use.

• If applicable, information about previous engagement with FDA’s Center for Drug Evaluation and Research’s (CDER) Emerging Technology Team(ETT)/the Center for Biologics Research and Evaluation’s (CBER) Advanced Technologies Team (CATT). All three programs—AMT Designation Program, CDER’s Emerging Technology Program, and CBER’s Advanced Technologies Program—focus on early engagement between FDA and prospective developers of CDER- or CBER-regulated products to discuss potential regulatory challenges and clarify related questions. CDER’s Emerging Technology Program allows potential applicants, before  application submission, to submit questions and proposals about the use of a specific emerging technology to the ETT, a group that serves as the primary point of contact for companies interested in implementing an emerging technology into their products regulated by CDER. CBER’s Advanced Technologies Program promotes dialogue, education, and input between  CBER and prospective developers of advanced manufacturing and testing technologies. The CATT facilitates such communications to promote the implementation of these technologies in the development of products regulated by CBER

• A proposed AMT that is intended for use in manufacturing an existing drug should include a cross-reference to the existing application and data demonstrating that the proposed AMT will increase or maintain the supply of the drug and will maintain equivalent or provide superior drug quality.

In addition, FDA says it acknowledges that requestors who are not also applicants may not have data about a specific drug to include in their AMT designation request. In these cases, FDA recommends that requestors include data generated using a model drug to provide the agency with a clear understanding of the proposed AMT’s parameters, limitations, and context of use.

Determination of eligibility
To determine eligibility, a team of FDA experts from the center with jurisdiction over the type of drug intended for development will review the request. This team, including members of CDER’s ETT or CBER’s CATT, where applicable, will evaluate the data and information submitted in the request, including information relating to the context of use, and will seek input from subject-matter experts, as needed, to determine if the proposed AMT meets the designation criteria and should therefore be granted AMT designation. For proposed AMTs that have potential cross-center impact, a cross-disciplinary team, including members from CDER and CBER, will evaluate the requests.

Benefits of AMT designation
In its draft guidance, FDA says that a key benefit of the Advanced Manufacturing Technologies Designation Program is FDA’s early interaction with requestors and applicants regarding the development of drugs that may be manufactured using a designated AMT. As resources permit, FDA says it intends to provide timely advice and to engage in additional communication, in the form of written correspondence or meetings, with requestors, designated AMT holders, and applicants for a drug manufactured using a designated AMT. Such communication may take place during both early drug development and subsequent application assessment and will be used to address proposed or designated AMT-related questions and issues, including AMT design or development issues, submission content related to a designated AMT, and other AMT-related topics.

AMT designation priority
In its draft guidance, FDA says it 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. Consideration for prioritization may also be given to drug-development activities and applications that are accepted into other expedited programs (e.g., fast track, breakthrough therapy).