The final version of the FDA Guidance for Industry on the Advanced Manufacturing Technologies Designation Program was released on 2 January 2025. The document reflects the comments received by the Agency during the public consultation on the draft guideline held between February and March 2024.
The Guidance describes the framework to request an Advanced Manufacturing Technology (AMT) designation. The procedure may interest companies (including applicants, contract manufacturers, and technology developers) based outside the US, and those activities and productions are intended for export in the United States.
The AMT program is regulated by section 506L of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The designation aims to facilitate the development of new high-quality medicinal products in a timely manner, thanks to the use of innovative manufacturing approaches. Other expected benefits include better regulatory predictability and early interaction opportunities with the Agency before submission of the MA application, so that the proposed approach can be optimised on the basis of FDA’s requests.
What is an Advanced Manufacturing Technology
According to the definition given in the guideline, AMTs may refer not only to completely new technological approaches but also to established techniques used in innovative ways or applied in a new domain where there are no defined best practices or experience. In the case of established technologies, they are expected to substantially improve the manufacturing process while ensuring that the quality of the final medicinal product is at least equivalent or even superior. Reduction of development time, the possibility to increase or maintain the supply of a particular product, and its presence within the drug shortage list are other criteria for eligibility.
The program pays particular attention to life-supporting medicines and drugs of critical importance. It can be applied to the development of new products (section 505 of the FD&C Act) and biological medicines (section 351 of the Public Health Service Act).
Data submitted to the FDA as a part of an AMT designation can be taken as reference by the holder of the designation or another authorised party to fill another application in the same context of use, i.e. for “the specified purpose and manner of use for a designated AMT that will be used in developing and manufacturing a particular drug type (e.g., dosage form or class)”.
AMT designation request and assessment
Requests to access the AMT designation program are entirely independent from submitting the application for marketing authorisation (MA), and can be forwarded to the FDA by the so-called “requestor” at any time along the development procedure.
Contents of the request for AMT designation should include suitable data to demonstrate fulfilment of eligibility criteria in the proposed context of use, including a sufficient state of maturity of the technology to allow consistent and reliable manufacture of the product. Should eligibility criteria fail to be met, requestors may seek advice from the CDER’s Emerging Technology Team (ETT) or the CBER’s Advanced Technologies team (CATT) to solve pending issues.
The provided information should refer to the description of the manufacturing method (or combination of methods), including a motivation supporting the designation. Improvement in the manufacturing process and the quality of the drug product should also be demonstrated.
Information on the context of use (e.g., class, and dosage form) may also refer to a representative model drug used to set up manufacturing or produce the submitted development data. This should help requestors who are not the same as the applicant, as requested data do not refer to an application-specific drug, but to a larger, particular class of drugs.
An outline of the proposed manufacturing steps and control strategy should also be included, together with the explanation of how the AMT would reduce the development time or address critical supply needs. Attention should be paid to the perceived regulatory or technical challenges that could be found in the implementation of the proposed AMT. Should the requestor be the same as the applicant for MA, details on the planned submission of applications should be provided.
A dedicated e-mail address ([email protected]) is available to submit the request for AMT designation. The application will be assessed by a team of FDA experts from the specific regulatory body (CBER or CDER, including members of ETT or CATT) entitled to evaluate the specific type of drug produced using the proposed AMT. Cross-disciplinary teams can also be established by the FDA to assess submissions with potential cross-center impact. The designated lead of the assessment team will be in charge of keeping contact with requestors to obtain additional information or to discuss specific aspects of the application. The entire process should close within 180 days from the submission.
New requests based on additional data can be forwarded in case an AMT designation is denied. Once granted, any update or proposed change to the designation should be communicated to the FDA. The guideline include all details about the information and documentation to be provided.
The review of applications referred to a specific designated AMT may also be transferred to the standard quality assessment process in the future once the FDA has gained significant experience in the assessment process and the specific designated AMT has been used in multiple approved applications. This type of occurrence would be graduated on a case-by-case basis and aims to support the adoption of novel manufacturing technologies.
Other key aspects of the AMT designation
The FDA Guidance specifies that the Agency should prioritise interactions with applicants that involve the use of a designated AMT, to speed development and improve product quality. User fee meeting type interactions should be the preferred occurrence to address AMT designation for new drug applications (NDAs), biologics license applications (BLAs), and abbreviated new drug applications (ANDAs) involving complex generic drugs. For ANDAs that do not involve complex generic drugs, the interaction would occur mainly through controlled correspondence. In any case, a product development and presubmission meeting can also be requested.
AMT designation is expected to support applicants in developing the CMC section of the application dossier. Using a designated AMT for manufacturing a specific drug in the same context of use of the original designation would be subject to discussion in presubmission meetings.
The Q&As section of the guideline better describes the respective roles and responsibilities of the requestors, designated AMT holders and applicants. Novelty of the proposed AMT technology refers to the FDA’s still limited assessment and inspectional experience in evaluating it. The guideline underlines the fact that novelty is not a sufficient criteria to ensure eligibility for AMT designation.
In case of multiple and separate submissions for designation, each will be independently evaluated. The AMT holder should grant authorisation to incorporate reference data and information about the designated AMT in NDA, ANDA or IND applications managed by other applicants. Each application will be assessed separately. The same applies to BLA applicants, but all reference data and information regarding the drug substance, drug intermediates and drug product should be submitted directly to the BLA and not incorporated by reference to a Drug Master File so as to demonstrate control and validation of the manufacturing process.
