FDA Begins Granting Advanced Manufacturing Technology Designations

In early April, Cellares became the first company to announce receipt of an Advanced Manufacturing Technology (“AMT”) designation from FDA. The designation was granted by CBER to Cellares for its automated cell therapy platform, the Cell Shuttle. We were excited to see the news and look forward to seeing the full implementation of the AMT program and its potential benefits.

First, some background on the AMT program. Section 3213 of the Food and Drug Omnibus Reform Act of 2022 (“FDORA”), (21 U.S.C. § 356l), directed FDA to establish the AMT Designation Pilot Program. The program is intended for 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.” Such improvements could include reducing development time or increasing or maintaining the supply of a critically important drug or a drug on the drug shortage list.

An AMT designation is distinct from other FDA designation programs in that it is independent of any application submission. The designation could be used to support the development of a specific investigational drug, or a new method of manufacturing an approved drug, but it could also be granted to a technology separate from any specific application. A designation is instead granted for a particular “context of use,” which should be specific to a particular class of drugs, but does not have to be specific to a single product. However, the benefits of the designation are realized only in the context of an appropriate application within the designated context of use.

The law directed FDA to issue guidance regarding the implementation of the program, which was finalized in December 2024. As described in this guidance, AMT designation requests may be made at any point in time; however, the technology must be mature enough to consistently and reliably manufacture product in the context of use for which an AMT designation is sought. FDA recommends early engagement with CDER’s Emerging Technology Team (“ETT”) or CBER’s Advanced Technologies Team (“CATT”).

The types of supporting data and information to include with a request depend on the specific method of manufacturing and its proposed context of use. The robustness of these data and information should be commensurate with the level of risk.

As described in guidance, an AMT designation request should include the following:

• A description of the method of manufacturing and why it should be considered for designation, including an explanation of how the method incorporates a novel technology or uses an established technology in a novel way (novel here generally means a new technology FDA has not previously seen in a submission, or a technology with which FDA has experience but with a significantly different use);
• The context of use under which the proposed AMT will be used;
• A detailed description of how the method meets statutory eligibility criteria in a particular context of use, including quality-related data generated through process development studies, and information that describes and justifies the proposed AMT’s context of use;
• Perceived challenges to implementation;
• If the requestor is also an applicant or prospective applicant, an anticipated timeline for drug development activities incorporating the proposed AMT;
• If the requestor intends to use the proposed AMT for manufacturing an existing drug, a cross-reference to the existing application, information demonstrating that the proposed AMT will increase or maintain the supply of the drug, and evidence that equivalent or superior drug quality will be maintained.

The guidance states that requestors who are not applicants should include data generated using a model drug to provide FDA with a clear understanding of the AMT’s parameters, limitations, and context of use.

Within FDA, the center with jurisdiction over the type of drug that would incorporate the proposed AMT reviews the request, along with members of ETT or CATT, as applicable. The statute requires that a determination on the request be made within 180 days of receipt.

If granted, designated AMT holders should communicate updates or proposed changes that could affect the context of use or AMT eligibility. FDA will assess the proposed changes to confirm that the designated AMT continues to meet AMT criteria and maintains the same context of use for which the AMT was designated. Whether the context of use is the “same” should be discussed with FDA, and FDA may determine that a new designation request is necessary.

The benefits of designation include efforts by FDA to expedite the development and review of applications submitted for drugs that are manufactured using the AMT as well as allowing the holder of a designation, or another authorized party, to reference or rely upon data and information about the technology in subsequent applications for use in manufacturing drugs in the same context of use for which the designation was granted. FDA also intends to provide timely advice and to engage in additional communication (e.g., written correspondence, meetings) with applicants for a drug manufactured using a designated AMT. FDA expects to give higher priority where the technology is expected to significantly improve product quality, address known quality issues, or increase or maintain the supply of drugs that are life-supporting, life-sustaining, or of critical importance to providing health care, or are in shortage. The designated lead for the AMT request will coordinate with the FDA quality assessment team in the context of an application with the aim of making the assessment process more efficient than for applications using non-designated manufacturing methods.

Perhaps most importantly, FDA intends to support applicants while they are developing the CMC section of their applications such that the incorporation of a designated AMT will not increase the time or number of assessment cycles required to reach a quality-related decision, and thus will not increase the time required to make a decision regarding overall application approval. While it remains to be seen how advantageous this will be in practice, one of the most significant obstacles related to implementing a new manufacturing technology is the concern that FDA’s relative unfamiliarity with it will cause delays. The possibility that such delays could be avoided with the use of the AMT designation is definitely appealing.

As described in guidance, once FDA has gained significant experience with a specific designated AMT and it has been used in multiple approved applications, FDA may “graduate” the technology from AMT designation and transfer the review of future applications referencing that AMT to the standard quality assessment process rather than an expedited process. Such graduation would keep AMT designation aligned with the statutory requirement of “novelty” and facilitate further innovation to focus on new AMTs that meet the program’s goal of encouraging adoption of novel technologies. We can certainly foresee challenges related to such “graduation” determinations as there is currently a lack of clarity about when it would occur. Hopefully, this will become clearer in time.

Cellares does not appear to have any products in development on its own, and the company, in public statements, describes the likely use of the designation as supporting development and marketing applications of partners. As such, the specifics of how this AMT designation may ultimately impact FDA review of applications are not yet known. It would not be a surprise to us if this was the beginning of a pattern where many such manufacturing organizations seek the designation rather than the applicants themselves. However, this remains to be seen.

Now that we have an example of an AMT designation, we will hopefully be able to gain a better understanding of the benefits of such designations. We have seen quality issues delay otherwise approvable applications on numerous occasions, especially for products with more novel and complex manufacturing processes. It is an exciting thought that companies can get some level of comfort that such issues may be avoided through this proactive designation pilot program, especially for the novel technologies for which it is intended.

Under the law, FDA must post on its website by the end of 2025 a report describing the details of the program, including the types of manufacturing approaches supported. This report will also include numbers of designations granted and numbers related to applications that have included designated AMTs. We eagerly await its publication. As it currently stands, the program is scheduled to begin sunsetting October 1, 2032, with no further designations being considered beyond that date. Hopefully before then, we will see the benefits of designation realized through more efficient approvals with technologies that accomplish the goals of the program.