ASGCT Responds to FDA’s Advanced Manufacturing Technologies Designation Program Draft Guidance

ASGCT submitted comments to the Food and Drug Administration’s (FDA) Advanced Manufacturing Technologies Designation Program – Guidance for Industry. The mission of the Society is to advance knowledge of, and access to, genetic and cellular therapies to alleviate human disease. Given this mission, ASGCT expressed concerns about the limited scope of the proposed program and its ability to be a catalyst for innovation in CGT manufacturing. 

Without a doubt, the pipeline for CGT is robust as reflected by a 6% increase in 2023; there are 3,951 therapies in development, ranging from preclinical through pre-registration. However, the adoption of advanced manufacturing practices leveraging novel technologies has been slow and burdensome. Traditionally, the FDA has provided binding feedback about manufacturing technologies during a biologics license application (BLA). This creates uncertainty for product sponsors who would need to make costly manufacturing changes to leverage a novel technology- while running the risk that it may not be approved by the FDA. The Advanced Manufacturing Technologies (AMT) pathway, mandated by Congress, would decouple the product from the advanced manufacturing technology and expedite applications with a designated AMT.  

The creation of a product agnostic pathway is an important step toward the adoption of new manufacturing technologies. If implemented properly, the AMT Designation Program could help address the challenges currently facing the manufacturers and sponsors of CGTs, as there is a current imbalance in how CDER and CBER products are treated in the assessment of manufacturing. Current FDA policy does not allow a BLA to incorporate information about drug substances, drug intermediate or drug product through referencing a drug master file (DMF). DMFs are the main way that propriety information from contract manufacturers, or other third parties, can be shared with the Agency without having to disclose it to a drug sponsor. Recently, FDA finalized a rule that codified this practice in regulation.  

The law creating the AMT program specifically takes a different approach, and directs FDA to “allow the holder of an advanced technology designation, or a person authorized by the advanced manufacturing technology designation holder, to reference or rely upon, in an application submitted under Section 505 or Section 351 of the Public Health Service Act [emphasis added], including a supplemental application, data and information about the designated advanced manufacturing technology for use in manufacturing drugs in the same context of use for which the designation was granted.” 

This is a clear signal from Congress that the AMT designation is supposed to represent a new, forward-looking methodology to assess manufacturing technologies which the Agency has previously reviewed. However, the draft guidance states that, unlike an NDA, a BLA cannot incorporate a designated AMT by reference, and all information must be submitted in the BLA. If finalized as is, this program would not have the intended effect of spurring the development and adoption of new manufacturing technologies in the CGT field. Moreover, it would be contrary to Congressional intent of the program. ASGCT recommends that FDA correct this discrepancy between the law and the implementing guidance. For additional clarity, ASGCT also recommends that FDA amend the rule on DMFs to clarify that the restrictions do not apply to DMFs containing information on AMT-designated technologies.  

While the draft guidance is a useful primer for the AMT pathway, additional clarity is needed to ensure the pathway meets Congressional intent. In the Society’s comments to FDA, a request was made for explicit detail in sections in the final guidance outlining the requirements of the AMT Designation Program for CGT manufacturing technologies. 

For more information on ASGCT’s comments, read the letter here. 

Margarita is ASGCT's Director of Policy and Advocacy.

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