Unleashing Innovation: The FDA’s Advanced Manufacturing Technology Designation

  Introduction:

In this era of technological revolution, the pharmaceutical and medical device industries are at the forefront of embracing cutting-edge innovations. The Food and Drug Administration (FDA) acknowledges the pivotal role that Advanced Manufacturing Technologies (AMT) play in shaping the future of healthcare. This blog post delves into the significance of the FDA’s Advanced Manufacturing Technology Designation. The main objective is shedding light on how this initiative catalyzes innovation within the industry.

As for the definition of AMT, it includes any innovative pharmaceutical manufacturing technology or approach that would potentially improve the reliability, safety, and robustness of manufacturing. Moreover, it would increase the demand in the supply chain for small molecules or biological drugs. AMT potentially benefits patients by improving the demand for manufacturing and supply chain.

Applications in Medicine:

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Section 21 USC 356L :

Section 21 USC 356L introduced in the Food and Drug Omnibus Reform Act of 2022 (FDORA). It was amended on December 29, 2022, in the FD&C Act section 506L Chapter V Drug and Devices. The assessment of requests for AMT designation involves a thorough review by a team of FDA experts specializing in quality assessment.

Their evaluation focuses on scrutinizing the data and information provided. The main objective is to determine whether the manufacturing method or combination of methods aligns with the criteria outlined in section 506L of the Food, Drug, and Cosmetic (FD&C) Act. Upon the successful granting of AMT designation, subsequent applicants for new drug applications (NDA), abbreviated new drug applications (ANDA), or biologics license applications (BLA) are permitted to utilize or refer to the designated AMT.

It is essential for these applicants to explicitly specify the application of the designated AMT about their product development. This information should be included in the submissions detailing the development and manufacturing processes for NDA, ANDA, or BLA.

Designation Request:

According to this section, the Secretary must institute a procedure for designating methods of manufacturing drugs. This includes biological products and their active pharmaceutical ingredients, as advanced manufacturing technologies. A manufacturing method or combination qualifies for advanced manufacturing technology designation if it incorporates a novel technology or innovatively employs an established technique or technology. This innovation must significantly enhance drug manufacturing while ensuring equivalent or superior drug quality. This improvement may manifest through:

Reduced Development Time:

The designated manufacturing method should decrease the time required for drug development.

Increased or Maintained Supply:

The manufacturing method should enhance or sustain the supply of drugs. Particularly those that are crucial for life support, life-sustaining, or of critical importance in healthcare. Additionally, it should address the drugs listed under section 356e of this title that are currently facing shortages.

Evaluation and designation of an advanced manufacturing technology:

1. Submission:

An individual seeking the designation of a manufacturing method as an advanced manufacturing technology under this section must submit pertinent data. Alternatively information can be submitted illustrating that the manufacturing method aligns with the criteria outlined in subsection (b) within a specific context of use to the Secretary. The Secretary has the authority to assist in the development and evaluation of such data or information by:

A) Timely Guidance:

Providing timely guidance and engaging in interactive communication with the individual regarding the manufacturing method’s development.

B) Involving Senior Managers and Seasoned Personnel

Involving senior managers and seasoned personnel from the FDA is suggested. It can be done in a collaborative and cross-disciplinary assessment of the manufacturing method, as applicable.

2. Evaluation and Designation:

As per paragraph (1), within 180 calendar days of receiving a request, the Secretary must determine whether to designate the manufacturing method as an advanced manufacturing technology within a particular context of use. This decision is based on thoroughly examining the data and information submitted under paragraph (1) and assessing how well the manufacturing method aligns with the criteria outlined in subsection (b).

Documents for Submission:

The AMT request must be designated and include data or information demonstrating the improvements in the methods being introduced in the context. This request must exhibit the capacity of the proposed AMT to significantly enhance the drug manufacturing process while preserving or enhancing its quality. Also, this improvement should encompass aspects such as reducing drug development time or increasing and sustaining the supply of a drug. Furthermore, the request must demonstrate how the proposed AMT achieves these objectives while maintaining or improving the quality of the drug. This includes drugs that play critical roles in life support, are life-sustaining, essential for providing healthcare, or are currently experiencing shortages. The risk levels should be minimal, and these data and information can be added to a marketing application.

Documents to Include:

• A brief description of the manufacturing method or production route applied for AMT designation where the novel technology is used.
• A brief description of the manufacturing process with the combination product, which should contain the following:

1. 1. An outline of the steps of the proposed AMT, including the overall manufacturing information.
   2. A brief description of the process, controls, quality information, and proposed critical steps and risk management procedures.
   3. Developmental data and information for the proposed AMT that evaluates and justifies the use context.

• The context in which the proposed AMT will be used in drug development. For the formulation, Dosage, and class of drug that is being submitted.
• Identified obstacles in the regulatory, technical, or other spheres that may hinder the successful implementation of the proposed AMT.
• The timeline for the AMT approval request and drug development activities for the proposed designation.
• Description of any previous engagement with ETT/CATT if applicable.

• A request for designation of an AMT intended for use in manufacturing an existing drug that is either a Critical Drug or on the FDA’s drug shortage list should also refer to the existing drug application and data showing that the proposed AMT will increase or maintain the drug’s supply and quality.

AMT Request:

You can submit the AMT request to the FDA via the email address AMT_designation_requests@fda.hhs.gov.

AMT designations are typically confined to manufacturing methods meeting the criteria outlined in section 506L(b) of the FD&C Act and section III. A team of FDA experts from the relevant jurisdictional center evaluates eligibility, reviewing data and information in the request. This team, including ETT or CATT members where applicable, assesses the proposed AMT’s alignment with designation criteria. For cross-center impact, a cross-disciplinary team involving members from CDER and CBER evaluates requests. The designated lead, with expertise in the manufacturing process, guides the review process and facilitates communication with the requestor. FDA aims to complete AMT designation determinations in writing within 180 calendar days of receiving the request. Section 506L(e)(2) of the FD&C Act includes the details. Submission of an AMT designation request does not guarantee acceptance, with incomplete or non-compliant requests likely facing denial.

Benefits:

This process may involve collaboration with the appropriate FDA quality assessment team in certain instances. FDA anticipates prioritizing applicant interactions to discuss using a designated Advanced Manufacturing Technology (AMT) in drug development or commercial manufacturing. Certain activities will get a higher priotity, such as drug development activities and applications utilizing a designated AMT with the potential for significant improvements in product quality, addressing known quality issues, or addressing drug shortages.

Consideration for prioritization may extend to drug development activities and applications accepted into other expedited programs. They manage the interactions for NDAs, BLAs, and ANDAs involving complex generic drugs under the relevant user fee meeting type.

The applicant determines the frequency and timing of these meetings based on the drug’s development stage. Controlled correspondence is the usual channel for ANDAs. It does not involve complex generic drugs, but applicants with a designated AMT can also request product development and pre-submission meetings. The designated lead for the AMT request will facilitate any additional necessary interactions. Utilizing existing tools and resources, the designated lead will provide advice and information pertinent to product quality. This leads to supporting the successful integration of the designated AMT. The designated lead will connect applicants with other FDA disciplines beyond product quality when necessary. 

References:

• Research, C. F. D. E. A. Advanced Manufacturing Technologies Designation Program. U.S. Food And Drug Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/advanced-manufacturing-technologies-designation-program
• Advanced Manufacturing Technologies Designation Program; Draft Guidance for Industry; Availability; Agency Information Collection Activities; Proposed Collection; Comment Request. Federal Register. https://www.federalregister.gov/documents/2023/12/13/2023-27309/advanced-manufacturing-technologies-designation-program-draft-guidance-for-industry-availability
• 21 USC 356l: Advanced manufacturing technologies designation program. (n.d.). https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section356l&num=0&edition=prelim
• ICH Q8 (R2) Pharmaceutical development – Scientific guideline | European Medicines Agency. (2009, January 6). https://www.ema.europa.eu/en/ich-q8-r2-pharmaceutical-development-scientific-guideline

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