New FDA Guidelines: Batch Uniformity and Drug Product Integrity / Advanced Manufacturing Technologies

In early January 2025, the U.S. Food and Drug Administration (FDA) announced the availability of two new documents.

Considerations for Complying with 21 CFR 211.110

The FDA explains that "this guidance, when finalized, will describe considerations for complying with the requirements in 21 CFR 211.110 to ensure batch uniformity and drug product integrity. In addition, this guidance discusses related quality considerations for drug products that are manufactured using advanced manufacturing. It also discusses how manufacturers can incorporate process models into commercial manufacturing control strategies."

The seven-page document opens with a concise introduction. The guidance is applicable to the manufacture of human drug products, including biological products, as well as animal drug products. However, it does not cover the manufacture of active ingredients. The background chapter sets a link to the use of advanced manufacturing and the use of process models as a part of commercial manufacturing control strategies.

The two main sections are titled:

• General considerations for in-process sampling and testing
• Additional considerations for advanced manufacturing and process models

Key aspects include:

• In-Process Sampling and Testing: Manufacturers are encouraged to develop scientific, risk-based strategies for sampling and testing at critical points in the manufacturing process. These steps ensure consistent product quality throughout production.
• Advanced Technologies: The guidance supports the use of real-time quality monitoring, process analytical technologies (PAT), and continuous manufacturing systems to streamline operations and improve efficiency.
• Control Strategies for Modern Manufacturing: The FDA emphasizes that while process models and advanced technologies are integral to modernization, they must be paired with in-process testing to ensure continued control and compliance.

This guidance is currently being distributed for public comment. Stakeholders are invited to submit their feedback by 07 April 2025. For further details and to download the document, visit the FDA's website.

Advanced Manufacturing Technologies Designation Program

The FDA has also announced the release of its final guidance for industry titled "Advanced Manufacturing Technologies Designation Program." This document finalizes the draft guidance of the same name, originally issued on 13 December 2023.

According to the FDA, "this guidance provides recommendations to persons and organizations interested in participating in FDA’s Advanced Manufacturing Technologies Designation Program, which facilitates the development of drugs manufactured using an AMT that has been designated as such under the program."

The 16-page document is organized into the following sections:

• Introduction
• Background
• AMT designation requests
• Benefits of AMT designation
• Questions and answers

Key benefits of the AMT program include:

• Early Engagement with FDA: Applicants gain access to early-stage discussions with FDA experts to address potential challenges in regulatory approval.
• Expedited Assessments: The program accelerates the review and assessment process for applications involving AMT-designated technologies.
• Improved Drug Supply and Quality: By integrating advanced control strategies, the program helps manufacturers meet demand for life-sustaining and critical medicines while minimizing quality risks.

The program highlights the importance of fostering innovation to enhance product quality and support the reliable availability of essential medications.

The full PDF document and additional details can be accessed on the FDA's website.