CMC Considerations for Complex Site Transfer Planning and Collaborating with Receiving Sites

Technology transfer involves transferring one or more pharmaceutical or biopharmaceutical manufacturing activities from a current site (sending site) to a proposed new site (receiving site). It is considered a natural phase of a pharmaceutical/biotechnology drug's lifecycle and may occur as a drug moves from research and development to commercial manufacturing or when additional manufacturing capacity is required by either bringing a new facility on-line or transferring production to another site or even another country (1, 2).

Ultimately, the goal of technology transfer is to meet global product supply demands while ensuring that a product continues to meet established/registered quality standards and critical quality attributes (CQA) when manufactured at different sites (1). According to Rob Baker, MS Director, Chemistry, Manufacturing and Controls at Cardinal Health Regulatory Sciences, “The early stages of technical transfer success are rooted in the meticulous definition of scope through a comprehensive evaluation of capabilities between sending and receiving sites.”

Getting Started

A first step in any technology transfer project is to form a dedicated project management team. Typically, project management teams are composed of qualified personnel from both the sending and receiving sites (1). To ensure a successful product technology transfer, it is vital that personnel from all affected departments and transfer functions are represented on the project team. Further, the respective roles and responsibilities of project team members should be clearly defined and individual activities/action items should be tracked and documented. “A cross functional team, composed of subject matter experts (SME), forms the backbone of this process, ensuring that the intricate dance of manufacturing, packaging analytical stability and regulatory expertise harmoniously orchestrates the transfer of knowledge and processes,” said Baker.

Once the project team is assembled a project manager is typically assigned to coordinate knowledge transfer activities, track action items/milestones and serve as the “point person” for communications between the sending and receiving sites.

One of the major activities of the project team is to craft a technology transfer document known as the project technical package (PTP). This document is a roadmap to implementing technology transfer between sending and receiving sites. It will contain all information pertaining to the manufacturing process including process development documents, process controls, critical process parameters (CPP), change control, product quality standards, stability testing, compatibility studies, qualification documentation, validation reports, and detailed analytical methods (3,4).

CMC Considerations in Technology Transfer

Regulatory compliance

During technology transfer it is critically important to adhere to regulatory requirements and standards governing CMC activities such as analytical methods, Current Good Manufacturing (cGMP) and any currently approved regulatory filings (4,5). All regulatory filings must be thoroughly reviewed during transfer to ensure that all documentation is up-to-date and compliant with mandated regulatory standards.

Facility fit assessment

A facility fit assessment typically includes an evaluation of the technological equivalency of manufacturing equipment at both the sending and receiving sites (4). Also included is an evaluation of manufacturing capabilities, process controls, analytical methods requirements, materials selection, and architectural facility design of the receiving site. An accurate facility fit assessment typically requires a complete and thorough understanding of the transferred manufacturing process, product characteristics and CQA.

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References:

1. Bender J. Brundidge B. Role of the regulatory CMC in pharmaceutical site technical transfers. Regulatory Focus.org 2023:1-11
2. Mayne J Kahn D, Youchak, BG Technology transfer of manufacturing processes: best practices 2016 https://ispe.org/pharmaceutical-engineering/ispeak/technology-transfer-manufacturing-processes-best-practices Accessed March 2, 2024
3. Pinto L. Addressing the key pitfalls hindering technology transfer success. Pharmaceutical Technology Europe, 2022: 46:30-33 https://www.pharmtech.com/view/addressing-the-key-pitfalls-hindering-technology-transfer-success Accessed March 2, 2024
4. Alexander P, Ramsey P. Essential elements of technology transfer. 2023. Bioprocess online https://www.bioprocessonline.com/doc/essential-elements-of-technology-transfer-0001 Accessed March 2, 2024
5. Khedir D, Bouslah D. Navigating Regulatory Guidelines for effective tech transfer 2023 https://www.outsourcedpharma.com/doc/navigating-regulatory-guidelines-for-effective-tech-transfer-0001 Accessed March 2, 2024

Featured Experts

Rob Baker, MS

Director, Chemistry, Manufacturing and Controls
Cardinal Health Regulatory Sciences

Erika Laws, MS

Director, Chemistry, Manufacturing and Controls
Cardinal Health Regulatory Sciences