Senior Manufacturing & Operations | BrevisRefero
Transitioning a manufacturing process from non-Good Manufacturing Practice (non-GMP) to Good Manufacturing Practice (GMP) is a significant endeavour and a resource intensive activity for any biopharmaceutical company. This shift is often driven by the progression of a product from early-stage development, where non-GMP material is sufficient for preclinical studies, to later stages that require GMP-compliant material for human clinical trials and eventual commercialization. This transition is not simply a procedural change; it encompasses a strategic overhaul involving substantial planning, financial investment, and a fundamental shift in both organizational mindset and operational processes. The transition may involve either transferring a process from process development to manufacturing or relocating the process from one facility to another, whether in-house or with a Contract Development and Manufacturing Organization (CDMO). In the following discussion, the focus will be a three-phase technology transfer approach between Sponsor and CDMO, emphasizing the need for a holistic, carefully planned approach to GMP manufacturing.
"A successful technology transfer requires diligent planning, open and transparent communication, teamwork, and proper documentation, executed with a team of Subject-Matter Experts (SMEs) who can navigate potential risks and challenges."
Phase I: Technology Transfer
With your GMP CDMO chosen, the first key phase is development of a comprehensive technology transfer document, often led by an appointed Project Manager. Technology transfer refers to a process of transferring the scientific knowledge, process details, Critical Process Parameters (CPP), Critical Quality Attributes (CQA) and analytical methods required to manufacture and test a product in compliance with regulatory standards and the predefined product specifications. A successful technology transfer requires diligent planning, open and transparent communication, teamwork, and proper documentation, executed with a team of Subject-Matter Experts (SMEs) who can navigate potential risks and challenges. Below is a breakdown of critical steps that establish a technology transfer process, providing a high-level understanding of the essential components involved.
Assessment of Drug Development: Evaluate the current state to ensure that process development has accounted for variations within the process and identified areas or gaps that need improvement to achieve a robust and consistent GMP process.
Planning: Although not all encompassing, to develop a comprehensive plan for technology transfer, it is essential to follow a structured approach. First, establish clear and well-defined objectives and allocate the necessary resources such as SMEs, equipment, time, and a budget. Second, create a communication plan that promotes open and transparent communication among all stakeholders involved in the technology transfer process. This plan should outline how information will be shared and distributed to ensure alignment among all stakeholders. Additionally, a documentation strategy should be established, specifying the types of documents that need to be generated, reviewed, and maintained throughout the technology transfer process. Leveraging collaborative document platforms can enhance efficiency in managing these documents and supporting knowledge transfer. Lastly, it is important to anticipate potential roadblocks and challenges that may arise during technology transfer and developing contingency plans will address these issues quickly and effectively.
Data Collection: Document all processes and procedures used in the non-GMP manufacturing environment. This includes detailing the raw material and consumable requirements, CQAs, CPPs, analytical method transfers, equipment specifications and operating variables. This extensive data dump of information will serve as the foundation for drafting detailed Standard Operating Procedures, process descriptions, as well as records for solution and buffer preparation, and of course the Master Batch Records.
Quality Management System (QMS): A resilient QMS is at the heart of GMP manufacturing. Transitioning to GMP requires the manufacturing process to come under the umbrella of documentation control, change control, risk management, vendor qualification, preventative maintenance and calibration program, raw material testing and a system for handling deviations and investigations. Refer to “How to Effectively Engage with your CDMO to Release a Clinical GMP Lot”. (LINK)
Equipment and Facility Qualification: GMP manufacturing demands a higher standard of equipment and instrumentation, capable of precise control and monitoring of biomanufacturing conditions. In some cases, a Sponsor may require dedicated or specialized equipment for their process. The timeline to acquire, install, commission, and qualify any additional Sponsor equipment will need to be factored into the overall technology transfer timeline.
"Overall, while scale-up and engineering runs can present challenges, they are a critical step in the technology transfer process."
Phase II: Scale-up and Engineering
The second key phase in the technology transfer process is often referred to as scale-up or engineering. These activities are critical in preparation for GMP manufacturing and designed to demonstrate process equivalency and product quality at larger scales of manufacturing.
Despite best efforts in developing a bulletproof technology transfer plan, it is common to encounter issues during scale-up and engineering. These issues may arise due to differences in equipment, raw materials, processing timeframes, product instability or other factors that can impact the process performance or product quality. In certain instances, these issues may require further process modifications and additional process development work.
Overall, while scale-up and engineering runs can present challenges, they are a critical step in the technology transfer process. By actively addressing issues and continuously refining the process during this phase, the Sponsor can reduce delays and costs, thus enhancing a successful transition to GMP manufacturing for clinical supply.
"It is essential to take a stage-gate approach with a conscience decision to proceed from non-GMP to GMP manufacturing by assessing technology transfer, development, and scale-up outcomes."
Phase III: GMP Manufacturing
Finally, once prepared a Sponsor and CDMO are ready for GMP manufacturing…or are they? It is essential to take a stage-gate approach with a conscience decision to proceed from non-GMP to GMP manufacturing by assessing technology transfer, development, and scale-up outcomes. An effective stage-gate process streamlines the final steps and provides insights to enhance performance, communication, productivity, and collaboration for the transition to GMP. Additionally, it serves as a valuable tool for optimizing strategies in future activities with the CDMO as the Sponsor transitions through clinical trial phases.
In summary, a three-phase technology transfer approach is essential to carefully assign and monitor critical resources and meet established objectives, starting with the development of a comprehensive technology transfer document, followed by successfully demonstrated scale-up engineering batches, and ending with a successful GMP manufacturing run to enable clinical supply.
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Senior Manufacturing & Operations | BrevisRefero