Process development is a crucial step in manufacturing a clinically and commercially viable therapeutic product.
The manufacturing of cell and gene therapy products is associated with specific challenges, including scale up and out, ensuring product quality, a changing regulatory, and the high cost of development and manufacturing. De-risking manufacturing processes and optimizing the protocols considering a phase appropriate approach (from pre-clinical to clinical and commercialization) will lead to a robust and reproducible process that meets the good manufacturing practice (GMP) design considerations and can smoothly transition into industrialized scale.
Different components of the manufacturing process including starting materials, the base technology, and final product requirements can all pose risks and challenges to the GMP manufacturing. Considering the best practices during process development, we propose starting with establishing a baseline process and identifying manufacturability gaps as well as Critical Process Parameters (CPP) and Critical Quality Attributes (CQA). The scope and extent of development can be adjusted depending on the customer needs through delivery of Lonza’s proprietary assessment tool. A comprehensive spectrum of development activities including process analytics and assays implemented or to-be-implemented in the manufacturing process will also be evaluated during the development phase to create a phase appropriate process: a current generation process versus next-generation process).
Once the baseline process is in place, appropriate bioprocessing and development studies need to be considered to establish a clinically and commercially viable process. These includes development of pre-defined unit operations and hold points, defining process specifications, and target criteria for early phase clinical trials and late clinical and commercial processes. Moreover, in process monitoring and controls are put in place for process robustness and quality assessments. The manufacturing process capacity, success rate and tolerance design for process limits based on quality attributes are also evaluated to ensure product stability and consistency.
Whether you are a small or large organization, ensuring process robustness for commercial manufacturing, collating supporting documentation for process performance qualification (PPQ) studies and biologics license application (BLA) filing, and identifying process and analytical gaps for commercial manufacturing are major steps that need to be considered during the development phase to prevent potential delays. It is critical to optimize the analytical methods and assays that are used as part of the decision making or release strategy as well as characterization of the product or intermediate products. Depending on the focus of the assays regarding the release, decision making or for information only, these analytical methods will be qualified or validated based on the standard guidelines and phase of applications.
Lonza’s Development Services capabilities specific to commercial manufacturing can support your journey to commercial readiness, through application of failure mode and effects analysis (FMEA) to risk assessment. Further gap analysis combined with FMEA can develop the scope of process characterization including process limit evaluation (PLE) studies. In addition to process characterization, assay validation studies would be necessary to assist the transfer of your process from preclinical and small scale – to commercial-scale.
The regulatory landscape
The timeline through clinical trial, approval and market can be compressed for gene therapies as they are expedited. Lonza can provide scientific advice as well as support in agency meetings and development of your regulatory strategy. During the clinical trial and BLA phase, benefit from detailed chemistry, manufacturing and control (CMC) information, summaries and reviews of sections of the filing as well as a partner in responding to regulatory agencies.
With 20 years of cell and gene therapy GMP experience and over 140 technical experts, Lonza has the flexibility to support small or large companies and provide regulatory support from pre-investigational new drug (IND) to commercialization.