COLLABORATE WITH THE OUTSOURCING PARTNER
To select the right partner for media design and optimization, several key factors must be considered, with the most important being the collaborative nature of the supplier. It is essential that the biopharmaceutical company and supplier work together in a partnership, with full transparency to all data. This helps ensure that proper decisions are made to increase the likelihood of success when the manufacturing process is implemented. Another key consideration is the supplier's understanding of biopharmaceutical production process requirements and the media optimization strategy it uses. A methodical optimization strategy, specifically created for production cell lines and including Design of Experiments (DOE) is essential for an optimized formulation. The designed experiments must be coupled with a strong analysis of spent media to ensure a thorough understanding of the entire process.In addition, significant consideration should be given to the facilities that will be used for the optimization of the media formulation and subsequent media manufacturing. The facility should not only be able to supply the resources needed to perform the media optimization and to scale up production of the cell culture media, but also must satisfy rigorous quality and regulatory requirements that meet and even exceed the high standards required by the biopharmaceutical industry.
PRE-AUDIT THE FACILITY
When outsourcing cell culture media manufacturing, one must consider the facility itself as a critical component of the overall process. To ensure product consistency and performance, the facility must be pre-audited before manufacturing begins. There are several key attributes of a cGMP cell culture media manufacturing facility that one should assess. A high level of control of the raw materials, such as animal-origin information and strategic sourcing for reliable supply, along with a highly segregated process and personnel flow, are paramount. These should include a stringent animal-free raw material policy and complete segregation of all manufacturing areas, including personnel flow throughout the facility, as well as individual equipment suites with zoned HVAC systems to eliminate cross-contamination risk. The facility must include modular cleanroom systems with hardened PVC-coated walls and ceilings with cove transitions for ease of cleaning and full-viewing corridors that allow complete access to the facility without compromising room integrity. Automated clean-in-place (CIP) and steam-in-place (SIP) processes must be available as well as robust business continuity systems, including emergency utility back-up systems. The facility must have fully integrated cell culture media and supplement manufacturing capabilities with the ability to produce complete formulations for the full range of expression systems, including mammalian cell culture, microbial fermentation, and cell therapy.
The facility must be highly versatile with a fully scalable lot size capability including flexible packaging suites, that offer a wide range of filling capabilities and custom-packaging solutions. State-of-the-art milling technologies, such as pin mills, are preferable to ensure excellent particle size consistency, minimal heat generation, and easy cleaning using a CIP system with ultra pure water. Powder production must be highly versatile and fully scalable, offering a wide range of filling capabilities and custom-packaging solutions. In addition, the water used for liquids should be water for injection and USP-purified water to reduce bioburden and control endotoxin levels.