Top 5 cGMP Facility Considerations
Cellular therapy products for use in the clinic, especially those for use in clinical trials, are increasingly manufactured using cGMP regulations in clean room facilities. cGMP refers to the Current Good Manufacturing Practice regulations enforced by the FDA. cGMPs ensure proper design, monitoring, and control of manufacturing processes and facilities. While there are many other considerations to think about when choosing the right cGMP partner, the design of the facility to control operations, careful consideration of the type of products, the stage of manufacturing, the flow and the HVAC requirements is an excellent place to start to assess.
Facilities- In deciding where processing should occur, the organization must consider the risk of contamination to the product during manufacturing. Greater risk requires a more restricted environment. Facilities for working under cGMP conditions can take many forms in which there can be aseptic processing:
- In a biological safety cabinet in an unrestricted lab where personnel basically wears street clothes.
- In a room with restricted access where personnel gowns up to protect products from contamination, but airflow is not controlled.
- In a certified clean room in which access is restricted, personnel is gowned up, and the lab environment is strictly controlled, including controls on air flow and active monitoring for contamination.
Products-Consider the type of product to be manufactured:
- Products manufactured in closed systems, where transfer bags and tubing are used have much lower risk of contamination than those using open, cell culture processes, even when performed in the biological safety cabinet.
- A lengthy, all day or multi-day process incurs greater risk than a short process, and each time a product is removed from an incubator to check cell growth or change media, risk increases.
Scale of manufacturing-Consider the scale of manufacturing. Is the facility licensed for commercial production or limited to early-stage clinical trial products? While cGMPs are expected throughout clinical studies, the level of control and validation will vary depending on the process and likely to increase as products move from one phase to the next.
- A focus on early stage clinical/investigational products will mean manufacturing many different products and frequent turnover of projects.
- Commercial or late stage manufacturing will mean consistently making the same product(s) most of the time.
- Products for multiple patients may need to be manufactured concurrently instead of consecutively. Thus more space, personnel and equipment are needed. Equipment should not really be shared between products or types of products and dedicated equipment requires more equipment for more products.
- In a facility with frequently changing projects different equipment might be needed from project to project and the expense and space must be considered.
- In a commercial production facility, the type of equipment is likely unchanging as the process and resultant product must be consistent.
Flow-Consider the flow. The flow of material and personnel is designed to control the manufacturing environment. The flow:
- Should maximize efficiency and minimize potential for product mix-ups. Ideally there is a unidirectional flow of personnel and processed material, including a changing room for personnel to change into scrubs before gowning and entering the lab and exit through a de-gowning room so personnel aren’t passing back into the clean gowning area when exiting.
- Should have designated adequate and separate areas for various activities including receipt and storage of materials and reagents, testing, and manufacturing processes.
HVAC System-Consider the HVAC system. What is the risk of contamination?
- If the risk is low, HEPA-filtered air in biological safety cabinets where critical manufacturing steps occur may be sufficient.
- For open processes, such as cell culture, HEPA-filtered air may be necessary throughout the entire lab.
- The optimal air-exchange rate varies, depending on factors such as:
- The number and frequency of personnel entering and exiting each day, effectiveness of the gowning protocol, manufacturing processes for lab projects, and lab equipment.
- The level of outside contaminants possibly entering the facility versus the level of contaminants being generated inside the lab during processing.
- Lower air-exchange rates result in smaller fans
Creating a cGMP facility from an existing laboratory, or from scratch can be an expensive, time consuming endeavor. Instead, choosing the right cGMP partner does not have to be. CCS is one of the few organizations that can provide in-depth service, expertise and support for your cGMP needs via in-house manufacturing or consultation and we take careful consideration of the current and potential needs for your organization and for the industry.