Environmental monitoring (EM) is an important laboratory control that provides information on the cleanliness of the area where aseptic processing is executed. A stringent EM program is critical to the success of biological products such as cell and gene therapies (CGTs). This blog post will provide an overview of EM and some key considerations.
EM is performed routinely and during active manufacturing runs. The main goal of an EM program is to ensure that the facility meets the regulatory requirements for manufacturing of safe and effective products. EM will not provide a direct readout of batch sterility, but instead generates important information about the cleanliness of equipment and clean rooms, performance of air handling systems, effectiveness of cleaning operations, and whether proper aseptic technique is being used by personnel.
Understanding the Main Types of Environmental Monitoring Tests1. Viable particle monitoring aims to measure the amount of particulate matter containing microorganisms that can affect sterility.
- Active air sampling: Surface air system (SAS) equipment captures air and uses standard culturing techniques to test for the growth of microorganisms.
- Passive air sampling: The settle plate method is a passive air sampling technique where culture plates are exposed to the environment for a specified time prior to incubation.
- Surface testing: Any surface can be a home for microbial growth if not controlled by an efficient cleaning regimen. Swabs and contact plates are used to test surfaces throughout the facility for unwanted growth of microorganisms. Plates are incubated at 25°C for 3-5 days to test for fungal growth and at 35°C for 2-3 days to test for bacterial growth.
2. Non-viable particle monitoring, also known as total particulate monitoring (TPM), measures total particulate matter in the air and provides a way to classify clean rooms. In Canada and the U.S., the International Standard Organization (ISO) classification is the primary system used to classify clean rooms and is based on air cleanliness. ISO classification is assigned based on the number and size of particles per volume of air. Under ISO 14644-1:2015, clean rooms fall into four classes ranging from ISO 5 (“cleanest”) to ISO 8 (“dirtiest”). Clean rooms are also classified according to regional regulatory standards such as the European Union’s Good Manufacturing Practices guidelines. These guidelines classify clean rooms as Grade A (“cleanest”), B, C, or D (“dirtiest”), based on particles per cubic metre of air.
Working With a CDMO to Avoid EM-Related Manufacturing Delays
As with every stage in manufacturing, bottlenecks can occur in EM. A first step in avoiding them is to review facility-specific EM Standard Operating Procedures (SOPs) during a facility audit. When client and CDMO have a mutual understanding of the EM requirements, potential slowdowns can be spotted early. For example, supply chain issues that affect key materials needed to carry out EM (e.g. contact/settle plates) can delay required testing and effect manufacturing timelines.
Facility cleaning is another common reason for delays. The CDMO should communicate which party is responsible for cleaning (e.g. in-house staff or third-party vendors) and provide a timeframe for completing the work. If there is a delay, the CDMO should be transparent and provide suitable mitigations early on. The most important factor for a successful EM program that runs smoothly and does not introduce delays is an integrated team of experienced Sterility Assurance, Quality Assurance, and Operations personnel that work together to anticipate and avoid common challenges.
Contact us (firstname.lastname@example.org) to learn more about how our team can support the manufacturing of your CGT with a strong EM program.