From: National Research Council Canada
June 15, 2022 - Montréal, Quebec
The Biologics Manufacturing Centre is one step closer to being ready for Health Canada inspection, which is needed before the facility can receive a drug establishment licence. After months of preparation, the team recently completed the requirements for the qualification for the facility's heat, ventilation and air conditioning (HVAC) system.
Commissioning, qualification and validation is required to prove that all of the activities used to produce vaccines consistently meet the strict requirements for compliance with good manufacturing practices (GMP). This meticulous, time-consuming testing and analysis is critical to ensuring the Biologics Manufacturing Centre meets the highest standards for vaccine production.
A significant part of this includes demonstrating that the conditions inside the facility are consistently optimal for safe production. The process of testing these conditions is called performance qualification. To complete this process, the HVAC system needs to go through 3 static (at rest) test periods and 3 dynamic (in operation) test periods.
During each test period, all specified locations are sampled and analyzed for particulate and microbial counts, temperature, humidity and pressure. Static testing involves checking everything in the clean rooms for dust, mold and other particulates. Experts place settle plates (like petri dishes) at various locations around the clean room and then they literally wait for the dust to settle. Analysts then run tests on the contents to see how many micro-organisms would be found during normal operations in these rooms.
They are looking for 2 types of particles. Non-viable particles are non-living things like dust and fibres from clothing. Viable particles are living organisms like bacteria and mold. There are strict allowable limits for each type of particle in a clean room.
The HVAC system might be able to produce perfect environmental conditions for an empty clean room. But that wouldn't accurately reflect the real conditions during vaccine production, when people will be inside the clean rooms working, talking and moving around. The presence of people and their actions will have an impact on the environmental conditions, which is why the qualification process for the HVAC system also requires dynamic performance qualification.
The obvious question is how do you accurately test the environmental conditions during vaccine production, when the facility is not yet producing vaccines? The solution: biomanufacturing experts role-play their jobs.
After following the precise gowning and cleaning techniques, the exact number of people who work in the clean rooms "perform" their exact activities in accordance with the standard operating procedures to simulate the exact conditions, as if they were producing a real vaccine.
Precise choreography is required to ensure the tests exactly mimic real-life conditions, and that the particulate count will represent what would be found during actual vaccine production. Many independent systems and processes, like the HVAC system, need to be operating in precisely the right way at the right time.
The team needs to be gowned, a complex process on its own, involving multiple air-locked doors between classified and non-classified areas. The equipment for production and sampling needs to be prepared. Even the cleaning needs to be timed perfectly so consistent testing can be done at varying intervals, various times of day and different days of the week.
Asking highly skilled experts to simulate the vaccine production process may sound unnecessary, but this performance must be carried out with absolute precision, because any significant variation in the results is likely to trigger an internal investigation and documentation of the root cause. The qualification team would then need to propose, evaluate, approve, implement and document corrective action, and then the testing would need to start over again.
The dynamic performance qualification process for the HVAC system must be repeated 3 times with the testing plates rotated frequently to ensure all the areas have been tested and the conditions inside the clean rooms are consistently maintained.
Experts at the Biologics Manufacturing Centre completed the testing of the HVAC system in the clean rooms earlier in spring 2022. The dynamic performance qualification included testing 5,070 samples from 2,325 surfaces in 1,160 sampling locations.
In addition to surface testing, they also placed small probes, called data loggers, throughout the room during static and dynamic testing periods to regularly sample room temperature, humidity and pressure levels to ensure consistency over time.
Every step, every test and every result from the static and dynamic performance qualification is meticulously recorded by the biomanufacturing experts as part of the overall commissioning, qualification and validation process for the Biologics Manufacturing Centre. This is required before Health Canada will issue a drug establishment licence for the facility.
Read the other stories in this series to learn more.
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