One of the important topics in the pharmaceutical and biotech industry or actually in the entire production industry is contamination control.
Since our customers are patients, we need to be extra careful and ensure that these vulnerable customers do not have contaminants in their medication.
Companies should do their utmost best to keep contamination contained. Which means that a contaminant should not enter a production line. You need to ensure that you have closed systems. But is there a system which is truly closed? All systems are open in a certain way.
This is why the GMP’s are full of requirements for controlled environments surrounding production. If you have multiple production suites in one facility, you have to make sure that contaminants do not transfer between your GMP production suites.
GMP facility design
This should be controlled. And there are many ways to control that. To start, you need to have a properly designed facility. And for that you need to fully understand your GMP manufacturing strategy, your GMP manufacturing strategy will be derived from the processing of your product. So that means that even before you start working on your manufacturing strategy, your production process should be nailed down to the smallest details. This prevents you from accidentally skipping a step when you’re assessing your contamination control measures.
Cleaning & zoning
Once you’ve laid the groundwork it’s time to assess your cleaning. When you use production equipment, production vessels, or production glassware you have to clean it at some point, no way around it. So once you have mapped your production process, the next step is to look at your manufacturing strategy. In other words, what happens at each step? Do the materials transfer from a bottle to a container? What are my tolerances? How many bottles do I need? Etc. You need to map the pipeline and it’s attributes.
This detailed analysis is skipped quite often by GMP manufacturers. This usually means that your contamination control strategy will be incomplete. Although it may be complete, but then it’s more luck than science. It’s much better to have a consistent, systematic approach to your manufacturing strategy.
But how do you actually segregate GMP production rooms from one another?, and how do you control the people enter the rooms for example? There are multiple solutions. The concept of a clean corridor, the concept of personal airlock and the concept of dynamic ballot boxes, etc. are all possible options.
Exposure to the environment
To use any of these solutions, you need to understand what will actually be exposed to the environment. Exposure might be limited, but if you’re producing viral, microbial or just cell lines (which are active, not inactivated), incidents may occur at any time. Simply put, you cannot consider a system closed. You’re making connections between steps that expose the product to contaminants. All these steps should be taken into consideration.
The third steps is cleanroom / zoning. You have to classify zones. Where there is an active material the zone should be considered “active”. When there’s dust, it’s a “dusty zone”. If you have a cleaning activity in a certain area, you produce a lot of particles, so that should be segregated at all cost. Once you have done that, then you go to the next step. How do I segregate that zone from other zones? That’s the concept of zoning by contaminants.
Another zoning concept to consider is aseptic zoning. All major agencies have excellent guidelines on that; the WHO, the EU GMP and the U.S. FDA can all be checked for reference. They do not only dictate GMP zoning/GMP facility requirements, but they detail requirements for personnel as well, how should they dress up for example.
How strict should they be dressed? And how do I control the gowning? Well, the guidelines are dictating in this case that you need to do environmental monitoring not only for the rooms, but for personnel as well. If you want to pass those requirements, careful consideration should be taken for the gowning of your personnel. We have a lengthy article on the qualification of cleanroom operators which you can find here: https://pcs-nl.com/blog/qualification-of-aseptic-operators-in-gmp-environments/