In the world of pharmaceutical manufacturing, the standard required of the environment is dictated both by regulatory obligations and production quality maintenance. Cleanrooms are specially designed spaces that provide the type of environment required for this type of production.
They are called cleanrooms because the space is free of microbes, air-bone particles, and any other contaminants, keeping them at levels that are acceptable for pharmaceutical processes. This is critical because if this environment is wrong, the end products will be wrong.
In this article, we will look at the planning and construction of these facilities. This is important because pharmaceutical cleanroom construction requires considerable attention to detail, an understanding of regulatory requirements, and the ability to translate design, material, and other components into a fully functional facility that meets the required specification. The process from conceptualization to completion must maintain the highest standards to ensure that they perform effectively when finally commissioned.
Successfully constructing any cleanroom, more so, one to be used for pharmaceutical work, requires that a clearly understood process or roadmap be implemented. Some important stages that must be understood for perfect implementation include:
· Classifications and Standards
· Design and Planning
· Material Selection
· Cleanroom Build-Out
· Environmental Control
· Testing and Validation
· Ongoing Maintenance
Let’s briefly discuss these stages so we have a better understanding of what they mean.
You cannot have a cleanroom if it does not meet the internationally accepted standards. Fundamentally, there is an acceptable level of airborne particles that a cleanroom must not exceed. There are nine cleanliness categories established under the ISO 14644-1 rating, which is where cleanrooms are categorized.
These nine cleanliness categories are based on the maximum amount of particles contained in a cubic meter of air. These are not arbitrary classifications but international benchmarks that give a clear understanding of the level of air purity offered under each classification and regulatory bodies like the FDA expect full compliance.
For example, a cleanroom with an ISO Class 7 categorization will have more particles (contaminants) per cubic meter of air than one with an ISO Class 5 classification. So, by understanding the different classifications, the cleanrooms can be better planned, and zones effectively created to allow for processes that require different ISO classifications to go on simultaneously.
You can find detailed information on these classifications here: https://www.m-pharmaguide.com/.
The first thing to be taken care of when constructing a cleanroom is the design. Without a well-laid-out design, a perfect execution will be impossible. At the most basic level, an ideal design must support a unidirectional workflow. This describes a workflow that moves from the lowest level of cleanliness to the highest level of cleanliness without compromising any of these controlled zones. Such a design will prevent contamination moving from and to the different zones and putting product integrity at risk.
As part of design planning, pressure differentials between zones are carefully determined. Usually, zones with higher cleanliness ratings have slightly higher pressure levels because this helps stop airborne contaminants from gaining access into these critical spaces. Additionally, planning takes into consideration the movement of materials and personnel, such that this movement does not introduce contaminants.
To this end, cleanrooms will often include airlock chambers, gowning areas, and separation spaces or barriers that act as transition zones to ensure that fewer contaminants get to the entry points. Equipment placement and routing of utilities, like HVAC systems, lighting, and electrical systems, must also be integrated into the design early so there are no conflicts that may affect the performance of the cleanrooms down the line.
As with other types of construction, the type of material used will have a major impact on the cleanliness, functionality, and durability of the cleanroom. For example, walls, ceilings, and floors must be made from smooth materials that are also resistant to cleaning and disinfecting chemicals
Some of the common types of materials preferred for these components include epoxy coatings, stainless steel, and special polymer panels. These materials are preferred because their particle generation is pretty low and they can take the harsh cleaning routines required in such spaces.
This is one of the most critical aspects of cleanroom construction. The level of cleanliness achieved in any cleanroom will largely be determined by the efficiency of the ULPA (Ultra-Low Penetration Air) filter or the HEPA (High-Efficiency Particulate Air) filters deployed. These filters have the ability to remove even micron-level particles, increasing cleanliness levels.
To ensure precise airflow patterns that allow for the channeling of airflow from one section to another, suitable HVAC systems are installed. These systems will also manage temperature, humidity, the rate of air change, and pressure differentials monitoring to ensure that the cleanroom performs efficiently in its designed classification.
At the completion of the construction, the cleanroom will not just be put to use. First, it will need to go through a series of tests to ensure that it meets the expected classification requirements. It will need to go through the following:
· Installation Qualification (IQ) - This verifies that system installation follows the design specifications.
· Operational Qualification (OQ) - This test confirms that every system is operating as intended.
· Performance Qualification (PQ) - Finally, this test will assess the cleanroom while it is operating as it would to ensure that it continues to meet the required standards under operational conditions.
A cleanroom is not just set up, and that's the end. There is a need for regular maintenance checks and re-certification. This is especially important after a major alteration has been carried out or after operating for about a year. These routine checks and recertification requirements are important to ensure it continues to perform as it should.
You can read this article for more information on how often a clean room needs to be recertified.
This article is not about building construction but about the process of carefully putting up a controlled environment where pharmaceutical processes can be safely carried out. This not only ensures that regulatory requirements are met, but that the lives of patients who are to benefit from the end products are protected.
Ensuring that the process of putting up these cleanrooms is as important as the quality of the products they produce. The process should therefore be handled only by experts who understand what is required and have the expertise to deliver at the highest level.
MBTpg