Cleanrooms in Sterile Pharmaceuticals
Cleanrooms are utilized in practically every industry where small particles can adversely affect the manufacturing process. They vary in size and complexity and are used extensively in industries like semiconductor manufacturing, pharmaceuticals, biotech, medical device and life sciences, also as critical process manufacturing common in aerospace, optics, military and Department of Energy.
A cleanroom is any given contained space where provisions are made to scale back particulate contamination and control other environmental parameters like temperature, humidity and pressure. The key component is that the High Efficiency Particulate Air (HEPA) filter that’s wont to trap particles that are 0.3 micron and bigger in size. All of the air delivered to a cleanroom passes through HEPA filters, and in some cases where stringent cleanliness performance is important , Ultra Low Particulate Air (ULPA) filters are used.
In cleanrooms, particulate concentration changes over time — from the development and installation of kit to its operational status. ISO has introduced three cleanroom classification standards: as-built, at-rest and operational.
as built : condition where the installation is complete with all services connected and functioning but with no production equipment, materials, or personnel present
at rest : condition where the installation is complete with equipment installed and operation during a manner agree upon by the customer and supplier, but with no personnel present
operational : condition where the installation is functioning within the specified manner, with the required number of personnel and dealing within the manner prescribed
Positive Pressure
Cleanrooms are designed to take care of positive pressure, preventing “unclean” (contaminated) air from flowing inside and less-clean air from flowing into clean areas. the thought is to make sure that filtered air always flows from cleanest to less-clean spaces. during a multi-chambered cleanroom, as an example, the cleanest room is kept at the very best pressure. Pressure levels are set in order that the cleanest air flows into spaces with less-clean air. Thus, multiple pressure levels may have to be maintained.
A differential atmospheric pressure of 10–15 pascal is suggested between spaces. so as to make sure that pressure differentials remain constant when doors are opened, or other events occur, control systems must be in situ .
Laminar and Turbulent Air Flow
ISO 5 / Grade A / Class 100 and cleaner facilities believe unidirectional, or laminar, airflow. Laminar airflow means filtered air is uniformly supplied in one direction (at a hard and fast velocity) in parallel streams, usually vertically. Air is usually recirculated from the bottom of the walls copy to the filtering system.
ISO 6 / Grade B / Class 1,000 and above cleanrooms generally utilize a non-unidirectional, or turbulent, airflow. this suggests the air isn’t regulated for direction and speed. The advantage of laminar over turbulent airflow is that it provides a consistent environment and prevents air pockets where contaminants might congregate.
Required Testing (ISO 14644–2)
These are following test to be performed for qualification of unpolluted rooms;
Particle Count Test
Air Pressure Difference Airflow
Installed Filter Leakage
Containment Leakage
Recovery
Airflow Visualization
Microbial Monitoring (Refer EU GMP Annex — 1, USFDA guidelines Aseptic Processing — September- 2004, USP 1116)
Cleanroom monitoring on regular basis:
First identify what the risks are for product and process. Also, it’s got to understand the planning intention of the cleanroom. this is often necessary, as we would like to settle on the proper instrument for the appliance. a category 10,000 (ISO Class 7) cleanroom wouldn’t be monitored effectively with a 0.1 micron. Using a 0.3 or 0.5 particle counter would be a far better choice.
Determine critical locations (locations where contamination can have an impact on the merchandise or an outsized number of products)
Determine busy locations (locations where the merchandise is moving or being manufactured).
Make an assessment of the cleanroom particle data during the operational state. Collecting data within the operational state (when manufacturing is really occurring) is vital to work out the locations where you’re in danger .
A contamination monitoring system are going to be ready to track, record and alarm when out of control limits are reached and/or exceeded.
Common audit observation on clean rooms in pharmaceuticals:
Smoke study has not been performed adequately. Actual aseptic interventions haven’t been simulated in dynamic phase.
Filter integrity test not been performed on regular basis. No data available for filter integrity test.
Environmental monitoring; settle plate, contact plate, personnel monitoring, air sampling for viable and non-viable count not been performed for each batch manufacturing duration. data aren’t available for non-viable particle count. Environmental monitoring weren’t performed during media fill.
Pressure differential not monitored; suitable instrument (pressure gauge) isn’t installed for monitoring.
Door aren’t capable enough to carry the pressure. Air balancing not performed adequately.
The aseptic area wasn’t sanitized with a validated disinfectant.
HVAC breakdown isn’t simulated during the media fill run.
Non-sterilized tools were utilized in the aseptic area.
Equipment utilized in manufacturing, processing, packing or holding of products aren’t located adequately to take care of uninterrupted airflow.
Cleanrooms in pharmaceuticals are considerably required to take care of aseptic conditions required to the manufacturing of Sterile medicines. Therefore, it’s very essential to satisfy the regulatory requirements and proposals. Join on telegram
