Contamination control practices are an essential element of working within cleanroom environments and have never before been so vitally important as today. Cleanrooms provide contamination-free and temperature-controlled room facilities in different industrial environments and aims to protect patients, products and processes against contamination of any sort.
High-end sophisticated research involving highly sensitive chemicals mixed to react at standard conditions definitely needs cleanrooms that provide suitable environment and conditions.
Since in medicine, a slightest contamination may result in loss of function, reliability, medical compatibility or other essential quality characteristics, the pharma cleanrooms aim to minimise the number of particles released by humans and equipment and eliminate them immediately.
Cleanroom technology is essential to safeguard the product at various stages such as in the filling of pharmaceutical dosage containers as well as for the worker’s safety who handles potent drugs. Asian pharmaceutical industry is widely adopting mini-environment technology after the US, with Europe being the foremost in implementation.
Contamination control is the generic term for all activities aiming to control the existence, growth and proliferation of contamination in certain areas. Contamination control may refer to the atmosphere as well as to surfaces, to particulate matter as well as to microbes and to contamination prevention as well as to decontamination
The aim of all contamination control activities is to permanently ensure a sufficient level of cleanliness in controlled environments. This is accomplished by maintaining, reducing or eradicating viable and non-viable contamination for either sanitary purposes or in order to maintain an efficient rate of production.
Cleanrooms are designed to provide control of environmental factors including:
- Viable and non-viable airborne particles
- Air flow patterns
- Temperature and humidity
- Air pressure differential
- Containment of hazardous aerosols
Applications include the manufacture of sterile and non-sterile pharmaceutical and biotech products, medical devices and implants.GMP requirements from the different Boards of Health, including the US Food and Drug Administration (FDA), for sterile pharmaceutical, biotech, medical devices and implants require the manufacture of these products are performed in clean environments that meet the requirements of standards such as ISO EN146441.
There are many preventive procedures in place within a cleanroom environment. They include subjecting cleanroom staff to strict clothing regulations, and there is often a gowning room where the staff can change clothes under sterile conditions so as to prevent any particulates from entering from the outside environment. Certain areas in the cleanroom have more stringent measures than others: packaging areas, corridors, gowning rooms and transfer hatches incorporate strict contamination control measures in order to maintain cleanroom standards.
There are many possible sources of contamination of the cleanroom environment. Equipment, structures, and surfaces can generate particles through friction, heat, exhaust, outgassing, and static electricity. Incoming production components may introduce contaminants. Still, it is the people working in the cleanroom that generate the most particles.
Of the many elements of cleanroom operations and processes, humans are the easiest to control, yet contribute the most contamination.
While non-particulate contamination is a concern in many applications, the fundamental aspect of the cleanroom environment is an effective cleanroom management program that keeps the environment free of airborne particles.
As cleanroom operators are working, they generate millions of particles with every movement. Schlieren thermal images show particles emitted from the human body. Particles migrate up through the cleanroom apparel toward the head and fall down the legs during cleanroom activities.
Bacteria, molds and yeast are viable organisms which are chemically active. Byproducts of their growth and replication can cause a variety of contamination in the cleanroom, based on the nature of the chemicals released during generation. Humans also release elemental chemicals that can cause contamination:
Spittle: potassium, chloride, phosphorus, magnesium, and sodium
Dandruff: calcium, chloride, carbon, and nitrogen
Perspiration: sodium, potassium, chloride, sulphur, aluminium, carbon,
and nitrogen
Fingerprints: sodium, potassium, chloride, and phosphorus
Things needed for effective contamination control
These are the things that need to be considered when building an effective contamination control room.
High Efficiency Particulate Air Filter - HEPA filters are extremely important for maintaining contamination control. They filter particles as small as 0.3 microns with a 99.97 per cent minimum particle-collective efficiency.
Clean room architecture - Clean rooms are designed to achieve and maintain a airflow in which essentially the entire body of air within a confined area moves with uniform velocity along parallel flow lines. This air flow is called laminar flow. The more restriction of air flow the more turbulence. Turbulence can cause particle movement.
Measurement and instrumentation - Some important measurements related to contamination control are particle count, air flow & velocity, humidity, temperature and surface cleanliness. Clean room managers usually have specific standards and/or instruments to measure these factors.
Electrostatic Discharge (ESD) - When two surfaces rub together an electrical charge can be created. Moving air creates a charge. People touching surfaces or walking across the floor can create a turbo-electric charge. Special care is taken to use ESD protective materials to prevent damage from ESD. Cleaning managers should work with their personnel to understand where these conditions may be present and how to prevent them
Ventilation and make up air- Ventilation and make-up air volumes are dictated by the amount required to maintain indoor air quality, replace process exhaust and for building pressurization.
Pressurization- Rooms in a clean facility should be maintained at static pressures higher than atmospheric to prevent infiltration by wind. The only exception to using a positive differential pressure is when dealing with specific hazardous materials where governmental agencies require the room to be at a negative pressure.
Temperature and humidity- Temperature control is required to provide stable conditions for materials, instruments, and personnel comfort. Humidity control is necessary to prevent corrosion, condensation on work surfaces, eliminate static electricity, and provide personnel comfort.
Air handling requirementsRoom air should be supplied by an external air conditioning system, preferably dedicated to the facility. Partial recirculation of room air is appropriate and this allows for optimal energy utilization. Sufficient fresh air should be supplied in accordance with ventilation codes, to balance exhaust air and to maintain specified pressures.
Unless, otherwise specified, typical temperature range for this kind of room is within the range of 16 to 19 °C and relative humidity of approximately 50 per cent is maintained. The type of equipment and number of people in the room may dictate where in the range you need to be to assure that during production the operations area is maintained at the right temperature and humidity levels.
Only HEPA filtered air should enter the cleanroom and the gowning areas The location of the HEPA filters and air return grilles should create air movement from the designated ‘clean zone’ to the ‘less clean’ zones. Return air grilles should be at a lower level to aid in laminar flow requirements.
Air supply to the cleanroom should provide a room air change rate of >20 per hour. Air cleanliness will be enhanced by higher air change rates. When the doors are opened the supply air volume should maintain an outward flow of air.
Sources of contaminationIn order to control contamination, operators and those in charge of a cleanroom need to be cognizant of sources of contamination. These include:
Facilities: walls, floors and ceilings; paint and coatings; spills and leaks
People: skin flakes and oil; cosmetics and perfume; spittle; clothing debris (lint, fibres, etc.); hair
Tool-generated: friction and wear particles; lubricants and emissions; vibrations; brooms, mops, and dusters
Fluids: particulates floating in air; bacteria, organics, and moisture; floor finishes or coatings; cleaning chemicals; plasticizers (outgasses); water
Product-generated: glass flakes; cleanroom debris; aluminium particles from vial caps
Cleanroom cleaning
Cleaning of an active cleanroom should be performed daily. However, if the room is not used daily, a different schedule may be implemented, but it should be cleaned after every use. Improper cleaning of the cleanroom can lead to contamination and compromise product quality. Proper selection of equipment, cleaning agents and cleaning materials is important for proper cleaning.
Only products that have proven cleanroom performance records should be considered for use. These products should be listed in appropriate policies or procedures and all vendors should be informed about the strict policies of how products are qualified. All procedures should be strictly enforced.
Commercial survivability of a company is dependent on the quality of its products. A cleanroom ensures production of products with high quality, adding to the overall success of a company.