Gone are the days when industry used to adjust to the readily available and non-customized clean rooms and clean room products that compromised certain non-serious regulatory standards. Of late, the dynamics of the clean rooms have changed drastically and is trending towards customized and customer specific designs rather than static or vendor specific. Currently, the demand for foolproof and highly customized clean rooms and clean room products are the latest trends in the pharma industry.
Thanks to growing competition among the pharmaceutical industry, companies are striving to prove to be the best and is leaving no stone unturned to incorporate all the necessary technological ingredients to make themselves cent per cent contamination free and maintaining the highest level of regulatory standards for producing safe and highly efficient pharmaceutical products. Particularly in pharmaceutical and biotechnology sectors, clean rooms play a vital role in research laboratories and new drug discovery.
According to K Gopi, Managing Director of ICLEAN Technologies, the pharma industry is in the forefront in incorporating the clean rooms and clean room products in the country. Now the trends are fast changing as every individual company is looking to have customized clean rooms as per their needs and wants. “With changing trends in pharma industry, catalysed by the government’s Make in India initiative, the clean room industry in India is poised to grow between 20-25 per cent. Hopefully we are expecting a better future for the clean room industry in the country,” said Gopi.
At present, the Indian clean room industry is about Rs. 1150 crores and is expected to touch Rs 1400 crores in the next two years.In 2014, the clean room market size in India was about Rs. 1000 crores with a growth rate of 15 per cent per annum.
Giving his perspective about the current clean room industry, Ajay Mehta, director, GMP Technical Solutions Pvt Ltd, opined that clean room industry is moving towards customisation of design/ size/ accessories and emphasis on quality of equipment. Moreover now the focus is also on higher efficiency, energy savings, sustainability and functionality. Clean room equipment that provides solutions to contamination potentials and maximizes usable space is in great demand. Coved surfaces, flushed/ smooth component transitions and smooth final finish of the equipment is also one of the major changes in product’s design.
Another major change in clean room equipment industry is in the containment solutions (Isolator technology). An isolator is a device that provides a physical barrier between a laboratory technician and a work process. This barrier is necessary to avoid any contamination happening to the product or human, which may result by human coming in contact with the product.
“Day by day Isolators are becoming a major part of equipment in pharmaceutical industries manufacturing critical pharmaceutical products i.e. hormones, oncology etc. These products have critical effects on human beings and vice versa. Hence a strong barrier is required to avoid any type of contamination. Another advantage of this technology is that it is used for maintaining the required cleanliness class and conditions in a small area instead of maintaining the same cleanliness class and conditions in the whole manufacturing area, so it in turn reduces the HVAC and other running costs drastically,” said Ajay Mehta.
Role of clean rooms
In fact the main role of a clean room is to provide a contamination free environment. This kind of an environment is typically used in manufacturing or scientific research. Research laboratories particularly in biotechnology and pharmaceutical industry demand a low level of environmental pollutants such as dust, airborne microbes, aerosol particles, and chemical vapors.
More accurately, a clean room has a controlled level of contamination that is specified by the number of particles per cubic meter at a specified particle size.
For a lay man to understand, the normal air outside in a typical urban environment contains 35,000,000 particles per cubic meter in the size range 0.5 µm and larger in diameter, corresponding to an ISO 9 clean room, while an ISO 1 clean room allows no particles in that size range and only 12 particles per cubic meter of 0.3 µm and smaller.
In the pharmaceutical industry, clean rooms play a crucial role in the manufacturing of products which are required to be free from microbial and particulate contamination and protected from moisture. Such pharmaceutical products are manufactured and manipulated in clean rooms, which are fitted with HEPA and, if required, ULPA filters as well as dehumidifier systems.
Historical perspective
The first and modern clean room was invented by American physicist Willis Whitfield. An employee of the Sandia National Laboratories, Whitfield created the initial plans for the clean room in 1960. Prior to Whitfield's invention, earlier clean rooms often had problems with particles and unpredictable airflows. Whitfield designed his clean room with a constant, highly filtered air flow to flush out impurities. Within a few years of its invention in the 1960s, Whitfield's modern clean room had generated more than $50 billion in sales worldwide. The clean room eventually entered the hospital industry in the United Kingdom, primarily in hospital pharmacies.
Clean rooms and rise in cost
There is a direct relation between cost of pharmaceutical products and clean rooms. Pharma companies which produce high quality and efficient products in clean rooms environment charge their products at a higher rate when compared to those not having clean rooms. This is because; the cost of maintaining a clean room is very high for the manufactures.
In fact in the pharmaceutical industry, the overall investments needed to bring a product to market are staggering. In many occasions, it is widely reported that the fully capitalized cost to develop a new drug can range from $800 million to nearly $900 million. The steep price of product rejects and recalls make it crucial to ensure high product yields by maintaining strict clean room cleanliness and sterility. That is one of the reasons that the US Federal Drug Administration (FDA) mandates that any product that is injected, or used in the eyes or on open wounds must be sterile, i.e., free from viable micro-organisms. That is because, if contaminated with micro-organisms, these pharma products can adversely harm patients.
Micro-organisms introduced into a clean room environment need only three things to grow: moisture, food and temperature – all of which exist in a clean room. Consequently, all incoming air, water, chemicals, and materials must be filtered or sterilized to meet high standards of purity and microbiological control, so as not to contaminate processes or products in production. Also to be ‘filtered,’ in a sense, is the clean room operator, who, most will agree, is the dirtiest thing to enter a clean room.
Facts about bodily contamination:
It is proved by researchers that every square inch of a human hand surface has an average of 10,000 micro-organisms. On an average every square inch of the human body has an average of 32 million bacteria on it. Every minute of the day, people lose about 30,000 to 40,000 dead skin cells off the surface of their skin. Even when stationary, people generate approximately 100,000 particles of 0.3 microns or greater. On the move, this rises to approximately five million.
Sterile rooms & operator suits
Having understood above facts, for manufacturing highly safe and fool proof contamination free medicinal products, the laboratory operators should keep the rooms sterile all the time and should mandatorily wear customised and fool proof contamination free suits. Keeping the operator’s dirt and germs out of the sterile clean room environment and away from sensitive products and processes is the main objective of the sterile clean room suit. The suit needs to protect the environment from viable particles such as bacteria and yeasts, and non-viable particles such as hair, dead skin cells, and dandruff. To that end, it is critical for clean room operators to select clean room suits that provide not only the highest levels of inherent sterility, but also the greatest chances of maintaining that sterility through the gowning process.
Sterile clean room suits
Sterile clean room suits are essential in pharma and biotechnology manufacturing industry. Though there are no federal regulations for sterile clean room garments used in the pharmaceutical industry, guidance for the industry is available from The Institute of Environmental Sciences and Technology (IEST), which publishes a recommended practice IEST-RP-CC003.3, “Garment Considerations for Clean rooms and Other Controlled Environments.” The recommended practice provides guidance for the selection of fabric, garment construction, cleaning and maintenance of clean room garments and testing of clean room apparel for use in aseptic and non-aseptic clean rooms.
While clean room garments can either be disposable or re-usable, according to industry analysts, most sterile facilities will opt for disposable garments due to contamination concerns relating to reusable garments returned from laundering facilities. In some companies, disposables may be used at some locations and reusable at others. This can depend on the classes of the various clean rooms at different locations. Disposable garments may be easier to manage from a cost standpoint as well.
Clean room garment fabric
For about a more than 50 years, the major fabric used for manufacturing clean room garments is flashspun polyethylene fabric. This has the ability to get less contaminated and can be easily disposed off.
According to industry analysts, flash-spun polyethylene provides filtration efficiency for sub-micron sized particles and micro-organisms and is suitable for light splash protection from non-hazardous liquids.
Disposable suits also can be made from spunbond-meltblown-spunbond (SMS) fabric, which has outer layers of spunbond polypropylene for strength and cloth-like comfort, with middle layers composed of a matrix of microfibers, which creates a torturous path for fine particles and liquids.
Re-usable clean room suits are typically made from woven polyester-blend fabrics, which may degrade after multiple laundering and sterilization cycles. Most operators in a sterile clean room environment in the pharma industry will wear three to four disposable suits in a day, each suit being worn for two to three hours at a time. Often, clean room protocol dictates that garment changes must be made each time the clean room is re-entered. Once discarded, these suits can be incinerated, or they can be re-purposed through a garment recovery service that will take the used garments and sell them back into non-sterile applications.
Sterilization of clean room garments
Clean room garments are sterilized through several methods, including gamma irradiation, e-beam sterilization and ETO posterisation. Gamma sterilization is widely considered to be the most cost-effective method. The desired Sterility Assurance Level (SAL) for garments to be used in sterile pharma manufacturing is 10-6, which translates into a one-in-a-million probability of a garment being non-sterile. Once sterile, clean room suits must be packaged in a way that this sterility is maintained throughout handling, transportation and storage.