Tech Trendz

Cleanroom technology in India

Cleanroom technology is crucial to the global plans of both pharmaceutical and biotechnology companies. Sachin Jagdale analyses trends in the industry

The desire to deliver products of a consistently high quality and credibility, has made quality control and quality assurance a 'must have' for the pharmaceutical and biotechnology industries. Among the many initiatives that pharma industry took to comply with all international norms, implementation of cleanroom technology may top the charts. Organisations like the US Food and Drug Administration (FDA) have formulated very stringent protocols for cleanroom operations. Managing cleanrooms is not an easy task. Slight irregularity in monitoring this vastly technical science could well be a matter of life or death for the end user. However, implementation of cleanroom technology is not an easy operation. There are many dos and don'ts that will decide cleanroom technology like cost of implementation, its efficiency, the level of cleanroom requirement in a particular project etc.

Principle functions

Amidst stringent regulatory requirements pharma and biotech companies have been forced to upgrade their product quality and standards. Cleanrooms help them in a great way to achieve this particular goal. Ajay Mehta, Director, GMP Technical Solutions, says, "In biotech and pharma industries, cleanrooms are used when it is necessary to ensure an environment free of bacteria, viruses, or other pathogens. In addition, the temperature and humidity may be controlled. GMP provides its customers all such data and information at the conceptual stage of the project." He adds, "Four fundamental rules apply to clean rooms. First, contaminants must not be introduced into the controlled environment from the outside. Second, the apparatus within the controlled environment must not generate or otherwise give rise to contaminants (for example as a result of friction, chemical reactions, or biological processes). Third, contaminants must not be allowed to accumulate in the controlled environment. Fourth, existing contaminants must be eliminated to the greatest extent possible, and as rapidly as possible."

Ramesh Shanbhag, Director, Clestra Modular System, puts across his views. The definition provided by Shanbag broadly summarises the principle functions of clean rooms. He says, "Cleanroom standard ISO 14644-1 specifies a ' A room in which the concentration of airborne particles is controlled, and which is constructed and used in a manner to minimise the introduction, generation, and retention of particles inside the room and in which other relevant parameters, for example, temperature, humidity, and pressure, are controlled as necessary."

According to Hamish Shahani, Vice chairman, Klenzaids, a cleanroom precludes and inhibits airborne contaminants from compromising vulnerable components or processes.

For successful cleanroom operations

Building a cleanroom is a complex exercise. Particulate count by different standards decides the cleanliness of cleanrooms. The particulate level has to be such that it will not affect sterility of the product in any way. Presence or absence of both viable and non-viable particles is detriment of successful cleanroom operations. Shanbhag enumerates some of the crucial arrangements made to achieve successful cleanroom operation:

a) The room is supplied with high quantities of HEPA filtered air into the room. The resulted high room air changes, dilute and remove the particles and microbial contaminates that are released by personnel or the operating machinery.

b) The room construction is such that the enclosure material does not emit or generate particles and could be easily cleaned. Usually material like modular metal panels is used for walls and ceiling while flooring could be of Vinyl or epoxy. These components are brought together to form a monolithic surface avoiding any cracks and crevices.

c) The operating personnel will have clothing and covering like gloves, head mask to contain and minimise the dispersion of particles and microbial into the room.

d) The room is pressurised to prevent the dirty air from entering the room.

And finally e) The operators are fully trained with regards to their behaviour within the controlled area.

"Cleanrooms are not only very expensive to build and but are also expensive to operate. Usually the user / buyer spends extensive time in keeping the initial construction cost to the minimum without giving second thought to the running and operating cost" - Ramesh Shanbhag Director, Clestra Modular System

Bipin Patil, Founder, Aerience, Institute of Air Science and Contamination Control and Managing Director, Snowline HVAC Systems has handled more than 200 projects in HVAC including turn key projects, clean-rooms, HVAC design consultation, HVAC TAB, HVAC energy audit, etc. He stresses on the importance of documentation. Patil opines, "The cleanroom design should be based on the current Good Manufacturing Practices (cGMP), for eg. type of product, process requirements, like temperature humidity, class of air filtration (HVAC), equipment, room dimensions, etc. by following User Requirement specifications (URS). The cleanroom design specifications should be prepared for example, functional specifications, technical specifications, drawings of all components etc." He adds, "The design specifications should be documented and qualified (DQ). The cleanroom erection should be executed according to DQ with proper monitoring and control during the period. The cleanroom should be installed according to DQ. It should be qualified for installation with the details documented (IQ). It should be qualified for operations (OQ) by ensuring that all required operating parameters of all equipment, systems, including HVAC, are operating within acceptable limits as required by process. The OQ should be documented. The performance of cleanroom should be checked, documented and qualified initially after DQ, IQ, OQ and should be performed periodically as required by process."

According to Mehta, the only way to control contamination is to control the total environment. Air flow rates and direction, pressurisation, temperature, humidity and specialised filtration all need to be tightly controlled. And the sources of these particles need to controlled or eliminated whenever possible. There is more to a cleanroom than air filters. Cleanrooms are planned and manufactured using strict protocol and methods. "Eliminating sub-micron airborne contamination is really a process of control. These contaminants are generated by people, process, facilities and equipment. They must be continually removed from the air. The level to which these particles need to be removed depends upon the standards required. Strict rules and procedures must be followed to prevent contamination of the product," says Mehta.

Expensive task

"A trend is the increased expenditure on cleanrooms in pilot plants. Until recently, construction costs for pilot projects were typically $10 to $50 million. Today, many are being built in the $300 million range" - Anand Bidarkar Vice President, Business Development, Siro Clinpharm

Cleanrooms guarantee high standards of product. However, setting up the cleanrooms is an expensive task. Though bigger players in the market can afford to invest huge sums, smaller players are not always in a position to step into their 'big brother's' shoes. This scenario is a challenge to cleanroom designers who can greatly reduce cleanroom implementation as well as operational costs. Patil feels that the optimisation of the design of HVAC considering energy saving concepts is necessary. Selection of equipment based on the requirements matters most. Optimal utilisation of equipments and accessories to control the energy and maintenance costs will also make a big difference.

Shanbhag agrees, "Yes, cleanrooms are not only very expensive to build and but are also expensive to operate. Usually the user/ buyer spends extensive time in keeping the initial construction cost to the minimum without giving a second thought to the running and operating cost. This cost can be a substantial chunk when considered through the life of the plant. An experienced cleanroom designer would normally have to study the type of application and use their experience in selecting proper classification and appropriate air changes. Over design obviously works but it is like using eight tyres on your car."

"As the cost of cleanroom operations increases, management of this space becomes a critical task. The state of cleanliness can only be maintained through a deliberate programme of training, personnel monitoring, proper gowning, cleaning and sanitisation, process controls and environmental monitoring. One of the most important parameters in cleanroom HVAC design is room differential pressure. It is easily understood that by maintaining positive pressure over its adjacent space, the infiltration of less clean air into a cleanroom is minimised," says Mehta.

Commercially important

The primary purpose of cleanrooms is to ensure production of a product with high quality standards. As the market always leans towards quality, pharma and biotech companies should strive to achieve the same. There is a common consensus on the fact that commercial survival of the company will largely be decided by initiatives like cleanroom implementation. T S Jaishankar, Managing Director, Quest Life Sciences, says, "Cleanrooms are absolutely important to atmospheric air. This will include material weighing for batch processing, and manufacturing area till primary packing."

Anand Bidarkar, Vice President, Business Development, Siro Clinpharm gives a more detailed explaination. He says, "The journey from drug development to commercial introduction can take 10 to 15 years and cost $500 million. In this period the drugs produced in pilot plants are used for clinical research. The process clinical research is an evaluation of the safety and efficacy of a drug that determines its eventual approval or rejection. It is very important that the product used in clinical research is free of contaminants and hence the use of cleanrooms in pharma R&D pilot plants. A trend is the increased expenditure on cleanrooms in pilot plants. Until recently, construction costs for pilot projects were typically $10 to $50 million. Today, many are being built in the $300 million range. The pilot plants are usually owned by the drug maker's research arm."

Global forays

"Cleanroom Service providers in India have done a remarkable job in the manufacturing of AHUs and cleanroom equipments of international standards" - T S Jaishankar Managing Director, Quest Life Sciences

Traditionally, technologically far mature overseas pharma companies used to easily outshine Indian pharma companies. However today, Indian pharma industry's flexible approach towards accepting concepts like cleanroom technology has strengthened their credibility in the global market.

Bidarkar informs, "Biotech companies are also moving from the small pilot-type facility to large production facilities with substantial clean rooms. Many global pharma majors outsource manufacturing to Indian companies, due to much lower costs (both capital and recurring) than their western counterparts. Many Indian companies have made their plants cGMP-compliant. India also has the largest number of USFDA-approved plants outside the US. The role of cleanroom suppliers is very important in making the facilities cGMP compliant and ensuring adherence to USFDA and other stringent regulatory requirements."

"Cleanroom Service providers in India have done a remarkable job in the manufacturing of AHUs and cleanroom equipments of international standards.

This has enabled Indian companies to set up manufacturing plants at a minimum level project cost than in the western world and at the same time to meet international standards," says Jaishankar.

Value added partnerships

According to Shanbhag, cleanroom service providers can and do go beyond providing robust cleanrooms with energy wise operating system. They are perfectly capable of providing the necessary certification and validation documents in order to meet various cGMP regulatory requirements.

In addition they need to partner / cooperate with the user in keeping the system in validated mode by maintaining and certifying the system on regular basis. Shahani says, "It's well established that sterile dosage forms became commercially viable due to Klenzaid's introduction of Laminar Flow and Depyrogenation technologies. That put India on the international map. Cleanroom providers have helped provide these affordable and fully supportable technologies to Indian companies who have been able to consequently produce products at lower costs and on par with the western world"

The final goal of cleanroom is to exclude the external environment. It is imperative to ensure that cleanrooms are put up in such a way that upon completion they stick to all regulatory requirements. Indian cleanroom service providers are indeed doing so.

This trend will only grow in the coming future and cleanroom service providers can claim a lion's share in Indian pharma and biotech's global success.

Mehta rightly says, "Indian cleanroom providers have helped / provided a indigenisation of the requirements that at one time were the sole domain of international consultants and cleanroom providers.

This has helped the users of cleanrooms to compete in the international market and produce goods/products as per global standards and helped its users obtain US FDA, MCA & WHO approvals and recognition."

sachin.jagdale@expressindia.com