The environment control, in and around pharmaceutical or biopharma facilities, has long been a key consideration for the manufacturers as well as for the facility designers. India has been long known for its prowess in generic medicines across global pharma circuits. However, on the other hand, the Indian pharma industry is also well aware of the fact that innovation is the only way to establish itself as a global pharma superpower. To meet the expectations of the global regulatory authority, Indian pharma industry is heavily investing into various technologies. Investment into the advanced cleanroom technologies is perceived as one such very crucial step.
Cleanroom industry: Coming of age
Pharma industry is changing and so are its cleanroom requirements. “Cleanrooms have become an integral part of the pharma manufacturing facilities. Being a highly regulated industry, it needs to evolve continuously, making sure it is in step with, if not ahead of regulatory expectations. Essentially, the cleanroom elements include the wall panels, the ceiling panels, the cut-outs and fixation of the HEPA filters, light fixtures, utility panels apart from the floors, view panels, doors etc. The cleanroom discussion hence must include all these elements,” informs PK Kulkarni, Managing Director, Technolutions Projects.
He adds, “Changes in cleanrooms since last few years have been more for better materials of construction. Also, a significant emphasis now is more on integration of the associated engineering requirements with cleanrooms namely the HVAC systems, the local decon systems, the integration of isolator requirements, integration of pass through devices like DPBs and DFLHs, autoclaves, VHP systems and so on. Thus, it is much more than panels now. Better communication systems between cleanrooms and other auxiliary rooms are also developing fast.”
Cleanroom in different industries should be designed according to their own manufacturing characteristics. Pharma industry is not an exception and moreover, it is one of the most regulated industries. Archana Sohoni, Principal Architect, Arena Consultants informs, “More and more companies are getting into microbial studies and research and it calls for higher standards and controls in cleanroom design and operations. Few companies are opting for very stringent BSL level 3 and 4 labs as well now.” Sohoni has vast experience in designing cleanroom facilities for many companies, including R&D labs for pharma companies.
Explaining the reasons behind the growth and changes in the cleanroom industry, Sohoni adds, “Many factors are responsible for the growth of cleanroom technology, firstly due to increasing market such as healthcare industry, defence, biotechnology, microelectronics etc. Other aspects are stringent healthcare regulations, demand for quality products, rise in healthcare spending, increased demand for sterilised pharma product, growing prevalence of contagious and infectious diseases etc.”
According to Kulkarni, as an industry, we now see more and more potent molecules in the market as well as in development pipelines. As a consequence, the emphasis on avoidance of cross contamination has become more and more challenging.
Kulkarni informs, “Apart from many other design requirements in processing like having a good HVAC system, closed transfers, use of Isolators etc. it is essential that all the surfaces are easy to clean, have no residues of previous product etc. Also the surfaces themselves must have a very low particle shedding profile. Another facet is the increasing flexibility required to accommodate changes in the facility, in case a new area is to be made or a bigger or smaller room is required. Although not very easy, it is easier than a brick mortar facility to meet such changes. Good cleanrooms meet all these requirements and have been in service in India since the nineties.”
Cost the factor?
The general perception is that cleanrooms are an expensive affair. Since not every pharma company is cash rich, heavy investments may not be the cup of tea for small time pharma operators. A cleanroom must meet its functional requirements of minimising particulate generation and support other engineering requirements as described above, apart from the ‘looks’ of a cleanroom. However, Kulkarni points out that only money can’t decide the quality of the setup. Investment without good strategy and design will meet dead end too.
“A very well designed cleanroom is not necessarily an expensive system. In fact, a poorly designed system just for the ‘looks’ will turn into a costly mistake when put into operation. More than the financial strength of the organisation, it is the understanding of the need for cleanroom and the methodology to get the same right the first time must be the focus. Surely cleanrooms are more expensive than conventional brick mortar constructions in the initial calculations of installation costs. However, a long term view including operational costs of maintenance would make them eventually much more cost effective,” opines Kulkarni.
He adds, “One must not go for exotic materials of construction just for the ‘feel good’ factor, even for cleanroom elements. As long as functional requirements are met, there is no reason to add cost for only the visual appeal. Using stainless steel is one such high cost decision, unless absolutely essential, as in case of washing rooms. As far as the standards are concerned, no regulatory agency says you must have this or that cleanroom. It specifies the viable and non-viable particulate limits as well as guidance on many other regulatory expectations on being able to disinfect the premises, maintain required pressure differentials and many others.”
Sohoni also believes that the huge financial inputs required for the establishment of cleanroom and the constant pressure on healthcare providers to reduce costs are some of the factors that are restricting the growth of this market.
In times to come
The industry is increasingly evaluating its response to the needs of product development and is in discussion with regulators to meet the challenges in increasing potency of the molecules. Kulkarni informs, “An effort in this direction is the ISPE’s engagement with the FDA on containment requirements. Many other initiatives will be worked out jointly on medical devices, biological products etc. Any global change would essentially have to be assimilated by the Indian industry as it looks for exports aggressively. Harmonisation of regulatory requirements is here to stay.”
He expects the cleanroom service providers to be in sync with these changes. While it is difficult to predict all such changes, Kulkarni wants the industry to strive to meet the requirements of increasing focus on quality by design, validation documentation, flexible systems, disposable components for avoidance of cross contamination, better and more effective sanitisation systems, easy to use isolation systems etc.
Use of isolators is one of the numerous trends currently evident in the cleanroom industry of India. Isolation technology decreases the dependance on manpower and so it is considered cost effective in pharma/biotech cleanrooms. Large-scale cleanrooms can be replaced by rooms with various smaller areas, utilising isolation techniques. Many pharma production facilities have availed this technology.
Sohoni highlights few more trends, “The increased expenditure on setting up cleanrooms in pilot plants is also a trend. The pilot plants are usually owned by the drug maker’s research division and are often as large as the final production plant. The time taken from drug development to commercial introduction may vary from 10 to 15 years. This calls for dire requirement of energy conservation, functionality, sustainability and simplified maintenance. Coved surfaces, smooth component transitions, and seamless joints are some of the architectural features that are trending in pharma cleanroom construction. Companies are looking for more modular and flexible designs, but they also want high-quality construction.”
Sohoni also points out that biotechnology, as an industry type by itself, is moving from the small pilot-type facility to large production facilities with substantial cleanrooms.
Not that the Indian pharma industry was not using cleanroom services. But the global pharma industry is rapidly changing and so is its technology. To be global, the Indian pharma industry will have to accept what is trending worldwide. Keeping pace with the global cleanroom trends will help this industry to not just survive but also grow in the world arena.