CLEANROOM July, 2015 by Indian Express

CLEANROOM COVER STORY

July 2015 Chairman of the Board Viveck Goenka Editor Viveka Roychowdhury* Chief of Product Harit Mohanty

Bengaluru Neelam M Kachhap Pune Shalini Gupta DESIGN National Art Director Bivash Barua Deputy Art Director Surajit Patro Chief Designer Pravin Temble Senior Graphic Designer Rushikesh Konka Senior Artist Rakesh Sharma, Vivek Chitrakar Photo Editor Sandeep Patil MARKETING Regional Heads Prabhas Jha - North Dr Raghu Pillai - South Harit Mohanty - West & East Marketing Team Rajesh Bhatkal GM Khaja Ali Ambuj Kumar E Mujahid Arun J Ajanta Sengupta PRODUCTION General Manager B R Tipnis Manager Bhadresh Valia Scheduling & Coordination Mitesh Manjrekar CIRCULATION Circulation Team Mohan Varadkar

CONTENT

BUREAUS Mumbai Sachin Jagdale, Usha Sharma, Raelene Kambli, Lakshmipriya Nair, Sanjiv Das

CHANGING DIMENSIONS Though clean rooms are a proven technology to prevent contaminations at the drug manufacturing facilities, according to experts, future will see even more advancement in this technology By Sachin Jagdale

9 10 12 15

INTERVIEW Our aim is to imbibe the best from the west so that our customers get future-tech at affordable prices

INTERVIEW ‘We develop plans to correct any issues that are uncovered'

INSIGHT Innovations in cleanrooms and environmental monitoring

INSIGHT Trends in cleanroom tech

Express Pharma® Reg. No.MH/MR/SOUTH-77/2013-15, RNI Regn. No.MAHENG/2005/21398. Printed for the proprietors, The Indian Express (P) Ltd. by Ms. Vaidehi Thakar at The Indian Express Press, Plot No. EL-208, TTC Industrial Area, Mahape, Navi Mumbai - 400710 and Published from Express Towers, 2nd Floor, Nariman Point, Mumbai - 400021. (Editorial & Administrative Offices: Express Towers, 1st Floor, Nariman Point, Mumbai - 400021) *Responsible for selection of news under the PRB Act. Copyright © 2015. The Indian Express (P) Ltd. All rights reserved throughout the world. Reproduction in any manner, electronic or otherwise, in whole or in part, without prior written permission is prohibited. July 2015

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FOREWORD

Cleanroom tech to go more hi tech

leanrooms are perhaps one of the most crucial parts of the lifesciences sector, given that regulatory agencies are upping the ante when it comes to monitoring good manufacturing practices (GMP). There is also increasing concern for safety of working personnel as well as the outside environment. Increasing environmental contamination has also increased the importance of these technologies. Manufacturers of cleanrooms are thus expected to provide an ever escalating number protective features yet at affordable costs, with energy efficiency built into the design. With India striving to remain an important part of the global pharma supply chain, it cannot afford to be hauled up for faulty GMP. Thus, it is a given that demand for cleanroom technologies is only set to rise in India. Express Pharma has therefore put together a selection of interviews and articles cataloging trends in lifesciences cleanroom technologies in this supplement. The lead article, 'Changing Dimensions' (see story on pages 5-8), explores how the cleanroom industry has come of age in India, with pharma companies demanding and willing to pay more for better designed cleanroom facilities. Basic cleanroom panels have given way to more advanced construction materials, as well as modular and flexible designs. Cleanrooms are also better designed today, incorporating energy efficiency aspects and integrating into the overall manufacturing plant's associated engineering requirements like

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The most expensive and advanced technologies in the world would be a waste if we do not also educate and train staff to use them effectively as per global GMP standards

the HVAC systems, etc. These demands are being met by local manufacturers. Aasif Khan, Managing Director, Fabtech Technologies, out their strategy saying, “Our aim is to imbibe the best from the west so that our customers get future-tech at affordable prices.” (See interview on page 9). Competition is fierce in this industry, with Prashant Kavale, Director, GMP Technical Solutions vowing that, 'We develop plans to correct any issues that are uncovered”. (See his interview on page 10) To share with us global insights on innovations in cleanrooms and environmental monitoring, we have Dr Tim Sandle, Head, Microbiology at Bio Products Laboratory and visiting tutor at the Department of Microbiology, University of Manchester, UK. His article touches on some innovations relating to cleanroom and clean device operations, together with personnel control and environmental monitoring. The article em-

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phasises the importance of ensuing that good cleanroom design factors necessary for ensuring contamination control are met. (See pages 12-16) But the strong demand for cleanroom technologies could possibly be hampered by access to skilled cleanroom operators in the future, points out Guy Tiene, MA, Director of Strategic Content, That’s Nice LLC / Nice Insight. (See pages 16-18). Pharma companies as well as cleanroom technology providers in India should take serious note of this warning and plan now to create a pool of specialist cleanroom operators. The most expensive and advanced technologies in the world would be a waste if we do not also educate and train staff to use them effectively as per global GMP standards. Besides a lack of skilled manpower, the high cost of setting up and maintenance will also restrain growth of the global cleanroom market. In India, financial resources will also always be a constraint. Smaller companies will see cleanrooms as a cost, while larger companies would be in a better position to reap the return on investment. Even given these constraints, the cleanroom technology market, projected to be globally worth $3,761.9 million by 2019, is set to grow at a higher CAGR in India and the APAC region (8 per cent compared to 5.5 per cent in the US, EU and other more matured markets). As global cleanroom tech players look at India and APAC for growth, here’s hoping that competition will make cleanroom tech more affordable.

July 2015

CLEANROOM

CHANGING DIMENSIONS Cleanrooms are a proven technology to prevent contamination at drug manufacturing facilities and expected to show even more promising growth in future BY SACHIN JAGDALE

PRESENTED BY

CLEANROOM

he 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

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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

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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 PK KULKARNI, MANAGING DIRECTOR, TECHNOLUTIONS PROJECTS

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 July 2015

CLEANROOM

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

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

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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

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CLEANROOM 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

MORE AND MORE COMPANIES ARE GETTING INTO MICROBIAL STUDIES AND RESEARCH AND IT CALLS FOR HIGHER STANDARDS AND CONTROLS IN CLEANROOM DESIGN AND OPERATIONS ARCHANA SOHONI, PRINCIPAL ARCHITECT, ARENA CONSULTANTS

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 highquality 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. sachin.jagdale@expresssindia.com

CONTRIBUTOR’S CHECKLIST ❒ Express Pharma accepts editorial material for

regular columns and from pre-approved contributors / columnists. ❒ Express Pharma has a strict non-tolerance policy of plagiarism and will blacklist all authors found to have used/refered to previously published material in any form, without giving due credit in the industry-accepted format. All authors have to declare that the article/column is an original piece of work and if not, they will bear the onus of taking permission for re-publishing in Express Pharma. ❒ Express Pharma's prime audience is senior management and pharma professionals in the industry. Editorial material addressing this audience would be given preference. ❒ The articles should cover technology and policy trends and business related discussions. ❒ Articles for columns should talk about concepts or trends without being too company or product specific. ❒ Article length for regular columns: Between 1200 - 1500 words. These should be accompanied by diagrams, illustrations, tables and photographs, wherever relevant. ❒ We welcome information on new products and

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services introduced by your organisation for our various sections: Pharma Ally (News, Products, Value Add), Pharma Packaging and Pharma Technology Review sections. Related photographs and brochures must accompany the information. ❒ Besides the regular columns, each issue will have a special focus on a specific topic of relevance to the Indian market. ❒ In e-mail communications, avoid large document attachments (above 1MB) as far as possible. ❒ Articles may be edited for brevity, style, and relevance. ❒ Do specify name, designation, company name, department and e-mail address for feedback, in the article. ❒ We encourage authors to send their photograph. Preferably in colour, postcard size and with a good contrast. Email your contribution to: The Editor, Express Pharma, Business Publications Division, The Indian Express (P) Ltd, 1st Floor, Express Towers,

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Nariman Point, Mumbai - 400 021. Tel: 91-22-2202 2627 / 2285 1964/ 6744 0000 Fax: 91-22-2288 5831 editorial.ep@expressindia.com July 2015

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Aasif Khan Managing Director Fabtech Technologies

INTERVIEW

Our aim is to imbibe the best from the west so that our customers get future-tech at affordable prices Fabtech Technologies, a recognised name in the cleanrrom market has grown expediently across the globe. The company has already explored different segments of the business which are interlinked with its niche. AASIF KHAN, Managing Director, Fabtech Technologies talks about the company's growth parameters with USHA SHARMA

Fabtech's corporate website mentions that the company offers cleanroom services affordable to all, without compromising on the quality, could you please justify? Fabtech has its own in-house design and manufacturing expertise which gives our clients the flexibility of customised solutions. Fabtech in fact is beyond and much more than cleanrooms. Quality now and

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ahead is a given. It is no longer a USP. We leverage our international presence to bring innovative solutions to India and vice-versa. What additional features are you planning to introduce for the Indian pharma market? How big is the Indian clean room market and at what pace is the company growing?

Innovation is the key and in our business, new innovative building material have begun to make an entry. The market will soon see, we launching innovations in the market. The market size is huge, unfortunately no one knows the number. And growth would depend on the speed at which new products can be introduced. We are currently growing at around 20 per cent CAGR and

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expect to stay that way in the panel business. Presently, many small and medium-sized companies are offering services similar to pharma companies. How healthy is this for your business? How do you plan to leverage the opportunities available in this arena? The marketplace has a slot for everyone. Our ticket (project)

sizes have grown from a few hundred thousand dollars to few million dollars. We are leveraging the market potential by focusing on becoming the 'one stop shop' for our customers. Offering concepts and solutions, projects and products aiming to get closer to the customer and fulfilling their needs. From air and container Continued on Page 11

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Prashant Kavale Director GMP Technical Solutions

INTERVIEW

'We develop plans to correct any issues that are uncovered' GMP Technical Solutions offers its services to various industries and constantly improving its services. PRASHANT KAVALE, Director, GMP Technical Solutions speaks about the company's key business endeavours with USHA SHARMA

GMP Technical has a mixed bag of client list. Which clientèle provides a better business opportunity and how? Yes, we have a mixed bag of client list ranging from pharmaceuticals, healthcare, industrial, commercial, government, hospitality industries. However, GMP Technical’s fundamental clientèle base belongs from pharma background located throughout in India, Middle East, Russia, East Africa, East Europe, Western Asia and many more regions. Our international business is growing at a steady

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pace and we feel we have better opportunity in Africa and Middle East region. The company has its state-ofthe-art manufacturing facility at Baddi in Himachal Pradesh. However, after the expiration of tax incentives regime, most of pharma facilities have become sick units. How are you managing your business in Baddi? Since from the inception our business is not localised in a single geography. Though we enjoy a very good market share in Baddi region it is

not substantial compared to our overall revenue figure and not affected our business significantly. Which services do you offer? GMP is poised for a bigger growth in areas of clean room solutions, Turnkey MEP (Mechanical, Electrical and Plumbing), IBMS (Integrated Building Management System), Containment and isolators, trunkey laboratory solutions and calibration and validation services . Whom do you consider as your competitors in the do-

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mestic market and how healthy is the competition? We operate as a Turnkey contractor for diversified industries with services ranging from MEP, clenrooms, Isolators etc. Each business unit has different challenges. We already have a competitive edge over other service providers in the industry for having a highly talented technical project team on board, our design build solutions are of superior quality, low-cost and definite project schedule sets us apart from the competition in domestic as well as international markets. We re-

main preferred choice of our clients. Update us on the company's hospital infrastructure venture. GMP Hospitec was formed in the year 2011. A team of 30 professionals manages operations in India and abroad. GMP Hospitec has its corporate office at Mumbai and branch offices in major Indian cities like Delhi, Goa, Bengaluru, Indore, Ahemedabad, Pune, Hyderabad. Hospitec division offers integrated turnkey solutions for healthcare institutions that July 2015

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CLEANROOM includes turnkey design projects, MEP and detailed engineering services, equipment planning, implementation and validation. Our product portfolio entails pre-fabricated OTs, modular ICU, CCU, NICU, medical gas pipeline system, nurse call system, BMS/ IBMS systems, modular furniture, door systems, IT and networking, and others.

TAKING INSPIRATION FROM 'MAKE IN INDIA' PROGRAMME WE HAVE COMPLETED JV AGREEMENTS WITH EUROPEAN AND US INDUSTRY LEADERS TO MANUFACTURE BIORECATORS, FERMENTORS, VAPOUR HYDROGEN PEROXIDE SYSTEM FOR DISINFECTION AND ASPETIC ISOLATORS FOR FILLING LINE. THE SAME WILL BE INTRODUCED IN DOMESTIC MARKET IN NEXT THREE TO SIX MONTHS

The company has also started GMP IT Infra Solutions. How it will be useful for the pharma companies? GMP IT infra solutions are highly driven by cutting edge technology and we will be in position to offer a compliant technology platform for both pharma and healthcare

Industry. How many new solutions are in the pipeline and for which sectors? When do you plan to introduce it in the domestic market? We have started a state of the art facility near Mumbai to manufacture pharma isolators,

containment systems, powder handling systems and laboratory furniture along with modular operation theatre. Taking inspiration from 'Make In India' programme we have completed JV agreements with European and US industry leaders to manufacture biorecators, fermentors , vapour hydrogen per-

oxide system for disinfection and Aspetic Isolators for filling line. The same will be introduced in domestic market in next three to six months . What are your plans to grow internally and what will be your strategies? We constantly assess and evalu-

ate organisation’s infrastructure, systems, processes, human resources and culture. Following the evaluation we develop plans to correct any issues that are uncovered. Our strategy is to maintain consistency in the quality of both our product/service and our customers’ experience to maintain and gain market share. What is your manpower strength and are there any plans to increase it further? Our present manpower, comprising site engineers is 1200 employees across India and abroad locations. Yes, we are constantly hiring new talent on board to equivalent our growth pace. u.sharma@expressindia.com

Continued from Page 9

Our aim is to imbibe the best... sterilisation equipment, integrated containment and process solutions to pharma infrastructure to clean room solutions and now Fabtech has also introduced automatic capsule fillers. The company has launched three new products; namely sampling booth, mist shower and dedusting tunnels (With flame proof execution). Tell us about their USPs? All our innovations stem out of our customers needs. All the above are critical for high potency product manufacturing process. These have to be equipped with online sampling booth and mist showers. Tell us how Fabtech's Sterling venture is performing? Here too, our philosophy of bringing continuous innova-

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tions has helped us stay on the growth path, and ahead of the crowd. Plaswall and Plasmolite technologies help our customers to save time and get to commissioning quicker than traditional methods. The product has clicked in the regulated market more than the developing world. Fabtech's Plaswall and Plasmolite replaces costly and time consuming steel, aluminium, and plywood framework, tell us about their advantages to the pharma industry? As mentioned, these materials help quick construction and commissioning of the factory. Also,facility expansion is lot cleaner enabling quicker cleaning and validation. Time is money, non tangible benefits compensate the cost hence it is

ALL OUR INNOVATIONS STEM OUT OF OUR CUSTOMERS NEEDS. ALL THE ABOVE ARE CRITICAL FOR HIGH POTENCY PRODUCT MANUFACTURING PROCESS

move to perfection in order to gain the confidence of the west. However, the industry has to align it's dominoes. Each and every bit of the manufacturing, supply chain has to run on zero defects. Entire industry has to rise. We are doing our bit. A big factor though is the users to realise the importance of this and be ready to support the allied industry by better prices, and payments terms. I m afraid the trend the domestic industry is showing( by making only the cost as criterion) it may take a long time to achieve this dream.

cost effective. The present government is encouraging ‘zero defect’, ‘zero effect’. What solutions are offered by your company to meet the PM's vision? The Indian industry has to

Update us on the company's two prestigious, multi-million dollar biotech turnkey construction projects in Syria and Germany? These projects in different geographies speak volumes on

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our project delivery capabilities. From under regulated to a highly regulated market. To gain trust of a European company is not easy. However this illustrates that given a cost anything can be delivered from India. If IT and BT can happen, why not projects outsourcing. What is your company's success mantra? And what are your business plans for the current fiscal? Growing globally by building strategic alliances with international players — we do not reinvent the wheel. Our aim is to imbibe the best from the west so that our customers can get future-tech at affordable prices. With the turmoil in the international market I feel India offers good potential. u.sharma@expressindia.com

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CLEANROOM INSIGHT

Innovations in cleanrooms and environmental monitoring Dr Tim Sandle, Head, Microbiology at Bio Products Laboratory and visiting tutor at the Department of Microbiology, University of Manchester, UK discusses some innovations relating to cleanroom and clean device operations, together with personnel control and environmental monitoring. The article emphasises the importance of ensuing that good cleanroom design factors necessary for ensuring contamination control are met

harmaceutical manufacturers of both sterile and non-sterile products, and medical devices, are required to demonstrate that manufacturing processes and procedures minimise any potential contamination to the product from the manufacturing environment. Contamination can arise from a number of sources: water, air, surfaces and personnel, each of which poses a potential risk to product. These risks of contamination are avoided by putting environmental controls in place (through correct grade of air-supply, satisfactory cleaning and disinfection practices and so on). Where controls cannot off-set every contamination risk, and also as a means to demonstrate the level of control, environmental monitoring programmes are devised and put into action(1). The primary protection from contamination is through wellconstructed and maintained cleanrooms. This is supported by trained personnel, following strict gowning protocols, and cleaning and disinfection(2). Once environmental control has been accomplished, verification is undertaken through environmental monitoring (for both particulates and vi-

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THE PRIMARY OBJECTIVE OF CLEANROOMS IN PHARMACEUTICAL PROCESSING IS TO MINIMISE AND CONTROL MICROBIAL AND PARTICULATE CONTAMINATION

able microorganisms).

CLEANROOMS Cleanrooms and clean air devices are typically classified according to their use (the main activity within each room or zone) and confirmed by the cleanliness of the air by the measurement of particles. The primary objective of cleanrooms in pharmaceutical

processing is to minimise and control microbial and particulate contamination. There are many sources of contamination. There are four principles applying to control of airborne microorganisms in cleanrooms. These are(3): ❑ Filtration (through the use of HEPA filters). The air entering a cleanroom from outside is filtered

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to exclude dust, and the air inside is constantly re-circulated through HEPA (High Efficiency Particulate Air) filters (alternative filter are ultra-low penetration air (ULPA) filters). This is controlled through a HVAC (Heating, Ventilation and Air Conditioning) system. ❑ Dilution (to ensure that particles generated in cleanrooms, in addition to those which pass the filters, are carried away by diluting the area with new “clean” air). ❑ Directional Air Flow (to ensure that air blows away from critical zones, as particles and microorganisms cannot “swim upstream” against a directional air flow). This is achieved through pressure differentials. ❑ Air Movement (rapid air movement is important for as long as particles and microorganisms stay suspended in the air they are not really a problem, for it is only when they settle out that they become an actual cause of contamination).

INNOVATIONS CLEANROOMS

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There have been several advancements or changes in approach relating to cleanrooms. These include the use of modular cleanrooms and studies in energy efficiency, designed to make

cleanrooms cost effective whilst still maintaining contamination control principles.

CLEANROOM DESIGN Modern approaches to cleanroom design is aimed at ensuring that the cleanroom is designed at optimising contamination control. It is important to dedicate time in designing cleanrooms and the equipment located in cleanrooms for, if there is a design fault in one part, this will affect the items of equipment and if there is a fault in conception stage this will be expensive and time consuming to rectify. For cleanroom design, modern approaches utilise Computer Aided Engineering software for the design process, such as Building Information Modelling (BIM) software. Such software covers geometry, spatial relationships, light analysis, geographic information, quantities and properties of building components (for example manufacturers’ details)(4). Systems, assemblies and sequences can be shown in a relative scale with the entire facility or group of facilities. When designing modern cleanrooms, the following approach should be adopted: ❑ The type and function of the cleanroom should be established. This should include the required July 2015

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CLEANROOM cleanroom grades or classes and how cleanrooms of different grades will interact (including requirements for air-locks and pressure cascades). ❑ The most important aspect is drawing up the process flow. Here the cleanroom management, together with engineers and quality assurance personnel, should map the path that equipment, product and operators will take in the cleanroom. ❑ Established quality risk management tools like HACCP (hazard analysis and critical control points) or FMEA (failure modes and effects analysis) can be used for this purpose. Areas which pose a contamination control risk should be noted and attempts should be made to design these risk areas out (the principles of quality by design). Other considerations can also be included at this stage, including whether there is adequate clearance under door frames for equipment to pass through. ❑ In the design, there should be sufficient space for equipment and connections. ❑ The cleanroom should be constructed from a material which is compatible with different cleaning and disinfection solutions. ❑ Ideally, a mock-up of the cleanroom should be constructed. This is particularly important for testing the process, product and personnel workflow. In terms of understanding contamination control it is essential to understand what objects are passed from one class of cleanroom to another.

MODULAR CLEANROOMS AND BESPOKE DESIGN Modular cleanroom are cleanrooms that are assembled from prefabricated modules. This process of cleanroom construction differs from standard (or 'common') cleanrooms in that: ❑ Common cleanrooms are assembled at the construction site from many elements ❑ For modular cleanrooms a sigJuly 2015

Of these types of micro-environments, the most widely used for contamination control in relation to aseptically filled products are isolators. Isolators intended for aseptic processing are required to be operated under positive pressure and are subjected to decontamination process before start of the batch processing. Modern isolators more often use vapourised hydrogen peroxide, although alternatives are available including peracetic acid or chlorine diox(6). ide These methods can also be deployed for the decontamination of cleanrooms.

nificant part of assembling works is done at the factory that produces modules. Only assembling of complete modules remains for the customer’s site. Common cleanrooms are tailor made cleanrooms. Their design follows specific layouts that are drawn by the technologist from understanding specific processes. Whereas modular cleanrooms are often designed to fit into existing spaces. With modular cleanrooms other restrictions can appear. This is because the cleanroom construction process is separated into two parts, which are executed in two different places: the modules manufacturer and the customer’s site. This can present certain difficulties in terms of transport and later assembly (5).

ANTIMICROBIAL COATINGS Some types of equipment and surfaces can be manufactured with antimicrobial coatings. One example is the incorporation of silver or copper which are effective against a range of micro-organisms. An advantage of silver ions, for example, is that although they have antimicrobial proper-

ties, silver is rarely toxic against human cells. Examples of the application of silver include implements like forceps. Also in relation to surfaces, the incorporation of wipeable surfaces onto equipment allows for the easier cleaning and disinfection. Some of these innovations include polythene covered computer keyboards.

ENERGY EFFICIENCY Cleanroom technologies are not only directed towards contamination control. The energy efficiency of cleanrooms is currently of great importance for companies who wish to save costs and to reduce the amount of carbon generated. To address this International Standard ISO 14001, which describes environmental management and practices and EN 16001, a European energy standard, are becoming increasingly used (both standards are likely to be amalgamated into international energy standard ISO 5001). Despite the appeal of controlling energy consumption, care must be taken when adopting such standards in relation to contamination control for actions to alter the operation of HVAC (heating ventilation and air conditioning) parameters can

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have an impact upon the level of non-viable particles and viable counts. Therefore microbiologists should always be involved in any energy saving projects.

BARRIER TECHNOLOGY The use of barrier technology protects critical cleanroom operations. Within many cleanrooms unidirectional airflow (UDAF) units are found. A UDAF is classified as a minienvironment; an alternative term is ‘separative devices’ (separative devices range from open to closed systems and include isolators and Rapid Access Barrier Systems (RABS)). These are localised environments created by an enclosure to isolate a product or process from the surrounding environment. The advantages in using a minienvironment include the following: ❑ Minienvironments may create better contamination control and process integration. ❑ Minienvironments may maintain better contamination control by better control of pressure difference or through the use of unidirectional airflows. ❑ Minienvironments may potentially reduce energy costs.

The key principles for isolator use are (7): ❑ The air exchange between the isolator and with the surrounding environment must occur only through a microbial retentive filter such as HEPA or /Ultra Low Penetration Air (ULPA). ❑ The positive pressure aseptic processing isolator must be decontaminated in a reproducible and quantifiable manner to ensure the sterility assurance level of 10-6. This is assessed through the use of biological indicators of a suitable population, species and resistance. For vapour phase hydrogen peroxide systems, geobacillus stearothermophilus is normally used. ❑ Entire activity / handling of materials inside an isolator shall be achieved remotely; any part of human body cannot enter the isolator. ❑ Asepsis shall be maintained for each unit operation and for material transfers. Any material entering the isolator must either be decontaminated inside the isolator or shall be sterilised and taken inside via a rapid transfer port.

DISPOSABLE STERILE PLASTIC TECHNOLOGY A major advance with cleanroom technology is with single-use sterile disposable technologies. Such technologies have reduced risks by allowing organisations to move away from equipment which

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CLEANROOM needs to be sterilised (such as stainless steel vessels). It also negates the need to use consumables that are recycled or which present a risk with their transfer into cleanrooms, to disposable and single-use sterile items. The advantages of this technology is that it eliminates the need for cleaning, eliminates the need for the pharma company to perform in-house sterilisation, reduces the use of chemicals, reduces storage requirements, reduces process downtime and increases process flexibility, and avoids cross contamination. Single-use items are typically sterilised using gamma rays (electromagnetic irradiation), which kill microorganisms by destroying cellular nucleic acid(8). ASEPTIC CONNECTORS A variant on single use technology is the aseptic connector. Innovations in aseptic connection technology have led to the development of single use connector systems. These are based on the so-termed alpha-beta principle which allows the connection to be performed in an environment this does not require unidirectional airflow or other capital equipment to maintain sterility.

DISPOSABLE HOLDING DEVICES Plastic technology has also led to an array of sterile plastic holding devices. An example is with disposable mixing systems. These can be connected to capsule membrane filters and a hold bag. These interconnected disposable systems have a considerable advantage in that they are gamma sterilised and ready to use.

GARMENTS Given that people are one of the primary sources of microbial contamination in cleanrooms (through shedding of skin flakes, many of which contain microorganisms), attention has been paid to gowning. While behaviours and techniques for gowning can be addressed through training and pro-

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THE PRIMARY PROTECTION FROM CONTAMINATION IS THROUGH WELL-CONSTRUCTED AND MAINTAINED CLEANROOMS. THIS IS SUPPORTED BY TRAINED PERSONNEL, FOLLOWING STRICT GOWNING PROTOCOLS, AND CLEANING AND DISINFECTION

cedures, aspects of the gown design require attention. Manufacturing gowns using continuous strong fibres of pure high-density materials, like polyethylene, fabrics can be constructed that are low linting and free of inherent contaminants that could represent a risk in critical environments. Cleanroom managers are more often requesting certification for gowns to show that they are low in particulates. For gowns that are re-laundered, stipulating the maximum number of times that a gown can be washed and irradiated is important.

POLYMERIC FLOORING A risk to cleanrooms arises from personnel transferring contamination into the area via footwear or through equipment transfer (such as trolley wheels). One way to minimise contamination is to use special mats which are designed to remove dirt, particles and micro-organisms. Where such mats are used they have traditionally been sticky-mats. Although these are fairly effective, more efficient contamination control can be achieved from polymeric flooring. Polymeric flooring is an especially designed ‘plastic’ which works through electromagnetic forces causing particles to be attracted from surfaces like footwear, and retained on the surface of the mat. This mechanism ensures that any contamination residing on the mat is not passed back onto the personnel who walk across it.

MONITORING TECHNOLOGIES The most significant advancement with microbiological moni-

toring methods has been the advent of Real Time Laser-Induced Fluorescence Systems. These instruments continuously monitor both inert particulates and viable microorganisms in real time. They are very sensitive, where the limit of detection can be down to 1 microbial cell. It provides both total particulate and viable counts. The instruments are based on optical spectroscopy. This is an analytical tool that measures the interactions between light and the material being studied. These instruments work by elastic light scattering. This measures two things (9): Particle counts: where the size of a scattering particle, as it passes through a light beam, is comparable to a certain wavelength of light. The intensity of the scattering is dependent upon the size of the particle. Such systems will detect and quantify particles within a 0.5 to 20 um range. Microbial counts: a 405 nm laser that intersects the particle beam, so that as a particle passes through the inelastic scattering measures the intrinsic fluorescence of the particle, from the metabolites (such as NADH and riboflavin) inside microorganisms. There is a growing trend within the pharma industry towards the use of Process Analytical Technology (PAT). The goal of process analytical technologies (PAT) are to improve consistency of product quality, provide "right first time" manufacturing (to reduce costs and reduce cycle time), reduce the regulatory delays associated with changes in manufacturing, and improve the safety of chemical processes. PAT could also be used to reduce the end-of-

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line laboratory testing. The ‘real time’ counters fit well with this paradigm. With more classical environmental monitoring methods (the use of agar plates), it is now commonplace to be able to track the use of the media through barcoding. Scanning bar codes allows the information about the plate, such as the media batch number and expiry time, to be transferred to a Laboratory Information Management System (LIMS). To ensure that the sample is not at risk to adventitious contamination, several types of Petri dishes now come equipped with lockable lids.

ENVIRONMENTAL CONTROL Arguably the most important aspect of environmental control in a cleanroom is the control of airborne particulates as this is a direct indicator of cleanroom contamination. Particles in the air are measured through particle counters. The most efficient means of monitoring particles is by linking particle counters to a facility monitoring system (FMS). It is consist of discrete particle counters, each with individual pumps, and the data is sent using wireless ethernet to a central data capture system. Modern particle counters have the advantage that they meet the more rigorous demands of the new international standard for particle counter calibration (ISO 21501). In the event of a counter breakdown a spare counter can quickly replace the malfunctioning counter due to ‘plug-and-play’ features and the particle counting software will record the serial number for audit purposes. This feature is important for aseptic filling where

continuous particle counting is a GMP requirement.

REFERENCES 1. Sandle, T. and Saghee, M.R. (2013). ‘Cleanroom certification and ongoing compliance’. In: Sandle, T. and Saghee, M.R. Cleanroom Management in Pharmaceuticals and Healthcare, Euromed Communications: Passfield, UK, pp169-184 2. Sandle, T. (2012a). ‘Application of Disinfectants and Detergents in the Pharmaceutical Sector’. In Sandle, T. (2012). The CDC Handbook: A Guide to Cleaning and Disinfecting Cleanrooms, Grosvenor House Publishing: Surrey, UK, pp168-197 3. Halls, N. (2004): ‘Effects and causes of contamination in sterile manufacturing’ in Halls, N. (ed.): Microbiological Contamination Control in Pharmaceutical Cleanrooms, CRC Press, Boca Raton, pp122 4. Sandle, T. (2013). Application of Quality Risk Management to cleanroom design, Clean Air and Containment Review, 13, pp24-25 5. Sandle, T. (2014) Modern Approaches to Pharma Cleanroom Design, Controlled Environments, 17 (1): 8-10 6. Mau, T., Hartmann, V., Burmeister, J., Langguth, P. and Häusler, H. (2004) Development of a sterilizing in-place application for a production machine using Vaporized Hydrogen Peroxide, PDA J Pharm Sci Technol. 58(3):130-46 7. Midcalf, B, Neiger, J. and Sandle, T. (2013). ‘Fundamentals of pharmaceutical isolators’. In: Sandle, T. and Saghee, M.R. (Eds.) Cleanroom Management in Pharmaceuticals and Healthcare, Euromed Communications: Passfield, UK, pp185-226 8. Sandle, T. and Saghee, M.R. (2012). “Application of Sterilization by Gamma Radiation for Single-Use Disposable Technologies in the Biopharmaceutical Sector”, Pharmaceutical Technology, Supplement: Bioprocessing and Pharmaceutical Manufacturing, May 2012, S20-S27 9. Sandle, T. (2012b). Real-time counting of airborne particles and microorganisms: a new technological wave?, Clean Air and Containment Review, Issue 9, pp4-6 July 2015

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CLEANROOM INSIGHT

Trends in cleanroom tech Various market reports point to a strong demand for cleanroom technologies, possibly hampered by access to skilled cleanroom operators in the future. Guy Tiene, Director Strategic Content, Thatâ&#x20AC;&#x2122;s Nice LLC / Nice Insight reviews some trends driving technology development as well as a selection of recent product launches

leanroom technology is crucial for the manufacture of sterile pharmaceutical products because it ensures not only prevention of product contamination, but also operator safety when handling highly potent drug substances. In enclosed cleanroom environments, temperature, humidity, pressure, electrostatic charge and magnetic flux are carefully controlled, and particulates (dust, hair and skin), chemicals (oil, grease, metal ions, and vapors), microorganisms (bacteria and fungi) and radiation are maintained at very low levels. The market is growing at a healthy rate in part due to increased demand for sterile biologic drugs, although access to skilled cleanroom operators will be an issue in the future. Cleanroom technology providers are also challenged to provide new solutions to meet increasingly stringent regulatory requirements and everhigher performance expectations from the industry.

GROWING MARKET

NEW TECHNOLOGY TRENDS FOR CLEANROOM APPLICATIONS THAT ARE CREATING OPPORTUNITIES FOR PRODUCT MANUFACTURERS INCLUDE MINIATURISATION, SEMICONDUCTOR TECHNOLOGIES AND NANOTECHNOLOGY

While different market research firms vary in their estimates for the global cleanroom technology market, they generally expect a compound annual growth rate (CAGR) of approximately five per centwith the value of the market reaching slightly more or less than $4 billion in 2020. Mordor Intelligence estimates that the global cleanroom technology market is

worth $3.0 billion in 2015 and projects it will increase at a CAGR of 4.98 per cent to $3.83 billion by 20201, while Persistence Market Research valued the market in

July 2015

2014 at $3.16 billion and growing at a CAGR of 5.5 per cent to $4.2 billion by 20202. Both reports include cleanroom technologies for the pharma, biotechnology, medical

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device, electronics, plastics, food and aerospace industries, with the pharma/biotech/medical device sectors accounting for significant portion of the demand. Currently North America accounts for the greatest share of the global market ($1.2 billion in 2014 and growing at a CAGR of 4.6 per cent to $1.6 billion by 2020 according to Persistence Market Research), followed by Europe2. However, continued economic improvement and expansion of the pharma market and continued government initiatives to provide safer and higher-quality drug products are leading to faster growth in emerging markets, particularly India and China, according to Mordor Intelligence1. Overall drivers of demand for cleanroom technology in the pharma industry include the generally healthy growth of the industry and increasing demand for biologic drugs, many of which are offered as sterile parenteral formulations. Other factors include increasingly strict regulatory requirements, the increasing potency of many new small-molecule and biologic drugs that require special containment systems and operating procedures, and increase safety operator safety requirements3. Challenges for manufacturers of cleanroom technology include the growing expectation for customised products, the high cost of constructing, installing and maintaining cleanrooms and the in-

creasing lack of operators with the requisite skills for working in cleanrooms, according to Persistence Market Research2. Cleanroom technologies include facilities (construction type e.g. hard walls, soft walls, terminal boxes/pass-through cabinets and standard/drywall cleanrooms), equipment (e.g. air diffusers and showers, heating, ventilation, and air conditioning (HVAC) systems, high-efficiency particulate arrestance (HEPA) filters, fan filter units (FFU), desiccator and biosafety cabinets, environmental monitoring systems, laminar air flow systems, glove boxes and isolators, apparel (e.g. suits, shoes, polypropylene garments, aprons, etc.) and consumables (i.e. cleaning materials such as wipes and disinfectants). While cleanroom equipment is the largest segment based on the type of cleanroom technology, demand for consumables is growing at the fastest rate. With respect to type of construction, standard/drywall cleanrooms currently account for the largest percentage of sales, according to Persistence Market Research2. New technology trends for cleanroom applications that are creating opportunities for product manufacturers include miniaturisation, semiconductor technologies and nanotechnology, according to Grandview Research. There is also growing interest in hardwall cleanrooms due to their flexibility in construction and low installation costs3.

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CLEANROOM TRENDS DRIVING TECHNOLOGY DEVELOPMENT Increased regulatory attention on cleanroom performance and more frequent production of higher value biologic drugs are key drivers of recent advances in various types of cleanroom technologies. There is significant financial incentive to ensure that production in cleanrooms proceeds according to regulatory requirements and results in products that meet specifications. Therefore, not only are high-performing filters and related equipment needed, but robust monitoring systems for air, water, humidity, and all aspects of cleanroom operations are also required to ensure that high performance is maintained4. The shift in the pharma industry – both for small and large molecule drugs – to smaller, more flexible manufacturing facilities that can be located to serve regional markets and manufacture a wide range of smaller volume, niche and targeted therapies is another important trend affecting the cleanroom technology market. Manufacturers have responded with the development of modular cleanroom systems that can be constructed rapidly to GMP requirements. Some contract manufacturers are also installing cleanrooms to establish a competitive advantage and attract new business. In addition, with the rigid controls inherent in cleanroom operations, yields can be increased and operator performance can also be improved4. Flexible containment solutions are also attractive for development work because often the toxicity of developmental products is not well understood, and cleanroom environment aid in the prevention of cross-contamination5. Retractable cleanrooms are also getting attention, particularly for companies that do not require constant access to cleanroom environments, do not need the production size generally available with traditional systems or who have limited room in their manufacturing facilities and cannot ded-

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icate a large space for cleanrooms. Retractable cleanrooms can offer a cost-effective solution6.

AWARD-WINNING CLEANROOM TECHNOLOGIES7 The importance of cleanroom technology to the pharma industry is reflected by three winners of the 2015 Facility of the Year Awards “FOYAs”, which are issued by the International Society for Pharmaceutical Engineering (ISPE). These three facilities included GMP cleanrooms for the cost-effective manufacture of advances therapies. AstraZeneca (AZ) China’s 533,000ft2 (50,000m2) solid dose facility in Taizhou, China, which was constructed in just 20 months at 18 per cent below budget and with an excellent safety record, took the prize in the Project Execution category. The facility comprises sterile dry powder filling for injectable cephalosporin and oral solid dosage products and includes formulation, tableting, labeling, packaging and distribution capabilities. The company relied heavily on local sourcing, including for cleanroom wall systems, most workers were

hired from the local area and provide expensive training and significant emphasis was places on simplicity and avoidance of over engineering. The 2015 FOYA for Facility Integration went to biologics and vaccine contract manufacturer IDT Biologika, a member of the Klocke Group, for its highly automated filling and freeze-drying plant in Dessau, Germany. The multipurpose facility is based on a modular design with horizontal division of the service areas for easy expandability and simple operation, with production at clinical and commercial scales. It is also certified to biosafety levels (BSL) 1 and 2 for live vaccines. Finally, for its success in balancing investment, appropriate compliance, efficient operations and business viability during the successful construction of a 70,000ft2 aseptic filling facility in Billerica, MA, an honorable mentioned was awarded to human injectables producer Pharmalucence Pharmaceuticals. The company consolidated four separate operations in one modern facility with state-of-the art aseptic processes in order to ensure long-

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term availability of its legacy and generic radiopharmaceutical products, for many of which there are market shortages.

SELECTION OF RECENT PRODUCT INTRODUCTIONS ABN Cleanroom Technology’s VIX cleanroom concept offers energy-efficient decentralised air circulation. Due to innovative air circulation systems, a high level of tightness and low-maintenance components, the energy requirements of this system are 10 times lower than those of comparable cleanroom concepts, according to the company. Air is guided out of the cleanroom in a permanent circulation loop through extraction fans into the air return filter system, then back through the ceiling plenum into the cleanroom. The re-use of the already cooled, only partially contaminated air saves the majority of the energy costs normally required for the humidification and cooling of air used from outside due to the lower particle count of the re-used air. The filters are under a lower pressure drop and the air exchange rate can be dynamic.

The facility monitoring software developed for TSI’s facility monitoring system (FMS) is designed using SQL databases for real-time mirroring. In addition, no data is lost if the connection to the database server is unavailable, and if the monitoring computer fails, a redundant monitor computer takes over automatically. Furthermore, data are collected without the need for a user interface. The system is also in compliance with 21 CFR Part 11 and allows for demonstration of GMP compliance through graphical charts, reports and data export tools. Finally, system views, status windows, alarm notifications and multi-level maps enable efficient communication and quality assurance, according to the company. PSL Powder Systems has developed a nano-containment isolator that includes a contained drum hoist mechanism and systems for dispensing, weighing and sampling with a containment performance of 30–100ng/m³ in eight hours total weight average (TWA), which will be tested and certified by a third party hygienist prior to the start of production. Getinge La Calhène has introduced several new product innovations, including the DPTE-XO alpha port, a compact Isoflex-R isolator, a Moduline isolator for filling lines a virtual reality tool for ergonomic isolator design and Steritrace III Noxilizer Inside, a new isolator biodecontamination system. The Minncare Dry Fog 2 System from Mar Cor Purification is the latest version of its Dry Fog Technology for modern cleanroom disinfection. The system is designed completely of 316 L stainless steel and engineered to be virtually maintenance free. It also allows for eight different nozzles or nozzle positions and is over 95 per cent faster than some conventional systems, according to the company. The latest filter products from HET Filter meet the requirements of the highest OEB level5. The Flecozip (Flexible Containment Zip) from Flecotec is, according to the company, a novel July 2015

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CLEANROOM system that offers contaminationfree docking, storage and transfer of toxic or sensitive bulk solids through the use of a patented, split zip fastener that joins two separate connections together in an airtight and dust-free manner. G-CON Manufacturing has enhanced and expanded its miniPOD portfolio to meet the stringent aseptic processing requirements of the cell therapeutic and personalised medicine industry. The miniPOD CT offers a unidirectional material and personnel flow design and can be sanitised by vapourised hydrogen peroxide if an environmental excursion occurs. These cleanroom systems are readily deployable (built within 15 weeks after design approval) and include their own air handling systems. The compact ductwork internal air handling system enhances containment and sanitisa-

tion of the entire cleanroom space, according to the company. PortaFab introduced a lightweight (½”-thick aluminum honeycomb panel and lighter-weight aluminum extrusions), flexible, framed cleanroom wall system that is lower in cost than traditional cleanroom wall systems without sacrificing quality or functionality, according to the company. The new system features vertical and horizontal members that are easily connected to each other and provide airtight seals. Modular cleanroom strut walls provide a cost-effective solution for bay- and chase-style cleanrooms; incorporation of standard strut-style metal framing into the wall system eliminates the need to frame out cleanrooms while still utilising standard strut connectors for piping, conduit, and other utilities.

FLEXIBLE CONTAINMENT SOLUTIONS ARE ALSO ATTRACTIVE FOR DEVELOPMENT WORK BECAUSE OFTEN THE TOXICITY OF DEVELOPMENTAL PRODUCTS IS NOT WELL UNDERSTOOD, AND CLEANROOM ENVIRONMENT AID IN THE PREVENTION OF CROSSCONTAMINATION

REFERENCES 1. Mordor Intelligence, Global Cleanroom Technology Market- Market Trends and Forecasts (2015 - 2020), June 2015, http://www.mordorintelligence.com/industry-reports/globalcleanroom-technology-market-industry?gclid=CNuv0rfIssYCFdccgQod3j cKhw 2. Persistence Market Research, Global Market Study on Cleanroom Technology: Consumables to Witness Highest Growth by 2020, April 2015, http://www.persistencemarketresearch.com/market-research/cleanroom-technology-market.asp 3. Grandview Research, Cleanroom Technology Market Analysis, Market Size, Application Analysis, Regional Outlook, Competitive Strategies and Forecasts, 2015 To 2022, http://www.grandviewresearch.com/i ndustry-analysis/cleanroom-technol-

ogy-market 4. Nikita Ernst, “Clearing the Way for Cleanroom Technology,” Pharmaceutical Processing, Nov/Dec 2014, pp. 22-23. 5. Jonathan Sutch, “Flexible Use of Cleanrooms”, Controlled Environments, April 28, 2015, http://www.cemag.us/articles/2015/04/flexible-use-cleanrooms 6. Lynne Beggs, “The Evolution of Cleanroom Design,” Controlled Environments, February 20, 2015, http://www.cemag.us/articles/2015/02/evolution-cleanroomdesign 7. “Pharma builds recognized for excellence,” Cleanroom Technology, Jun 12, 2015, http://www.cleanroomtechnology.com/technical/article_page/Ph arma_builds_recognised_for_excellence/109185

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CLEANROOM PROFILE

Cleanrooms of future GR Peshkar, Director, Pace Air Management, gives an outlook on the futuristic designs of smart cleanrooms for nuclear medicines, genetic, virology and bio — technology facilities

Advancements in medical science ◗ DNA codification/genetic mapping/ stem cell developments/production of cell and tissues/ genetherpy /virology bone marrow transplanting

Needs and requirements ◗ India should be identified as a global hub for developing AIDS vaccines, stem cells, various vital tissues biosensors etc. ◗ Increase the necessity of more and more smart, clean rooms ◗ Design, maintain and operate smart cleanrooms which are technologically advanced, economical, viable and suits our existing and futuristic infrastructure

fatiguing, bending or abrading ◗ Is non-magnetic and non-conductive when particles enter (these characteristics are specifically required) ◗ Should not be inordinately expensive ◗ Should be readily available ◗ Should be easy to form or otherwise fabricate with current manufacturing techniques

to the outside. ◗ In a high risk area a class-III cabinet would be used. ◗ A pass through autoclave may be available to allow for the sterilisation of contaminated material. ◗ Rooms in which the hazards are high would contain the hazard with in class-iii type cabinet and provide a shower area between the air lock and the room.

Finishes choosen to keep clean room free contamination and minimise the generation of particles within the room

Supply of liquid and gases to bio – cleanroom

◗ Air leaks through the walls around window, piping etc. ◗ Air filter leaks in gaskets and in the filter itself ◗ Filtration efficiency of different filters ◗ Fire proof material construction ◗ Wearing resistance of surfaces ◗ Air movement in the cleanroom ◗ Humidity temperature pressure etc.

◗ Specific chemical composition to exclude substances likely to interfere with the work in the room ◗ Low particle shedding ◗ Low out gassing ◗ Good impact resistance, including to local cracking and crazing due to hard body impact ◗ Resistance to microbial growth and survival ◗ Electrostatic characteristics that are comparable with rooms and help to create surface with low dust attraction, these are less likely to become dirty and so facilitate the maintenance of cleanliness

The surface of perfect cleanroom material area:

Containment of contamnation

◗ Has a smooth texture ◗ Has abrasion resistance ◗ Easy to clean ◗ Does not emit particles ◗ Does not store static charge ◗ Does not become electrically charged with in the laminar airflow of the clean room ◗ Is durable enough to accomplish the design table without wearing,

◗ Active pharma products such as hormones, active radioisotopes must not reach the operator. ◗ Microbiology laboratories dealing with diseases producing micro organisms requires to ensure that the personnel working highly in them or the people passing near them are not infected. ◗ The technology associated with

List of relevant tests:

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IT IS ALSO COMMON TO FIND CLEAN ROOM WITH CONTAMINATION FACILITIES WITHIN THEM

design of these containment rooms is similar to that used in cleanrooms and it is normal that containment rooms should also be cleanrooms. ◗ It is also common to find clean room with contamination facilities within them.

Containment rooms and cabinets ◗ Clean air is supplied to the room, but more air must be extracted. ◗ The air that is extracted must be filtered through a high efficiency hepa filter before being discharged

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◗ Not only the air is free of contaminations, but the other gases and liquids supplied to rooms are also free of contamination. ◗ In pharma products and radio pharma cleanroom there is a requirement for large quantities of water used to make up pharma and in semiconductors fabrication area pure water is used to wash silicon wafer during the manufacture and so also radio pharma, various gases for formation of isotopes are needed. This input must be provided with extremely low level of contamination.

Design guidelines for industries: The following guidelines are given to aid in reducing these costs: 1)Don’t over design/design flexibility. 2)Provide bulkhead mounting of the process equipment, where ever possible, in critical contamination – sensitive areas. 3) Provide a cleanroom environment only where it is needed, and only to the level needed. 4)Always examine process equipment design for freedom

from vibration and electromagnetic interference. 5)Define how the cleanroom is to be built, design utility distribution system to provide ready access for attachment to process equipment without the necessity for shutting down the system or cleanroom. 6)Provides adequate flow rate to prevent stagnation and impurity pickup. Prevent pressure fluctuation during operating ‘runs', even slight variations can have disastrous effects on the product. It is true not only on supply, but on the extract as well. It pertains to all systems of process utilities supply return such as : Gases supply and extract (exhaust liquid supply and drain)

Design methodlogy for radio pharma, bioclean and biotechnology applications A simplified step wise approach can be summarised as follows: ◗ Analyse production stages ◗ Prepare process flow diagram ◗ Define activities associated with rooms ◗ Define environmental quality requirements ◗ Quantifying production, process and space requirements ◗ Prepare room association diagrams ◗ Define the accommodation needs ◗ Develop layout and scheme ◗ Prepare designs and specification ◗ Undertake the detailed design and construction process PACE AIR MANAGEMENT E-mail : paceairmanagement1@ rediffmail.com July 2015

CLEANROOM Airotek Systems: Offering superior quality range of cleanroom equipment Sandip Lagad, Proprietor, Airotek Systems talks about the company's services

irotek Systems manufacturer and supplier of a superior quality range of cleanroom equipment, cleanroom panel and door, air filter, laminar air flow unit. The company offered products are widely used in various places like pharmaceutical/biotechnology laboratories, R&D, hospitals, hotels and shopping malls. These products are broadly acclaimed for their perfect finish, enhanced durability, easy to use, low maintenance and corrosion resistance. These are extensively appreciated for their robust design, low maintenance, durability and long service life. These products are available in various specifications as per clients’ exact requirements at market price. These products are manufactured using high quality raw material and advance technology by our skilled team of professionals as per the defined international quality standards. In order to meet the exact requirements of our valuable clients, the company offer the entire product range in a number of specifications as per their requirement. Airotek Systems is backed by a sound and sophisticated infrastructure facility that helps in carrying out all its tasks in a proper manner. To execute all the activities in a smooth and streamlined manner, its infrastructure unit has been segmented into varied subunits like manufacturing facility, quality checking laboratory and warehousing and packaging section. The production unit is installed with the latest machinery and modern technology that enable the company to cater the diversified requirements of their clients. This infrastructural base is maintained by a team of skilled workmen, who make sure that bulk as well urgent demands of the clients fulfilled within the promised time frame. Its professionals are selected after a stringent examination procedure. These professionals are skilled in their respective domains and thus strive hard to

July 2015

achieve the best possible outcome. The company is actively engaged in manufacturing and supplying superior quality range of cleanroom equipment, cleanroom panel and door, air filter, laminar air flow unit. The offered products are manufactured using optimum quality raw material and sophisticated technology.

Clean room equipment ◗ Dynamic pass box ◗ Static pass box ◗ Sampling / dispensing booth / reverse laminar air flow ◗ Horizontal / verticle laminar air flow bench ◗ Vertical laminar air flow unit ◗ Biological safety cabinets ◗ Garment storage cabinets ◗ Air shower ◗ Air curtain

Cleanroom moduler panels and doors ◗ Partitions and ceiling panels ◗ AIR filters ◗ Pre filters ◗ Fine filters ◗ Hepa filters ◗ Filters housing

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CLEANROOM NEWS Cleanroom consumables to witness highest growth by 2020 Lack of skilled professionals, high cost of setting up and maintenance restraining growth: Persistence Market Research ACCORDING TO a market report published by Persistence Market Research in June this year, titled 'Global Market Study on Cleanroom Technology: Consumables to Witness Highest Growth by 2020', the global cleanroom technology market was valued at $ 3,156.0 mn in 2014 and is expected to grow at a CAGR of 5.2 per cent from 2014 to 2020 to reach an estimated value of $ 4,290.1 mn by 2020. Globally, the cleanroom technology market is witnessing significant growth due to growing regulatory concerns regarding the packaging, manufacturing, and processing of better quality products, and safety of the working personnel. Additionally, increasing demand for sterilised pharmaceutical formulations, and development of new biologics and its wide applications in the medical devices industry is driving the growth of the cleanroom technology market. However, factors such as lack of skilled professionals and high cost associated with the setting up and maintenance of cleanrooms are restraining the growth of the global market for cleanroom technology. North America is the largest segment in the global cleanroom technology market. This is due to technological advancements and growing applications of cleanroom technology in the region.

July 2015

GLOBALLY, THE CLEANROOM TECHNOLOGY MARKET IS WITNESSING SIGNIFICANT GROWTH DUE TO GROWING REGULATORY CONCERNS REGARDING THE PACKAGING, MANUFACTURING, AND PROCESSING OF BETTER QUALITY PRODUCTS, AND SAFETY OF THE WORKING PERSONNEL

The North American market for cleanroom technology was valued at $ 1,209.3 million in 2014 and is expected to reach $ 1,580.8 million by 2020, growing at a CAGR of 4.6 per cent. In terms of type, cleanroom consumables are the fastest-growing segment. In terms of construction, standard/drywall cleanroom is the largest segment in the global cleanroom technology market. Kimberly-Clark Corporation, Illinois Tool Works, and E.l. Du Pont De Nemours And Company are some of the leading players in the global cleanroom technology market. Some of the other major players in the cleanroom technology market are Azbil Corporation, Taikisha, Royal Imtech, Ardmac, M+W Group, Clean Air Products and Alpiq Group. Asia is expected to experience a high growth rate in the global cleanroom technology market in

the future. This is due to improving healthcare infrastructure, rising popularity of certified products, and increasing adoption of cleanroom technology by the healthcare industry in Asian countries. Various factors such as increasing demand for better quality products and safety of the working personnel are driving the global cleanroom technology market. Additionally, increasing demand for sterilised pharmaceutical formulations, and development of new biologics and its wide applications in the medical devices industry are propelling the growth of the cleanroom technology market. However, lack of skilled professionals and high cost associated with the set-up and maintenance of cleanrooms are restraining the growth of the global cleanroom technology market.

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Cleanroom tech market worth $3,761.9 million by 2019 APAC region to clock highest CAGR of 8.2 per cent: MarketsandMarkets report ACCORDING to a MarketsandMarkets report, the global cleanroom technology market was valued at $2,726.9 million in 2013 and is expected to grow at a CAGR of 5.5 per cent during the forecast period of 2014 to 2019. The report titled, “Cleanroom Technology Market by Equipment (HVAC System, HEPA Filter, Air Shower, Air Diffuser), Consumables (Apparel, Gloves, Wipes, Disinfectants), Construction (Hardwall, Softwall), and by End User (Pharmaceutical, Biotech) – Global Forecast to 2019”, analyses and studies the major market drivers, restraints, and opportunities in North America, Europe, Asia-Pacific, and the Rest of the World (RoW) over the forecast period of 2014-2019. The global market has experienced steady growth in the past few years mainly attributed to the stringent healthcare regulations, emergence of biologics, growing healthcare industry in the developing countries, and rising application of cleanrooms in medical devices industry. However,

high cost associated with installation and use of cleanrooms hinders the growth of healthcare cleanrooms market to a certain extent during the forecast period. The global market is segmented by technology, by type of construction, end user, and geography. It also discusses the key market drivers, restraints, and opportunities of this market and its submarkets. The market is expected to grow at a moderate CAGR of 5.5 per cent from 2014 to 2019. In 2013, North America was a major market for cleanroom technology with around 38 per cent share of the global market, followed by Europe, Asia-Pacific, and RoW. Asia-Pacific region represents the highest growth opportunity for the market during 2014 to 2019 and is expected to grow at a CAGR of 8.2 per cent during the forecast period. The growth in this market is majorly driven by increasing development of pharmaceutical and biotechnology industries in this region.

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CLEANROOM Global cleanroom disposable gloves market to reach $1.4 billion by 2020 China, India,Vietnam and Philippines set for double digit growth rate from 2014-2020 ACCORDING to a recent report by Allied Market Research entitled, "Global Cleanroom Disposable Gloves Market (Product Types and Geography) - Size, Share Trends, Regional Trends, Segmentation and Forecast, 20132020", the global cleanroom disposable gloves market is expected to reach $1.4 billion by 2020, registering a CAGR of eight per cent during 2014-2020. Neoprene disposable gloves would emerge as the fastest growing segment, at a CAGR of 17.5 per cent during the forecast period. In order to maintain aseptic and contaminant-free environment during production, controlled environmental conditions

are the prerequisites for pharmaceutical, semiconductor and electronics manufacturing companies. The prerequisites can be achieved by setting up distinct and separate cleanrooms, which necessitates the need for clean room disposable gloves in the production environment. Factors such as a large base of consumers, stringent regulatory requirements and the popularity of 'cleanroom-customised' gloves are driving the growth of the market. Following the positive strides in the adoption of the clean room disposable gloves, the market is expected to reach 35.6 billion pairs by 2020. Natural rubber/latex disposable gloves, despite its conventional nature,

NATURAL RUBBER/LATEX DISPOSABLE GLOVES, DESPITE ITS CONVENTIONAL NATURE, CONTINUES TO DOMINATE THE MARKET

continues to dominate the market. It held about 2/5th of the market share in 2013 making it the leading market segment, and shall continue to lead the market during

forecast period. Unchallenged physical attributes such as comfort and dexterity supplement the growth of natural rubber/latex gloves. The study finds that nitrile gloves hold second highest CAGR i.e., 9.2 per cent during 2014-2020 while natural rubber/latex gloves would account for the largest market share, both in terms of volume as well as value through 2020, followed by vinyl gloves. Asia Pacific accounted for the 48 per cent of the global market in 2013, followed by North America, at 28 per cent of the global market share. China emerges as one of the most lucrative markets during 2014-2020. Geographically, the market

share of developed countries in the global cleanroom disposable gloves market is expected to decline due to the use of industrials robots; whereas, the developing nations would witness a steady rise in their market share due to surplus work force and outsourced pharma manufacturing operations. Thus, countries such as China, India, Vietnam, and Philippines exhibit a double digit growth rate during the analysis period. Presently, US is leading the market in terms of volume and value; however, China would surpass US in the coming years and would subsequently emerge as a market leader.

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ensuring long-lasting reliability. The modular structure of the curtains, assembled and joined by anodised aluminium extrusions, provides for a wide range of polyester

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dental tearing, saves money and time. The alternating metal tubular structure there inserted ensures high wind-resistance. prime doors are the ideal solution for in-

Contact details Gandhi Automations 2nd Floor, Chawda Commercial CentreLink Road, Malad (W) Mumbai â&#x20AC;&#x201C; 400064, IndiaTel: +91 22 66720200 / 66720300(200 Lines) Fax +91 22 66720201 Email: sales@geapl.co.in Website : www.geapl.co.in July 2015