Cleanroom 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 ever-higher performance expectations from the industry.
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 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 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 increasing 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 bio-safety 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.
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 dedicate 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-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 bio-decontamination 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 system that offers contamination-free 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 sanitisation of the entire cleanroom space, according to the company.
PortaFab introduced a light-weight (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.
1. Mordor Intelligence, Global Cleanroom Technology Market- Market Trends and Forecasts (2015 – 2020), June 2015, http://www.mordorintelligence.com/industry-reports/global-cleanroom-technology-market-industry?gclid=CNuv0rfIssYCFdccgQod3jcKhw
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/industry-analysis/cleanroom-technology-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-cleanroom-design
7. “Pharma builds recognized for excellence,” Cleanroom Technology, Jun 12, 2015, http://www.cleanroomtechnology.com/technical/article_page/Pharma_builds_recognised_for_excellence/109185