A 25-Year Retrospective on Cleanroom Management

Cleanrooms have evolved since 1988 because of the advances in science and technology. These innovations have benefitted consumers worldwide. New products, medical advancements, space exploration, travel, computers, and communications all have one major common denominator—better living through cleanroom technology.

STANDARDS

In 1992, at the instigation of the Institute of Environmental Sciences and Technology, the American National Standards Institute (ANSI) petitioned the International Organization for Standardization (ISO) to create the Cleanrooms and Associated Controlled Environments technical committee, formally established in May 1993. The mission of this committee was to develop an international standard for cleanrooms and associated controlled environments encompassing standardization of equipment, facilities, and operational methods. In accordance with ISO procedures, the work would be performed in "working groups." On November 29, 2001, ISO 14644-1 and 14644-2, officially replaced US Federal Standard 209 Airborne Particulate Cleanliness Classes in Cleanrooms and Clean Zones. This change was necessary because until the formation of TC 209, each country had its own standard, which differed from Federal Standard 209. The difference was confusing for companies with multiple plants worldwide. Federal Standard 209 also had limitations on particle classifications and size ranges. ISO/TC 209 pulled together the best of all of the existing standards into one set of standards that could be applied to all cleanrooms, irrespective of product or process.

View the 1988 article, "Clean Room Management," by Anne Marie Dixon, at BioPharmInternational.com/Retrospectives.

The ISO/TC 209 working groups addressed additional areas of interest beyond Federal Standard 209, such as Test methods (ISO 14644-3), Design, Start-up and Construction (ISO 14644-4), Operations (ISO 14644-5), Separative Devices (ISO 14644-7), Bio-contamination (ISO 14698-1,2), Classification of Air Cleanliness by Chemical Concentration (ISO 14644-8), and Classification of Surface Particle Cleanliness (ISO 14644-9).

In 2009, ISO/TC 209 work began under a new scope that would specify the minimum requirements for classification, design, and operations of nanotechnology facilities as they differ from cleanrooms described in the existing other ISO/TC 209 documents. A committee draft was published in 2012 and the working group is anticipating the publication of the first document, Classification of Air Cleanliness by Nanoscale Particle Concentration as a DIS (Draft International Standard) in early 2013.

OPERATIONS

Cleanroom costs for design and construction have greatly increased over the past 25 years. Materials of construction have improved and designers are more aware of the need for surfaces that can be cleaned and withstand aggressive disinfectants. However, degradation and the aging process are major concerns of the cleanroom user community. The internal surfaces of the cleanrooms and the HVAC system have become a major issue in older facilities. Ductwork wear and damage, surface finishes, electrical systems, computer systems are some of the areas that are affected by sporicidal agents that are used routinely in the sanitization process.

Environmental monitoring limits have changed—many regulators have lowered the limit standards. Some of today's cleanrooms were designed when the limits for air viable and surfaces were much higher. These changes to standards have resulted in additional cleaning (drowning) of the facility with disinfectants and sporicidal agents.

The cost of operations (i.e., utilities, supplies, salaries, support staff, security) has increased dramatically over the past 25 years. Today, companies must take into consideration the process, product, regulatory or customer requirements, risk, and quality requirements when designing a facility. The focus should be on "clean air" over the product and not create a "clean the world" facility. Designs are changing to include closed systems, separative devices, robotics, continuous monitoring, controls, and an understanding of contamination control. The final cleanroom layout and design should support the product and process.

PERSONNEL TRAINING

Personnel working in a cleanroom environment require specific training. As an example, if the subject was aseptic gowning, the understanding of the risk during gowning and the cross-contamination to the product, process, and/or patient is important. Since 1988, limit for the allowable colony forming units (CFUs) per plate in qualifications has decreased dramatically. Common training in 1988 included brief training, practice, and qualification. Understanding the sequence of gowning and the techniques for performing gowning are crucial. Training for aseptic gowning must allow for the student to observe the complexities; therefore, the student must perform gowning to become proficient. The training must allow the students to practice. Today, practice requires time.

Electronic or eLearning was becoming popular in 1988, but some facilities lost interest because of an inability to maintain a current program. Many companies did not invest in the time or personnel required to maintain these programs. Some firms have eLearning available but only on a limited basis. The technical support for eLearning is GMP and standard operating procedures (SOPs). Federal regulations do not necessarily change dramatically every year, but hundreds of SOPs do change annually, making change control and management of any eLearning program difficult.

SOP training is performed every day in every cleanroom and controlled environment in all industries. The "read and understand" method of SOP training requires employees to read and sign a training form stating that they understand the information. For some SOPs, this may be sufficient. But for other SOPs, this may not be successful. Some SOPs must be taught and explained. Others will require a demonstration of the task to be performed. One example of this type of SOP would be for the admittance of items into an airlock or pass-thru. How do you sanitize? How do you remove a layer of wrap or bag? How do you unload a cart? How do you clean the cart? The admittance of items is the second largest source of contamination for any cleanroom or controlled environment, yet little time is spent in training on the proper transfer techniques.

Operator turnover is a way of life in many facilities. In 1988, there were many plants that had employees with tenure. Today, many companies are using temporary staffing because of the high benefit package for employees. This environment creates a challenge for the training staff. New employees may arrive on site monthly or, in some plants, weekly. Trainers must be available to handle the basic GMP courses, cleanroom courses, gowning, and the extensive number of SOPs.

THE FUTURE OF CLEANROOMS

What is the cleanroom of the future? The world of nanotechnology will lead us into the next evolution of cleanrooms and controlled environments. The design and operations of cleanrooms and the types of products to be manufactured are far more extensive than anyone could have imagined in 1988. The biopharmaceutical industry is rapidly growing, developing new products for future generations.