A Quality Management System necessitates forethought into the myriad number of variables that must be managed in a Corrective Action, Preventative Action (CAPA) approach. A well thought out cleaning, disinfection and decontamination program for the pharmaceutical manufacturing environment is one of the fundamental components of a successful operation. In order to manufacture safe and quality products, one must satisfy the strict demands of the federal and international regulatory agencies as well as the exact demands of their customers. This means understanding what types of contamination damages your products as well as all sources of those contaminates.
The cleanroom environment is under constant attack by potentially fatal contaminants generated by three major factors: cleanroom personnel, the endless stream of supplies, materials and equipment brought into the cleanroom environment daily, and the manufacturing processes that take place within the cleanroom.
A properly designed cleanroom staffed by personnel who understand and follow proper cleanroom protocols can keep these particles to extremely low levels. But extremely low levels many not be good enough. Particles impregnated with microorganisms travel along air currents in the cleanroom and most are carried back to the air filtration system for entrapment and removal. However, many of the particles tend to settle on the surfaces they come into contact with. Some of these are at or near critical production areas.
Settling particles are affected by numerous physical forces such as static, ionic attraction, humidity, gravity and Van der Waal forces -- to mention just a few -- which cause them to bond to surfaces in such a manner that their removal becomes very difficult, at best. This is where a specialized crew of technical cleaners who are properly educated, trained and equipped can remove environmental contamination threats to your process and product.
Personnel Training is mandatory
Training is the essential element in developing a good cleanroom cleaning technicians. Workers must have a thorough understanding of exactly what a cleanroom is, how it functions and what purpose it serves. Equally important is imparting knowledge of exactly what kinds of contamination causes problems for their specific process and products. This way explaining what contamination needs to be eliminated and why is easy to comprehend. Technical cleaners do not need a degree in particle science or microbiology, but some knowledge of contamination ID’s and characterization,microorganisms and habitat, particle size, movement and adhesion qualities is essential if they are expected to perform their duties at the required levels. Without this basic knowledge, all subsequent training means nothing.
First focusing training on the contamination burden introduced by each of us is a good way to establish personal awareness and self-responsibility. Instilling good personal hygiene habits and teaching the proper gowning procedures are perhaps the two most important aspects of this initial training phase. These should be followed closely by a comprehensive understanding of proper cleanroom protocols.
Only after trainees have mastered the above, should they be introduced to the methodology -- or good science -- of cleaning and disinfecting a cleanroom. This methodology includes defining a list of prohibited materials that must never be taken into a cleanroom and the introduction of accepted chemicals, supplies, materialsand equipment. Proper instruction in precise cleaning procedures and verification of cleanliness levels round out a proper cleanroom cleaning and disinfection methodology.
Tools, materials and chemical selection are keys to success
The cleaning needs of any particular cleanroom are not necessarily related to the class of cleanroom being serviced. Each case requires individual analysis of not only the cleanroom`s cleanliness requirements (class of cleanroom), but also of the amount and type of contaminants generated within the cleanroom by manufacturing processes and personnel. The gowning requirements of cleanroom personnel must also be taken into consideration, along with the airflow characteristics of the cleanroom. If a cleanroom has underperforming utility needs, overcompensation in contamination control protocols will be required.
It is important to note that not all areas or surfaces within a specific cleanroom will require the same cleaning methodologies and frequency of cleaning. Once the cleaning needs are established, thought should be given to the types of cleaning tools, materials and chemicals that should be used in a cleanroom environment.
Caution should be used when purchasing a vacuum. Just because a vacuum claims to be HEPA filtered, does not mean that it performs to ANSI standards. Most of the vacuums that can be purchased at the local hardware store would raise eyebrows with the FDA and other Quality auditors. A cleanroom vacuum filters the exhaust with a HEPA filter. There seem to be only three brands that occupy this market, Nilfisk, Tiger Vac and Hako Minuteman.Central vacuum systems are also used, but not as much in the pharmaceutical industry. The absence of exhaust airflows in the cleanroom itself is very attractive. The length of the hose and the ribbed structure of it, render it almost impossible to keep clean.
Portable vacuum systems are used in cleanrooms that don`t have a central system and as a supplemental system for those who do. The selection of a portable vacuum system to fit the task is essential. Portable backpack-type vacuums with the proper HEPA filtration have become a popular choice for cleanroom use. They allow more mobility for hard to reach areas, such as behind process equipment, and in areas such as ceilings, high walls and stairs. Care must be taken with these vacuums, as the exhaust air flow happens at work station level and will cause turbulence that could be problematic.It`s imperative to maintain all filters and ancillary equipment for all vacuum systems in proper working order and cleanliness. Ancillary equipment includes hoses, nozzles and other precision cleaning attachments of various sizes and shapes. Equally important is the selection of materials used in these attachments. You wouldn`t want to use a material that could scrape the surface being cleaned, thereby creating additional particle generation.
Although used for many non-hazardous but still critical cleaning operations, the "hazardous materials vacuum" was originally designed for cleaning up wet chemical spills. The recommended procedure for dealing with chemical spills is to notify the facility`s Chemical Safety Officer before anyone attempts to clean up the spill. In most cases, this individual will deal with the problem.There is always a possibility that housekeeping staff could become involved with a chemical cleanup. Therefore, it`s important that they are properly educated in this area because of the ever-present danger of fire, explosion, and harmful or poisonous fumes. It`s also imperative that your tools -- in this case, the hazardous materials vacuum -- are properly cleaned after each use to avoid any potential chemical incompatibility or harmful reactions during its next use.It is also important to have a variety of materials available for cleaning up wet chemical spills. Chemical compatibility is equally important and each cleanroom housekeeper should know what products to use with what chemicals.
Mops and related floor cleaning equipment are perhaps the next most important item in a cleanroom maintenance program. Mop handles are available in a variety of non-contaminating materials, such as fiberglass, plastic or stainless steel. Selection is usually based on need; lighter products are best for cleaning ceilings and walls, while the heavier and more durable handles are better suited for floor cleaning applications. Stainless steel is an unnecessary expense unless you are autoclaving them for use in an aseptic environment.
The proper selection of a mop head for specific applications is even more important, however. Mop heads also are available in a wide variety of materials and configurations. Typical examples include sponge mops, which can be self-wringing, and string mops, which typically are made of polyester fibers or PVA for electronic environments.Routine autoclaving of all mop heads prior to use in Class 100 critical/sterile environments is the only way to stop the introduction of any bacterial contamination into the sterile cleanroom environment. In sterile environments, throw them away after just one use. That may sound expensive, but the damage that can result from transferring live bacteria or viruses can be devastating to a company`s bottom line. Also, think carefully about cross contamination. You may not want to take a mop head that was used to clean one area of a cleanroom, such as the gowning area, into another area of the cleanroom, especially from a noncritical area to a critical area. Mop heads are expensive, to be sure, but not as costly as the damage cross contamination can cause.
Cleaners probably use more wipes than any other single cleaning product or tool. The most important thing to remember is that selection should never be based on cost. Selection criteria should be based on intended usage, cleanliness, particle-shedding properties, chemical residue of the wiper content, static properties, absorbency and size. It`s important to remember that each specific cleanroom cleaning application may require a specific type of wiper. A wiper manufacturer should be consulted for the best wiper for various applications.
It is important to use the same process grade water at a given facility, for the cleaning functions in that facility. The most commonly usedis Water for Injection (WFI), Deionized Water (DI), and Reverse Osmosis (RO). City water is not recommended due to the large amount of minerals and microorganisms in it.
There are a variety of commercially available floor, wall, ceiling, glass and multipurpose cleaning and disinfection products. Chemicals must be selected to remove all the possible contamination variables the will damage the process and product.Some of the major concerns when selecting cleaning materials include:
- Product compatibility. Let`s not kill the product.
- Process compatibility. Let`s not damage the equipment.
- Facility surface compatibility. Make sure the product can do its intended job, while at the same time ensuring that it doesn`t cause unwanted results. For example, IPA tends to remove moisture from whatever surface it comes in contact with. On unsealed vinyl floors, IPA reacts with the plastercizers and produces a fine, white powdery film that can shed or flake. When walked on, it creates small particle storms that can quickly throw a cleanroom out of spec. IPA also tends to remove paint and can etch plastic and Plexiglas. Despite these examples, IPA is a very popular cleaning and disinfectant. However, care should be given to its use and applications.
- Environmental compatibility. Check all ingredients. Some cleaning detergents have unacceptable levels of minerals and microorganisms, which can damage process and products.
Establish cleaning protocols
The Institute of Environmental Sciences (IEST) WG 18 Cleanroom Housekeeping defines the cleanroom industries standard for cleaning and disinfecting cleanrooms. Further clarification can be found in ISO14644-5 Cleanroom Operations and the soon to be released PDA Technical Report on Cleaning and Disinfection Fundamentals.
Vacuuming pulls loose particles from surfaces. Wiping or mopping provides the mechanical energy to remove more tightly bound particles, and cleaning/ disinfection solutions break the surface tensions and reduce adhesion forces. It is a time-tested method proven to be the most reliable and applicable to most general cleanroom cleaning applications.
The following are recommended protocols for specific cleaning applications:
Vacuum with a soft brush attachment. Wipe or mop gently in a single direction using slightly overlapping strokes. Remove soil, with a commercial cleaner, DI water and a woven polyester wiper.
Vacuum horizontal surfaces with a soft brush attachment. Wipe surfaces ofthe light lenses with a mop or wipe dampened with process grade water and disinfectant. Wipe trim pieces.
HEPA filtration units
Use extreme caution not to make contact with the HEPA filter.
Most SOP’s that I’ve read instruct one to gently wipe exposed surfaces dampened with process grade water and disinfectant. I personally prefer to use a plastic bottle with the desired solution and spray the units without touching them at all.
Vacuum with a soft brush attachment. Mop or wipe with a solution of process grade water and a commercial cleaning detergent or disinfectant. Wipe in one direction using slightly overlapping strokes. The strokes can be performed either horizontally or vertically, but the mop or wiper must proceed from top to bottom. While achieving a certain dwell time for the solution being applied, use a minimum of liquid to avoid splashing or dripping on undesirable equipment, instruments and materials. Remove smudges with an appropriate cleaning chemical and lint-free wipe.
Squirt glass cleaner (typically IPA and Water) on woven polyester wipe. Apply to surface with dampened wipe. Wipe with a dry woven polyester wipe.
Vacuum with a curved pipe attachment. Use a wipe damped with a solution of process grade water and a cleaning/ disinfectant chemical. Wipe in one direction only, using slightly overlapping strokes. Wipe top to bottom whenever possible.
Consult with a process engineer and/ or a group leader of the area, prior to cleaning any process equipment, clean only as specifically instructed. Use wipes damped with appropriate solution -- again use caution when determining chemical compatibility and necessary contamination removal. First vacuum with soft brush attachment, then wipe surfaces in one direction only, using slightly overlapping strokes. Wipe from top to bottom and back to front, avoid splashing or dripping of cleaning/ disinfection solution.
Vacuum the entire surface starting from the dirtiest area to the cleanest and from the back or furthest area toward the front. Clean/ disinfect floor with an appropriate solution of process grade water and a cleanroom detergent/ disinfectant. Use a clean, lint-free mop head. Whether applying a detergent or a disinfectant, dip the mop back in solution approximately every 20 linear feet. Using a clean mop is critical to the operation. The bucket of solution should be changed approximately every 400 sq. ft. Failure to change the water on a regular basis can lead to cross contamination, dragging potentially damaging contamination from one area to the next.
There are a few general rules to remember when cleaning or disinfecting a cleanroom floor, regardless of its composition. The three secrets are clean solution, clean solution, clean solution.
Regardless of what type of flooring a cleanroom has, it is typically the dirtiest and most highly contaminated part of a cleanroom. After all, more than 80 percent of all cleanroom contamination winds up on the floor at one time or another and is then stirred up by foot traffic and put back into the air flow. A clean cleanroom starts with a clean cleanroom floor.
Most companies that I visit are still using a nylon brush and solution to scrub the drains. This is an inherently contaminating practice, as the bristles clear the top of the drain on the up stroke and snap contamination into the airstream. I like to prepare a gallon of the disinfection solution in rotation, remove both the grate and the screen and place them in the solution to soak for the mandated dwell time. Wipe both with a lint-free wiper, then pour the solution down the drain and wipe the upper portion of the drain pipe without your wrist entering the pipe. Put the screen and grate back in place.
The verification process used to determine if the cleaning crew has done a good job in decontaminating the cleanroom varies by industry and can be as simple as a visual inspection or as sophisticated as microbial identifications.Different types of verification include, a visual inspection, by far the most widely used method. However, it is not nearly as reliable as more scientific methods. In the regulated industries microbial samples are pulled from different surfaces and then counted and identified. These give only a snap shot of the particular surface area sampled. More than 99% of any given manufacturing cleanroom room is not tested by QC during a RODAC sampling process. This, to my mind, necessitates inclusion on the sign-off logs of more than a Verification signature that the forms were filled out correctly. It demands a Witness signature that the cleaning and disinfection process steps explicitly detailed in the SOP’s were observed by someone who understands them.
A Quality Management System must becreated with the understanding that contamination control is not just a function, but a science and technology that continuously interacts with all individuals, equipment, facilities and all aspects of the manufacturing process. Such an approach creates a mindset of process and product protection, and of quality that will ensure success.
Cleaning and disinfecting the manufacturing facility, equipment and contents is one of the most important components in any Quality Program. It is also the least expensive andgreatestinsurance in protecting the enormous investment required for today`s GMP manufacturer.
Ian M. Wallis, president of Wallis and Associates of Newburyport, Mass. He can be reached at [email protected]