Consider these recommendations for evaluating, validating, and implementing a USP <797>-compliant garment program
By Jan Eudy, Cintas
The latest revision to United States Pharmacopoeia (USP) General Chapter <797> Pharmaceutical Compounding–Sterile Preparations, was released in June 2008. The implementation of USP <797> in compounding pharmacies in the United States has been erratic at best. The information provided in this article is based on a case study of a company that operates compounding pharmacies in 23 metropolitan areas of the United States and its evaluation, validation, and implementation of a cleanroom garment program compliant to USP <797>.
The pharmaceutical cleanroom industry is acutely aware of the many possible sources of contamination that threaten production operations. The most significant threat is also the threat that is easiest to control–the people working in the cleanroom. These concepts of contamination control are the focus of USP <797> for compounding pharmacies.
One of the most significant methods for reducing human contamination in the cleanroom is through a complete cleanroom uniform program. Cleanroom apparel is designed to capture and entrap particles and not allow contaminants to be dispersed into the critical environment. Apparel protects from numerous contaminants that are generated from the human body, including:
- Viable particles such as bacteria and yeasts
- Non-viable particles such as hair, dead skin cells, and dandruff
- Elements such as sodium, potassium, chloride, and magnesium
It is important to note that because the human body produces these contaminants in such large quantities the cleanroom apparel may be overwhelmed. Therefore, change frequencies and garment system configurations must be evaluated for the room cleanliness that each operation is expected to achieve.
USP <797> mandates that all compounding must be performed in an ISO Class 5 cleanroom environment or better. When the classification of the compounding pharmacy cleanroom has been determined and the decision made whether to use gloveboxes, unidirectional flow hoods, and barrier isolator systems to meet the cleanroom classification requirements of USP <797>, then cleanroom apparel can be selected. The compounding pharmacies in this case study chose to wear “tech suits” (also known as cleanroom undergarments) under the sterile coverall, hood, and boots as recommended in IEST-RP-CC003.3 for ISO Class 5 cleanroom applications.
The Institute of Environmental Sciences and Technology (IEST) published the recommended practice for garments, IEST-RP-CC003.3, “Garment Considerations for Cleanrooms and Other Controlled Environments,” in 2003. This document is a useful resource, providing guidance for the selection of fabric, garment construction, cleaning, and maintenance of cleanroom garments, and testing of cleanroom apparel and components for use in aseptic and non-aseptic clean-room environments.
Using ASTM and AATCC test methods
The contamination control industry has developed innovative fabrics and apparel to encapsulate workers in the cleanroom, thereby protecting the product and processes from possible deleterious contamination. There are several ASTM (American Society for Testing and Materials) and AATCC (American Association of Textile Colorists and Chemists) test methods used to evaluate new fabrics.
The weight of the fabric determines its strength and durability; however, a lighter fabric contributes to operator comfort. The grab tensile and tongue tear tests give an indication of the strength and durability of the fabric.
The pore size is an indicator of barrier efficiency. More particles will be entrained with a fabric that has a smaller pore size. Therefore, consideration of this characteristic is important to the evaluation of the fabric used in the cleanroom garment construction.
The moisture vapor transmission rate (MVTR) evaluates the ability to move moisture through the fabric and translates to more comfort for the operator. Moisture buildup causes the operator to feel hot due to the increase in humidity between the fabric and the body.
Air permeability is the ability of a fabric to allow air to pass through it, which is quantified by the volume-to-time ratio per area. Airflow in heating and cooling processes, such as the cooling process of the body, contains contaminants that can be transferred to the product. The lower the permeability or transfer of air from within the garment to the outside, the lower the contamination to the product.
There are several tests to determine the fabric’s splash resistance or ability for the fabric to resist absorption of liquids. These characteristics allow the operator to be better protected from spills in the cleanroom environment.
Static decay and surface resistivity testing is performed to document that the fabric is static dissipative. Fabrics outside of the static dissipative range of 105 to 1,011 Ω/square may cause an electrical discharge and subsequent product failure.
All testing of fabrics should be performed over time and exposure to gamma radiation. The results over time should not be significantly different from the original results, therefore demonstrating durability of the fabric characteristics over time.
These same tests may be used in the evaluation of the garment system (fabric and components of garments) to withstand chemicals used in the cleaning of the cleanrooms, the cleaning of the garments, the application of gamma radiation, and, in some cases, autoclaving.
Evaluation of seams and components via RP-CC003.3
Currently all reusable cleanroom garments are constructed of 99 percent polyester and 1 percent durable carbon yarns with cleanroom-compatible, gamma-compatible snaps, zippers, and binding. These garment systems are lightweight, non-linting, economical, and control both non-viable and viable particle contamination. The IEST document details recommended seam construction and components for cleanroom garments.
Using body box testing
All cleanroom garment systems will deteriorate over time due to multiple wash/dry/wear and sterilization cycles. The ability of the garment system to act as a barrier to contamination and its filtration efficacy is evaluated in a “body box” test. The body box is a mini-cleanroom. The particle cleanliness of the area is determined by typical room particle measurement with a particle counter and probe. Wearing the garment system, the operator inside the body box performs a series of prescribed movements to the prescribed cadence of a metronome. The particle measurement during the prescribed movements determines the garment system’s efficacy.
A compilation of the test results and information including the validation of the selected fabrics and garments was evaluated by the quality department of the compounding pharmacies during this case study.
Evaluation of the cleaning of the garment system
The latest revision of IEST-RP-CC003.3 details recommended parameters for the cleaning of cleanroom garments and revised the performance of the Helmke Tumble test for particle cleanliness. This revised version has established test parameters that, when followed precisely, produce results that are more robust, repeatable, and reproducible over various test laboratory settings. The Helmke Tumble test is specifically designed to test the particle shedding of a garment over time. This test evaluates the integrity of the garment as well as the cleanroom garment laundry’s overall ability to render the garment item “particulately clean.” The Helmke Tumble test evaluates particle shed at 0.3 μm and larger. The ASTM F51 test evaluates the same characteristics but at a larger micrometer particle (>5 μm) and fibers. This test is less reproducible due to technician variability over various laboratory settings.
Additionally, extraction testing can be performed to determine if residual elements and/or compounds are present in the cleanroom garments after cleanroom laundering.
Validating a cleanroom garment system supplier
There are numerous steps involved in validating a cleanroom garment system supplier:
- Complete an installation qualification that audits the garment system supplier and evaluates their qualifying tests and testing results.
- Perform an operation qualification that includes a trial at the customer site and evaluation of the customer-qualifying tests and results.
- Conduct a performance qualification that includes evaluation of the performance of the fabric and garment system over time within the customer’s cleanroom.
All of these steps are necessary to ensuring that a garment system meets the expectations and apparel needs of the individual operation. This information, reviewed during an on-site audit, comprised the validation of the regularly scheduled cleaning of the garments and the cleanroom garment system supplier for the compounding pharmacies in the case study.
Jan Eudy is corporate quality assurance manager at Cintas (www.cintas.com) and President Emeritus of the Institute for Environmental Science and Technology (IEST). She is also a member of the editorial advisory board for CleanRooms magazine.
For more information on the revised USP Chapter <797>, visit http://www.usp.org.