Isolators are increasingly installed in pharmaceutical production laboratories due to the increased handling of hazardous drug ingredients as well as the need for smaller batches and more flexible production environments. Isolators can potentially lower the installation and maintenance costs compared to large-scale cleanroom environments. While manufacturing facilities have established SOPs for isolators, this article focuses on the importance of proper cleaning and wiping procedures.
Isolators and Decontamination
Decontamination is the reduction or removal of biological or chemical agents, including non-active particles to non-hazardous levels to products, processes, or the environment by means of physical or chemical procedures.
Specifically in pharmaceutical manufacturing environments, research laboratories, and hospital pharmacies, the effective decontamination of biological agents like bacteria, viruses, fungi, protozoa, prions, and spores is essential.
Isolators like fume hoods, bio-safety cabinets, and glove-boxes are used to create environments with low levels of environmental pollutants such as biological agents, aerosol particles, and dust. These separative devices have a controlled level of contamination, specified by the number of particles with a defined size per cubic meter, providing controlled environments that are specifically tailored to the needs of its operator. This classification of cleanrooms and isolators, however, is not taking into account specific requirements regarding biological contamination. In order to maintain the low levels of environmental pollutants, isolators have to be decontaminated on a regular basis.
Isolator cleanliness levels are defined by different clssifications, shown in Table 1 and Table 2. These classifications are evaluating the environmental pollution by particles, however, not taking into account specific requirements regarding biological contamination. In order to maintain the low levels of environmental pollutants, isolators have to be decontaminated on a regular basis.
Quality supervisors in facilities using isolators have to determine the acceptable level of biological agents in their respective environment and decide on the method to achieve these levels. Several factors influence the choice of method and materials.
Isolators are used in a variety of industries working with different material and under different requirements. Potential contaminates in isolators can therefore range from biological contaminates (e.g. pharmaceutical industry, hospital pharmacies), radioneclides (e.g. pharmaceutical industry, research laboratories), to general particulate contaminates (e.g. semiconductor industry).
Chemical Agents: Inactivation
Spills of hazardous chemical agents in isolators or potential reaction products immobilized on isolator surfaces have to inactivated or diluted to non-hazardous levels. The chemicals and chemical processes used for inactivation depend on the contaminant.
Biological Agents: Disinfection and Sterilization
To reduce the level of biological agents in an environment, disinfectants/sanitizers and sterilants can be used. Sanitizers and disinfectants are terms used in different industries for the same kind of product. Whereas the food and food-processing industry uses the term sanitizers, the pharmaceutical industry, laboratories, and hospitals are predominantly using the term disinfectant.
Disinfection describes a process that eliminates many of all pathogenic microorganisms on inanimate objects, except bacterial spores¹. On the other hand, Sterilization describes a process that destroys or eliminates all forms of microbial life and is carried out by physical or chemical methods². Depending on the biological agent and the material or media holding it, sterilization can be achieved through the application of heat, chemicals, irradiation, high pressure, or filtration. It is essential to understand the difference between both processes to assure that contamination level requirements of work environments are met. Whereas some commercial and technical literature us confusing readers by using both terms interchangeably, it should be noted that Disinfection and Sterilization describe two processes with very different requirements in outcome. It is not appropriate to talk about partial sterilization or even replace the word disinfection with sterilization.
The efficacy of sterilization depends on a number of factors like:
- Prior physical cleaning (effective surface and biofilm reduction)
- Presence of organic and inorganic load-level and type of microbial contaminants
- Concentration of sterilant
- Exposure time of sterliant
- pH, temperature, and humidity of environment
- Geometry of object and spaces
- Physical properties of objects
- Always clean from the cleanest to the dirtiest surface
- Clean with overlapping strokes and change wiper surface with each stroke
- If using an isolator cleaning tool or mop, change out cover material with each surface side of the isolator
- What contaminates am I concerned about?
- Would they contaminate my processes (inside) or the environment (outside)?
- Are these contaminants inert, chemically-, biologically-, or radio-active?
- What contamination limits have to be considered?
Production Automation understands the needs of cleanrooms, pharmacies, and laboratories so we strive to bring our customers the highest quality, the widest selection, and the technical support they need to identify and purchase the proper consumables needed.
- Healthcare Infection Control Practices Advisory Committee (HICPAC), “Guideline for Disinfection and Sterilization in Healthcare Facilities”, 2008
- McDonnell, G.; Russell, A.D.; “Antiseptics and Disinfectants: Activity, Action, and Resistance” Clinical Microbiological Reviews, Jan. 1999, p. 147-179
- Mehmi, M.; Marshall, L.J.; Lambert, P.A.; Smith, J.C.; “Evaluation of Disinfecting Procedures for Aseptic Transfer in Hospital Pharmacy Departments” PDA Journal of Pharmaceutical Science and Technology, Vol. 63, No. 2, p. 123-138
- † Block, S.S.; ‘Disinfection, Sterilization, and Preservation” Philadelphia: Lea & Febiger 1991
- ‡ Siegerman, H. “Wiping surfaces Clean” A2C2 Magazine, April 2003
- †† “Isolator Cleaning Guide” 01 Aug 2010 Berkshire Corporation