N.51 – Training of personnel in Cleanroom, Isolator, RABS according USP 38 – The United States Pharmacopeial – Document (1116) Aseptic Processing Environments – Page 1195

TRIO

-The personnel performances

Good personnel performance plays an essential role in the control of contamination, proper training and supervision are central to contamination control. Aseptic processing is the most critical activity conducted in Microbiological Controlled Environments, and manufacturers must pay close attention to details in all aspects of the endeavor. Rigorous discipline and

strict supervision of personnel are essential in  order to ensure a level of Environmental  quality appropriate for  aseptic processing.

Training of all personnel working in controlled environments is critical.

This training is equally important for personnel for the microbial monitoring program, because contamination of the Clean working area could inadvertently occur during microbial sampling. In highly automated operations, monitoring personnel may be the employees who have the most direct contact with the critical surfaces and zones within the processing area.

Microbiological sampling has the potential to contribute to microbial contamination caused by inappropriate sampling techniques or by placing

personnel in or near the critical zone. A formal training is required to minimize this risk. This training should be documented for all personnel who enter controlled environments. Intervention should always be minimized, including those required for monitoring activities , but when interventions cannot be avoided they must be conducted with aseptic technique that approaches perfection as closely as possible.

-The management of the facility

Management of the facility must ensure that personnel involved in operations in Clean Rooms and advanced aseptic processing environments are well versed in relevant  microbiological principles. The training should include instructions about the BASIC principles of aseptic techniques and should emphasize the relationship of manufacturing and handling procedures to potential sources of product contamination. Those supervising , auditing, or inspecting Microbiological Control and Monitoring activities should be knowledgeable about the BASIC principles of microbiology, microbial physiology, disinfection and sanitation, media selection and preparation, taxonomy, and sterilization. The staff responsible for supervision and testing should have academic training in medical or Environmental Microbiology.

Sampling personnel as well as individual working in Clean Room should be knowledgeable about their responsibilities in minimizing the release of microbial contamination.

Personnel involved in microbial identification require specialized training about required laboratory methods. Addition  training about the management of collected data must be provided. Knowledgeable and understanding of applicable standard operating procedures are critical, especially those procedures relating to corrective measure taken when environmental conditions required.

Understanding of contamination control principles and each individual’s responsibilities with respect to GMP should be an integral part of the training program, along with training in conducting investigations and in analyzing data.

-The significant sources of contamination

The only significant sources of microbial contamination in aseptic environments are the personnel. Because operators disperse contamination and because the ultimate objective in aseptic processing is to reduce end-user risk, only healthcare individuals should be permitted access to controlled environments. Individuals who are ill must not allowed to enter an Aseptic Processing Environment, even one that employs advanced aseptic technologies such as isolators, blow/fill/seal or closed RABS.

-The importance of Good Personal Hygiene

The importance of Good personal hygiene and a careful attention to details in aseptic gowning cannot be overemphasized. Gowning requirements differ depending on the use of the controlled environment and the specifics of the gowning system itself. Aseptic processing environments require the use of sterilized gowns with the best available filtration properties.

The fullest possible skinhead coverage is desirable, and sleeve covers or tape should be considered to minimize leaks at the critical glovebox-sleeve junction.

Exposed skinhead should never be visible in conventional Clean Room under any conditions. The personnel and gowning considerations for RABS are essentially identical to those for conventional Clean Room.  

Once employees are properly gowned, they must be careful to maintain the integrity of their gloves, masks, and other gowns materials at all times.

Operators who work with isolator systems are not required to wear sterilized Clean Room gowns, but inadequate aseptic techniques and employees borne contamination are the principal hazards to safe aseptic operations in isolators, as well as RABS, and in conventional Clean Rooms. Glove and sleeve assemblies can develop leaks that can allow the mechanical transfer of microorganisms to the product. A second glove, worn under or over the primary Isolator / RABS glove, can provide an additional level of safety against glove leaks or can act as a hygienic measure.

-Conclusions

Also, operators must understand that aseptic technique is an absolute requirement for all manipulation performed with gloves within RABS and Isolator systems. The Environmental Monitoring program, by itself, cannot detect all events in aseptic processing that might compromise the microbiological quality of the environment. Therefore, periodic media fill or process simulation studies are necessary, as is thorough ongoing supervision, to ensure that appropriate operating control and training are effectively maintained.