Understanding and evaluating the level of containment achieved by a containment system or equipment is crucial for the processing of APIs, particularly potent pharmaceutical compounds. Based on toxicological evaluations, APIs can be placed into hazard or control bands depending on their potency and toxicological effects. This is the first step in the identification of the hazard potential of the new chemical entity (NCE) or API and the associated exposure controls to ensure personal protection and minimize product cross-contamination. Each hazard/control band should be associated with safe handling guidelines that outline the appropriate facility, equipment, and administrative controls to ensure exposure is maintained below the occupational exposure limit (OEL) for the NCE/API. In general, a potent API is defined as one with an occupational exposure limit (OEL) at or below 10 µg/m3 and a highly potent API as having an OEL below 1 µg/m3 (1).
Good industrial-hygiene practice dictates that engineering controls are the primary means to control personal exposure. Containment equipment, such as isolators, contained transfer systems, and other contained chemical and pharmaceutical process equipment, are examples of engineering controls in use today. Containment systems and equipment with integrated containment systems are being designed and used by biopharmaceutical manufacturing facilities for all pharmaceutical operations (i.e., chemical production of bulk API to product formulation to packaging) and for all dosage forms, including solid, parenteral, and others, including inhalation and dermal, to control personal exposure and minimize cross contamination in a multi product facility.
The process of selecting containment equipment and systems should include:
To provide consistent and repeatable data to evaluate the equipment and/or containment system prior to installation, upon installation, and during operation, it is crucial that testing be performed following a standard methodology. Because the potential exists for both airborne emissions and surface contamination, industrial-hygiene sampling methodologies for both air and surface sampling are used to evaluate the potential emissions that may be generated during normal processing and cleaning of containment systems and equipment (2,3).
- Performing a process review of the process steps, unit operations, and tasks
- Identifying the APIs, intermediates, and finished products to be handled and processed, including their associated OELs and/or hazard/control bands
- Setting a containment performance target (CPT) for the process
- Specifying and selecting the containment equipment based on the task list and the CPT
- Verifying containment performance by performing a factory acceptance test (FAT) and site-acceptance test (SAT)
- Evaluating containment performance and occupational exposure to workers during actual operations processing the NCE or API.