01 November 2016

Points to consider for design

There is not a single “right” way to construct an aseptic processing facility or cleanroom, as each should be designed to accommodate the processes and products contained in the cleanroom. There are, however, general principles of design that should be followed in constructing a cleanroom or aseptic processing facility.

Many points to consider can be found in ISO 14644-4, the FDA aseptic processing guideline, and in EU Annex 1. I highly recommend these references.

The following points should be considered:

Floors, walls, and ceilings should be constructed of materials that are smooth, hard, and easy to clean. Transitions between floors and walls should be designed with a smooth transition (coved) to allow for easy cleaning.
Temperature and humidity controls in cleanrooms and supporting areas should be sufficient to maintain operator comfort when gowned and maintain adequate humidity for the process. Consider humidity and temperature loads from operating equipment such as autoclaves, CIP/SIP, etc., when designing temperature and humidity controls.
Cleanrooms should be designed to facilitate personnel, equipment, and material flows to prevent microbial contamination of sterilized or sanitized equipment and facilities, sterilized components, and sterile filtered drug product. Personnel should enter the cleanroom through gowning facilities. Equipment and materials should either enter through sterilization or dehydrogenation equipment or through airlocks using a validated sanitization procedure. Multiproduct facilities should be designed to eliminate or minimize instances where product streams cross.
Pay careful attention to locations of return ducts in Grade A/B rooms, as they can affect the unidirectional airflow over critical processing zones.
Investing in a computational flow dynamics (CFD) analysis of the cleanroom design may be worthwhile, as this can reveal unforeseen problems in the design. CFD analysis will require accurate representation of the equipment as installed, accurate locations of HEPA filters and returns, and accurate estimates of supply volumes of the HEPA filters.
The cleanroom should be positive by at least 10-15 Pascal to all surrounding zones of lower classification. This is accomplished by a cascade-type design, in which the cleanroom is surrounded by areas of lower classification, which are then surrounded by areas of even lower classification, eventually leading to an external unclassified area.
When setting up pressure monitoring in an existing building monitoring system (BMS) or when installing a new BMS, consider where the reference area for differential pressures is located. It is important that a stable reference point is used to ensure good control of differential pressures. Referencing one clean zone to another clean zone can be problematic, as it can cause fluctuations in one clean zone to cascade to other clean zones.