The current USP 797 requirements for particle monitoring can be summarized as to prove that a cleanroom, or clean device, meets the defined ISO 14644-1 classifications. Therefore, laminar flow hoods used in the manipulation of sterile product should meet ISO 5 limits. Background areas and ante rooms should meet either ISO 7 or ISO 8, depending on the activities performed in those areas.

To ensure that the designated zone is maintained in a clean state, a particle monitoring program should be designed based upon contamination risk to finished product quality. The ISO 14644-2 standard is referenced and is the recertification schedule for proving continued compliance. However, this is not a monitoring program. The Parenteral Drug Association (PDA) offers guidance pertaining to monitoring frequency which is based upon risk in manufacturing environments and is in accord with FDA requirements.

Certification to ISO 14644-1

Several industry papers have been written on the certification of clean areas to ISO 14644-1 and they should be read for more details. Our purpose here is to highlight the general requirements of the program:

1. Measure, calculate, and record the area of the ISO 5 laminar flow hood (LAF). The number of particle monitoring points necessary is the square root of the area in m2.
2. The area of the background ISO 7 area is the total room area minus the ISO 5 area. The number of samples required for the ISO 7 is the square root of the ISO 7 area in m2.
3. Sample points must be equidistant and at work height, irrespective of the activity at the sample location. The intention of the certification process is to determine if the filtration system is operating in accordance with a defined standard and has no bearing on product or process risk (at this point).
4. Samples are taken in a grid pattern at the identified locations and the PASS / FAIL criteria calculated for ISO 14644-1.
5. The exercise is repeated for the background ISO 7 area. The room's geometry may make it difficult to determine the sample points. In this case, an equal area formula can be done (i.e. 1 sample every x m2).
6. A final report is created and marks the end of the certification process.

For details of calculations performed, refer to the ISO14644-1 document.

The steps above can be done in either an operational or at-rest state. Once this is done, a baseline has been set in accordance with ISO 14644.

Particle Monitoring to Meet Compliance The PDA issued a recommendation for routine monitoring for all Aseptic Grade areas using portable particle counting devices; these recommendations are:

Table 1 (download pdf for all figures and tables)

Figure 1: Handilaz Mini Portable Particle Counter used for USP <797> Monitoring (download pdf for all figures and tables)

USP<797> provides recommended frequencies for environmental testing of microbial contamination; this frequency should also be adopted for proof of control over non-viable contaminants. Routine testing of the clean areas using a particle counter provides real-time information about the activities in that area. Also, if a high risk process can be identified in advance, the particle counter can be used to qualify that process. The sample data can provide information that helps the user determine whether to change the process or install barriers to protect the patient from contamination.

Author: Mark Hallworth, of Particle Measuring Systems

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