Particle Monitoring to Meet USP <797>

The current USP 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. 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 rooms 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.

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

Particle Monitoring to Meet Compliance

The PDA issued a recommendation1 for routine monitoring for all Aseptic Grade areas using portable particle counting devices such as the HandiLaz Mini. These recommendations are as follows.

Air Cleanliness Classification Grade A - ISO 5 Grade B(1) - ISO 7 Grade B(2) - ISO 7 Grade C - ISO 8 Grade D - unclassified

Type of Operations Critical aseptic preparations Immediately adjacent to Grade A Aseptic rooms and corridors, component storage, gowning Non aseptic filling, terminally sterilized product. Areas for washing and handling components.

In Operation Not less than 1 x each shift Not less than 1 x each shift Not less than 1 x each day Not less than 1 x each week Not less than 1 x each month

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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 Handilaz Mini 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. The HandiLaz Mini comes with Operations and Validation documents to help you meet USP <797>. For help with your USP 797 solution, contact us at info@pmeasuring.com or 303.443.7100.

References
1. PDA Journal Vol. 57 No. 2 March/April 2003.
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Author: Mark Hallworth 2012 Particle Measuring Systems. All rights reserved. App Note 77 9/18/2012
HandiLaz is a registered trademark of Particle Measuring Systems, Inc. Reproduction or translation of any part of this work without the permission of the copyright owner is unlawful. Requests for permission or further information should be addressed to Particle Measuring Systems, Inc. at 1-800-238-1801

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