SMEPAC is an acronym for the International Society of Pharmaceutical Engineers (ISPE) “Standardized Measurement of Equipment Particulate Airborne Concentration” Guideline (First Edition 2005). In 2012, ISPE published its Second Edition and changed the title to “Assessing the Particulate Containment Performance of Pharmaceutical Equipment” (hereafter known as the “Guideline”) and incorporated the document into ISPE’s Good Practice Guide collection. It should be noted that a revised Guideline is expected to be published in 2023-24.

SMEPAC testing provides a standardized methodology to assess the particle containment capabilities of pharmaceutical manufacturing equipment (i.e. isolators, flexible containment, split butterfly valves, downflow booths, etc.) or related equipment such as ventilated balance enclosures. SMEPAC testing (otherwise known as containment validation monitoring) is generally used in factory acceptance testing (FAT) and/or site acceptance testing (SAT), but is often used in the operation of new facilities, and performing potent compound safety gap assessments.

Why is SMEPAC testing necessary?

In the pharmaceutical industry, as the percentage of active pharmaceutical ingredients becomes more potent (OELs < 10 µg/m3), in order to prevent occupational (worker) exposure or to prevent cross-contamination, the need for greater containment is required. Therefore, to test the actual performance of containment equipment and devices, testing is required. SMEPAC provides a standard methodology for such testing.

How is SMEPAC testing performed?

SMEPAC testing is generally performed by positioning industrial hygiene air sampling pumps in specific stationary locations to collect airborne particulate matter of a surrogate compound (lactose, naproxen sodium, mannitol, etc.) on a specific filter media. In addition, surface swipe samples are collected to assess the potential for surface contamination.

In order to ensure the proper calibration of air sampling equipment and the collection of samples, SMEPAC testing should be performed by a Certified Industrial Hygienist or Occupational Hygienist or someone with similar qualifications and/or experience in SMEPAC testing. Furthermore, to ensure the integrity and independence of the analysis of the collected samples, all laboratory analytical work should be performed by an accredited industrial hygiene laboratory that specializes in the pharmaceutical industry.

What are the limitations of SMEPAC testing?

There are numerous limitations to SMEPAC testing that must be considered. These limitations are as follows:

• You need a containment performance target (CPT). Without knowing how low (in µg/m3) you need to control your process, you may be in store for unexpected results. This requires having a good understanding of the types of compounds you currently are processing and ones that you plan on processing in the future. You will need OELs and ADEs for each of these compounds. Depending on the number of iterations (3 or more), the CPT could be as low as 0.1 of the lowest occupational exposure limit (OEL) of the active pharmaceutical compound (API) that your company will be processing. Consult with DS/EN 689:2018 Workplace exposure - Measurement of Exposure by Inhalation to Chemical Agents - Strategy for Testing Compliance with Occupational Exposure Limits.
• SMEPAC testing is only for powders (not liquids, vapors, or gases). Therefore, if you have APIs that undergo sublimation (such as dimethyl fumarate), the results of the SMEPAC testing may be invalid, require further analysis, and/or interpretation.
• SMEPAC testing is highly dependent on the amount of API that is being processed, the equipment used, and the duration of the activity. If your actual conditions are different than the testing conditions then the SMEPAC testing results will not apply.
• SMEPAC testing does not consider any additional protection afforded by respiratory protection.
• Testing needs to be performed on a periodic basis. SMEPAC testing was never intended to be a one and done activity. Over time there are changes in activities, personnel, and equipment wear and tear that may impact performance. The current guidance document does not provide a specific retesting interval.

Conclusion

As the percentage of active pharmaceutical ingredients become more potent, the need for greater containment exists. However, once the containment devices have been designed, built and installed, SMEPAC testing should be performed by an independent firm with qualified personnel to ensure that they meet or exceed the desired containment performance target.

About Affygility Solutions

Since 2002, Affygility Solutions has been providing potent compound safety, occupational toxicology and industrial hygiene services to biotechnology, pharmaceutical and medical device companies throughout the world. With Affygility’s longevity in the toxicology industry, you can have confidence you are receiving OEL / PDE monographs you can trust in order to implement risk-management controls. Contact Affygility to discuss how we can become your trusted occupational toxicology service provider.

Published October 11, 2022

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