MA Board Adopts Rapid Microbial Methods for Sterility Testing

MA Pharmacy Practice Resources & Guidance

Published May 1st, 2025

Detected February 12th, 2026

Summary

The Massachusetts Board of Registration in Pharmacy has adopted a new policy allowing the use of Rapid Microbial Methods (RMMs) as an alternative for sterility release testing of compounded sterile preparations (CSPs). This policy outlines requirements for licensed sterile compounding pharmacies to ensure public safety when using these advanced technologies.

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What changed

The Massachusetts Board of Registration in Pharmacy has issued Policy 2025-01, establishing requirements for the use of Rapid Microbial Methods (RMMs) as an alternative to traditional USP <71> sterility testing for compounded sterile preparations (CSPs). The policy, effective May 1, 2025, mandates that any RMM used must be validated, demonstrate non-inferiority to USP <71>, and be suitable for the specific pharmacy environment, including the ability to detect relevant microorganisms and support investigations of failed tests.

Massachusetts-licensed sterile compounding pharmacies considering RMMs must conduct thorough due diligence, including method validation and risk assessments, to ensure the RMM is equivalent or superior to compendial methods. Pharmacies must verify the RMM's limitations, such as its ability to identify all microbes and whether it is destructive to the sample, necessitating sample retention for investigations. Failure to adhere to these standards could result in non-compliance with state law, which requires adherence to current USP standards for sterile compounding.

What to do next

Review MA Board of Registration in Pharmacy Policy 2025-01 regarding Rapid Microbial Methods (RMMs).
Verify that any RMM technology used for sterility testing is validated and meets USP <71> non-inferiority standards.
Conduct a risk assessment for any RMM, considering its limitations and impact on sterility failure investigations.

Source document (simplified)

Adopted: 5/1/25 Page 1 of 5 Board of Registration in Pharmacy Policy 2025 - 01: Rapid Microbial Methods (Rapid Sterility Testing) The Massachuse tts Bo ard of Registration in Pharmacy (“Board”) adopts this policy regarding the use of Rapid Microbial Methods (“ RMMs ”) as an alternative for sterility release testing of compounded sterile preparations (“CSP”) by Massachusetts-licensed sterile compounding pharmacies. The purpose of this policy is to safeguard the public by outlining requirements for the use of such technologies. It is the position of the Board [Draft 247 CMR 17.17 (2) ] that a pharmacy may not dispense a CSP that requires sterility testing unless and until it first receives negative sterility test results. In accordance with USP <797>, sterility testing must be performed according to USP <71> or a validated alternative met hod that is noninferior to USP <71>. As a reminder, state law requires sterile compounding pharmacies to “ adhere to the most current standards established by USP, all chapters, when engaging in any form of sterile compounding.” I. General Considerations A. Has the RMM method been validated and demonstrated to be suitable for its intended use in accordance with USP chapters Validation of Alternative Microbiological Methods < 1223 > and Validation of Compendial Procedures < 1225 >? B. Does the RMM get comparable results (non -inferior) to the standard compendial test (USP <71>)? What is the limit of detection of microorganisms with the specific technology (i.e., does the RMM de tect low levels of microorganisms)? For growth-based RMMs, does the RMM detect microorganisms in a short incubation period? For example, slow growing microorganisms or a lag in growth due to any antimicrobial activity of the drug formulation (i.e., active drug and / or excipients). The Commonwealth of Massachusetts Executive Office of Health and Human Services Department of Public Health Bureau of Health Professions L icensure 250 Washington Street, Boston, MA 02108- 4619 Tel: (617) 973-0960 TTY: (617) 973-0960 www.mass.gov/dph/boards

Adopted: 5/1/25 Page 2 of 5 C. Do the microorganisms used in method suitabili ty challenge testing resemble microorganisms typically found in the specific pharmacy’s sterile compounding environment and / or sterility test failures (i.e., those beyond USP challenge microorganisms). Does the chal lenge testing include slow growing microorganisms (e.g., penici llium, etc.)? Would the laboratory be able to incorporate additional microorganisms into the testing? D. What are the limitations of the selected RMM? 1. Does the met hod identify all microbes? For example, some O2 methods may not be able to identify anaerobic microbes. 2. Does it enable the pharmacy to recover and identify microorganisms to conduct full investigations for failed sterility tests in accordance with USP <797>? For example, is the RM M destructive to the test sample? Does it require the pharmacy to retain additional samples to aid in such investigations? 3. If applicable, does the RMM method require different types of growth media and incubation procedures (e.g., times, temperatures, etc.)? II. Pharmacy Responsibilities Pharmacies considering the use of RMM’s must exercise due diligence by: A. verifying that the specific alternative met hod / technology has been fully validated (i.e., method validation) to demonstrate that it is equivalent or superior to the compendial method outlined in USP <71>. B. conducting a risk assessment to ensure that there is built-in quality. For example, is the specific method destructive to the sample? If so, how will sterility failures be investigated? Does it require the pharmacy to retain additional samples to aid in such investigations? C. ensuring that met hod suitability challenge testing for CSPs is performed. The method suitability challenge test ing must demonstrate recovery of low levels of the microorganisms (bacteria, yeast, and mold) specified in USP <71>. 1. verify that th e method suitability challenge testing has been conducted for each CSP for mulation to validate that it does not inhibit or interfere (e.g., false positives, false negatives, etc.) with the rapid sterility test and provides the same result as the standard (USP <71>). 2. verify that the met hod suitability challenge testing was conducted with the pharmacy’s sample (e.g., specific concentration, same API Chemical Abstracts Service (CAS) Number, etc.). 3. consult with the laboratory to determine if challenge testing should include additional microorganisms that have been identified in the pharmacy’s environmental monitoring, person nel monitoring, and failed sterility testing.

Adopted: 5/1/25 Page 3 of 5 4. Method suitability must be r epeat ed for CSP formulation changes or any other pertinent product composition changes. 5. utilizing a properly credentialed / qualified laboratory capable of conducting rapid sterility testing with a specific RMM(s) and appropriate method suitability challenge testing. Conduct an audit to: a. evaluate credentials and training of microbiology analysts / professionals. b. evaluate the laborator y’s policies and procedures for such testing. c. assess the facility by conducting an in-person or virtual tour of the facility, if possible. III. Documentation Requirements Pharmacies must maintain the following documentation obtained from the qualified laboratory conducting RMM testing and have it readily available for the Board upon inspection or request. A. The primary validation package received from the supplier of the equipment / technology proving / verifying that the RMM being utilized is non -inferior to USP <71>. B. Reports / statements from the qualified laboratory of completed method suitability challenge test ing for each CSP formulation. Reports / statements must include at least the following: 1. description of CSP formulation (e.g., drug, concentration, volume, etc.) 2. specific organisms used in challenge testing. 3. type(s) of media used, if applicable. 4. incubation details (temperature / duration), if applicable. 5. documented results (pass or fail per USP <71>). 6. signature of a microbiologist. C. Once the method suitability challenge test results are received, the Manager of Record or De signated Pharmacist- in -Charge must review, sign, and date the document. Please direct any questions to: Pharmacy.Admin@mass.gov

Adopted: 5/1/25 Page 4 of 5 References DeHaven, Wayne. “ STAT Results for STAT Samples: Im plementing Modern Rapid Micro Methods.” Charles River Laboratories, 2025, https://www.criver.com/resources/webinar- pi - ms -stat-results-stat-samples- implementing-modern-rapid-micro-methods. “ Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice.” FDA, September 2004, https://www.fda.gov/media/71026/download. Hu, Haijing. Alternative Microbiological Methods Used at Compounding Facilities. Powerpoint Presentation. Miller, Michael. “Rapid Microbiological Methods (RMM).” RapidMicro, Microbiology Consultants, LLC., Copyright 2010- 2025, https://rapidmicromethods.com/files/tutorial.php. Miller, Michael. “ Validating Rapid Microbiological Methods.” RapidMicro, Microbiology Consultants, LLC., Copyright 2010- 2025, https://rapidmicromethods.com/files/validation.php. Sandle, T. Approaching the Selection of Rapid Microbiological Methods, Journal of Validation Technology, Vol. 20, Issue 2, Jun 2014, https://www.researchgate.net/publication/283644831_Approaching_the_Selection_of_R apidMicrobiologicalMethods “ SCANRDI®.” bioMérieux, accessed April 2025, https://www.biomerieux.com/us/en/our- offer/industry-products/scanrdi-rapid-microbial-detection.html. USP General Chapter <71> Sterility Testing USP General Chapter <797> Pharmaceutical Compounding – Sterile Preparations USP General Chapter <1071> Rapid Microbial Tests for Release of Sterile Short -Life Products: A Risk-Based Approach USP General Chapter <1223> Validation of Alternative Microbiological Methods USP General Chapter <1225> Validation of Compendial Procedures U.S. Pharmacopeial Convention, Rockville, Maryland https://www.uspnf.com/ USP Pharmacopeial Forum 43(5): Sep.-Oct. 2017. Stimuli to the Revision Process. The Development of Compendial Rapid Sterility Tests. pp. 595- 610.