USP <797>: Conforming to the Rules, Understanding Inherent Risks
Microbial Solutions
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Rachael Kerr

USP <797>: Conforming to the Rules, Understanding Inherent Risks

Pharmaceutical compounding-sterile preparations’ future impact and best practices for microbial identifications

Headshot of Abby RothAbby Roth is the Senior Director of Business Operations at CriticalPoint, LLC, a health care training and development company. In addition to operational responsibilities, she develops curriculum for CriticalPoint’s eLearning modules and live training classes. Abby has over 16 years of experience in supporting the testing and consulting needs of the pharmaceutical, medical device, and compounding industries. Her background in pharmaceutical microbiology includes extensive knowledge of environmental monitoring, including program development, sampling technique, sample analysis, and data trending. Abby also has experience in consulting on microbial contamination sources and remediation.

USP General Chapter <797> for sterile compounding establishes standards that are required to avoid preparing contaminated medications and maintain patient safety. Consideration of both versions, 2008 and 2019, should be used to ensure you are meeting or exceeding all current and future regulatory requirements and compounding safe and effective sterile preparations. Compounders should be working towards the changes put forth in the 2019 version and making sure respective state boards support plans for process and testing changes. To hear more of Abby’s insights on USP <797> download her on-demand webinar: Microbial Identification: How to Comply with the Current and Future Versions of USP Chapter <797>.

Rachael: How are the global pandemic and resulting urgent needs affecting the compounding pharmacy industry?

Abby: Like so many other industries, sterile compounding pharmacies have directly felt the effects of global pressures and shortages in medical and personal supplies caused by the COVID pandemic. With growing and ongoing demand for pharmaceuticals, compounders have been forced to prepare the increased needed volumes faster while sometimes lacking appropriate and required garb, such as face masks, gowns, gloves, and shoe coverings. The shortage of these materials has forced personnel to conserve the garb they currently have on hand and continually reuse these necessary materials that are normally a single-use disposable item.

This reusage of garb, while acceptable during this time, should be followed by more frequent environmental monitoring (EM) since basic contamination control principles associated with garbing are not being maintained. Reusing materials that are otherwise never reused dramatically increases the risks of contamination. It is extremely important during these times to have an understanding of the microorganisms you are recovering within the sterile compounding environment. We understand major reuse issues, due to supply shortage, is interrupting pharmacies’ state of control, but we need to ensure we monitor the environment more frequently, understand the specific microorganisms appearing in the environment, know what cleaning and disinfecting procedures will mitigate contamination risks, and keep patient safety our main focus.

Rachael: With the upcoming USP <797> regulatory changes, what are the biggest challenges facing the sterile compounding industry?

Abby: Right now, with the 2019 update to USP <797> on hold, the biggest challenge is the Beyond-Use Date (BUD) paradigm. Organizations performing large volume compounding and extending use dates will have strict limits on dates assigned to the Compounded Sterile Preparations (CSPs). These new dating rules will severely impact the BUDs that can be used.

In regard to EM and identification requirements, those will continue to be in line with requirements released in the 2008 version of USP <797> (the current accepted version of the chapter). This requires that every colony recovered during environmental monitoring be identified, at minimum, to the genus level. Gram stains are not acceptable and lack information required to take the appropriate action in the event an exceeded action level or an organism of concern is recovered. Especially now, it is important to evaluate increasing EM sampling, go beyond the minimum requirements to obtain accurate genus, or even better, species level identifications.

Rachael: For a sterile compounding pharmacy to fulfill all USP <797> requirements, what ISO certifications are required by either the compounding pharmacy or contract laboratories they utilize for testing?

Abby: There isn’t any requirement for the sterile compounding pharmacy to have an ISO accreditation. However, when looking for a vendor (especially a laboratory), the vendor’s ISO accreditation, preferably ISO/IEC 17025 Testing and Calibration Laboratories, is a critical point. The sterile compounding organization is responsible for ensuring the vendor they are utilizing has appropriate quality systems in place. Ideally, the vendor should comply with Current Good Manufacturing Practices (CGMP), again ensuring the highest quality of testing and documentation.

In addition to the vendor having relevant ISO certifications, the sterile compounding organization should also have confidence in the vendor’s ability to resolve complaints and issues through an effective Corrective Action Preventive Action (CAPA) program.  Validation and the reliability and robustness of the laboratory testing must also be considered.  While the ISO accreditation is not a mandatory requirement of a vendor, it absolutely helps support that sterile compounding organizations are partnered with and utilizing the best service providers possible and that all standards and requirements of maintaining quality control and quality assurance are being met.

Rachael: How are sterile compounding pharmacies held to the same standards as other regulated industries when it comes to testing, tracking data, and maintaining quality-controlled facilities?

Abby: Requirements for the sterile compounding pharmacies, set forth by the regulators, are still slightly behind other regulated industries. The 2019 version of USP <797> has made significant changes, making the chapter more quality focused. It even added an entire section on quality; Quality Assurance and Quality Control, as well as a section on Standard Operating Procedures. The purpose of a good quality assurance program is to provide guidance on handling adverse events, reporting, documentation, and maintaining quality control of the environment. Another USP General Chapter, <1163> Quality Assurance in Pharmaceutical Compounding, contains information on quality related to compounding with plans to provide a more robust chapter in the near future. Both versions of  USP <797> chapters, 2008 and 2019, mention tracking and trending data.

The specific wording in the new chapter states to ‘evaluate trends’ as well as ‘evaluate previous trends’ when conducting any investigation. Looking at data trends over the last six months to a year can provide clear indication of appropriate corrective actions. The more specific your data is, such as having species-level identifications, the more accurate and concise your investigation will be. There is extreme value in understanding the microflora of the sterile compounding environment to quickly manage, eliminate and prevent future product contamination risks. To ensure sterile medications are getting to the patients the environment must be understood and controlled with appropriate material handling, precise hygiene and garbing techniques, and a robust EM program trending accurate identifications.

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