Compounding Pharmacies in a More Regulated World

With the new USP <797> chapter now official, here is how to address regulatory expectations and ensure patient safety

This is the fourth and final piece in a series about regulatory updates in the compounding pharmacy industry.

So, November 1 has passed and you’re admiring all the work you’ve done to comply with the newly official version of USP <797> Pharmaceutical Compounding – Sterile Preparations. What’s that? Oh, you’re still looking for ways to streamline your micro QC processes to handle increased testing requirements. That's great that you're still looking to improve your workflow! It’s also important to remember that USP chapter requirements are seen as the minimum to ensure patient safety.

The team at Microbial Solutions put together a great series on USP <797> changes. Let’s review the series to help you identify areas you can target for improvements.

Part 1: Environmental monitoring lessons learned from tragedy

The first article of this series reviewed the tragic contamination event at the New England Compounding Center (NECC), regulatory enhancements that came from the fiasco, and some challenges the industry still faces today. While the compounding industry continues to grow and face new (and sometimes not-so-new) challenges, new regulations and resources have since been created to further define regulatory expectations that ensure the safe compounding of medicines. 

According to the NECC’s 483 issued on Oct. 26, 2012, one of the many unmet expectations at the company was the failure to identify microorganisms found in their facility and subsequently investigate those findings. (As an interesting side note, 483s from any company in general are a good way to figure out what not to do). If you found a gap in your microbial identification strategy, you may be wondering what the best practices are or what guidelines to follow. The short answer? Get an accurate identification.

It’s obviously more complicated in practice, but accuracy is critical. Accurate identification of microorganisms improves reporting capabilities, facilitates full investigation of root causes for contamination and informs decision-making. With accurate data, it is possible to fully understand issues that arise and develop meaningful corrective and preventive actions to reduce production down-time and increase patient safety.

Overall, species-level identifications will provide the best resolution in your microbial data sets.  A species-level identification is also critical for investigating an environmental monitoring excursion or a sterility failure. As part of your root cause analysis, you will compare your isolate of interest to historical data obtained from environmental monitoring of your facility. If your historical data are full of genus-level identifications, or worse yet, just Gram stain results, it becomes difficult to track down where the particular species may be coming from. 

For more content on the NECC event, what went wrong, and how compounders can avoid making similar mistakes in the future, check out this Sounds of Science podcast. Abby Roth of Pure Microbiology joined me for a discussion about global implications from the whole ordeal. The podcast was moderated by Senior Scientific Writer Mary Parker.

Part 2:  Simplified testing for endotoxin

In the second blog, my colleague Sherri Hopple dove right in with a crash course on endotoxin testing, why it’s important to test for endotoxins, and how to do that accurately, quickly, and efficiently (yes, all three of those at once!). Fortunately, there is an endotoxin testing method that is easy to use, compendial globally, meets data integrity requirements, and provides fast, quantitative results. Charles River Laboratories’ cartridge technology is designed to eliminate costly specialized training and streamline testing using only 100 µL of sample. New test methods can seem difficult to perform and manage in-house. With FDA licensed cartridge technology, the benefits outweigh the hurdles. 

Part 3: Rapid sterility optimizes shelf life

In the third installment of our compounding blog series, my colleague and blogging phenom Jon Kallay focused on the benefits of implementing a rapid sterility method. Why is this important? The compendial USP <71> sterility method takes at least 14 days to complete. Changes to Beyond-Use Dates (BUDs) in the updated USP <797> chapter will result in some products having shorter shelf lives. Waiting two weeks for a sterility test significantly cuts into your BUDs. These changes have important implications for production schedules and supply chain robustness. There are some ways to extend the BUDs that are outlined in the new revision. Most notably, performing a sterility test on each lot can often double the BUD window. Rapid sterility tests can extend your BUD window even further.

The previous version of USP <797> stated that “A method not described in the USP may be used if verification results demonstrate that the alternative is at least as effective and reliable as the USP Membrane Filtration method or the USP Direct Inoculation of the Culture Medium method where the Membrane Filtration method is not feasible” but did not provide a clear roadmap on how to demonstrate method effectiveness.

The new version of USP <797> remedies this with a deceptively simple change. The official version of USP <797> contains three cross-references to another USP chapter, <1223> “Validation of Alternative Microbiological Methods”. Consider USP <1223> your regulatory BUDdy for extending the shelf life of your products. 

Using a rapid sterility test boosts the BUD timeline while minimizing the impacts of the traditional incubation period. Jon has more information about <1223> in another Eureka blog. His team at Charles River put together a package that could be used by Celsis^® rapid method users to validate their system and gain regulatory approval. Prominent service laboratories that work with compounding labs, including ARL Bio Pharma and Pharmetric Laboratory, have also completed their own independent Celsis validation per USP <1223>. Don’t delay, rapid methods in good regulatory standing are available to you today.

All three of these posts were written before November 1st.  They speak to the upcoming USP <797> changes. But November 1st has come and gone. The new USP <797> chapter is now official. By partnering with experienced, proven leaders in the industry, your compounding pharmacy can effortlessly exceed regulatory expectations while demonstrating the highest levels of patient safety.

Dr. Doug Botkin, PhD, is a Technology and Market Development Manager at Charles River Laboratories. He is a subject matter expert in the Microbial Solutions group, focusing on Accugenix products and services for microbial identifications. Doug has over 24 years of experience in infectious disease research, spaceflight microbiology, and pharmaceutical microbiology, including working as a QC microbiologist at 503B outsourcing, cell and gene therapy, and non-sterile manufacturing sites. He holds a bachelor’s degree in Biological Sciences from Illinois State University and earned his PhD in Microbiology and Molecular Genetics from The University of Texas Health Science Center at Houston.