Stat results for Stat samples: Implementing modern rapid micro methods
Pharmaceutical manufacturing and compounding industry expert Dr. Wayne DeHaven, Director of Quality at Pharmetric Laboratory, offers answers to some frequently asked questions regarding the importance and impact on rapidly and safely releasing drugs, specifically during COVID-19.
Rachael: What actions have you seen pharmaceutical manufacturing and compounders making given the current situation with COVID-19?
Wayne: Manufacturers are ramping up certain drugs and therapies to meet increasing demand for these pharmaceuticals in response to the pandemic. Due to the shortages of needed medications, several of our clients are increasing the types of compounding they do and are requiring rapid testing of these drugs so they can be quickly released due to major shortages. We are specifically seeing significant rapid testing demands for Fentanyl, Hydromorphone, Ketamine, Midazolam, and Norepinephrine for caregivers’ needs when treating COVID-19 patients for pain, respiratory issues, and critical care cases requiring intubation when being placed on ventilators.
As a side note, some regulators are removing state restrictions when it comes to microbiological testing. California, for instance, does not presently allow for any rapid microbiological testing, but due to the current situation regulators are allowing waivers for rapid testing to be utilized if it comes to increasing production on a COVID-19-needed basis. With this being such a stressful time, everyone wants to produce quality products more rapidly. Everyone wants to improve their processes to be able to help wherever they can. Compounders are at the forefront, producing drugs that provide huge benefits to helping people. Compounders’ production and release capabilities take pressure off caregivers and doctors and provide an absolute symptom-easing need for patients. Many of our clients are sending batch samples overnight rush for next day testing and release. This is around the clock, 7 days a week, for the time being, so that we can get these medications right to the hospitals and safely to the patients in need.
Rachael: What struggles are sterile compounding pharmaceutical manufacturers currently facing when utilizing traditional bioburden and sterility methods?
Wayne: All sterile compounders struggle with testing time and releasing inventory, especially given the guidelines and requirements for beyond use date (BUD) regulations. With prescription-based production, there is minimal or no anticipatory compounding that can be done. Compounders are required to be prepared to have the appropriate ingredients to make the drug and be able to test quality and release the drug quickly. USP <797> guidelines pushed back pertaining to sterility testing over time and eliminated sterile compounders’ ability to accomplish this. Pharmacies wanted extended shelf life of the active ingredients and compounded pharmaceuticals since compounders don’t make just one variety—they make complex products with complex formulations. In some formulations traditional sterility tests just take too long because the formulated product is turbid itself. The suggestion of sterility testing over time would require extended incubation and lengthy testing in order to get an accurate result. By the time testing would be complete and the product ready for release, the actual shelf life would only be a few days.
In the case of sterile compounding, rapid detection methods are needed. ATP-bioluminescence testing is used as a presence/absence test: either there is or is not evidence of growth. You process the sample and receive an output of an amount of ATP, a numerical read-out in relative light units (RLU). This is a perfect test method for sterile products that have low water content and high preservatives, short beyond use dates (BUD). Compounders can release product within 4-7 days, as compared to traditional sterility release in 14 to 18 days.
Sterile compounders have an appreciation for a rapid approach to testing. Many companies, especially in these trying times, would be out of business if not for shorter testing duration. Rapid microbial testing has made ordering one day, and compounding, testing, and getting pharmaceuticals into patients in 4-7 days a reality, rather than in 14-18 days.
Rachael: How have you been educating and supporting the industry and your clients regarding method suitability testing and utilization of ATP-bioluminescence technology?
Wayne: I share information about the validation of system and product testing processes with clients. Many compounders are unsure of rapid detection methods, and some are even unaware of ATP-bioluminescence and how it relates to the compendial method. Educating my clients so they understand the processing side of the test method and how it is identical to a compendial method eases their concern and reassures confidence in a rapid method. I describe Celsis specifically as a standard compendial test, using the same media, with a new readout technology. There is nothing new between the rapid method and the traditional method other than the incubation duration and detection, which is done by a machine, removing the subjectivity and improving confidence in the quality of products.
The validation guidelines for implementing a rapid method may appear vague, so I do explain that the validation is technology- and product-specific, requiring the need to determine equivalence of the rapid detection method to the compendial method, and manually figuring out product ingredient effect on the test and product concentration. There is an additional component to method suitability where we require more product and understand that additional product can become costly for our clients. But there is reason to test for background and false signal of ATP. Even if ATP is in the product, as long as the product can be enriched, this rapid ATP-bioluminescence test will provide microbial detection.
In addition to this interview, Charles River partnered with Dr. DeHaven to describe his first-hand experience in providing his customers test results utilizing Rapid Microbial Methods; Click Here to download our webinar.
Learn more about our entire Quality Control Microbial Solutions products and services and see how partnering with Charles River Laboratories will enhance your processes, testing and ability to release your products rapidly, confidently and safely to market.