A number of different rapid microbial methods are available to drug manufacturers today, and more companies are applying them. In fact, a recent NDA approved by FDA specified the use of RMM. Validation is relatively easy to achieve, and FDA is reportedly receptive to well-validated rapid methods. In this brief interview, John Albright discusses the specific benefits of Celsis’ platform.
PhM – We’re hearing a lot more about rapid microbial methods in general. Celsis has always emphasized the connection between Lean Manufacturing and its product line in its message. But most people associate Lean with the production floor and may not see how it applies to the quality lab and to microbiology. How does Celsis RMM product line advance Lean?
JA - When I was working in the pharmaceutical industry, involved with getting my production lots through the floor and out to the customer, there was always a lag time when it came to testing, most notably microbial testing. When you had stuff going through analytical labs and efficacy testing, it was often a question of putting it into the queue and getting it done.
With microbial testing, however, there’s a certain time period that has to be automatically built into the test time period. For example, with the traditional pharmaceopeial tests, it typically lasts anywhere from 3 days up to 14 days. That time frame was a requirement and there was no way to speed that up until rapid microbial methods came along.
Rapid tests, including Celsis’, can reduce the time required for results, which could be 3, 8 or 14 days, down to 24 hours. That reduction is significant when you’re talking about manufacturing cycle time. It is not part of the manufacturing process itself, but esting is ultimately part of the cycle time of any product going from beginning stages to when product is shipped out.
PhM – What skill sets are needed to use Celsis’ RMM equipment? Traditional microbiological testing methods rely on training and are labor intensive. Are rapid methods any easier to use?
JA - In microbiology labs, testing is often a matter of streak plating or pore plating and then identifying organism morphology and phenotypes to determine whether it is a contaminant or wasn’t. There were often cases when a new person to the lab would see false positives and subsequent tests would show they were negative. Celsis’ system is very automated. Using the equipment requires knowledge of the basics of aseptic technique, essentially not contaminating product while testing it, which is straightforward lab practice that technicians are very used to. It’s basically a matter of pipetting.
PhM – So the RMM advances the Lean concept of error proofing?
JA – It does remove the subjective part of determining the results, because it gives you a positive or negative. With traditional methods, there may be times when consultation or additional testing are required.
PhM - What kind of ROI can users of Celsis’ RMM expect?
JA – ROI will vary depending on applications, products and product hold times involved. We do have offer a value creation model developed by Arthur D Little, which will help determine ROI. Typically we see 6-12 month ROI after initial purchase.
PhM – What kind of impact can a user of RMM expect to see on cycle times and inventory requirements?
JA – Cycle times, depending on the microbial test you’re using now, typically go from 5 days to 1, which will minimize warehouse spacing. If you have to have a week’s worth of hold on a certain product, for instance, that can be reduced to a three-day hold.
PhM – Are there any limitations to the type of microorganisms that can be detected using Celsis’ system?
JA – Celsis’ method is not species specific. Basically if the organism has a cell wall and ATP, which every living thing does, it can be detected.
PhM – Can you distill a description of how Celsis’ rapid methods work, compared to alternatives?
JA – To use Celsis’ system, tou take a sample of product and add it to a growth medium, similar to the compendial system, but instead of using agar plate you use liquid growth media. You incubate that for roughly 24 hours, take a small (50 microliters) aliquot and run on the Luminometer, which will determine presence of microbes.
Flexibility is one benefit, since the system can be used with liquids, solvents and nonfilterables. A single bench top unit, 2 feet by 2 feet, can easily fit into existing microbiology labs, so there are no configuration issues, you just have to plug it in. Also, having a high throughput allows customers to use it for multiple products
PhM – Does the Celsis system give a qualitative or quantitative result?
JA – It gives a qualitative result, which is a benefit, since, for the vast majority (95-99%) of products that come off negative, there is no need to get a count. If you do get a positive, we recommend you move to traditional systems, or other methods, to enumerate.
PhM – How is FDA responding to rapid methods?
JA – FDA is very accepting of rapid methods. All that FDA requires is that, if you are going to convert to a new technology, that you prove that it works. That’s easily done, and there are numerous validation documents out there, there are chapters in the U.S. and European Pharmacopeia, as well as PDA TR 33. I’m on a committee that has been working on that. Those guidelines that are out there are very thorough about implementation. In addition, FDA has recently written a draft guidance of its own on how to implement rapid methods.
So why are pharma companies hesitant to embrace rapid methods? In my opinion, from my experience working in the industry, pharma tends to be most conservative when it comes to change. A lot of companies hesitate to implement new technologies, taking the approach that “if it ain’t broke don’t fix it.” However, we have found several global pharma companies that are a little more forward thinking, which are implementing rapid methods because they don’t want to be using hundred year old methods.
PhM - How much training required for using Celsis’ system?
JA - We provide a three-day training system including IQ and OQ. When the instrument shows up, our technicians provides training. By the end of that period, the system would be up and running and ready to use.
PhM - You’ve discussed the lean benefits of Celsis RMM. What types of scenarios come up in a typical plant, what types of contamination can occur where this method would be an excellent defense to have?
JA - Celsis’ RMM can help in response to contamination events. I’ve experienced several situations in the past where a contamination event would shut down a line, a lab or a facility or you’d have to stop and put several subcomponent products on hold. During that time, you were essentially losing money because other products could not be manufactured.
Sometimes an entire line would be down and would have to be tested in several different spots. Considering that each test would take a certain amount of time, a week or so, that’s a fair amount of time that a line would be down and unable to function. With a rapid method, those lines would be back up and running rather quickly, within a day, rather than a week. That’s rather signficiant. If anyone’s ever had a line go down due to microbial contamination they’re familiar with how much that can cost.
In addition, I once worked in facility where we made a product, then two others back-to back. One day, they all failed due to microbial contamination. If the first one had been tested, the subsequent lots would not have been prepared. The cost of those two failed lots would have paid for 2 Celsis RMM systems. That’s just one example where benefits of using Rapid Methods exceed costs.