Contract Manufacturing: Orchestrating the Dance
Lean Six Sigma, expertise in microbiology, and shop-floor experience all contribute to running a flexible, efficient contract facility, says DPTís new director of sterile ops.
By Paul Thomas, Senior Editor
Earlier this year, Michael Curry joined DPT Laboratories as its Director of Sterile Operations at the company's Center of Excellence for Sterile & Specialty Products in Lakewood, New Jersey. In this position, Curry manages manufacturing operations for nasal products, small volume parenterals and other sterile and specialty products, and for all aspects of aseptic manufacturing
Curry’s background is intriguing. He’s a Lean Six Sigma Green Belt who has worked with The Medicines Company, Dendreon Corp., Wyeth Pharmaceuticals, Baxter Bioscience, and Schering-Plough in a variety of roles. He is also former Director of Field Applications for BioVigilant Systems (Tucson, Ariz.), which specializes in rapid microbiological methods (RMM’s) for pharmaceutical applications. Curry has an M.S. in Microbiology from Seton Hall University.
We spoke with Curry about his experiences and ambitions:
PhM: Your background is extremely varied (in microbiology, Lean Six Sigma, regulatory, etc.). Is this kind of diversity really a prerequisite these days for a director of sterile operations or someone in a similar position?
M.C.: Is it a prerequisite? Probably not. Is it helpful? Extremely. I’ve been in the industry over 18 years now, and I started out in operations. They gave me a nice title because I had a bachelor’s degree in biology, but essentially I was an operator, and that was the best thing for my experience because I was on the floor, making batches, and really got a good experience as to what goes into making products, and I was fortunate to be working on an aseptic product as well.
I was also able to move around in different roles, with different companies, and that sure broadened my experience and understanding of not only how to make an aseptic product, but the whole process of developing it, making it, and manufacturing it commercially in a GMP way.
PhM: Was learning Lean Six Sigma something you did consciously from a career perspective, and is that something you apply in everything you do at DPT?
M.C.: Absolutely. If I was to define Lean Six Sigma, it’s really all about quality. It’s about first time right, and reduced waste, which is work that’s not done well or needs to be redone. What we’re implementing here are detailed records that allow our operators and compounders to execute flawlessly each time out. We’re taking away the opportunity for error, doing what I call mistake-proofing. For Example: making an inlet and an outlet hose connection different does not allow someone to hook up the hose lines incorrectly. Since my outlet is a different shape than my inlet, we can prevent someone from making a mistake in hooking up the lines. That’s really what Lean Six Sigma is, reduced errors, and less mistakes—first time right.
PhM: What work is going on in the Centre of Excellence for Sterile & Specialty Products? Can you share a few key projects that are ongoing, and any partners (clients, OEM’s, etc.) that might be involved? What kinds of things are on your agenda, as the new head of the centre?
M.C.: We want to be viewed by the industry, not just in the U.S. but in Europe and other countries, as DPT’s center for excellence for sterile and specialty products. We’ve established the small-volume parenteral capabilities that we’re looking to expand in Lakewood, and we’ve also validated syringe, nasal spray, ointment and tube-filling technologies, as well as multi-dose technologies. So we do have a broad spectrum of expertise here, and it’s a matter of continually improving and getting better at making these products, if not in an aseptic cleanroom, then in a cleanroom that complies with regulations and specifications globally, as opposed to just the U.S.
PhM: So the work that you’re doing will be applied globally at all DPT facilities?
M.C.: That’s correct. We may be working on a product for a client in which they’re trying to get an NDA approved, knowing full well that the client is thinking about filing in Europe. When we’re at the development and validation stage, we’ll bring that into the process. There are subtle differences between Europe and the U.S. where they consider a vial to be sealed, basically. We’ve already built in the full gamut of making sure that the crimping process is performed in a class 100 environment, so we know that we’re ready for the FDA and we know we’ll comply with European regulations.
PhM: When you started your job, what were the two or three things that you saw that were opportunities to make a difference right away?
M.C.: A few things right off the top that we wanted to do was to understand that the aseptic business is much different than the non-aseptic business, and it requires a little more of a dedicated headcount and staffing that will work in a particular area or zone so that things are done very well all the time. It’s not easy to move people around all the time as you would for, say, a secondary packaging operation that has a little more flexibility and leniency. When you’re in that aseptic area, the way you work, the cleanliness of your work, and the control that you need to demonstrate is of the utmost importance. That’s one thing that we’re building—small teams and groups of people that can not only work in those areas but take ownership and demonstrate their expertise over and over again.
We’re also bringing more detail into our records—taking the detail that was typically found in standard operating procedures and bringing that into the actual manufacturing records so that there is no ambiguity as you need to execute a step or a task.
PhM: Are you mainly talking about paper or electronic records?
M.C.: Right now we’re just looking to improve our paper records. Those paper records do not go into the aseptic fill zones. But it’s all the work that surrounds that effort that I’m speaking of. I’ve been in the industry for a while. Electronic records has been on the radar for a lot of companies, and as many advantages as it brings you, there are also challenges. It’s definitely something we’re going to do in the future, but it’s not on the near horizon.
PhM: What are some of the new technologies that you believe in that ensure sterility in a facility?
M.C.: I’m a big supporter of isolator technology. We have some of this technology that we’re already using where we completely keep the operator out of the process, and raw materials are sterilized in line and any openings, closings, aseptic connections or additions of API are done with the operator using glove ports. Moving from open-fill operations to more of a RABS or isolator technologies—there are always improvements that DPT and other companies are looking at.
PhM: You have a background with BioVigilant Systems and rapid microbial method technologies—how will this play into your work?
M.C.: The experience I had with BioVigilant was a good one, and it opened my eyes to rapid microbial methods. There’s definitely a place for those technologies in the near future, but like any technology you have to understand how it applies to your product. Part of what I was working on with BioVigilant was helping customers to understand that. It’s not one-size-fits-all, but there’s definitely a place for real-time understanding of what those particles are, and the potential for those particles to be any type of bioburden nature that could be affecting your product. It’s definitely technology that’s on the horizon that we’ll look at, as we move into more of the small-volume parenteral business.
PhM: Will you look at RMM more for process, for environment, or for both?
M.C.: Both. As you start to move into a RABS or isolator technology, rapid methods really come into play. Not that they’re not as important with your typical aseptic fill lines, but there’s also a better understanding of what could be contributing to your counts. It could be product, it could be environment, it could be gown material, anything. I believe in the rapid method technology, I believe in BioVigilant, but really for us at DPT it’s a matter of understanding how we can best utilize the technology in making our products the best that they could be.
PhM: Do see the synergies that rapid methods have with Lean?
M.C.: I do. Again, it’s a matter of understanding them in a level of detail that’s happening at all different companies now. We need to understand how these rapid methods will help us from a resource perspective or from a leaning out perspective. In some instances there may be no difference, or may actually require more in terms of resources or expenditures because some of the rapid methods that are out there are not all in one, they’re not all-inclusive. In the position I’m in, it’s all about patient safety, and. making sure we take care of our customers The lean part is important, but if we can see the rapid methods ensuring the quality of our product, then that would really be the rate-determining step.
PhM: An issue that has increased in importance for contract facilities is the possibility of product cross-contamination. What kinds of things are you focused on?
M.C.: Any time you run more than one product in a facility, let alone any fill zone or fill line, we spend a lot of time, effort, and money making sure our validation activities are of the highest level to ensure that the previous product can be 100% removed from the process before we can move into the next product. As far as improvement goes, I would say that DPT has that part of the business well-defined and that’s basically a benchmark and staple of the company.
PhM: Are you surprised by how many manufacturers struggle with the issue of cross-contamination?
M.C.: That’s a good question. Sure, it surprises me, but to some extent, no, because we see it happen over and over again. We all get the newsletters and go on the FDA web site. Our compliance folks at DPT are very good about communicating current trends. It happens too much in industry not to make it forefront in our minds to make sure that it never happens to us.
PhM: You said that you’re operating more of a team concept in implementing Lean. What are some of things you see the operators picking up on and appreciating?
M.C.: They’re all linked together. One thing that I talked about when I joined the company is these small teams that work together so that the redundancy or headcount is already built into that team, so that we’re not having to pull people from other lines or teams to backfill to meet a production schedule.
That doesn’t mean that we don’t spend a lot of time and effort on cross-training. It’s absolutely critical that we cross-train our people to not only give them the breadth and understanding of what we do, but to give us the flexibility to make our products. At the same time, we’re building in that flexibility and cross-training so that we can be lean and so that the folks who are operating that particular fill area or zone are very experienced and can repeat that process, batch after batch. That’s the key for a high-quality product is to manufacture in a repeatable way. As you know, that’s a benchmark of GMP manufacturing.
With that said, it plays right into the Lean Six Sigma concept, which means that you are making that product with the least amount of time wasted. The phrase I use is “the orchestration of the dance.” How you make a product from compounding to filling to packaging all needs to be orchestrated in a well-defined way. Everybody knows they’re role, they’re trained in that role. Folks are already preparing for the fifth, sixth, seventh step right now, so that if I have a 30 or 45 minute mix time, I’m already preparing for the next several steps in my process, so that there’s absolutely no delay, the product’s moving through as it should be, and errors are reduced.