How To Take Charge Of Your Manufacturing Process

By Rob Wright, Life Science Leader magazine

Jim Robinson grew up just 20 miles away from Merck’s massive, 397-acre, West Point, PA, campus. His brother, a proud union member, has spent the past 37 years working on the Merck manufacturing line. During the course of his 29 years in the pharmaceutical industry, Jim tried to join his brother as a Merck employee, applying for a job six times. “They never responded to me,” he admits. “It was quite demoralizing.” He theorized that he must not meet the typical Merck hire profile. That all changed when one of his former Sanofi Pasteur colleagues, Jacks Lee, who joined Merck in 2007, recommended Robinson to fill a position in early 2010. Merck had just completed a merger with Schering-Plough and was in the process of a major restructuring, including considerable layoffs. Some might view this as a rather precarious time to come on board, especially if you don’t fit the typical hiring profile. For Robinson, however, the timing to become one of Merck’s approximately 86,000 employees couldn’t have been better. As the VP of vaccine product & technical operations, he explains the lessons learned throughout his career which he feels can help improve vaccine manufacturing.

Lesson 1: Getting Your Staff To Be Advocates
Having worked 20+ years at both large and small pharmaceutical companies, he has experienced the contrast of complex versus simplified manufacturing operations. One of the most important things he has been exposed to is the potential benefits and simplicity of single-use manufacturing systems. “You can see the flow which helps you to understand better what’s happening,” explains Robinson. “When you have stainless steel pipe network and automation panel, you’re told what should be happening, but you can’t see it. You can’t confirm it, and you’re relying on the technology to tell you that it’s right.” His experiences have forced him to think differently and to consider other ways to be innovative and creative in the manufacturing process. He feels that if you want to bring these ideas to your vaccine manufacturing process, you must first obtain a critical mass of advocates, and the best place to start is with your own team. But before you can convince them that there might be a better way, you must first change their mindset.

For example, during his first six months at Merck, he asked the question of his team “Why are you here?”, and he gave them one sentence to answer the question. Answers typically included ”Merck is a great company”, and “we create products which save lives.” These weren’t what he was looking for. He wanted to get his team to think much differently about their work, a technique he learned from one of his first mentors. Robinson defines a leader as “someone who takes you to a place you wouldn’t otherwise go.” In order to accomplish this, one must get people anchored around the concept of showing up to work on purpose and truly understanding why they went to work every day.

In order to change the way people think about and how they approach work, a leader needs to help their team self-discover how they can bring more value to the company. People must understand that just because you are smart enough to create truly complex systems doesn’t mean you should, especially when a simpler, more pragmatic approach can be just as effective and less costly.

Lesson 2: Challenge Your Team To Simplify Your Manufacturing Processes
As companies look to expand outside of the developed world, affordability becomes more important and difficult to achieve when you have high fixed costs and high complexity. Robinson recalls reviewing a manufacturing skid for a stainless steel system that contained more than 240 valves, several thousand feet of stainless steel pipe, about a dozen sterile vessels, connected over four different floors in the building. “Some of the piping was running through noncontrolled mechanical space,” he describes. “This whole system was designed to be maintained sterile, and so, hypothetically, if a valve happened to leak, and it leaked in an area where it was noncontrolled, the question would become, ‘what is the impact on the disposition of those batches?’” Robinson saw the process of managing deviations within this type of system to be a huge time sink, so he decided to have his team think about the process differently, asking them to design a system that had half the number of valves and pipes. The team came back to him with a design which was about 1/3 the size of the original system. Robinson asked them to cut their new design in half. “And then I asked them to halve it again,” he states. When this was done, the team had created a simple system, with ~40 valves, 3 tanks, and a very small sterile boundary, which fit within one room. “You can actually see the sterile boundary,” he describes.

According to Robinson, the exercise demonstrated to the team the benefits of simplification and reminded the team that they only need a level of complexity necessary to achieve the desired outcome with good management controls. “When a system is incredibly complex, very few people understand the system, and those who designed it have usually moved on to other projects,” he states. “This inhibits your ability to transfer knowledge of how the system works to those who operate the manufacturing process every day, which doesn’t help the company operate efficiently.” By simplifying the manufacturing process, the system can be run with fewer people, resulting in manufacturing throughput efficiency, as measured by the number of vaccine doses produced per number of manufacturing line employees. Robinson points out another benefit to simplification. “When there are fewer things that can go wrong, you reduce batch deviations and potential investigations,” he states. The team took this new design and applied the same concepts to simplifying two similarly complex systems in the network.

Lesson 3: Know Your Manufacturing Process — Intimately
The exercise of system simplification helped Robinson to facilitate his next objective — creating process intimacy. According to Robinson, process intimacy is a term he formed and which he feels can help any team to conceptualize how they could truly bring value to their company. Robinson believes that if you don’t really know your process, your system, and what can go wrong — much like a failure-mode analysis approach — you won’t be able to predict problems and proactively prevent them, and you will end up spending most of your time looking at what went wrong, rather than at continuous improvement and risk reduction. “When you start talking about process intimacy, it seems self-explanatory,” he relates. “But process intimacy is much more than knowing the process technically. When you’re on the shop floor of an industrial operation, it has a rhythm, a feel, sound, and smell.” According to Robinson, when you have that sense of rhythm, the result is such a deep and knowledgeable understanding of the process, it creates a relationship between you and the process. “For example, I could tell when a fermentation wasn’t going well by the smell of the off-gases outside when I was on my way to lunch,” he explains. This cannot be achieved by simply looking at a P&ID (piping and instrumentation diagram). According to Robinson, this “organic connection,” rather than technical understanding, can only be achieved by frequently walking the shop floor, perhaps three times a day. The other benefit of being on the floor is that you really get to connect with the group leaders there, who will be critical in helping you to understand when something goes wrong.

Robinson’s process intimacy program requires engineers to get on the shop floor, watch the process, talk to operators, and understand their issues. “If we can’t first help them fix their issues, we can’t earn their trust, and as a result, we aren’t really going to know what the true issues are,” he affirms. Process intimacy involves assigning people to a single product, and then asking them to look end-to-end for that product to develop a deeper understanding of how the manufacturing steps throughout the process relate to each other. “Before this,” Robinson explains, “people would go from product to product, issue to issue, and not own the process or the performance on an ongoing basis.” People-to-product alignment strongly contributes to the ability to develop process intimacy. “Seeing various operators with slightly different techniques and developing the standard work for all employees is only possible if you are there on the shop floor for deep observation,” he says.

Prior to Robinson implementing process intimacy, some staff rarely left their offices when tasked with solving a problem on the shop floor. The problem with this approach became evident when, for example, a team had an issue with a really complex manufacturing system. To gain process intimacy, the mindset had to change from being a technical organization full of really smart people, to that of a service organization — incredibly engaged with the shop floor, manufacturing leadership, as well as the manufacturing process. In so doing, you will not only understand how a system works, but learn the difference between the way a system is designed to be used and the way people who actually operate the equipment decide to use it (see sidebar on page 22).

“We serve by making manufacturing better,” he affirms. “We don’t serve by creating technology. Merck doesn’t sell technology. We sell product, and if our technology doesn’t make product better, then it’s not good technology.” Want to make your product better? Try Robinson’s approach of gaining advocates, challenging your team to simplify manufacturing processes, and then strive to have manufacturing process intimacy.

Deep System Understanding Prevents Negative Consequences

During his career, Jim Robinson (currently VP of vaccine product & technical operations at Merck) always looked for opportunities to deepen his staff’s technical competency via the implementation of his process intimacy program. “Over the years, I’ve spent a lot of time with complex manufacturing systems, walking them with staff members from end to end, with the valve sequencing tables, and the P&IDs (piping and instrumentation diagrams),” he states. One of the things one team found during a walk-through was that a system had a water, air, and steam system, all connected to the same header.

Water was used to wash the line, sterile air to remove excess water, steam to sterilize; and then to cool it down, sterile air would be blown through the line again. “This is something you don’t really think of, until you get into the detail of exactly how it works,” Robinson explains. “Water pressure is 60 pounds, air pressure, 20, and steam, 15. So, if you use water to rinse out the line, the line is sitting at 60 pounds. If you close that valve and open the air valve at the same time to blow the line down, that water will back up into the air system. You no longer have a sterile air system. You steam sterilize the line, and then you blow it out with sterile air, which now has contaminated water in it.”

Robinson advises to make the time to really understand the way a process works via process intimacy to avoid negative consequences. In the above example, if you didn’t make sure that people using the system understood the importance of having a lag time between turning the water off and turning the air on, to prevent backflow, you would end up running a contaminated system, which would result in loss of batches, potential recalls, and lost productivity spent investigating the system to determine when the contamination occurred and if it could have negatively impacted the quality of previous batches.

Lack Of Standards Leads To The Creation Of The Single-Use Network

Jim Robinson, VP of vaccine product & technical operations at Merck, believes a lack of singleuse standards is one of the reasons many companies have been slow to adopt the technology, including Merck. When he initially started talking about utilizing single-use systems at Merck, he found there were many Merck advocates for single-use manufacturing systems. “When we started to share our positive experiences we created some of that critical mass of advocates and in time, the Single-Use Network was born,” he relates.

The Single-Use Network (SUN) is an internal program created to facilitate the adoption of single-use systems within Merck. SUN is in the process of creating a book of standards for single-use components. Robinson is careful to point out that he wasn’t the inventor of the Single-Use Network (SUN), but notes that it evolved from this early group of advocates who shared a common interest and passion for change. He realizes that for single-use manufacturing companies, differentiation represents a competitive advantage. However, differentiation does not serve to facilitate rapid adoption of single-use by Merck. The more different the product, the more difficult it is to duplicate (or substitute). According to Robinson, in the vaccine business, reliable supply is paramount. “We like to have interchangeable parts, so that if a vendor has a problem,” he explains, “we don’t have to live with or stop production for that problem.” Standards created by SUN could not only help accelerate Merck’s adoption of single-use technologies, but perhaps push companies which manufacture single- use systems to more quickly create and adopt standards for certain singleuse components. “If we build connectivity and interchangeability, there will be greater use of single-use systems,” states Robinson. “Even if there is more competition, vendors will compete in a bigger business. It’s a win-win.”