The Greek philosopher Heraclitus famously coined the phrase “There is nothing permanent except change.” Change, especially recently, has been an ever-present reminder that in the pharmaceutical industry, and more specifically in the biopharm portion of the industry, change will come and can bring with it great opportunities.

Olympus Biotech, a biopharmaceutical contract manufacturing organization (CMO) based in Lebanon, NH has seen plenty of change over its history and has emerged as a company with the expertise, experience, technologies and facilities to handle the inevitable changes the industry has in store.

Background

Olympus’ current facility dates back to 1989 when it was owned by the Verax Corporation. Verax was a maker of fluidized bed bioreactors and they built the facility to do contract manufacturing which became Verax Bioprocessing Centers. In 1993 Verax sold the facility to Creative Biomolecules which was in partnership with Stryker Corporation on Osteogenic Protein-1 (OP-1™ or rhBMP-7). Creative continued to do contract manufacturing.

Peter Gariepy, Olympus’ Vice President of Operations has been with the company for 22 years and explains how the company eventually became what it is today. “We continued working with funding from Stryker with OP-1 and doing contract manufacturing all the way up to 1998. That’s when Stryker saw an opportunity to take over the manufacturing rights to the OP-1 molecule and the facility in 1998. At that point in time, Stryker also made the strategic decision that they did not want this facility to operate as a CMO. They wanted this location to be a single product facility to work on OP-1 products and bring those to market. We started getting our approvals to get the OP-1 product to market; that was in the 2000– 2001 time frame.”

“We continued down that path, manufacturing the OP-1 products, until Styker decided to divest themselves of the biotech program in 2010. That was when Olympus came in and created the Olympus Biotech Corporation and took ownership of the assets here in 2011. Just recently, looking at our strategic plan going forward, we decided that it made sense to go back to the contract manufacturing world because of the capacity that we have here. That was something, that as part of Stryker we had already implemented many process improvements, and numerous facility enhancements in preparation of the OP-1 approval.”

Currently, Olympus’ facility is divided between producing the OP-1 product and offering a range of cell culture scale-up and processing services for biopharmaceutical customers.

Broad Range of Cell Culture Services

As a CMO that offers services ranging from clinical to commercial scale the company is quite adept at cell banking – laying down the master working cell bank – for further processing. Currently Olympus is primarily doing mammalian cell culture but is open to working with other batch cultures\processes such as insect cells.

‘The cell culture suites we have currently manufacture our product at a 1000 liter scale and we have a second suite that offers twin, 2500 liter working volume,” notes Gariepy. On the downstream side the company’s processes are very flexible for whatever needs come up and they are quite experienced with multiple filtration types and multiple column chromatography types. Further enhancements to their capabilities include aseptic processes for small batch clinical programs, which the company expects to be available later this year.

Standing Out in the Crowd

It’s no secret that there are many biopharm CMO’s out there that offer similar services. In order, to stay viable and to stand out you have to offer good quality, good service and have an impeccable regulatory record. On all three counts, Olympus is proving its capabilities, as Gariepy explains. “It comes down to the fact that we are a commercial facility that is heavily regulated. We have a great track record with a very robust quality system. The site inspection history and our capabilities in manufacturing continue to improve. In addition our company culture is a key part of our offerings. We have been recognized for our culture and we have a really good balance to offer other companies to work with us.”

Delving deeper into the company’s quality systems Gariepy explains that Olympus’ quality systems are integrated through the facility and ingrained in their culture. “We have an operational excellence team that is integrated throughout the organization. We have made continuous improvements within the operation of the facility, and with process improvements. By focusing on operational excellence and the improvements it provides we have seen significant gains in process efficiency.”

More Scrutiny – From the FDA and Clients

Quality – everyone wants it. No one wants to be responsible for a recall. Over the last several years the FDA has increased its focus on facility inspections all in the quest for greater quality products. As a result of this increased scrutiny, product sponsors have also upped their facility and company audits to make sure their manufacturing partners have quality systems and technologies in place.

“We are a commercial site,” says Gariepy, “and we are under routine surveillance.” He continues, “We have a minimum of two inspections per year from the global regulatory authorities. We are ISO certified and have the ISO audit every year. Then we have the FDA or EMA come in and inspect us –  this is routine surveillance. Our quality is ingrained into our culture here. We work with the regulatory agencies and take feedback.”

“We have been very successfully with our audits – it’s a cooperative experience. We want to learn – and make sure we are doing the right things.”

Implementing New Technologies

New equipment and technologies for biopharmaceutical manufacturing are constantly being introduced. The real trick for any biopharm CMO is to decide when and where to implement new technologies based on product and customers needs. Speaking to the use of new technologies, Gariepy offers his perspective.

“Its important, (new technology) we have to stay up with technology to see what’s out there – and stay on the cutting edge. We have to use what makes the most sense for us as we move forward in a contract. Not everything might make sense – it might be process specific. For example, there might be certain things that a client has in their process that would make us adapt our processes. I think you need to be open and need to take in account the cost efficiencies and the risk. You want to be somewhat risk adverse, you don’t want to put something in that is so cutting edge and then find out it is not doing the job intended. You have to balance out all the factors and make decisions based on what makes the most sense and gives the most value.”

Managing Facility Capacity

Contract manufacturers have the unenviable task of needing to have enough capacity and the right technology to appeal to new clients, but not too much that it goes under utilized. The key to successfully juggling these two opposing forces is to be open and flexible.

“As we work with a partner,” says Gariepy, “we have to asses their process and needs and how it will fit in our facility, for example – do we need to modify a bioreactor, etc.”

“We have a whole building available if someone wants to come in and partner with us. We would have those discussions to see how they fit. You have to be flexible.”

“At the same time you have to be open. If someone came in and said ‘We have a fermentation process’ well we don’t have fermenters here, but we would still talk to them about partnering on a project and build something out. We could work with them on a process transfer.”

“The key is to have an open dialog. We want it be a win-win. We want to be successful and we want our partners to get the products they need.”

According to Olympus’ Director of Materials and Procurement Michael Mayo, all options need to be weighed when considering new technology.

“If a client comes to us and needs a new unit operation, something we don’t have in this facility, maybe that’s an opportunity to partner with them to bring in the new technology, then have it available for someone else down the line. If it’s unique and only going to be used for one client – we evaluate it on a case by case scenario.”

Inside the Facility

Olympus’ facility is divided between production of its own product – the OP-1 compound and space for contract manufacturing. The company’s manufacturing and support staff work on the company’s commercial products as well as contract projects – offering the same expertise to both.

The company’s contract manufacturing space offers a wide range of equipment for bringing product from scale-up to production quantities including:

• 50 L and 200 L single-use bioreactors
• 35 L, 140 L, 525 L and 2 x 2500 L stainless steel bioreactors
• Highly flexible downstream processing
• Depth and microfiltration
• Column chromatography
• Viral filtration and inactivation
• Ultrafiltration/Diafiltration
• Bulk aseptic filtration
• Manual filling using barrier isolator technology

And as mentioned earlier, later this year the company will be adding clinical aseptic fill/finishing services (liquid & lyophilized); One of the interesting aspects of the facility is the use of disposable technology. Single-use and disposable technologies are gaining a good reputation as an ideal technology for biopharmaceutical applications and in particular appeal to CMOs for their cost-efficiencies and ability to reduce, or eliminate, cross contamination.

Gariepy explains that the use of disposables is growing at Olympus. “We tend to push the use of disposables, as they do a couple of things for us – including fast turnaround from one product to the next and the removal of residuals. We don’t want to have any chance of cross-contamination.”

Newest Additions

Olympus has seen the future of aseptic filling and its going to be done with isolator technology. They have recently installed a new isolator for their aseptic filling needs which mates up to their lyophilizer. Currently the isolator is set up for hand fills, but future plans are to expand its use with an automated filler.

“Our design here is for protection of product,” says Gariepy “to create an environment where the human is out of the environment. We have to create the proper environment where vials can be filled and sent to the lyophilizer and then back out again and crimped in an aseptic environment.”

“If we had to do this in an ISO Class 5 room – as opposed to using an isolator, we would have had to spend a lot of money for an air handling unit to be able to generate that environment. Then there is also the cost of training to operate the isolator – but even with the costs of gowning etc. – we saw that as a higher hurdle than bringing in an isolator. We felt that this was a quicker path – and a more robust path.”

A Look at the Future

With systems, technologies and personnel in place, the folks at Olympus are excited about the future. “We definitely have a balance,” says Gariepy. “We have capacity available for long-term partnerships and we continually improve our processes so we can maintain our capacities and share our facility with other companies. We will continue to offer manufacturing services as well.”