A cGMP Facility That's Built For Quality

Working with a CMO that can meet the FDA’s standards is of paramount importance to drug companies. The right CMO can mean years of trouble-free operations, while the wrong one could mean failed inspections, warning letters, delayed production, drug shortages, and loss of revenue. With the amount of risk aversion that exists in pharma, it’s a wonder that drug CEOs who outsource production get any sleep at all.

Tedd Green’s goal is to put those fears to rest, and he believes his company, contract manufacturer Cook Pharmica, is taking the right steps to make that happen. Green, Cook’s president, spent time at Arthur Anderson and Eli Lilly before joining the CMO eight years ago. When talking to him, you get the idea he could easily be an industry spokesperson for how to manufacture from a quality and cGMP perspective. Because Cook Pharmica is involved in manufacturing sterile injectables, a category that makes up 70% to 80% of the drugs on the FDA shortage list, it’s safe to say that Green thinks about quality every day.

But don’t just listen to Green. Each year Life Science Leader magazine and Nice Insight present awards to the leading CMOs in the industry, as determined by their customers. At the CMO Leadership Awards in New York City in March, Cook Pharmica was one of only four companies to win the 2012 award in all five categories: Quality, Regulatory, Reliability, Productivity, and Innovation.   

A Quality Focus From Day One

From its origins, Cook set out to build a facility that would be a one-stop shop for biopharma firms. The company has full-barrier isolation systems which sit on top of its filling lines. “This was a conscious decision we made in 2008,” says Green. “When we installed the lines in our sterile filling operations, they were under full isolation from the start. We could have used the more traditional approach (a restricted access barrier system [RABS]), but we felt the next step up was full isolation. We took a close look at industry trends and client expectations regarding systems and equipment, and this is where we saw the industry going. Taking that additional step of ensuring aseptic filling by removing the human component of potential contamination, protects not only our client and patients, but our employees as well.”

Green notes the isolation systems required a much higher capital investment on the front end but were worth the cost. “We wanted to build a first-class facility and believed this approach was the best long-term investment,” he states. “We have a system that was purpose built from day one to focus on maintaining the syringe and vial lines in a GMP compliant manner.”

Acquire The Right People And Training

Knowing the FDA looks at the training and skills of personnel, Green sought to hire the most qualified professionals available. “Quality and cGMP are important to us, our clients and their patients, and FDA investigators,” he says. “With that in mind, we sought people with manufacturing backgrounds who had a good understanding of cGMP and setting up and working within quality systems. Those individuals benefitted from the quality systems we had in place for our drug substance business unit and worked to ensure that we appropriately established the necessary requirements for our new fill finish offerings.”

Having the right people and equipment, according to Green, is the best way to keep abreast of current regulations and to stay at the forefront of industry innovation. He notes Cook Pharmica is audited weekly by many different companies, each providing thoughts, opinions, and information relative to their own view of quality. As a CMO, he believes Cook needs to be constantly reading, analyzing, and acting upon the information they receive.

“Our emphasis is on continuous improvement,” he says. “I believe CMOs need to constantly look at where they are today and where they need to be in the future. Firms need to be diligent in making sure what they are doing is still relevant and efficient. Identifying inefficiencies and potential quality concerns, and eliminating them quickly, is the best way to endear a company to its clients and potential clients, and is the right thing to do for the patients that ultimately rely on the products we produce.”      

Convince The FDA

It might be easy to convince yourself that you have the right people and equipment, but it is much harder to convince the FDA. If anyone doubted the company’s focus on quality, Green believes his team has helped put those fears to rest. Early last year Cook underwent its first FDA pre-approval inspection (PAI) to produce a drug product. Later in the year, when it was scheduled for a second PAI, the FDA waived the inspection. This was not the first time the FDA has waived a PAI and will certainly not be the last. But for Green and Cook Pharmica, it was a significant step.

“No client wants to be the first to run on a new line or with a new CMO,” he acknowledges. “When you are brand new, you need to find a client willing to take the risk with you. Even when you have everything up and running, it can take a couple of years to get your first commercial approval. Our first approval and the waiving of the second inspection shows that our efforts are bearing fruit.”

Regarding the waiver, Green believes the process worked the way it should. CBER (Center for Biologics Evaluation and Research) did the first inspection. CDER (Center for Drug Evaluation and Research) was tasked with doing the second. “I believe CDER referred to the recent inspection report for the same filling line by CBER, and made its decision based on that information. I believe we were able to adequately meet their expectations in regard to both our quality systems and our capabilities.”

Cleaning Up Inspectional Observations

If you’re wondering about Cook’s initial PAI, it was not spotless. The FDA issued three 483s. A response was drafted and submitted, and Cook gained approval of the line in a timely fashion. “We approached those 483s like anything else – they were an issue that needed to be addressed,” says Green. “We had a dialog with the agency to ensure we understood the issues and then provided a solution we felt corrected the observations and would be sustainable. We took the 483s very seriously, and our team convinced the FDA we had the situation under control and were prepared to rectify any situations that might arise in the future.”

While the waiver of the second PAI was a win for Cook, Green believes the real winners are his clients. Having the inspection waived means one less step for those customers and a time savings of perhaps up to 120 days. “For potential partners, knowing we have passed inspection on our fill finish line has real value,” he says. “Given that we are a pure play CMO, our customers will always look closely at our regulatory record. But more importantly, all our personnel are aware that the products we manufacture will at some point be injected into a human. That is a charge no one in the pharmaceutical industry should take lightly.”

Getting more involved with those sterile injectables on the FDA’s shortage list would certainly be a great win for Cook. Green notes he would like to gain some traction in this area to ensure patients who have missed treatments due to shortages will once again have consistent access to the medicines they need. Cook has attended the FDA’s drug shortage workshop and has also reached out to manufacturers that currently have drugs on the shortage list. Green will continue to reach out to firms that may be able to use Cook’s assets and capabilities for greater production and delivery assurance of products in shortage, and is willing to be either a primary or secondary supplier. “Any time a drug is in shortage, the pain is ultimately felt by the patients,” he says. “For that reason, any company producing a product on just one manufacturing line should strongly consider employing a secondary manufacturing backup strategy. This has to be considered from a risk mitigation standpoint.”

Going forward, Green believes Cook will remain a pure contract manufacturer. His short-term goal is to make sure all assets are up and running at optimal capacity. He notes he will continue to monitor the market and industry trends to ensure that his company has the right mix of equipment and capabilities.