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Single Source Solution

Thu, 11/17/2011 - 9:11am
Jeff Reinke

Although millions in the Hoosier state might disagree, there is something at least as prominent as basketball that’s beginning to define Indiana. In addition to the number of medical implant and device companies that have put Warsaw, Indiana on the map, the state also houses a contingent of leading biopharmaceutical manufacturers. Combined, they’re re-defining the region as a hotbed for life science companies – not the least of which is Cook Pharmica.

One of the Cook Group’s nine business units, its location in Bloomington (home to Indiana University) entails two 450,000 sq. ft. facilities that cover 50 acres. Formerly home to the world's largest TV assembly plant, employees and locals have seen a dramatic change in the location as it transitioned from RCA to DNA. Purchased in 2004, the buildings were stripped down and customized to handle a very different type of production flow.

Founded in 1963 as Cook Medical in Bloomington, the Cook Group is privately held by the Cook family, making Cook Medical both the largest business unit and the largest privately held medical device company in the world. Cook Pharmica has used the parent company’s resources to expand their contract development and manufacturing capabilities to include:

• Biologics manufacturing.

• Analytical method development.

• Formulation development.

• Aseptic vial and syringe filling.

• Lyophilization.

• Secondary packaging.

So basically, the company can play a role in producing or developing a wide range of pharmaceutical or biopharmaceutical products from their single facility.

One And Done

“The current trend in drug development is to stay within your core competencies, and outsource the rest,” offers Cook’s Brian Lange. “That trend has fueled significant growth in a number of our contract business segments, including both drug substance and parenteral drug product manufacturing.”

With Cook capable of handling so many different customer needs, as well as varying aspects of development and manufacturing, one of their most powerful sales tools in attracting new customers has been a simple Benefit Calculator.

“We use this to show prospective customers how having our full portfolio of capabilities all at one location saves time and money in contrast to working across different CMOs from drug substance to final product,” states Lange. “It’s a great way of showing how the process is simplified with a consolidated supply chain, as well as with fewer agreements and audits amongst multiple organizations and/or locations. There are a few CMOs that offer similar capabilities to Cook, but they still must work across different locations,” adds Lange.

Although quality controls are obviously prominent elements of any production process, this focus is ratcheted up when dealing with pharmaceutical applications. “Cook has always been about quality – the patient comes first,” states Lange. “To help ensure the highest levels of quality, we implemented barrier isolators with our automated fill lines, as opposed to restricted access barriers, for the simple fact that barrier isolators provide the best aseptic environment possible for producing quality product, while protecting our operators at the same time.”

Additionally, Lange says the company’s choice to use barrier isolation systems also allows for validated and automatic decontamination (or cleaning) inside the barrier to further reduce risk to the product.

On The Floor

With capabilities ranging from development to production, Cook has a number of operational systems in place:

           Development: As part of the one-source, one-location model, Cook’s development capabilities include an upstream lab with 2, 5 and 20-liter systems, a scale-up lab with systems up to 250 liters, a downstream lab with chromatography and tangential flow filtration systems, and an analytical laboratory with full bio-analytical capabilities. A formulation lab to support the development and optimization of both liquid and lyophilized formulations is also present in the massive facility.

 

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           Bulk Drug Manufacturing: To address the tremendous growth of the biologics market, Cook’s bulk drug substance manufacturing capabilities include GMP production areas that can support both clinical and commercial mammalian cell culture manufacturing projects.

                       Biologics Production includes multiple single-use reactors, a 600-liter stainless steel seed tank and two 2,500-liter stainless steel production bioreactors. The small-scale production area includes 10-liter and 25-liter single-use wave reactors along with a 250-liter single-use, stirred-tank production bioreactor.

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                       Product Recovery & Purification includes two 3,500-liter harvest tanks, depth filtration, centrifugation, tangential flow filtration and multiple chromatography systems and columns.

           Parenteral Drug Manufacturing: Flexible facility and process design allows for parenteral drug manufacturing of both commercial and clinical-scale formulations. Fully-automated aseptic filling lines for both liquid and lyophilized vials, and prefilled syringes – all of which are complimented by inspection, labeling and secondary packaging capabilities – can also be accommodated.

Cook’s lines can process up to 600 syringes per minute, or approximately 70 million units per year and in a wide array of batch sizes. They can also process up to 150 vials per minute, or approximately 15 million units per year, again, in a variety of batch sizes.

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On the vial line, a 250 sq. ft. lyophilizer is included within the isolator to allow for filling, stoppering, lyophilization and capping all under barrier isolation to maintain the highest quality standards. Cook’s status as a privately held company also helps them to move very quickly if they need to invest in new equipment in response to industry demands, trends, or meet the needs of their customers.

As mentioned earlier, the company’s facility was a former RCA building that was completely renovated to produce biopharmaceuticals. While this was obviously a large undertaking, it did provide the company with an opportunity to make the work flow as efficient as possible, as Lange explains.

“With essentially an empty shell of a multi-level facility, we had the good fortune of being able to design the building around product and personel flows, visuals, and operating mechanisms that would leverage the principles of Lean when creating our manufacturing spaces and operations (build-outs in 2005 and 2008).” 

“As we created our processes, our personnel really facilitated the practice of reducing variation and utilizing data to better understand and control our processes. We maintain a site lead for continuous improvements in our facility, operations, and processes to ensure that we maximize the potential of our assets. Continuous improvement is part of our everyday culture, as operational and process optimization will only further benefit both our operations and our clients.”

Big Versus Small Molecules

With all of the company’s manufacturing capabilities, one might ask how the company handles the inherent differences in big molecule and small molecule drug production.

“As our Technical Services and Development teams would say, ‘Each molecule has its own personality’” quips Lange.  “With that there are small, but important equipment and process capabilities that enable the flexibility needed to work with both small and large molecule projects.

“Bottom mount magnetic drive mixers and time pressure filling, for example, help ensure large molecules are handled more gently and minimize sheer. Our filling equipment can provide nitrogen overlay, catering to small molecules that have oxygen sensitivity. There are also other sensitivities for large molecules such as ultra low levels of residual peroxide that one needs to account for whether using vaporized hydrogen peroxide within a barrier isolator for decontamination or manual application of sanitizing solution.”

Looking Forward

Lange sees Cook’s future growth coming from the industry’s increased focus on biologics and parenteral drugs, which is the core of the company’s expertise. Despite the company’s current level of success and bright future on the CMO landscape, Lange also knows that Cook needs to maintain its focus in order to continue growing and improving all of its capabilities.

“Ultimately, our aim is simple…to continue to build on our relationships and track record with our clients, and that will earn us opportunities to service more and grow in this expanding market. We are a company that has invested heavily into our facility, equipment, and people with the idea of doing things right and providing the biopharmaceutical industry with the best possible resource for contract development & manufacturing.”

 

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