Issue link: https://www.e-digitaleditions.com/i/648486
technology agnostic." Nor does every customer's product involve a capsule. Among the products DFS helped cus- tomers formulate and file with the FDA in 2015, there are a variety of dosage forms, including hard capsules, multipar- ticulates, softgels, and tablets, Patel said. "We do have deep capsule-related expertise, but we're also dosage form agnostic." At Metrics, many customers must reach certain mile- stones to get their next tranche of funding, and for them, "speed is everything," Ross said. It's one of the reasons Metrics expanded its product development area last year to include a non-GMP space. "That's been the key factor for us. It's really allowed us to make tasks that once happened consecutively to now run in parallel. Prior to that expan- sion, we didn't really have any space on site that was suit- able for non-GMP, quick-in, proof-of-concept work. It miti- gates some of that upfront investment in time and overhead," he said. "You can be a little bit more expedient in your experimentation." Last year, one project went from inception to the clinic in 9 weeks. "That was aided by some early formulation activity in that space. Now we're kind of wishing we had made it bigger." The quest for speed has also led Metrics to start making more changeovers when its equipment is idle and by doing more off-shift cleaning and swabbing. "That way we can get the analytics done on equipment—at least in some cases— overnight. We're principally a one-shift operation but we're starting to add bits and pieces to take advantage of the time when equipment is typically idle." For yet more speed, the company also continues to look for simpler or less expen- sive containment options. "The diversity of compounds that we introduce into our site is incredible," Ross said. "Anything that can expedite cross-contamination control without losing any effectiveness would be huge. It'd give companies like ours a better ability to manufacture and package potent substances or cytotoxic substances, exploit equipment turnover, and ensure employee safety," he said. At Patheon, solubilization enhancement is a key initia- tive, van den Dries said. "We can look at different technolo- gies to overcome your bioavailability issues in parallel, sup- ported by in silico modeling and predicting formulation properties. We can also do some molecular modeling to see what solutions work best." That may mean creating a solid dispersion or something else entirely. "There's no single solution to overcome bioavailability issues; it depends on the API's properties. But we have no presumptions on what the best approach is. We approach it agnostically." The company has also begun work on a system to con- tinuously manufacture tablets and capsules at its Greenville, NC, site. "The concept is very clear, as are the benefits," van den Dries said. "It addresses the time and money lost in the development cycle on scaleup. It also can be a nice benefit to existing manufacturing processes." (See the related article on page 14.) Cost and time savings are also a priority at Rottendorf. "We consider ourselves a very good value-based company, meaning we bring a high level of skill, capabilities, and commitment at a very reasonable price," Haines said. "We partner with you to ensure that we understand what you're trying to do and we help you achieve your overall goal, not just produce a pill." The company also seeks opportunities to improve products and save money. "It's not just 'Give us a recipe and we'll make it.'" In some cases, the company might suggest switching to an excipient that Rottendorf buys in bulk. "If you're OK qualifying a new supplier for a like excipient, we can cut the cost of your formulation." Haines said the company is committed to "total process ownership. We act as if we're part of the customer's com- pany to help them reach their goals." It also entails close process supervision. In one case, Rottendorf workers noticed that a batch of excipient had extremely low pH compared to other batches. "By definition, it met all the critical parameters, but based on our experience, it raised production issues," Haines said. After tests showed it would be a problem, Rottendorf made small process adjustments, and the excipient was approved for use. "So the customer was happy because we didn't just blindly accept the excipi- ent and because we figured out how to use that excipient and not create bad product." More services and more partnerships Clearly, the business and technology landscape for CDMOs has changed. "The number of organizations that have now decided, fundamentally, that they're not going to invest in infrastructure has grown dramatically," Ross said. "When I started 15 years ago, the CDMO was rarely the expert and most customers were only looking for additional capacity." Not so today. "Clients are looking to us and our Metrics' expertise includes developing high-potency drug products and using fluid-bed technology to create multiparticulate dosage forms. Photo courtesy of Metrics Rottendorf's development group employs more than 40 scientists, all of whom work on solid oral dose products. The photo shows a worker load- ing ingredients into a granulator. Photo courtesy of Rottendorf Tablets & Capsules March 2016 13