Rottendorf Pharma USA’s president and CEO Gordon Haines noted in a recent website blog that there are three aspects of contract pharma that are virtually universal and most are likely to agree. Worldwide, he said, pharma companies are outsourcing older product production and allocating internal capacity to high-value, non-generic or “flagship” products. He explained the notion of using a European supplier to produce E.U.-destined drugs (or a U.S. CMO for U.S.-bound drugs) is blurring and while drug companies may initially target select geographical markets, drug production processes are increasingly being designed to stand up to more universal regulatory standards in an effort to meet the ‘highest common denominator’ of key regulatory regimes.
In response, Haines said, CDMOs like Germany-based Rottendorf are broadening their reach, and working harder than ever to position themselves as the first place sponsors will take their high-potential formulas to assure their commercial success in diverse global markets. Rottendorf is extending its reach and positioning itself based on a strategy that has a distinct focus: solid dose forms.
“For us,” says Bruno Buss, senior director of product performance, “the decision to concentrate on solids is very strategic.” This primary strategy, says Buss, is linked to most all their operations-oriented strategic decision making. “This is our core competence,” explains Buss. “Our Transfer development and Upscaling centers are based on this strategic decision to have the absolute competence and the best technologies to produce solids.”
Rottendorf explains the continual demand for development and upscaling capacities in a GMP and FDA-compliant environment encouraged them to invest in the company’s new Development & Transfer Center to manage laboratory lots 1.5 kg and stability and clinical batches of 15 to 150 kg, representing the entire spectrum of all production technologies for solids. Additionally, the company offers extrusion technologies for pellets and melt granulation, as well as access to high-pressure melt extrusion and nano-encapsulation. Rottendorf says it places a special emphasis on improving the bioavailability of poorly soluble APIs.
Citing recent and significant investment in both centers, and the emphasis on the professional depth of the company’s specialists, Haines points out staff are doing development from the first steps of formulation on through to clinical trial and upscaling batches. Buss stresses that Rottendorf is very deliberately organized to link strong formulation and development with equally strong scale-up and commercialization capabilities. “Sometimes you have development companies that are really strong in development and good formulation development; our formulation development is really focused on robust processes in production.”
Rottendorf says its customers really trust its expertise in formulation development and some come in at a very early phase. “For example,” says Buss, customers often come to us with “basic information about their new API and its early formulation. They want us to participate in the development at an early stage in formulation so that later on, the drug is ready for clinical trial batches without bigger changes over the whole lifecycle process.” Buss says Rottendorf’s experience covers some 500 different formulations, and that knowledge translates into real wisdom when it comes to seeing a promising molecule commercialized successfully.
To assure the quality and manage risks associated with the intake and production of a sponsor formula, Rottendorf relies on a dedicated transfer group made up of highly trained, highly educated staff to take care of all transfer activity be it transfer from the development phase or from another plant; or another development company into Rottendorf’s plant. “We have a design process for this at Rottendorf,” says Buss, “Which is linked to the quality-by-design process and promotes a quality transfer.”
UP TO SCALE
“At any point in time,” says Haines, “we have upwards of 200 customers and potentially 600 different SKUs that we’re running through the year.” He explains the company’s upscaling group is part of the development group. “We bring those staff managing full-scale production into this group. They follow the products when we go into the upscaling phase — compiling the product — defining the process in the production down to the machine level. Together they have the knowledge from the development or transfer phase to production. They have accountability for all this work and report directly to the head of manufacturing — due to this, we bring the small-scale and the full-scale world together.”
In March 2015 Rottendorf announced three formulation development projects and two commercial transfer projects with “Top 5” Pharmaceutical and Biopharmaceutical companies. At the time the company said its five new projects capped a strong year of growth for its U.S.-based subsidiary, which has more than doubled its share of corporate revenue since 2011.
“The new projects signed in the last quarter reflect the industry’s positive response to our business model and our commitment to Total Process Ownership,” said Haines in the company’s press release. Be it vision, mission or branding strategy, Haines said the company’s total process ownership philosophy relies on open communication and exchange of ideas with our pharma partners and draws on the company’s 85 years of formulation development and manufacturing experience.” Fundamentally, under this TPO regime, Rottendorf assumes a high degree of process responsibility and ownership. And delivers to customers reduced management oversight, reduced supply chain complexity and a better cost structure overall in which to make and market their products.
Haines explains that currently approximately 150 active products are being managed for customers at the plant annually. The facility is designed and equipped to fulfill and support the company’s strategy which, above all else, is based on extremely strong technical acumen as well as internal process and procedure design that delivers operational excellence. In its literature, Rottendorf says it offers all standard technologies for solid dosage forms and is able, in combination with its development and upscaling centers, to manufacture all batch sizes up to 1 ton, and coating up to 750 kg per sub-lot. Additionally, says the company, high-potency products such as Tamoxifen, Flutamid and Clomifen can be manufactured in segregated production areas.
PACKAGING'S PROMINENT ROLE
Rottendorf Pharma has a full service packaging operation for primary and secondary packaging of bottles and blisters for original prescription, generic and OTC solid oral dose products. About midway through 2015 Rottendorf reorganized its packaging operations. “Packaging is fully included now in our standard transfer group and standard documentation group,” Buss explains, “and now under one roof, one QSM, following the same internal processes and quality control.”
“Our lines can handle a broad range of materials and multiple configurations,” says Haines. “As a Top 20 CDMO, we are ready to help our customers design, customize and/or optimize their packaging in a form most appropriate for the marketplace. At Rottendorf, we package more than 4 billion tablets, capsules and pills a year on nine blister lines and two bottle lines.”
Rottendorf says its customers want help to meet new serialization requirements without having to make the total capital investment themselves. To accomplish this, says Haines, Rottendorf consultatively works to design packaging with efficient, cost-effective materials and operations. “Packaging choices can have a significant impact on the finished cost of a product, says Haines. “If packaging suppliers are involved early in the process, appropriate packaging can be designed and optimized for dependability and cost. The bottom line is Rottendorf wants its customers to stop treating packaging as an afterthought. “At Rottendorf, we try to make our customers aware of the potential impacts of incorporating packaging design early, to try to move it up on their list of priorities, but practice is still behind where it needs to be,” says Haines.
Haines says many new clients come to the company as a result of word-of-mouth referrals from clients who have benefited from its TPO philosophy and proactive approach to process improvement, as well as its proven ability to engineer commercial success into solid dose formulations. Others think so, too. A prominent industry publication recently presented Rottendorf with five separate 2015 CMO Leadership Awards reflecting, it said, the laser-sharp focus the company has on long-term customer success. “Clients also appreciate Rottendorf’s unique corporate structure,” says Haines. “We are owned by a charitable foundation, which allows us to focus more on long-term success of our business and the goals of our customers, rather than needing to satisfy shareholders on a quarter-by-quarter basis.”
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