May 29, 2018 PAP-Q2-18-CL-016
For many reasons, the preferred route of administration for new drugs is oral delivery, ideally using oral solid dosage (OSD) formulations. In addition to being the most cost-effective dosage form to produce, they have the advantage of extended storage stability, generally without need for refrigeration, and are easy to ship.1 Brand recognition can also be built directly into tablets and capsules through the use of unique combinations of shape and color.2 OSDs are also relatively easy for patients to take, with no need for dosage measurements or uncomfortable/painful injections.1 They can also be formulated in a variety of modified/extended release formats to reduce the number of dosages — all properties that lead to increased medication adherence.2 In addition, advanced delivery technologies provide enhancement of bioavailability and, in some cases, targeted delivery for improved efficacy and safety.1
With these factors as drivers for growth, it is not surprising that the global market for oral solid dosage pharmaceutical formulations is predicted to expand at a compound annual growth rate of 6.5%, rising from $493.2 billion in 2017 to $926.3 billion in 2027.1 In 2017, North America was the dominant region, accounting for 37% of the consumption of OSD drugs.
The fastest-growing segments of the OSD market include small-scale, high-value dosage forms such as pediatric, geriatric, anti-abuse, controlled-release and taste-masked drugs.3
Advances in rapid synthesis technologies are leading to the preparation of new classes of compounds with attractive therapeutic properties — but with challenging physicochemical and pharmacokinetic profiles, particularly with respect to solubility and bioavailability. Approximately 40% of currently marketed drugs and 80% of pipeline candidates meet the Biopharmaceutical Classification System (BCS) definition of poorly soluble (classes II and IV).4 These issues are creating significant formulating challenges. There is also growing expectation in the pharmaceutical industry for new therapies to be designed with the patient in mind.
Often, advanced, specialized drug delivery technologies are required to overcome poor physicochemical and pharmacokinetic properties and enable the design of patient-centric medicines.2 Application of many of these technologies requires access to advanced equipment and highly skilled and experienced scientific experts. For most pharmaceutical companies, maintaining these capabilities in-house is not practical or possible.
Many of the molecules under development today are also structurally complex and require advanced synthetic chemistry capabilities, as well as the ability to conduct multistep syntheses involving a broad array of chemical and engineering expertise. Drug substance and formulation complexity are, therefore, driving demand for support from contract service providers. The most successful CDMOs not only have the specialized technologies, expertise and experience needed for these complex projects, but also have achieved high efficiency and productivity levels, thus reducing development and commercialization costs and timelines.
They also offer integrated services from the preformulation stage through to commercial manufacturing, allowing for consideration of special formulation needs earlier in the development process, while eliminating the cost and time associated with tech transfer.2 Close collaboration between CDMOs and their pharma customers is essential to the success of these complex projects. Flexibility in terms of development and manufacturing capabilities and partnering arrangements is also an asset.3
At Tedor Pharma, we have provided the pharmaceutical industry with contract services for 16 years from our Cumberland, Rhode Island facility, which specializes in oral solid dose formulation development and manufacturing. We take projects from the earliest formulation stages through scale-up to commercial manufacturing. We have extensive experience working with the FDA in filing both new drug applications (NDAs), abbreviated new drug applications (ANDAs) and 505(b)(2)s — as demonstrated by the 16 approvals we have received.
Our FDA- and DEA-audited, 40,000-square-foot facility has 14 production-ready GMP suites, 2 formulation suites, and quality assurance and development labs for the production of high-quality OSD formulations with annual capacity to produce 620 million capsules to 2.5 billion tablets. On-site analytical labs provide support for in-process testing and product release. In addition to dry blends, we have a dedicated suite for fluid-bed coating, drying and granulation. We manufacture coated and uncoated single and multilayer tablets and capsules that contain powders, beads or granules. We also have the ability to produce immediate-, modified- and extended-release formulations, as well as controlled substances (Schedules CII–V).
Demand for CDMO support of oral solid dosage drug development and manufacturing is coming from all sectors of the pharmaceutical industry — from large pharma and start-ups to virtual companies and generic firms. While Tedor Pharma provides support to customers of all sizes, our focus is on small to midsized organizations.
Tedor Pharma is small enough to care about customers on an individualized basis and yet experienced enough to deliver for all companies, but particularly for smaller firms. These smaller firms might not get the attention they deserve from larger CDMOs serving larger customers.
We are very focused on the customer experience and pay the utmost attention to the needs of each and every customer we serve. With our milestone-based project management system, we provide one point of contact from the start of a project through to its completion. The project assessment phase includes consideration of ways to improve efficiency and productivity and reduce costs. With planning, implementation and launch considerations integrated into the project management system, we are able to focus on the process, quality, speed and cost — all of the factors that drive performance and ensure an outstanding customer experience.
Small and midsized customers also benefit from our extensive formulation development and regulatory expertise. Our formulators apply their extensive product development experience to identify the optimum formulation solution that is also robust and ready for scale-up and manufacturing. They are also experienced at lifecycle management and can, for instance, convert existing formulations to controlled- or modified-release versions to extend patent life. Similarly, our regulatory experience is very deep. We can assist customers with the turnkey filing of NDAs, ANDAs and 505(b)(92)s, ensuring that documentation is correct and complete.
Another differentiator for Tedor Pharma is our extensive experience with DEA scheduled products. Currently, 90% of our project portfolio comprises schedule II through V drugs as defined by the Controlled Substances Act (CSA) in the U.S. These products include a wide variety of controlled APIs that must be manufactured, stored and distributed following specific protocols to prevent their illegal use. The medical applicability and potential for creating dependency and being abused determine which schedule applies, with schedule II products more dangerous than schedule V drugs.
Manufacturers of these products must first install appropriate facilities, equipment and management systems to ensure control, traceability and accountability, and then obtain a State Board of Pharmacy license, after which they can register with DEA. The agency then conducts annual audits to ensure ongoing compliance.
Tedor Pharma understands the severe consequences that can result from noncompliance. We have an excellent relationship with DEA and are very familiar with the quota process and the steps needed to obtain appropriate quotas for the controlled substances we manufacture for our customers. As our long track record demonstrates, our employees have extensive experience working with scheduled products and efficiently meeting the extensive recordkeeping requirements and protocols that ensure prevention of the diversion of controlled substances.
Part and parcel of our commitment to ensuring an outstanding customer experience is working hard to anticipate our customer’s future needs. Rather than making facility investments only when specific customer projects require us to do so, we are proactive. Through our close collaboration with our customers and based on our understanding of the OSD market, we anticipate future customer needs and invest in the new technologies we believe they will require.
Recent examples from 2017 include an investment of $7 million for a dedicated fluid bed suite and the construction of several multipurpose manufacturing bays, all of which are qualified and ready for use. The new fluid bed suite was added because many manufacturing processes for the complex OSD formulations being developed require fluid-bed manufacturing processes. With this new capability, we are even better positioned to help our customers create optimum formulations.
Multipurpose manufacturing bays allow us to provide more flexibility for our customers. The complex projects brought to Tedor often require special handling and/or the use of multiple technologies to implement optimized processes that provide robust, high-quality differentiated formulations. With numerous multipurpose bays, we are able to meet the wide variety of needs of existing and future customers. To keep pace with these needs, we are currently exploring other opportunities for investment and will likely have additional capabilities later in 2018.
Terry Novak has over 35 years of experience in the pharmaceutical and biotech industries, most of that in executive leadership in business development, sales, marketing, and operations. Terry currently serves as Chief Operating Officer of Tedor Pharmaceutical LLC. Prior to joining Tedor, Terry served as the Chief Operating Office of Pernix Therapeutics, a specialty pharmaceutical company and has been an executive at Norwich Pharmaceuticals, Patheon and DSM. Terry currently serves on the Advisory Committee for the North Carolina Biotech Organization.