Advancing Commercial Manufacturing from Orphan Drugs to Blockbusters

Originally published on December 6th, 2019 at Pharma's Almanac.

The key to success for pharmaceutical contract development and manufacturing organizations (CDMOs) is to understand the needs of the market and evolve the business to ensure that it can always meet customer needs as they change and grow. UPM Pharmaceuticals is dedicated to optimizing manufacturing processes for both small- and large-volume projects to ensure the best production of high-quality drug products.

Taking Projects to the Commercial Stage

To ensure that we grow with our customers as they graduate their products from early- to late-stage clinical trials and through to commercialization, UPM has taken a series of proactive steps. We have enhanced our services for clients involved in later-stage development projects, such as scale-up and the production of registration batches. We have also advanced the manufacture of commercial products as a second supplier.

By combining our early- and late-stage R&D groups into one unit, we are more fully leveraging the talents of our highly skilled and experienced staff. Overall, an updated, clearer review process for incoming project requests allows us to give each project the level of attention required.

All of our clients, whether their projects require one or 100 batches per year, benefit from these upgrades. UPM works hard to accommodate all projects, carefully selecting those that fit our equipment train, manufacturing expertise and available capacity.

For all projects that are accepted, whether blockbuster or orphan drugs, we apply lessons learned about improving efficiency and productivity to provide reliable, high-quality services at the most cost-effective prices possible. Greater efficiency also increases reliability and predictability and boosts our available capacity. Customers with projects of all sizes benefit directly from these improvements, as well.

Maximizing Efficiencies at Scale

Large-scale commercial projects provide the greatest opportunities for increasing efficiency and productivity. Running multiple batches on a frequent basis allows for greater process optimization. Operators repeating the same process many times are able to identify opportunities to improve the yield, reduce the run time, reduce error rates, and optimize other parameters, all of which lead to increased efficiencies and better productivity. In addition, ongoing improvement efforts lead to greater reliability and tighter quality assurance. Operators are also able to do cross-training and increase their knowledge and experience, which is then applied to future projects.

Streamlining Orphan Drug Production

Orphan drug projects, on the other hand, may require batches to be completed only a handful of times per year, or less. Our staff takes great pride in the work they are doing in this space and the knowledge that they are having a significant positive impact for patients suffering from rare diseases, especially in cases where we can help provide the first real treatments for an unmet medical need. They are committed to improving these processes as much as possible in order to reduce not only the cost to produce these critical therapies, but the time to get them to market and in the hands of patients. Even though the batch sizes may be smaller and the number of batches fewer, the products are produced using the same equipment trains employed for high-volume projects. Many efficiencies identified for large-volume projects are product-independent and can be applied to any product produced using the same manufacturing line. Every process and product has nuances, so we learn new things that can be applied to future projects every time we run a batch, regardless of the batch size.

Tech Transfer Expertise

UPM has an experienced group of scientists and engineers working on technology transfer, with backgrounds in formulation, manufacturing equipment, process development, scale-up and validation. Our heads of formulation and manufacturing, for instance, have over 40 and 30 years of experience in the industry, respectively. Members of our staff, in general, have 5–25 years of experience in formulation development and technology transfer and are adept at managing projects from the ground floor up.

We start each tech transfer project with an appropriate transfer plan and provide dedicated project management, technical and analytical support via a tech transfer team that is closely aligned and in close communication with our client’s team. We also take a collaborative approach to our projects, with frequent internal discussions on technical issues and troubleshooting to leverage our knowledge and provide value-added work to our clients.

Open and transparent communication between the scientists and engineers within and between both teams facilitates all stages of the project, from development/optimization of manufacturing and analytical processes, execution of the validation strategy, performance of stability studies and, ultimately, regulatory filing. Team members take ownership of and pride in each project in which they are involved. With these experienced and committed teams and our internal consulting approach, UPM is capable of rapidly investigating and effectively troubleshooting issues that do arise, enabling us to keep projects on track and to consistently meet timelines.

UPM is capable of rapidly investigating and effectively troubleshooting issues that do arise, enabling us to keep projects on track and to consistently meet timelines.

Flexibility is Key

Another crucial characteristic for pharmaceutical CDMOs is flexibility. In addition to the ability to accept both small- and large-volume projects, successful CDMOs have technical flexibility, capacity flexibility and operational flexibility.

Technical flexibility is essential for developing effective, safe and robust formulation and manufacturing process solutions for the challenging drug candidates moving through the pharmaceutical pipeline today. UPM’s experienced group of technical services scientists — with extensive backgrounds in scale-up, technology transfer, process development and validation — can support client products of all sizes through commercial manufacturing.

In addition, UPM has established expertise in a number of different complex chemistries and delivery technologies, from highly potent compounds to many different types of controlled substances and oral peptide therapies, to modified-release technologies and dosage forms. We have worked on successful applications for particle coating, sustained-release matrix tablets, tablets with modified-release coatings and complex combination products.

We also have the flexibility to produce both generic and branded products, which enables us to more fully utilize our process knowledge and maximize efficiencies for increased cost-effectiveness and output. At present, we have the capability to produce 700 million capsule units and 3.5 billion tablet units per year, with 50% of this capacity spoken for by 2021.

Finally, although we take a structured approach to project management that includes assigning each client project to an interdepartmental team headed by a project manager with daily scheduling meetings, unexpected challenges cannot be completely avoided. When they do arise during process development and commercialization, UPM has built-in operational flexibility to address unexpected manufacturing issues, as well as changing client and market needs.

Full-Service CDMO

UPM’s Bristol, Tennessee plant includes a Solids Formulation R&D Facility, modern manufacturing suites and a state-of-the-art, full-service analytical laboratory to support the production of solid and semi-solid products from 100 g to approximately 1 ton annually.

The analytical lab provides method development for raw material release, API and drug product characterization, stability testing, in-process testing and product release. Two high-speed packaging lines with serialization capabilities enable basic packaging for many products. A secondary packaging line is available for production of sample kits, product displays and other items that require manual manipulation. UPM also has a separate 250,000-ft warehouse and provides warehousing and distribution services. Offering final product manufacturing, packaging, warehousing and distribution capabilities in one facility helps clients streamline their supply chains and reduce time to market.

Throughout our history, we have been approached about orphan drug projects that require only one or two small batches per year, as well as commercial transfer projects requiring hundreds of millions of doses annually. We have requests for products that are ANDAs, NDAs, INDs, 505(b)(2)s, new formulation development projects and clinical supplies. As a full-service CDMO, UPM has the capability, capacity, expertise and experience to succeed in all of these categories and scales of work.

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