Manufacturing Chemist – September 2016.

Accelerating successful drug development to meet global demand.

A drug’s ultimate market and therapeutic success increasingly depends on strategic alliances and access to flexible, scalable development and manufacturing resources on a global scale. Drug owners and developers are finding that partnering with contract development and manufacturing organisations (CDMOs) is now an even higher strategic and tactical necessity if they are to accelerate the successful development and commercialisation of novel and challenging small- and large-molecule drugs.

To meet the increasing challenges presented by competitors and global society’s growing demand for high value, high performance therapies, drug developers and owners are channelling R&D investment in new ways to support evolving product strategies for current products. At the same time, they’re pursuing promising development pathways for high-potential new chemical entity (NCE) and new molecular entity (NME) targets that deliver better therapeutic value to the patient.1

To help meet mounting competition, price cuts, social and regulatory headwinds, many pharma companies followed a strategy of diversifying into a business model of developing product lines that are less exposed to R&D and market risks. Regardless of the difficulties, the therapeutic achievements of the industry are accelerating at a pace not seen since the passing of the blockbuster business model. This approach has been relatively successful; but, for industry to advance and achieve long-term sustainability, a more dynamic and flexible approach will be required.

This approach requires innovative thinking and more collaborative alliances with key strategic partners. Drug development on a global scale is incredibly complex and the risks incumbent to such an enterprise can be daunting. Engaging partners to share and manage risk is both a prudent and increasingly popular strategy to successfully address the challenges of introducing new drugs to global markets and health systems.

Such risk sharing has become an effective partnering strategy for CDMOs, and has fuelled the industry’s acceptance of new collaborative, virtual models among drug owners and contract service providers, which is allowing the industry’s innovators to explore a variety of next-generation business models for their existing products and development targets. These emerging pharma business models are prompting pharma and biotech companies to pursue strategies that play to core strengths and secure critical, strategic collaborators to span any gaps or deficiencies in R&D, manufacturing and similar operations.

For most sectors of the pharmaceutical economy, the compelling desire to accelerate drug development and time-to market is being met by aligning and integrating the core strengths of their supply chain partners.2 According to a Poole College of Management case study, outsourcing rates for generic companies vary from 10–20%. These firms are most likely subcontracting more complex products that they are unable to generate with existing resources.

Emerging biotechnology companies are also moving to more virtual supply chain models, increasingly relying on outsourcing to take them every step of the way along the development continuum. Some 75% of the biotech sector is reliant on outsourced partners. Midsize and speciality pharmaceutical companies often lack capacity and are outsourcing significant parts of their value chain at rates as high as 50%. Large pharma company outsourcing practices range downward from 10–20%, but this may begin to trend upward as companies close obsolescent facilities and seek to shift capital spending to the operations side of the expense sheet.3

Leveraging Effective Partnering Models

Les Laboratoires Servier (Servier Group) has leveraged an effective partner model to establish itself as France’s second largest pharmaceutical company, one that is committed to delivering patient-centric medicines worldwide (92% of Servier’s products are prescribed outside France).

During the last few decades, Servier has successfully established itself as a company committed to better health outcomes based on highly targeted, advanced, science-based therapies. Currently the company is developing 23 drug candidates (small and large molecules) in oncology, cardiology, metabolic diseases, neuropsychiatry and rheumatology.

Expertise and Capacity Available

In late 2014, Servier Group embarked on an initiative that would offer the company’s highly developed operations, quality culture and global drug supply chain development skills to interested parties. Servier announced that it was forming a contract services group (Servier CDMO), bringing its collaborative, high-performance operational infrastructure and skilled teams to pharma to deliver a range of contract services, technical lab and processing competencies.

Ranging from complete manufacturing operations to the supply of discrete research and processing tasks (from starting materials and clinical trial batches to finished products), Servier offers its extensive experience and the organisation’s core strengths to take on the industry’s most challenging patient-centred development strategies and operational tactics.

Immediate Access to Patient Centered Product Strategy

Servier CDMO is also positioning itself as one of pharma’s key business developers globally, seeking collaborative relationships with partners looking for growth, new markets or extra capacity near home markets, or to support opportunities in developing economies pursuing Westernstyle healthcare based on pharmaceutical therapies.

To meet the increasing demand for manufacturing and development resources globally and to support companies looking to gain strategic access to new international regions, Servier can now leverage its 11 facilities to create the flexible, scalable network necessary for industry to deliver the potential of the industry’s most promising molecules and compounds. Servier’s network of facilities and processing capacity is located to serve key international regions, including Brazil, China, Egypt, France (API, drug product), Ireland, Morocco, Poland, Russia and Spain (chemical intermediates, drug product).

For example, nine new molecular entities are in clinical development for oncology — including breast, lung and other solid tumours — as well as leukaemia and lymphoma. Servier CDMO offers analytical services, extensive experience and commercial-scale manufacturing capacity for solid and liquid dosage forms. Broad expertise in organic chemistry is another core strength, from scale-up to the commercial-scale processing of highly potent APIs, catalytic hydrogenation, preparative chromatography, crystallization processes and flow chemistry.

Dosage form and formulation are important factors to a given therapy’s commercial and therapeutic performance, and experience in most popular galenic types — including tablets (layered, time release, etc.) capsules, inhalants, parenterals, powders and viscous liquids — is a strategic necessity. For many drugs, it is at this point in development that critical decisions will be made to address the patient-centric issues of dose adherence and promote overall effectiveness and therapeutic value throughout a drug’s lifecycle.

Offering extensive process and analytical development experience to address product features, Servier CDMO employs current best-practice process design and analytical methods, including synthesis, isolation technology and advanced drying/solid treatments, as well as full testing of active pharmaceutical ingredients (APIs), raw materials (RM) and finished product (FP), stability studies, method development, cleaning validation and comparative dissolution studies.

Packgaging, Supply Chain and Beyond

One core strength in high demand by global developers and owners — and something increasingly playing a direct role in supporting dose adherence and effective drug delivery strategies — is packaging experience. Servier’s competency in this area is well developed, with extensive knowledge in processing primary and secondary packaging in most forms, which can be leveraged to support drug delivery and tactics to comply with upcoming serialisation regulations. Servier CDMO services include custom packaging, integrated serialisation and aggregation capabilities, data matrix support and, increasingly important, tamper-evident technologies. Access to global distribution support is available with regional warehousing, temperature controlled storage, distribution and export/import management services.

Quality that is Institutional

Servier’s quality and compliance track record has few peers. Quality is a distinct organisational imperative and an integral, institutionalised element of Servier’s quality culture. With the same quality management system applied to all its sites, Servier is able to deliver the right product with the right quality at the right time. Servier incorporates Quality by Design (QbD) to create best-in class processes to produce any quantity of drug to meet demand through scale-up and commercialisation. The company offers pilot batch manufacturing (for clinical trials), scale-up development to process industrialisation, contract manufacturing (fluid bed dryer/one pot technology), as well as advanced intermediates production and high-potent compound handling capability.

As the global industry gains momentum in response to a broad range of market, regulatory and social trends, there’s been a resurgence in pharmaceutical development.

But many companies are choosing not to go the entire journey alone and are using highly integrated partnering models to advance their drug-development agendas. Advancing science, especially in the biotech sector, as well as emerging markets and healthcare models are driving new avenues for innovation and therapeutic success for patients — something that has become increasingly dependent on collaboration across the supply chain. Ultimately, it is this collaboration that will hold the key to successfully responding to market demand and collaboration among all segments of the industry and its service providers.

References

1. www.phrma.org/sites/default/files/pdf/2015_phrma_profile.pdf.

2. http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/ucm439082.htm.

3. https://poole.ncsu.edu/i/com/weblogs/alumni/2008/Patheon%20Case%20Study%20-%20Bringing%20Customers%20Back(1).pdf.