April 12, 2019 PAP-Q1-2019-CL-006
One of the ways in which drug companies are seeking to boost operational efficiency and productivity is through increased outsourcing. Contract service providers are responding by adjusting their business models in order to better meet existing and future customer needs.
It is important for service providers to remain aligned with the current and future direction of the pharmaceutical industry as they adjust their business models.1 It is critical to not only consider the demand and supply of manufacturing services and products, but the roles of supplier and customer within these strategic partnerships and the performance expectations for both.
Servier offers contract development and manufacturing services for drug substances and drug products across 11 sites in France, Spain, Ireland, China, Russia, Poland, Egypt, Morocco and Brazil. Where we do not have our own facilities, we have established relationships with reliable partners. This global network is embedded within the Servier Group, a global pharmaceutical company with more than 60 years of experience and a presence in 149 countries. All of our CDMO services leverage the Servier Group’s knowledge, quality culture and support functions (e.g., regulatory, supply chain, finance).
Despite the strong growth of the biologics segment of the pharma market, demand for outsourcing support from pharma sponsors remains greatest for small molecule intermediates and APIs.1 There is also growing demand for packaging services and products. While demand for development and manufacturing services are highest for solid-dosage drugs, there is also increasing interest in parenteral manufacturing services.
Small-molecule intermediate/API and drug product manufacturing, including highly potent compounds, has been a core expertise at Servier for more than 60 years. We have three sites for the production of APIs and advanced intermediates, each of which includes an industrial research center for clinical manufacturing and process development. We offer classical and novel technologies and apply quality-by-design to process development. Environmental considerations are always factored in at the beginning of the route selection process.
Servier also has capabilities in formulation development and small molecule drug product manufacturing; we are focused on achieving the right quality for many types of dosage forms, such as modified release, FDC and liquids. One of our key advantages is our experience with successful technology transfer. Servier has a team dedicated to implementing new products or transferring products between facilities within our global network. Additionally, Servier can meet demand for small molecule manufacturing at all scales, from process development to early-stage development and commercial production.
When pharma companies outsource manufacturing, they are often driven by the need to access specialized services they lack in-house. Serialization is one such capability currently in high demand. Others include continuous manufacturing of APIs and drug products and specialized analytical services.1 Our packaging services are also spread throughout our global network to meet client demands and favor local market access.
Like our clients, Servier, as a drug manufacturer, must be compliant with serialization requirements. Our CDMO services are embedded within the larger pharma organization, which means our clients benefit from our previous compliance investments.
We expect approximately 80% of the markets we serve to have serialization/aggregation regulations in place by 2021. We have taken a proactive approach to these capabilities, and, in 2014, established a corporate-level serialization team that developed a centralized track-and-trace solution maintained at all sites in our global network. The system is sufficiently versatile to facilitate compliance with different country serialization schemes and ensure full compatibility and connectivity with external client systems. It addresses the need for both serialization of individual product packages and aggregation of those packages into larger bundles.
With respect to continuous manufacturing, Servier has been practicing commercial-scale flow chemistry for 20 years — we are currently producing more than 200 tons per year of advanced intermediates using the technology. We have also introduced new flow reactors that can be used to deliver clinical-stage APIs faster and also limit the environmental impact in production. Flow chemistry expertise resides within Servier’s Innovative Technology Department, which works closely with experts in chemical development. Our 100-mL plugged-flow reactors allow effective development in a design that is readily transferrable to industrial scale (20–50 L), allowing rapid commercialization of optimized processes.
In October 2018, we launched InnoPreP™, our preparative chromatography service, which leverages the 30+ years of experience our team has in this field. The service encompasses the capability for either continuous processing using simulated moving bed or 6-column batch chromatography at lab to industrial scale and can reduce time-to-market by as much as three months. Our preparative chromatography infrastructure at the Bolbec site has been expanded to include a dedicated 500-m2 space that includes a high-containment area for handling highly potent compounds through OEB 5.
Looking forward, it should not be surprising that more pharma companies will be seeking biologics outsourcing partners.1 While many biopharma companies initially retained biologics manufacturing in-house, as the sector has matured and contract manufacturers have proven to be reliable in this area, more companies are looking to increase efficiency and productivity through outsourcing biologic drug substance and product manufacturing.
Servier currently outsources its biologic drug substance manufacturing at clinical scale. In 2018, we began the construction of a new ~ €50 million facility for the production of monoclonal antibodies and cell therapies at our Gidy, France site. The facility includes a workshop for clinical biologic drug substance manufacturing and space for the fill/finish of both clinical and commercial products. The workshop is expected to be operational by 2021, with our fill/finish capabilities available for contract manufacturing shortly thereafter.
Servier has the capabilities to support our client’s end-to-end service needs, from development to API to drug product manufacturing, packaging and distribution. We also have a dedicated tech transfer team to ensure the project progresses seamlessly through all stages. Indeed, collaborating over the long term with an embedded CDMO with decades of experience in the pharmaceutical industry and an integrated, global network of facilities covering all aspects of the drug development life cycle can help minimize risks while ensuring quality, facilitating access to growing markets and reducing time to market.
There has been a long-standing debate among CDMOs about end-to-end offerings. For instance, is there a real market for end-to-end services, or is it self-persuasion that originates in marketing departments? We are not convinced that there is real potential there. From the perspective of an outsourcer, there is a strong barrier between drug substance and drug product. As such, we prefer to promote our expertise in each field — drug substance and drug product.
Our developed global quality systems management (QSM) infrastructure proactively assures the implementation of quality assurance/quality control best practices at all of our facilities, resulting in the implementation of the same advanced technology quality and management systems across the entire network.
Similarly, our regulatory affairs team has a deep understanding of the specific requirements of different regulatory agencies and strong, collaborative working relationships with them. One person follows a client project from start to finish, leading to more efficient development of high-quality regulatory dossiers, optimal regulatory strategies and manufacturing controls throughout the entire product life cycle.
While pharma companies see strategic partnerships with outsourcing providers as long-term relationships, some providers see key accounts as long-term partners, while others view them on a financial/transactional basis.1 Regardless, the level of integration within strategic partnerships is important to both.
Servier favors strategic partnerships and takes the time to develop long-term relationships. In this complex and heavily regulated world, difficulties, delays and increased risks can easily occur if a pharma company switches from one contract provider to another. Since we are also a pharmaceutical company, we understand the expectations our CDMO clients have for the partnerships we form, and, as such, we behave as a contract manufacturer as we would expect contract manufacturers to behave for us as a pharma customer.
At the beginning of each project, we work with customers to establish a plan forward in order to eliminate any chances for hidden surprises or delays. Of course, the unexpected should always be expected, and we work closely with our customers to put response protocols into place to manage those issues that do arise.
Furthermore, it is important for us, as a CDMO, to share our development strategies with our clients. At the same time, as a contract manufacturer we have the same need for visibility into a customer’s strategies. This information helps us develop processes more efficiently, anticipate potential problems and propose long-term solutions. This type of sharing is essential in successful long-term strategic partnerships and is part of building a trusting relationship.
At Servier, we value our customers’ projects as though they are our own, giving them the same attention and level of service we give our internal work. During the first project meeting, we discuss a client’s preferred performance metrics and come to a consensus on which to implement. Because Servier does not want clients looking only for a “push-button manufacturer,” we feel it is very important to discuss this matter and agree on performance metrics at the beginning of a project. This is yet another way we prioritize and build trust at Servier, enhancing the likelihood of our partnership’s success.
Nice Insight, established in 2010, is the research division of That’s Nice, A Science Agency, providing data and analysis from proprietary annual surveys, custom primary qualitative and quantitative research as well as extensive secondary research. Current annual surveys include The Nice Insight Contract Development & Manufacturing (CDMO/CMO), Survey The Nice Insight Contract Research - Preclinical and Clinical (CRO) Survey, The Nice Insight Pharmaceutical Equipment Survey, and The Nice Insight Pharmaceutical Excipients Survey.