October 28, 2019 PAP-Q3-19-CL-025
Approximately one-third of all drugs in the pharmaceutical pipeline are oncology treatments.1 Many of those are formulated using highly potent active pharmaceutical ingredients (HPAPIs). As a result, close to one-quarter of newly approved drugs in recent years have been highly potent therapies.2 That percentage will likely expand, given that the market for HPAPIs is estimated to be growing at a healthy CAGR of 8–10% through 2025.3–7 While most HPAPIs are found in anticancer drugs, they are also used to formulate drugs for the treatment of cardiovascular, central nervous system, musculoskeletal, hormonal imbalance and eye diseases.3
Highly potent HPAPIs and drug products cannot be produced under normal manufacturing conditions, as both operators and the environment must be protected from exposure to potent compounds. The level of containment required depends on the potency of the product, and significant expertise is needed to determine the level of containment necessary to adequately prevent exposure. Effective containment is achieved through a combination of appropriate facility and equipment design, including engineering and proper processes, process management systems and training.
Potency is determined by the occupational exposure limit (OEL) and various toxicity properties of the HPAPI or drug product. Typically, the HPAPI or high potency drug product is assigned an occupational exposure band (OEB) or placed into one of the categories established by the International Society for Pharmaceutical Engineering (ISPE).8 The higher the OEB, the higher the level of containment must be.
Potent compounds are considered to have an OEL of 10 µg/m3 of air or lower, as an 8-hour time-weighted average. Ultra-highly potent compounds have OELs of less than 0.1 µg/m3. Unfortunately, there is no single regulatory standard. In addition to the ISPE category approach, guidances have been published by the ACGIH, AIHA, ILO, IOHA, NIOSH, OSHA and the WHO. 21 CFR part 210 (211), 29 CFR 1910, ICH Q7A, OSHA (& NIOSH) and the Controlled Compound Act cover various aspects of potent product manufacturing and handling.
The manufacture of highly potent drug products is becoming more challenging as compounds become more potent and guidelines for the production of potent therapeutics evolve and tighten. The required level of containment has been shifting over time, in some cases resulting in the movement of some products from a lower band to a higher band.
Servier is a leading European pharmaceutical company that has successfully commercialized 50 products during the last 60 years. We have operated the Arklow, Ireland site, which is currently our second-largest manufacturing facility, for 30 years, for the production of a variety of drug products.
Servier Arklow has been working in the high containment space for 10 years. During that time, Servier has established strong high-containment capabilities and extensive experience handling and managing highly potent drug products. We have established processes and procedures and a highly qualified, dedicated team of operators with years of expertise.
We are committed to the oncology field through the development of our own pipeline candidates, with 50% of our 2018 research spent focused on R&D for anticancer therapies. We have a breadth of diverse potent product manufacturing, packaging and distribution capabilities across our global portfolio. The highly potent drug product manufacturing unit at Arklow are complemented by HPAPI capabilities at our facility in Bolbec, France.
The increasing number of highly potent drug candidates is creating demand for high-containment manufacturing capacity. Many contract development and manufacturing organizations (CDMOs) are expanding capabilities for the production of HPAPIs, and outsourcing by biopharma companies of all sizes is increasing rapidly as they seek to gain access to these specialized capabilities.9 Less attention has been paid, however, to the expansion of potent drug product manufacturing capacity.
Recognizing the growing demand for outsourcing services to support development and commercialization of increasingly more potent products, Servier has expanded our high-containment capabilities at the Arklow site to support the production and packaging of OEB-5 (<1 µg/m3) drugs.
Manufacturing services including granulation, tablet compression, tablet coating, packaging and analytical services, have all been incorporated into the dedicated, highly engineered, state-of-the-art high containment unit. At Servier, we are constantly modifying our services based on market demands and responding to customer requirements — in fact, plans for expanding our capabilities are already in progress.
The first batches of an in-house Servier product were produced in September 2019, and qualification for customer products is ongoing.
With flexible batch size and solid dose form production, packaging capabilities, serialization and aggregation expertise, the new dedicated high containment unit enables Servier to provide fully integrated services for highly potent drugs. Our dedicated high-containment team was involved in the design and construction of the new high-containment suite and has the intimate knowledge required to ensure optimal operations. With our location in Arklow, we are ideally positioned to support the rapidly growing pharmaceutical sector in Ireland and pharma companies worldwide. We export product to over 100 countries worldwide, supported by Servier’s extensive global footprint.
Servier continually invests in strategic growth and is committed to being a strong player with high quality, reliable capabilities in oncology, potent manufacturing and high containment. The new high-containment suite at our Arklow site was designed and engineered to optimize containment within the room structures and equipment trains. We worked closely with suppliers to engineer containment into each piece of equipment, in each room and in the self-contained suite, itself. The approach reduces the need for operators to rely on personal protective equipment (PPE), streamlining processes and shortening timelines while considerably mitigating the risk of operator or environmental exposure. Importantly, the suite is dedicated to a single product at any one time.
Servier’s investment in the new high containment facility enables more flexibility in capacity and batch sizes, alongside higher levels of containment. Our high potent drug product manufacturing capabilities at Arklow integrate well with all other capabilities included in Servier’s full-service contract development and manufacturing offering within our global network of 11 sites.
In addition to manufacturing and packaging, we provide all support necessary for commercial launch, including regulatory, analytical, distribution and other services. We can be your unified, long-term, seamless partner. Our customers can therefore fully advance their products within Servier’s network.
HPAPIs can be purified down to OEB-5 at our Bolbec, France facility through InnoPrep™, the industrial-scale preparative chromatography service. This is complemented by the latest upgrades at our Arklow site for final drug product manufacturing, which support the rapid advancement of anticancer therapeutics.
As a result, collaborating with Servier over the long term can help minimize risks while ensuring quality, facilitating access to growing markets and reducing time to market.
Servier’s CDMO services are embedded within our long-established, international pharmaceutical operations and thus offer flexibility backed by the resources and operational, technical and regulatory expertise of an internationally recognized pharmaceutical manufacturer.
The same teams that work on the development, analysis, scale-up and commercialization of Servier products are involved in external client projects. As such, they apply their strong industry experience and effective, responsive decision-making to each new project. This embedded expertise is backed by a strong quality culture and project management capabilities.
Furthermore, the longstanding expertise of Servier is complemented by leading-edge technologies proven to accelerate time to market. Our integrated supply chain enables highly efficient workflows, quality assurance and regulatory expertise across global markets.
Servier has invested in a brand new, state-of-the-art OEB-5 high-containment facility at our Arklow, Ireland, site, supporting our commitment to oncology therapeutics and our capability to offer the highest levels of containment and flexible manufacturing solutions to third-party customers.
This new workshop builds on a foundation of more than a decade in high containment at Arklow. The new capacity has been designed with containment engineered into the suite itself, optimizing the mitigation of risk and process efficiency in working with potent compounds, enabling projects to progress rapidly without compromising quality and reliability.
This latest investment in Ireland reflects Servier’s commitment to high-containment manufacturing of highly potent drug products. We are excited about integrating this capability directly with our CMDO business supporting drug substance and drug product development and production. At CPhI Worldwide in Frankfurt, we look forward to launching a new brand around this capability that will provide our customers with an additional streamlined long-term partnership opportunity.
Suzanne is a Business Development Manager for Servier CDMO. With 18 years’ experience in the pharmaceutical industry at Servier (Ireland) Industries, Suzanne has extensive knowledge of key areas including quality, GMP and regulatory requirements. In the role of business development manager, Suzanne supports Servier’s CDMO business worldwide and CDMO activity at the Arklow site. She identifies new business opportunities and brings them to completion, working diligently with customers and the Servier team to respond to customer needs and deliver their product requirements at the right cost, quality and time.