June 20, 2018 PAO-06-18-CL-003
Regulatory affairs (RA) are a key contributor to the development and commercialization of new drug products, and developing an approval strategy is a crucial activity. RA teams also communicate with the authorities and write, submit and maintain clinical trial application and marketing authorization dossiers during the lifetime of the product. In some cases, they provide updates to dossiers due to the evolution/optimization of manufacturing and control processes. Ensuring ongoing compliance with constantly changing Good Manufacturing Practice and other regulatory requirements is also an important RA responsibility.
In essence, regulatory affairs activities are involved in numerous process and business considerations during the lifetime of drug development projects. If done correctly, RA teams can thus contribute to the shortening of project timelines and help clients get their product to market more quickly.
There is, in fact, growing recognition of the positive impact that effective regulatory affairs teams can have on the drug development process. According to Grand View Research, a focus by life science companies on core R&D activities combined with the outsourcing of other operations, including regulatory affairs, to drive down costs and increase efficiency is driving demand for RA services. The market research firm estimates the global regulatory affairs outsourcing market, which includes regulatory consulting, legal representation, regulatory writing and publishing, product registration, clinical trial applications and other services was valued at $4.53 billion in 2016 and will expand at a compound annual growth rate of 11.9% from 2016 to 2025.1
Given that effective regulatory affairs activities are crucial to successful drug development and commercialization and involve complex and constantly changing requirements, a RA team with extensive experience supporting ongoing regulatory compliance and both new drug approvals and updates to dossiers for marketed products is highly beneficial.
Servier CDMO offers a comprehensive, integrated range of services, from development through to marketed product manufacturing for chemicals as well as pharmaceuticals. Our regulatory experts support the clients in CMC for Drug Substance and Drug Product sections.
At Servier CDMO, the regulatory affairs team in charge of the Drug Substance sections comprise the same experts that perform RA activities for Servier Group. Consequently, the team has extensive experience in supporting a wide range of projects for the development of both novel APIs and generic versions of existing branded products from early development stages through commercialization and throughout lifecycle management efforts.
Our skilled RA team has a strong understanding of synthetic and analytical chemistry, as well as API manufacturing processes, and we are able to effectively identify impurities, predict/confirm their fate and provide justification for the impurity assessments, product specifications and control strategies established for a given product. In addition, with our knowledge of applicable guidelines, we are able to guarantee the compliance of all of our activities.
With our long history of successful regulatory compliance and dossier development in more than 140 countries around the world, we are not only aware of the specific requirements of different regulatory agencies, but have established strong, collaborative working relationships with them. Indeed, clients of Servier CDMO benefit directly from the regulatory intelligence that exists across the entire Servier Group, which ensures that all sites within the company are up to date with new guidelines and are well prepared to respond to any questions that health authorities may raise.
Unlike for many contract development and manufacturing organizations (CDMOs), Servier CDMO considers regulatory affairs to be an operational activity on the same level as our development, manufacturing and analytical groups. As such, the RA team works very closely with all of these groups and is highly involved in client projects from the very start.
Importantly, the RA team is located at the API manufacturing facility. This deep integration with Servier CDMO’s other operational groups enables close collaboration between regulatory experts, chemists, analysts, scientists and operators working in the pilot and manufacturing plants, as well as support services such as Quality Assurance. The collective intelligence and knowledge gathered through these multiple interactions helps ensure the development of optimum regulatory strategies and high-quality regulatory dossiers.
Compliance is also facilitated due to the close working relationships between the RA team and the development and production teams. For instance, the RA team is always involved in the change control process, which is managed by the Quality Assurance group, in order to determine if the change will have a regulatory impact on the dossier. If necessary, the RA team initiates the process to update the dossier (variation). Whatever the classification of the variation, the clients are informed and may give their approval before submitting the variation and implementing it.
In addition, the use of a Quality-by-Design (QbD) approach during development and validation of manufacturing processes and analytical methods ensures the development of processes with operating parameters that consistently fall within the optimum, validated design space, thereby allowing the identification of an optimum regulatory strategy.
In fact, by advising our clients on optimum regulatory strategies for achieving development and marketing authorizations, Servier CDMO helps them avoid unnecessary business risk. Based on our extensive experience and expertise, our regulatory affairs team can recommend relevant studies and when to conduct them. For instance, if a customer is unable to predict with certainty the demand for a new product following its approval, Servier CDMO’s regulatory affairs team can develop a strategy that minimizes the initial investment and risk but allows for rapid scale-up if demand grows rapidly, taking into account the time required to modify the regulatory dossier. By planning in advance, it is possible to avoid the need to produce large quantities of product that will sit in inventory.
Given the complexity of regulatory affairs activities and their contribution to all aspects of drug development and commercialization, it is essential for CDMOs to simplify the process for clients to every extent possible.
At Servier CDMO, we have recognized the importance of providing continuity of regulatory support throughout the entire lifetime of a drug product to both simplify client interactions and fully leverage project knowledge. At the beginning of 2018, our regulatory affairs team supporting API development activities (including dossier preparation) along with the team responsible for updating dossiers for marketed products, were combined into a single RA organization.
Following this development, one person from the regulatory affairs department now follows a client project from start to finish, carrying through the knowledge from the initial stages of development through to commercialization and lifecycle management. Clients have direct access to this single point of contact to discuss all regulatory aspects of a project, leading to more efficient development of high-quality regulatory dossiers and establishment of optimum regulatory and control strategies throughout the entire product lifecycle.
The new RA organization at Servier CDMO is also implementing a number of new tools and assets designed to further improve RA activities, including an innovative mindset for more effective project and performance management, which ensures client timelines and needs are consistently met.
When a client brings a potential new project to Servier CDMO, a member of the regulatory affairs department is involved in the process from the start. Even before a contract is signed, some of the regulatory aspects of the potential project are discussed and a possible strategy outlined. Once a contract has been signed, a face-to-face kickoff meeting with the full project team, including the RA representative, is held to discuss the product and the project and ensure that all stakeholders understand the goals and details.
One of the initial jobs of the RA team member is to determine what information the client can provide on the new project, such as API characterization data, stability data and analytical methods, etc., and what information is required for the regulatory dossier preparation and assurance of compliance. A gap analysis is then conducted in order to outline the list of specific studies that must be performed to fulfill all the regulatory requirements prior to marketing authorization submission by the client.
As the project progresses, the RA team member keeps the client informed about the progress of any studies or testing that is being completed, the steps taken to ensure ongoing compliance and dossier preparation. Once the dossier is drafted, it is submitted to the client for review. Collaboration between the client and the RA team through the RA representative leads to a final version of the dossier that is then submitted to the regulatory authorities by the client. Throughout this period, the Servier CDMO RA expert will support the client to prepare scientific advices with the regulatory agencies as needed. The Servier CDMO RA expert will also provide support to the client during the evaluation procedure of the regulatory dossier by the competent authorities, by responding to the questions raised by the authorities on the API.
As demands from regulatory authorities continue to increase and the complexity of projects continues to heighten, we expect that more and more pharmaceutical companies will be seeking CDMOs that can provide reliable, robust regulatory affairs support. In addition, the emerging and specialty biopharmaceutical firms developing a growing percentage of novel drug candidates may not have the RA experience and expertise required to ensure ongoing compliance, the development of high-quality dossiers and the updating of dossiers for marketed products.
At Servier CDMO, we view regulatory affairs as an integral part of our business model. As part of Servier Group, we have a long track record of working collaboratively with regulatory authorities around the globe. We have the demonstrated capability to develop effective regulatory strategies, maintain a high level of compliance and prepare and update dossiers that meet their expectations.
In the coming years, we look forward to leveraging our unique regulatory affairs skillset/expertise to help clients of Servier CDMO accelerate their projects and get needed medicines to patients in a timely and cost-effective manner.
After obtaining a PhD in medicinal chemistry and a master’s degree in law, Maryse became a member of the Servier Group in 1989. She worked as an analytical development head of the department for 24 years, in the API manufacturing site located in France. In 2014, she became in charge of the Regulatory Affairs (RA) department for development, pre-marketed projects. Since the beginning of 2018, she has been the head of a new RA department featuring all API regulatory submission matters, from early development to post-marketed products.
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