OR WAIT null SECS
Collaborative partnerships can foster success in formulation development projects.
The formulation development outsourcing market is expected to grow at a compound annual rate of 7.2% between 2021 and 2026 (1). Major factors driving growth in this sector are expected to be increasing innovation of novel drugs due to patent expirations, a focus on developing poorly water-soluble compounds that require bioavailability enhancement, and overcoming the risks associated with development (1).
To learn more about the industry trends, common requests, biggest challenges, and benefits of outsourced formulation services, Pharmaceutical Technology spoke with a panel of experts. The panel includes Sabine Hauck, senior vice-president of Corporate Development, Leukocare; Alexander Faude, director Process Science, Downstream Processing, and Marvin Kadisch, director Process Science, Upstream Processing, both at Rentschler Biopharma; and Stefan Heindl, business development manager, Coriolis Pharma.
PharmTech: Could you provide some insight into industry trends that have been impacting the formulation development outsourcing market in recent years?
Hauck (Leukocare): Formulation development has gained momentum in recent years. Beyond the stabilization of the drug substance by molecular design, formulation development is a key opportunity in the process of drug product development that offers potential to generate further commercial value. To accommodate this trend, continuous expansion of formulation expertise is recommended so that client requirements for viral vector stabilization, vaccines and advanced therapy medicinal products (ATMPs), higher drug substance concentration, longer storage time at higher temperature, or creation of new intellectual property can be met. For example, Leukocare has successfully managed the development of targeted formulations by applying its database and algorithm-based formulation development approach.
Formulation development itself has developed rapidly, making use of highly sophisticated analytical methods and bioinformatics. This trend supports outsourcing formulation development to a specialized provider, such as Leukocare, that excels with high-end scientific expertise, an analytical toolbox, and bioinformatics excellence. Especially for smaller companies, using an outsourcing partner allows access to best-in-class formulation development.
Faude (Rentschler Biopharma): The value and benefits of early formulation development have increasingly gained recognition and acceptance across the industry. Hence, companies are looking closely at all aspects of biopharmaceutical production, from start to finish, to identify opportunities for timeline optimization. As a result, it has been the experience of Rentschler Biopharma that the trend of collaborating with external experts in formulation development is picking up.
Heindl (Coriolis Pharma): Coriolis began specializing in formulation development in 2008 when formulation was often not the highest priority during drug product development. This has changed and the formulation development outsourcing market has been in a sustainable growth phase for several years now. Daily work at Coriolis has demonstrated a clear trend towards more complex products, for example, highly concentrated liquid formulations (HCLFs) with protein concentrations of up to 300 mg/mL or higher, or novel protein formats that require dedicated scientifically driven formulation strategies, rather than standard platform approaches. Also, requests regarding vaccine development, particularly in the context of the ongoing coronavirus pandemic have increased in the past two years; nucleic acid-based therapeutics gain more and more importance. However, the most important trend in my view is the increase in ATMPs, such as viral-vectors, oncolytic viruses, and other genetically modified organisms, that are entering the scene. Many of these products require new and innovative formulation approaches, analytical strategies, as well as special facilities.
PharmTech: What type of formulation work is more commonly outsourced and has the type of project changed over the years?
Heindl (Coriolis Pharma): Formulation development services are requested across all stages of development, from early-stage pre-formulation work to late-stage reformulation projects, in-use studies, or trouble-shooting activities. Two different trends have been seen at Coriolis. One trend is an increasing demand for the outsourcing of complete packages, including pre-clinical tox manufacturing and good manufacturing practice (GMP) manufacturing (e.g., for first clinical phases of the developed formulation). To meet this demand, it is important to expand the service portfolio, for example, by expanding tox-batch manufacturing capabilities for liquid and lyophilized formulations. Moreover, it is necessary to seek out and maintain partnerships with other established players in the field to cover GMP manufacturing. These close partnership networks allow for comprehensive outsourcing packages to be offered while keeping the number of interfaces for the client low. The second one is outsourcing of highly challenging and individual formulation tasks that require a scientific background and a very specialized formulation approach. For this trend, it is important that the service provider has the required track record, experience, and scientific background for the task.
Hauck (Leukocare): All kinds of formulation development are outsourced, depending on the needs of the sponsors. Early pre-formulation development supports stability already in tox studies and allows de-risking success of a clinical candidate due to stability issues. Fully fledged formulation development is outsourced in all stages of clinical development, depending on the clinical development strategy. Even if the asset is planned for out-licensing after clinical stage, a well-designed formulation will increase the value of the drug product package. In general, time has become more critical over the years, while quality requirements are still increasing. That´s why it is key to outsource formulation development to an expert contract development and manufacturing organization (CDMO) developing high-quality formulations in an accelerated period.
PharmTech: What are the biggest challenges for outsourcing partners when approaching/working on a formulation project with a sponsor company?
Faude (Rentschler Biopharma): When collaborating with a sponsor company, the success of early formulation development depends heavily on material that has been generated via ‘preliminary’ processes. These processes are themselves undergoing development and optimization. Hence, they are bound to change right until first current GMP production for clinical development. Moreover, the process may undergo further improvement or adaptations for market approval. Therein lies a challenge for the outsourcing partner but also great benefit for the sponsor company’s product. This is because these adaptations can be sequentially incorporated into formulation development to further maximize product potential.
Kadisch (Rentschler Biopharma): The role of the outsourcing partner as an expert consultant for the sponsor company is also very crucial. It is essential that the outsourcing partner sees the project as an extension of their own operations and advises the client from this point of view. Aspects such as which formulation best suits the molecule in question, subsequent implementation and regular project status updates are central to a successful collaboration.
Heindl (Coriolis Pharma): Well, every client is different, and each molecule of interest and target product profile require a dedicated strategy. A common aspect is that the timeline is always key. While in early stages, drug substance availability is often a challenge, though mostly manageable, real challenges arise when formulation development is squeezed in between other development activities such as drug substance development and drug product manufacturing. Depending on the drug substance and client, knowledge about the stability profile of the API can be very scarce. Due to all these reasons, an understanding of the specific requirements of each client, a smart, scientifically-sound study design with built-in flexibility and a clear expectation management is important.
Hauck (Leukocare): Formulation development is always linked to other aspects of product development, such as process development for upstream processing and downstream processing, pharmaceutical development or fill/finish, logistics, and product administration. It is important to consider interactions and interdependencies.
PharmTech: How do outsourcing partners overcome these challenges?
Heindl (Coriolis Pharma): At Coriolis, for example, a lot of investment is made into the upfront discussions with the client to understand the particular needs for the project. In combination with our experience as a formulation specialist, these discussions provide the basis for a tailored and scientifically-sound proposal considering all specific requirements of the client. During an ongoing project, open and transparent discussions on a regular basis (e.g., in weekly or biweekly meetings) help to align development efforts and allow for quick reactions to scope changes or unforeseen issues. Especially during early-stage projects, a high degree of flexibility is often needed, requiring a specific skill set of the team working on the projects to quickly provide a stable formulation backed-up by a suitable analytical toolbox and stability data.
Kadisch (Rentschler Biopharma): A very helpful solution to tackle these challenges are access to a large database, as well as experience with different classes of molecules. This includes tools like in-silico modeling and more targeted wet-lab trials. This can significantly accelerate the development of suitable formulations for the sponsor company’s product.
Hauck (Leukocare): Requests for faster formulation development should be met with innovative strategies; extending the analytical toolbox can help to save time and material. Moreover, automation in formulation and analytical technology supports parallelization and thus supports higher turn-over. Making use of bioinformatic expertise leads to timesaving as well as quality improvement for projects.
Faude (Rentschler Biopharma): To overcome these challenges a review of the ‘fit of the formulation to the product’ can be continuously addressed during preclinical and clinical product development. This allows one to quickly identify ‘constellations of fitness’ that can then be focused on to further optimize both formulation and the end product.
PharmTech: What are the key benefits for outsourcing formulation development?
Kadisch (Rentschler Biopharma): Based on the experiences of projects undertaken by Rentschler Biopharma, it is believed that the seamless integration of formulation development into the entire product life cycle and timelines harbors two key benefits: it allows for exceptionally efficient product optimization and ensures that project delays are avoided. Furthermore, the consultation provided by the outsourcing partner is key in defining the best-fit for both client and product.
Faude (Rentschler Biopharma): Outsourcing partners, such as Rentschler Biopharma, have holistic offerings where the entire process and formulation development is offered in an optimally integrated form. In this manner, clients can greatly benefit from the experience and expertise of the outsourcing partner for an ‘improved’ product within optimal timeframes.
Hauck (Leukocare): Essentially, it enables companies to gain access to best-in-class formulation development. For smaller companies with few products, an external formulation development team can be used just for the short period of time needed and avoids the efforts required of recruitment and training. Typically, it is much easier for an outsourcing partner to answer short notice demand on higher required effort. Formulation development can be performed whenever it suits best.
Heindl (Coriolis Pharma): In the context of the increasing complexity mentioned before, the outsourcing of such projects to specialized and experienced service providers can significantly improve development times and the probability of success. Outsourcing to service providers offering all required analytical capabilities in-house also expedites development as shipment between third-party labs and time-consuming data consolidation can be avoided. Finally, following a first-time right approach with a specialized formulation partner in the long run also saves money, and includes the possibility to generate and protect intellectual property in a collaborative and transparent approach.
The outsourcing of formulation development activities should be seen less like a one-way service and more like a collaboration between two partners. If both parties work together collaboratively and maintain an open and transparent communication, a positive project outcome is almost guaranteed.
1. Mordor Intelligence, Formulation Development Outsourcing Market—Growth, Trends, COVID-19 Impact, and Forecasts (2021–2026), Market Report (May 2021).
Felicity Thomas is the European editor for Pharmaceutical Technology Group.
Vol. 45, No. 8
When referring to this article, please cite it as F. Thomas, “Developing the Best Formulation Partnership,” Pharmaceutical Technology 45 (8) 2021.