Optimizing Drug Development: The Benefits of Early involvement of a CDMO

In the latest issue of Chemistry Today, our Global Business Project Director, Fabien Bonhoure, shares insights about the benefits of early involvement of a CDMO in the Panel discussions dedicated to Biotech and CDMO collaboration. Read the full interview here and in the Sept/Oct Chemistry Today magazine edition.

At what stage in drug discovery do you recommend CDMO involvment to ensure smoother downstream development ?

Anticipating the involvement of a CDMO is crucial for ensuring smoother downstream pharmaceutical development. Engaging a CDMO at the transition from drug discovery to pre-clinical development, specifically during the pre-formulation and formulation development stages, provides significant advantages. At this point, CDMOs can help optimize the drug’s chemical and physical properties, anticipate manufacturability challenges, and design robust analytical methods in line with relevant specifications, all of which are essential for later pre-clinical, clinical and commercial speed and success. Early CDMO involvement enables the seamless transfer of technology and knowledge from laboratory to pilot and commercial scale, minimizing potential costly delays and technical setbacks.

For example, when a company developing a novel small molecule involves a CDMO at an early stage, the latter can potentially identify different polymorphic profiles that can affect the solubility of the molecule, its formulation and eventually its bioavailability. By optimizing the process to generate a robust and stable polymorph profile, or to master the impurity profile, including genotoxic impurities such as nitrosamine and by developing the related analytical methods upfront, the company can avoid costly reformulation or change in manufacturing process.

Importantly, involving a CDMO during route scouting will allow to select the most robust and cost-efficient process for further scale-up development. Thanks to R&D chemists expertise and capacities, such as solid state characterization, process safety studies, and challenging process parameters (such as critical and operational parameters) by using statistical and modelling tools and high throughput experimentation platform will bring considerable value for time and cost reduction.  

At this stage a CDMO can also support in navigating critical regulatory decisions such as the choice of regulatory starting material (RSM) or the definition of the GMP process window.

Choosing the optimal RSM is a complex process that balances regulatory requirements, process control, and manufacturing efficiency. If a CDMO is engaged early, it can apply a science– and risk-based framework to justify the selection of starting materials, ensuring that regulatory expectations are met while avoiding unnecessary GMP requirements on upstream intermediates. 

For example, if a company selects a RSM too late in the synthetic route for a new drug, regulators can require the company to apply full GMP controls to several upstream intermediates, significantly increasing manufacturing costs and causing a multiple month delay in clinical trial supply. A CDMO with regulatory expertise involved earlier could have advised on selecting an RSM further upstream, balancing regulatory expectations and process efficiency, and avoiding these costly setbacks. CDMO has also knowledge of the RSMs market and therefore can identify the most reliable suppliers for future industrial production.

In summary, the optimal stage for CDMO engagement is immediately after candidate selection and before starting any toxicity & safety studies that can be impacted by the presence of impurities. This proactive approach streamlines the path to pre-clinical, clinical trials and commercialization, ultimately enhancing the probability of success for new drug candidates.

How do you communicate timeline risks and mitigation strategies effectively to Biotech partners ?

Effective communication of timeline risks and mitigation strategies is fundamental to building trust and achieving success in CDMO-biotech partnerships. The usual communication process begins with a comprehensive risk assessment at project initiation, where all potential technical, operational, and regulatory risks are identified and prioritized based on their likelihood and potential impact. This transparent approach ensures that biotech partners gain insight into potential challenges and understand the rationale behind risk prioritization.

To communicate these risks effectively, it is essential to establish a clear, scheduled communication plan. This includes regular updates, milestone tracking, and review meetings, where progress is measured with predefined KPIs and any emerging risks are openly discussed. Assigning clear responsibilities for each deliverable and risk owner fosters accountability and keeps all stakeholders aligned.

Mitigation strategies should be shared proactively, including contingency plans for high-priority risks, such as alternative technical solutions or backup resources. By continuously monitoring risks and updating partners on both challenges and solutions, the CDMO demonstrates its commitment to transparency and shared problem-solving.

Ultimately, open, structured, and regular communication, anchored by data and clear action plans, enables biotech partners to make informed decisions, respond quickly to challenges, and maintain confidence in the project’s trajectory. Selecting a CDMO that brings end-to-end solutions from route scouting to manufacturing with cutting-edge R&D expertise and capacities is a game-changer.

What’s your approach to analytical method development and tech transfer when receiving incomplete or early-phase packages from biotechs ?

When partnering with small or medium-sized biotech or pharma companies, CDMOs often receive incomplete or early-phase technology transfer packages, which can present significant challenges for method development and tech transfer. A comprehensive package ideally includes:

• Detailed chemical process descriptions
• Release specifications for the molecule
• Analytical methods (developed and validated, if available)
• Reference standards
• Impurity profiles or initial assessments
• Safety data sheets (SDS)
• Process flow diagrams
• Batch records
• Stability data
• Regulatory filings or status
• Information on raw materials and critical process parameters

In practice, certain key elements may require further refinement. Common areas for development include ensuring completeness in analytical methods, establishing robust reference standards, thoroughly characterizing impurities and carryover, providing comprehensive safety data, and more detailed process descriptions.

For example, a biotech company might submit a preliminary HPLC method that could benefit from defined system suitability criteria, or a process description that would highlight more details on critical steps and impurity controls. In some cases, chemical processes may currently be optimized for lab-scale application and may need adaptation for safe and efficient scale-up. Additionally, some reagents may pose handling challenges in workshop environments, or initial project assessments may suggest the need for further economic feasibility analysis.

To mitigate the previous risks, our approach begins with a thorough gap assessment: we systematically review the package using a standardized checklist, then organize technical discussions with the client to clarify missing or ambiguous information. If analytical methods are incomplete, our team develops or optimizes them, ensuring phase-appropriate validation. When reference standards are unavailable, we propose sourcing or synthesizing suitable materials. For impurities, we conduct risk assessments and, if needed, design studies to identify, control them and follow their evolution over the process. Up to date ICH guidelines are also applied according to the stage of the development and stability studies are systematically proposed to allow prompt regulatory dossiers filing (IMPD, NDA or CTD).

Transparent communication and collaborative problem-solving are essential. By proactively identifying gaps and working closely with the client, often through regular meetings and shared documentation, we ensure the tech transfer proceeds efficiently, even when starting from an incomplete foundation. This flexible, solutions-oriented approach is critical to meeting aggressive timelines and regulatory expectations in early-phase projects.