Accelerating Drug Development Through Drug Substance and Drug Product Integration

In the fast-paced world of pharmaceuticals, the race to bring new drugs to market is more competitive than ever. Sponsored by Almac

The traditional drug development process, segmented into distinct linear phases, can be time-consuming and costly. However, integrating drug substance and drug product activities offers a promising approach to streamline this process, reduce costs, and accelerate the delivery of life-saving medications to patients.

The Traditional Drug Development Process

Traditionally, drug development follows a linear path, with drug substance and drug product activities conducted sequentially. The drug substance, also known as the active pharmaceutical ingredient (API), is the component responsible for the therapeutic effect of the medication. While the drug product encompasses the API in a dosage form appropriate for the patient, to maximise therapeutic effect by delivering the drug to the appropriate disease target receptor. The sequence of the clinical trials is conducted in stages to support the demonstration drug’s effectiveness and safety.

Bringing safe and effective drugs to the market is vital for global health, and the faster we can accomplish this, the sooner we can support patients. Therefore, integrating drug substance, drug product and clinical supply activities can significantly enhance speed on delivering necessary development and commercial drugs, whether for clinical trials or directly to market.

Challenges and Considerations

There are challenges to consider:

• Regulatory Compliance: Navigating the regulatory landscape can be complex when integrating activities. Regulatory agencies may have specific requirements for documentation and validation, necessitating careful planning and coordination to ensure compliance.

• Resource Allocation: Effective integration requires careful allocation of resources, including personnel, equipment, and budget. Balancing these resources to avoid bottlenecks and ensure smooth progress is crucial.

• Risk Management: Concurrent development introduces the potential for increased risk, as issues in one area can impact the entire process. Implementing robust risk management strategies and contingency plans is essential to mitigate these risks.

With those considerations in mind Almac Group has developed a strategy to support a client to enable acceleration of the development and manufacture of drug substance, through to drug product design and manufacture and packaging for use at the clinical site.

The scope of the project included early toxicology studies to First-In-Human (FIH) supply, focusing on both non-cGMP and cGMP process development for the drug substance. The drug product involved the development of an API in capsule form, with stability studies and clinical manufacturing.

Key project requirements included a 7-step synthesis procedure, control of impurities and regioisomers, and the development of analytical methods for validation. The drug substance supply involved the production of a 500g non-cGMP demo batch and a 15 kg cGMP batch, with micronization for clinical studies. The physical properties of the API were critical to the successful manufacture of the drug product and scientists from Almac Sciences and Almac. Pharma Services worked collaboratively to enable the definition, process design and delivery of API with appropriate physical properties.

The drug product deliverables included the cGMP manufacture and release of three dosage strengths (5 mg, 25 mg, and 100 mg), with capsules packaged and placed on stability. The project also included the development and validation of analytical methods, and process optimization.

The project was delivered in just over 12 months which included a 3-month hold for client discussions on dosage with a number of weeks saved by overlapping the API manufacture and formulation development activities. Working under the same systems provide a significant advantage in terms of speed and consistency, which is even more vital for the later phase of development.

In addition, we completed further development and manufacturing of drug substance and drug product for Phase II studies. Enabling project progression to the next phase of development.

Almac’s integrated CMC’s single project team approach, with weekly teleconferences reviewing all aspects of the project, is highly effective to enable project acceleration. The team provides real-time scheduling adjustments, analytical and formulation efficiencies and seamless logistics. The project management governance structure enhances continuity of operations, regular meeting, logistical efficiencies, and timely delivery. The collaboration between Almac Sciences and Almac Pharma Services ensured continuity of operations, enhanced communication, and logistical efficiencies while maintaining a high standard quality.

Overall, Almac’s streamlined approach resulted in significant time and cost savings for our clients while maintaining and improving group-wide innovation and best-in-class business offerings.

Conclusion

In an era where speed and efficiency, whilst maintaining high quality, are paramount, integrating drug substance and drug product activities offers a transformative approach to drug development. By breaking down traditional silos and fostering collaboration, pharmaceutical companies can accelerate the delivery of innovative therapies to patients. While challenges exist, the potential benefits in terms of reduced development time, cost savings, and improved quality make integration a compelling strategy for the future of drug development.

Authors:

Terry Ernest, Director Manufacturing Science and Technology, Almac Pharma Services. Terry has extensive experience within the pharmaceutical development and manufacturing industry, including a deep knowledge of a variety of dose forms including modified release formulations, tablets, capsules, oral liquids and sterile liquids. Terry joined Almac Pharma Services in 2024 from GSK where he held a number of senior positions over his 30-year tenure, including his most recent role as Director, Product Development at its site in Ware, UK. In 2025 Terry was appointed Board Member of the Academy of Pharmaceutical Sciences (APS).

Franciane Chevot, Senior Business Development Manager, Almac Sciences Franciane joined Almac in 2014 as a Process Chemist and transitioned to Business Development in 2016. As a Senior Business Development Manager, Franciane’s industry knowledge and insights within the pharmaceutical industry support pharmaceutical and biopharmaceutical companies of all sizes within mainland Europe. Franciane supports the drug substance part of Almac Group promoting Almac Sciences services: peptide and small molecule API development and supply, biocatalysis, flow chemistry, physical sciences, carbon 14 radiolabelling, and stand alone analytical DS/DP. With a Phd in Medicinal Chemistry and a postdoctoral position at Trinity College Dublin, Franciane combines her academic prowess with practical expertise. Her deep understanding of the pharmaceutical landscape is a valuable asset to build strong technology driven connections towards successful working relationships.