CMC (Chemistry, Manufacturing, and Controls) is a critical component of the overall drug development process and must continuously evolve in response to the fast-changing landscape of the biopharma industry. Digital innovation is transforming CMC, just as it is impacting every other area within the industry. Indeed, whole conferences are now dedicated to the topic[1].
Technologies such as artificial intelligence (AI) are becoming increasingly vital to CMC activities, influencing everything from regulatory trends and drug development to the supply chain[2]
Navigating the regulatory and lifecycle management landscape
AI has the potential to transform the regulatory and lifecycle management landscape by providing advanced analytics, automation capabilities, and insights to improve efficiency, compliance, and decision-making across the product lifecycle[3].
AI can support regulatory processes in many ways, including enhancing the accuracy of regulatory submissions by helping to reduce human errors and analyzing and cross-checking data to support compliance with all regulatory requirements2. AI can also enhance regulatory and lifecycle management by automating tasks, improving data analysis, and enabling real-time compliance monitoring. This allows regulatory professionals to focus on strategic initiatives and boosts efficiency.
Nevertheless, AI requires continuous adaptation to ensure algorithms comply with changing regulatory standards and the development of AI-specific regulatory frameworks3.
How AI impacts CMC in advanced therapies
Artificial intelligence is helping to speed up the identification of promising candidates from months to weeks and assisting in drug design, particularly in cell and gene therapies and vaccine innovation known as advanced therapy medicinal products (ATMPs)[4].
When it comes to CMC, AI algorithms play essential roles in developing the right product for the right patient.
Examples include algorithms to predict protein structures, such as the AlphaFold Protein Structure Database and system, which can be used to model how patient-specific mutations affect protein structure binding[5]. These techniques are also relevant to constructing mRNA- or DNA-based cancer vaccines.
AI is also being leveraged to help optimize cell culture conditions to maximize cell yield and therapeutic potency. This helps to address the many challenges with formulating the right culture environment, such as finding the right combination among thousands of potential ingredients, tackling the biological complexity of cell types and disease indications, and overcoming non-linear responses[6].
Another essential step is identifying critical process parameters (CPPs) influencing product quality. Companies use the design of experiments (DoE) studies and multivariate statistical methods to determine CPPs and their relationship with product yield and critical quality attributes (CQAs). However, CQAs often involve complex, nuanced, and sometimes subjective quality aspects that are difficult to quantify and translate into data suitable for machine learning algorithms. Nevertheless, AI is being used effectively to identify CPPs and CQAs through analysis of large datasets, helping to ensure production of high-quality products2
With CRISPR/Cas9 gene editing, detecting and minimizing off-target mutations is crucial. Here, the use of algorithms to predict CRISPR target sites can pinpoint genomic sequences or epigenetic features that improve editing efficiency and minimize off-target effects in viral therapeutics[7].
Enhancing the supply chain with data and AI
CMC data is crucial in the pharmaceutical supply chain. It is leveraged to ascertain the quality and safety of drug products, support regulatory compliance and reliable product availability, identify risks such as raw material variations or impurities, and facilitate necessary changes to maintain quality standards[8].
CMC data provides vital insights into raw materials, manufacturing, and product specifications, helping companies identify quality issues early to prevent recalls and supply chain disruptions. It is essential to helping companies meet regulatory requirements, identify CPPs and variability, and optimize manufacturing processes for improved efficiency. And, crucially, CMC data allows companies to trace drug products in the supply chain, facilitating quick identification of quality issues and rapid response to problems2.
By leveraging AI, pharmaceutical companies and their contract research organizations (CROs) and contract development and manufacturing organizations (CDMOs) can gain greater insights into their CMC data. This allows them to better manage shipping and delivery, oversee warehouse capacity, track inventory, forecast demand, improve worker safety, and achieve transaction integrity in global supply chains.
Among the many benefits of AI in the supply chain is the ability to model real-world uncertainties in demand and supply, optimize inventory levels, and improve order fulfillment rates. By analyzing historical data, AI allows companies to predict demand changes, support shortages and disruptions, and use that information to adjust their strategies.
Overall, combining AI with CMC quality control enables CMOs and CDMOs to build a more resilient supply chain while maintaining product quality and consistency during disruptions. CMOs can utilize AI to analyze data from production processes, supplier networks, and market trends to identify and address potential bottlenecks. By integrating AI into their CMC practices, they can enhance risk assessment, detect disruptions early, and develop effective mitigation strategies[9].
Connecting the CMC dots with AI
Across CMC, AI has the potential to improve efficiencies and advance product innovation, speed up processes and allow safe and innovative products to get to patients faster. From supporting ATMP innovation to optimizing manufacturing processes and supply chain management, AI not only addresses the challenges of today but also lays the groundwork for a more resilient and responsive industry.
The onus is on companies to remain agile, including by leveraging digital solutions to navigate the complexities of drug development, and ultimately improve patient outcomes.
About the author:
Cori Gorman, Ph.D., is Senior Director, Biopharmaceutical CMC and Regulatory Affairs at Biopharma Excellence. She has more than 25 years of expertise in integrated drug development including modulating gene expression in vivo/in vitro and in innovative drugs in the field of monoclonal antibodies. Her career includes the development of innovative drug modalities such as non-viral gene therapies (Valentis), cancer vaccines and cell therapies, both autologous and allogeneic (Agenus).
[1] The future of high-performance drug development is here, Digital CMC Summit. https://www.qbdvision.com/digital-cmc-summit-2025/
[2] Artificial intelligence-driven pharmaceutical industry: A paradigm shift in drug discovery, formulation development, manufacturing, quality control, and post-market surveillance, European Journal of Pharmaceutical Sciences, Dec 2024. https://www.sciencedirect.com/science/article/pii/S0928098724002513
[3] Digital Innovation in Medicinal Product Regulatory Submission, Review, and Approvals to Create a Dynamic Regulatory Ecosystem—Are We Ready for a Revolution? Front Med, May 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC8183468/
[4] How AI can accelerate R&D for cell and gene therapies, McKinsey & Company, Nov 2022. https://www.mckinsey.com/industries/life-sciences/our-insights/how-ai-can-accelerate-r-and-d-for-cell-and-gene-therapies
[5] AI-Driven Deep Learning Techniques in Protein Structure Prediction, Int J Mol Sci., Aug 2024. https://pmc.ncbi.nlm.nih.gov/articles/PMC11313475/#:~:text=The%20three%20main%20methods%20for,structure%20of%20a%20related%20protein.
[6] The Benefits of AI and Automation in the Cell Culture Process, Lab Manager, Dec 2023. https://www.labmanager.com/the-benefits-of-ai-and-automation-in-the-cell-culture-process-31566
[7] Principles of CRISPR-Cas9 technology: Advancements in genome editing and emerging trends in drug delivery (6.1. Off-target effects and specificity concerns), Journal of Drug Delivery Science and Technology, Feb 2024. https://www.sciencedirect.com/science/article/pii/S1773224724000066
[8] Breaking barriers: the future of CMC powered by AI, Regulatory Rapporteur, Oct 2024. Breaking barriers: the future of CMC powered by AI | Journal | Regulatory Rapporteur
[9] AI’s Promise for ATMPs https://ispe.org/pharmaceutical-engineering/november-december-2021/ais-promise-atmps
