As a fundamental part of the drug development and life cycle management process, CMC (Chemistry, Manufacturing, and Controls) is evolving in response to technology innovations, geopolitical developments, regulatory challenges, and industry shifts.
As drug development becomes more complex, the importance of maintaining robust CMC principles grows. In 2025 and beyond, several key trends will dominate CMC, pushing professionals in the space to respond with a more flexible and integrated approach that is focused on innovation, quality, and compliance.
This article explores five areas expected to have a profound impact on CMC.
Where digitalization is taking CMC
Companies are increasingly leveraging AI or automation tools to streamline regulatory documentation through digitalization of data, which paves the way to improving speed and accuracy and, in the longer-term, driving cost savings[1].
Another key digital tool is the growth of cloud-based data platforms to support modern CMC processes by allowing real-time data storage with security and quality tracking. Structured content and data management solutions are paving the way for a more seamless data exchange platform to support CMC submissions1. AI, machine learning, and big data analysis are other tools that could create predictive modelling and algorithms. This allows companies to accelerate decisions, avoid issues, optimize processes and improve quality[2]. Increasingly, regulatory authorities are offering guidance to support companies with the use of AI in their regulated processes[3],[4].
Digital innovations such as AI are also expected to gain prominence using Quality by Design principles for new medicines[5].
Additionally, newer methods such as Real Time Release Testing (RTRT) are predicted to improve quality assurance[6] . The ICH and the European Medicines Agency (EMA) has defined RTRT as “the ability to evaluate and ensure the quality of in-process and/or final product based on process data, which typically include a valid combination of measured material attributes and process controls (ICH Q8)[7]”.
A renewed focus on sustainability
The year ahead is expected to see a heightened focus by regulators on green manufacturing and environmental compliance.
For example, merging entities are increasingly expected to be evaluated not just on product quality but also on their environmental footprint and compliance with evolving green standards. CMC functions can support these objectives by embedding sustainability and green chemistry in pharmaceutical development processes[8]. That includes using components with low toxicity, that are more eco-friendly, and that do not require special precautions for handling.
An important step for CMC functions is to evaluate supply chains for sustainability practices, including energy efficiency and waste management[9]. An increasingly important area of focus in the year ahead will be medicine packaging and recycling, balancing the importance of patient safety with effective ways to reduce the carbon footprint[10].
Designing energy efficient processes would also allow companies to meet regulatory emissions targets set by national health systems and to reduce operational costs. By way of example, the UK’s National Health Service is committed to a net zero target for its operations and supply chain by 2045, which will depend on suppliers, including pharmaceutical companies, supporting those objectives[11].
Building resilient supply chains
Disruptions to manufacturing sites for many different reasons have underscored the importance of resilient and robust supply chains[12].
Covid-19 demonstrated the problems with relying on a few markets to supply essential medicine materials, which has prompted regulatory authorities to act to protect the supply chain. In Europe, the EMA’s Medicines Shortages Steering Group (MSSG) has established recommendations to address supply chain vulnerabilities for critical medicines[13].
Managing global suppliers adds complexity to maintaining compliance across sites and countries. CMC must ensure product quality and regulatory compliance of the supply chain. Pharmaceutical manufacturers must also act to prevent supply chain disruption and product shortages.
An increasing focus in future will be to integrate supply chain mitigation and product security through a dedicated regulatory/CMC-focused role to manage complex global supply chains and address the questions likely to come from bodies such as the MSSG and the EMA’s Medicine Shortages Single Point of Contact (SPOC) Working Party, which monitors and reports events that could affect the supply of medicines in the EU[14].
CMC’s role in post-merger operations
CMC is a key enabler of operational excellence and regulatory success. When it comes to mergers and acquisitions (M&A), CMC is integral to evaluating drug manufacturing processes as part of due diligence. One important trend is the inclusion of CMC experts during M&A negotiations to assess regulatory compliance, such as ensuring the acquired product meets current regulatory standards.
The emphasis in future should be on due diligence that extends beyond financial forecasts from sales and considers the cost of dossier remediation, where applicable. For example, where there are older product portfolios, CMC experts can help to determine the potential impact if existing data does not comply with the latest regulatory guidance. For example, there are requirements around entering clinical trial data into the European Medicines Agency’s Clinical Trials Information System (CTIS)[15] and the IRIS submission platform for marketing authorizations[16]. Our colleagues at PharmaLex have previously talked about the implications if these requirements are not adequately addressed.
One ongoing challenge for CMC will be harmonizing different manufacturing processes and documentation systems between the acquiring and acquired companies, requiring careful data analysis and potential process adjustments.
Personalized medicine and small batch manufacturing
The trend toward personalized medicine and small batch manufacturing creates additional complications for CMC since these products typically have a short shelf life. This creates regulatory complexities, challenging quality assurance and control standards – for example, real-time release.
This will require very careful management of the supply chain, which puts the onus on companies producing these products to have or turn to CMC experts in personalized medicine. Importantly, CMC should be embedded as part of the development strategy[17]. Inevitably, these CMC processes and the oversight involved will contribute to cost increases.
Conclusion
As the CMC landscape continues to evolve, industry focus will increasingly turn toward how to respond to fast-moving changes. One area that companies are expected to emphasize is the integration of digital tools such as AI and cloud-based platforms to enhance efficiency and accuracy in regulatory processes
Building resilient supply chains will remain a critical priority, particularly in light of the disruptions experienced during recent global events. At the same time, an emphasis on environmental compliance will reshape manufacturing practices.
The role of CMC in post-merger operations will be paramount to support regulatory compliance and operational excellence during transitions. Additionally, the shift toward personalized medicine will necessitate a more sophisticated approach to manufacturing and quality assurance.
These trends underscore the importance of a flexible and innovative CMC strategy. As the industry navigates these complexities, CMC professionals will play a crucial role in driving progress and helping to keep quality and compliance at the forefront of drug development and life cycle management.
About the author:
Matthew Cotten is a Senior Manager in Regulatory Affairs at PharmaLex, with more than 11 years of experience specializing in CMC post-approval lifecycle management. His experience includes managing UK, Ireland, and EU medicinal product portfolios for EU-based clients and providing global regulatory support for multinational consumer healthcare clients.
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[9] Avoiding medicine wastes: Introducing a sustainable approach in the pharmaceutical supply chain, Journal of Cleaner Production, Oct 2021. https://www.sciencedirect.com/science/article/abs/pii/S0959652621028985
[10] Recycling pharmaceutical packaging, ABPI. Recycling pharmaceutical packaging (abpi.org.uk)
[11] Pharmaceutical Company Targets and Strategies to Address Climate Change: Content Analysis of Public Reports from 20 Pharmaceutical Companies, Int J Environ Res Public Health. 2023 Feb. https://pmc.ncbi.nlm.nih.gov/articles/PMC9967855/#sec2-ijerph-20-03206
[12] Building a Resilient and Secure Pharmaceutical Supply Chain: The Role of Geographic Diversification, Duke-Margolis, Nov 2024. https://healthpolicy.duke.edu/publications/building-resilient-and-secure-pharmaceutical-supply-chain-role-geographic
[13] New recommendations to strengthen supply chains of critical medicines, EMA, April 2024. New recommendations to strengthen supply chains of critical medicines | European Medicines Agency (EMA) (europa.eu)
[14] Medicine Shortages Single Point of Contact (SPOC) Working Party, EMA. Medicine Shortages Single Point of Contact (SPOC) Working Party | European Medicines Agency (EMA) (europa.eu)
[15] Guidance and Q&As, About CTIS. https://euclinicaltrials.eu/guidance-and-q-as/
[16] Euro Roundup: EMA answers IRIS questions as variation and notification notices move to new portal, RAPS. https://www.raps.org/news-and-articles/news-articles/2024/1/euro-roundup-ema-answers-iris-questions-as-variati
[17] Patient-Centric Product Development: A Summary of Select Regulatory CMC and Device Considerations, Journal of Pharmaceutical Sciences, April 2023. https://www.sciencedirect.com/science/article/pii/S0022354923000515
