A Data-Driven CMC Approach Can Shorten Drug Development Timelines
By Life Science Connect Editorial Staff
The chemistry, manufacturing, and controls (CMC) portion of drug development is an integral part of designing a seamless manufacturing process for your molecule. CMC teams must define the critical quality attributes (CQAs), critical process parameters (CPPs), and manufacturing protocols to yield consistent product batches. Beginning CMC activities as early in process development as possible helps stakeholders design more comprehensive strategies to guide the trajectory of a product. To aid the efficiency of CMC, many sponsors and contract research organizations (CROs) are assessing how to better incorporate data and innovative software to allow for more collaborative analysis.
In a recent Bioprocess Online Live event, CMC leaders Brian Kirk, Ph.D., lead author, global regulatory affairs CMC for plasma derived therapies at Takeda, and Blair McNeill, Ph.D., senior vice president and head of cell therapy at Sumitomo Pharma America, caught up with Bioprocess Online Chief Editor Matt Pillar to discuss how the CMC space is shifting to become more precise and data-driven. Given their experience, both leaders emphasized the impact of investing in innovative data analysis platforms that leverage artificial intelligence (AI) and other predictive technologies.
Current Challenges In The CMC Space
One of the biggest challenges for CMC teams is the breadth of factors to consider. According to Kirk, “CMC describes a range of activities that ensure quality is built into any drug product. There are numerous elements involved to guarantee batch-to-batch consistency and safety. This all stems from the identification of the lead compound and goes back to verifying the quality of the raw materials before use. A concerted CMC initiative should carry through every stage of the pipeline.”
Without diligent CMC protocols, your drug development is destined to be difficult. Remaining compliant with the dominant health authorities requires companies to be proactive about monitoring regulatory changes, a task that ultimately falls to CMC teams. For small companies with limited resources and bandwidth, it may be challenging to conduct adequate regulatory intelligence to keep up with rapidly evolving regulations. McNeill recommends consulting with other sponsors: “We've run into a number of [instances] where thanks to collaboration with [external] colleagues, we [realized] we were getting the same feedback from the FDA. Thus, we knew it was a hot button issue that we had to solve.”
Regulators are looking for safe, efficacious, and reproducible processes. To achieve this, sponsors and manufacturers need to develop a thorough understanding of their processes and CQAs. “The better you understand the manufacturing processes and corresponding clinical operations, the better equipped you are to fix any issues that you run into. You need real-time feedback to refine and improve processes as you go through the development pipeline,” notes Kirk. High-quality data and corresponding analysis are viable routes to improving the CMC landscape.
Benefits Of Data-Driven CMC
Traditionally, data was shared among internal and external colleagues in meeting rooms via notebooks and discussion. As technology has advanced, sponsors, CROs, and manufacturers are shifting toward using electronic lab notebooks, improved information technology (IT) infrastructures, and software platforms to allow for integrated data management. Moving to digital data sharing platforms allows key CMC stakeholders to communicate virtually to manage and analyze critical data. By investing in novel data management platforms, teams glean more information from data and engage in far more collaborative analysis.
McNeill notes that the pharma industry is approaching this from multiple angles: “There's a growing industry rolling out software platforms to sell to organizations. We also invest time, energy, and money to develop internal data analytics platforms and digital infrastructure, including having digital integrators who develop novel ways of looking at data for more information.” As for any remaining notions that the pharma industry is behind the curve on data and IT analytics, Kirk clarifies that it really depends on the company and their capacity: “At some smaller companies, it is the conference room and the notebooks. Some of the larger organizations try to be attuned to the latest developments in technology, [including] data science and analytics, and in a few cases, AI platforms and statistical software to optimize manufacturing processes. It tends to be based on the company’s ability to financially support advanced technologies.”
The data-driven agenda starts at the top with leadership teams striving to make digital advancements. From there, it becomes an organization-wide initiative with functional groups working with IT to integrate a reliable digital infrastructure. By better streamlining data, Kirk notes that: “As you gain more information about the process and understand how to achieve a certain level of quality, that information can fuel the refinement and development of more CQAs to provide better governance over the production of a high-quality drug product. It’s all part of an iterative feedback loop.”
Key Considerations To Evolve Your Approach
The pivot to more data-driven CMC protocols has been driven by changes made by leading health authorities, including the ICH, FDA, and EMA. As these major players shape the future of CMC and regulatory, the goal is to find greater harmonization across the industry. Historically, rolling out a manufacturing process change has been a challenge, particularly for a globally licensed product that is manufactured at multiple sites. ICH Q12 outlines the technical and regulatory considerations for product life cycle management. It provides a framework for marketing authorization holders to approach post-approval CMC changes, allowing sponsors to rapidly identify which quality factors will have the biggest impact in terms of making changes to the manufacturing process.
By following the tenets of ICH Q12 and securing the buy-in of health authorities on their proposals, sponsors might shorten their timelines to approval from one year to four or five months. The Knowledge-Aided Assessment & Structure Application (KASA) and Pharmaceutical Quality/CMC (PQCMC) initiatives designed by the FDA both aim to streamline and harmonize the process for submitting structured data. The aim is standardizing information for product quality submissions so that sponsors can submit a common set of data elements in a consistent format.
Kirk notes that, “Until recently, a lot of companies relied on structured offerings, where the structure of a document and what content goes into each section is predefined. This hasn't been widely embraced because with so many mergers and acquisitions, you end up with a blend of reports in different formats. We have to harmonize things. Companies are starting to look at the idea of using AI for regulatory writing situations.” Automated regulatory writing uses natural language processing (NLP) to generate quality sections for a regulatory dossier, alleviating some of the workload for CMC teams.
Finally, raw material considerations should also be top of mind. Per McNeill: “The grade of raw materials that regulators are expecting in early phase versus late phase has an increasingly narrow gap between what is GMP and non GMP. We implement GMP level raw materials in early process development to avoid potential surprises.”
The Bottom Line
Data-driven CMC requires a major investment of time, energy, and money that can yield significant synergy for your systems. Ultimately, both McNeill and Kirk emphasize the importance of staying on top of the latest regulatory information and using data-centric software to your advantage. If your organization is small and doesn’t have the bandwidth for dedicated regulatory personnel, consider outsourcing surveillance initiatives, working with consultants, and collaborating with other sponsors in your field to ensure you are leveraging the most effective data management software to produce CMC success.
Ready to learn more? To listen to this full episode of Bioprocess Online Live, click here