You need to reach market readiness? What now?

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Advancing a drug to market readiness is a major milestone. After successfully completing clinical studies, manufacturing and analytical processes must be adapted and optimized for commercial scale. Partnering with an experienced CDMO can help develop a strategy that balances speed, risk, and flexibility. But how do you find the best partner? Here’s a checklist.

Identifying the ideal CDMO for a project the first time around can be vital not only for the market success of a new molecule but also for the fate of the entire company. Experience with production scale-up, process optimization and validation, and working with regulatory authorities are the main parameters to check when assessing a potential CDMO partner.

✓ Ensure efficient scale-up

Laure Valognes, Deputy Global Head of Operations, working with the BioReliance® End-to-End Solutions portfolio of Merck

Concurrent with clinical phases, manufacturing processes need to be scaled up for patient cohorts and eventually for commercial scale. Building a manufacturing facility means a huge financial and organizational effort that is not economically viable for most biotech companies

Even if setting up a production site is an option, there’s a risk that the facility cannot be operative fast enough, upon receipt of a breakthrough designation or fast-track approval, for example. Besides, approval timelines for different countries or regions can be uncertain, making it challenging to adequately plan the required production capacity and batch sizes. Outsourcing to a CDMO can solve all of these issues.

During scale-up, the main task is to ensure that the necessary production capacity is reached without compromising product quality. An ideal CDMO partner will have experience in manufacturing similar molecules and technologies and in optimizing process economics. 

Single-use bioreactors available at different scales can reduce risk and facilitate drug manufacturing. Plus, they can increase productivity and allow a quick expansion of manufacturing capacity to meet changing market demand, for example, during a disease outbreak.

Our team has established a direct scale-up method from bench to 2000-liter commercial scale that matches the timeframe required by a fast-track application. The elimination of intermediate steps accelerates time to market and delivers a competitive advantage,” said Laure Valognes, Deputy Global Head of Operations, working with the BioReliance® End-to-End Solutions portfolio of Merck*.

✓ Optimize the process to match the production strategy

Typically, the existing manufacturing processes will have to be optimized to match the production capacity needs of the new drug determined by clinical development plans, drug filing strategy, and anticipated market size. 

An experienced CDMO partner will conduct a gap analysis, meaning a process to identify the missing steps between current operations and the required performance and provide recommendations on how to achieve the goal. 

Even more importantly, the CDMO needs to analyze the consequences of manufacturing process variations on product quality, cost, and manufacturing timelines. Ultimately, process optimization should be guided by an understanding of which modifications will deliver the highest value without causing a cascade of other necessary changes.

It is vital to strike an effective balance between the time and money invested and the expected benefit. For example, if we replace a raw material with a lower-cost alternative, this may affect protein stability, requiring additional studies that delay the process and increase the cost,” Valognes explained. 

✓ De-risk process validation

Corinne Lavie-Cambot, Head of Innovation and Industrialization Department, working with the BioReliance® End-to-End Solutions portfolio of Merck

During process validation, data is collected and evaluated to ensure the process can continuously deliver a quality product. Removing or changing a step not only impacts the process itself but may also affect the documentation that has already been submitted to the regulatory authorities. Previously collected clinical data may become obsolete, making a re-validation necessary. 

At the same time, process validation not only applies to the marketing authorization application but must be considered throughout the entire life cycle of a molecule. 

The simplification and standardization provided by single-use tools translate to faster, easier and de-risked process validation, increase productivity and enable rapid addition of capacity in response to changing market demand.

 “You need to demonstrate that the manufacturing process is capable of consistently producing acceptable quality products. Regulatory authorities must be confident that a process is always under control and can remain in control”, Corinne Lavie-Cambot, Head of Innovation and Industrialization Department, working with the BioReliance® End-to-End Solutions portfolio of Merck, said. 

A reliable CDMO partner will take a systematic, risk-based approach that oversees the entire process from bench scale to commercial production and coordinate a significant amount of documented data, enabling informed decisions and sharing with the regulatory authorities. 

✓ Manage the regulatory authorities

Regulatory processes are complex and highly variable between different countries and regions, and also differ between therapeutic approaches, such as gene or antibody therapies. A trusted CDMO will be familiar with agencies around the world and capable of supporting all aspects of compliance for all types of treatments all the way to the post-approval phase. 

Regulations must be applied to the needs of the individual project, translating the authorities’ expectations into a concrete action plan. Last but not least, a CDMO must effectively tailor communication to ensure the success of the process validation and the reliability of the commercial process. 

When a commercial submission is planned, we can support our customers in communicating with the regulatory authorities. We are aware that while the core validation work is the same, individual agencies and inspectors focus on different aspects of the process in their submission and audit reviews,” concluded Marie-Gaelle Roger, Global head of QC, op QA and Regulatory, working with the BioReliance® End-to-End Solutions portfolio of Merck.

At the final stage of drug development, the goal is close, but the risk remains. At this stage, the support of an experienced CDMO to reach market readiness can be more valuable than ever. 

Learn more about how BioReliance® End-to-End Solutions can take your project to market success.

*The life science business of Merck KGaA, Darmstadt, Germany operates as MilliporeSigma in the U.S and Canada.

Merck, the vibrant M and BioReliance are trademarks of Merck KGaA, Darmstadt, Germany or its affiliates. All other trademarks are the property of their respective owners. Detailed information on trademarks is available on publicly accessible resources.

Images via Merck

This article was originally published in May 2021. 

Explore other topics: BiomanufacturingMerck

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