Embarking Upon the Commercial Manufacturing Journey for a Biologic: Strategies to Achieve Successful Approval & Launch

Sponsored by Catalent Biologics

February 10, 2021

In this Q&A, four Catalent Biologics experts share how scale-up, regulatory expectations, demand forecasting and process validation all play a role in the success of a biologic when embarking upon the commercial manufacturing journey.

Authors:

  • Kelly Davis, Director Regulatory Affairs, Catalent
  • Christophe Douay, Supply Chain Manager, Catalent
  • Sophie Evrard, Qualification & Validation Aseptic Lead, Catalent
  • Sylvain Flandroy, Project Engineer, Catalent

Bringing a biologic to market is not easy, and there are several key considerations to how sponsor companies should approach commercial-scale manufacturing that may aid the success of their product’s commercial launch. Many biopharma companies choose to partner with a contract provider for commercial launch and manufacturing. In some cases, they have performed development inhouse or have been working with a development partner that does not have the commercial launch and manufacturing capabilities to support the next steps. Therefore, there is a need to identify a new partner to support this next stage in the product’s life cycle, and the brand owner should have a clear understanding of their requirements if a successful manufacturing partnership is to be formed. In this Q&A, four Catalent Biologics experts share how scale-up, regulatory expectations, demand forecasting and process validation all play a role in the success of a biologic when embarking upon the commercial manufacturing journey.

Q: What is the most important thing biopharma companies should consider before embarking on the commercial manufacturing journey?

Flandroy: First, they need to consider whether they need a manufacturing partner, and if so, who that partner should be. A successful commercial product starts with a successful partnership between a sponsor company and its manufacturer, so they need to be clear about what factors are important to the company and to their product’s success.

Choosing a reliable and experienced biologics manufacturing partner is crucial. They need to have the required knowledge in biologic products and the technology necessary to manufacture the product, while also supporting the sponsor company’s ambition to achieve the commercial goals when the product comes to market. In some instances, sponsor companies may have a limited knowledge of the regulatory requirements, how to scale-up from late-stage clinical to commercial supply, or the exact volume of product required to supply the market. An experienced partner can help guide the sponsor company on the journey to commercial launch while working alongside them to meet demand and contribute to improving more patients’ lives as soon as the product is ready for market.

Q: How should companies approach scale-up of their biologic from Phase 3 to PPQ/commercial manufacturing?

Flandroy: Sponsor companies should consider using a risk-based approach, allowing for the quickest path to market. Such an approach is best achieved in a culture of collaboration with open, honest and clear communication. Preparing for PPQ/commercial batches is very different than preparing for what is often a single Phase 3 clinical batch, as multiple other operational points must be taken into consideration. A manufacturing partner can provide advice on these operational aspects to ensure commercial supply is as trouble-free as possible.

Manufacturing partners need to acknowledge that every sponsor, every product, and every process is different. To address this, Catalent Biologics creates a specific working environment during the late-stage phases with the objective of capturing enough detail to increase the chance of success. For example, during the scale-up program, every parameter related to the process will be assessed using a “quality by design” approach, resulting in a robust risk analysis that is built in association with the sponsor. The partnership between parties is, in any case, absolutely crucial during this transition phase to ensure that the knowledge of the product and the process will result in a successful transition from development to product supply.

Q: What are the regulatory expectations pertaining to biologics manufacturing?

Davis: Regulatory requirements provide the quality backbone that must be incorporated into all drug product manufacturing processes. However, there are requirements that are unique to biologics. Since many biologic products are sourced from living organisms, whether microorganism, yeast, animal or human, there are additional safety precautions that are needed to ensure the source material does not contain viral contaminants. As a result, a rigorous sourcing and viral decontamination process must be demonstrated as part of the regulatory submission.

Because biologic products are more susceptible to contamination than small molecule products, a biologic manufacturer must implement a robust evaluation process for each product manufactured at its site. This evaluation should include any potential cross-contamination along each step of the process, from incoming to receipt, sampling, filling, and packaging or labeling, as well as any additional control measures which must be implemented. To reduce risk of cross contamination, Catalent Biologics implements several quality measures, including the use of unidirectional product and material flow across the production floor, single-use systems, ready-to-use filling components, and isolator and robotic technologies thereby minimizing human manipulation.

Due to the sensitive nature of biologic products, the EMA and the FDA’s Center for Biologics Evaluation & Research (CBER) expect a robust understanding of the manufacturing process, analytical methods, product attributes and process parameters at the time of submission.

Q: How do demand forecasting and flexibility in manufacturing play an essential role in commercial launch?

Douay: Developing a good demand forecast and a market intelligence culture is critical to both the success of a commercial launch and to ensuring supply in the critical period immediately following the launch. A better understanding of the market dynamics allows companies to reduce variability in plans, and thus, better anticipate manufacturing needs. Monitoring forecasting performance will also help sponsors better recognize where they’re more exposed to unexpected changes in market demand.

Having high performing demand forecasting is an operational asset, and the sooner before commercial launch it is in place, the better. It allows sponsor companies to be in position for optimal success by facilitating fine-tuning of their launch strategies, such as optimal inventory levels, supplier selection, supply plans, and capacities. Even more importantly, companies will have the proper information to determine the adequate flexibility needed to support a successful commercial launch.

In most cases, some variability cannot be avoided, and a manufacturing partner will need to assist the sponsor company to be ready to adapt. Example strategies to address variability include setting up an agile and flexible organizational culture, building plans to quickly react to capacity requirements, and working collaboratively with suppliers to turn changes in plans around fast.

Q: What successful process validation strategies does Catalent Biologics employ for drug product?

Evrard: Before explaining strategies for successful process validation, one must first understand what is considered successful process validation. In the simplest description, Catalent Biologics must demonstrate, through the collection of appropriate data, that the production process of the biologic drug product is highly robust and consistently provides the desired product within all specifications. This means that successful process validation cannot be achieved unless Catalent Biologics thoroughly understands the specific process and the impact that process parameters have on the product quality. To achieve this level of knowledge, Catalent Biologics and the sponsor company must first build a strong relationship, particularly in the case of biologic drug products, which are inherently variable. This close collaboration needs to start at the earliest phase of the project, as process validation is most effectively achieved when quality is designed into the product and process from the start.

There are many factors to consider and identify during the product filtration, filling and packaging steps: Is the filtration membrane compatible with the product? / Is the filling pump suitable for the product? / Does the container fit with the product? / Does it require specific measures for light or oxygen? These factors must be identified and captured in the early stages through a risk-based analysis, with both partners providing input into the process and product. The sooner the risk analysis is generated, the sooner the design phase can begin, and the production of batches can occur. The closer sponsor companies and partners collaborate during the risk analysis, design phase and actual production, the higher the likelihood of a successful process validation for biologic products.