OR WAIT null SECS
Industry lessons from a fast-track technology transfer of a soft-gelatin capsule (softgel) are multifold. This case study reviews the success factors for effective execution of the technology transfer, which include: strong relationship between the customer, the contract development and manufacturing organization, and other partners based on deep knowledge in the technology; established and proven quality-by-design processes; risk mitigation management; project leadership; flawless execution; and mutual trust.
Technology transfer plays a vital role in the process of drug discovery to product development and full-scale commercialization. The Pharmaceutical Research and Manufacturing of America’s Quality Technical Committee defines technology transfer as, “The body of knowledge available for a specific product and process, including critical-to-quality product attributes and process parameters, process capability, manufacturing and process control technologies, and quality systems in infrastructure” (1). In-licensing of promising compounds within the product development pipeline continues to increase, with more than 40% of recent approvals involving a change in compound ownership. In such cases, efficient technology transfer is crucial to maintain the increasingly accelerated development timelines required, especially for specialized designations, such as breakthrough medicines, orphan drugs, and products pursuing the new drug application 505(b)2 or similar regulatory pathways.
Expertise in technology transfer is even more important when confronting a regulatory issue that requires an immediate solution to ensure continuous access to a medicine that is critical to patients. This case study reviews the key success factors that enabled a time-sensitive or “fast-track” technology transfer of a well-known medicine from a soft-gelatin capsule manufacturer experiencing regulatory issues to a contract development and manufacturing organization (CDMO) to maintain product supply to the French market. From start to finish, the technology transfer occurred within nine months.
The pharmaceutical company’s single subcontracted encapsulation site was affected by a decision by the French authorities to suspend its manufacturing license. This action left the company without an active encapsulation site to manufacture a leading medication delivered via a softgel capsule, which was critical to patients in France.
At the time of the decision, the product supply of the medicine to the market was limited by the amount of stock available in the supply chain channel. Therefore, the time to transfer, manufacture, and gain regulatory approval of a new manufacturing site was severely limited.
The challenge to the pharmaceutical company was to find a CDMO partner who could rapidly advance the medicinal product to market to ensure the continuity of supply to patients.
The project was “fast tracked” with a three-phase approach executed over nine months from feasibility to product release.
In executing the project, there were six key success factors. Although not common in the industry so far, the pharmaceutical company asked the CDMO to be the project lead.
Robust product knowledge. In the pre-project phase, considerable pre-work had been done by the pharmaceutical company’s team. There was tremendous technical knowledge about the product, a focused scope that resulted in fewer analytics required for the transfer, and well-informed partners. This provided a clear understanding of what was critical and what was not critical in the technology-transfer process.
Project leadership. The pharmaceutical company delegated the product transfer lead to the CDMO given its established expertise in softgel capsules development and manufacturing and quality by design (QbD) know-how. Roles and responsibilities of both the pharmaceutical company and the CDMO had to be clearly defined.
In advance of execution, the team was clear on who oversaw each part of the project to ensure efficiency. Importantly, the project lead at the CDMO was highly influential within the company. The project leader must be well connected, maintain the project as a high priority, and manage through a regulated GMP-compliant transfer process. Without this type of leadership, a project can become mired in delays.
Trust and transparency. Processes were established to make quick and robust decisions. Challenges had to be resolved in no longer than a week between two project calls. Every member of both the pharmaceutical company and the CDMO teams was required to attend weekly conference calls to ensure that the teams had open conversations. This simple attendance rule enabled project pace and better team focus. With trust and transparency between the CDMO and the pharmaceutical company, issues were resolved efficiently.
Planning and management. The team carefully maintained documentation, reinforcing team seniority and expertise. Every detail was meticulously mapped, including facilitating manufacturing slots at the CDMO. Resources and budget were managed in parallel with the project to ensure that there was no operational impact.
Established QbD processes. The use of QbD know-how and process developed by the CDMO was paramount to accomplishing this project. Using its softgel manufacturing experience, the CDMO developed a QbD approach for softgel development, scale-up, and manufacturing. The approach included ICH-based risk assessments and design of experiments to quickly identify the manufacturing design and process space for a specific softgel product, taking into consideration the critical formulation and process parameters for the softgel product.
At the outset, there was significant time invested to develop and understand-as a team-the critical process parameters and how the QbD process worked. Therefore, by the time the team moved to the feasibility phase, there was a clear understanding of the QbD processes, which enabled a knowledgeable and cohesive team that could stay on schedule and on task.
Risk mitigation and management. Engaging early on with regulators was crucial to mitigating risk. The pharmaceutical company met with regulators at the outset to understand potential concerns that informed risk-mitigation processes. These learnings were employed with a risk-based approach and allowed for risk-based decisions to be made during the transfer. Pre-existing risk assessment formats were used to monitor and reduce uncertainty and minimize risk. Development of new documentation was not required because the CDMO already had existing processes and procedures in place.
The project was closed with a “Lessons Learned” session involving all partners involved in the project, enabling the teams to identify and share project key success factors that were relevant industry wide.
The fast-track technology transfer was completed in nine months, and considered a success by the customer. The success of this project was a result of a team-based approach where the partners interacted efficiently to drive a fast-track technology transfer for a soft-gel capsule to ensure supply continuity for patients. The team maintained a focus on results, planning, and adherence to timelines to minimize market supply disruption.
1. PhRMA Quality Technical Committee, 2003.
Supplement: Partnerships in Outsourcing 2018
When referring to this article, please cite it as J. Vertommen, “Case Study: Fast-Track Technology Transfer of a Soft-Gelatin Capsule,” Pharmaceutical Technology Partnerships in Outsourcing 2018 Supplement (February 2018).