Case Study: Implementation of a Large-Scale Validation Process at a Biotech Company
Background
At the beginning of 2024, Marco Albrecht, senior consultant at Progress, started a challenging project at a biotech company in the Amsterdam region. The company, which produces drug substance and drug products, faced a major problem: seven batches of one of their drug products were contaminated with N-toxins two years ago and had been in the warehouse ever since. Marco was called in to validate a large-scale process to remove these toxins. This endotoxin removal step was previously successfully tested on a smaller scale in one of their other facilities.
Project objectives
The primary goal of the project was to scale up and validate the small-scale decontamination process for handling the contaminated batches stored in Amsterdam. Marco explains: ”The other facility had the facilities to conduct the case study on a small scale, using small vessels and volumes. Once it was proven to work, the task was to replicate this on a larger scale in Amsterdam, where the batches were originally produced.” Marco was hired to validate this process. He wondered: “Suppose we have the process set up on a large scale, and we have the recipes ready for the operators to execute. How can we prove that it was indeed successful? Which documents do we need for this, which tests are required for this? What requirements must be met to state that process consistency and efficacy have been successfully demonstrated and that validation has been successful?” The project began with some urgency because the batches were two years old and nearing the end of their validated shelf life. This tension made it difficult for him to get everyone on the same page.
Challenges and Lessons Learned
One of the major challenges Marco faced was the abrupt termination of the project due to organizational decisions. Reflecting on this, Marco said: “In the end, nothing concrete came out of it. Not because of our efforts, but because the project was stopped.” This decision was driven by internal priorities and an upcoming major regulatory inspection. Before the inspection, the company decided to prioritize only those projects that had a direct impact on the inspection result. “My project was put on hold, among other things” Marco explains.
Nevertheless, Marco highlighted the most important lessons, especially in the areas of project management and stakeholder alignment. He noted: “In retrospect, we should have agreed within our project to stop until the QP was on board. We could have been successful in reworking the batches with the decontamination process step and ensuring the drug product was free from the endotoxin contaminations. However, if the QP had not released this product, all efforts would have been in vain. On the other hand, we could have decided to proceed only if the senior management of manufacturing and quality would give unanimous support.”
Team Dynamics and Contributions
Throughout the project, Marco worked closely with a focused, dedicated team. He emphasized the importance of teamwork and clear documentation: “I helped with documentation, including process descriptions and risk analyses. Although the project was halted, it was very satisfying to see how much we achieved with a relatively small and dedicated team.”
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Marco’s role also included significant, useful interaction with the Progress team. He recalled a crucial presentation he gave that made clear different positions within Progress. He says: “During my presentation there were almost two camps within Progress: several colleagues pushed for the project to be stopped and those on the substantive side argued for its continuation. From a compliance perspective, it said that reworking a drug product is only allowed in exceptional circumstances and strict criteria should be applied, taking into account that there is a good chance that the regulatory authorities will not approve the rework. It was very educational to hear these perspectives.”
Conclusion
Despite the premature termination of the project, Marco’s involvement provided valuable insights and personal growth. The experience underscored the complexity of large-scale process validation in the biotech industry and highlighted the critical role of comprehensive planning and stakeholder coordination. Marco concluded: “Even though the project did not reach completion, the discussions, questions and potential obstacles we identified provided valuable lessons for everyone involved.”
Leveraging his expertise in validation and process development, Marco continues to make significant contributions to projects at Progress, applying the lessons learned from this and other experiences to future efforts.
