In the world of biopharmaceutical manufacturing, precision and quality are paramount, and any unexpected anomaly can pose significant risks. Recently, KBI Biopharma, a leading contract development and manufacturing organization (CDMO), faced such a challenge when a batch of cell culture media provided during a tech transfer unexpectedly began to turn pink. This issue, rooted in an impurity present before the media ever reached KBI Biopharma, had the potential to disrupt the entire manufacturing process. Thanks to KBI Biopharma’s expertise in advanced mass spectrometry techniques and quick teamwork action, a costly crisis was averted.
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A potential crisis with setbacks in mind
The problem emerged during the final stages of preparing for a crucial GMP (Good Manufacturing Practice) run. The cell culture media, a vital component in the production of biologic drugs, was observed to have an unusual pink coloration. This was alarming, as the media is expected to be clear, and any deviation could indicate a contamination or chemical reaction that might compromise the batch. The stakes were high—if the issue wasn’t resolved, the entire batch could be lost, leading to significant financial and time-related setbacks for the customer.
The process development team at KBI Biopharma quickly hypothesized that the pink hue was likely due to a chemical transformation involving vitamin B12, which is commonly added to cell culture media. They suspected that the vitamin had converted into hydroxycobalamin (B12-OH), a compound with a distinct pink color, possibly due to exposure to light. However, this theory needed confirmation before any corrective actions could be taken. The customer was faced with a critical decision: should they invest in further investigation using advanced analytical techniques, or risk losing the entire batch?
The power of mass spectrometry: finding the root cause
Fortunately, the customer decided to proceed with the investigation, and KBI Biopharma’s Mass Spectrometry Core team was called into action. Known for their deep expertise and cutting-edge technology, the Mass Spectrometry Core team utilized the Xevo G2-S QTof, a state-of-the-art mass spectrometer, to get to the bottom of the issue.
The team began by isolating the suspected impurity, hydroxycobalamin (B12-OH), from the rest of the biotherapeutic mixture using a cold ACN (acetonitrile) crash. This technique effectively separated the pink compound from the bulk of the media, leaving a concentrated supernatant ready for detailed analysis. The supernatant was then analyzed using liquid chromatography-mass spectrometry (LC-MS), a method that allowed the team to separate the compounds based on their retention time (RT) and identify them by their molecular weight (MW).
By comparing the data from the LC-MS analysis with a reference standard of B12-OH, the Mass Spectrometry Core team confirmed that the pink discoloration was indeed caused by the presence of hydroxycobalamin. This confirmation was crucial; it not only validated the process development team’s hypothesis but also provided a clear path forward for remediation.
Avoiding a costly mistake: the value of expert intervention
Had the customer chosen not to proceed with the mass spectrometry investigation, the consequences could have been severe. Without identifying the root cause of the coloration, the entire GMP batch might have been discarded, resulting in a loss of both time and money. The cost of losing the batch would have been approximately a hundred times greater than the cost of performing the analysis. By choosing to invest in the investigation, the customer not only saved their drug candidate batch but also avoided significant financial loss and production delays.
It’s important to note that not every CDMO has the in-house capability to perform such advanced mass spectrometry analysis. Carefully selecting a CDMO that invests in cutting-edge technology and expert personnel allowing for comprehensive impurity detection and identification, can be the difference between salvaging a batch and facing significant setbacks.
A collaborative solution: expertise and transparency
Once the cause was identified, KBI Biopharma’s teams moved quickly to implement a solution. The answer was as simple as it was effective: shielding the media from light would prevent further conversion of vitamin B12 to hydroxycobalamin, thereby preserving the integrity of the batch. This solution was put into action immediately, allowing the GMP run to proceed on schedule and without further issues.
Throughout this process, KBI Biopharma’s project management team maintained clear, proactive communication with the customer. Their transparent and solution-oriented approach, combined with a risk-based strategy for process development and tech transfer, ensured that the customer was kept fully informed at every stage. This approach not only resolved the immediate issue but also strengthened the trust and partnership between KBI Biopharma and their customer.
Witnessing excellence: the customer’s perspective
A key aspect of this successful collaboration was the presence of a Person In Plant (PIP), which KBI Biopharma had enabled for the customer. This arrangement allowed the customer to witness the process firsthand, providing them with real-time insights into the situation and fostering a deeper level of trust and engagement. The customer was able to see the dedication and expertise of the KBI Biopharma team up close, from the precise mass spectrometry analysis to the swift implementation of the solution.
The customer’s appreciation was evident in their feedback. They praised KBI Biopharma not only for their scientific expertise but also for their practical application of that knowledge on the shop floor. The customer acknowledged that the decision to proceed with the mass spectrometry investigation was pivotal in saving both their batch and their investment.
A success story: lessons learned and moving forward
This incident underscores several key lessons for the biopharmaceutical industry:
- The importance of advanced analytics: The use of state-of-the-art tools like the Xevo G2-S QTof mass spectrometer was crucial in diagnosing the issue and guiding the resolution. Advanced analytical techniques like mass spectrometry are indispensable for ensuring the integrity of biopharmaceutical manufacturing processes.
- Cost-effectiveness of proactive investigation: The decision to invest in a detailed investigation saved the customer a significant amount of money and time, highlighting the value of proactive problem-solving.
- Collaborative transparency: The success of this project was built on transparent communication and close collaboration between KBI Biopharma and their customer, reinforced by the presence of a PIP.
A bright future: building on success
For KBI Biopharma, this experience reinforced their reputation for scientific excellence and their commitment to customer satisfaction. This success story is more than just a resolved issue; it’s a clear demonstration of KBI Biopharma’s role as a leader in the industry, ensuring that every batch, no matter the challenge, is delivered with the highest standards of quality and reliability.
As the industry continues to evolve, the ability to swiftly and effectively apply experience to address unforeseen challenges will remain crucial for managing risks associated with biopharmaceutical production and ensuring the delivery of safe and effective therapies to patients around the world. KBI Biopharma is committed to being the confident foundation for every customer, empowering them to bring their solutions for the most challenging diseases to patients around the globe.
For more details on KBI Biopharma’s Mass Spectrometry capabilities and how they can address complex challenges, please visit the KBI Biopharma website.
Image Courtesy: KBI Biopharma