Despite all the controls, protocols, processes and practices to ensure quality control in drug substance manufacturing, deviations or excursions can arise that could compromise the integrity of the drugs being developed.
CMOs that proactively address any issues that could compromise quality protocols or jeopardize their current Good Manufacturing Practice (cGMP) compliance, however, often ward off such issues by getting to the root cause of the problem, addressing it and learning from it.
Here at PCI Synthesis, quality investigations are performed in response to any deviation from an established process or product specification. These investigations systematically review the circumstances or conditions in which the deviation occurred, and evaluate the resulting impact of the deviation on a product, a process, a system or the safety of staff.
Even in a tightly controlled cGMP manufacturing environment, process deviations and quality excursions can occur, so all team members must be committed to quickly identifying the cause of root incidents, fully investigating and analyzing them, and documenting them to ensure they enable continuous improvement.
At PCI Synthesis, a specially assigned Quality Assurance Group launches a quality investigation immediately upon notification of an excursion, and tailors the investigation response to the individual event. All actions, meetings and pertinent facts from the investigation are included to provide a comprehensive narrative and to ultimately assign a root cause. A thorough trend analysis and impact assessment also is performed to identify all corrective and preventative actions.
In addition to raw materials testing, in-process monitoring, release and stability testing and process validation, adequate investigations of any deviation, or Out-of-Specification (OOS) result, is required by the FDA to ensure cGMP compliance.
FDA regulations state that an investigation should be conducted to determine the cause of any OOS issue and the source of the aberration – either in the measurement process or in manufacturing. Even if a drug batch is rejected based on an OOS result, a quality investigation is necessary to determine if the result is associated with other batches of the same drug product or other products.
According to FDA guidelines, to be meaningful the investigation should be thorough, timely, unbiased, well-documented, and scientifically sound. The first phase of a quality investigation should include an initial assessment of the accuracy of the laboratory’s data. If this initial assessment indicates that no meaningful errors were made in the analytical method used to arrive at the data, a full-scale OOS investigation should be conducted.
While it’s clear that quality audits are necessary to ensure cGMP compliance, what questions should you ask to ensure your CMO is putting the right focus on them? Below are five key questions to ask:
There’s no doubt that deviations and excursions can occur when it comes to manufacturing chemical entities. Yet in regulated environments, CMOs must implement aggressive measures to minimize the severity and frequency of these issues. A commitment to sound and effective quality audits is the only way to counter these challenges, by finding the root cause of these events and learning valuable lessons to ensure future projects don’t confront the same challenges.
Do you have questions? Talk to Ed.