Transcript
Hi everyone. Welcome back to the channel. Today we are diving into a topic that's absolutely critical in the pharmaceutical industry, but often mishandled. It's the OOS and deviation investigations. Whether you are a pharma professional responsible for conducting those investigations within your firm, or you are in a quality organization trying to make sense of them, or even you need to respond to a warning letter from one of the regulatory bodies, this video is for you and let's get started.
First things first. What exactly are OOS and deviation investigations? In simple terms, they are the processes through which pharmaceutical companies use to identify, understand, and fix issues that could affect the quality of their products.
This could be anything from a batch of tablets, not meeting specifications, to a piece of equipment malfunctioning during production. And the goal is to ensure that every single product that reaches patients is safe, effective, and meets strict regulatory standards.
Examples of FDA 483 related to OOS:
One of them is the lack of thorough or inadequate investigations. Next to that is failure, that the investigations are not conducted or completed in a timely manner. For example, not conducting timely stability investigations. And then, reports do not indicate if similar OOS results were reviewed and if other lots are impacted or affected.
Next to that, if the company's investigations did not extend to other batches or to other products manufactured at the same time. Or if the investigation report does not include the corrective and preventive actions necessary to prevent similar future recurrence.
Based on that, let me share with you some trends of investigation failures. So the failure to investigate deviations accounts for about 27% of the reason for a 483, and then incomplete investigations account for 25%. Inadequate documentations and reporting accounts for 14%. Inadequate corrective actions accounts for 11%. Inadequate management review or oversight accounts for 9%. Unjustified conclusions accounts for 9% of the 483s, and also finally a failure to assure timely investigation and closure accounts for 9% of the 483s.
So how does an OOS investigation work? Let's break it down into key steps.
First of all, a detection of the issue. This could come from a routine quality testing, or a customer complains, or even internal audits.
Next comes the initial assessment. The team evaluates the severity of the issue. Is it a minor deviation or is it a major quality risk or is it a critical quality risk that might impact patient safety?
Next to that is the immediate action that needs to be taken.
Following that, there is a study of the scope and impact of the deviation or the out of specification.
Following that, there has to be a study or a discussion of the root cause analysis. This is where the real detective work happens. To pinpoint the exact cause, teams use tools like 5 Whys, Fishbone Diagrams, FMEA, which is a failure mode and effects analysis.
Following that, a corrective and preventive actions, the CAPAs, need to be identified. The team implements these fixes to prevent the issue from happening again. And along the way, documentation and reporting. Every step of the process is meticulously documented to ensure the transparency and compliance with regulations like the FDA and EMA or the WHO guidelines.
Now, you might be wondering why is this process so important? Well, it all comes down to patient safety. A single quality issue can have serious consequences, from ineffective treatment to harmful side effects. Plus, regulatory agencies like the FDA or the EMA have zero tolerance for non-compliance. Failing to properly investigate and address quality issues can lead to hefty fines, product recalls or even shut downs.
To give us some insider perspective, if you ask me as a quality assurance expert with over 20 years of experience in the pharmaceutical industry, what's the biggest challenge companies face during compliance investigations? Great question. One of the biggest challenges is balancing speed and thoroughness. Investigations need to be done quickly to minimize disruptions. But they also have to be incredibly detailed to ensure nothing is missed. It's a delicate balance.
My advice for companies looking to improve their investigation process is to invest in training your teams, leverage technology like data analytics, and foster a culture of transparency where employees feel comfortable reporting issues without fear of blame.
To wrap things up, here are three key takeaways for effective quality compliance investigations:
1. Be proactive. Don't wait for issues to escalate. Regularly review your processes and systems.
2. Focus on root causes. Treat the problem, not just the symptoms.
3. Document everything. Good documentation is your best defense during regulatory inspections.
And that's a wrap. Quality compliance investigations might seem complex or daunting, but they are essential for ensuring the medicines we rely on are safe and effective. If you find this video helpful, don't forget to give it a thumbs up. Subscribe to the channel and hit that notification bell so you never miss an update. And if you’ve got questions and or topics you would like me to cover, drop them in the comments below. And thanks for watching, and I'll see you in the next video.
Tamer Helmy is an independent consultant with Quality Executive Partners, Inc. (QxP) and brings over 30 years of global experience in pharmaceutical regulatory affairs, CMC strategy, and quality systems. He has supported top-tier companies across the U.S., Europe, and the Middle East, and is known for his ability to communicate complex regulatory concepts with clarity and insight.
