Quality Risk Management

To mitigate risk in a pharmaceutical manufacturing pipeline, expert review is essential.

by Susan Thompson, Technical Director at VxP Pharma

In the pharmaceutical manufacturing industry, as in all others, risk is an unavoidable aspect of product development. The engineering and manufacturing of a novel pharmaceutical product entail risks to invested capital, encompassing the risks of lost or damaged supplies, inefficient production processes, logistical hurdles, and regulatory difficulties.

While none of these risks can be entirely eliminated, it is possible to take steps to mitigate them as much as realistically possible. This is known as quality risk management (QRM). A solid QRM program systematically assesses risks throughout the development and production pipelines, and takes proactive steps to review, control, and communicate about those risks, so they can be addressed efficiently and effectively.

The QRM process breaks down into four essential steps: pinpointing the process in which risk exists, describing that process and how it functions, diagramming the relationships among components of those functions, and creating a worksheet that summarizes all relevant information about the process in question. These diagrams and summaries may be qualitative, quantitative, or a combination of both; though the risk priority number (RPN) scale is often used to assign a hoh, medium or low level of risk to a given component.

Here are the basic stages of a QRM process, and how they might play out when assessing risk in a pharmaceutical development environment.

1. Select a risky process, and examine the pipeline for potential QRM failures.

Select a risky process, and examine the pipeline for potential QRM failures.

The first step of an effective QRM process is to seek out a process that may invite a heightened level of risk. Such a process is often easy to find in the pipeline. Look for lengthy processes with many stages, in which some of those stages produce inconsistent results. Those might be processes that are unusually vulnerable to human error, performed on older equipment, or dependent on rapid changes; or all the above.

2. Create a team of expert reviewers to assess the process for QRM issues.

Once you’ve identified a process that’s vulnerable to heightened risk, the next step is to assemble a team of expert assessors to determine how that process might be improved. These reviewers should not only be subject matter experts, but should also have a practical on-the-ground grasp of the process in question. If possible, they should be people who’ve worked with the process in person. Above all, they should possess strong analytical abilities, and a talent for seeing solutions that others might miss.

3. Pinpoint possible modes, causes, and effects of failure.

Any complex process will likely have multiple points at which failures are likely to occur, and multiple failure modes for those potential failure points. Your team of expert reviewers should walk through each of the steps in the process under review, investigating what could potentially fail, why that failure would occur, and how it would impact other processes throughout the production pipeline. The team should then rate the severity and probability of each potential failure, using the same consistent scale to rank each failure mode.

4. Assess the “what, where, when, and why” of the most critical failure modes.

Assess the “what, where, when, and why” of the most critical failure modes.

After determining the likelihood and impact of a each of the failure modes, the team should next prioritize investigation of the mode deemed most critical. Focusing on that particular failure mode, the team should assess the most likely reasons for that failure, the time and frequency with which it might be likely to occur, the physical location where it is most likely to emerge, and the most immediate impacts it will have in related steps of the pipeline.

5. Re-engineer the process to reduce the risk of those failure modes.

Once your team of reviewers understand the causes, timeframes, locations and effects of the most critical failure mode, the final step is to identify specific improvements that will mitigate the risk of that failure. The team should brainstorm together, designating concrete steps that can be taken to reduce the likelihood of that failure mode, mitigate the negative impact of its possible occurrence, and otherwise control its causes and prepare for its effects.

The more you encourage your internal team, as well as your partners, to proactively report risks instead of trying to hide or downplay them, the better-prepared you’ll be to face regulatory inspections, and ensure that your production pipeline is in full compliance with all rules. In other words, risk investigation and mitigation not only protect your investments at the facility level; they also protect against risks in the regulatory sphere, enabling your organization to meet your targets and achieve maximum impact in your market.