Risk Management: Practical Applications and Value

Philadelphia, PA (July 25)-When industry thinks of risk management and risk assessment, they often think regulation and what they have to do to comply. They complete their risk assessments, write their reports, and file them away for any future data requests by the US Food and Drug Administration. But this data can be used again, says Rebecca Fuller, president of BioAssist Consulting Services (Alberquerque, NM) and a former FDA investigator. In fact, Fuller provided an attentive audience at the 2007 Pharmaceutical Technology annual conference* with a number of practical ways to apply, grow, and improve pharmaceutical manufacturing with risk management approaches.

ICH Q9, the quality guideline on risk from the International Conference on Harmonization, focuses on the principles for integrating risk management into decisions by regulators and industry in an effort to establish a risk management framework that will lead to more consistent science-based decision-making, explained Fuller at the meeting. “Even though ICH Q9 is not in official FDA regulations, we do it and we have to do it,” said Fuller, stating that FDA continues to repeat the fact that industry needs to quantify its risk management process and that the effort and documentation need to be commensurate with the level of risk.

“Risk management is an ongoing approach-it’s something we apply early in the conception phase all the way to postmarket surveillence, when we’re deciding whether or not to investigate complaints,” said Fuller. For this reason, FMEA (failure mode and effects analysis) should be perceived as “a living document,” she said. “Employees should continue to feed results into their FMEA continually.”

The steps for risk management include: risk analysis (i.e., intended use, potential hazards), risk evaluation (i.e., acceptable level of risk), risk control (i.e., mitigation plans), decision-making regarding acceptable residual risks, and postproduction surveillance. “You have to determine which failure modes are the most important and create a quantitative scale of those risks. You have to consider what risks could potentially lead to-in a worst-case scenario-in terms of actual manufacturing quality and operations as well as for the patient.” Once this assessment is done, companies can build written procedures around what to do if something is, for example, a risk level 4 on a scale of 1 to 5. “Now, you’re doing risk-based decision-making.”

There are a number of tools that can be used to assess risk during product and process development, many of which are identified in ICH Q9: hazard analysis, FTA, FMEA, FMECA, HACCP, and HAZOP. “The trick is realizing that they all relate to each other,” said Fuller. “You don’t have to just pick one, you can do your FMECA, but you need your FMEA first to complete it. Use the tools in combination.”

Another important factor to the risk-management approach is to have a team in place to review and maintain risk analysis. Make sure you have one staff member each from clinical, research and development, engineering, and quality. “This way, you can learn from each other collectively and figure out together what are the most critical problems.” A team is also critical in ensuring that risk data is accurate.

Once your FMEA or other risk management tools are working efficiently and continuously being updated, you can put them to practical use in process development and validation, advised Fuller. If you use a flowchart to hold your risk data including process steps, risk descriptions and effects, severity rankings, etc., then you can turn the information in the flowchart into a process control plan. “Going forward, you can say ‘What can I measure to see if failure X has occurred?’ This is how you take a traditional FMEA one step further,” explained Fuller. “In the end, you have a risk-based decision-making system for an entire process.”

Trying to implement ICH Q9 into your processes may seem like an overwhelming task, but there is an easy way to approach it, recommends Fuller. “Start with a product you currently have under development to do an FMEA with, then put a second team in place to do a PFMEA for the process. You’ll see the value and can then start applying the concept across the board.”

*The 2007

Pharmaceutical Technology

Annual Conference was held in Philadelphia, Pennsylvania July 24–26.

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