FDA's Risk-based Model Leads to Strategies for Optimizing Site Risk Potential

Site risk potential (SRP) for a pharmaceutical manufacturing facility is an oftenoverlooked element of the US Food and Drug Administration’s (Rockville,MD, www.fda.gov) major initiativeof a risk-based approach for pharmaceutical current good manufacturing practices(CGMP). Justin O. Neway, PhD, executivevice-president and chief scientific officer at Aegis Analytical Corp. (Lafayette,CO, www.aegiscorp.com),outlined at Interphex this week how FDA calculates SRP and the approaches thatdrug and fine chemical manufacturers can use to improvetheir SRP scores.

FDA inaugurated its risk-based inspection program in September 2004 with the release of the report, “Risk-Based Method for Prioritizing CGMP Inspections of Pharmaceutical Manufacturing Sites—A Pilot Risk Ranking Model,” (www.fda.gov/cder/gmp/gmp2004/risk_based_method.htm).

“FDA realized that it did not have sufficient resources to meet the rapidly growing demand for facilities’ inspections and initiated the SRP program in response to that,” explained Neway. “It is part of the overall shift by the FDA moving from rule-based thinking to a science-based approach as part of the agency’s risk-based CGMP initiative.”

Last year, FDA piloted a risk-based inspection model for prioritizing inspections based on SRPs. “All manufacturing sites in the US have been assigned an SRP score,” explained Neway. “These scores have been supplied to FDA field offices. Field offices used these scores to prioritize roughly 40 percent of their site inspections in 2005. The goal is to direct resources to areas of highest risk.”

The SRP is composed of three main elements: facility risk, product risk, and process risk. The year of the last CGMP inspection also is factored into the total score. The facility risk takes into account the production volume and the history of inspection, compliance, and previous CGMP violations of that particular facility. Product risk looks at elements such as whether the product is a prescription drug or is over the counter, sterile or not sterile, and the therapeutic significance of the drug. The process risk assesses the process controls and contamination potential of the processes within that facility.

For pharmaceutical manufacturers in 2006, the key is to understand ways in which to minimize their SRP score for a given facility and to have the supporting processes and data access and analysis capabilities in place and in use before the next inspection.

“You can’t change the fundamental business or production processes you’re already running that dictate the facility and product portions of your SRP score, or change your record of past inspections,” said Neway. “But you can improve your understanding of your current processes and use that to identify and improve control of variability going forward and to make better choices when you design your next manufacturing process, thus reducing the process risk portion of your SRP score and improving your future inspection record.” To that end, Neway stressed the need for effective collaboration and information sharing between process development and manufacturing to improve process understanding collaboratively as early as possible in the product life cycle.