We at GMP Trends have noticed a rising number of 483’s pertaining to “Risk” for both medical devices and pharmaceuticals. The introduction of QMSR for medical devices has launched Risk-Associated 483’s to the top of the most cited observations since February 2, 2026. We attended a RAPS Quality Conference on June 9-10 where we heard directly from FDA personnel confirming this increased FDA scrutiny of Risk.
The following 483 belongs to a USP Tablet Manufacturer, citing a fundamental failure in the quality risk management (QRM) for high-potency drug products with low Acceptable Daily Exposure (ADE) values.
…..The responsibilities and procedures applicable to the quality control unit are not in writing and fully followed.
Specifically, your Quality Risk Management (QRM) assessment for the manufacture of high-potency …products, specifically … Tablets USP (… strengths) and … Tablets USP (… strengths), is inadequate and fails to comprehensively evaluate critical risks associated with these compounds. The following deficiencies were observed in QRM documents …
a. Your risk assessment fails to evaluate the risks associated with recirculating … of air in areas manufacturing multiple … products
b. Your risk assessment fails to evaluate the potential for environmental release of … compounds through exhaust air systems, despite manufacturing products with low Acceptable Daily Exposure (ADE) values.
c. No assessment is provided for the adequacy of air treatment systems … or other containment technology) to prevent … residue discharge into the environment through facility exhaust systems.
Over the last 3 years, your firm has manufactured approximately … Exhibit batches and … commercial batches of … and … The commercial batches are for the Canadian market,and the Exhibit batches include US submission batches.
This 483 reflects FDA’s intensified focus on Quality Risk Management, driven by:
- ICH Q9(R1) implementation demanding formal, documented risk processes
- High-potency product proliferation requiring heightened rigor for low-ADE compounds
- Lifecycle risk management expectations beyond one-time assessments
Risk management has evolved from supporting documentation to a primary inspection target. Please do your due diligence for assessing risk in your quality systems.
Here is a link to a great article published by RAPS from the RAPS Quality Conference we attended on June 9-10 In Baltimore, Maryland. This sample from the article illuminates FDA’s increased scrutiny of Risk:
“Our inspection approach is risk-based, not only the selection model for determining who gets inspected, but also the approach itself,” said Keisha Thomas (associate director for compliance and quality at the Center for Devices and Radiological Health CDRH). She noted that element selection is based on firm-specific risks. Investigators also review pre-inspection information, such as medical device reports (MDR), recalls, and complaints, and there are no standardized sampling tables.”
Here are some guidance documents from FDA:
ICH Q9 (R1) – FDA Guidance on Quality Risk Management
Risk Based Approach for Monitoring Clinical Investigations – FDA Guidance
Email [email protected] if you would like us to send you a Sample GMP Trends Report.
Have a great weekend.
