USFDA Top 10 Observations (Form 483) trend of last 8 years for Pharmaceutical Industries

BACKGROUND:

This short review summarizes analysis and trending on top 10 inspectional observations called FORM -483 issued by US-FDA on the close-out of an inspection program at a firm (categorized as top 10 observations), the analysis of 483s follows for the last 8 years from 2014 through 2022. Data analysis is done based on US-FDA open access data available at US-FDA website on inspectional observations, data is organized and analyzed to see the trending in the last 8 years have been in various CFR codes, the intent is to share crisp analysis with pharmaceutical professionals to explore, learn from an external environmental analysis and improve the compliance-health state of QS through deepen the level of analysis on the internal Quality system.

No of inspections performed by USFDA in last 8 years (2014-2022) Drug Category:

Trending reveals that the number of inspections performed in the drug category was 5% increase from 2014 to 2015 and then remains almost constant next 3 years (until 2017). A marginal increase of 3%, 5% are seen in the year 2018 & 2019 respectively, a significant decline around 54% is clearly apparent owing to the Covid-19 pandemic started from early 2020 and continued in 2021. The recovery trend is seen in 2022 as number of inspections in 2022 is 216% in comparison to 2021 and seems next year/FY-23 will be normal back to normal as the pre-pandemic period and more inspections are expected in FY-23.

Description of top-10 deficiencies listed in descending order is tabled below, issued in the year-2022:

Summarized- Analysis and learning:

1. Recent past inspection data for last two years -2021 & 2022 shows an increase in the rate of observations, indicating 30-40% rise in the rate of observations per audit w r t these category, rate of observations per audit in top 10 categories was ranging 1.2 to 1.4, however an upward shift to 1.7 & 1.5 observations per audit is apparent in last?2 years,
2. Overall review shows, the top 4 category of observations remains consistent to be at top 4 nos shows non-compliance in QS – Procedures, QU responsibility & lab controls, indicating Quality system & Lab controls are the two areas being in focus in almost every regulatory inspection.
3. While QC/lab controls QS – procedures are the two key areas to focus on during the regulatory inspections, overall trending shows the key area's industry and professionals should focus on to ensure compliance with:

• Procedures not followed in full or deviation from written SOPs
• Lack of rigour in the investigation process or deficient investigations
• Lack of sound scientific lab controls, OOS, inadequate investigations/RCA
• Absence of required procedures /QU is unable to exercise their responsibility
• Control over the computerized system, audit trials /DI concern
• Inadequate Equipment or facility design and or maintenance issues
• Lack of Process controls, PPQ, PV and CV, contamination and cross-contamination

Open access database to 483s inspectional observations or WLs available at USFDA website provides an opportunity for the pharmaceutical industry and professionals to understand the trend in the external environment on form 483/observations pertaining to pharmaceutical - category-specific, like drugs, medical devices, foods, biologics etc.

In fact -operations specific observations immensely help to improve the quality & compliance-health state of quality systems of a pharmaceutical firm by ensuring compliance with regulatory standards all the time, reduce down failures, recycles. NCs and build internal capability in teams through quality culture performance through which the goal of pharmaceutical professional is achieved, i.e to provide access to safe and quality medicines to each & every deserving consumer across the globe.