USFDA-Top 10 -483/Inspectional Observations trend of last 9 years - Analysis & Learnings for Pharmaceutical Industries

BACKGROUND

This short review summarizes an 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 last 7 years from 2016 through 2022.

Data analysis is done based on US-FDA open access data is available at US-FDA website on inspectional observations, data is organized and analyzed to see the trending in last 9 years have been in various CFR code, the intent is to share crisp analysis with pharmaceutical professionals to analyze, learn from external environmental analysis and improve compliance-health state of QS through deepen level of analysis on internal Quality system and its sub-systems!

No of inspections performed by USFDA in last 9 years (2014-2022)- Drug Category:

Trending reveals that, number of inspections performed in drug category was 5% increase from 2014 to 2015 and then remains almost constant next 3 years (until 2017).

Marginal increase of 3%, 5% are seen in the year 2018 & 2019 respectively, a significant decline around 54% is clearly apparent owing to Covid-19 pandemic started from early 2020 and continued in 2021.

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 pre-pandemic period and more inspections are expected in FY-23.?

AN ANALYSIS TREND ON 483’S ISSUED IN LAST 9 YEARS (2014-2022):?

Key Review - Comments on last 9 Years 483- Trending

§?Trending on number of deficiencies recorded during the year 2022 in comparison to 2021 were higher around 200%.

§?Though increase in number of deficiencies is relative to the decrease in number of inspections, this is found to be in-line with number of inspections as number of inspections in 2021 were around 46% in comparison to 2022, and major reason is pandemic effect.

§?Procedures not in writing and/or not fully followed as per 21 CFR 211.22(d) remains to be one of the topmost deficiencies in last 9 years consistently, remains to be on top in last 9 years with 1412 cumulative numbers.

§?Ref. CFR No: 21 CFR 211.192, cited deficiency on Investigations of discrepancies, failures or inadequacy in investigation process remains to be 2nd top-most deficiency in 2022, and this is most area of focus remains to be in 2nd position as cumulative deficiencies in last 9 years, counting 950 observations.

§?Ref. 21 CFR 211.160(b), deficiency on Scientifically sound laboratory controls remains to be on 3rd most recorded observation as per cumulative numbers in last 9 years, however 3rd number is surpassed by 21 CFR 211.100(a), Absence of Written Procedures being the third most cited deficiencies in last two years in 2021 & 2022.

§?An upward shift in Obs category- “21 CFR 211.63, Equipment Design, Size and Location” is seen to move on to 5th nos against cumulative 10th position as per history of last 9 year , this indicates that facility and equipment design – production area is an emerging area of focus during the inspection.

§?Similarly, an upward movement in Obs no – “21 CFR 211.68(b), Computer control of master formula records” is apparent, as it is placed on 6th nos against the 9th position per cumulative trending of last 9 years observations. This indicates that, computerized system, it’s audit trials review and importantly DI controls are an area to focus on.?

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

Summarized- Analysis and learning:

§?Recent past inspection data of last two years -2021 & 2022 shows an increased in rate of observations, indicating 30-40% rise in rate of observations per audit w r t these category, rate of observations per audit in top 10 category 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,

§?Overall review shows, 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 each regulatory inspection.

§?While QC/lab controls QS – procedures are the two key areas to focus on during the regulatory inspections, overall trending shows the key areas industry and professional should focus to ensure compliance with: ??

-???????Procedures not followed in full or deviation from written SOPs

-???????Lack of rigor in 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 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 data base to 483s inspectional observations or WLs available at USFDA website provides an opportunity to pharmaceutical industry and professional to understand the trend in external environment on form 483/observations pertaining to pharmaceutical - category specific, like drugs, medical device, foods, biologics etc.

In fact -operations specific observations immensely help to improve quality & compliance-health state of quality systems of a pharmaceutical firm by ensuring compliance to regulatory standards all the time, reduce down the failures, recycles. NCs and build internal capability in teams through quality culture performance through which goal of pharmaceutical professional is achieved, i.e to provide access to safe and quality medicines to each & every deserving consumer across the globe, in-fact is not a privilege but right of every-consumer/patients!!?!!?