An Analysis of 2015 to 2019 FDA 483 Data

What does a five year analysis of FDA 483 data show?  Are certain observations common, or does each year provide a fresh slate of never-before-seen observations?

In a follow-up analysis to the popular webinar he presented, (“Comparing and Analyzing Russian, UK, and US Top Ten Pharma Inspection Findings FY 2019”), Jerry Chapman, Senior GMP Quality Expert, Redica Systems, answers these questions and more.

To learn more about the top 10 FY2019 GMP inspection findings from FDA, UK MHRA, and Russian Federation State Institute of Drugs and Good Practices (SID&GP), watch the webinar and read the earlier blog posts:

• Comparing and Analyzing Russian, UK, and US Top Ten Pharma Inspection Findings FY 2019 (Webinar)
• Top 10 Pharma Inspection Findings from FDA, MHRA, and the Russian Drug Regulator
• Russian Drug Regulator, MHRA, and FDA Processes for Evaluating & Escalating Drug GMP Inspection Findings

[Related: Want to do your own 483 comparison?  Sign up for a complimentary 483 Observation Report.]

Are Certain 483s Common?

The FDA/PharmaLink conference presentations covered FY2019.  Chapman used 483 data from Redica Systems for longer-term trends. 

He reviewed the top 10 483s for fiscal years 2015 through 2019, first comparing FY2018 to FY2019 (Figure 1). In addition, he also provided the top 10 483s for FY2006 (Figure 2).

“In 2019, there were 779 drug GMP 483s that were issued compared to 716 in 2018,” Chapman said. “As I go through these, you’ll see that 2018 and 2019 tracked pretty well with each other. 2019 has more, but they’re really similar to each other. “

In looking closer at the specific 483s listed for each year, “you can see that the first one, 211.22(d) procedures not in writing or fully followed, appeared on roughly one out of every four of the 483s that was issued in fiscal year 2019. And then you can see the others as well, investigations of failures, scientifically sound lab controls, written procedures, cleaning, sanitizing, and maintenance of equipment…these round out the top 10.” 

When compared with 2018, the similarities are striking. 

“From year to year, there is not a lot of variation, at least in 483s,” he said.  “At least between these two years, those top five are pretty much the same. They move around a little bit from one place to another, but they are pretty much the same.”

But what about from FY2015 to FY2019, plus the FY2006 data included “just for fun?”  Chapman provided this data using a color-coded table (Figure 2).

“We see that the same top four observations are frequently observed from year to year to year over and over again,” he said.

These deficiencies are:

• Procedures not in writing or fully followed
• Investigations of discrepancies and out-of-specification results
• Validated production and process controls
• Lack of established control; while this may differ, the root CFR for these observations remains the same pretty much from year to year to year

A “Shared Responsibility” for Quality

Why are these deficiencies seen year after year by FDA investigators? In Chapman’s opinion, the issue boils down to “shared responsibility.”

By this, he referenced lack of support for the Quality Unit. 

“The regulations really give the quality unit a lot of responsibility,” he said.  “Often, I have seen within pharma organizations, it is not appropriately funded or staffed, or not always staffed with the appropriately trained and experienced people.”

He pointed to a lack of training until recently.  Often, he has seen someone from a science background move into a quality role and training occurs “via osmosis.”  Within the past year, however, Pathway for Patient Health created an undergraduate Quality minor available for science majors that is free of charge and online (https://www.pathway4ph.org/). 

The regulations really give the quality unit a lot of responsibility

Chapman also cautioned manufacturers to avoid viewing regulators as adversaries.  While cutting corners can lead to short-term gains, this will prove more costly later. 

“I can tell you by personal conversations with agency investigators that a culture of quality or lack is apparent when they do their walkthroughs of manufacturing facilities,” he said.  “It’s really a feeling of an atmosphere, and they can sense it on inspection.”

He also recommended using the Redica Systems platform as a resource on 483s. 

“The best place I think you can find 483s is at Redica Systems where we have nearly 40,000 483s responses and EIRs,” he said. “They are searchable and it is by far the largest collection in the world now.”

Other Redica Systems capabilities Chapman highlighted include functions for researching FDA investigators and the ability to find 483 data for contract manufacturing organizations. 

[Related: Want to do your own 483 comparison?  Sign up for a complimentary 483 Observation Report.]