FDA’s Top 483 Observations for 2018: A Reflection of Industry’s Compliance

May 30, 2019 by James Meckstroth, Principal Compliance Consultant

Understanding industry’s compliance direction, and how this data can help evaluate the capability and key quality indicators of a quality system.

At the beginning of each federal fiscal year, the US FDA posts the previous year’s Form 483 observation metrics issued by each product center.

TABLE 1
Inspections ending between 10/1/2017 and 9/30/2018, for select product centers

Reviewing these metrics provides a valuable snapshot of industry’s compliance direction. Understanding these common issues can help highlight focal areas when evaluating potential quality management system (QMS) gaps and improvement opportunities within your company.

Summaries of the top five observation occurrences reported in Form 483s per product center are as follows:

The 2018 top 5 observations reported by the Drug sector are:

  • Procedures applicable to the quality control unit are not in writing and/or not fully followed
  • Laboratory controls are not scientifically sound and appropriate
  • Failure to thoroughly review unexplained discrepancies
  • Lack of written procedures for production and process controls
  • Written procedures are not followed for the cleaning/maintenance of equipment and utensils

The 2018 top 5 observations reported by the Devices sector are:

  • Procedures for corrective and preventative action have not been adequately established
  • Procedures for receiving, reviewing, and evaluating complaints have not been adequately established
  • Procedures to ensure that all purchased or received products/services conform to specifications have not been adequately established
  • Written MDR procedures have not been developed and/or established
  • Processes inspections and testing results have not been adequately validated

The 2018 top 5 observations reported by the Biologics sector are:

  • Written standard operating procedures were not always established or available
  • Failure to submit a biological product deviation report
  • Records are not concurrently maintained with the performance and traceability of each significant step
  • Failure to submit a biological product deviation report within 45 days
  • Failure to use supplies and reagents in a manner consistent with instructions provided by the manufacturer

The 2018 top 5 observations reported by the Veterinary sector are:

  • Treatment records were not maintained
  • Causing a residue of an approved human or animal drug above an established safe level
  • Causing an illegal residue in a food-producing animal of an approved human or animal drug
  • A prohibited drug or substance was administered in an extralabel manner to a food-producing animal
  • Lack an adequate inventory system for quantities of drugs used to medicate livestock

Focusing on the Drug Sector, the top five observations reported by FDA over the last three years are as follows:

TABLE 2

This data shows that the FDA is encountering the same issues year-over-year with the exception of the fifth place observation in 2016. As an industry, we should be prepared for FDA’s increased focus on these recurring themes.

I find that a good starting point for risk reduction is understanding industry’s trouble areas. One way to approach this is by taking a closer look at the governing quality systems that cover the top ranking observations. For instance, review the thoroughness of your site’s training program and simplify complex or confusing SOPs to help avoid a “procedures not followed” observation. To prevent observations relating to “inadequate investigations”, look to Root Cause Analysis procedures for possible gaps. Monitoring the status of your site’s QMS and reacting to reported quality metrics helps to avoid these common observations and facilitates continuous improvements. Has a holistic gap assessment recently been performed on your firm’s QMS? Are your operations susceptible to these common findings?

Evaluating another aspect of the data, nearly 2,000 Form 483s were issued by FDA’s Office of Regulatory Affairs in 2018 across the following four FDA regulated industries, Drug, Device, Biologics, and Veterinary.  As seen in the graphs below, the total number of Form 483’s issued by inspectors hasn’t changed drastically across the sectors in the past five years, neither has the average number of observations cited per each 483 issued.

TABLE 3

What do these observation numbers suggest, what can we learn from this data, is your site at risk for one of these observations? As an industry what can be done to help avoid receiving one of these common observations? Is industry compliance not improving?

To fully answer these questions and measure industry’s overall compliance health, one needs to know the total number of inspections performed for each sector. Are there now fewer inspections and a higher rate of 483s issued or more inspections and a lower rate of 483s issued? Is industry improving quality but inspectors applying more scrutiny?

While the regulations haven’t changed drastically in recent years, the compliance expectation is ever increasing. FDA utilizes computerized applications that allow inspections to be more risk-based and better focus inspections on industry trends, guiding inspectors towards common noncompliance areas within industry quality systems. The trend shows not following procedures, inadequate record handling, and inadequate investigations and CAPA assignment are frequent themes in industry.

I like to keep common industry pitfalls in mind when evaluating the capability and key quality indicators of a quality system, this helps me determine whether a site has a good handle on their quality system and that its state of control is maintained throughout product lifecycle. This allows me to gauge how effectively the facility manages risks or how capably the facility can react to unforeseen issues. This approach helps me direct the quality system towards improvement and increased compliance.

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