M-10: Trend Analysis of the Top 20 Most Frequently Issued Form 483’s by the Food and Drug Association (FDA) From 2006 to 2016.
Rutgers, The State University of New Jersey United States
The objective of the study is to analyze the most frequent trends for FDA Form 483 citations from 2006-2016 to further comprehend the process for FDA site inspections and regulatory requirements.
The top 20 issued drug-related Form 483’s was specified from the FDA inspection observation database from 2006-2016. Trends were measured based on frequency of the form 483’s that recurred within the top 20 each year and the top 20 most frequent citations of 2006 and 2016 respectively.
The preliminary results of the trend analysis indicate that 13 out of the top 20 citations remain consistently the same within the top 20 from 2006-2016. The most frequent citation the FDA issued each year was regarding procedures of the quality control unit that were not fully followed or in writing. Additionally, some other common citations were regarding control procedures, unexplained discrepancies, laboratory controls, absence of written procedures, standard of procedures, testing and release of distribution, training operations, failure to follow written procedures, cleaning sanitation, written records, failure of routine inspections, and equipment design. Citations related to batch production, written stability program, analysis reports from component suppliers, no written records, and review of representative number of batches decreased from 2006-2016. Citations related to environmental monitoring systems, procedures for sterile drug products, aseptic cleaning systems, computer control master formula records, observation of master formula records, and validation lacking for sterile drug products increased from 2006-2016.
Understanding the common citations that the FDA issues on a year by year basis can help companies understand areas of improvement in terms of inspection readiness. It is critical to know what citations had a higher prevalence in recent years and citations that had a general decrease in prevalence. When the FDA issues a 483, a corrective action plan must be drafted, approved, and implemented by the company which is time consuming and expensive. Therefore, knowing which citations are issued frequently on a year to year basis can strengthen their regulatory compliance appropriately and efficiently prior to FDA inspection. If the 483’s are not responded to thoroughly, a warning letter may be issued signifying a violation of regulatory significance. Some consequences of warning letter include, enforcement action may be filed by Department of Justice, contracts with the government might be halted, and company reputation may be tarnished. Therefore, understanding the general trend of Form 483’s issued by the FDA can help companies become more proactive in their inspection readiness.