FDA Form 483 Frequently Asked Questions

1. FDA Form 483 Frequently Asked Questions Those who are in pharmaceutical industry as well as medical device industry are familiar with term “form 483”. One this is mentioned one understands that the industry deals in products manufactured in USA or exported to USA. Why is it called 483? When FDA investigator does an audit of any facility under their purview and records the observation in one defined form which was designated as form 483 by US FDA in their internal documented system. It is like unit gives various formats numbers to be used in their documented system as per its quality system. It contains Header information, (FDA district office information, date of inspection, name and address of facility, Name and title of person to whom this form is given, brief description of the facility including facilities FEI (Facility establishment identification) number. Observation including annotations. This section is heart of the form for which this is made and may run into several pages. It starts with disclaimer stating that these are inspectional observation and does not represent a final agency determination regarding your compliance. Annotation:As of 1997, the FDA established an annotation policy for medical device inspections. The investigator(s) should offer to annotate the 483 with one or more of the following: 1. Reported corrected, not verified. 2. Corrected and verified. 3. Promised to correct (may be appended with "by xxx date" or "within xxxx days or months"). 4. Under consideration. The actual annotation of the 483 occurs during the final discussion with the firm's management; if the firm prefers no annotation, then annotation will not be performed. The annotations may be after each observation, at the end of each page, or at the bottom of the last page prior to the investigator's signatures. Signature: Investigator’s name and designation are printed. Signature will come on first and last page and if more pages are there then initial is done. On reverse side it contains addenda and amendments. If nay error is discovered by inspector after issuing 483, and if 483 is created using EIR turbo system then amendment is issued or else addendum is created. Addenda does not involve addition of This form is sent to the unit which is inspected by investigator. This also gets recorded in US FDA internal system for tracking and tracing and available to generalpublic for learning and improvement in general. (While making public non-public information’s are removed) It may be handwritten, typed or computer file like PDF file or completed FDA’s computer system Called turbo EIR. What is the purpose of issuing 483? The observation mentioned in the form notifies company management its objectionable condition and the same is to encourage that firm to act upon those observation as corrective and preventive action.

2. Is 483 is exclusive list of all possible non compliances? No, it is not. It is only list of observations investigator found during audit and firm should do thorough internal audit to verify its compliance and correct those objectionable situations which were not found during FDA audit. Firm shall also take corrective actions on those observations too. How is it shared with company? Form is not just completed and handed over at the end of inspection but it is thoroughly discussed with company management at its conclusion of inspection. Each observation is read and discussed so there is full understanding of the same. What are the implications of form 483 for agency enforcement and what happens next? Mere issuance of form 483 does not become final determination of violation of FDA F&DC act. Final document will comprise of form 483, along with written EIR (Establishment inspection report), all evidence and documentation collected at site, and any response made by company. Sum of all these information determines what action agency may take which may be appropriate to protect public health. Since they are available for public why not study them and see if your firm also has such observation. Go proactively in your internal audit and see if you can find such observations. Let us review what types of observations comes during such audits which were recorded in agencies EIR 483 reports. (FDA’s Turbo EIR) 2021 file lists: Top 3 observations 1.Procedure for Corrective and Preventive Action have not been adequately established (found in 77 sites) 2.Procedure for receiving, reviewing and evaluating complaints by formally designated unit have not been adequately established. (Found in 49 Sites) 3.Procedure to ensure that all purchased and received product and services conform to specified requirements have not been adequately established. (Found in 31 sites) If you consider 2020 list then first two observations are same in the top list chronology with frequency (1. At 165 sites and 2. At 139 sites) while third topmost observation is on MDR. For 2019 also order is same as 2021 with frequencies (1. 312, 2. 240, 3. 151) and MDR falls on 4th Written MDR procedures are not developed, maintained and implemented. Please do not mix term MDR with EU MDR. FDA MDR means medical device reporting. (Found at 68 sites) while 3rd observation of 2021 falls on 4th with frequency of 62. Form 483 compliance: Are you legally bound by 483 compliances if you do not respond to FDA then what? If the findings are serious enough or response to 483 is deficient or insufficient, FDA warning letter is likely to be issued to your firm. Warning letter is FDA’s advisory notice suggesting firm’s significant violations of FDA regulation. The letter will identify violation and firm must correct the same and inform the FDA for firm’s plan for

3. correction and preventive action plan for similar problem preventing from re-occurring. The FDA will check the same for adequacy. It is therefore advisable to respond to form 483 promptly and to warning letter and identify plan to correct the problem in FDA’s specified timeframe. Detailed action for each observation is required. The quality and promptness of your response is extremely important. If you do not have proper resource and expertise, it is advisable to hire good consultant’s services who are familiar with such activities to get your actions first time right.