10 Steps to Effective FDA 483 Responses: Medical Devices

According to its Foreword, the Investigations Operations Manual (IOM) is the primary operational guide for FDA employees who perform field investigational activities in support of the agency's public health mission. As defined in the IOM, “An establishment inspection is a careful, critical, official examination of a facility to determine its compliance with certain laws and regulations administered by FDA.”¹

If, during an establishment inspection, an investigator identifies what (in his or her judgment) are believed to be objectionable conditions, these conditions will be communicated to the organization during the inspection and at the conclusion of the inspection via discussions and issuance of an FDA 483 List of Inspectional Observations.² The FDA 483 observations are, in the investigator’s judgment, potential violations of a regulatory or statutory requirement, as discussed in Section 5.2.3 of the IOM³. The investigator’s observations will also be documented within the Establishment Inspection Report (EIR) representing the inspection for review by FDA management and potentially an FDA compliance officer. FDA investigators will not typically advise a manufacturer with respect to corrections and corrective actions relative to FDA 483 observations raised during an establishment inspection.

The issuance of an FDA 483 is not an FDA enforcement action. However, if the FDA 483 observation reflects a “major deficiency” as defined in CP 7382.845 Inspection of Medical Device Manufacturers, Part V A.1.a⁴, an FDA official action may be taken. Major deficiencies relative to 21 CFR Part 820, the Quality System Regulation include (but are not limited to) absence of corrective and preventive action procedures (including procedures describing the analysis of quality data), absence of design control procedures (including design change control procedures, where required), failure to validate processes requiring validation, non-correction or inadequate correction of major deficiencies from previous inspections, and other quality system deficiencies such as deficiencies in both purchasing controls and acceptance activities. Official actions available to FDA include advisory actions (e.g., Untitled Letters and Warning Letters), administrative actions (e.g., administrative detention of devices, civil money penalties) and judicial actions (e.g., mandated recall, seizure of devices, injunction, criminal prosecution).⁵

According to its “Review of Post-Inspection Responses” policy described in FR Vol. 74, No. 153 (Docket No. FDA-2009-N-0335)⁶, if FDA receives a response to the FDA 483 observations within fifteen (15) business days, a “detailed review” of the response will be conducted prior to a decision to issue a Warning Letter. Elements of initial responses may be plans to conduct activities with a timeline and a promise to provide additional responses as activities progress, and these plans should be supported with objective evidence (e.g., corrective action procedures to be followed, risk management procedures to be followed, failure investigation procedures to be followed, results of the implementation of these procedures to date).

The chart below summarizes ten steps to creating effective FDA 483 responses.

Initial response must be submitted within fifteen (15) business days.
(Refer to policy in link below)
FR-2009-08-11.pdf (govinfo.gov)

A timely, well-thought out, thorough and organized response to medical device FDA 483 observations supported with objective evidence may be the difference between your organization receiving a Warning Letter or not receiving a Warning Letter.

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Sources

¹ FDA, Investigations Operations Manual, Section 5.1.2, available at www.fda.gov/media/76769/download (2020).

² FDA, Form 483 Frequently Asked Questions (9 Jan. 2020), available at www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-references/fda-form-483-frequently-asked-questions.

³ FDA, Investigations Operations Manual, Chapter 5, Section 5.2.3, available at www.fda.gov/media/113432/download (2020).

⁴ CP 7382.845 Inspection of Medical Device Manufacturers, Part V A.1.a, available at www.fda.gov/media/80195/download

⁵ FDA, Compliance Program Guidance Manual, Program 7382.845, Section V.A.1.a, available at www.fda.gov/media/80195/download (2 Feb. 2011).

⁶ FR Vol. 74, No. 153 (Docket No. FDA-2009-N-0335), available at www.govinfo.gov/content/pkg/FR-2009-08-11/pdf/FR-2009-08-11.pdf