Regulatory Open Forum

When an FDA-regulated firm receives a Form FDA 483 containing inspectional Observations citing objectionable conditions, it is crucial that the firm formulate a proper corrective action plan and implement it faithfully. If thereafter the firm doesn't implement the actions as planned and fails to properly manage the deviation, then there could be a variety of consequences.  As other respondents have noted, it's not possible to effectively characterize such consequences without knowing more details about the particular case.  Yet some general rules and principles are given herein that will usually serve the needs of most scenarios.

First, remember that FDA's general preference and operating procedure is to give individuals and firms an opportunity to take voluntary and prompt corrective action before the agency escalates to formal enforcement action. There are of course certain caveats to this general rule.  Most notably, such enforcement discretion must be consistent with the nature of the violation(s) and the agency's public protection responsibilities (i.e., guarding against danger to health and against intentional, gross or flagrant violations).  In order words, if a firm's 483 Observations are numerous, significant, and/or indicate a high risk to public interests, then such factors can lead to escalation for more official or formal actions.  Also noteworthy is that before taking enforcement action, FDA is under no legal obligation to warn individuals or firms that they or their products are in violation of the law, except in certain scenarios.  But in over two decades of resolving hundreds of Form FDA 483 Observations and Warning Letters, my experience has almost always been that firms large and small can qualify for such enforcement discretion if they approach the agency with the proper attitude, tone, and narrative.  In contrast, there are of course the famous major FDA enforcement actions we see from time to time where large multi-national firms are subjected to consent decrees or other FDA enforcement actions; but I believe those are the exception, not the norm.

It is costly and burdensome for FDA to initiate formal enforcement actions like mandatory recalls, seizures, injunctions, administrative detention, civil money penalties and/or criminal prosecutions. Accordingly, FDA uses a graduated process of escalation in hopes of realizing the aforesaid voluntary compliance and alleviating the need for enforcement action.  The FDA's first step is often that which we've already mentioned: the Form FDA 483. Even at this preliminary advisory level, FDA already starts giving an opportunity for the firm to voluntarily comply.  For example, FDA Investigators are trained to advise the 483 recipients that their firm's response may impact FDA's determination of the need for follow-up action if FDA receives an adequate response to the FDA 483 within 15 business days of the end date of the inspection.  Note that an "adequate response" doesn't necessary mean fully-implemented corrective actions.  This can (and most often does) mean a properly-constructed corrective action plan written commensurate with risk and including the firm's projected schedule for completion of the planned actions.  This also can warrant, especially for more significant 483s, a commitment and schedule for written progress reports to be submitted to FDA.   Every 483 recipient regardless of its size, or the nature or number of 483 Observations, should make these tactics standard operating procedure after receiving an FDA 483.

Sometimes a firm will deviate from the FDA 483 corrective plan, either by revising the action plan itself, or because the projected schedule was not met. In either case, it is most advisable to promptly provide FDA a written explanation of the deviations and, as appropriate, a revised plan.  While such transparent gestures may be frightening for many firms, it will most often pay big compliance-dividends; remember that FDA by procedure prefers voluntary compliance.

For example, last year I completed a 483-remediation effort that, for various reasons, needed an additional year of time beyond what was originally planned. But because we kept open lines of communication with the Compliance Officer, and because we showed at least some evidence of ongoing progress, we were allowed to complete the revised plan without further FDA enforcement actions.  As astute readers may note, the fact that there was a "Compliance Officer" involved means that the particular case had in fact already experienced a measure of escalation where the case had been transferred from FDA's standard inspection management personnel to those who handle troublesome inspections.  Yet the firm still (via a corrected attitude, tone, and narrative) subsequently enjoyed FDA enforcement discretion even after deviating from the original plan.  As mentioned before, there will be some scenarios that won't qualify for this kind of FDA enforcement discretion, so each case must be carefully assessed on its own merits.  But it still remains that FDA's general standard operating procedure is to prefer voluntary compliance.  Indeed, a basic tenet of FDA's enforcement policy "…is the belief that the majority of persons will voluntarily comply with the law when given information as to what is required, what violations appear to exist, and, in the case of violations of regulatory significance, that failure to comply may result in the initiation of enforcement action…"

Now if (due to delays, changes, general inadequacy, etc.) a firm's 483-response fails to measure up with FDA's expectations, then FDA can change the case's classification from "VAI" (Voluntary Action Indicated) to "OAI" (Official Action Indicated) and/or otherwise escalate the case (as in the aforementioned scenario). Often, such OAI takes the form of a "Warning Letter".  Other actions include "Untitled Letters" and/or Regulatory Meetings.  Each case must be considered on its own merit, but generally speaking, FDA will use a Warning Letter for matters of "regulatory significance".  Failure to submit Medical Device Reports is an example of a violation with regulatory significance.  As another example, a few years back I was called into an FDA inspection resulting in a significant 483 and involving the apparent initiation of FDA administrative detention of the firm's products.  Thereafter, the client chose not to adhere to the promised 483 action plan schedule and it elected not to promptly provide FDA with a written explanation of the deviation.  A Warning Letter was issued shortly after missing a promised progress-reporting milestone.  This shows the importance of maintaining transparent lines of communication with the agency, especially if the firm deviates from promises made.  And for firms afraid to make any promises to FDA, I refer you to the aforementioned 15-day response policy.

Though "Official Action Indicated" may sound terrifying, and despite their infamous reputation, Warning Letters are still just informal advisory actions. Though still "official", they do not rise to the level of an enforcement action.  Indeed, by procedure, FDA issues Warning Letters to achieve voluntary compliance and to establish "prior notice" (i.e., to establish that responsible individuals continued violating the law despite having been warned by the agency) before initiation of enforcement action.  In fact, FDA says that Warning Letters are the principal means by which the agency provides prior notice of violations and of achieving voluntary compliance.  So yet again, even at the "official" Warning Letter level, FDA is still seeking voluntary compliance to avoid formal enforcement actions.  Therefore, if a firm receives a Warning Letter, then the appropriate action is to, within the timeframe given in the Warning Letter (usually fifteen business days), prepare and submit a properly constructed corrective action plan written commensurate with risk and including the firm's projected schedule for completion of the planned actions and written progress reports.   Every Warning Letter recipient regardless of its size, or the nature or number of Warning Letter citations, should make these tactics standard operating procedure after receiving a Warning Letter.

Upon receipt of a firm's response to a Warning Letter, FDA will evaluate the response. If the response is inadequate, or if no response is received, FDA will begin follow-up action as necessary to achieve compliance. Such additional actions include but are not limited to, judicial enforcement actions like seizures, injunctions, inspection warrants, search warrants, prosecution, and civil penalties. Yet even in these situations, FDA may still first employ a last-ditch mechanism to avoid such actions.  For example, FDA's "Section 305 Notice" where a person against whom a criminal proceeding is contemplated is first given appropriate notice and opportunity to either orally or in writing present his/her views (via a Section 305 meeting) before criminal prosecution is recommended to a U.S. Attorney with regard to such contemplated proceeding.

Time and time again I've proven the merits of being transparent and cooperative with the FDA. But I'm not advising anyone to be push-overs either, as time and again I've also successfully pushed back on FDA positions when I had proper statutory and regulatory grounds.  In the end, those experiences have resulted in superior compliance outcomes and also caused me to have more of a sense of trust rather than distrust of the agency when working through the dynamics of resolving Form FDA 483s, Warning Letters, and Untitled Letters.

When an FDA-regulated firm receives a Form FDA 483 containing inspectional Observations citing objectionable conditions, it is crucial that the firm formulate a proper corrective action plan and implement it faithfully. If thereafter the firm doesn't implement the actions as planned and fails to properly manage the deviation, then there could be a variety of consequences.  As other respondents have noted, it's not possible to effectively characterize such consequences without knowing more details about the particular case.  Yet some general rules and principles are given herein that will usually serve the needs of most scenarios.

First, remember that FDA's general preference and operating procedure is to give individuals and firms an opportunity to take voluntary and prompt corrective action before the agency escalates to formal enforcement action. There are of course certain caveats to this general rule.  Most notably, such enforcement discretion must be consistent with the nature of the violation(s) and the agency's public protection responsibilities (i.e., guarding against danger to health and against intentional, gross or flagrant violations).  In order words, if a firm's 483 Observations are numerous, significant, and/or indicate a high risk to public interests, then such factors can lead to escalation for more official or formal actions.  Also noteworthy is that before taking enforcement action, FDA is under no legal obligation to warn individuals or firms that they or their products are in violation of the law, except in certain scenarios.  But in over two decades of resolving hundreds of Form FDA 483 Observations and Warning Letters, my experience has almost always been that firms large and small can qualify for such enforcement discretion if they approach the agency with the proper attitude, tone, and narrative.  In contrast, there are of course the famous major FDA enforcement actions we see from time to time where large multi-national firms are subjected to consent decrees or other FDA enforcement actions; but I believe those are the exception, not the norm.

It is costly and burdensome for FDA to initiate formal enforcement actions like mandatory recalls, seizures, injunctions, administrative detention, civil money penalties and/or criminal prosecutions. Accordingly, FDA uses a graduated process of escalation in hopes of realizing the aforesaid voluntary compliance and alleviating the need for enforcement action.  The FDA's first step is often that which we've already mentioned: the Form FDA 483. Even at this preliminary advisory level, FDA already starts giving an opportunity for the firm to voluntarily comply.  For example, FDA Investigators are trained to advise the 483 recipients that their firm's response may impact FDA's determination of the need for follow-up action if FDA receives an adequate response to the FDA 483 within 15 business days of the end date of the inspection.  Note that an "adequate response" doesn't necessary mean fully-implemented corrective actions.  This can (and most often does) mean a properly-constructed corrective action plan written commensurate with risk and including the firm's projected schedule for completion of the planned actions.  This also can warrant, especially for more significant 483s, a commitment and schedule for written progress reports to be submitted to FDA.   Every 483 recipient regardless of its size, or the nature or number of 483 Observations, should make these tactics standard operating procedure after receiving an FDA 483.

Sometimes a firm will deviate from the FDA 483 corrective plan, either by revising the action plan itself, or because the projected schedule was not met. In either case, it is most advisable to promptly provide FDA a written explanation of the deviations and, as appropriate, a revised plan.  While such transparent gestures may be frightening for many firms, it will most often pay big compliance-dividends; remember that FDA by procedure prefers voluntary compliance.

For example, last year I completed a 483-remediation effort that, for various reasons, needed an additional year of time beyond what was originally planned. But because we kept open lines of communication with the Compliance Officer, and because we showed at least some evidence of ongoing progress, we were allowed to complete the revised plan without further FDA enforcement actions.  As astute readers may note, the fact that there was a "Compliance Officer" involved means that the particular case had in fact already experienced a measure of escalation where the case had been transferred from FDA's standard inspection management personnel to those who handle troublesome inspections.  Yet the firm still (via a corrected attitude, tone, and narrative) subsequently enjoyed FDA enforcement discretion even after deviating from the original plan.  As mentioned before, there will be some scenarios that won't qualify for this kind of FDA enforcement discretion, so each case must be carefully assessed on its own merits.  But it still remains that FDA's general standard operating procedure is to prefer voluntary compliance.  Indeed, a basic tenet of FDA's enforcement policy "…is the belief that the majority of persons will voluntarily comply with the law when given information as to what is required, what violations appear to exist, and, in the case of violations of regulatory significance, that failure to comply may result in the initiation of enforcement action…"

Now if (due to delays, changes, general inadequacy, etc.) a firm's 483-response fails to measure up with FDA's expectations, then FDA can change the case's classification from "VAI" (Voluntary Action Indicated) to "OAI" (Official Action Indicated) and/or otherwise escalate the case (as in the aforementioned scenario). Often, such OAI takes the form of a "Warning Letter".  Other actions include "Untitled Letters" and/or Regulatory Meetings.  Each case must be considered on its own merit, but generally speaking, FDA will use a Warning Letter for matters of "regulatory significance".  Failure to submit Medical Device Reports is an example of a violation with regulatory significance.  As another example, a few years back I was called into an FDA inspection resulting in a significant 483 and involving the apparent initiation of FDA administrative detention of the firm's products.  Thereafter, the client chose not to adhere to the promised 483 action plan schedule and it elected not to promptly provide FDA with a written explanation of the deviation.  A Warning Letter was issued shortly after missing a promised progress-reporting milestone.  This shows the importance of maintaining transparent lines of communication with the agency, especially if the firm deviates from promises made.  And for firms afraid to make any promises to FDA, I refer you to the aforementioned 15-day response policy.

Though "Official Action Indicated" may sound terrifying, and despite their infamous reputation, Warning Letters are still just informal advisory actions. Though still "official", they do not rise to the level of an enforcement action.  Indeed, by procedure, FDA issues Warning Letters to achieve voluntary compliance and to establish "prior notice" (i.e., to establish that responsible individuals continued violating the law despite having been warned by the agency) before initiation of enforcement action.  In fact, FDA says that Warning Letters are the principal means by which the agency provides prior notice of violations and of achieving voluntary compliance.  So yet again, even at the "official" Warning Letter level, FDA is still seeking voluntary compliance to avoid formal enforcement actions.  Therefore, if a firm receives a Warning Letter, then the appropriate action is to, within the timeframe given in the Warning Letter (usually fifteen business days), prepare and submit a properly constructed corrective action plan written commensurate with risk and including the firm's projected schedule for completion of the planned actions and written progress reports.   Every Warning Letter recipient regardless of its size, or the nature or number of Warning Letter citations, should make these tactics standard operating procedure after receiving a Warning Letter.

Upon receipt of a firm's response to a Warning Letter, FDA will evaluate the response. If the response is inadequate, or if no response is received, FDA will begin follow-up action as necessary to achieve compliance. Such additional actions include but are not limited to, judicial enforcement actions like seizures, injunctions, inspection warrants, search warrants, prosecution, and civil penalties. Yet even in these situations, FDA may still first employ a last-ditch mechanism to avoid such actions.  For example, FDA's "Section 305 Notice" where a person against whom a criminal proceeding is contemplated is first given appropriate notice and opportunity to either orally or in writing present his/her views (via a Section 305 meeting) before criminal prosecution is recommended to a U.S. Attorney with regard to such contemplated proceeding.

Time and time again I've proven the merits of being transparent and cooperative with the FDA. But I'm not advising anyone to be push-overs either, as time and again I've also successfully pushed back on FDA positions when I had proper statutory and regulatory grounds.  In the end, those experiences have resulted in superior compliance outcomes and also caused me to have more of a sense of trust rather than distrust of the agency when working through the dynamics of resolving Form FDA 483s, Warning Letters, and Untitled Letters.