FDA Inspections

I am often asked how best to prepare for an FDA inspection when you know that you have problems. My first response is that they have already taken the first step: acknowledging that there are problems. Believe me. That is a huge first step. Just like AA’s 12 step program, it’s not until you are willing to admit this aloud that you are on the road to recovery. But just knowing that problems exist is not enough to survive an FDA inspection.

Here are the various positions that firms find themselves when the FDA comes knocking. You can decide which of these scenarios is the best possible position.

1.We know what our problems were, but they have been resolved.

Let’s say an FDA investigator stumbled upon a manufacturing work order system that allowed changes to production equipment without a review by QA on the impact on the state of validation. The best position to be in is to say that you were made aware of the problem; the system has been revised and employees trained; a retrospective review of maintenance work orders was conducted for product impact and appropriate action taken.

It engenders confidence when an inspector can see evidence that a problem has been resolved and a product impact analysis has been performed. It portrays the firm as being responsive to self-detected problems as a normal course of business.

2.We know what our problems are; we have a comprehensive plan; we are executing the plan on schedule.

A common strategy for firms that anticipate a Warning Letter or a Consent Decree is to have a third party conduct a thorough systemic audit and to develop a comprehensive corrective action plan. It’s a way of saying to the FDA, “You can’t force us do anything that we aren’t already forcing ourselves do.” The plan is in writing, deliverables defined, reasonable target dates are established, responsibilities assigned, and management is tracking accomplishments versus the plan.

It can diffuse an otherwise nasty inspection when management demonstrates that it is taking the initiative to deeply understand its state of compliance and holding itself responsible for timely results. The FDA inspector may still give you observations, but the Establishment Inspection Report (EIR) will note the initiative you have taken. Also, the FDA may quibble over the scope of the plan, or the timetable for completion, but it is far better to have the plan be the center of discussion than inaction.

3.We know what our problems are; we have a plan.

The difference between this position and the one above is the failure to execute according to the schedule provided in the comprehensive corrective action plan. In my opinion, failure to execute is one of the most significant issues that separate the wheat from the chaff. Some companies just cannot get out of their own way to accomplish meaningful change. Administration substitutes for real work; team meetings substitute for personal accountability; and production schedules take priority over executing the comprehensive compliance plan. Something else always is more important—there is no discipline, no organization alignment, and no leadership.

It becomes evident during an FDA inspection that it is all talk and no action. FDA cites repeated observations from previous inspections. With FDA on record that there will be no multiple Warning Letters, this places you in the crosshairs of increased enforcement action.

4.We know what our problems are; we have no plan.

This is perhaps the most dangerous position to be in. Consciously not taking action when there are known problems is irresponsible. When faced with an issue during an inspection, you are either forced to say that you were not aware of the problem, or that you were aware of the problem and have not taken action. Neither response is very pretty. One of those responses is a falsehood.

This signals to the FDA inspector that CGMP compliance is not considered to be important to the firm, and that the dots have not been connected between regulatory compliance and patient safety. To be clear, management is personally legally liable for knowing its problems and resolving them. This is a real slippery slope.

5.We don’t know what our problems are.

What problems? This describes companies that rely on FDA inspections to tell them what the problems are, and the firm is always aghast to learn about the problems and ready to call someone on the carpet. This describes management that thinks an FDA483 with five observations is an improvement over the previous one with ten. This also describes the company that does not have established processes to take responsibility for the effectiveness of the quality management system such as: management review of quality system performance metrics, internal compliance audits—or just generally thinking that it is someone else’s job to worry about it.

You would be surprised at the number of senior management who can’t even tell you what their top five problems are. FDA calls this “inspecting into compliance,” and they have very little patience for this unenlightened perspective. These are the bottom feeders in our industry.