Finessing an FDA 483, Part 2

Responding to FDA 483 observations was my focus in part 1 of this series. Responses lead to commitments, and commitments lead to changes that are intended to prevent recurrence of the underlying problem that led to the observation.

Here, I’ll share my views on getting the work done to fulfill commitments made to the FDA. The following have become benchmarks from those who are the best at getting the job done and getting the problems behind them:

Form teams
This might seem obvious, but forming cross-functional teams representing stakeholders is often overlooked. The solution will likely involve different ways of working those cross-functional lines. It’s a rookie mistake to think that the fix is something for the quality department to do on its own, or just an editorial change to a procedure. Depending on the problem, the team may need to be dedicated to the project to allow focus, particularly if accelerated timelines are involved. Include subject-matter experts who have the scientific, technical, and cGMP backgrounds to provide appropriate guidance.

Use consultants judiciously
Consultants can provide valuable additional support. They should bring relevant industry experience that can help scope the project, and give practical advice that keep the project moving toward the solution. The best consultants are good listeners who can help you design the right solution that works for you. However, if the only team members who show up to meetings are the consultants, something is terribly wrong. Do not outsource your responsibility to consultants. Let them help you, but it’s your company and you own the results.

Determine the deliverables
Many teams go off the rails because they fail to determine the tangible deliverables that address the problem. You can’t grasps the degree of effort, determine the resource needs, or estimate the timeline until there’s a clear vision of what “done” looks like. If you cannot describe that, then you don’t know the problem well enough.

Solve the problem, not just the commitment
Make a careful assessment of what it will take to prevent recurrence of the observation, not just satisfy the specific commitment. The FDA always states in its 483 notices that the observations are just examples and are not all-inclusive. Companies are expected to determine all that is necessary to permanently resolve the problem that underlies the observation wherever it applies. Perform a root cause analysis and ensure that the solutions are operational and sustainable. That invariably involves more work than the narrow view of a specific example cited in an observation or the response given.

Determine how you will know the problem is solved
In true fashion of a CAPA, determine how you will measure effectiveness. What will tell you that the solution worked? What will be your first sign that it did not work? Consider whether this is another attempt at solving the same problem. Remember that recurring observations lead to increased levels of enforcement. Be sure you know the problem is truly solved.

Avoid IT solutions
This may sound a bit strange, but in my personal experience, nearly every commitment made in a FDA 483 response that involved an IT solution missed the commitment date by light-years. I know that it shouldn’t have to be that way. I’m just saying that during my 20 years of consulting experience, that has always been the case. Consider applying an IT solution as a later improvement, not within the commitment timeline.

Use project management principles and tools
Quality system development work is not like a capital project where much of what is needed to estimate the time and cost is known upfront. Quality system and compliance projects are more often like exploratory surgery, where a lot is learned once you open it up. You may discover that multiple, linked systems are affected after you start looking more deeply. Recognize that plans will need to be adjusted along the way. Don’t confuse progressive revelation with scope creep. Be adaptable. Establish plans and reports based on the work and target dates, not subjective feel-good dashboards with perpetual dates that slip. Anticipate problems with hitting the date and mitigate them before failure is a foregone conclusion. When you see that the timeline is slipping, first consider what it will take to get back on track and then ask for help. Don’t just keep moving the target date back.

Provide infrastructure support
Remediating compliance problems often requires new ways of thinking, not just new ways of working. Compliance problems frequently go hand-in-hand with company culture problems. A progressive company that recognizes the business value of an effective quality management system also recognizes the opportunity that regulatory inspections provide to examine its culture and values. Change management coaches can help a company adapt to the changes required to support a quality and regulatory compliance culture. Recurring compliance problems are frequently a culture problem.

Provide management support
Ensure that each project team has a sponsor who is the best fit based on the functional owner of the process being remediated. Clearly identify the role of the sponsor and ensure that it includes removing obstacles such as lack of organizational alignment, stalled decisions, team dysfunction, and inadequate budget. Sponsors are the champions who are willing to delve into the team level to provide visible support, rather than sit on the management team and undermine their own folks during project update meetings. Quality system remediation provides a unique opportunity for function heads to understand dependent processes across functional lines.

Establish governance oversight
The work associated with fulfilling commitments is tightly connected to managing risk. Thus it’s important to keep site governance councils frequently updated about progress and informed about unacceptable risks. These risks would also include the risk of not meeting a commitment date made to the FDA. Other unacceptable conditions uncovered along the way should also be communicated to the governance body. Establish clear lines of communication and escalation between the team actually doing the work and governance. Learn how to escalate and resolve potential problems quickly.

Verify that deliverables solve the problem
Take an independent look to ensure the work is completed and that the tangible deliverables are in place and in use. This is a good role for an independent consultant. It’s far better to find out for yourself that the mark was missed than for the FDA to call it to your attention as a repeated observation in a Warning Letter.

Revisit commitments
Although you may have verified that the solution is in place and in use, revisit the problem after an appropriate time interval to ensure that the organization hasn’t reverted to the old ways of working.

In part 3 we’ll examine a remediation team methodology to help derive solutions that are operational and sustainable.

First published Oct. 23, 2014, on The QA Pharm.

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