Part 2: Responding to FDA483 Observations and Fulfilling Commitments

Part 2: Organizing to Get the Work Done

Responding to FDA483 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.

In Part 2, I share my views on getting the work done to fulfill the FDA commitments. The following have become benchmarks from those who are the best at getting the job done in a sustainable way 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 very likely involve creating different ways of working that cross functional lines. It is 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 allow focus, particularly if accelerated timelines are involved. Include subject-matter-experts that 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 keeps the project moving toward the solution. The best consultants are good listeners who can help you design the right solution that works for you. But, if the only team members that 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 cannot grasps the degree of effort, determine the resource needs, or estimate the timeline until there is a clear vision of what "done" looks like. If you cannot describe "done," then you do not 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 the FDA483 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 that 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 yet another attempt at solving the same old problem. Remember that recurring observations lead to increased levels of enforcement. Be sure you know the problem is truly solved.

• Avoid Information Technology (IT) Solutions. This may sound a bit strange, but in my personal experience, nearly every commitment made in a FDA483 response that involved an IT solution missed the commitment date by light-years. I know that it should not have to be that way. I'm just saying that in 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 time line if at all possible.

• 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 the patient. You may discover that multiple linking systems are affected after you start looking at the problem more deeply.  Recognize that plans will need to be adjusted along the way. Do not 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, ask for help and consider first what it will take to get back on track. Don't just keep moving the target date back as the default solution.

• Provide Infrastructure Support. Remediating compliance problems often require new ways of thinking, not just new ways of working. Compliance problems frequently go hand-in-hand with company culture problems. Progressive companies that recognize the business value of an effective Quality Management System also recognize 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 that discounts the value of an effective Quality Management System and regulatory compliance to the business. 

• 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 organization alignment, stalled decisions, team dysfunction, and inadequate budget. Sponsors are the champions who are willing to delve into the level of the working team to provide visible support, rather than sit on the management team and undermine their own folks at project update meetings. Being sponsors of quality system remediation projects 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 is important to keep site governance councils frequently updated with progress and informed about unacceptable risks. These risks always include the risk of meeting a commitment date made to the FDA. Take commitment dates seriously. 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 that actually does the work and governance. Learn how to escalate and resolve potential problems quickly. Nothing consumes the timeline as much as reluctant escalation and indecision.

• 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 is 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. Be a healthy skeptic and ask, "How do we know for sure the problem is permanently solved?"

• Revisit Commitments. Although you may have verified that the solution is in-place and in-use, revisit the problem at an appropriate time interval to ensure that the organization has not reverted to the old ways of working.

How have you managed regulatory commitments? What are your success stories? What have been epic failures, and why?

The QA Pharm