Maintaining pharmaceutical manufacturing facilities (Part 4): Creating an action plan

October 22, 2019 Doyle Johnson

You’ve been hit with negative findings from a regulatory inspection or audit. Now what?

 

In previous blogs, we covered the ideal amount of maintenance, some of the ways to put the brakes on obsolescence, and the proper procedures for keeping things clean. In our final blog, we will discuss how to create an action plan to address problems surfaced during an audit or regulatory inspection.

Effectively addressing these problems will enhance your organization’s reputation and shareholder value. We will use the example of FDA 483 observations, but any regulatory authority or customer audit finding could apply here. At the end of an FDA inspection, the FDA team will review its Form 483 findings with you. You will be provided with a written copy of these findings and are expected to reply with your Corrective and Preventive Action (CAPA) plan within 15 business days.

Some of the CAPAs may be procedural, but there may be some that are capital projects. Oftentimes, your regulatory affairs group will coordinate a series of response meetings with all stakeholders over the 15-day period to review the observations and formulate the responses. The capital projects on the list will present challenges to your organization that are different, such as:

  • The stakeholders are not as usual, as they probably include regulatory affairs, legal, executives, and others that do not normally participate in capital project scoping exercises.
  • You only have 15 days to respond, and the response needs to state what you are going to do to address the issues and when you are going to do it. The deadline you set to complete the project is extremely important as it is legally binding. You need to show the FDA that you are committed to address the issues in a timely manner. Unfortunately, some stakeholders may want to set—at least what you think are—unrealistic deadlines to demonstrate that urgency.
  • It may be difficult to achieve a consensus as to how to exactly fix these issues. The quality assurance (QA) team may have one idea, but engineering may have another. The legal department may want to phrase the commitment as imprecisely as possible. Communications can be difficult with the great variety of technical backgrounds in the room.
  • You don’t know what the costs will be and there is not usually enough time to do a good quality cost estimate. This is particularly challenging during projects undertaken in old plants, as they carry many more cost risks than projects in newer, better-documented plants. There is no budget in place since these issues were unplanned, but fortunately in these cases the budget is not as important as the quality of the result and the timing. If possible, ignore costs until after the response is sent.
  • Your organization may be experiencing reduced morale, as these “defects” can put stress on a team and the broader company reputation. Let’s face it, the meetings can be tense!

 

It may be difficult to achieve a consensus as to how to exactly fix these issues. The quality assurance (QA) team may have one idea, but engineering may have another.

 

Now create a plan of action

The morale issue is best addressed by considering the findings as an opportunity, rather than a problem. The plant may have experienced underinvestment for years, and this is a chance to correct that. The findings offer the political clout that may have been missing before. For the remaining items, I suggest that the agenda for these response meetings be divided into at least two separate sessions:

  1. Decide on the scope for each corrective action. You must determine the root cause for each observation. Some observations may require that you investigate whether the same type of problem occurs in multiple places, not just the location of the observation. You need to define the scope that completely addresses the root cause before you can determine how long it will take to correct. End the meeting at this point to allow for time to study the scope outside the meeting.
  2. Determine the time needed to complete each corrective action and be sure to allow extra time for contingencies. You will need to consider if your staff can manage multiple concurrent projects—along with their usual responsibilities—or if you need to bring in outside help. Remember that the time commitment to complete each CAPA is legally binding, so plan accordingly.

 

The morale issue is best addressed by considering the findings as an opportunity, rather than a problem. 

 

For many CAPAs, the amount of work to be done may be much larger than on-site staff can typically undertake. Since they are frequently called to emergencies in the plant, they can also understandably become distracted from advancing the multiple projects that these findings create.

_q_tweetable:Effectively addressing problems surfaced during an audit or regulatory inspection will enhance your organization’s reputation and shareholder value._q_

In my experience working at engineering and design firms—as well as in operations and facilities management for biopharmaceutical institutions—I’ve found that it’s usually best to call upon outside resources to do the bulk of the work. This will be more expensive, but remember: the goal is to complete the corrections on time, not at the lowest cost. 

A consultant or professional architecture/engineering services firm is the best place to start. Let the situation determine whether to use the existing supplier(s)—which already have contracts in place and know your specifications—or consider using new suppliers who are better able to avoid the same mistakes and can apply fresh thinking to the problem.

This is also a good time to bring in desirable new vendors if it is necessary to get the work done correctly and on time. You should prefer a time-and-materials contract since there is little time to get a lump sum type proposal. Your goal? To complete the CAPAs on time—no matter what!

 

Break the project into milestones so that reporting on progress can be made unambiguous. Make sure you know when your company is providing progress updates to the FDA and plan your meetings and reports accordingly.

 

Hit the ground running

Form the team as you normally would, using outside sources wherever you lack the internal capacity. Emphasize in the kickoff meeting that on-time completion is the paramount concern, and you are to be informed immediately of any delay so that it can be addressed. Having the executive in charge attend this meeting and any subsequent meetings is helpful to emphasize this point.

Break the project into milestones so that reporting on progress can be made unambiguous. Make sure you know when your company is providing progress updates to the FDA and plan your meetings and reports accordingly.

The CAPAs can be considered complete when all the paperwork and training is complete. You should have tangible evidence to share with the FDA so that they have confidence you have addressed the issues. You should also be prepared for a follow-up visit from the FDA to verify that the CAPAs are complete. CAPA projects are different from typical capital projects but can be successful if seen as an opportunity and if the focus is on time and quality, not on budget.

This is the final part in our blog series that explores best practices for maintaining pharmaceutical manufacturing facilities in light of changing regulations and shifts in product development. For more on this topic, don’t miss Doyle’s presentation on October 30 at the 2019 ISPE Annual Meeting & Expo in Las Vegas.

Read the full series: Part 1 / Part 2 / Part 3 / Part 4

About the Author

Doyle Johnson

Doyle Johnson is a principal in our Science & Technology market, working from Boston, Massachusetts. Doyle's team and clients are collectively driven by a passion to care for the patients who are helped by the medicines produced in these advanced facilities.

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