Cartoon: The QA Quarantine Cage

The QA Pharm

Are Commitments Made to FDA to be taken Seriously?

Responses to FD483’s and Warning Letters are usually fully of commitments. They involve “what” will be done to correct compliance problems, and “when” it will be done. FDA has even started to ask “how” they will be done, meaning—Do you have the resources to do the work?

If these questions are not fully addressed in the FD483, then FDA will say so in the subsequent Warning Letter in the part where they acknowledge receipt of the firm’s FD483 response—and the inadequacy of it.

My first point is that there is no excuse for an inadequate response to an FD483 or a Warning Letter.

There are plenty of Warning Letters on the FDA website that provide examples of poor responses and what the FDA thinks about them. There’s no excuse for not knowing how to respond. (Also see The QA Pharm, October 10, 2010.)

Reasons for poor responses are:

·       Arrogance (What problem? Let me explain why we have no problem.)

·       Bad advice from house counsel (Dance around the edges, but never admit having a problem.)

·       Minimalism (Commit as little as possible and don’t look for other problems.)

·       Being far removed from the problem (Responses are so bad that it makes your technical insiders embarrassed.)

·       No root cause (Doing lots of stuff, but very little directed toward the real problem.)

·       Poor writing skills. (Difficult to follow the story line, because you have no idea what you want to say.)

My second point is never, ever miss a commitment date.

If anyone were to ask the leadership of any company under FDA enforcement action whether FDA commitments should be taken seriously, the response would be a resounding “Of course.”

Yet actions say differently.

It continues to amaze me how many companies miss commitment dates. And even more amazing—the senior management had no clue they had missed them. This is totally unconscionable and an indicator why the company has compliance trouble in the first place.

Reasons for missing commitment dates are:

·       No system to track responses and commitments

·       Responses and commitments are buried with hundreds of other TrackWise records, most of which are also overdue

·       Overly project managed until there is more planning than action

·       Lack of visibility as a standing agenda item in the management boardroom

·       No accountability at any level for results

·       Agency responses are kept a secret, or not sufficiently distributed to employees

·       Those responsible for doing the work had no idea that a commitment was made

The best way to think about the seriousness of a commitment to the FDA is to remember that the FDA already suspects a noncompliant firm to be untrustworthy—or at best they are neutral about their credibility. To not deliver on a commitment date just confirms their suspicion and puts the relationship between the firm and FDA on shaky ground.

Not providing an adequate response simply indicates being out of the mainstream of pharmaceutical industry know-how. And missing commitment

dates is nothing less that breaking a promise.

How would you feel if you were not taken seriously?

The QA Pharm

FDA Calls for Corporate Commitment and Leadership at PolyCarbon Industries

Just when you think that the FDA has to stick to the script by quoting chapter and verse of CGMPs, they get very progressive and offer straight talk about corporate commitment and leadership.

We have reported before that the FDA expects corporate oversight of the Quality Management System. (The QA Pharm 4/17/11.) The Johnson & Johnson debacle is just one recent example where the FDA cited the corporate folks for taking their eye off McNeil where Tylenol is manufactured.

But the Warning Letter to PolyCarbon Industries recently posted on the FDA website has an added dimension—a call for commitment and leadership. The Warning Letter dated December 2, 2010, reads as follows:

“It is essential that your firm establish and maintain a corporate commitment to an effective pharmaceutical quality system. Your firm’s management should demonstrate leadership and ultimate responsibility by participating in the design, implementation, and monitoring for quality throughout the company. Management should establish policies that describes your firm’s overall approach to ensuring drug quality and communicates your expectation of compliance with all requirements of applicable federal law and FDA regulations.”

There’s a lot of insight packed into this paragraph. The most important aspect is what commitment and leadership behaviors look like from an FDA perspective.

So, let’s do a little behavior analysis:

1.    Does your corporate group participate in the design, implementation and monitoring of quality at your company?

The best example of this that I have seen was a corporate group that facilitated a focused discussion of internal and external experts that led to the creation and deployment of company compliance policies.

The worst example was a company that hired a consultant to write the corporate policies. The policies appeared one day on the company intranet with the edict that they be deployed within six months. The old “right click on properties” revealed that the consultant had used the same policies for another client. The only thing different was the logo.

2.    Does your corporate group establish and communicate policies regarding regulations and compliance requirements?

The best example of this that I have seen was a company that deployed the policies with the business message that compliance was important to patients and the ability to compete. Compliance was to be valued and the operating norm.

The worst example was a company that couched the compliance message in terms of FDA inspections getting tougher, and that—right or wrong—the bar was being raised. “We just have to face reality.”

Regulatory compliance is no different than any other area of the company that requires commitment and leadership. Frankly speaking, when there is little leadership in this area, I find little leadership in other areas too.

So to our friends at the FDA, I say: “Spot on.”

Sometime what needs to be said can’t be referenced to the Code of Federal Regulations, but is truly at the heart of the problem.

The QA Pharm

What Does it Mean to Operate in a State of Control?

Once upon a time, I asked this question of a senior management group at an off-site “strategy” meeting. You know—one of those meetings where a working breakfast was followed by a day of golf, and I was the one doing the working.

The question was particularly germane to the purpose of my invitation, because these executives did not want to follow the path of other major industry giants into ruin by taking their eye off the proverbial CGMP compliance ball.

After a bit of awkward silence, someone offered a stab at the answer: Zero Defects. Another rebuked his colleague: That’s so passé. It should be Right First Time. The next ten minutes was Battle of the Buzzwords and I was the game show host. Conversation erupted in a murmur across the room.

I responded by saying that perfection was a worthy goal, but statistically impossible. I am highly suspicious of perfection, and firms that reward the strict definition of perfection drive bad behavior. In fact, when things are too perfect—I suspect fraud.

That quieted the room.

To operate in a state of control does not mean perfection. It does mean; however, the capability of a firm to detect and self-correct trends before it becomes a problem. And whenever a problem does emerge, the firm is capable of taking action to understand the reasons behind the problem, and make decisions that favorably effect the trend, or that prevent recurrence of the problem.

To make this more relevant, I drew an analogy with their Sales and Marking Department.

Their markets are broken down into regions and further into territories. Each territory manager has sales targets that they track and report up to the regional director. The regions report to countries. Eventually, all the performance metrics reach the company boardroom. Unfavorable trends and problems are investigated, decisions made and actions are taken. An eye is kept on the metrics to see if their decisions and actions were effective in increasing sales.

There is nothing here about perfection.

In this analogy, the market represents the Quality Management System and the regions and territories are its various parts organized by discipline. The territory managers, regional directors and the boardroom are the system owners and responsible management that exercise governance. Sales performance metrics are quality system performance metrics.

It was one of those beautiful “ah ha” moments.

  

I was intentionally being provocative with my question because I wanted this group that was responsible for a multi-billion dollar business to seriously consider how they were exercising stewardship of their pharmaceutical portfolio—for patients and investors.

What they expected to hear were Strategies for Avoiding a 483, but what I gave them was a refresher in Management 101 followed by one heck of a round of golf.

The QA Pharm