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

FDA: For Corrective Action Plans, Where are the Resources?

Can you imagine the stream of firms that venture in to their respective FDA district offices to give presentations on their Warning Letter response and to offer their assurance that they truly “get it”?

You can be sure that theses firms had several dry runs and dress rehearsals to hone their material before stepping into what they perceive to be hostile territory. Their presentations were carefully crafted by the VP, SVP, EVP and vetted by the lawyers. Consultants who claimed to have "been there and done that" were invited guests to the prep meetings to give their insight into what “sells” at the FDA. 

When the meetings at the FDA are over, the firm’s representatives heave a sigh of relief and offer each other congratulations that it went well, because it “felt good.” It “felt good” because no one on the FDA side of the table objected or got upset. So they go back to their colleagues and claim victory. The story gets exaggerated and turns into something like, “They really liked our presentation.”

In my experience, the only thing that “sells” at the Agency is results. The FDA “response” is a practiced, neutral expression that never is meant to signal agreement or acceptance. It’s all part of their “We’ll see it for ourselves when we come back to re-inspect,” modus operandi. 

However, we are starting to see a very interesting twist at FDA that suggests they have finally figured out that there is more they can do to ensure effective action than sit through fancy presentations acting nonplussed while having smoke blown up their proverbial tailpipe.

The new twist is embedded in the Teva Warning Letter dated January 31, 2011, but only recently posted on the FDA website. (The delay of which I always find curious.)

The theme of Teva’s Warning Letter is a problem of cross-contamination. Teva dutifully responded with their corrective action plan, which baited the usual response from the FDA--with a bit of a twist.

We recognize that your October 7, 2010 response states that you are in the process of developing a risk management program for control of cross-contamination of the products produced at the Jerusalem Oral Solid Dosage (OSD) plant. However, you did not submit that plan, or data to support the effectiveness of the plan, with your response. We also recognize your commitment to finish the risk assessment within four months. Please provide us with any update on your timeline, and the identification of resources allocated to address this issue. 

It is not uncommon for the FDA to expect a plan and timeline in a response. In fact, it is a frequent failing of companies to not provide a plan or timeline for completing corrective actions. However, in the case of Teva, FDA also requested the allocated resources to be identified.

That's the twist, and that's huge.

Frankly, this makes a lot of sense. The most successful corrective action plans have been those where the direct responsible individuals are named and appear in detailed project plans. There is a clear picture of what success looks like and how to get there. But most of all, the resources are identified to execute the work.

The regulation has always required sufficient numbers of qualified individuals to perform operations; so specifically asking about resource allocation to do the work is fair game. 
Unusual—but fair.

In the past, the sincere delivery of a good presentation might have passed with the usual skepticism. Now be prepared to tell about the resources to pull it off.

Without the resources, it's just another pretty presentation.

The QA Pharm

Current Pharmaceutical Industry CGMP Compliance Trends

It must be that time of year again when conference planners rack their brains on how to bolster dwindling attendance, because several have contacted me through this blog to ask my opinion on major trends in the pharmaceutical industry.

So with this edition I offer my opinion not only to those conference planners, but also to my readers. After all, why should you—my loyal readers—have to attend a pricey conference to hear what I told them?

But first, a note about—well, these pricey pharmaceutical conferences.

There are worthwhile conferences in our industry, but you really have to consider whether they are worth the price of admission. I have always thought that the best conferences were those with a strong FDA presence on the speaker roster. However, FDA speaker materials eventually become accessible to the general public. So, shortly thereafter, you can Google the name of the FDA speaker you saw in the pre-conference e-brochure and bingo. If it’s content you’re after, why not use your favorite search engine?

The worst conferences are those that recycle the same industry consultants—free advertisement. I'll save that subject for another time.

So—now to the subject at hand: current pharmaceutical industry CGMP compliance trends. Here are the top three, in my opinion:

1.    There is an emboldened FDA intent on measuring up under a keenly interested Congress.

·       There are sixteen (16) major pharma consent decrees dating from 1989 to 2010. What do they all have in common? No, it’s not bodies in the street. It’s GMP violations. Of these, only six (6) consent decrees have been vacated.

·       Eric Blumberg, FDA Chief Deputy Counsel for Litigation, has been saying for the last ten (10) years that the FDA cannot expect progress until individuals are criminally charged. We’re starting to see that now. (Enter stage left: KV’s Marc Herelin, InterMune’s W. Scott Harkonen, Forrest’s Solomon, Glaxo’s Lauren Stevens.)

·       Margaret Hamburg, FDA Commissioner, said that the FDA will no longer issue multiple Warning Letters. Criteria have been developed for selecting cases for criminal prosecution of individuals.

2.    When there are repeated observations, the FDA questions the willingness and ability of the Quality Unit to exercise its responsibility.

·       Repeated FDA483 observations are considered a failure of the Quality Unit, as stated in numerous Warning Letters.

·       Warning Letter language recognizes that Quality Unit failure may be attributed to either an unwillingness to exercise its responsibility, or an inability due to lack of independence.

·       Recent high-profile cases have ineffective quality units in common.

3.    FDA expects the global deployment of the Quality Management System and oversight by corporate management.

·       Corporations are expected to have oversight of the quality and regulatory compliance of their operating units.

·       Some companies have “flattened” their organizations into non-compliance and lack of oversight upon the questionable advice of efficiency and cost-reduction experts.

·       The Parke Doctrine holds management responsible although they may not have been directly involved or aware of violative conditions. Some of these individuals have appeared before Congress.

Now, here’s the funny thing. One conference planner asked if this anonymous blogger would agree to be a speaker. What part of “anonymous” didn’t they understand?

Perhaps I could make it work? Perhaps a backlit screen projecting my trademark silhouette?

The QA Pharm