When FDA Recommends a Consultant: Implications for the Pharma QCU

If there was any doubt before, then read the recent Warning Letter for the BMS facility in Manati, PR¹ to understand the FDA expectation of how the Quality Assurance must operate within a pharmaceutical company.

Three phrases jump off the pages that should hit any pharmaceutical Quality Assurance organization in the proverbial solar plexus. These are:

“on-going problems…”

“failed to thoroughly investigate…”

“without adequate justification or scientifically sound statistical analysis…”

Tucked amidst three straightforward observations, these phrases attack the heart of the regulatory-mandated purpose for what the FDA calls the Quality Control Unit. (See The QA Pharm 8/28/10.)

In the case of BMS, the FDA made an unusual, but not an entirely unheard of recommendation:

“Engage a third party consultant having appropriate CGMP expertise to assess your firm’s procedures, processes, and systems to ensure that your drug products have their appropriate identity, strength, quality, and purity.”

In other words, hire a third-party expert to do your Quality Assurance Department’s job.

FDA further added:

“Repeat citations from prior inspections indicate that your quality control unit is either not appropriately exercising its responsibilities or does not have the authority to carry out its responsibilities.”

Ouch! That’s gotta hurt.

“So, which is it—unwillingness or inability?” asks the FDA. This is one of those double-bind questions like “Do you still beat your wife?”

It’s a very serious situation when the FDA is compelled to recommend a third-party CGMP assessment, which is in effect a “vote of no confidence” for your Quality Assurance Department.

So, if you are a Quality Assurance professional, ask yourself these related three questions:

1.    Have manufacturing problems become routine with stock work-arounds, rather than infrequent with permanently engineered solutions? (i.e.,ongoing problems?)

2.    Do investigations stop short of identifying the costly root cause and all implicated batches, rather than truly getting to the heart of the matter and full impact?  (i.e.,failed to thoroughly investigate?)

3.    Are nonconformance decisions rationalized based on operational and financial pressures, rather than justified based on scientific, objective data? (i.e., without justification or scientifically sound statistical analysis?)

If you answered any of these in the positive, then before consultants start circling your carcass, take a long hard, soul-searching look to determine the underlying cause.

Is it unwillingness or inability?

History bears out that when these core expectations are exercised well, there is better economic control of quality due to less manufacturing variation and supply disruption.

When they’re not, unpredictable production; regulatory agency enforcement; customer advocate group petitions; and stockholder lawsuits start sequential waves of attack—a pattern seen with most major regulatory enforcement cases.

In that battle, whether it’s unwillingness or inability, it is QA that always falls on the sword and is offered up as a sign to the regulatory gods that “once I was lost, but now I am found.”

So to the QA professional, I say: battle “unwillingness” by finding another line or work where there is less effect on the lives of other people. Battle “inability” by competence and the courage of conviction.

¹FDA Warning Letter 10-SJN-WL-06, August 30, 2010.

The QA Pharm

http://theqapharm.blogspot.com

A Cure for Customer-Activated Tone Deafness

We hear much about the importance of listening to customers and meeting their needs. Lean Six Sigma devotees say that metrics from the customer’s vantage point are at the center of their philosophy.

Some pharma companies embed their high view of the professional community and patients into company credos or mission statements. I’ve heard of some companies that appoint team members whose sole role is to bring the "voice of the customer" into key discussions.

In the pharma industry we have built-in scientific processes that formally connect us with the patients and medical community we serve. For example, clinical research studies the patient outcome when deciding the strength, formulation, dosage form and frequency of administration, etc.

Other technical processes such as process development, technology transfer and validation also support the patient with well developed and consistent processes that ensure continuous supply of quality product.

Done well, these customer-connecting processes are proactive and early in the “customer fulfillment” cycle. Put in the lingo: it’s Quality by Design, or intentionally meeting customer needs, which—speaking of design and intent—are what the FDA regulatory requirements had in mind. Safety, Efficacy, Potency, Purity, Quality—it’s all from the patient’s perspective. Right?

Unfortunately, it’s not until the product is actually used over long periods that data are sufficiently amassed to tell us how well customer satisfaction has been achieved. There are also instances where customer feedback is nearly instantaneous that tell us that a problem got out the door, and FDA regulatory requirements tell us to listen and fix the problem.

This is where some in our industry are just plain tone deaf.

Just when I thought the prize went to a company that recently wanted to change the color specification on a cream product to “tan to slight brown on storage” in response to 30 customer complaints for discolored product, there came along another company that logged 570 customer complaints for a drug delivery patch that wouldn’t stick. Yet another company had a smoke-and-mirror complaint trend algorithm over rolling time periods that had to be met before the customer complaint was taken seriously and investigated.

Needless to say, the FDA took exception to the way these companies handled customer complaints, and it took a Warning Letter to prompt each to re-think how they’re treating their customers.

The good news—there really, really is a cure for customer-activated tone deafness: Caring!

The best-of-the-best companies have complete transparency to customer complaints at the most senior level. Well-designed metrics are presented to a panel of top functional heads that includes quality, regulatory, medical, manufacturing, technical service and marketing. Some companies have a “Listening Booth” where anyone in the company can hear the conversation between their 800 number callers and the Call Center. They want to actively listen to the customer and make effective decisions—because they care.

And when the serious and unexpected occurs, they own up to their responsibility and report it and recall product, if necessary. They don’t have to be told during an inspection that they failed to file a field alert—because they care.

So when it comes to our customers—patients, doctors and nurses—let’s be sure our auditory acuity is operating at peak performance as well as our manufacturing operations and the Quality Management System that uphold them.

As the truckers say over their two-way radios: “10-4 Good Buddy, Got ur ears on?”

The QA Pharm

http://theqapharm.blogspot.com

The FDA's "Park Doctrine" and BP

BP issued a 200-page investigation report this week into the Deepwater Horizon disaster that resulted in eleven deaths and spilled an estimated 205 million gallons of oil into the Gulf over 87 days. It concluded that the failures were multiple and complex.¹

BP summarized, “Multiple companies, work teams and circumstances were involved over time." BP, Halliburton and Transocean have repeatedly pointed fingers at each other.

Representative Ed Markey, D-Massachusetts commented on the report, "Of their own eight key findings, they only explicitly take responsibility for half of one…BP is happy to slice up blame, as long as they get the smallest piece."²

The lack of a BP mea culpa caught my attention because pharma industry management cannot blame shift because of the "Park Doctrine."

Park, a CEO, was found guilty on all counts involving food held in a building contaminated by rodents. His personal defense claimed that he had an organizational structure responsible for such matters.

Chief Justice Burger delivered the opinion of the court, “…by reason of his position in the corporation, responsibility and authority either to prevent in the first instance, or promptly to correct the violation complained of, and that he failed to do so…the imposition of this duty, and the scope of the duty, provide the measure of culpability…”³

One could summarize the US versus Park case as: “The buck stops here.”

For years, every FDA conference speaker has mentioned this landmark Supreme Court case at least once. This is because it’s an underlying tenant of FDA regulation enforcement—It is ultimately the responsibility of management to control its operation and to comply with the regulations, regardless whether parts of the operation have been delegated to others in the organization or third-party providers.

However, it looks like this is now more than an idle threat.

FDA Commissioner, Margaret Hamburg cited an internal committee recommendation to increase the appropriate use of misdemeanor prosecutions, a valuable enforcement tool, to hold responsible corporate officials accountable. Criteria now have been developed for consideration in selection of misdemeanor prosecution cases and will be incorporated into the revised policies and procedures that cover appropriate use of misdemeanor prosecutions.⁴

One has to believe that the timing of dusting off the 1975 Park Doctrine at the FDA Commissioner’s Office is no coincidence. Things could get interesting.

¹Deepwater Horizon Accident Investigation Report, September 8, 2010.

²BP Report Spreads Blame Across Gulf Spill Actors, CNN Wire Staff, September 8, 2010.

³U.S versus Park, 421 U.S. 658 (U.S. Sup. Ct., 1975)

⁴Letter from Margaret Hamburg, FDA commissioner, to The Honorable Chuck Grassley, ranking member of the Senate Finance Committee, Mar. 4, 2010.

The QA Pharm

http://theqapharm.blogspot.com

Good Metrics Practices--the Other GMPs for Finished Pharmaceuticals

The adage “You can't manage what you don't measure” certainly applies to the Quality Management System (QMS). Keeping a watchful eye on QMS performance metrics is essential for any compliance sustainability strategy.

Performance metrics enable the feedback necessary for a self-detecting and self-adjusting—thus sustainable—QMS. Without performance metrics there is no data-driven knowledge of whether the operation is in a state of control. Metrics also offer a company hope to get out of the "firefighting" mode and  become an anticipating organization.

Other than the seriously “lagging” annual product review required by 21CFR211.180e for pharmaceuticals and the mention of “quality data” in 21CFR820.20 for medical devices, CGMPs offer little direction on effective QMS performance measures.

The International Conference on Harmonization (ICH) Pharmaceutical Quality System Q10 offers a bit more on what to measure (complaints, deviations, CAPA, changes and inspection observations). However, all these are measures of failure. Quality Assurance needs to go beyond measuring failure to maximize value to the organization.

What is measured drives the organization’s conversation and behavior.

What is measured, analyzed, reviewed with management naturally affects decisions, allocation of resources, capital investment and department expense budgets.

I have sat though many management reviews of QMS performance metrics ranging from mind numbing detail to high-level, sketchy dashboards. They’re boring, and from what I can tell, nobody wants to attend. 


Some company reviews are all-day events without a single decision or action item that truly impacts the organization. For some, by their own admission, they simply fulfill a regulatory obligation.

I wonder if a management review of region sales performance is such a perfunctory exercise.

QMS performance metrics are meant to provide important answers. But in many instances the questions are forgotten. Reviews often degrade into a charade of color-coded dribble and “happy speak.” It is a fearful experience for the presenters, and the net effect is the perpetuation of the emperor's nakedness.

Put aside popular metric “buzzwords” for a moment, and think about the questions that need to be asked to manage each element of the QMS. For example:

·       How do I know that the system is operating well and being well managed? Are there bottlenecks or lack of execution?

·       What will help us anticipate a potential problem before it becomes a real, more serious and more costly problem?

·       What problem(s) is the system detecting? Are they indicative of “one-off” issues, or is there evidence of a systemic failure? What should we escalate to senior management?

·       What are the few, high-leverage actions that will have maximum effect and reduce exposure? What issues need to be incorporated into the short and long-term business plan?

After the right questions have been asked, then consider the appropriate sources of data and how best to present them. Remember these principles:

·       Define where the data originate and how calculations are made. This helps to make a fair comparison within and across company sites. (Keep your sister sites honest.)

·       Metrics need to be time related with “event markers” in order to be comparative, i.e., before versus after an improvement is implemented. Are we getting better?

·       Metrics have direction and scale. Pick either up or down to signify getting better and stick to it, and don’t play visual tricks by altering the scale.

·       Measure the opportunity, not the success. Ninety percent “Right First Time” sounds really upbeat, but the ten percent “Wrong First Time” is the opportunity.

·       Accompany metrics with analysis. Don’t publish colorful charts and graphs without interpretation and discussion. “Red, Yellow, Green” alone does not constitute meaningful analysis. Be sure to answer the question: “So what?”

·      Arm yourself with proposed actions and cross-functional allies before proposing recommendations to management. Make the job of management so easy that the right decision is obvious. (Most VPs would rather you do the lobbying.)

Giving your QMS performance metrics purpose and discipline adds value to the organization.  These are Good Metrics Practices—the other GMPs.

The QA Pharm