Writing a Procedure Doesn't Make it Happen

A firm correctly interpreted that the FDA had lost patience with their inability to sustain compliance as evidenced by repeated FDA 483 observations and the inevitable Warning Letter that arrived by certified mail to the corner office.

Rewind. What happened?

The firm had written an eloquent response to the observations that hit all the right notes. Improvements were evidenced by a revised procedure that was attached to the response, which satisfied the FDA for the moment—though the FDA noted they would see for themselves upon re-inspection.

And see for themselves they did—or rather, they didn’t.

The General Manager was stunned to hear the inspector declare at the close out meeting that there was no substantial improvement since the previous inspection.

“How can this be?” The GM’s question reverberated through the building as everyone ducked for cover and the search for the guilty began.

Unfortunately, this is a common problem, and it’s based on the unfounded notion that if you write a procedure, you make it so.

So, I’m here to declare that writing a procedure doesn’t make diddly happen.

In this instance, the theme of the FDA feedback was the ubiquitous “failure to thoroughly review the failure of a batch or any of its components to meet any of it specifications whether or not the batch has already been distributed.” But the specific issue doesn’t really matter. It could have been anything—the underlying problem remains the same.

It boils down to two things: organization capability and governance.

In this case, reasonable commitments were made to the FDA and appropriate changes were made to their deviation management procedure. However, the client still lacked the resources and technical bench strength to conduct a thorough investigation and inadequate process knowledge to execute an effective corrective and preventive action.

Nothing in their response changed their organizational capability.

Further, there was no process or forum to monitor how well the deviation management system was working—before or after changes to the system were made. There were no management reviews of quality system performance metrics, neither had there been any attempt to verify whether they had actually fulfilled their commitment to the FDA.

They had to learn about their failure from the FDA.

The net effect was a continuation of inadequate data gathering, misjudged root cause, poorly written investigations, misguided CAPAs—and the same persistent nonconformities. (Need I mention a mountainous backlog of deviation reports and unpredictable product supply?)

So who are the guilty?

I think that the GM and the head of quality assurance equally share the blame.

The GM is certainly responsible for the overall capability of the organization. However, the head of quality assurance is responsible for reporting on the health and welfare of the quality system—and, he/she should possess no less than the skills of the head of marketing to get the right metrics to the right people at the right time to take action on data-driven decisions.

But, alas—most of us in QA are nerds.

 The QA Pharm

Tylenol and Toyota: Lean Stigma

I’ve noticed that the Lean Manufacturing zealots in the pharmaceutical industry are quietly removing their copies of Toyota Culture and Improving Healthcare Using Toyota Lean Production Methods from prominent positions on their bookshelves. That’s one way to avoid a conversation about the cultic following of so-called “lean manufacturing” and the eventual drinking of the Kool-Aid that has left bodies of trusted brands and reputations lying writhing on the ground.

That includes Johnson and Johnson’s McNeil Consumer Healthcare, the maker of Tylenol—you know, the medicine we give our babies.

So, I wonder who will show up at the 2^nd Euro Lean Sigma and Kaizen for Life Sciences conference in Berlin this September where McNeil’s Director of Process Excellence will be giving a featured presentation entitled Case Study: McNeil’s Approach to Lean Implementation and Strategy Development for Roll-Out?

That’s like BP offering a seminar on the prevention of catastrophic oil spills.

This hasn’t been the first time that Johnson and Johnson’s regulatory woes have been oddly juxtaposed to their trendy quality programs.

In the early 1990s, LifeScan, a J&J medical device company, had the following on their website while federal marshals were seizing their glucose monitoring devices—no, seriously.

Every product is built to exacting standards and must pass rigorous quality control tests throughout every phase of design, manufacturing and packaging. We have implemented a continuous quality improvement process that incorporates the principles of Total Quality Management and World Class Manufacturing techniques. Innovation in quality manufacturing has earned us the distinguished Shingo Prize for manufacturing excellence. We were the first U.S. manufacturer of our monitoring device to be awarded ISO 9001 certification, an international standard of quality systems.

This was obviously the contest winner for the most quality buzzwords in a paragraph.

Recent examples should be enough for the pharmaceutical industry to take a cynical look at these costly-turned-devastating “operations excellence” programs. At least someone should be asking how these programs went extremely bad, and have, ironically, irreparably damaged quality, customer service and their reputation.

Since I have seen the gangrenous effect of “operations excellence” programs on regulatory compliance many times. I offer the following antidote:

1.    Recognize the difference between regulatory compliance and efficiency.

Rarely does the FDA say how exactly something should be done, so there is latitude for establishing ways of complying to the regulations to be as efficient as possible. But comply you must. But, beware of “leaning” to the point where the infrastructure collapses and the quality management system become unsustainable. The successful company will comply efficiently and fully with the regulations.

2.    Lead operations improvement initiatives with highly experienced subject-matter experts, and support them with your black belts.

The expert majors in applied sciences of the pharmaceutical industry, the black belt majors in team processes and toolkits. After all, it is a science-based industry. When the latter takes the lead or is put into power positions, it dumbs down the organization. Black belts don’t know what they don’t know. Combined with authority, they become lose cannons.

3.    Have a robust, process validation program.

A validation program provides documented evidence to you (and to product injury attorneys) that you have a process that consistently and capably manufactures a product to predetermine specifications. Unless the validation program has been “leaned” into a meaningless, ceremonial exercise, ensure that manufacturing processes are supported by a solid validation program. Validation has been an FDA requirement for decades, so there’s no guesswork as to current industry practice.

(Never allow a black belt to go unaccompanied anywhere near this system, or they will claim it gets in the way of new product launches.)

4.    Do not put your quality assurance function in a position of conflict of interest.

The quality unit is the only function that has a job description in the Code of Federal Regulations. One of the most significant responsibilities is to review and approve changes that could potentially affect the safety, potency, purity, efficacy and quality of a drug product. Quality assurance should not be put in a position where they are approving their own lean initiatives, or incentivized financially to do so.

5.    Have a robust, technical change control system.

The quality assurance function should never stifle creativity or advances in process improvement. However, quality assurance is required by law to ensure that changes do not negatively affect product quality. So they must remain neutral in their judgment on the effect of change on the validated state and license/drug application commitments, etc. Don’t bully them or tell them that they are not team players if they cannot approve the change. They just might be saving your ass.

(Never allow a black belt to go unaccompanied anywhere near this system either, or they will claim it gets in the way of capturing the savings this month.)

We have had a quartet of disasters in America that has required adding a wing to the waiting room for congressional hearings: Wall Street, Toyota, British Petroleum, and Johnson and Johnson. It’s sad to see our industry in this sorry lineup.

Since there’s no sign of either “operations” or “excellence” in the April 30, 2010, McNeil FDA483, I guess I won’t be going to Berlin.

The QA Pharm

Patients Take the Individual, not the Average

Many decades ago, my high school science club sponsored a field trip to Eli Lilly. Our little group of longhaired and bell-bottomed kids (after all it was the 60’s) was ushered into a little room to watch the introductory video about the history of the company and Colonel Lilly. This was followed by a guided window tour by a Lilly employee who would never know that he started a sequence of events in my life that led me to the pharmaceutical industry.

I have often thought about that day, which gave focus and purpose to my academic studies. But these many years later, I mostly remember the tour guide.

I recall how he pointed to each piece of equipment and explained what it did, how it worked, why it was important to the process, and even who was important as he pointed to each operator in the area and told us their roles.

When we finally arrived at the end of the tour, our guide showed us the final product being filled and packaged and said that everything we had seen up to this point was important for each and every vial that was coming off the line. It was with a reverential awe that our guide said that each vial would be going to a person whose life depended upon it.

That tour guide got it right. Patients take the individual, not the average.

It is manifestly impossible to sample a sufficient quantity of finished product to assure the conformity down to the unit level. However, it is the unit level that is taken by the patient, sometimes daily for their entire life.

So, if we cannot provide adequate assurance down to the unit level by testing alone, and if it is important that we must for the sake of each use by the patient—then what gives? Is this a double bind?

The answer is in the Quality Management System.

The purpose of each element of the Quality Management System is to collectively work together to control the manufacture of the drug product from the suppliers’ materials received at the dock to the final product in the shipping containers coming off planes and barges around the world and onto hospital and pharmacy shelves—through to the end of the expiration date.

Each step along the way from dock to stock is based on science and engineering. The Quality Management System ensures that the science and engineering foundation is vigilantly protected from undesirable and unintentional variation that could negatively impact the product at the patient level. And if it does, the problem and product impact are thoroughly investigated and the underlying cause is engineered out.

This is the field of Quality Assurance. It’s all about the patient and the individual unit, as well as the controlling the way we work to ensure consistency and predictability. Patients deserve no less.