When All is Said and Done, there is More Said than Done

I couldn’t help but contrast the claims made by NexgenPharma on their website¹ with the responses to observations cited in the recent FDA Warning Letter about their operation.²

Website: Each pharmaceutical product undergoes rigid process validation…

Observation: Your firm has not conducted adequate cleaning validation or provided scientific justification.

Response: We’ve done it this way for the past [redacted].

Website: We test and analyze raw materials, products in production and finished goods using advanced analytical techniques…

Observation: Your firm does not have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance…including the identity and strength of each active, prior to release.

Response: …are closely related in structure and thus, do not necessitate individual testing for strength…We will test each drug product component at least once a year…

Website: Each pharmaceutical product undergoes rigid… stability…

Observation: Your firm does not have a written testing program designed to assess the stability characteristics of drug products…

Response: …stability studies are only performed if the customer pays to conduct the studies…(we) rely on stability data recorded in the years before and after to support the label expiry…

Website: Nexgen adheres to the strict standards of the current Good Manufacturing Practices (CGMPs) established by the US Food and Drug Administration…

Observation: …we remind you of your responsibility for ensuring that your firm’s drug manufacturing operations comply with applicable requirements, including the CGMP regulations. FDA expects NexgenPharma, Inc. to undertake a comprehensive and global assessment of your manufacturing operations to ensure that drug products conform to FDA requirements.

Response: None. (What can possibly be said after that?)

It’s a really impressive website. But it reminds me of the adage: “An ounce of image is worth a pound of performance.” On behalf of all the patients dependent upon their performance, good luck.

The QA Pharm

¹ http://www.nexgenpharma.com

² http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm233276.htm

Roche Watch: 'Hit" with Operations Excellence--or What?

Roche reported this week that it will cut 4,800 jobs over two years, mostly in the U.S. to help save $2.4 billion by 2012. Sites specifically “hit” were listed as: Florence, SC; Boulder, CO; Nutley, NJ; Madison, WI; Vacaville, CA; and Oceanside, CA.

“Hit” with what?

According to reports, these locations will be “hit” the hardest by Roche’s “Operational Excellence.”¹

So we, the readers, are to conclude that Roche conducted a thorough evaluation of its operations and determined that they will be able to operate in a more excellent manner after cutting 6% of its global workforce.

We are led to believe that by using the tools of quality to analyze waste and unwanted variation; by performing value stream analyses, redundant and unnecessary steps are being removed; that each initiative has been carefully assessed and will be verified to ensure the goal was achieved—and, by the way—all the requirements have been met.

In my experience, downsizing, restructuring, vertical integration—or being operationally execellenced—isn’t quite that disciplined. Typically, each operating division is given a reduction quota, which in turn is divvied across its operating departments.

It is top down, not bottom up.

There is no ground swell of quality excellence initiatives that perk up to the top causing executives to glean them across the organization and declare a savings for the greater good of the company, shareholders and patients. There’s nothing DMAIC about it.

In reality, area managers sweat how they are going to be a team player and turn in their layoff list to the boss and still operate their departments. After all, the workload really hasn’t changed. It’s a fight for survival, a fight to save your own job.

I have no insider information as to how Roche really went about determining who to let go, or if they consciously studied the impact to the organization other that the short-term financials. I sure hope they did.

STOP THE PRESSES—STOP THE PRESSES—THIS JUST IN

Now, according to reports, Roche CEO Severin Schwan has been telling investors that the company will have to downsize because of healthcare reform.²

So, which is it? Operations Excellence, or reaction to healthcare reform?

Anyone who follows me for long knows that I am not a huge OpEx fan. Not because of the ideals and methodology, but because  (1) it is strategically and chronically misused in the pharma industry, (2) it is a misunderstood substitute for the regulatory-required quality assurance and quality management system, (3) black belt plebes overreach their product, process and regulatory knowledge, and (4) it is often a precursor to systemic FDA regulatory compliance problems—due to all of the above.

However, I am now coming to the defense of Operations Excellence. (No, really.)

I would strenuously object to having my process improvement program being identified as the means by which opportunities for workforce reduction were identified. That gives the company far too much credit for taking any sort of disciplined approach that will benefit the customer—the patient.

Didn’t we read about Johnson and Johnson’s “restructuring” in 2009? ³ Now, fast forward to the current quality and regulatory compliance problems at McNeil and the 2^nd Euro Lean Sigma and Kaizen for Life Sciences conference in Berlin this past September where McNeil’s Director of Process Excellence gave a featured presentation entitled Case Study: McNeil’s Approach to Lean Implementation and Strategy Development for Roll-Out? (See QAPharm 6/19/10.)

The Quality Management System (QMS) is like an ecosystem. There are interdependencies. One change affects the others. The QMS is more than words in a set of standard operating procedures. (See The QA Pharm 7/30/10.)

I will be the first to say that there are always opportunities to make the QMS more efficient. But there are regulations that must be satisfied to ensure that changes do not affect the state of control of the operation and negatively impact product quality and the conditions under which the product was approved. And rarely, if ever, does a pharmaceutical firm consciously evaluate the cost-and-effect of a major workforce reduction on the state of control.

Layoffs are mandated. You fall in line. And when the CGMP compliance wheels fall off the cart, you are not to mention the effect of the workforce reduction as a root cause or contributing factor during deviation investigations.

Fast forward to about 2015. What will we have heard about Roche product quality from the patients’ perspective? I really and truly wish them all the best, because I am all about the patient.

However, Roche is going on “The QA Pharm FDA Compliance Watch List.”

The QA Pharm

http://blogspot.com/theqapharm

¹ Frank Jordans, Associated Press, Drugmaker Roche will cut 4,800 jobs, mostly in U.S., 11/17/10.

² Jim Edwards, BNET.com, Why Roche’s CEO is wrong to blame Obamacare for 4,800 Layoffs, 11/17/10.

³ Tracy Staton, FiercePharma, J&J restructuring claims up to 8,000 jobs, 11/3/09.

Routine Problems, Routine Explanations

Here I am at a foreign airport with time on my hands due to a significantly delayed flight. Usually I roll with the punches when travel is disrupted, and I have even grown accustomed to routine, scripted explanations. Same problems; same explanations. This time it was the ubiquitous "delayed incoming plane." The gate agent started to get annoyed when I said that “delayed plane” is a symptom, not a root cause. (It’s not her fault.)

This triggered a thought about disruptions—or more to the point—manufacturing problems that become commonplace, and routine ways I recall having seen them handled—or not.

One clever approach to handling a particular recurring deviation was to have a pre-printed form. The investigation was already written with the exception of the slight nuances, which were accommodated by blanks. This "Mad Lib" approach was completed in a matter of minutes, and a QA approval was handily secured.

Another very "efficient" approach was to use a "planned change" system to work around the recurring (planned?) problem. Another variation on this theme was an "emergency change" system used to document the quickie permission to urgently deviate from the established process—as it had many times before for the same emergency.

I would be the first to acknowledge that "things" happen, and that there needs to be a mechanism to efficiently and expeditiously handle the unusual. CGMPs would not have provided for a deviation investigation system if we lived in a perfect world.

But when the "unusual" becomes standard practice, and when quickie methods routinely substitute for permanent technical solutions, then we are buying into form over substance; ad lib over defined; accommodation over discipline; rationalization over justification. Our patients, which is to say—our business—deserve better.

Warning Letters are replete with observations about recurring problems. So, why do we tolerate habitual humans errors, aging equipment, half-baked processes, retro facilities, and uncoordinated support services that cause problems that are more predictable than our processes?

You tell me.

The best practice I've seen is the "Three Strikes You're Out." When a recurring deviation and obviously ineffective CAPA happens the third time, you no longer own the deviation/ investigation/ CAPA—your boss does. Each time thereafter, it goes up the chain of command. Now that is taking solving problem seriously—or a reaction out of frustration.

Besides, isn’t “repeat CAPA” an oxymoron?

I see the premium members queuing at the gate. I just might get stateside today.

The QA Pharm

FDA Enforcement Inflation: What's Next?

I grew up in a home where just a cast of my mother's glance was enough to cause me to stop dead in my tracks. I knew "the look" quite well. There were no raised voices.

When a parent doesn't follow through on the gentlest of correction, then the parent is communicating that an appropriate response is optional. Out of frustration, parents often up the ante by resorting to yelling and making idle threats. Nothing really changes, because nothing has to. There is more yelling than consequences.

Such has been the history of FDA regulatory enforcement. The threats had to escalate. Their voice had to get louder. The stakes had to get bigger to get industry attention.

I remember the day (now I sound really old) when an FDA483 caused you to clutch your chest and wonder whether your career was over. Over time the FDA483 just became a "calling card" as we used to call it. It was just evidence that the FDA paid a site visit. “It’s just a short one,” we’d say. “No biggie.”

Then Warning Letters became more prolific because FDA483s just didn’t get sustained compliance. “Everyone takes their turn in the barrel,” we’d say. “It was just our turn.”

Then the yelling started.

Eli Lilly (1989), Warner Lambert Consent Decree (1993) and American Red Cross (1993) ushered in a new era and a new FDA enforcement lever. There are now over sixteen major Consent Decrees, not counting those from the swath cut through the medical gas industry in early 2000.

Rather than the "pay-as-you-go" investments in improving the manufacturing operations and ensuring the state of control, some apparently have chosen profits over control until one day all goes wobbly and the FDA finally blows its stack. Even so, a fine of multi-millions of dollars is a drop in the bucket to the company. (The cost, of course, is passed on to patients.) “A blip in the stock price. A one-time hit,” we’d say.

But last week things started getting personal, and the FDA is threatening to up the ante again. Now mom is throwing the china to get attention.

Although the Parke Doctrine had been at the FDA's disposal since 1975, apparently it is being dusted off because, well—it has to be.

The Parke Doctrine is all about personal accountability. Individuals—not corporations—are personally charged with a crime. Their careers are over, and a criminal record taints them for life. (See The QA Pharm 9/11/10.)

Unfortunately, this just might be what it takes for the management at some companies to take their personal role seriously in assuring that they are in compliance with FDA regulations enacted to ensure public safety.

Thankfully, not all pharmaceutical companies are recidivists. Hopefully, reading the trade news about Consent Decrees will not become passé. 

Threat of personal prosecution needs to grab industry attention—like Consent Decrees, ah…like Warning Letters, um…like FDA483s used to.

The QA Pharm