Saturday, August 28, 2010

Quality Control Unit: Invertebrates Need Not Apply

The Quality Control Unit (QCU) is the only pharmaceutical function that has a job description codified in the CGMP regulations.

Don’t you find this remarkable?

In fact, an entire section is devoted to describing the responsibility of the QCU and how it is to operate within the organization—namely independently.

Concerns about an independently operating QCU were raised when CGMPs were first proposed in 1978, and some companies have struggled with “independence” ever since. The Commissioner responded to those concerns in the Preamble to the CGMPs1, which we often consult for insight into the intent of the regulation.

Basically, “independent” means…well, “independent.” The regulatory authority and responsibility of the QCU is not to be subordinate to any other unit where there is the potential for a conflict of interest.

Operating independently does not mean being insular, or elitist. It does mean, however, to have the ability to make objective, scientific, data-driven decisions and being sufficiently articulate to make the case for doing the right thing—then doing it.

However, there appears to be a big gap between the requirement and practice at some companies.

This was evident in the article by Mina Kimes, Why J&J’s Headaches Won’t Go Away that recently appeared in CNNMoney.2 The article tells about the finger pointing within McNeil over repeating tests in order to bring the average into the passing range.

Apparently some involved felt a twinge over participating in this unacceptable practice known in the industry as “testing into compliance” or “reflexive retesting” in order not to reject the batch. (This practice became taboo as part of the legendary federal case against Barr Laboratories in 1993.3) The quality employee was quoted as being resigned to “doing what you’re told.”

The author ultimately concluded “quality oversight declined.”

Recent industry events should serve to remind company management as well as the QCU that nothing good—personally or corporately—ever came out of succumbing to pressure to do the wrong thing. In fact, company management should make every effort to be accessible by establishing ombudsman programs and hotlines into neutral territory (e.g., Legal Department) where individuals can confidentially report concerns.

Anyone who has worked in the QCU of a pharmaceutical company has had his or her mettle tested at one time or another. We have all been in the situation where we have had to stand by an unpopular decision. In some cases we were the lonely voice crying out against the louder, more powerful ones. But we’re not the only ones who have had to deliver and defend bad news. It comes with the territory and sometimes takes spine.

For sure, the QCU is no place for invertebrates.

1Federal Register Vol. 43, No 190 – Friday, September 29, 1978, Preamble to the Drug CGMPs.

2CNNMoney:  Kimes, Mina, 8/19/10, Why J&J’s Headaches Won’t Go Away,

3United States vs. Barr Laboratries, Inc. Civil Action No. 92-1744, US District Court for District of New Jersey: 812 F. Supp. 458. 1993.

The QA Pharm

Saturday, August 21, 2010

Trusting: What it Means to be a Patient

Social media is an amazing technological development. With the nexus of smart phones, the Internet and social media sites, we have eyewitness Tweets and blog posts instantly as developments occur around the world.

Some users bring us into their momentary existence—“Dining on peacock and quail egg souffle tonight.” However, I have chosen not to inflict my readers with the minutia of my daily life. (You're welcome.)

That is—until now, because at the moment I’m in the hospital.

From the time I checked in, I have been in constant surveillence mode. My radar has been sweeping the perimeter as I’ve been handed off: patient registration, medical history, blood work, patient room check-in, intravenous tech, surgeon consult, anesthesiologist consult (lamenting the shortage of propofol)—z-z-z-z—recovery room, back to my room.

My radar detected: Becton Dickinson, Kimberly Clark, Hill Rom, Baxter, Welch Allyn, GE, Ortho-McNeil-Jennsen, Hospira, Teva.... all in the hands of smiling and caring medical practitioners.

My professional demons have forced me to scroll through my mental Rolledex of Warning Letters, consent decrees, and industry intelligence. But in the end I have to let go and trust, not only in the doctors and nurses, but in the medical products in their hands.

That’s what it’s about, right? Trust.

We work in an industry of high, implicit public trust. Patients shouldn’t have to wonder whether the sterilization load pattern was validated; whether suppliers of components and raw materials are under control; whether the active ingredient in the tablet is uniformly distributed; whether the label is correct; whether the impact of process changes and manufacturing deviations were reviewed on their technical merits by process engineers and scientists and approved by quality assurance....

Why? Because patients in general, and I specifically have other things on our minds. And the medical products we use while in our most vulnerable state should be the least of our worries.

I don’t wish ill on anyone, but perhaps it’s good to be the patient once in a while.

Today I’m on the receiving end and not all that concerned about the medical products being used for my care...really—sorta, kinda—not.

The QA Pharm

Saturday, August 14, 2010

Quality Assurance: To Count the Cost—or Not?

One of the regulatory responsibilities of the Quality Control Unit is the release decision for drug batches into the market. When I was first given that responsibility early in my QA career, it was impressed upon me to not count the cost of the batch when making that decision.

That was good advice. But looking back, I would have modified that admonition slightly in order to put the financial arms length of the QA role in a broader perspective.

For sure, QA must not allow the cost of the batch to influence its release decision. One needs to be objective and independent—no apples to polish, no axes to grind. Patients deserve no less.

But QA needs to do more than call balls and strikes.

It was Phil Crosby, the ghost of gurus past, whose apparition onto the quality scene said that the Price of Nonconformance (PONC) is the measurement of quality, not indexes.1 With Genzyme's manufacturing write off of $21.9 million dollars in July and an additional write off of $6.5 million dollars in August 2, along with an expected consent decree disgorgement fine of $175 million dollars3—and costs associated with third-party control and quality system and facility upgrades—we're talking real money. Real PONC.

In the grand, cosmic, economic scheme of "pay now, or pay later," an upfront investment in quality by design through qualified personnel, training, facility design, product development, technical transfer, process validation, supplier qualification, environmental monitoring, etc., for any pharmaceutical company has got to be the best dollar spent.

When things go wrong, it always happens at the worst possible time and when the solution is at the highest possible cost. The most painful cost is the effect of the loss of patient and consumer confidence, and perhaps, the loss of a brand.

So, here is an admonition to the quality assurance professional:

Do not count the cost of the batch when making the batch release decision. Regardless of the lost standard and opportunity costs, to reject a batch when it is the right decision is not only the ethical, moral decision, but also it is the best financial decision for the company the long run.

However, do count the cost of PONC. Picture yourself at the edge of the landfill tallying the cost of everything going into the pit.


Because behind every rejected raw material, component, bulk, finished product; behind every stale item on "hold" taking up space in the “morgue” section of the warehouse; behind every inefficiency and "do over" is lurking a frank or potential quality system failure and regulatory compliance problem. Counting the PONC is an effective measure of the health and welfare of the quality management system, which is a QA responsibility.

So, in these economically difficult times, before your profit improvement committees launch suggestion boxes or start unscrewing half the light bulbs in order to save the company money, zero in on PONC, and begin to systematically reduce the budgeted line item known as “standard waste,” the planned product write offs. It will be an effective, bottom line and quality improvement strategy.

So, the question is: Should QA count the cost, or not?

The answer is: yes, they should and shouldn’t.

1 Crosby, Philip. (1984) Quality without Tears, McGraw-Hill, p. 86.

2 Genzyme Reports Financial Results for Second Quarter of 2010, 21 July 2010,

3  Genzyme Corp. Signs Consent Decree to Correct Violations at Allston, Mass., Manufacturing Plant and Give up $175 Million in Profits, FDA Press Release, 24 May 2010,

The QA Pharm

Saturday, August 7, 2010

Lean Pharma: First Things First--Just Sayin'

Pharmaceutical companies must comply with the regulations and be efficient. It’s like sending your child to school with a good night’s sleep and a good breakfast. Both are necessary. The company that learns to do both well will survive to compete.

But it appears that pharma is behind the Lean curve.

In the recent article How Lean is Pharma? A 10-Year Progress Report1 the author decries the lagging pharmaceutical industry in average inventory turns saying that there is much to learn from leading-edge companies in other industries.

The author attributes pharma implementation failures to isolated implementation and manufacturing operations focus. He also cites the reasons that cross all industries: lack of leadership commitment, excessive cost reduction focus, improper project selection and suboptimal execution.

I agree.

However, there is a 500-pound gorilla in the room: Lean antagonism toward CGMP compliance, which becomes self-destructive.

Admittedly, my world has been comprised of companies reeling from self-inflicted FDA enforcement wounds. So my sample group is skewed—hopefully.

Here are some common themes that I have encountered when companies cannot seem to harmonize their compliance (CGMP) and efficiency (Lean) efforts.

·       Antagonistic view of CGMPs by management.

Often “GMPs” and “the business” are viewed as at odds with each other. GMPs are a seen as a regulatory burden, rather than an expression of a product quality assurance system for patient protection.

Take for example the site head that gave her employees the mixed message that following procedures is important, “but we must also remember that we make medically necessary products and must do whatever we can to get the batches released.”

·       QA enabling continuous problems.

Rather than designing, implementing and measuring the effectiveness of the quality system and independently ensuring that all requirements have been met, the QA unit rationalizes batch deficiencies.

The QA director whose performance was measured on cycle time is a prime example. He thought he was being customer focused when he released the batch before the product impact of associated deviations had been fully determined—“after all we, we know the product is good, and we cannot interrupt supply.”

·       Lack of robust manufacturing process.

Inadequately developed processes are transferred to routine manufacturing operations to reduce the “time to market” cycle resulting in continuous manufacturing problems and production schedule volatility.

In one company deviations became routine and tolerated. The true root cause pointing to the need for further process development was untouchable, since it could lead to re-opening the NDA or impugn product already distributed.

·       Lack of product knowledge and technical expertise.

Companies have suffered from “brain drain” as a result of “vertical integration,” but there was no analysis of the effect on the scientific and technical capability of the organization. This significantly reduces technical input to improvement projects and permanently engineering out the problem.

An example is the decision made (with inadequate technical input) to retrofit an existing aqueous filling line to fill suspension products in order to decrease the new product launch timeline, which resulted in content uniformity failures.

There is no reason for conflict between Lean principles and regulatory compliance; battle lines do not have to be drawn. I cannot believe that Lean principles seek to destroy a company’s compliance profile with the FDA, or purposefully seek to make uninformed decisions.

I’m just sayin’ it is what it is.

Here are a few suggestions for any pharmaceutical company (not just those in trouble with the FDA) that wants to integrate their compliance remediation and Lean initiatives.

< Start the Kumbaya music, please. >

·       Conduct a thorough baseline CGMP assessment.

Know for yourself where you stand with respect to current industry practice of applying CGMPs. Conduct a baseline compliance assessment that begins with product development and technology transfer, through product delivery to the pharmacy shelf. It is misguided to think that you can start Leaning from a deficient state of compliance. That could only make matters worse.

·       Perform a risk analysis on the compliance gaps.

Based on the results from the baseline assessment, perform a risk analysis for each element of the quality management system in order to prioritize the remediation effort. Consider beginning with document management, change control and employee training systems, since all improvements to other system elements will funnel through these pillar systems.

·       Develop a comprehensive improvement plan.

Create a project plan that becomes one of the highest company priorities. Establish project teams to redesign each element of the quality management system. Ensure they are fully resourced and funded. Track progress through Plan, Design, Implement, and Operate Phases with active governance and phase gate reviews. Determine whether any legacy issues need to be resolved. Remember that the goal is to design a sustainable system. (See The QA Pharm: What is a Quality Management System? Perhaps More than you Think, July 30, 2010.)

·       Use subject-matter-experts to lead the effort.

Use your internal subject-matter-experts (SME) to lead the teams. Go outside the company to get good, results-oriented consultants to avoid the “not invented here” syndrome, particularly for companies that tend to be insular and inbred. In the process, develop “system owners” and develop their sense of ownership.

·       Involve Lean experts to facilitate and ensure efficient system design.

Use your Lean experts to facilitate—not lead—the compliance remediation effort. They can bring a useful perspective and tools that will help to ensure that improved system elements are efficient, while the SME ensures compliance requirements are met.

By it very nature, Lean “takes out.” Compliance improvement more often than not “adds in” because something has been fundamentally lacking.

When Lean is applied without first ensuring regulatory compliance, more can be taken out from an already non-compliant system.

When a compliance system is implemented without Lean principles, inefficiencies and non-value-added activities may go unchallenged.

In other words, put first things first: start with a compliant system. Resist all temptation to Lean a system into compliance. But both are necessary.


The QA Pharm