Part 1: Five Obstacles to Management Oversight of the Pharmaceutical Quality System

Part 1: Five Obstacles to Management Oversight of the Pharmaceutical Quality System

Introduction

Compliance to current good manufacturing practice (cGMP) regulations is, in fact, a part of normal pharmaceutical business that requires diligent management oversight. Just as it is with other business functions, management has the responsibility to ensure that systems are in place to effectively monitor the state of control in order to intervene with timely decisions to manage risk, achieve goals, and add stockholder value.

However, the number of pharmaceutical companies that have received FDA warning letters or that are under consent decrees indicates that management oversight of cGMP compliance is a significant and continuing problem in the industry. There have been tarnished reputations, loss of brand loyalty, stockholder lawsuits, and unprecedented financial impact. At some point, the warning signals were undetected, unheeded, or rationalized away.

This is the first in a five part series that explores the issues that can affect the ability of management to detect the warning signals of significant cGMP compliance problems and offers suggestions on how to gain control over this essential part of the business. 

Obstacle 1: There is a Perceived Disconnect between cGMPs and the Business

Not only is there a perceived disconnect, but cGMPs are often viewed as an obstacle to daily operations. There is no greater impediment to devoting personal attention to any given matter than to question the value, or, at best, to think it a burden for someone else to bear. When this is a dominant belief of those in authority, it translates into speech and actions that are observed and emulated by subordinates. Over time, this view is widely adopted and becomes part of the company culture that influences the way daily work is performed.

  

Deep-seated beliefs such as these are very difficult to change. Defending the business value of cGMPs can only be successful if management actually believes it is true. Unfortunately for many in leadership positions, this understanding is not part of their education or experience. At best, their background may include a training course or seminar, but their daily experience with the pharmaceutical quality assurance and cGMP compliance functions are the frustrating hurdles to release product to market.

The Opportunity?

To win the hearts and minds of management to embrace the business value of cGMPs, one must put forward a rational argument that cGMPs are a business enabler and to integrate this belief into the company’s formal value statement, new employee orientation, and ongoing training. However, this requires a deeper understanding of the foundation principles of cGMPs and recognition that they are no different than those of the business.

The rational argument goes like this:

• Patients take the individual dose, not the average—sometimes every day for their entire life. Patients deserve the assurance that their drug will meet every quality requirement for each dose, not just on the average. That’s the objective of cGMPs, and that should be no less the objective of one’s business.
• Manufacturing processes are fraught with opportunities for unwanted variation to creep in from incoming raw materials and components to equipment, test methods, operators, facilities, utilities, and warehouses. Manufacturing a product that is continually faithful to what market approval was based on and all quality requirements only happens when done so intentionally. One can’t test quality into products.
• Standard operating procedures declare how a company intends to control variation and ensure predictability. The operative word is “standardize.”  A company has the liberty to standardize how it works to be as efficient as possible to meet regulatory requirements. Contrary to common belief, cGMPs do not prescribe exactly how to comply, but the expectation is to keep up with current industry practice. A company is responsible for applying product and technical knowledge to the practice of cGMPs.
• When following standard operating procedures, records are created that document how the work was performed and the results. The way and when information is recorded and is important. Sometimes it is so crucial to the outcome that recording information must be witnessed. Documentation is how one proves and defends one’s work.
• Records contain data that describe how well the intent was achieved. The data can be collected, translated into performance metrics, interpreted by process owners and subject-matter experts for analysis and decisions to target actions to continuously improve processes, reduce waste, increase efficiency, prevent future failure, and enhance knowledge.
• A regular review of these performance metrics by a cross-functional management team is part of the mechanism to provide oversight and governance. When taking action on unacceptable trends a company becomes an anticipating organization, rather than a reactive one. A management review of the quality management system (QMS), like any other business review, is the primary source of data-driven confidence that one is operating in a state of control and is the basis for the confidence that one is maintaining an economical control of quality, increasing operational capability, and the ability to compete while meeting cGMP compliance expectations.
• Compliance to cGMPs supports the business by ensuring continuous quality and continuous supply of products to customers and patients. Continuous quality is quality that can be trusted. Continuous quality enables business performance to be predictable.

Although the argument may be logical, often those who are in the best position to make the argument, the quality function, referred to in cGMPs as the quality control unit (QCU), may not be up to par. Part 2 will deal with the QCU.

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A Tale of Two Deviations

It stands to reason that pharmaceutical companies in compliance trouble also have problems with their Deviation Management and Corrective and Preventive Action (CAPA) System(s). After all, to maintain a good compliance profile, as well as an efficient operation, requires the ability to detect problems, determine the root cause and permanently eliminate the problems.

Good companies rejoice that a problem was detected and reward the one who detected it. It's another opportunity to improve---one more problem that they never have to deal with again. They rise to the challenge to find technical solutions and engineer-out the problem. They are thinkers who mindfully apply their education and experience. They celebrate finding and permanently expunging recurring problems. Management is aware of and measures recurring problems. They have no tolerance for it and hold department managers accountable for measurable results.

For poor companies, deviations are a way of life. Deviations are anticipated and the rewards go to those who heroically work the long hours to jump through the usual hoops to close the deviations so the lot can get out the door. They know that they will have to go through the same effort the next time. It is an exercise in onerous paperwork and checking procedural boxes. They celebrate getting the lot out the door---finally. Management measures delayed investigations and backlogs. Everyone knows what the routine problems are, and management asks no more than they be handled in the routine way---just more quickly.

Like in A Tale of Two Cities, they are worlds apart in organization culture. One cannot change culture by policies or procedures. It's a force that emanates from the top. It's a force that cannot help but to become infused into every breathing soul. Culture invigorates and identifies who we are in our very essence.

It's leadership. And leaders that build a positive culture would ask, "Why would we not permanently irradiate problems at their festering roots---even if it's one of us?"


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Seven Success Criteria for Hiring (and working with) a Good GMP Consultant

The high layoff numbers in the pharmaceutical industry and poor job prospects in a weak economy have flooded the market with would-be consultants to pharma companies that need extra help. Here are my suggestions for hiring and working with a good GMP consultant.

1. Define the scope of work before you start scouting for a consultant.

There is nothing worse than throwing a bunch of consultants at a problem without knowing the boundaries of the project or defining the expected results. Unfortunately, it happens all the time. It ends in  frustration for all parties involved, and the tragedy is--nothing gets better.

A formal Scope of Work (SOW) helps both the client and the consultant to set expectations of each other and agree on basic assumptions that are critical to success. A draft SOW is the basis of a discussion with the perspective consultant, and the final version becomes a formal understanding that both parties can agree to. Sometimes it is beneficial to have an initial scope of work that is limited to a survey of the present situation with recommendations for an approach to the problem and a breakdown into phases or discrete chunks of work.

2. Determine the hard and soft skills required.

Consultants have been everywhere and done everything. If you don't believe so--just ask them. Resumes are inflated and each universally saved their previous client from the jaws of destruction. Many arrive like a one-person wrecking crew. Their know-it-all and negative behaviors will overshadow any remnant of dignity that your work group has left.

Explore the range of skills necessary to do the job and ask pointed questions about how the candidate's skills were applied to previous situations. Some skills may be hard technical skills, while others may be the soft skills needed to engender trust and collaboration with your team. In the back of your head you should be thinking: "Will the skills of my people be better as a result of having worked with this consultant?"

3. They really must have worked in the industry.

With due respect to my FDA friends, especially those who are now consulting, it really is better to hire someone who has actually made medicine, not just conducted inspections. The reason that FDA experience is highly valued is because the client thinks that they will get some insider perspective on what the right answer is--or what the FDA is looking for at the next inspection. There are plenty of people who can tell you what's wrong, but fewer people who offer a range of solutions or who had been responsible in their careers for results.

Inspection results have never been and never will be the true measure of future performance. Look for someone who understands the complexity of operational, technical, social, cultural issues that must be considered when resolving fundamental GMP problems. Nothing replaces specific operational knowledge.

4. Avoid career quality assurance consultants.

QA experience is important, particularly when it comes to designing the interrelating elements of a quality management system. But I am skeptical when I see a resume that is all QA experience. There is nothing like having operational experience to fully understand the practical environment in which GMP systems reside. If a quality system is not practical and useable, then users will find a workaround just to survive.

Explore the operational experience of the consultant candidate and ask how that experience has made them a better QA professional and consultant. Also, there in nothing worse that a consultant that has 25+ years experience only in QA---and all at the same company.

5. Don't write off failure.

There are some consultants who have had failures in their career. Or it may seem like a failure to you, and feel like a failure to the consultant. Experience has taught me that good people have been terminated for wrong reasons. There are those who were fired for standing up to the company against doing the wrong thing. Also, many older folks who have valuable experience were the victims of layoffs just because they were high in the salary band.

I know it goes against conventional wisdom, but be open to the person who you sense has a "history" that he or she is reluctant to talk about, or gaps in a work history. It's just not unusual these days, particularly in QA. I would take someone like that in a heartbeat over someone who had been in QA his entire career at the same company. (Talk about someone who has learned to keep his head low!) It's more about the lesson learned, what they did next and whether it built character.

6. Keep engaged with consultants and own the problem.

Unfortunately, some companies in trouble with the FDA hire consultants in the same way they would engage a contract manufacturer. You cannot sub-contract your problem. Just like a CMO, you are still ultimately accountable for results and managing the relationship. There will be no sympathy at the FDA District Office if you whine about your consultants.

The consultant and the client need each other to succeed, so keep the lines of communication open. Rarely can management solve a problem without some consultant help, and for sure a consultant cannot do it alone. Quite often, the underlying problem touches upon the bigger issues of company culture and leadership. The consultant needs the forum to openly discuss these issues.

7. Don't overcomplicate the oversight.

Consultants are typically involved in project teams that are comprised of client system owners and subject-matter-experts. While there must be management oversight, these project teams need to keep focused on getting the work done. The last thing you need is to have them distracted by preparing tedious PowerPoint updates and administrative activities to multiple layers of oversight and stakeholders.

I have always said that in the absence of real work, administrative activities will creep in and fill the void. Be sure that the consultant and your people who comprise the team are allowed to focus on what you chartered them to do.


I would be pleased to hear advice from you, my readers, from your experience working with GMP consultants.


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Drug Shortage: A Story of Self-Inflicted Management Tragedies

My blood boils when I read an article such as the one that appeared in the New York Times yesterday entitled Supply of a Cancer Drug May Run Out Within Weeks, by Gardiner Harris. This is one of many articles that has appeared lately about the mounting crisis of drug shortages across the country. This time it is the drug to treat acute lymphoblasic leukemia, which most often strikes children ages 2 to 5.

The article quotes the president of the American Society of Clinical Oncology saying that he hopes that the FDA's hard work can help avert a crisis. The FDA is always brought into the middle of the political quagmire of pharma companies, medical professionals and patients. But the FDA is not the "bad guy."

If you were to map the drugs that are in short supply to the FDA's Inspection Observations, Warning Letters and Consent Decrees, you will find a long history of problems that would have given any reasonable management plenty of time to permanently solve the problems.

The truth is that the problems are self-inflicted. There is not one problem that cannot be solved with the right management and the right technical and scientific expertise to establish a capable manufacturing process and facility.

Quality Assurance is not totally off the hook. Often QA cannot see the forest for the trees. They strain the gnat and swallow the camel. Often they are busy policing the proper use of indelible blue ink that they do not see the cumbersome, non-value-added administrative activities that are choking the quality management system.

I read Mr. Harris' article and though of my healthy grandchildren. Thank God.

My heart goes out to those patients who are dependent on life-saving drugs.

C'mon people get your act together!



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