PharmaManufacturing.com's Sound Off

A Control Room Makeover Contest Was Just Launched Today. How About a QC Lab Makeover?
Pharmamanufacturing.com editor Agnes Shanley writes:

Pharmaceutical manufacturing plants in need of better workstations, monitors, alarm management and training services, take note!

Today, Invensys Process Systems' Foxboro Automation unit launched a "Control Room Makeover" campaign to identify the North American process plant control room most in need of a complete overhaul. The winner will have its control room redesigned, and receive upgrades and training worth up to $350,000. Inspiring the move were all those TV reality shows involving everything from plastic surgery to interior design.

Wouldn't it be interesting if instrumentation and sensor vendors joined forces and launched a "QC Laboratory Makeover" campaign for pharmaceutical facilities? Pick an overburdened facility with an overburdened QC laboratory---certainly no shortage of those. The winner would receive preliminary consulting services on statistical process control, PAT sensors to install on its unit operations lines, electronic notebooks, software, and IT and PAT consulting services. It would cost in the millions of dollars, but those costs would be divided among many more suppliers.

Winners would be required to share with the industry the economic and efficiency results they saw one year later.

With all the "waiting and seeing" going on with PAT, more aggressive outreach and, to put it bluntly, a "gimmick" might be just the way to break the ice and allow more manufacturers to experience, first hand, its benefits. What do you think? Would you nominate your firm for such a contest?

Old manufacturing sites tell tales
From PharmaManufacturing.com managing editor Paul Thomas

I journeyed to Pfizer Global Manufacturing’s Kalamazoo operations last week, to present two teams there, collectively, with one of our Team of the Year awards. (Read about them and all of our Team of the Year finalists in our April issue, or at http://www.pharmamanufacturing.com/articles/2005/261.html.) My Kalamazoo stop included a tour of the main facilities—primarily Building 41, a massive tan brick structure built by Upjohn in mid-century to be its manufacturing hub. (Upjohn much later became part of Pharmacia, which was bought by Pfizer.)

I’m told the Kalamazoo site, with some 3,500 employees, is the largest of the more than 70 that comprise the company’s global manufacturing operations. Building 41 houses injectable operations, as well as some solids and semi-solids. Building 41 is a blend of the old and the new. Within the old brick walls are new glass-encased cubicles for offices and secured manufacturing zones. A trusty 30-year-old cartoner on the packaging line might sit immediately downstream from a just-purchased descrambler.

My tour guide, Mark Palkowski, inspection manager for injectable operations, displayed reverence for the building as we walked its halls. And walked. And walked. From east to west, Building 41 is one-quarter mile. In the basement there’s a broad, open hallway that covers the entire span of the building—not surprisingly, it’s a favorite for lunch-time power walkers, Palkowski says.

A competing publication to ours recently ran a facility of the year competition, and awarded its top prize to an ultramodern, ultra-expensive new site with all the latest technological bells and whistles. That’s all well and good—the march of progress must go on—but give me a building with a little history behind it any day.

Special thanks to site director Niall Condon, Right First Time director Jill June and the rest of the Kalamazoo staff for the tour. If I may, I’d like to make a request of Pfizer: Someone, please, write the history of the Kalamazoo site, including Building 41. Walls can talk, and what stories they have to tell.

Is there a building you care about? Let us know.

Can FDA maintain its independence without resuming its old "adversarial" stance?
Pharmamanufacturing.com editor Agnes Shanley writes:

This week, we heard FDA safety officer David Graham say that the new Drug Safety Oversight Board established by the Agency to help ensure drug safety, is "severely biased in favor of industry."

In a June 8th article in the Washington Post, Graham said that the makeup of the panel made "drug safety in the U.S. worse today than it was in November."

At the same time, Senate Finance Committee Chairman Charles Grassley has issued his own criticisms, the Post reports, calling for a move to "improve transparency and accountability."

These criticisms and closer scrutiny on the front end of the approval process can only improve the safety of the U.S. drug supply. But one hopes that political pressures won't force FDA to backtrack on the very positive direction it has been taking toward regulating manufacturing: specifically, its move to universal risk-based and scientific principles, applying to both regulators and industry, and its adoption of a less adversarial stance toward drug manufacturing.

FDA must maintain its independence at all costs. But we've seen what an adversarial FDA has brought manufacturers: a backward mindset, a reluctance to try new technologies or to embrace change, and more attention to the "letter" than the "spirit" of the law. And this approach ultimately costs the U.S. consumer.

Today, leadership within FDA recognizes that the Agency and industry should share one top priority: the interests of the final end user, the patient, and that their actions should advance that goal. Making FDA plant inspections completely objective and giving companies credit for achieving real understanding of their processes is part of a necessary change in FDA mindset. One hopes that U.S. lawmakers don't misunderstand it.

Given the mounting political pressure, it will be interesting to see how the Agency maintains this delicate balance between rigor and conciliation. Any thoughts?

One in three drug researchers take shortcuts, survey says
from Pharmamanufacturing.com editor Agnes Shanley:

I remember an old acquaintance, definitely not a close one, who was working on a graduate thesis in psychology at a third-tier private university in New York. She even boasted about fabricating data for her research---not all that difficult to do in a "soft science" such as psychology.

Today, I hear, she is working in some capacity in the New York City public school system. Occasionally, I've wondered whether her cavalier approach to research has colored her approach to her job, and what the fallout for her young charges has been---particularly at a time when there is a knee-jerk approach to labeling students as having ADD, and suggesting medication that may be far more dangerous.

But at least in psychology, unlike medicine or drug research, the impacts of dishonesty or incompetence are limited. Even a truly evil school psychologist such as "Dr. Pikell" immortalized by Louis Sachar in his "Wayside School"---who hypnotized his subjects without their knowing it--- only has access for a few hours a day and can't actually prescribe medications.

Today, news came out of a new survey by HealthPartners Research Foundation in Bloomington, Minnesota, published in the U.K. journal, Nature, which suggests that a surprising number of drug researchers may be committing scientific misconduct.

The study, which followed more than 3,200 scientists who had received grants from the National Institutes of Health, indicates that one in three U.S. scientists have committed misconduct---such as claiming credit for someone else's work. Over 12% admitted to overlooking others' use of flawed data. 15% admitted to changing the design, methodology or results of a study due to funding pressure. Fortunately, fewer than 1% admitted to faking research data, but 27% kept inadequate records, and 15% dropped empirical observations or data from analyses.

Study authors speculate that pressure to produce results is leading some to taking a "Procrustean" view to research, and cutting results to fit their goals.

One can only speculate on the impact that this pressure has on corporate research scientists---and even staff involved in clinical trials and scaleup. What are your thoughts?

"We're so far out of compliance. Let's not make it any worse"
A quality manager writes in:

"We're so far out of compliance. Let's not make it any worse." What would you do if you heard that statement made by a director-level quality professional? Would it matter if the statement was made within a major pharmaceutical company two years after the organization agreed to a consent decree with the FDA?

Believe it or not, this “declaration of non-accountability” was repeated so often by members of the site’s quality organization that it became a much-repeated joke within the entire manufacturing facility.

Perhaps the initial statement was said out of stress and frustration at the mind-boggling number of changes that needed to take place within quality assurance and compliance systems.

But when it’s repeated often enough to become a standard joke or to excuse noncompliance with meeting consent decree commitment dates, then you know there’s a deep-seated problem within the ranks of leadership.

The implications of this startling lack of accountability and failure in leadership were numerous and symptomatic of a compliance culture in deep denial of basic regulatory and quality assurance obligations. The FDA ultimately agreed with the deep-seated nature of problems by documenting 40+ observations in 483 inspection findings over a 2-year period after the consent decree was initially announced.

Think this was (is) the only example of a consent decree site with compliance and operational problems? Think again.

I recently became aware of two individuals who were terminated within the last six months at FDA consent decree sites for raising issues to senior compliance managers and third-party consultants regarding progress against commitment dates. For those of you unfamiliar with consent decrees (and let’s hope you will never have this career opportunity), a commitment date is a deadline established between the company and FDA for implementing improvements conforming to CGMP regulatory requirements.

In recent years, FDA has delegated some of their oversight responsibilities to third-party consulting firms who are required to “verify” that quality assurance and compliance systems have been successfully implemented, are operating within new and improved standards, and can withstand the pressure of daily operations to “sustain” GMP compliance. The third-party firm documents these results in excruciating detail and provides verification reports to FDA compliance officials. In theory, the FDA can choose to inspect consent decree sites at a moments notice to ensure this oversight system is working, but in reality defers responsibility to the third-party consultants.

It is at this point where the oversight system seems to be breaking down, according to the two internal whistleblowers who claim they lost their jobs for questioning integrity of the consent decree verification process. In the rush to meet consent decree commitment dates and avoid fines of $15,000 per day for each violation, these compliance project managers said their companies refused to investigate concerns related to the accuracy and integrity of verification audit results being submitted to third-party consultants who then forwarded this information to FDA consent decree compliance officials. Concerned with falsifying GMP documents and contributing to fraudulent business practices, these individuals “blew the whistle”, only to suffer retaliation and ultimately, dismissal.

We’ve seen big consent decree fines recently and rumor has it that a major player and FDA currently are in negotiations over another “whopper.” But is the process of improving, verifying, and sustaining GMP compliance per consent decree requirements in fact a sham?

If these statements and incidents keep surfacing, then consent decrees will become another cynical joke like the statement “we’re so far out of compliance, let’s not make it any worse.”

Crossing the ethical line
What’s more important to you – personal integrity or financial security?

Every employee, manager, and executive within the pharmaceutical industry has been faced at one time or another with the difficult choice of confronting questionable business practices. Why do some choose the high road of ethical behavior and conduct while others play at the edge or cross the line?

For several years, I worked in a manufacturing facility producing a biological that was, without question, non-compliant with the most basic of GMP regulatory requirements.

There was no dispute that corporate quality auditors, outside compliance experts, and senior executives from a variety of organizational functions knew of the facility’s GMP compliance “issues.” The audit trail of internal inspection reports, GMP documents and records, and e-mails confirmed the dire situation.

The release of intermediate and finished product despite these documented regulatory deficiencies constituted product adulteration, a serious situation that has affected the business of corporations like Schering-Plough, Abbott Labs, GlaxoSmithKline, and recently, Able Laboratories.

Yet, inspectors and officials from CBER/FDA who suspected the “worse case scenario” chose not to thoroughly investigate or take action. Even worse, they trusted the misrepresentations of company regulatory affairs and compliance executives without confirming or disconfirming allegations that had been surfaced to in-house attorneys and investigators.

The adulterated release of product violated terms of a consent decree previously brought against this company for a five-year pattern of ongoing manufacturing and quality assurance violations. Even more serious, the adulterated release of product allowed this company – still under the long shadow of its consent decree today – to book revenue and report earnings and profit to shareholders and Securities and Exchange Commission regulators knowing full well that its own publicly stated commitment to sustainable compliance was fraudulent.

Yet, most senior decision makers within this facility and organization who were in a position to put an end to GMP noncompliance and adulterated release of product refused to do the right thing. Long-term employees who had witnessed years of shortcuts were silent in calling attention to the issues, even refusing to speak anonymously to the “internal ethics hotline” or directly to the FDA. Senior executives close to retirement chose to take the easy way out and avoid controversy in their final years and months on the job.

In a business that formulates a potentially toxic mix of compounds which are then injected into human being's immune systems, everything related to GMP manufacturing and quality control matters. If it didn’t matter, then why spend millions of dollars in review, validation, and inspection of protocols, procedures, and systems to ensure compliance with a company’s own policies and procedures?

Justifying shoddy documentation or quality assurance system failure as not relevant to the “safety profile” of a regulated product is a stark admission of professional failure, cowardice, and the placement of personal financial security ahead of the well-being of consumers, patients, and shareholders.

My tenure within this organization was short lived. In fact, I predicted my demise just six months into the job due to the chronic nature of denial and resistance to GMP compliance requirements within the corporate culture. What is sad about the memory of this situation, however, is not the legalistic mumbo-jumbo issued by corporate attorneys or outside counsel, but the silence of employees who knew better then and still know better today, and yet, continue to remain silent.

The disappointing choice made by many people was confirmed within this manufacturing facility – financial security is more important than personal integrity. We claim vision and mission statements that call us to prevent illness and disease, or lead the way to a healthier world. Yet, we remain silent when called to the task of speaking up against business practices which jeopardize these visions and missions.

What’s more important to you? Do you know? Do you care?

Peter Rost On the Spot
Did any of you watch "60 Minutes" last Sunday? Pfizer executive Peter Rost was interviewed extensively on his views about drug importation. He has been expressing these views openly for the past few years, in public forums and before the U.S. Congress.

On Tuesday, though, Rost says, he found that his work cell phone had been disconnected as well as his office e-mail. No word since.

Clearly an excellent marketing executive with a long track record, Rost is also a man with a conscience, evident from his past, when he took on the "whistleblower" mantle and reported financial reporting issues at another major pharma company. Now, Rost's future with Pfizer and in the industry seems unclear.

Instead of cutting his phone and email access, why don't Pfizer and industry representatives offer to debate these issues publicly, in a televised forum?

Firing anyone for his or her views is clearly untenable for any company today---particularly if the employee's work is consistently good. And if we are to believe "Confessions of a Viagra Salesman," the company did not fire a certain salesman whose "numbers were good," even though he took unscheduled personal trips and did some other unethical things on company time.

So far, Pfizer has managed to keep from crossing that line where Peter Rost is concerned. I hope it continues to hold that position. But maybe it could take the next step and engage in open, honest debate before the public, rather than hiding behind "official statements" and press releases.

A plant project manager responds to marginalization, Part III
A pharmaceutical plant project manager who is being marginalized realizes that change must begin with him.

The consultant replied, “It sounds like you’re starting to move through your own denial and resistance to confront this situation and make a change for the better.”

“Yeah, I’m starting to see that if my team and I are going to stop being marginalized, then we need to approach the issue from a different point of view. And that means I have to start the process.”

“Good, now that you’ve seen the light, let’s talk about the final two stages of the change process. The Exploration Phase is where your new sponsor or sponsors will be willing to take on some risk in proposing a change in project sponsorship. You have to also be willing to entertain new ideas and possibilities, including the possibility that the hoped for change might not happen. Are you ready for this?” asked the consultant.

“Yes, I am. But I’m starting to realize as a result of our discussion that I first need to have a conversation with my supervisor, the managing director, about my perceptions of being marginalized. I guess I’ve been dreading this dialogue because of his reputation for responding emotionally to negative situations.”

“How might you start off the discussion?”

“I’d use the same approach that I just mentioned a second ago with the two individuals I thought might make better sponsors for this consent decree project.”

“And they still could become sponsors, could they not?” asked the consultant.

“Well, you’re right. But that’s a solution that might come about as a result of having an honest, heart-to-heart conversation with my boss. Once I work this person through the denial and resistance phases, this is something that could pop out of our exploring possible solutions together. I know the managing director will be looking for solutions, so I need to have a number of practical options available for him to consider. One of these could be a change in sponsorship.”

“My friend,” intoned the consultant, “you’ve just worked through the last phase of change, the Commitment Phase. This is where people take ownership and responsibility for new and improved ways of doing things. People with commitment feel in personal control and they take ownership. They feel comfortable and hopeful about the future. They reflect on what they’ve learned or just been through. Congratulations, but you did a great job of talking yourself through the process of change. You’re back on the road to implementing this consent decree project and meeting the upcoming commitment date.”

“I want to thank you for helping me think through this situation. Do you have any other words of wisdom for me?”

“Of course, that’s what I get paid for,” chuckled the compliance consultant. “If you’re going to be a “change-meister”, then you are in the business of helping people (1) see why they have to change, (2) let go of old ways and habits, (3) align with new requirements or direction, (4) adapt to new values and behaviors, (5) commit to what needs to be done to make it work, (6) get involved with creating success, (7) develop resiliency by learning new skills, and (8) view continuous improvement as just a part of their jobs.”

As the story goes within this pharmaceutical plant, our compliance project manager was successful in getting required support, a project completed by the commitment date, and a better opportunity within the organization.

A plant project manager grapples with marginalization, Part II
In this second part of the conversation with an external compliance consultant, a pharmaceutical plant project manager searches for ways to avoid being marginalized within his organization and workplace.

“So, what information would you present to a potential new sponsor about the need for change with the consent decree project?”

I replied, “Well, I would bring this individual up-to-speed on what’s been happening - or not happening - in the last 10 months. I would go back to the “business case” for why we as a manufacturing site have to do this. I would provide documented examples of failures within this quality system that have impacted our ability to meet both GMP compliance and delivery requirements. I would also ask this individual for their perspective and then their advice.”

“Very good,” the consultant replied. “You have been paying attention to some of the topics we’ve been reviewing in the change management classes. How do you think your potential new sponsor is going to react?”

“Probably in the same fashion as everyone else – negatively. There seems to be a built-in, automatic reflex in this organization to immediately deny that anything is wrong. I know the company has been besieged with lawsuits over the past eight years, but sticking your head in the sand isn’t going to make the situation better.”

“This second phase of change – the Denial phase – is tricky,” the consultant said. “Most responses to even the prospect of change are negative. Change is viewed as a threat to stability, but it’s really a fear of the unknown. People in denial usually say some pretty interesting things. What do you think your new sponsor might say?”

“Certainly, I hope this individual would be different, but they might initially say, ‘I’m too busy right now.’ They might minimize the potential impact of not taking action by saying, ‘it’s not a compliance or consent decree risk.’ They might even want to wait until someone else takes action to reduce any perceived political risk.”

The consultant replied, “I’m glad you’re starting to anticipate typical responses of people in denial. Of course, if you select your person correctly, the amount of time you and he or she spend in this phase will be minimal. What do you think happens next?”

“I remember all of the discussions about ‘resistance to change.’ Resistance occurs when people begin to let reality sink in. People in the Resistance phase show anger, complain, and sometimes sabotage. They provide excuses, act burned out, and won’t let go of old habits or ‘comfort zones.’”

The consultant said, “You’ve met some major resistance to the changes proposed by your consent decree project. How might your potential new sponsor facilitate the transfer of this project? And, how do you both do it in a way that saves face for the managing director?”

“If I select an individual that the managing director respects, then I think we have a chance. But it’s going to take a person with a strong personality and armed with a lot of data to work this individual through denial and resistance.”

“Do you think your new sponsor will understand these first three phases of the change process?”

I replied, “I can think of two people who might be willing to provide me with advice as well as consider taking on project sponsorship. I’ll need to work them through any denial or unwillingness they have to face up to these critical issues. I need to help them understand that we’ve had unrealistic expectations about the type of change we’ve asked of ourselves and the amount of resources needed to accomplish it. I need to frame the issue as less of the managing director’s treatment of the project or myself and the team and focus instead on how we can find a win-win solution.”

The consultant replied, “It sounds like you’re starting to move through your own denial and resistance to confront this situation and make a change for the better.”

To Be Continued…

Wake up! You're Being Marginalized (Part I of III)
“You’re being marginalized.”

The words from the outside compliance consultant hit me right between the eyes. So that was the official diagnosis for the incredible frustration and stress my team and I felt in trying to reach a consent decree commitment date at this manufacturing site. It should have been apparent for at least the last 10 months that this was a commitment no one else oo high really supported, despite the presence of the FDA decree.

I asked, “So, what can I do about it?” The consultant replied, “What do you want to do?”

I told the consultant that I wanted this situation to change and improve. I wanted other directors to demonstrate support and accountability for reaching milestones and commitment dates that had been promised the FDA. I told the consultant that I wanted to get the voices of my team members heard so we could reduce work pressure and make life easier for everyone.

“I don’t know if I can promise you all of that, but here’s what I can promise,” the consultant replied. “You’ve got to change your strategy and approach if you’re going to get what you want and especially if you’re going to stop being marginalized in this environment.”

I was eager to learn how to work through this difficult and frustrating situation. The consultant shared with me that from his observation post, we had no real or effective sponsor for our work. “I hate to break it to you, but the managing director doesn’t care about this part of the quality system as much as you do. His expectations are far, far lower than yours. In fact, he sees your efforts as slowing down the manufacturing process and preventing product from getting shipped.”

Before I could say anything, the consultant said, “I know, I know, it’s hard to believe, but that’s the situation and other directors are just taking his cue. I’m going to tell you that you’ll need to get a new sponsor without alienating or creating any more friction with the current director. In fact, this little shift in sponsorship may be a win-win solution considering the workload and stress this person is experiencing.”

“So, how do I go about persuading someone else to sponsor this consent decree project?”

“Before we talk who, let’s discuss how you’re going to approach this someone else and what information you’ll be presenting and why. Look, in the process of accepting change, people go through predictable and normal responses. I don’t care who you are or what topic you’re talking about, this is the process you have to work other people through. What do you think the first step is?”

“Well, I’ve got to let someone know about the current situation.”

Correct. This step of the change process is called Awareness. We see thing through eyes that are accustomed to “business as usual.” It doesn’t really matter if there’s a consent decree or not, or if there’s a huge market for the new product you’ve developed or whether senior executives have given speeches on this topic. People have two questions at this stage of the game: Why do I (or we) have to change and what’s in it for me?”

“I thought we did all of this at the beginning of the project. I thought we had consensus during the project kickoff. Why aren’t we just getting on with it?”

“You had an agreement 10 months ago, but something has changed in the environment and you haven’t changed your thinking or strategy in response to this change. Many leaders, including you, mistakenly believe that people should automatically know what’s going on and change or improve because they have to.”

The consultant continued, “So, the Awareness that’s required today is different than when you started the project 10 months ago. What information would you present to a potential new sponsor about the need for change with your consent decree project?”

To Be Continued...

When a Pharma H.R. Department Resembles a Soap Opera
One reader says his company's Human Resources department operates like the soap opera “Desperate Housewives”

Every now and then you come across the report of a situation that could rival the intricate twists and turns in plot of a prime-time television show. For example, where could you find in the space of 18 months in a Human Resources department within a major player in this industry the following?

• Financial embezzlement
• Passing of trade secrets to a competitor
• Gross sexual misconduct
• Firing for incompetence and public drunkenness
• Failure to investigate and document harassment complaints
• Public intimidation and provocation of employees
• Employment counsel lying to federal investigators
• Power struggles between corporate and site professionals
• Profane descriptions of HR skills and capability by internal customers

It was hardly a laughing matter if you were one of the unfortunate employees or managers who had to live in and work through this real-life debacle. One would think that the HR function, and all of the various personnel administration, recruiting, benefits, and organization development professionals would rise above the typical pettiness and politics of corporate intrigue.

What do you suppose the problem was? If you guessed dysfunctional leadership, you would be accurate. But where was the leadership lacking? In site Human Resources? At the corporate level? Was it exclusive to just HR or did it cut across to a dysfunctional work culture led by absentee senior executives?

Unfortunately, outrageous conduct and unethical behavior on the part of supposed professionals in Human Resources was tolerated (or condoned) by senior executives in this pharmaceutical corporation. It was a major distraction that took away the focus on achieving sales, operational, compliance, and financial goals of the vast majority (the silent majority) of workers who wanted nothing of the drama encountered in site and corporate HR.

How does one survive this type of work environment without having to jump ship and look for another position? (The grass may not always be greener and you may not want the hassle of finding a new job, moving, etc.). Should you take the step to write an anonymous letter to the senior executive in charge of the division or business group? Write a letter to the chairman of the board of directors? Just hunker down and hope the storm blows over soon? Resolve to stay away from any interaction with Human Resources?

I wish I knew the correct advice to provide. I heard reports of and saw employees doing all of the above.

The Human Resources department is the first place to go to for help in finding solutions to difficult people management issues (usually). It’s a bit disconcerting when HR is living its own version of “Desperate Housewives.” Let’s hope your workplace doesn’t have the drama associated with this type of soap opera. It’s difficult enough to meet delivery or sales goals without the distraction.

Employees are jumping ship: it's sink or swim. What would you do to turn this situation around?
A plant manager writes in...

Retaining top performers and talented employees is a strategic business issue for pharmaceutical manufacturing organizations. What kind of a business case and action plan would you make to the vice presidents of finance and human resources if your organization was faced with this hypothetical case study?

Pharma X is a small biotechnology firm developing, manufacturing, and marketing vaccines. The organization won approval from the FDA twenty years ago to market a vaccine that attacks a debilitating respiratory illness. The organization has grown in size from a small start-up team to over 500 employees with annual sales revenue of $250 million and profit margins in the 25-30% range.

Recently, two new biotechnology firms have started operations in the area, locating their facilities only 30 miles from Pharmaceutics research, manufacturing, and administrative facility. Although producing and marketing different products than Pharma X, these competitors utilize similar skill sets and technical competencies. They also offer starting salaries 25% higher than Pharma X's base salary for entry-level employees.

As a result, over 33% of manufacturing operators and quality assurance specialists have left Pharma X in the last two years, many after receiving skills training worth $75,000+. Another 10-15% have stayed with the company, but transferred to other departments within the organization. The management team has experienced considerable turnover in the last two years as well, having replaced 40% of the senior leaders.

Exit interviews were not done until recently, but operators and quality personnel have been voicing complaints for some time about the “work culture” inside manufacturing and quality operations. Specifically, concerns have been raised about the pay-for-skill compensation system, the lack of training required to learn skills and maintain regulatory compliance, as well as the lack of employees and supervisors to properly staff each team and area. Many employees complain about the “shortcuts” which management seems to reinforce with their constant nagging about getting product “on the truck.”

Pharma X recently obtained FDA approval for a new vaccine that is forecast to grow to over $1.5 billion in sales within 5 years. This product is extremely complex to manufacture with a production cycle of 10-12 months. The organization is just starting to finalize hiring plans, but the preliminary estimate is for employment to grow and reach 1,500 employees within a few years.

The vice presidents of finance and human resources are concerned about the vulnerability of the organization, the financial impact of this turnover, and the range of options and potential solutions.

What possible recommendations might you consider in a presentation scheduled for next week?

How important is safety at your site?
A pharma safety manager writes in:

Is your work site considered a safety conscious work environment? Do employees perceive they have the ability to raise safety concerns without fear of retaliation?

I recently visited an organization on the Internet that caused me to start thinking about the “safety culture” without the pharmaceutical manufacturing facility I work. We meet minimum safety compliance requirements, but I’m not so sure we qualify as a “safety conscious work environment.”

The non-profit organization, Employee Concerns Program Forum (www.ecpf.org) is “dedicated to industry professionals who provide alternative dispute and conflict resolution services to nuclear utilities and companies doing business in highly regulated industries such as Department of Energy, petroleum, aviation, healthcare, and financial services.”

At first glance, I didn’t think the website would have anything to offer companies in pharmaceutical or biological manufacturing businesses. But there is enough merit in the ideas being advocated that would help drive improvements in both the safety and GMP compliance culture of any workplace dedicated to continuous improvement. As the pharmaceutical industry is often accused of being arrogant and unwilling to listen, perhaps we can learn from the mistakes or lessons of other industries.

The discussion at the Employee Concerns Program Forum website reminded me of a conversation I had with two manufacturing operators concerned with the use of a dangerous and toxic chemical within their production area. These two individuals were so concerned about the use of cyanide in the manufacturing process that they were getting ready to refuse to work in the area because of their concerns about the lack of training, lack of supervision, and adequacy of protective clothing and equipment.

I asked these operators if they had approached their supervision or the manager of environmental, health, and safety. Yes, they had discussed their concerns, but to no avail. They perceived a “take it or leave it” ultimatum and resigned themselves to face a potentially deadly exposure to this fearsome chemical. I asked if there was something my department could do to help raise these issues to the surface and resolve the problem. The two operators asked if we could intervene and help mediate a solution. Unfortunately, the result of our intervention was much the same, with our diplomatic approach brushed off as “something that is not your concern.”

This incident told me a lot about the culture of the organization I was working in. I was disappointed and frustrated that we “blew off” the concerns of these two experienced operators. How many other people had concerns about the use of this toxic chemical and just weren’t voicing their opinions? Wasn’t there a better way to approach the concerns of these employees?

The Employee Concerns Program Forum website offers a potential solution to this dilemma, if an organization’s leadership is willing to put forward the effort to listen to the perceptions and concerns of employees and then take action to resolve the underlying root cause problems in a work climate of “no shame, no blame, and no retaliation.”

The elements of a “safety conscious work environment” incorporated within an “effective process for problem identification and resolution” as recommended by the Employee Concerns Program Forum include:

1. Employees are encouraged to raise safety concerns.
2. Management is promptly notified of concerns.
3. Concerns are promptly prioritized and reviewed.
4. Concerns are appropriate resolved.
5. Timely feedback is provided to the concerned individual.
6. An appeal process for concerns is available.
7. Self-assessment of the problem identification and resolution process is conducted.
8. An alternative process to line management is implemented (as warranted).

This approach looks like a reasonable alternative to recording and investigating lost time accidents (or worse). Maybe I’ll slip the website address to some senior managers who might be able to make a change in our “don’t be the tall pole” environment.

Cn u reed yr SOPs?
A training director writes in:

Is GMP documentation enabling or hindering performance and compliance within your organization?

When was the last time you examined the readability and usability of your SOP’s from the point of view of employees?

I was reminded recently of a conversation with a corporate quality auditor for one of the biggest pharmaceutical and biomanufacturing companies in the world. This auditor was an extremely well-educated and capable professional assigned to support a task force and project team charged with improving the GMP document control system. The organization had realized that its system for controlling GMP documentation was outdated and incapable of supporting rapid business growth and tighter compliance standards.

Unfortunately, project team members did not examine the quality of GMP documentation flowing in and out of the system, nor did they investigate the linkages and integration with other key quality assurance systems, including GMP training, change control, or investigations. These obvious oversights were very much a reflection of the “worldview” and bias of the corporate quality auditor who dominated initial process improvement activities of the task force and project team.

For example, investigation of GMP documentation by other departments within this organization concerned with both direction of the task force and lack of direct operator involvement in the process revealed:

• The majority of SOPs were written by Ph.D. developmental scientists at a 12th grade reading level.
• Authors were paid bonuses for writing SOP documents tied to the number of pages produced; in addition, there was no cross-checking or correlation of SOP documentation with GMP batch records or training documents and records.
• The average reading level of biomanufacturing operators was determined to be between the 8th and 9th grade reading level.
• SOP’s for the growing product line exceeded 250 with the majority of documents running 50-60 pages in length.
• The site managing director issued an opinion that there was no connection of SOP document quality to GMP compliance.

When confronted with this information, the corporate quality auditor’s response was: “Operators need to learn to read at the 12th grade.” Needless to say, it did not take long for this arrogant “sound-bite” to travel throughout the facility. Complaints surfaced immediately in the manufacturing, quality, and human resource departments. One manager likened the response to Marie Antoinette’s statement before her beheading in the French Revolution (“let them eat cake”).

It was not long before the organization determined a change in leadership was required for this task force and project team. A more experienced quality assurance manager with a background in GMP documentation and quality control system improvement was hired. In addition, the charter and scope of the project was enlarged to ensure documentation quality and systems integration with other key GMP systems. Finally, representatives from other departments with a critical stake in the project team’s outcomes were added to task force membership.

What lessons can you take from this experience? What would your frontline employees say about your SOP documentation and document control processes?

We don't have time for training!
“We don’t have time for training.”

Can you imagine a site managing director within the pharmaceutical industry making that statement in front of a group of employees assembled to meet with the company president to discuss progress of FDA consent decree requirements?

Can you believe that nothing happened in this organization as a result of this public confession of non-accountability and non-compliance? I hope this isn’t your workplace, but unfortunately, this visible lack of commitment to one of the key components of any quality assurance and compliance system did take place recently within a consent decree site.

And absolutely nothing happened – unless you count the endless hours of wasted talk and negative speculation from employees and supervisors on the shop floor and in the quality labs. As you would expect, the level of trust and commitment to GMP compliance within this company’s workforce declined. I don’t have to mention the credibility that was lost by the senior executives gathered in the room.

Contrast this inexcusable state of affairs with two other organizations marketing medical devices produced by world-class manufacturing operations with outstanding reputations for quality and compliance. GMP training – whether it’s delivered as foundational training, refresher training, skills training, or cross-training, is considered sacrosanct – a fancy term for “we take it serious.”

There are no shortcuts to developing the attitudes, knowledge, and skills of operational, technical, management, and professional employees in these two companies. In looking at the success of their manufacturing operations, key managers from both organizations – using similar concepts, but slightly different words - highlighted the following reasons for why training makes a difference in their workplaces:

1. “We hold managers and supervisors accountable for training compliance and performance.” In these organizations, work team leaders are tasked with the primary responsibility for ensuring people are trained, qualified, and certified prior to working independently on their own. GMP auditors double-check records for compliance on a monthly basis. Needless to say, performance is at 100%.

2. “We link training outcomes with key operating metrics and business results.” For these manufacturing operations, training is about performance, not just training hours, classes, or SOP reviews. The end result of training is 100% task or SOP performance within standards expected in daily operations.

3. “We integrate training with other quality assurance functions, including document control, change control, and manufacturing or laboratory investigations.” In these world-class manufacturing plants, the GMP training system is tightly linked to other quality processes. SOPs are not just cross-referenced as in other organizations. There is strong cross-functional teamwork and integration of information systems which produce records and reports.

4. “We use training and career development to attract and retain top performers.” In these organizations, training is considered an investment in people and improved performance versus an expense to be minimized. As might be expected, these operations experience above average retention levels and use training and career planning to maximize the contribution of top performers.

5. “We use talent from the ranks to drive training system development and operation.” The training function, whether centralized or decentralized, consists primarily of employees who have “been there, done that.” These individuals have the credibility, technical know-how, and savvy to keep training lean, relevant, and effective. They are supplemented by outside resources as necessary to learn new approaches to training or training system operation.

If you’re not taking the time for training, then you’re missing out on an opportunity to improve performance in your workplace. If these world-class manufacturing organizations can figure it out, you can too!

Did FDA cuase recent vaccine supply problems? Would abolishing cGMP's help?
A reader responds to a very provocative article:

Did the Food and Drug Administration cause recent vaccine-supply problems? Would abolishing Current Good Manufacturing Practices rehabilitate the crippled U.S. vaccine industry?

These are two questions posed in a provocative 2004 article written by Arthur E. Foulkes in The Independent Review. In this article, “Weakened Immunity: How the Food and Drug Administration Caused Recent Vaccine-Supply Problems”, Mr. Foulkes – a free market economist - makes no effort to hide his disdain for the FDA. The premise of his article is simple: the FDA was the cause for the serious supply problems involving nearly all childhood vaccines recommended by the U.S. Centers for Disease Control and Prevention in the last five years.

Foulkes contributes fuel to the recent debate over the FDA’s role in ensuring safety and efficacy of drugs, vaccines, and medical devices by stating that “CGMP’s and the FDA are patently unnecessary and, indeed, do far more harm than good.”

He makes his case for abolishing CGMP regulations and allowing private providers of assurance to compete with the FDA by describing (1) how the FDA caused vaccine supply problems, (2) how CGMPs are a threat to the supply of vaccines and other health-care products, and (3) how life would be better for vaccine manufacturers and consumers without the Food and Drug Administration.

Foulkes minces no words in placing blame for vaccine supply problems with the FDA. He describes how the FDA’s inspection of vaccine plants changed in 1999 with the creation of Team Biologics, a new program created for inspecting the biologics industry. Foulkes writes that inspections soon changed from focusing on scientific and technical issues to a broader emphasis on CGMP compliance. Further, he finds fault with the FDA for failing to inform the industry that “they were changing the rules of the game.”

For each of the “factors” reported by manufacturers as well as the FDA for the recent supply problems, Foulkes traces the “root cause” back to the “government granted monopoly” held by the FDA for health-care product certification. As a first step, Foulkes would abolish CGMP regulations, writing that “despite the name, ‘good manufacturing practice’ violations usually have nothing to do with actual manufacturing or with the quality of the product that reaches the consumer; they almost always consist of failures to fill out countless forms in the minute detail that only a bureaucrat could care about.”

In one section of his article titled “Life Without the FDA,” Foulkes argues that there is no reason that the government (FDA) has to be the guarantor of quality assurance and regulatory compliance. Foulkes presents evidence that the FDA’s record has in fact harmed many more people than protected, citing four examples of “deadly FDA obstruction.” He concludes that “economists who have studied the FDA agree almost unanimously that the agency does far more harm than good.” As a result, Foulkes recommends a private system of product quality assurance by given the opportunity to develop in order to balance the costly excesses and delays inherent within the current system of government oversight.

Although provocatively written to force us to think about the value of FDA regulation, “Weakened Immunity” contains factual errors and naïve assumptions about the vaccine business which undermine the argument that life could be better without governmental “checks and balances.”

For example,

• The often-cited figure of 36,000 annual deaths due to influenza has not been supported by data and statistics from the Centers for Disease Control itself.
• The “record” $30 million fine paid by Wyeth-Ayerst in 2000 was a slap on the wrist compared to fines paid by Lilly, Abbot, and Schering-Plough (to the tune of hundreds of millions of dollars).
• The scientific “link” between thimerosal (49.5% ethyl mercury) and developmental disorders in children has been thoroughly researched and although controversial, could have been fairly reported (reference the newest book on this subject, “Evidence of Harm”).
• The evidence cited for the complexity of vaccine manufacturing focuses on the yearly decision by the CDC for which strains to include in the flu vaccine and does not investigate other vaccines with production cycles of 6-12 months.
• The allegation of “vague regulatory language” fails to point out that CGMP’s originated from industry “best practices” and are supplemented by internal policies and procedures of manufacturers (which have not been followed if you closely read consent decree documents from the last six years).

In the world according to free-market economists, there is little possibility that a vaccine earning hundreds of millions of dollars each year could be introduced into the marketplace without adequate manufacturing capacity and capability to meet projected demand gained through approval as one of the recommended (mandated) vaccines on the children’s immunization schedule.

At the very least, Mr. Foulkes could have assigned “joint accountability” for decisions made by both the CDC/FDA and industry which years later, result in predictable “supply problems” and “shortages.”

“Weakened Immunity” gives the biological vaccine industry a free pass, which for those of us who report on this industry and who previously worked diligently and closely with professionals at both the FDA and within major corporations, is irresponsible and reckless.

Are you a boiling frog where compliance is concerned?
What happens in your organization when people responsible for GMP compliance or business integrity fail to do their job? Does anyone in positions of authority get excited and demand answers as well as improvement? Or is the slow-motion reaction one of “business as usual” and/or defensive cover-up?

Unfortunately it seems, many workplaces and organizational leaders in the pharmaceutical and biomanufacturing industry operate with a “boiling frog” mindset. Remember that story? You place a frog in a boiling pot of water – and it immediately jumps out. But if you place that same frog in lukewarm water, it just sits in the pot. As you begin to turn the heat up slowly, the frog continues to sit. From the frog’s perspective, nothing has really changed in their environment. Given enough time, the frog is boiled to death as the heat continues to rise.

The same thing happens in an organization which tolerates attitudes and behaviors out of alignment with company and regulatory requirements in the areas of GMP compliance, business ethics, or professional integrity. This “accountability failure” starts at the top of a manufacturing site and/or corporate organization and slowly filters down to frontline employees.

It manifests itself when audit findings and recommendations from committed quality or compliance professionals are marginalized or go unheeded and unanswered. It’s easily identifiable when “action plans” or “legacy plans” are constantly put in place, but never actually or fully implemented. It reveals itself when internal complaints are whitewashed or worse, the “offending” employee with the “bad attitude” is retaliated against.

In the end, the organization establishes and reinforces a workplace culture where employees are expected to act like “frogs.” They sit and wait for the next round of “heat” without taking action to escape an unacceptable environment. The net result is a workplace where expensive lessons are learned: wasted materials, recalled product, warning letters, consent decrees, or ongoing inspections and investigations.

And if you’ve ever worked in one of these types of organizations, then you know they’re stressful, tense, and unsatisfying places to practice your profession or craft.

This failure in accountability needs to be identified and resolved at every level of an organization, if it’s really dedicated to compliance, integrity, and performance. Here are some warning signs – in the form of justifying statements - that might alert you to the presence of attitudes or behaviors setting your organization up for the “boiled frog” mindset”:

1. “We don’t have a compliance or ethics issue.”
2. “It’s someone else’s job to stand up or speak up.”
3. “Let’s worry about it later, we have too much to do right now.”
4. “The FDA never found it in all their inspections.”
5. “Well, the FDA approved it.”
6. “This complaint is from a disgruntled employee.”

Do any of these sound familiar? If so, it may be time for a reality and attitude check. Is the “heat” starting to rise in your organization and you just haven’t noticed or been paying attention?

Maybe it’s time to quit thinking like a frog in the safe environment of your pot of water. Maybe it’s time to jump into action!

Don't blame your own quality issues on FDA!
A Pharmaceutical Manufacturing reader writes in:

Yet another GMP manufacturing disaster has been reported in the news. This time, a major player in the industry had several of its products seized from warehouses after failing to resolve two years worth of quality control issues. Manufacturing and distribution of these products – representing over a billion dollars in sales - was halted until FDA regulators were satisfied the company had taken necessary steps to fully resolve problems found in previous inspections/warning letters.

The response from the company placed blame on the FDA for failing to accurately communicate its expectations. As a former manufacturing executive and now GMP consultant to the industry, I hear this “excuse” too many times from the spin-doctors in corporate communications (and the legal counsel telling them what to disclose or not disclose to consumers or shareholders).

From my perspective, there are four issues at work here: accountability, arrogance, awareness, and anticipation.

Let’s start with the easiest one – it’s not about the FDA. Sure, they’ve got their organizational problems, their bureaucratic politics, and their hopelessly conflicted missions. But, you and only you – Corporate Decision Maker - can make decisions in your workplace which bring manufacturing processes and quality control systems into compliance. So, stop pointing fingers at the FDA. Look at yourself in the mirror and accept the accountability that comes with having an approved drug or biological product on the marketplace. Then, get serious about taking actions which both systematically and systemically solve the GMP problems you’re experiencing.

Next - get over your arrogance. If you think the FDA won’t “shut you down” or make life miserable for you, think again. Yeah, you may have the only product on the market – for awhile, but that doesn’t mean the agency won’t use its power to get your corporate thinking and behavior back in line. I know of a former company president who admitted that the FDA had effectively shut one of his operations down for six months after years of contentious discussions and poor relations. He said his ego and aggressiveness cost the company over $300 million in lost sales as a result.

Moving to the next issue – raise your awareness about GMPs. You need to get yourself informed and educated about GMP expectations. When I say expectations, it’s not just Parts 210 or 211 or 600. It’s not solely about your own corporate policy and procedures, although I see lots of corporate decision makers ignorant about their own SOPs and protocols. It’s the whole body of decisions, guidelines, best practices, and directives that come out of the Food and Drug Administration and their counterparts in Canada and Europe.

Finally, I’ve got to say something about “unintended consequences.” Enlarge your thinking to consider what the positive and negative implications of your decisions are going to be – whether you decide to take action or whether you decide not to act. It’s like the ripples in a pond when you throw a stone into it. In the tightly controlled world of GMP manufacturing, it’s never the first ripple that negatively impacts your operation or organization. If you start to anticipate what might or could happen, then you’ll make better decisions.

And those decisions may prevent you from becoming the next GMP manufacturing disaster.

Shaking things up: the right management can work wonders
A supervisor writes in

Today, I want to tell you about a success story. I work at a manufacturing plant that never had a positive track record in treating employees well - until recently. It’s not that people were mistreated. It was more a “feeling” that management did not want to hear about our day-to-day concerns. Some of my fellow workers joked about the “blind arrogance” of site directors. Unfortunately, that arrogance sent a very mixed signal to the workforce and told us that management did not care about our ideas for improving productivity.

Some of my fellow workers internalized this message in a negative way. For example, I know several people that vowed never to report problems with GMP compliance or bring up issues getting in the way of producing batches. I’ve seen millions of dollars of product go down the drain because people didn’t speak up about equipment problems or maintenance. This attitude was common as most of the employees hunkered down, did their jobs the best they could, and went home.

That “attitude” changed about eighteen months ago. We got a new plant manager who actually cared about the problems and issues that were preventing us from delivering the product. We know this individual cared because he communicated it and demonstrated his concern by spending time in the manufacturing process areas.

He would gown up and despite being “mechanically challenged,” would help us position and set-up equipment for the next phase of operation. He was always asking questions too, particularly around “why” we did certain things. It wasn’t the “grilling” we had to endure from the previous plant manager, but a genuine interest to know what was going on and how he could make our lives easier.

At first, we were skeptical about his intentions. Several of the cynics among us thought he was down here to find the “weak links” so he could terminate a few employees and show corporate he was a “good manager.” But none of that happened. Now, the grilling he gave department managers – at least what we heard through the grapevine – was another story. Several of those individuals elected to find jobs elsewhere because they couldn’t handle new expectations about treating front-line employees.

When we heard about these events, the griping started to go away. This new plant manager started to meet with us regularly. We learned about the operating budget at this workplace, something that had never been communicated. He called it “open book management.”

With help from some new GMP trainers he brought in, we learned how to voice our concerns in a positive manner so we could quickly implement solutions to the nagging problems we had been experiencing. He called this a “team involvement” process.

And for some of the tougher problems, he allowed us to participate in cross-departmental problem-solving meetings. Imagine having a production operator sitting down with folks in quality assurance, engineering, maintenance, and validation!

The performance of our plant has improved dramatically these last eighteen months. We’ve broken production records, increased the uptime of equipment, and reduced the number of batch record errors. Our new plant manager still gowns up and spends time with us on the floor. I saw him the other morning at 7:00 a.m. after he had already worked three hours with the team on third shift.

Like I said, a success story now!

"Let's get this over with and go back to making product." Oops. Your microphone is still on
A compliance officer recalls an unguarded moment at a very public event when a consent decree is announced.

It finally happened. The FDA’s patience with our company’s lack of dedication to cGMP compliance expired. The verbal warnings that inspection teams started to give us over six years ago for several of our manufacturing plants did not get the attention of senior management. Then we started getting warning letters for “ongoing failure to adequately follow cGMP requirements and expectations.” Now, we’ve just been notified of a consent decree and the biggest fine in pharmaceutical industry history.

I use to work in several of these manufacturing facilities before bailing out for a position in corporate quality compliance. We use to have a good reputation for compliant manufacturing and quality control. I hate to point fingers, but our company started on a strategy of rapidly acquiring other product lines about eight years ago. We’ve been attempting to merge four different organizations and “compliance cultures” ever since. No matter what the senior executives say to the press or shareholders, we’re still living with some difficult situations in manufacturing and quality operations.

It’s no wonder the FDA got fed up and banged us over the head. I mean, when you find repeated and ongoing violations in such basic areas of GMP compliance as documentation (employees signing off on records for work they did not perform or were qualified) or staffing (some manufacturing areas shared supervisors just fresh out of school) or investigations (where do you want to start?) or quality control lab operations (lack of validated methods), then you’ve got to sit up and take notice.

But because we’ve been so successful for so long, we thought we knew better than the FDA and resisted making any real changes to our QA, QC, and manufacturing systems. I mean it wasn’t like plant management or corporate executives didn’t have findings from internal quality auditors pointing out these issues. Maybe it had something to do with the incessant arguments and furious (sometimes personal) debates that took place over these findings versus just getting on with improving regulatory compliance.

I wish we had stood up a little more independently as the quality unit and enforced compliance with these basic, common sense procedures. No doubt we missed an opportunity to avoid this crisis.

So, I hope we can respond to the FDA body blow. It’ll take a lot to change our work environment around here. For example, at the satellite broadcast for the consent decree announcement, one of the vice presidents of manufacturing (I won’t tell you which division) made a statement when he though his microphone was tuned off. Just 10 minutes before the CEO of the company came on, he said in a frustrated tone of voice: “Let’s get this over with so we can go back to makin’ product.”

I was sitting with a group of people from several different departments when we heard that. One person looked at me and asked “if I had heard what he heard.” You can imagine how the story has circulated through this corporate grapevine.

So, wish our company luck in meeting consent decree commitments. I think we’ll need it.

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