The Little "c" Isn’t What It Used To Be!

My career began in typical fashion, in the corner of a QC lab working for a mid-sized multi-national pharmaceutical company.  But the path from that point forward was anything but typical; in less than a decade, the site was sold 4 times, technology was transferred in and out and then in again, and between owners our little site racked up four fairly newsworthy FDA enforcement actions.
After that decade of stress and change, I decided to try consulting.  I knew thatconsulting wasn’t heralded for stability, but at least my path would be mine to blaze; where the path took me would be a direct result of my own effort.  Right?  Not always…
I invested a great deal of effort, and I seemed to make successful contributions to each assignment, and that did seem to lead to more projects, but who the clients were and what they needed, seemed to be a complete surprise each time.  It appeared that I was not at all in control of the direction of my path, only whether or not I stayed on it.  And it was clear, to stay on that path, I would have to not only tolerate, but to thrive on change.
Through the years, the variety was staggering, clients that came in every size and shape, from global pharma to cutting edge bio-pharm to a privately owned medical device company.  The projects hit every phase of the product life cycle, from the feasibility studies to site retirement, giving me a front row seat to the show that is the free market interacting with regulators.
I stayed on that path, and along the way I was wildly fortunate.  I was exposed to an array of technologies that forced me to keep the learning skills honed. I have worked with 50 year old products, whose facilities use equipment that hasn’t been manufactured for decades – micro-sized combo bio products whose manufacturing lines fit on a 4′ table top, and a light sensitive product manufactured in complete darkness.
The learning curve wasn’t limited to technology.  I learned a great deal watching the private sector struggle to function within the constraints of expansive regulation.  The organizations that struggled most were often my clients, needing help maintaining or re-establishing supply chains in the face of every enforcement action regulators have the legal authority to hand down, including Warning Letters and Consent Decrees, voluntarily and involuntary product recalls, clinical trial holds, and your standard negative audit observations.  After my experience in that aspect of the industry grew, I became involved in industry groups attempting to harmonize industry’s compliance efforts and public committees formed to interface with FDA.

In the past two decades, we have all seen dramatic changes in industrial models, technologies, and the regulatory framework that governs our work environments. Here are some of the highlights:

  • The expansion of Title 21(part 11, part 820)
  • An reinvented procedure for the federal agents that inspect us (the birth of System Based Inspection techniques (QSIT))
  • New Guidance Documents on compliance (Risk Management)
  • Updates to existing Guidance Documents (Process Validation)
  • Acceleration of International Harmonization Efforts (ICH, WHO, ISO)
  • Paperless Labs, Warehousing and Manufacturing
  • Advances in BioEngineering (Personalized Therapies, Genetic Therapies, Stem Cell Solutions)
  • Robotic and Computerized Implantable Medical Devices
I have seen firsthand that no matter an organizations’ size, revenue stream, or product line, dealing with the significant impact that regulations have on our business is the tie that binds us all, making the work environments of every person who works in this industry more alike than different.
The changes that effected everyone in this industry, the ones that made everyone flock to seminars and lit up the chat rooms, were never a function of breathtaking advances in medicinal therapies, rapid innovation manufacturing technologies, or headline grabbing mergers.
When it came right down to it, the changes that had immediate impact on what we did every day, how we approached our objectives, and how we communicated with each other were the changes that forced us to consider strategies for compliance.
Those of you that have been tasked with developing, changing, or completely up-ending business friendly methods of complying with federal regulations know what a challenge it can be, especially when you’re dealing with regulations like Title 21, that give inspectors and agents so much discretion. If I had to wager a guess as to what was the most commonly had conversation in any American industry, I wouldn’t guess the auto industry and foreign competition or unionization, I would guess the Pharma industry – and the meaning of the little “c”.
Day 1 of everyone’s entry level training starts with the little “c”, and it seems that we spend every day after trying to reach agreement on what it actually means in industrial terms on any given day.  If there are a group of precisely worded laws, shouldn’t it be easier to ensure and measure our own compliance with them?
It should be, but historically it hasn’t been.  I have seen companies spend more time developing and implementing cost effective compliance models than they spent initially developing their product.  Developing a compliance plan that fits easily and cost effectively into the manufacturing plan is not a simple thing.  It begins with a room full of decision makers, representing different functional units that have unique goals, debating the meaning of words like ‘control’ and ‘comply’, and trying to agree on theoretical ideas.  Eventually, someone ends up drawing the inevitable flow chart on the white board that isn’t large enough to contain it, and they all leave the room confident that they have a process that will leave them in control, and therefore, compliance is assured.  Realizing the choices those people just made is another matter altogether –how long that takes, and how well it’s done, will be determined by a legion of realities that come with conducting day to day business.
At least at the end of the clinical testing phase, we know how to measure the effectiveness of our own product.  But after manufacturing that product for a decade, we don’t know whether or not our facilities comply with the little “c” until federal agents inspect and let us know.  In the past, even small changes in regulations meant that we needed to re-start this process, kicking off new reviews all of our procedures and identifying every potentially impacted attribute of each one, and trying to determine the most business friendly way to implement large scale change.
Our industry bought a lot of whiteboards.
So if that is what happens when there are small changes to regulations, what happens when there is big change, or even a fundamental change? Fundamental change is what came our way when the regulators set about modernizing the cGMPs.  FDA’s 21st Century initiative was well publicized while it was being undertaken, and the effort did include the federal agency inviting input from the industry.  The end result (part 820, The Quality System Regulation) was a systems-based approach to declaring regulations, and at first it seemed as though everything we knew would need to change.  And now that we are farther down that road, it’s clear we were right – our compliances model did change.  At the time though, no one could have convinced me that the change would be so business friendly.
The modernized systems-based regulations were defined in an integrated manner, and they not only allowed but actually encouraged the employment risk-based compliance models. For the first time in my career, I believed a large scale regulatory change was driven by an understanding of the real challenges of manufacturing that needed to profitably produce, and also needed to demonstrate compliance.
The beauty of the Quality System Regulation is that the scope and concepts of the regulations took into account the systems that that were already incorporated into most industrial manufacturing models.  It was a

direct alignment of the control objectives of the GMP with the process flow of a typical manufacturing model, and the alignment preserved the visibility of the original GMPs.

 If you were one those that had to respond by mapping and implementing the changes that came from this act –it was clarity of the path that was needed to get from old to new that took you off guard.  You wouldn’t be needing a bigger whiteboard after all….
The act did many things, but most notably it:
  • Reinforced pro-active controls (e.g., Document and Record Control, Metrology)
  • Modernized existing systems (Internal Auditing and Process Validation)
The systems required by this regulation were already represented in our facilities, as were the tools that were expected by the original cGMPs.  The original cGMPs approached manufacturing facilities from a brick and mortar perspective: Personnel, Facilities, Equipment, Materials, Labels, Packaging, Procedures, Warehousing, Testing, etc.  But the QSRs approached control from a system perspective, focusing on those systems that would affect and strengthen the infrastructure, providing support to every worker, performing any function, in any building, using any equipment in accordance to all procedures.
This was not change to fear or loathe, this at last was change that was clearly developed with the modern manufacturing plant in mind.
This was a change that would enable us to model our control programs in the same way, and with the same level of flexibility, as industries who were not regulated.  Finally, we would be able to focus on the systems that enabled us to track profit, measure impact of change, and track efficiencies.  I began to think that maybe after all these years, I would be able to start writing for an Engineering journal, instead of a compliance journal!
Although I felt the new regulations were straightforward, clear, and rather elegant, it was pretty clear that not everyone in the industry was so easily impressed.  In my role as a consultant, I was surprised that I continued to observe Quality Systems that were implemented, but not at all useful.  Terms like “design control” – “risk assessment” – “bracketed validation strategy” – “continual improvement” were being used everywhere, but I wasn’t seeing an increase in the control of processes or facilities.  I wasn’t seeing an increase in the quality of data driven decision making, and I absolutely wasn’t seeing CAPA metrics on the whiteboards in Executive boardrooms.  It seemed that many in the field were viewing the systems as one more thing that had to be endured in order to comply – instead of embracing the systems for the business control tools they should be.
What was the root cause of that?  I believe in the cases I have seen, it most often boils down to:
  • Management Review tools that do not present the right type of data to the right people, in a timely manner  – this information rarely gets to decision makers, and if it does, it’s value has been diminished by the length of time it took to be delivered
  • Internal Audit Programs that limit themselves to verifying local compliance to internal procedures – and provide no feedback as to the effectiveness of all the other Quality Systems
  • Validationprograms that blur the integration points between design, validation, and metrology – often increasing the burden of testing in one area only to fail to serve the true purpose of the other areas
The reality is that the industry can use of all those programs (systems) to make product in a manner that will assure consistent and quality results in a profitable manner.  I believe that if designed and used correctly, these systems will reduce recalls, investigations, and product loss while increasing profit margins.  Perhaps the most important of these systems is the one that is intended to make sure all the other are visible, effective, and utilized – management.  Management with Executive Responsibility is defined in the regulation – and a Management Representative for each system is required by law.  However, it is the component that is most often absent in the models that are struggling to make themselves useful.
During inspections the agency determines whether or not an adequate quality system is established and maintained at the facility.  If it is not, for the first time, inspectors have the legal authority to cite Management with Executive Responsibility for failing to do his or her job.
If you think about why this type of regulation was written, inevitably you realize that the FDA felt that holding management legally responsible was needed in order to ensure that they all did their jobs.  Prior to the birth of 820, there was no regulatory authority to hold them accountable if they did not.  Too often, the first time that Executives learned or evaluated their own systems was when a Warning Letter came to them via the U.S. Postal Service.
As a consultant that is typically invited in only when the size or skill set of the workforce is undersized for the immediate challenge, I can tell you, we all need the Executive level of management to be much more involved on a routine basis. The quality systems should be as valuable to executives as sales and marketing data.  A well designed quality system can be just as responsible for the magnitude of a profit margin as the results of a sales and marketing campaign.
Part of the art of engaging Executives is knowing how to present current data in terms that they understand.   It only follows then that designing effective quality systems involves creation of output mechanisms engineered to produce visible results simply. Internal audit and CAPA programs should be smart enough to understand the magnitude of observations and should ensure that the visibility of serious issues be immediately raised.  Otherwise, how can top level decision makers react accordingly? Speaking not only as a consultant, but as a business owner, I can tell you with certainty, Executives need to be able to see what everyone on the ground knows.
If you review the terms of recent consent decrees you will find, in almost every one issued since the QSRs were codified, a section on Management Controls. These terms almost always involve requiring the company to appoint an executive to monitor all output of the quality systems and report regularly to the corporate Executives on issue resolution progress or lack thereof.  Life would be much easier for all of us if this attention to the output of the systems was implemented on the front end, instead of in response to a federal injunction.


The following is a published quotation from FDA leadership with regard to their expectations of the management’s role under the QSRs:

Looking at this from the consumer-centric point of view of the FDA, it’s clear that they feel the role of the investigator should be limited to quickly assessing and measuring compliance; consumer protection should not need inspections to find and correct every problem.  The systems should be doing that, by their very nature; they are meant to feed each other, providing a constant loop of useful information.  The output of one system should be the data the next system uses, and so on and so on.  If  that isn’t what the systems look like in your organization – they are either designed badly, under-staffed or under-supported by management.

When trying to determine which of those conditions are true for your site, remember:
  • The central goal of a quality system is the consistent production of safe and effective products, via processes that are controllable, measurable and reliable.
  • Successful quality systems share the following characteristics:
    • Scientific methods that produce measurable data
    • Decision making processes that require consideration of consumer centric interests and to reach data driven conclusions
    • System integration points that understand and acknowledge the objectives of the other systems
    • Methods of assessing output that incorporates elevating observations that are critical and making them visible to management
    • Management support with regard to staffing and supporting the groups that maintain the systems
It’s clear – the pace of change in our industry has and continues to increase and  the only way to thrive is to assess, evaluate, and continue learning.  The evolution of the little “c” into a group of systems was an effort to do just that; to create a work place environment where assessment and self-evaluation resulted in the identification of opportunities to grow, refine, and perfect.
Now, it’s up to each and every one us to make the choice that will determine success.  Will we choose to reject and mistrust this change, or will we embrace it and find ways each day to make those changes work for us and for our customers?
Speaking on behalf of Coda, because luckily, in our shop, I am the Executive that can make this choice, we’ll be embracing change and encouraging everyone else we know to do the same!
© Coda Corp USA 2013. All rights reserved.
Gina Guido-Redden
Chief Operating Officer
Coda Corp USA
(p) 716.751.6150
“Quality is never an accident; it is the result of high intention, sincere effort, intelligent direction and skillful execution. It is the wisest of many alternatives.”
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