Sunday, August 3, 2014

Three Essentials for Sustaining an Operational Pharmaceutical Quality System: The Quality Management Triad.

After nearly twenty years helping the biopharmaceutical industry to regulatory enforcement by implementing a operational and sustainable Quality Management System, I have come to the conclusion--at the most fundamental level--there are three quintessential elements required for success. I call it the Quality Management Triad.

The first element is Quality Governance. This is the body that provides:

    • the Vision—the aspirational view of the future, and how Quality Management is integral to the business strategy;
    • the Leadership—the top business unit and functional heads who motivate, align, plan and engage the organization toward its quality goals;
    • the Standards—the policies and standards that are endorsed by Leadership that establish the quality requirements—the “what” is required?

    • the Oversight—the communication channels and forums that provide to Leadership the direct visibility of product quality and compliance risks and trends—in order to make effective data-driven decisions.
The second part is the Pharmaceutical Quality System (which is the ICH Q10 term for the Quality Management System). The PQS:

    • establishes the Document Architecture—the hierarchy of the official, approved written instructions and executable records;
    • implements the Procedures—the processes—or the “How” to apply—the requirements of the Standards to your operation;
    • maintains Control—quality is about controlling variation, and the Pharmaceutical Quality System establishes your intentional and consistent ways of working to control variables—including the human variable—to operate in a state of control.
    • includes the Records that captures the product history and the manufacturing and environmental information that surrounds it.
The third part is Quality System Ownership , which is the specific application of the concept of Business Process Ownership that sets expectations and accountability for the constituent parts of the Pharmaceutical Quality System:  Ownership includes responsibility for:

    • Execution—the daily management of the quality processes described in procedures to ensure it works and is being followed;
    • Maintenance—to ensure that the quality process remains current with regulatory requirements and industry practices; and remains applicable to your changing business;
    • Performance—the measurement of how well the process is working and being managed, as well as the problems and opportunities the process is detecting;
    • Escalation—the identification of unacceptable conditions or events that puts the patient and the business at risk—and taking the immediate actions necessary to mitigate the risk, and making recommendations for permanently solving the problem.
At the center is the Quality function whose responsibility it is to engineer the processes for these three parts, and to ensure that they work—and work together effectively. 

To be clear—quality is everyone’s responsibility. But much like “Safety” is everyone’s responsibility, it is Quality’s responsibility to establish the ways and means of the Quality Management Triad, and to report on the effectiveness of the processes and manage risks.

Why is The Quality Management Triad important?

The pharmaceutical industry is a dynamic business environment.  Acquisitions, operational realignment, portfolio changes, manufacturing relocation, facility repurposing, and organization restructuring and integration are among the strategies to increase stockholder value. These continual changes impact the Quality Management System, and like any other aspect of the operation, it must be managed to remain effective and relevant.

Take this hypothetical example of the single-ingredient, solid-oral tablet manufacturer that constructed a dedicated facility for their new product.

Later, high-potency, multi-ingredient tablets were introduced into this facility as line extensions. The facility was then expanded to manufacture oral liquids and eventually retrofitted to produce oral suspension products.

Plans were being made to introduce parenteral drugs into the facility when the decision was made to enter into an agreement with a contract manufacturing operation—a CMO—for that technology, which was the firm’s first venture into a third-party partnership.

All the while, volumes were increasing, markets became global and the company turned to a twenty-four seven operation to keep up with demand. The increased profitability was directed toward the development of promising new drugs, while operating expenses were reduced and tightly controlled to fund new initiatives.

While this was great news for investors and employees, an unintended consequence was quietly undermining the business. The Pharmaceutical Management System had not evolved with the business, and was no longer capable of reliably detecting and managing product quality and compliance risks.

“Loss of management control” was the theme of the series of FDA483s and the eventual warning letter when the site was fraught with recurring manufacturing deviations and missed target dates to the FDA for solving the problems.

Although this is a hypothetical case, many people identify with some parts of this story when I share it.

Unfortunately, the Quality Management System is often viewed as a resilient tome of instructional content with little susceptibility to changes to the business. Nothing could be farther from reality.

Quality professionals across the industry who have looked back at their past quality problems and regulatory enforcement action, say—ironically—that their Quality Management System was a victim of their success.

Whatever the environment, the Quality Management System must be managed to ensure that it is Fit-for-Purpose and that it continually serves and protects the business.

What are your thoughts? How mature is the Quality Management Triad at your company? 

Please engage in this conversation. I would be pleased to hear from you,  and I would like to help your management team improve on these vital processes.

How healthy is your Quality Management Triad?
Please contact me to discuss how we can work with your senior staff and quality leadership to ensure these essential elements are in place at your company.

Please Contact Me:
John Snyder
John Snyder & Company, Inc.

Also, find me on LinkedIn for peer-reviewed articles on Quality Management System Topics.

John Snyder
The QA Pharm

Wednesday, April 16, 2014

CAPA backlogs? Five underlying causes.

You would think that the Corrective and Preventive Action (CAPA) system would be a business enabler---you know, a disciplined approach to permanently resolving problems once and for all. Unfortunately, the way most CAPA systems are designed and used, it is more of a stumbling block. The system gets so chucked full of stuff that backlogs are the norm, and a logarithmic increase in staff is required if you really want to keep current—or at least close as many CAPAs as you open for any given week.

You know the story. We have to get ready for the next inspection. EMA said they were coming in, and we are also overdue for an FDA inspection. There is a clutching of the chest because we know we're not in great shape. Our backlogs are back up again, and we cannot afford another observation about overdue CAPAs, and they are really on to us about liberally doling out extensions to the point that original target dates were meaningless to begin with. We keep kicking the preverbal can down the road.

Regardless, we form Tiger Teams of our best and brightest to focus full-time for the next several weeks to reduce the backlog--typically viewing the exercise as just paperwork. These stellar players let the work of their normal day job slip while well intentioned management asks for daily updates that chip away at time normally intended for sleep. The only metric that matters at this point is the backlog so that the very least we would be able to show a downward trend to the next inspector. 

Thus the saw-tooth cycle continues for years with the backlog steadily going up, followed by focused efforts to drive them down. And somehow we really feel good about our Can-Do attitude. It may not be fun, but we know how to pull together and deliver in times of crisis. Management rewards us once again for the firefight.

Sound familiar?

Such story only serves to show that the spirit and intent of the CAPA system has long been lost, and in reality, our CAPA system is out of control—and has been for a very long time.

The CAPA system is not making us any better and has actually become a "hidden factory" within our organizations that has found some self-serving purpose that has no relationship to making our products, processes or systems any better.

I really think we need to step back and do a reality check and admit that our CAPA system is broken and that we need to determine the underlying cause that lead us to this situation and prevent it recurrence.

That sounds like a CAPA for the CAPA system.

Whatever we call it, we need to examine just about every aspect of the way we manage CAPAs, and be willing to let go of some deep-seated beliefs. One thing I have learned about the CAPA system over my 35 years is that beliefs about the CAPA system are held very deeply with doctrinal zeal.

So, let's look at some fairly common CAPA practices that I believe are the underlying causes of the phenomenon I call “The CAPA Paradox.” In other words, with all these CAPAs, why aren't we getting better?

1. The CAPA system is has become a quality work order system

The Corrective and Preventive Action (CAPA) system, by definition, is intended to address problems and prevent them from recurring. However, CAPAs are opened for sundry reasons that range from delving deeper into a subject, to giving visibility to the team determining how frequently to change the pink ice in the urinal. In fact, a common practice is for every chartered project to also have a corresponding CAPA that contains the purpose, team member composition and roles, and major milestones. There is no problem statement, no data, no root cause analysis, no action plan, no defined deliverables that correlate to the root cause—and no mention of how effectiveness will be determined. In other words, very little content having to do with the intent of a CAPA system.

2. TrackWise has become a project management tool.

TrackWise is a valuable enterprise computer application that gives visibility to its contents through its capability of tracking, notifying, and reporting. Unfortunately, rather than seeing these TrackWise features as a tool to support the CAPA system, TrackWise has become an end to itself. Anything that we want to give such visibility automatically goes into TrackWise. Thus, the capability of the tool has defined the CAPA system. The floodgate is opened to all who have access, which inflates the number of “CAPAs," which causes the periodic panic.

3. CAPAs are opened without knowing the root cause.

When the unguarded portal of the CAPA system is open to the masses, then we should expect a wide variation in practices and applications. Although Quality Assurance may be required to review and approve CAPAs, they are doing so against the long-eroded purpose—enabling bad practices. If there were just one high-leveraged change that would start the shift back to the fundamental purpose of the CAPA system, it would be to require a root cause (or most probable root cause) as the price of admission to the CAPA system. No root cause—no CAPA. A root cause provides the target for the purpose: Correct what? Prevent what? Right behind this would be for Quality Assurance to be the gatekeeper to the CAPA system and to launch aggressive root cause analysis training and a strategy to reduce the number of employees that have access to the system.

4. CAPAs are not associated with things that matter.

One could go further to say, in addition to requiring a root cause, the root cause must be an output of the Deviation Management System for which a root cause can be assigned to a nonconformity or unacceptable trend. By considering Deviation Management and CAPA as one continuous process, the CAPA system is properly directed toward product, process and quality system events that have some probability of product impact. Adopting this view screens out the myriad of misapplications that come just short of the company suggestion box. Not only is the number of CAPAs reduced, they are CAPAs that matter—a better representation from a regulatory inspection perspective..

5. The low deviation threshold is debilitating.

Even though we associate the Deviation Management and CAPA systems, when events that are many degrees removed from product impact are treated with the same rigor, it is difficult to distinguish the significant issues from the noise. Providing alternative, risk-based pathways that permit rapid, real-time corrections and documentation is reasonable and compliant. Taking a “…for the want of a nail the shoe was lost, for the want of a shoe the horse was lost, for the want of a horse the soldier was lost….” to every event is neither noble or compliant, especially when valuable resources are equally directed toward the employee who used a “non-GMP ink” as the recovery of a microorganism in product not previously identified in the manufacturing environment. Management 101 better handles the former, and a CAPA the latter.

 Take this simple test to determine whether you need to examine how well your CAPA system is working.

1.   Do you have a saw-tooth backlog of CAPAs that result from heroic efforts?

2.   Are your CAPAs only directed toward something that you can actually correct and prevent?

3.   Do you have recurring, predictable deviations?

4.   When you compare the total deviations per year for the last five years, is there a downward trend?

5.   When you get a TrackWise report, is it readily apparent the most significant problems that require immediate attention.

6.   Does your company have intolerance for recurring deviations?

If your results are troubling, then it’s time to take a look at the design of your CAPA system and, perhaps, get back to the fundamentals.

The QA Pharm

Sunday, February 23, 2014

Quality System Design Attributes: Criteria for an Operational and Sustainable Pharma Quality System

There are many instances when a pharmaceutical quality management system (QMS) must be improved in part or as a whole. In some cases improvements are made in response to regulatory inspection observations. In other cases improvements are made when new company standards are deployed in order to remain current with changing regulatory requirements and current industry practices. Still other improvements are made to support the changing mission and product portfolio of the business.

Whatever the driver may be, a mindful approach must be taken when designing the quality system to ensure that the organization is capable of operating and sustaining the system. Unfortunately, improvements are often viewed as an SOP-writing exercise without considering the factors that help to ensure that implementation is successful.

The following is a discussion of ten Quality System Design Attributes (QSDA) that must be considered as part of the quality system improvement process to ensure that the organization is ready and capable of operating and sustaining the system. These attributes can be considered essential design criteria, because these attributes are the most common root causes for the failure of the quality management system and consequent regulatory enforcement actions.

These attributes are worthy of serious consideration by those who are engaged in quality system development, as well as change management coaches that support adoption of new systems.

1. Standards and Site Procedures
These are part of a document hierarchy that collectively comprise the Quality Management System (QMS) and declares how a company intends to operate in compliance with laws, regulations and company requirements. While standards establish the requirements, procedures provide the detail for how they are applied to a specific operation. This architecture provides the structure for the library of interlinking requirements and instructions. Without standards and procedures, there is no control over the way work is performed and how decisions are made.

2. Process
An orderly process flow facilitates a common understanding of how work is performed. Process flow diagrams commonly appear in procedures, and process mapping is often the first order of business when designing a new system, or improving an established one. Process flows also support value stream analysis and employee training by showing the big picture, key interactions and decision points. Incomplete, inefficient and disjointed processes open the door to informal practices to develop over time due to the lack of a fluid, practical or understandable way of working. Designing the process to be Fit-for-Purpose and useable is essential for compliance.

3. Decision Processes
Most processes have decision points. While some decisions may be very straightforward, others may require critical thinking skills to weigh available information, assess the risks and implications in order to make the best-informed decision. Some decisions require the participation by other stakeholders, or escalation to higher levels of management, especially when events or conditions arise that create an unacceptable risk. Ensuring that decision processes, decision makers and escalation criteria are clearly described in procedures helps to establish appropriate responsibilities, governance and risk management.

4. Role of Quality Assurance
Quality Assurance (QA) has a unique, independent decision-making role codified by the Code of Federal Regulations. It involves review and approval of all cGMP matters, as well as the release of product into interstate commerce. QA also has a role within each quality system that must be procedurally established. This will include QA reviews and approvals, as well as a description of the type of events and conditions where QA must be notified. QA must not be put into a role where there would be a conflict of interest such as expediting production or approving its own work. Establishing the role of QA ensures the independent oversight and support required by our industry.

5. Records and Documentation
Equally important to procedures are the records created when procedures are followed. Examples of records include batch records, forms, logbooks, drawings, recording charts, and printouts. Instructions are given in procedures on how to complete associated records. These records are signed and dated by the one performing the work at the time the work is performed. Some records are considered so important that the work and the entries must be witnessed. It is common to have standards and training on good documentation practices to promote clear and consistent written entry conventions, as well as to prevent the perception of fraud. The design and content requirements, as well as storage and archiving of records are very significant. Complete, accurate, and timely records provide the batch history and facilitate data mining and support investigations.

6. Performance Metrics
Performance metrics are at the core of managing the quality management system. Performance metrics are designed into system procedures and are intended to help the system owner manage the performance of the system, and to detect problems. Metrics also help to identify improvement targets and measure the effectiveness of decisions and actions. The review of quality system performance metrics is the main content of the Quality Management Review (QMR) process. The QMR is at the core of Quality Governance, since it brings together cross-functional management, system owners, and performance metrics for the purpose of ensuring that risk are identified, effective decisions are made, and that the quality management system is continually effective. Performance metrics are essential for becoming an anticipating organization.

7. Infrastructure
Infrastructure is an attribute that encompasses a wide variety of tangibles that support the effectiveness and efficiency of the system. These could include facilities, equipment, software, and co-location of system users. Supporting infrastructure may be mentioned in procedures if they are part of the process (e.g., TrackWise software). Sometimes infrastructure is assumed (e.g., space and computers). Since infrastructure support takes significant lead-time to implement, be sure to allow sufficient time in the implementation plan in order to meet commitment dates.

8. Organization, Skills and Resources
To effectively execute the process and make appropriate decisions requires skilled system users and a supportive organization structure. Changes to each quality system require that the organization structure, skills and resources be evaluated to ensure that the organization is capable and ready to operate the new system.  Each role specified in a procedure must have identifiable personnel that have the education, experience and skills to perform the assigned activities. Implementation of the new system requires role-based training and a learning assessment in advance of start-up to ensure organization readiness. The bigger the change, the more effort will be required to be ready for effective implementation.

9. Dependent Linkages
The QMS is a network of interrelated systems. When designing a quality system, it is important to consider not only the inputs and outputs within a system, but also between systems. Inadequate linkages between systems create “short circuits” and can cause the quality management system to fail. Ensuring effective linkages can be a challenge when undertaking a comprehensive quality system remediation effort, since the state of the relevant linked systems can be a moving target, or the sequence of remediation targets may not be optimized. Nonetheless, the identification and continual assessment of dependent linkages is essential for an integrated and well functioning quality management system.

10. System Ownership
Each quality system must have a defined owner who takes responsibility for the design, procedures, operation, performance, reporting, and improvement of the system. The system owner also ensures that the system continually evolves as regulatory and industry expectations change, and when there are changes to the business portfolio, organization structure and function. Clear system ownership and ownership behavioral expectations are essential to fundamental quality system management. Establishing systems owners sets apart key personnel who can work together within and across sites for internal benchmarking and continuous improvement. These system owners also become a sub-set of company experts where investment of continuous education and development is well placed.

A Word About Working with OpEx Change Management Coaches

Quality system development efforts definitely require the organization to be ready and capable of adopting and adapting to changes required for sustainable implementation. The value of the effort in terms of time and cost can only be realized if the improved quality systems that are the result can be sustained. So this area of the business is definitely worthy of Change Management attention (not to be confused with the Change Control quality system). The challenge is to align and leverage quality system development and change management activities and targets. Here is where the ten Quality System Design Attributes come in.

These ten Quality System Design Attributes represent the areas where the most significant changes will occur and where support may be needed. Teams must identify the anticipated changes for each of these ten attributes. Each change must be clearly described (from what to what?) and expressed as a tangible quality system design deliverable. These changes must be assessed to determine whether the change is incremental or transformational. Change Management coaches can facilitate the conversation and organization preparation to receive and operate the new or improved system, particularly where the most significant changes will occur.

The QA Pharm