Friday, May 20, 2016

Good Metrics Practice for Quality Management Reviews

A Quality Management Review (QMR) of quality data with responsible company leadership is a CGMP requirement.  QMR practices vary, but there seems to be a struggle with presenting data from across the Quality Management System is a meaningful and consistent manner when there are multiple contributors. Here are a few suggestions:

Report the opportunity for improvement
Reporting the opportunity helps to focus where to improve. For example: Ten percent (10%) of investigations were overdue, rather that ninety percent (90%) were completed on time.

A decrease shows improvement
A downward trend means improvement toward zero problems. For example: Following root cause analysis training, recurring deviations were reduced from twenty percent (20%) to five percent (5%) in six months.

Compare versus historical performance
Comparing current performance versus previous period, or this time last year, helps to illustrate improvement over time. For example: This quarter, ninety-five percent (95%) of supplier audits conducted versus plan was accomplished compared to five percent (5%) previous quarter.

Index metrics for relative comparisons
Indexing eliminates the effect of arbitrary data sets and helps to make comparisons. For example, there were seven (7) Complaints per Billion Units Manufactured Year-to-Date versus eighteen (18) for the same period the previous year.

Report absolute numbers for critical issues
Indexing should be avoided when the issue is critical or numbers are low. For example, report that two (2) batches were recalled, rather than 0.2% batches were recalled.

Note events with markers on the timeline
When data is reported versus time, it is helpful to note significant events that had an effect on the data. For example, the trend line for environmental monitoring excursions started to increase when building construction started.

Define an unacceptable trend
Trends should be defined for run chart performance data. For example, consider statistical process control method of five (5) consecutive movements in the same direction, or seven (7) seven consecutive points on same side of average.

Report measure of variability with averages
When reporting averages, be certain that that data can be legitimately combined, and provide a measure of variability. For example, reporting an improvement with a decrease in the average number of seventeen (17) deviations per batch record for the last ten batches compared to an average of twenty-five (25) with the previous ten batches, is misleading when the range of deviations increased from five (5) to forty-five (45) compared to twenty-three (23) to twenty-eight (28).

Chart scales must be sensitive for intended purpose
The scale of a chart should sufficiently large to illustrate the range of normal variation, and small enough to include all excursions within the time frame depicted. For example, the chart scale for Percent Overdue Nonconformance Investigations of 0 to 100% is inappropriate for a 12-month performance chart with normal variation of 3-6%.   A more appropriate scale would be 0-12%. If the same time frame included an excursion of 18%, a chart scale of 0-20% would be appropriate.

And remember---Data talk; opinions walk.

John Snyder
The QA Pharm

The QA Pharm is a publication of John Snyder and Company, Inc.

John Snyder and Company, Inc., provides consulting services to companies regulated by the Food and Drug Administration. We help our clients to build an effective Quality Management System to enable reliable supply of quality products to their patients. We also help our clients to develop corrective action plans to address regulatory compliance observations and communication strategies to protect against accelerated enforcement action.

Friday, October 30, 2015

Management Responsibility for GMP Oversight and Control: A Review of Requirements

Supreme Court Cases
Historically, the FDA has cited the Supreme Court decisions of  United States v. Dotterweich (1943) and United States v. Park (1975) as FDCA legal cases that establish that the manager of a corporation can be prosecuted under the Federal FDCA, even if there is no affirmation of wrong-doing of the corporation manager individually.
In the Dotterweich case, the jury found Dotterweich, the president and general manager of a drug repackaging company, guilty on two counts for shipping misbranded drugs in interstate commerce, and a third for shipping an adulterated drug. One dissenting judge of the Circuit Court of Appeals reversed the decision on the grounds that only the corporation was the “person” subject to prosecution, thus protecting the president personally. But the Supreme Court reversed the decision thus holding Dotterweich individually responsible, not just the manufacturer. Justice Frankfurter delivered the opinion of the Court, “... under § 301 a corporation may commit an offense and all persons who aid and abet its commission are equally guilty….”
In the Park case, the chief executive officer was found guilty on all counts involving food held in a building accessible to rodents and being exposed to contamination by rodents, resulting in the adulteration of the food within the meaning of the Federal Food, Drug, and Cosmetic Act (FDCA). Park’s defense was that he had an organizational structure responsible for certain functions to handle such matters. However, evidence from inspections of multiple locations indicated the same problems and inadequate system for which he had overall responsibility. Chief Justice Burger delivered the opinion of the Court, “... by reason of his position in the corporation, responsibility and authority either to prevent in the first instance, or promptly to correct, the violation complained of, and that he failed to do so... the imposition of this duty, and the scope of the duty, provide the measure of culpability...”
More recently, Public Law 112-144 (July 9, 2012) called the Food and Drug Administration Safety and Innovation Act (FDASIA) added to the definition of CGMP in the Food and Drug Cosmetic Act (Section 501, 21 U.S.C. 351) to explicitly include management oversight of manufacturing to ensure quality. Section 711 of FDASIA states:
  • For the purpose of paragraph (a)(2)(B), the term “current good manufacturing practice” includes the implementation of oversight and controls over the manufacturing of drugs to ensure quality, including managing the risk of and establishing the safety of raw materials, materials used in the manufacturing of drugs, and finished drug products.
The addition of oversight and controls to the definition of CGMP has strengthened the FDA position with specific language for management’s responsibility for oversight and control as a requirement in the Act. The question remains how to practically and operationally to perform this responsibility. The following model describes essential elements of a CGMP Management System for oversight and control.

Management System 

The implication of the impact of CGMP noncompliance on the business is not theoretical. There are ample examples in the pharmaceutical industry where ineffective implementation of CGMP systems resulted in the loss of control that materially affected product quality, which, in turn, affected inventory and patient supply. Establishing a Pharmaceutical Quality System (PQS) that effectively implements the CGMPs is the means for maintaining a state of control—the fundamental intent of these regulations.

Management does not assume positions of responsibility with the intent of neglecting CGMP compliance. However, management may not enter the top position fully equipped to assume responsibility for CGMPs in a practical way. Management may delegate all CGMP matters to the Quality Department and take a hands-off approach and rely on this function to bring matters to its attention at their discretion. Such passivity leads to hearing only the bad news when it is far too late to contain and resolve the problem in the most cost-effective way with least risk to public safety.

Likewise, some Quality Departments may not be adequately equipped to bridge the space between top management and daily operations with effective structures and processes that enable management to exercise its responsibility for CGMP oversight. Too often the default position is to rely upon the outcome of regulatory inspections. But as one might expect, a good outcome can give a false sense of security, and a poor outcome can be viewed as the exhaustive list of problems. As in any area of the business where risks must be managed, there is no better approach than having an intentional management system in place that provides actionable data to know internally where your daily operation stands at any given moment.

Assess, Improve, and Implement--and Perform

For nearly 20 years, John Snyder and Company has served the pharma industry to assess, improve, and implement the Pharmaceutical Quality System (PQS). Our Management Triad Model will help you to assess and develop the crucial structures, systems, and processes for Management Oversight and Control for monitoring your state-of-control and to become an anticipating organization.

Please contact me at I want to partner with you.

John Snyder
The QA Pharm

The QA Pharm is a publication of John Snyder and Company, Inc.

John Snyder and Company, Inc., provides consulting services to companies regulated by the Food and Drug Administration. We help our clients to build an effective Quality Management System to enable reliable supply of quality products to their patients. We also help our clients to develop corrective action plans to address regulatory compliance observations and communication strategies to protect against accelerated enforcement action.

Saturday, March 28, 2015

12 Ways to Improve Procedures

At the risk of sounding like a pharmaceutical quality assurance heretic, standard operating procedures (SOPs) often do not work as intended. In fact, they can do more harm than good by giving a false sense of security: "We must be okay; we have procedures for that."

Having procedures is certainly important. FDA cites the absence or inadequacy of procedures as  a compliance problem. Industry spends a lot of money on staff and infrastructure to put procedures in place. And ironically, more money is spent on validating a document management system than ensuring the SOPs that flow through the system are effective.

Procedures are often more form than function. Words on a page do not necessarily make things happen as intended. I have observed the general neglect of procedures for many years and have concluded that there are common reasons why procedures don't work.

Let me turn the problems around and list these 12 ways to improve the effectiveness of procedures:

1. State the purpose of procedures.

Without a clear understanding of why we place such a high value on procedures in our industry, we can easily end up with a random collection of documents that vary in quality and content as much as the differences among authors who create them.

The purpose of procedures is to declare how the firm will operate in compliance with applicable laws and regulations, as well as how the business chooses to operate within its own norms. This purpose acknowledges that ad libbing is not acceptable in the pharmaceutical manufacturing industry. Thus, the second purpose is to control the human variable and ensure operational consistency.

With these purposes in mind, the author of a procedure takes on a significant responsibility to apply the regulations to the business, as well as understand the operation where procedures are used.

2. Make process flow the backbone of procedures.

Since procedures declare "how" an activity is intentionally performed, then they should read in a logical, straightforward manner that is followable. Nothing is more frustrating than being accountable for performing an activity in a compliant manner with SOP that are disjointed and nearly impossible to tell who does what, when, where and how. If we want people to follow procedures, then we need to write procedures that people can follow.

A good practice is to start with a process flow diagram that depicts a technically correct (compliant), and operationally efficient sequence of activities. The traditional SIPOC flow diagram is in everyone's toolbox, and this is also an effective tool for writing procedures. Process flow diagrams help to develop a common understanding of the process, and it establishes the sequential steps needed to write an orderly procedure. If you can't make a process flow diagram, then you probably do not know the process well enough to write a procedure.

A procedure that is based on a good process flow diagram practically writes itself, because a procedure is the text that surrounds a process flow.

3. Seek input from the procedure users.

A process flow diagram is only as useful as the informed input that goes into writing it. Certainly this means including functional experts with technical and compliance knowledge. But active engagement by the users is essential. Review and approval of procedures by users' management is no substitute for thorough participation by actual procedure users.

Users know the obstacles and inefficiencies to the existing processes and are eager to remove the pain from their daily lives. The depth of knowledge, experience, and willingness of users to participate should not be underestimated. They will be the first to identify better ways of working that will promote compliance to procedures and efficiency.

It is a double bind to insist on strict compliance with procedures but not to create procedures that reflect the realities of the user. Ineffective procedures written in a vacuum invite work-arounds, which might--in the end--have been the more efficient process.

4. Promote clear writing of procedures.

Procedures should be straightforward and easy to follow. If you have ever assembled a do-it-yourself piece of furniture, you know how important clear instructions are. Too often procedures lack detail to perform an activity consistently, or the detail is scattered throughout the procedure.

There is a difference between clear writing and technical writing. Improving procedures is more often a communication problem, not a technical problem. We need to recognize that writing instructions for another person to follow is a high-level skill, and not everyone is qualified. We make the mistake of assuming that anyone is capable of authoring a set of instructions if they are the subject-matter expert.

Identify your clearest writers. Have them edit procedures for clarity, not just technical content. It should not be too much to ask for procedures to have clear and logical steps to follow.

5. Establish a style guide for authors of procedures.

Editorial style is a distinctive manner that makes a set of procedures belong together. Style is notably missing when procedures are significantly different and disorderly. One author may improperly write user process instruction in the responsibilities section; another author may carelessly refer to a form or other procedure that does not exist; another author might redundantly give the title "Procedure for..." when it is obvious that you are holding a procedure.

A style guide is useful for authors. A style guide not only standardizes the content of procedures, but it helps a procedure to make sense from a reader's perspective. Much like Instructions for Authors in a professional journal, a style guide helps procedures to be a document type that belongs together and has a common purpose.

Setting style expectations helps authors to write effectively and gives a body of procedures the level of professionalism that reflects the significance of the work being performed. It also shows respect for the user.

6. Ensure procedures are part of a document architecture.

Architecture is the overall organization and relationship of all pharmaceutical document types. But there is also architecture for procedures as a specific document type. The randomness of the table of contents for standard operating procedures often reveals lack of architecture. This is usually a symptom of an unstructured pharmaceutical quality management system.

The architecture of procedures typically reflects elements of a pharmaceutical quality management system such as Product Development, Manufacturing Controls, Engineering and Maintenance, Laboratory Operation--sub-groups of the pharmaceutical quality management system with related procedures that belong together.

Establishing an architecture for procedures elevates procedures to that of a pharmaceutical library that contains a wealth of operational knowledge and the best, compliant practices. Like any library, you know how its organized and where to go for the information you need.

7. Link processes between procedures.

Procedures connect to one another because inputs may come from one process, and the output may be received by another process. The linkage between these off-page connectors must be present and adequate for processes to be fluid across procedures. Short circuits are created when there is a reference to a process outside the scope of a procedure, but a procedure for that off-page process does not exist, or it is an informal practice.

When new procedures are created, or existing procedures changed or deleted, the effect on all other procedures within the pharmaceutical quality management system must be assessed. Maintaining working interrelationships between procedures is a challenge, but essential. Whether making seemingly innocuous editorial changes to undertaking a major quality system improvement initiative, the impact on other procedures must be addressed.

The pharmaceutical quality management system is like an ecosystem. Rarely can a change be made that does not have an impact somewhere else. Effective procedures not only make reference to other procedures where essential linkages exit, but the processes are also seamlessly stitched together.

8. Exercise control over procedures.

Procedural control takes many forms. The most obvious is a mechanism to ensure that only approved and effective procedures are accessible. Less obvious is understanding when historical revisions were in effect and what significant changes were made. Also, with various practices for procedure lifecycle milestones such as approval date, training date, mastered date, issue date, and effective date, the most important dates can be lost: When was the procedure approved by QA? When was the procedure made effective?

An unintended consequence of control is having a document management system that is bureaucratic and cumbersome. When the view is taken that manufacturing operations is central to the organizational purpose, then it is incumbent upon a service organization to provide an appropriate service level. Likewise, an understanding and elimination of the root cause for excessive changes is just as important to help to reduce the volatility of the pharmaceutical quality management system.

There is a balance between central control and responsiveness to the needs of the operation. The most effective companies find the sweet spot while providing the value add of maintaining the integrity of procedures, document architecture, and the pharmaceutical quality management system as a whole.

9. Identify procedure (system) owners and ownership behaviors.

Having an owner for set of procedures related to a given quality system is essential for accountability. That accountability includes being the most knowledgeable person internally about the system, the most informed person with respect to industry practice and regulatory enforcement trends, the point person for reporting the health of the system, and the one who ensures the system is continually effective for a dynamic business environment.

But ownership of procedures is often like a game of hot potato: you don't want to be caught holding it. But lack of ownership opens the door for anyone and any opinion to infiltrate procedures. The most problematic procedures are the result of lack of ownership and investment in the owners to become industry experts in the CGMP requirements and application of the requirements to the dynamic business. Identifying owners also establishes a network across business units for best practices and harmonization.

Selection of system (family of procedures) ownership should be thoughtfully made with the owner being the most responsible manager closest to the use of the system in daily operations. While there are high expectations for the owner, there should also be high rewards and priority given to invest in their training to keep current in CGMPs and industry practices.

10. Demonstrate respect for procedures.

Behaviors of immediate supervisors and top management define the boundaries of allowable practices. If procedures are just considered guidelines that are selectively followed, then there is no expectation for defined ways of working with predictable outcomes. When there is a disregard for procedures, there may be a company culture problem, or there may actually be problems with procedures. It's okay to say, "I can't follow this procedure, but I know how to make it better."

Procedures are made for man, not man for procedures. When procedures are well written and effective, there is comfort in knowing variation is controlled and the outcome is predictable. Supervisors must model respect for procedures not only by following them and expecting others to follow them, but to be actively engaged to ensure that procedures are as best they can be for their operation. No one should be the victim of poorly written procedures.

Nothing will sabotage regulatory compliance or quality system improvement more quickly and lastingly than lack of respect for procedures.

11. Train on procedures.

We say that we provide training on procedures. But do we really teach the purpose and importance of procedures, how they fit into the architecture, or how a given procedure contributes to the state of control and value to the patients we serve? Unfortunately, the common default is Read and Understand, check the box and then go on to the daily work.

The training effort is magnified for companies that undergo a lot of change either through voluntary quality system improvement, or involuntary regulatory enforcement action. There can be a false sense of security when the training statistics are published and high training percentages achieved. The reality is that such statistics are not a measure of learning. And when a nonconformance is detected, or a procedure is not followed, we compound the problem by requiring retraining as the corrective action.

Procedures are the primary content for training, and not all content is best learned by a Read and Understand approach. The training system should establish a gradient of training approaches that takes into account the subject matter along with a learning assessment.

12. Manage the change.

The field of Change Management has entered the CGMP compliance world. During my forty years helping companies to establish and improve pharmaceutical quality management systems, I have come to understand that CGMP compliance remediation and improvement is just as much about company transformation as it is system design and procedures.

Procedures are words on a page. They can be the best and clearest words on a page. They can even be the most respected words on a page. In the end, they are just words on a page, and words on a page do not necessarily make anything happen. Sometimes procedures and changes to procedures are difficult to embrace with the best of intentions. Some changes may be simply editorial, but there are some changes may go entirely against the way things were done before. Thus the behavioral sciences enter the technical world of pharmaceutics and CGMP.

Done thoughtfully with facilitation by change management professionals with experience in pharmaceutical manufacturing and CGMPs, change can be embraced and results sustained.

What are your experiences and recommendation?

Please share your thoughts with The QA Pharm community. Your participation is valued and appreciated.

John E. Snyder
The QA Pharm

The QA Pharm is a publication of John Snyder & Company, Inc.

John Snyder & Company, Inc., provides consulting services to companies regulated by the Food and Drug Administration. We help our clients to build an effective Quality Management System to enable reliable supply of quality products to their patients. We also help our clients to develop corrective action plans to address regulatory compliance observations and communication strategies to protect against accelerated enforcement action.

Contact us at

Thursday, March 26, 2015

4 Reasons Companies Come Under a Consent Decree

When you peel back the layers of causes leading to serious FDA enforcement action, it comes down to a handful of fundamental reasons.

1. Management does not know what is required.

Executive and senior management may not have regulatory experience. MBA programs may offer courses on Quality, but it is more about the popular concepts of Lean Manufacturing, not the Food and Drug Cosmetic Act or the Code of Federal Regulations and CGMPs. Some may go as far as to think that if you are doing Six Sigma, you have a quality program. If you have a quality program, you have the FDA base covered. There is a mental disconnect with CGMPs as legal requirements. It just so happens that CGMPs are also a business enabler that drives reliable processes, product quality, and uninterrupted patient supply. And management must acknowledge and embrace these legal requirements just as much as it does SEC, EPA, EEOC, and other business laws.

2. The Quality Unit lacks the capability to detect problems and report to management.

Management may have regular status updates on how well the market is responding in Europe to a new product launch, or how the new ad campaign is affecting the Southeast Sales Region. But management often flies blind when it comes to knowing at any moment whether the operation is in a state-of-control. That knowledge is thought to come with regulatory inspections. You deal with the FDA483 when it comes, and that buys you time until the next inspection. The Quality unit often buys-in to this reactive mode of problem detection since this is when resources are most likely to be justified. The Quality Unit must develop the systems and the capability to detect unacceptable trends and be empowered to report problems directly to management. Such a mindset is essential to move from a reactive to an anticipating organizational culture.

3. The organization cannot plan and execute permanent solutions.

It’s one thing to know about a problem and something entirely different to do something about it. The best position to be in prior to a regulatory inspection is to be able to say, “There’s nothing you will find that we don’t already know about. Not only do we have a plan to address these problem, but also our plan is on schedule.” But all too often projects to prevent failure move to the bottom of the priority list for resources. If they do get funded, the projects are not directed toward a permanent solution, or managed to a verifiable conclusion. Not only must compliance projects must be resourced and managed, they also require oversight and governance to ensure that the projects are supported and completed on time.

4. Lack of integrity.

Then we have the phenomenon of doing whatever it takes for self-preservation over the health and welfare of the patients we serve. No degree of knowledge of the requirements or the presence of highly effective detection and escalation systems can prevent dishonest individuals from violating public trust. What we can do is have a zero-tolerance Integrity Policy that is part of every employee’s training curriculum, and to make it safe for someone to voice his or her concern should they witness a violation. In addition, training on Good Documentation practices will help to standardize record entries and how to document correction of errors. This will counter the perception of fraud for honest mistakes. The dishonest ones—well, that’s another matter.

Opinion Survey:  Reasons Companies Come Under Consent Decrees

When the FDA starts moving against your company is not the time for introspection. Take this quick survey and use the results in an internally facilitated discussion. Now is the best time.

How would you rate your company? What are the implications for your collective results? Most of all—take action.

5 = Strongly Agree
4 = Agree
3 = Not sure
2 = Disagree
1 = Strongly Disagree

_____ a. Our management demonstrates visible support for CGMP projects to ensure our compliance position is strong.

_____ b. Our Quality Unit has robust processes that provide management the means to know the state-of-control and to take decisive action.

_____ c. We have a good history of directing teams toward potential compliance problems and finishing on time.

_____ d. We have an Integrity Policy and everyone knows how to confidentially report a potential violation.

John E. Snyder
The QA Pharm

The QA Pharm is a publication of John Snyder & Company, Inc.

John Snyder & Company, Inc., provides consulting services to companies regulated by the Food and Drug Administration. We help our clients to build an effective Quality Management System to enable reliable supply of quality products to their patients. We also help our clients to develop corrective action plans to address regulatory compliance observations and communication strategies to protect against accelerated enforcement action.

Contact us at