Friday, February 13, 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 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 john@john-snyder.com.





Thursday, November 20, 2014

10 Points to Consider Before Becoming a Pharma Consultant

I am often asked for my advice on entering the consulting field, and I am happy to share my opinion from my own personal experience and what I have observed.

So here are 10 points to consider:

1. Family support is essential. You will be away from home most weeks. If you are someone with a young family; someone who likes to make all the decisions at home; someone who has a partner that has difficulty having you away from home---don't go into consulting.

2. Be financially stable. The consulting world is becoming more competitive and hourly rates are declining in many specialty areas. If the next on-time paycheck is critical for survival; if you cannot be without an income for six months--don't go into consulting.

3. Form your business entity. Don't mix personal and business money. Protect yourself by forming some type of a corporation. Talk to a accounting advisor who can listen to your unique situation to determine the best option for you. I am a "C Corporation," but make your decision on your needs, not what other consultants do.

4. Be realistic with your skills. Determine what your product is and refine it into tools, methods, approach, etc. Clients will readily detect when you have overstated you expertise. While it is acceptable to hone your skills and accrue more experience when consulting, it is not acceptable learn the subject on the clients' dime.

5. Charge by the hour. Consulting is typically billed by the hour, not the job. You have more control. Some clients may never agree when you are done.

6. Show something for your work. Agree upon deliverables with the client. What does "done" look like? Develop a common understanding of the client support required for the project to succeed. Know when you add value or not. When you no longer are adding value and just billing hours, discuss with the client. Warm-body-consultants give consultants a bad name.

7. Market through people who know you. Most projects come from people who know you directly and personally. Hopefully you have been building a network throughout your career from places you have worked and professional conferences. Being out in the consulting world is not a time to start thinking a network.

8. Be a consultant, not an employee. Study the IRS test rules for determining the difference between and employee and an independent consultant/ contractor. Don't allow either yourself or the client to cross the line emotionally or legally. If you feel you are "going to work" like you have all your life, you are not consulting.

9. Keep careful records. Not all clients require time and expense records. You should require it for yourself. Keep every cotton-picking receipts and a meticulous record of your hours: what you do and time. Never, ever pad the expense report or bill unreasonable hours.

10. Build-up, not tear down. You are there to help, not criticize. Avoid coming across as a "know-it-all". Lead the client to the point where they internalize and embrace your teaching. Find those among your client personnel who have that unexplainable spark, mentor them, and leave a legacy.

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 john@john-snyder.com.


Thursday, October 23, 2014

Part 2: Responding to FDA483 Observations and Fulfilling Commitments

Part 2: Organizing to Get the Work Done

Responding to FDA483 observations was my focus in Part 1 of this series. Responses lead to commitments, and commitments lead to changes that are intended to prevent recurrence of the underlying problem that led to the observation.

In Part 2, I share my views on getting the work done to fulfill the FDA commitments. The following have become benchmarks from those who are the best at getting the job done in a sustainable way and getting the problems behind them:
  • Form teams. This might seem obvious, but forming cross functional teams representing stakeholders is often overlooked. The solution will very likely involve creating different ways of working that cross functional lines. It is a rookie mistake to think that the fix is something for the Quality Department to do on its own, or just an editorial change to a procedure. Depending on the problem, the team may need to be dedicated to allow focus, particularly if accelerated timelines are involved. Include subject-matter-experts that have the scientific, technical, and cGMP backgrounds to provide appropriate guidance.
  • Use consultants judiciously. Consultants can provide valuable additional support. They should bring relevant industry experience that can help scope the project and give practical advice that keeps the project moving toward the solution. The best consultants are good listeners who can help you design the right solution that works for you. But, if the only team members that show up to meetings are the consultants, something is terribly wrong. Do not outsource your responsibility to consultants. Let them help you, but it's your company and you own the results.
  • Determine the deliverables. Many teams go off the rails because they fail to determine the tangible deliverables that address the problem. You cannot grasps the degree of effort, determine the resource needs, or estimate the timeline until there is a clear vision of what "done" looks like. If you cannot describe "done," then you do not know the problem well enough.
  •  Solve the problem, not just the Commitment. Make a careful assessment of what it will take to prevent recurrence of the observation, not just satisfy the specific commitment. The FDA always states in the FDA483 that the observations are just examples and are not all-inclusive. Companies are expected to determine all that is necessary to permanently resolve the problem that underlies the observation wherever it applies. Perform a root cause analysis and ensure that the solutions are operational and sustainable. That invariably involves more work that the narrow view of a specific example cited in an observation or the response given.
  • Determine how you will know the problem is solved. In true fashion of a CAPA, determine how you will measure effectiveness. What will tell you that the solution worked? What will be your first sign that it did not work? Consider whether this is yet another attempt at solving the same old problem. Remember that recurring observations lead to increased levels of enforcement. Be sure you know the problem is truly solved.
  • Avoid Information Technology (IT) Solutions. This may sound a bit strange, but in my personal experience, nearly every commitment made in a FDA483 response that involved an IT solution missed the commitment date by light-years. I know that it should not have to be that way. I'm just saying that in my 20 years of consulting experience, that has always been the case. Consider applying an IT solution as a later improvement, not within the commitment time line if at all possible.
  • Use Project Management Principles and Tools. Quality System development work is not like a capital project where the much of what is needed to estimate the time and cost is known upfront. Quality system and compliance projects are more often like exploratory surgery where a lot is learned once you open it up the patient. You may discover that multiple linking systems are affected after you start looking at the problem more deeply.  Recognize that plans will need to be adjusted along the way. Do not confuse progressive revelation with scope creep. Be adaptable. Establish plans and reports based on the work and target dates, not subjective feel-good dashboards with perpetual dates that slip. Anticipate problems with hitting the date and mitigate them before failure is foregone conclusion. When you see that the timeline is slipping, ask for help and consider first what it will take to get back on track. Don't just keep moving the target date back as the default solution.
  • Provide Infrastructure Support. Remediating compliance problems often require new ways of thinking, not just new ways of working. Compliance problems frequently go hand-in-hand with company culture problems. Progressive companies that recognize the business value of an effective Quality Management System also recognize the opportunity that regulatory inspections provide to examine its culture and values. Change management coaches can help a company adapt to the changes required to support a quality and regulatory compliance culture. Recurring compliance problems are frequently a culture problem that discounts the value of an effective Quality Management System and regulatory compliance to the business. 
  • Provide Management Support. Ensure that each project team has a sponsor who is the best fit based on the functional owner of the process being remediated. Clearly identify the role of the sponsor and ensure that it includes removing obstacles such as lack of organization alignment, stalled decisions, team dysfunction, and inadequate budget. Sponsor are the champions who are willing to delve into the level of the working team to provide visible support, rather than sit on the management team and undermine their own folks at project update meetings. Being sponsors of quality system remediation projects provides a unique opportunity for function heads to understand dependent processes across functional lines.
  • Establish Governance Oversight. The work associated with fulfilling commitments is tightly connected to managing risk. Thus, it is important to keep site governance councils frequently updated with progress and informed about unacceptable risks. These risks always include the risk of meeting a commitment date made to the FDA. Take commitment dates seriously. Other unacceptable conditions uncovered along the way should also be communicated to the governance body. Establish clear lines of communication and escalation between the team that actually does the work and governance. Learn how to escalate and resolve potential problems quickly. Nothing consumes the timeline as much as reluctant escalation and indecision.
  • Verify that Deliverables Solve the Problem. Take an independent look to ensure the work is completed and that the tangible deliverables are in-place and in-use. This is a good role for an independent consultant. It is far better to find out for yourself that the mark was missed than for the FDA to call it to your attention as a repeated observation. Be a healthy skeptic and ask, "How do we know for sure the problem is permanently solved?"
  • Revisit Commitments. Although you may have verified that the solution is in-place and in-use, revisit the problem at an appropriate time interval to ensure that the organization has not reverted to the old ways of working.
How have you managed regulatory commitments? What are your success stories? What have been epic failures, and why?


John 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 john@john-snyder.com.

Friday, October 17, 2014

Part 1: Responding to FDA483 Observations and Fulfilling Commitments

Part 1: The FDA483 Response

In this two-part series will discuss responding to the FDA483 and getting the work done to fulfill the commitments in a sustainable way.

Unlike a Warning Letter, a response is not required--but highly advisable. It is standard industry practice to respond to FDA483 observations. Responsible companies that want to have a good relationship with the FDA respond to each observation by saying exactly how problems will be addressed.

There is plenty advice available, even from the FDA, on what constitutes a good response. For certain, the difference between a good and a poor response may differentiate how you are viewed by the FDA.

From my experience, the following are points to consider that have worked well when forming a response:
  • Do you agree with the response? Stating up front that you either agree or disagree, in part or on the whole, stages the rest of the response. Think twice before you say you completely disagree especially with everything-- because the FDA will always have the regulations, industry good practice, and the facts on their side. But it is quite possible that the FDA investigator got the facts wrong or drew the wrong conclusion. This is why a close-out meeting with investigators at the conclusion of the inspection is important. It is better to straighten out the record at the close-out meeting than in the FDA483 response.
  • Defend what you are doing right. The examples of violations cited in observation are just a snapshot in time. Although you may not be proud of what was found, the finding may not be representative of the current state of control. The example may pre-date significant improvements that you have made on your own initiative, although they may be in progress and not fully implemented. Be sure to give yourself credit for such improvements. The last thing you want to do is give the impression that the FDA was the first to call a problem to your attention.
  • Take product lot numbers seriously. When the FDA mentions specific lot numbers associated with a problem, it immediately puts you in the position of having to defend why those lots are still on the market, and why you have not shut down manufacturing associated with that product, process, or facility. Put your best minds and writers to work to lay out the defense of your release decision and the state of control. Be objective and use data. If you come to the conclusion, albeit late in the game, that the product should be recalled, seriously consider the right thing to do. Also take into account causing a critical drug shortage, because the FDA will work with you to avoid a shortage while you resolve inspection-related problems.
  • Defend State of Control. Some types of observations paint a picture of being out of control, particularly when it is associated with validation, sterility assurance, potency, content uniformity--you know--the SISPQ issues. Also, taken collectively, observations that run the gamut of the quality system can indicate a precarious state of control. Take your best, realistic, honest shot at how you know you are manufacturing and distributing a safe, quality product. And, for goodness sake, do not--I repeat--do not anchor your defense that there have been no complaints or dead bodies in the street. Meeting all end product specifications may be the best defense you have if statistically treated, but be aware that a "final product spec" defense will always peg you as a 1970s time traveler.
  • Commit to Action. Address the specific issues that were called to your attention, but do not stop there. Carefully determine the root causes of the issues cited in the observations. There will not always be a one-to-one relationship of root cause to observation. Nonetheless, run the problem to ground and understand what is behind the problem. Determine the action required to prevent the reoccurrence of the problem cited. Undoubtedly, the solution will require changes in multiple areas at the system level. Be sure to convey that you are taking system-level action, not just addressing the superficial, specific examples. Remember, observations are just examples. Indicate the action you promise to take and target completion date. Be clear in advance what "done" looks like and the specific deliverables that will provide the evidence of successful completion.
  • Commit to Developing Appropriate Action. If you do not know exactly what all is necessary to fix the problem, it is completely acceptable to indicate that the scope of activities and target dates will be established in a plan to be provided later. But state in the response when indicate the plan will be completed and provided. Major milestones and target month are usually acceptable in a follow-up communication.
  • Recognize the Minimalism. Very likely you have taken a minimum essential approach to the commitment. By the time all the internal reviewers have edited the response, you have pared down the work to something manageable for normal business. However, the work associated with FDA inspection observations in not normal business. The scope of the actual work required to prevent recurrence of the observation may be more than expected when you actually delve into the root cause and prevent recurrence through systemic changes. 
  • Provide Realistic Target Dates. There is always a balance between showing responsiveness with aggressive target dates and over committing to unrealistic dates. When dealing with operational and quality system problems, there may be more work involved than meets the eye. Some problems may require engineering studies or process development in order to understand the right approach to take when solving a problem. Take time to really think through all that is involved in order to provide realistic target dates. You don't want to go back to the FDA--at least not too often--to revise target dates. Do inform the FDA of changes in completion dates. Don't let a broken promise be a surprise when they return to reinspect. It's far better to inform them in advance.
  • Engage Your Internal Associates. I cannot tell you how often I discover the situation where commitments and target dates were given to the FDA in very well written responses, but those who carry out the work were not involved--even totally clueless. It's best to involve those who have to fulfill the commitments in the actual writing of the response. Time is of the essence when preparing a response, but cutting out those who actually do the work will always uncover significant execution issues at the worse possible time.
  • Take FDA Suggestions. When the FDA makes a suggestion about retaining a GMP consultant to assess your overall quality system and help you to improve--take the suggestion. This recommendation usually comes in Warning Letters where the FDA has come to the conclusion from the breadth of problems and recurring problems that there is no confidence in your Quality Unit or Management Oversight. Consider such a recommendation as a direct hit and taking on water, not just a shot across the bow. So be responsive and act accordingly.
What is your experience with preparing regulatory observation responses? What has worked well? What has not worked well?

In Part 2 I will talk about organizing to get the work done to fulfill commitments.


John 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 john@john-snyder.com.