Saturday, December 25, 2010
New heads of Quality Assurance come into pharma companies all the time for various reasons. If you are the new head of quality, hopefully you were able to get some sense for the reasons for the vacancy during the interview process. I recognize that this is not always easy in an interview situation.
I have heard such explanations as: we’re looking for a fresh approach; we’re looking for someone with more of a business perspective; we’re looking for a partnership with QA; we’re looking for an operations-oriented QA; or we’re looking for a more progressive QA.
Actually, these all sound very positive and a highly desirable situation for a new, enlightened head of QA looking for a challenge. But like the Rorschach test, these explanations could be interpreted various ways, some of which would be troublesome for the newbie who understands the regulatory role of QA.
Rarely is the expectation as clear as one example in my own career when a company president that interviewed me spoke very directly and took out all the guesswork.
The interview lasted three minutes—because I ended it. The president of the company said, “If you reject my product, blood will be let.” After a moment of nervous laughter I understood him to be quite serious, and that he was talking about my blood. I responded by plucking my resume out of his hand, tucking it back into my briefcase, and responding, “Would you please ask your admin to call me a cab?”
But there is no more popular reason for changing of the guard than being the incumbent on whose watch the company received a Warning Letter. The termination of the QA person is served up as a peace offering and symbol of turning over a new leaf.
The problem with turning over a new leaf is that sometimes it looks the same on both sides. The new QA head has the same struggles as the former head of QA, because the issue was not one of understanding and applying CGMPs, but facing a pervasive company culture of antagonism toward FDA regulations.
The FDA recognizes the possibility of antagonism when we read in recent Warning Letters: “QA was either unable, or not permitted to exercise its responsibility.” (See The QA Pharm 9/25/10.) However, neither is an excuse, because you had the option to resign.
As the new head of QA, you want to make a positive impression as a leader who can be trusted; who is a collaborator; who is a builder; and who makes mindful decisions. So here are some suggestions on what should you do before the honeymoon period is over.
1. Know for yourself the state of compliance.
Gather your own intelligence on the effectiveness of the Quality Management System QMS) and the general state of regulatory compliance. This should include CGMP compliance as well as compliance to the Chemistry and Manufacturing Controls (CMC) of your drug application. Don’t rely on hearsay, or solely on the results of previous inspections.
2. Establish a governance process.
Determine the appropriate performance metrics for each element of the quality system that reports both how well the system is working, as well as what the system is detecting. Report these in a decision-oriented forum of your peers. Solve the problems at a lower level, if possible. However, ensure that each problem rises to the appropriate level and person who has the approval authority for the cost of the solution. Be sure you have allies in the room. Document the decisions, even if the decision is to do nothing, or to postpone action.
3. Build relationships with other functional heads.
Build trust with your peers. Work together to identify and resolve problems. Give credit to other areas when they identify problems and come forward to resolve them. Don’t blindside a peer in a public governance process. Offer to resolve problems that other areas have with inefficient quality system processes.
4. Integrate the quality/ compliance plan into the business planning process.
Develop a quality planning process based on the problems and risks identified from the management review (governance) processes. Integrate the quality plan with the normal business planning process.
5. Speak the universal language of money.
Resolving waste streams, rejections, and nonconformance, etc. all have associated cost. Resolving these issues not only save money, but improves quality and CGMP compliance. Never allow cost to enter your judgment when making a market release decision; however, keep focus on problems that improve the bottom line, and get the compliance for free.
6. Use the fine art of writing proposals.
Write proposals to improve the way of working, to implement a new program, or to make a capital expenditure. Putting proposals in writing helps you to make the case to support. Be sure to capture the return on investment, cost avoidance, or risk mitigation. Shop your proposal to other functional heads, and allow them to sign on to the proposal to signify support.
7. Strengthen the Quality function.
Make time to visit each functional head during the first month of your tenure to ask: What does the quality function need to do more of? What does the quality function need to do less of? Be willing to accept the feedback. Loop back with each one to let them know your assessment of the situation and the action you are taking.
I invite you to share your thoughts and experiences that would benefit our readers, especially the person walking into a new QA leadership position.
The QA Pharm
Saturday, December 18, 2010
I understand on a philosophical level that everyone owns “quality.” Much like safety, everyone has responsibility for following safe practices and calling attention to potentially unsafe conditions. However, there also is a Safety Department that is responsible for establishing safety policies and procedures, as well as conducting periodic safety inspections. They also report the safety metrics such as “OSHA Reportable” incidents and near misses. Members of the Safety Department keep current with the latest safety equipment, changes in the regulations, and benchmark against best industry practice. Management takes these reports and metrics quite seriously, because it is ultimately responsible for ensuring a safe work environment.
This is fairly analogous to the Quality Management System (QMS). Everyone has personal responsibility for following CGMPs in general and procedures in particular. The Quality Assurance Department is responsible for establishing and measuring the effectiveness of the QMS. They periodically conduct internal audits and report quality system performance metrics. The findings are reported to management, because they are ultimately responsible for ensuring that products are manufactured in a state of control and in accordance with CGMP regulations.
But allow me to break away from generalities and get very specific, because it is in the specifics where I believe the QMS falls apart in practice. It has to do with the notion of “ownership” and having a person—by name—for each element of the QMS who “owns” that particular element and exhibits defined “ownership behavior.”
In my opinion, creating an environment where “ownership behaviors” are defined and expected is a powerful part of a compliance sustainability strategy.
What are some “ownership” behaviors? Take these for example:
· Own the (System) Procedure: The Owner is responsible for ensuring that the procedure or set of procedures for his/her particular element of the QMS remains current with regulatory expectations and best industry practice. The Owner does not wait for negative feedback from a regulatory agency or corporate audit to identify the problems or to be motivated to improve to the system. For example: the Owner is the first to know that an identity test is required for each drum of active ingredient and is the driver to ensure that the procedure is changed.
· Own the Implementation: The Owner is responsible for ensuring that the particular element of the system is deployed. It is in the Owners best interest to know that all the employees required to be trained on the procedure have been identified and the procedure is incorporated in the employee’s curriculum. For example: the Owner of the Complaint Handling system ensures that anyone who could possible receive a product complaint has been trained. It would not be unusual for the Owner to conduct the training as the subject matter expert. In fact, the collective Owners in the company should be the focus of a “train the trainer” program.
· Own the Performance Metrics: The Owner is responsible for identifying the best possible performance metrics that would indicate how well the system is being managed, as well as what problems the system is detecting. It is the Owner who first detects an unacceptable trend and calls it to management attention. It will be the Owner who presents the system metrics to the management review forum. For example: it is the Owner of the CAPA system who reports to management about the significant backlog and the associated regulatory and product quality risk.
· Own the Recommendation: The Owner is responsible for knowing what the solution to the problem is. The Owner will have consulted with the users of the system to understand implementation issues and identify targeted action to address the problem. When the Owner presents metrics to the management review forum, recommendations are suggested. In many cases, it will not be necessary for management approval to proceed with the solution. For example: it is the Owner of the preventive maintenance system that first detected the backlog, but has also determined with the production manager that an integrated PM-Production Schedule is required. So they just do it and inform management.
· Owns the Knowledge: The Owner is the subject matter expert (SME). The company has supported the continuing education for the Owner to ensure that he/she remains current in the field. The Owner takes the initiative to identify educational opportunities. When companies cut back on the training budget, they certainly want to “red circle” the Owners to ensure that they are exempt from the budget cut. The Owner shares the knowledge to continually raise the competency bar. The Owner is the person who represents the system for problem solving, as well as addresses questions during regulatory inspections.
“Ownership” does not mean isolated or autonomous. But in this world of managing the business and decision-making through teams and consensus, “ownership” and personal accountability tends to get lost or totally diffuse.
Just imagine the organization strength if “ownership behaviors” were expected and nurtured within an operating site, as well as across the company sites.
Just imagine the framework for continuous improvement at the site and company network levels to turn the Owners loose to drive best compliant practices.
(1) Make a list of the elements of your quality system (e.g., deviations, CAPA, batch record review, incoming inspection, etc. and enter the name of each Owner.
(2) Develop a strategic plan to support and enhance ownership behaviors.
Watch awesome things happen!
The QA Pharm
Tuesday, December 14, 2010
Please share your experience if this cartoon from down on the QA Pharm resonates with you.
The QA Pharm
Saturday, December 11, 2010
I am often asked how best to prepare for an FDA inspection when you know that you have problems. My first response is that they have already taken the first step: acknowledging that there are problems. Believe me. That is a huge first step. Just like AA’s 12 step program, it’s not until you are willing to admit this aloud that you are on the road to recovery. But just knowing that problems exist is not enough to survive an FDA inspection.
Here are the various positions that firms find themselves when the FDA comes knocking. You can decide which of these scenarios is the best possible position.
1. We know what our problems were, but they have been resolved.
Let’s say an FDA investigator stumbled upon a manufacturing work order system that allowed changes to production equipment without a review by QA on the impact on the state of validation. The best position to be in is to say that you were made aware of the problem; the system has been revised and employees trained; a retrospective review of maintenance work orders was conducted for product impact and appropriate action taken.
It engenders confidence when an inspector can see evidence that a problem has been resolved and a product impact analysis has been performed. It portrays the firm as being responsive to self-detected problems as a normal course of business.
2. We know what our problems are; we have a comprehensive plan; we are executing the plan on schedule.
A common strategy for firms that anticipate a Warning Letter or a Consent Decree is to have a third party conduct a thorough systemic audit and to develop a comprehensive corrective action plan. It’s a way of saying to the FDA, “You can’t force us do anything that we aren’t already forcing ourselves do.” The plan is in writing, deliverables defined, reasonable target dates are established, responsibilities assigned, and management is tracking accomplishments versus the plan.
It can diffuse an otherwise nasty inspection when management demonstrates that it is taking the initiative to deeply understand its state of compliance and holding itself responsible for timely results. The FDA inspector may still give you observations, but the Establishment Inspection Report (EIR) will note the initiative you have taken. Also, the FDA may quibble over the scope of the plan, or the timetable for completion, but it is far better to have the plan be the center of discussion than inaction.
3. We know what our problems are; we have a plan.
The difference between this position and the one above is the failure to execute according to the schedule provided in the comprehensive corrective action plan. In my opinion, failure to execute is one of the most significant issues that separate the wheat from the chaff. Some companies just cannot get out of their own way to accomplish meaningful change. Administration substitutes for real work; team meetings substitute for personal accountability; and production schedules take priority over executing the comprehensive compliance plan. Something else always is more important—there is no discipline, no organization alignment, and no leadership.
It becomes evident during an FDA inspection that it is all talk and no action. FDA cites repeated observations from previous inspections. With FDA on record that there will be no multiple Warning Letters, this places you in the crosshairs of increased enforcement action.
4. We know what our problems are; we have no plan.
This is perhaps the most dangerous position to be in. Consciously not taking action when there are known problems is irresponsible. When faced with an issue during an inspection, you are either forced to say that you were not aware of the problem, or that you were aware of the problem and have not taken action. Neither response is very pretty. One is actually a falsehood.
This signals to the FDA inspector that CGMP compliance is not considered to be important to the firm, and that the dots have not been connected between regulatory compliance and patient safety. To be clear, management is personally legally liable for knowing its problems and resolving them. This is a real slippery slope.
5. We don’t know what our problems are.
What problems? This describes companies that rely on FDA inspections to tell them what the problems are, and the firm is always aghast to learn about the problems and ready to call someone on the carpet. This describes management that thinks an FDA483 with five observations is an improvement over the previous one with ten. This also describes the company that does not have established processes to take responsibility for the effectiveness of the quality management system such as: management review of quality system performance metrics, internal compliance audits—or just generally thinking that it is someone else’s job to worry about it.
You would be surprised at the number of senior management who can’t even tell you what their top five problems are. FDA calls this “inspecting into compliance,” and they have very little patience for this unenlightened perspective. These are the bottom feeders in our industry.
So, which position would you rather be in during an FDA inspection when you know you have problems?
The QA Pharm
Saturday, December 4, 2010
The Warning Letter to Claris Lifesciences1 was one that went on and on, page after page citing violations of fundamental, block-and-tackling practices. This was surprising and a disappointment given that Claris is one of the largest sterile injectable pharmaceutical companies in India with a market presence in 76 countries worldwide.
From a patient’s perspective, their products are injected directly into the human body and are used in the treatment of critical illnesses.
So extensive is the Warning Letter that it is organized into sections that conveniently walk the reader through the logic of the inspection: CGMP Violations (that cover the gamut), Field Alert Reporting Violations, Unapproved New Drug Violations, Adverse Drug Experience Reports, and a Conclusion.
In layman’s language: you are not operating in a state of control, you are not reporting the product problems, and you are even introducing unapproved products into interstate commerce.
This Warning Letter, issued on November 1, 2010, might be viewed as another example of the FDA interest in contract manufacturing operations. (FDA considers Claris a CMO.) To me, however, it appears to be a combination of Rick Friedman's interest in sponsor oversight of CMO's as well as the general trend of the Agency toward accountability.
Why? Get this.
To my recollection, client/ distributor names associated with the problem products are usually not mentioned, or at the very least have been redacted before being posted. In this case Sagent Pharmaceuticals and Pfizer get honorable mention for the world to see as being distributors associated with Claris’ problems.
Another interesting feature of this Warning Letter that it is fairly direct in stating what the FDA expects to see in Claris’ response. For each observation, there was a paragraph that began with: “In your response to this letter, include…”
For example, FDA requested:
· Explain your failure to initiate the complaint investigation promptly.
· Explain the discrepancy between finding fungi in the IV bag as well as the overwrap and reporting that no leak or contamination was found.
· Explain why defective parts were being used and how the supplier of these defective parts was qualified.
· Explain how and when Claris identified and informed all customers affected by your IV bag manufacturing problems.
· Explain why other products filled in the same packaging line, with the same bags and printing process, were not affected or contaminated.
“In conclusion,” wrote the FDA, “you are under FDA Import Alert so we will refuse admission of your products into the U.S…”
That’s a pretty big conclusion statement.
This is unfortunate indeed, given their medically necessary products including anesthesia, plasma volume expanders, nutrition and oncological infusion therapies.
I’d say that the FDA delivered not just a shot over the bow, but rather a direct hit—and Claris is taking on water. Unfortunately, the availability of medically necessary products to needy patients is going down with the ship.
Are there any remaining questions about CGMP compliance and its relationship to being able to compete in the marketplace, or patient impact?
1 Claris Lifesciences Warning Letter, November 1, 2010. http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm233010.htm
The QA Pharm