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 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 a 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. Sponsors 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?

The QA Pharm

The Quality Management Triad: a Model for Performance Sustainability

Establishing a sustainable Quality Management System that helps a company to become an anticipating, rather than a reactive organization requires intentional effort to bring three essential element together. I call these elements the Quality Management Triad.

The first part is Quality Governance, this is the body that provides:

• Vision—the aspirational view of the future, and how Quality Management is integral to the business strategy for operational performance and continuous product availability to patients;

• Leadership—the top business unit and functional heads who motivate, align, plan, and engage the organization toward its quality goals;

• Standards—endorse the policies and norms, which establish the quality requirements—the interpretation of laws and regulations to your operation—the “what” is required;

• Oversight—the communication channels and forums that give Leadership visibility to product quality and compliance risks and trends—in order to make effective data-driven decisions—and provide Leadership the means to exercise management responsibility.

The second part is the Pharmaceutical Quality System (which is the ICH Q10 term for the Quality Management System). The Pharmaceutical Quality System—or PQS:

•  Management System—the totality of policies, standards, processes that directs and controls activities with regard to quality;

• Processes—to ensure consistency and intentional ways of working when applying the standards to your operation—and to control variables, including the human variable;    

• State of Control—quality is about controlling variation, and the Pharmaceutical Quality System provide the capability of self-detecting and self-correcting problems and give us a clear picture of our current state of control.

• Continuous Improvement—knowing the top regulatory compliance risks at any give time and having project teams directed toward resolving them with verifiably effective solutions.

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 managing the constituent parts of the Pharmaceutical Quality System:  Ownership responsibility includes:

• Execution—they manage the daily operation of the quality processes described in procedures and ensure procedures are effective;

• Maintenance—they ensure that the quality process remains current with regulatory requirements and industry practices; and remain applicable to your changing business;

• Performance—they measure how well the process is working and identify problems with the process, and problems that the process detects—and always seeking ways to meet the requirements in the most efficient way.

• Escalation—they identify unacceptable conditions or events that puts the patient and the business at risk—and take the immediate actions necessary to mitigate the risk, and make 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. Much like Safety is everyone’s responsibility, it is the Quality function’s responsibility to establish the ways and means for the Quality Management Triad; and ensure effectiveness.

Why is The Quality Management Triad important?

The pharmaceutical industry is a dynamic business environment.  Acquisitions, operational realignment, portfolio changes, manufacturing relocation, facility re-purposing, 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: 

A 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 underlying theme of the series of FDA483s and the eventual warning letter when the site was fraught with recurring manufacturing deviations, missed target dates, and ineffective solutions promised to the Agency.

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 in the business environment. 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.

The Quality Management Triad is a key element of a business strategy to sustain performance and ensure a continuous supply of quality product to patients.

The QA Pharm

Part 5: Five Obstacles to Management Oversight of the Quality System

This is the fifth and final part in this series that addresses underlying obstacles to management oversight of the pharma quality system as evidenced by the the continuing serious compliance and product quality problems in our industry.

Part 1 dealt with the management perception that cGMPs are not relevant to the business, and it laid out the defense that cGMPs enable a predictable quality outcome that serves the business and its patients very well. 

In Part 2, the quality function was indicated to be in the best position to make the defense of the relevance, but all too often it has problems of its own and should be the focus of serious organization development. 

In Part 3, it was recognized that although management may be responsible for the quality system, they may not know how to exercise that responsibility. It is the responsibility of the quality unit to provide a forum where management can make data-driven decisions and monitor quality system performance. 

   In Part 4, the case was made for the importance of a company to have channels throughout the corporate structure to be able escalate product quality and compliance risks, as well as disseminate corporate directives, since there are many examples in our industry of problems at one site affecting all the others.

   When it comes to taking site-wide and company-wide action, there are tools at hand to establish priorities and drive behaviors. The same tools can apply to improvements to and problems identified by the quality management system.

   Obstacle 5: Quality Planning and Performance Management Systems are not Leveraged for Large-scale cGMP Performance Improvement

Warning letter observations are commonly phrased as a failure of the QCU to establish an adequate system for the cited problem. Although it is the responsibility of the QCU to establish the QMS, a capable QMS and a continuous state of compliance rely upon everyone in the organization to do his or her part. Problems are often site-wide or corporation-wide, and it often requires multiple functions to collaborate. Unfortunately, the priority of one group is not necessarily the priority of another and initiatives stall from lack of support. Sometimes the lack of progress on a significant problem is barely perceptible. Regrettably, it comes to light too late when the same problem is detected at a subsequent regulatory inspection at the same or different site. The enforcement heat is turned up, and management is left wondering why all were not pulling together.

Aligning the organization to work with singleness of purpose to become a highly capable organization is one of the most important jobs of management and one of the most difficult. It is no less challenging for resolving cGMP compliance issues. The annual business planning process and performance management systems are often overlooked as management oversight tools for unifying support for important cGMP compliance initiatives, yet these processes are used throughout the industry to bring focus on the current priorities and to align resources. Tapping into the power of declaring what is important and rewarding achievement is a highly effective strategy for culture change by modeling and directing behavior since what is valued is rewarded.

The Opportunity?

So, what can be done to promote integration of cGMP initiatives into the business plan to affect meaningful change and achieve business results?

The answer is to use established QMS processes to identify the right initiatives, use established objective-setting processes to focus broad attention, and expect results because achievement is rewarded and there is accountability.

The following are important considerations when leveraging the business planning process and performance management systems as cGMP management oversight tools:

• Use the established quality management review and governance processes to identify cGMP highly leveraged improvement targets as site-wide objectives.

If designed and operating properly, the QMR and quality council processes will point to problems that require a significant attention and collaboration to improve predictable quality and consistent compliance performance. These established systems should be the basis for identifying data-driven improvement targets rather than creating new processes that may serve only to agree on dominant opinions at one point in time. Spend site-wide focused attention judiciously on initiatives that leverage exceptional benefits that can be annualized. Thus, annual planning objectives should be directed toward developing a more capable organization than fire-fighting projects.

• Partner with operations functions to develop mutually beneficial objectives.

The QCU is often criticized for not being interested in manufacturing efficiencies and productivity. Cycle times and unit cost are often considered business concerns, not quality or compliance. However, behind every inefficiency and lack of productivity could be a latent compliance problem. Consider, as examples, examining waste streams and permanently eliminating recurring deviations through engineered solutions. These are worthy targets of cross-functional collaboration as an operational goal. Every dollar of eliminated waste and redundancy is directly applied to the bottom line. The operation is more profitable and the cGMP compliance improvement is a side benefit.

• Manage the work and remove impediments.

Team composition with the right leadership, subject-matter expertise, and team skills are tremendously important. Facilitation, OpEx, and project management may be additional support roles needed but are not a substitute for pharmaceutical quality system management and regulatory compliance knowledge and experience. Project teams also benefit from senior-level sponsors who will champion the effort and help to remove stumbling blocks that devour valuable time and energy. Sponsors also jealously guard the teams’ time to allow them to get the job done and protect them from insidious administrative and dog-and-pony show distractions. However, most important is for the team to have a clear picture and alignment on what “done” looks like and how to tell when it is reached. This requires agreement on the vision of the future and how success will be measured. Both are anchors to keep teams from going adrift.

• Reward results, not the process.

Certainly, how work is done is important, and the tremendous effort by team members is appreciated. However, when it comes to compensation and public recognition, nothing less than accomplishing the objective should be rewarded. To do otherwise enables mediocrity and does not drive performance. Most important is to verify that the intended result was achieved in behavioral terms. In the cGMP environment, improvement initiatives usually result in changes to written procedures, yet, remember that changing words on a page does not necessarily change the behavior. Assess the performance metrics and records to determine if the objective was achieved. Capture the cost savings where possible to model compliance improvement as worthy targets that improve the bottom line.

Conclusion

This series has made the case for the intrinsic value to the business of compliance to cGMP regulations. Although there is a negative case to be made given the high stakes of non-compliance, the positive aspect of cGMPs as a business enabler is emphasized here. However, this is highly dependent upon the mindful and collaborative application of cGMP regulations by the QCU and the creation of an integrated QMS based on specific operational knowledge. Management has oversight responsibility of the QMS, which is facilitated by an action-oriented QMR and aligning the organization behind large-scale transformation objectives. Ultimately, through the combination of applying the underlying principles of cGMPs and the ongoing measuring, responding and learning from an effective QMS, additional benefits are obtained. These include accruing knowledge, preventing failure, enhancing organization capability, and increasing product quality predictability.


The QA Pharm

   

Part 4: Five Obstacles to Management Oversight of the Pharmaceutical Quality System

This is the fourth of a a five-part series that addresses underlying obstacles to management oversight of the pharma quality management system as evidenced by the continuing serious compliance and product quality problems in our industry. 

Part 1 dealt with the management perception that cGMPs are not relevant to the business, and it laid out the defense that cGMPs enable a predictable quality outcome that serves the business and its patients very well. 

In Part 2, the quality function was indicated to be in the best position to make the defense of the relevance, but all too often it has problems of its own and should be the focus of serious organization development. 

In Part 3, recognized that although management may be responsible for the quality system, they may not know how to exercise that responsibility. It is the responsibility of the quality unit to provide a forum where management can make data-driven decisions and monitor quality system performance.

But management oversight can still be handicapped if there are no governing bodies or processes to communicate regulatory compliance and product quality risks.

Obstacle 4: Governance throughout the Corporation does not Actively Review and Escalate cGMP Compliance Risks

When regulatory inspections turn up recurring violations, it becomes apparent that the company lacks the ability to permanently resolve problems that potentially or materially compromise product quality. The situation is exacerbated when FDA believes that unless the company is restrained, the company will continue violating regulations. In cases of consent decrees, it is a vote of no confidence in the management and the QCU; the effects are serious to the business. Penalty and remediation costs are extraordinary. A third-party consultant group is usually mandated to serve as a surrogate QCU with legal responsibility to review and approve investigation and batch records. The third-party conducts an extensive baseline audit and reports the findings directly to FDA. Consultants are retained to help lead a transformation of the QMS and the organization. Timetables to achieve milestones specified in the consent decree are aggressive, and additional resources flood in at an unmanageable rate. Delayed new product launches and disruption to market supply of existing products may be irrecoverable. Thus, corporations at the highest level cannot afford to be uninformed of cGMP compliance problems at any of its operations because the effect extends beyond a given operating site to the far reaches of the global network.

Governance in the broadest sense relates to how a company manages compliance to applicable laws and regulations. The term has come to mean self-oversight in areas that affect stockholders, such as accounting practices. However, cGMP compliance issues and operating in a state of control are also key issues that affect the profitability and viability of a company. The management agenda from operating sites to the corporate boardroom must effectively cover cGMP compliance risks, product quality implications, and regulatory enforcement action to get the true picture of company vulnerability.

The Opportunity?

So, what can be done to protect the extended corporate network from regulatory compliance risks that may exist at any given operating site?

The answer is to establish a governance process that creates a network throughout the organization that focuses product quality and cGMP compliance. The interdependence of the compliance performance among sites for consumer protection and the financial health of the company justify that there are governance boards to oversee this significant part of the business.

The following are features of an effective corporate governance body for cGMP compliance oversight:

•   There is a network of quality officers that represent each level of the company.

A top-level quality professional must be established for each level of the corporation. These typically are the operating site, the business unit, and the corporate levels. These individuals are designated as quality officers and have ultimate responsibility for the QMS and the QCU at their respective locations. A significant portion of their time is spent working together as a quality collegium to develop quality and cGMP compliance strategies for the company in an effort to support its current and future business. As such, evaluation of the personal performance of a quality officer is heavily weighted on their contribution to this collegium and effectively deploying its mission to their respective sites.

Quality councils are established at each level of the company to oversee matters relating to product quality and cGMP compliance. The local quality council is where the fullest understanding of process capability resides and initiatives for site improvement are driven. The quality officer chairs the quality council and membership is comprised of the ranking executive (e.g., general manager, president, etc.) and the functional department heads. The quality council should be a stand-alone forum in order to maintain the focus on a product quality and cGMP compliance agenda. The agenda should include topics such as establishing and deploying quality policies, review of regulatory inspection findings and verification of resolution throughout the network at a systemic level, setting quality goals and measuring progress, review of critical deviations and the status of associated corrective and preventative actions (CAPAs), and reviewing risks escalated from QMR and lower quality councils. Quality councils are focal points of knowledge assimilation and sharing.

•   A process and criteria are established to rapidly communicate critical issues.

The quality officers must establish channels of effective communication from the functional areas to the quality council and among the quality officers at all levels of the corporation. Conditions and criteria must be established for which direct and immediate escalation occurs. Although different for various levels of the corporation, the escalation criteria must be clear and embedded into quality council procedures. When it becomes necessary to exercise the escalation requirement, it is essential that it happens within a specified timeframe and is apolitical and unfettered by local approvals. After escalation has occurred, the added value is the assessment and mitigation of risk, notification to other sites, follow-up and network-wide verification, and closure.

•   Key quality metrics of importance to the corporate network are established.

During the course of the operation of the quality councils, the quality officers may determine key quality performance indicators (QPI) to be measured and reported across the corporation. The QPIs may vary year-to-year and focus on topics related to current FDA enforcement trends or areas of known recurring problems, such as supplier performance, recurring deviations, and CAPA effectiveness. Collecting corporate-wide QPIs is a challenge since sites are typically competitive and want to keep performance measures to themselves—or define the parameters and calculations to their advantage. Quality officers can address parochial behaviors by setting the expectation that their personal performance is based on working collectively as a quality officers in a collegium setting for the greater good of the corporation. A quality officer may wear a “site hat,” but the larger one is a “corporate hat” when the meet together as a collegium.

•   The corporation supports an Ombudsman program.

Ombudsman programs provide direct access between any company employee and a neutral third-party that takes reports of suspected conditions or activities that are illegal, unethical, or against company policy. Employee concerns about cGMP compliance fall into all of these categories and should be included in the program along with other areas such as finance, safety, and human resources. In order to preserve confidentiality and engender openness, the Ombudsman program should be managed independently by a third-party and coordinated by a neutral group such as the legal department. The quality officers and their respective quality councils will have a role to play in investigating and responding to reports.

The issues described thus far in this series have centered on management embracing the value of cGMPs and establishing the quality leadership roles and functions in order to organize, measure, and report on the performance of the QMS and govern this important aspect of the business throughout the corporation. However, some cGMP compliance problems may be so pervasive and entrenched that redirection of a large number of personnel and sites are required. The temptation is to embark on costly, trendy, and non-specific quality programs when some important tools are already on hand. In Part 5 we will look at leveraging these tools as a means of exercising responsibility and oversight of the quality system

The QA Pharm

Part 2: Five Obstacles to Management Oversight of the Pharmaceutical Quality System

Part 2: Five Obstacles to Management Oversight of the Pharmaceutical Quality System

This is the second of a a five-part series that addresses underlying obstacles to management oversight of the pharma quality management system as evidenced by the continuing serious compliance and product quality problems in our industry. Part 1 dealt with the management perception that cGMPs are not relevant to the business, and it laid out the defense that cGMPs enable a predictable quality outcome that serves the business and its patients very well. The quality function should be in the best position to make this defense, but all too often it has problems of its own.

Obstacle 2: The Quality Function Does not Fulfill its Regulatory Responsibility and is Detached from the Operation.

The QCU is the only pharmaceutical function that is established by the Code of Federal Regulations. It is required to exercise its regulatory mandate without a conflict of interest. Part of its responsibility is to establish the QMS, which, as described above, contains the body of procedures that declare how the company intends to operate in compliance with cGMPs. However, too often the QCU develops procedures in isolation, and the rest of the company is willing to let them do so. Without collaboration and integration with the business, the procedures will be disjointed and invite “workarounds.” In these cases, the QCU may actually contribute to compliance problems. Thus, the cycle continues and cGMPs are viewed as being disconnected from the business—primarily because they are.

The quality function has a responsibility to lead the effort to establish a compliant QMS that efficiently applies to the operation. Both are required to be competitive. The modern-day quality organization must have the ability to protect the business from compliance risks as well as the ability to be integrated with the business. It is not an adversary empowered by a sense of external authority, nor does it cross the line and lose its independence and objectivity. Rather, the QCU is a partner whose role adds a valued perspective. However, the quality organization may not have the skills to assess how to apply cGMPs to differing operations or how the QMS must evolve to meet the changing mission of the plant site.

The Opportunity?

So, what can be done to establish a business-integrated QCU that fully meets the intent of cGMPs?

The answer is that management must challenge the QCU to a higher performance level by establishing an organization development strategy. The strategy must include an objective assessment against factors critical to its success.

Critical success factors for the pharmaceutical QCU include:

• Roles mandated by cGMPs for the QCU are incorporated into the QMS and are faithfully practiced.

The regulatory mandated roles of the QCU center on its authority to operate independently and objectively as a reviewer and approver of matters related to cGMPs. This includes procedures, specifications, nonconformance and complaint investigations, and product release into the market. Such authority does not preclude collaboration with other functional departments and subject matter experts. The reporting relationship and financial incentives for the QCU must not create a conflict of interest.

Non-regulatory activities that divert time from their primary responsibilities should be challenged and properly positioned in the organization. For example, the QCU should not be the training function or the validation function simply because training and validation are important cGMP requirements. This would create a conflict of interest where the QCU would be approvers of its own work. Rather, the training and engineering departments must know how to apply cGMPs to the practice of their respective professions in a pharmaceutical company, and the QCU review and approve their procedures and records.

• QCU professionals have a working product and process knowledge.

Product and manufacturing process knowledge is essential to fulfill the responsibilities of the QCU. An effective review of procedures, batch records, and investigations is not possible without a fundamental understanding of the science and technology of the product portfolio. It is far better to transfer and promote experienced manufacturing personnel into the QCU who have demonstrated the ability to apply and practice cGMPs than to inbreed QCU personnel.

Compliance without product and process knowledge becomes legalism, and the QCU is often reduced to an administrative function that becomes distracted by minor issues; the significant risks that require management attention are lost in the noise.

• The QCU has the skills of quality science, not just cGMP compliance.

Engineers, microbiologists, chemists, and pharmacists have defined curricula for their professional degrees. The pharmaceutical quality professional may have a scientific or technical degree; however, there is no defined body of knowledge that is widely accepted across the industry to equip the QCU. Many individuals start as bench chemists or microbiologists and rise through the ranks. Many build their resumes by transferring between companies. Others are recruited from companies with high visibility compliance problems to benefit from their remediation experience.

Management must consciously enhance the core skills of the QCU to enable it to operate from product development through technical transfer and to daily manufacturing. They must know how to measure and control variation as well as understand the effect of change on a technical level. They must possess tools to assess risk, reduce waste, and calculate price of nonconformance. The QCU must know how to speak the language of finance and risk management to make the business case for its proposals using polished presentation skills. They must not continually resort to the scare tactics of presuming to know exactly what FDA does and does not like.

Even with a top-notch QCU and a QMS that effectively and efficiently supports the business, there is still the possibility that compliance problems will evade the attention of management without a formal review mechanism. In Part 3 we will look at the effectiveness of the Quality Management Review process.

The QA Pharm