During this August, FDA 483s month here at FDAzilla, we repost some of our favorite pieces related to 483s. Here’s another from the QA Pharm.
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.
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.
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