During this August, FDA 483s month here at FDAzilla, we repost some of our favorite pieces related to 483s. Here’s one from the QA Pharm.
Compliance to current good manufacturing practice (cGMP) regulations is, in fact, a part of normal pharmaceutical business that requires diligent management oversight. Just as it is with other business functions, management has the responsibility to ensure that systems are in place to effectively monitor the state of control in order to intervene with timely decisions to manage risk, achieve goals, and add stockholder value.
However, the number of pharmaceutical companies that have received FDA warning letters or that are under consent decrees indicates that management oversight of cGMP compliance is a significant and continuing problem in the industry. There have been tarnished reputations, loss of brand loyalty, stockholder lawsuits, and unprecedented financial impact. At some point, the warning signals were undetected, unheeded, or rationalized away.
This is the first in a two-part series that explores the issues that can affect the ability of management to detect the warning signals of significant cGMP compliance problems and offers suggestions on how to gain control over this essential part of the business.
Obstacle 1: There is a Perceived Disconnect between cGMPs and the Business
Not only is there a perceived disconnect, but cGMPs are often viewed as an obstacle to daily operations. There is no greater impediment to devoting personal attention to any given matter than to question the value, or, at best, to think it a burden for someone else to bear. When this is a dominant belief of those in authority, it translates into speech and actions that are observed and emulated by subordinates. Over time, this view is widely adopted and becomes part of the company culture that influences the way daily work is performed.
Deep-seated beliefs such as these are very difficult to change. Defending the business value of cGMPs can only be successful if management actually believes it is true. Unfortunately for many in leadership positions, this understanding is not part of their education or experience. At best, their background may include a training course or seminar, but their daily experience with the pharmaceutical quality assurance and cGMP compliance functions are the frustrating hurdles to release product to market.
To win the hearts and minds of management to embrace the business value of cGMPs, one must put forward a rational argument that cGMPs are a business enabler and to integrate this belief into the company’s formal value statement, new employee orientation, and ongoing training. However, this requires a deeper understanding of the foundation principles of cGMPs and recognition that they are no different than those of the business.
The rational argument goes like this:
- Patients take the individual dose, not the average—sometimes every day for their entire life. Patients deserve the assurance that their drug will meet every quality requirement for each dose, not just on the average. That’s the objective of cGMPs, and that should be no less the objective of one’s business.
- Manufacturing processes are fraught with opportunities for unwanted variation to creep in from incoming raw materials and components to equipment, test methods, operators, facilities, utilities, and warehouses. Manufacturing a product that is continually faithful to what market approval was based on and all quality requirements only happens when done so intentionally. One can’t test quality into products.
- Standard operating procedures declare how a company intends to control variation and ensure predictability. The operative word is “standardize.” A company has the liberty to standardize how it works to be as efficient as possible to meet regulatory requirements. Contrary to common belief, cGMPs do not prescribe exactly how to comply, but the expectation is to keep up with current industry practice. A company is responsible for applying product and technical knowledge to the practice of cGMPs.
- When following standard operating procedures, records are created that document how the work was performed and the results. The way and when information is recorded and is important. Sometimes it is so crucial to the outcome that recording information must be witnessed. Documentation is how one proves and defends one’s work.
- Records contain data that describe how well the intent was achieved. The data can be collected, translated into performance metrics, interpreted by process owners and subject-matter experts for analysis and decisions to target actions to continuously improve processes, reduce waste, increase efficiency, prevent future failure, and enhance knowledge.
- A regular review of these performance metrics by a cross-functional management team is part of the mechanism to provide oversight and governance. When taking action on unacceptable trends a company becomes an anticipating organization, rather than a reactive one. A management review of the quality management system (QMS), like any other business review, is the primary source of data-driven confidence that one is operating in a state of control and is the basis for the confidence that one is maintaining an economical control of quality, increasing operational capability, and the ability to compete while meeting cGMP compliance expectations.
- Compliance to cGMPs supports the business by ensuring continuous quality and continuous supply of products to customers and patients. Continuous quality is quality that can be trusted. Continuous quality enables business performance to be predictable.
Although the argument may be logical, often those who are in the best position to make the argument, the quality function, referred to in cGMPs as the quality control unit (QCU), may not be up to par. Part 2 will deal with the QCU.
adapted and reposted with permission from The QA Pharm
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