Over the last decade, it seems that there have been a steadily increasing number of pharmaceutical products recalled, either by the U.S. Food and Drug Administration (FDA) or voluntarily recalled by their manufacturers. Offenses have ranged from the egregious (potential glass shards and incorrect product in package) to the mundane, less patient-threatening (slight “musky” odor, slight errors on the label or improper package inserts), but all have constituted “adulteration.” Speaking at PhRMA’s annual conference in Washington, D.C., FDA Commissioner Margaret Hamburg highlighted recent reasons for concern that quality standards are not being adhered to, as well as the agency’s renewed focus on enforcing those standards: “We are … trying to really reshape some of how we address the quality issue, to try to incentivize better practice and more accountability around quality … And I think this is the time when we need to be recommitting to it.”
In response to Commissioner Hamburg, the question at this point becomes: “How does one increase and enforce both compliance and quality in the industry?” Perhaps this sounds either naïve or even overly ambitious, but ultimately the dialogue must start. Consider the following observations based on more than 40 years of experience working in the industry:
There needs to be an overall atmosphere where the Board/Executive management supports quality goals as much or more than financial goals. General Motors has been in the news recently because the company appeared to care more for profits than the lives of their customers. Media reports point to how GM’s internal culture led executive managers and others in disparate operational and legal departments shuffle and silo the problem without actually working to resolve it in an ethical, straightforward manner. One can only imagine the memos calling for “better data,” or “another study,” or waiting for some “other” department or administrator to provide more information. Add to this purposeful obfuscation by some, then buck passing and CYA behavior from others, and it becomes less hard to imagine how the company sacrificed its reputation for the sake of first green-lighting a potentially problematic component design (created under tremendous pressure on the supplier to squeeze every cent of cost they could out of the part to meet GM purchasing’s price target) and then delaying a recall on a part that cost 56 cents.
When a company’s executive management makes it excessively clear that quality has the highest priority and then acts on that principle (investment, training, rewards, warnings, dismissals, etc.), only then will there be a chance for the rank and file (middle managers, directors and department heads) to deliver compliance and consistent quality to consumers. So often, CFOs see things in black and white; that is, numbers on paper, but seem not to perceive the negative ripple effect harsh cost-containment financial policy can have on corporate culture and ethical behavior. It’s likely rare that a Pharma manager blatantly told an employee to perform an illegal or unsafe act. The message is usually more subtle, i.e., “We have a cost containment goal” or “Remember, your raise is based on the number of units made/assayed/packaged each year.” When the manager asks for results, does he/she phrase it as, “When will you finish the assays on that lot?” or, more likely, “When will you pass that lot?” How he/she asks for results gives the worker a subtle goad to move more quickly (and get the “right answer”), no matter what.
What is needed is a change to an atmosphere of “Do the best you can, no matter what the answer.” Then, and only then, will the workers feel comfortable to follow rules and not a manager’s whims. Would it hurt to have a manager’s year-end evaluation acknowledge exemplary compliance performance and proper adherence to cGMPs along with production and other output targets?
It is hard enough to keep employees adequately “trained,” especially if quality or compliance regimes are confusing or contradictory, guided by SOPs so numerous, poorly understood and badly administered that the only “standard” procedure is to work around them. Hard to believe? Several years back, a major company came under a consent decree for, among other offenses, “excessive and contradictory” SOPs (Some 35,000 were identified). No amount of training or training investment will ever truly ensure compliance when SOPs are nearly too numerous to count and contradict one another.
In addition, no human Quality Assurance (QA) or Compliance officer could possibly keep up with the paperwork for that may SOPs. It’s more likely that when faced with overwhelming workload (paperwork and associated administrative tasks), work that’s rarely checked by any QA authority, the human thing to do is prioritize and assign a rough hierarchy to various SOP-related tasks so as to avoid the “appearance” of non-compliance — such behavior often leads to a 483 observance. In addition, when faced with contradictory SOPs, one version has to lead to either product failure or a non-compliance citation, so what does the operator do (especially when there is a tight production schedule)?
PERSONNEL AND WORKFLOW
In the age of contraction or downsizing and “lean,” apparently the prevalent business model driving operational resource planning, adding headcount or training existing personnel to be fluent in modern analysis methodology or multivariate analyses, is likely out of the question.
In general, just implementing a standard GMP-based process for a solid-dose product requires a number of procedural steps. With this much complexity (granulation, drying, blending, compaction, coating and packaging) involved in a step-wise process (that has not changed all that much over the last 50 years), each arrow may represent a large number of steps, each time-consuming and often tedious … and all of which must be documented. The time between steps can be as long as days or even weeks, adding to the cost and time of production … all of which may lower quality.