You missed Part I?
Are pharmaceutical quality systems too complex to be effective? According to an industry expert and a regulator they are, and an injection of simplicity will help manufacturers to improve their quality performance.
In Part I Bob Rhoades, VP, Quintiles, who represented industry, and Ian Thrussell, Head of Inspections, World Health Organization, representing regulators, talked about quality systems in the industry today and the challenges of simplicity and GMP compliance.
Both of them spoke at the “Quality Systems” Session of the 2012 PDA FDA Joint Regulatory Conference. Despite representing opposite sides of the industry, both concurred that a quality system can be designed user-friendly without sacrificing expectations for clear and direct information.
Ian Thrussel then discussed what regulators are looking for when they visit a facility. Ultimately, they’re looking for the company’s “degree of compliance.”
“We’re interested in the things you do well, the things that you do right, the things you excel in, not just the things you don’t do so well in,” he emphasized. “The deeper things we are asking ourselves is can you be trusted, do we trust you, when we walk out the door will those good things that you showed us in the procedures and so on…will they continue to do that same standard of work?”
He then pointed out that an inspector, like himself, must often differentiate between what a company considers a GMP and what the regulatory agency believes is sound GMP, noting that WHO’s GMP guidelines are often more proscriptive than in industry.
Along with a good quality system, Thrussell identified leadership as a core area than an inspector looks at because “without that commitment those powers around there trying to erode your controls will continue at pace. If there’s not leadership at the top and belief at the bottom meeting then there’s going to be problems sooner or later.” In fact, ICH Q10 specifically mentions senior management’s responsibility to ensuring quality systems.
As with Rhoades’ presentation, Thrussell also keyed in on risk analysis, pointing out that risk is not a new concept; it’s mentioned 90 times within 20 different documents in EU GMP legislation and guidances.
“What’s perhaps new is the lifecycle approach,” he said. “But the concepts are not new.”
As to why inspectors look at a company’s quality management systems, Thrussell said that it’s quite simple.
“Looking at how companies react when things go wrong is a really, really good diagnostic tool.”
So, why are companies still having issues as far as quality since quality systems are standard across the industry?
“Well, clearly the management practices have failed,” said Thrussell. “Risk management has failed. Identification has failed.” Often these boil down to lapses in communication or even failures to leverage existing knowledge bases.
He then highlighted the features of a good quality system. These include: systemic monitoring of process performance and product quality using QRM, CAPA methodologies that result in improvements not just data, change management, and management review of processes, product performance, and quality. In essence, he said that quality should be the lifeblood of a company, so that even if it is not spoken of continuously, it is still present within the company’s culture.
On that last point, he referenced a colleague who told him that “the more times people talk about quality and inspection, the more I know it’s missing. So, if nothing else, when facing your inspectors try and use other words and do walk the walk and walk the talk and show that you are doing things.”
Ultimately, an inspector wants to leave a site with the confidence that when something does go wrong, the company has procedures in place to deal with the situation effectively.
Richard Friedman, Associate Director of Risk Science, Intelligence and Prioritization at CDER, U.S. and moderator of the session, opened the Q&A portion with a query of his own for Rhoades and Thrussell: “How do you know you have a good quality system,” he asked the two.
Thrussell responded that it helps to have something tangible to measure. “You can also measure the absence of things,” he added, although he cautioned that the absence of defects could also mean that they are under-represented and present. He then pointed out that other industries do proactive surveys as to the quality of their products yet this is not typical of pharma. He also recommended following CAPA processes.
“If they have too few deviations they don’t have a good quality system,” he said he often tells companies, particularly in India since he is skeptical that few things could wrong despite the high level of activity.
“Either they’re employing super-humans or robots” he said. “Or there is some underreporting.”
Rhoades added that he thinks one measure of effectiveness in the industry is how often bad events recur. He noted that some companies do after-action reviews when things do go wrong. Just recently, he worked with company that was forced to recall a significant batch of medications and analyzed what factors led to the recall and developed suggestions for preventing the situation from repeating itself.
Another audience member asked how a company can balance simplification while expectations for explicit information.
“Well, don’t confuse simplicity with not having clarity,” responded Rhoades. “We have a complex business to run, there’s no question about it.” He noted that overcoming complexity is a significant challenge for larger companies employing massive amounts of staff and managing multiple facilities across several locations. The industry can’t get away from the need from the need for clear specifications and processes. Yet, the goal of simplicity, Rhoades emphasized, is to get away from the minutiae that clouds thinking and understanding.
“Do you really need an 80-page SOP,” he asked. “Do you really need 80 pages—79 of which are written by somebody who is in another department? Do you really have clear understanding of how those intricacies and inter-relationships between departments and how they have to work?”
The effectiveness of training was also brought up during the Q&A. Rhoades admitted that training is “always a tough nut to crack.” Yet it is often a key point that his investigations must address, such as operator errors due to lack of adequate training.
“In terms of effectiveness,” he said. “There are a myriad of solutions out there in terms of the mechanisms to try and test. It’s a sore spot. I think a lot of companies struggle with the resources that are required to really have an effective training system at every level.”
On the point of training, Friedman indicated that a way to evaluate the effectiveness of training would be to measure compliance with SOPs. He told the audience that when he was doing inspections, he would often sit next to a manufacturing supervisor who was blatantly ignoring an SOP that he had just read.
Toward the close of the session, Thrussell discussed his involvement in shutting down the British facility involved in the infamous flu vaccine recall. He talked about how for the four years after the shut-down, inspections were conducted by both the FDA and the Medicines and Healthcare Products Regulatory Agency. The company ultimately implemented procedures to prevent a recurrence. This illustrates that even breakdowns in quality, no matter how disastrous, can provide a learning opportunity for an organization. In the end, bad quality has the potential to give birth to good quality.
“Sometimes,” Thrussell said. “Good things happen out of bad experiences.”
About the Experts
Bob Rhoades is Vice President, Quality & Compliance Consulting, at Quintiles. Bob has designed and implemented compliance improvement initiatives for major manufacturers in the United States, Europe, India and China. Bob has worked in concert with client counsel on a variety of legal cases and was selected to advise in the contaminated heparin crisis in 2008.
Ian Thrussell is currently one of the UK MHRA GMP Inspectorate Expert Inspectors and a member of the UK’s GMP Inspectorate’s Strategic Group which amongst its roles represents the Agency’s GMP interests at an EU and international level. Ian has a wide experience of international guidance development and implementation. He is rapporteur for the current amendments to Chapter 1 and 2 of the EU Guide.