Drug plant staff who remain silent, give inappropriate responses or straight-up lie during a facility audit make inspectors suspicious, former US Food and Drug Administrator (FDA) national expert investigator Rebecca Rodriguez told delegates at AAPS in Denver, Colorado last month.
“[Operators] don’t have to spill the beans and reveal everything that’s bad about a company, but they have to be truthful and provide complete answers, otherwise this raises suspicions. Before you know, you can end up with the inspector going into the mode of questioning everything, and that can be very unpleasant and full on… Investigators can smell fear!”
Her comments were met with interest by delegates, many of whom worked for drug and API makers and had been taught to “never open their mouths” during an inspection.
We reached out to another expert, Anders Fuglsang - an advisor to regulatory agencies and private companies, and a consultant and inspector for the World Health Organisation (WHO). In this article he speaks on behalf of himself only.
“It is not uncommon that I ask questions that auditees or inspectees cannot answer,” he told in-pharmatechnologist.com. “That is perfectly fine, they are experts of their own systems and often I ask questions that I realise may not make sense to them, simply because I am too unfamiliar with their systems.”
But problems arise when questions go unanswered because the auditee or inspectee doesn't wish to enter a dialogue about a specific topic.
“This sort of behaviour is very obvious and immediately starts alarm bells to ring. Instead, full transparency from operators – even if it discloses problems the inspector has yet encountered – leads to more successful audits and better conversation between the facility and regulator.”
Fuglsang conceded a drug making facility is unlikely ever to have a perfect audit as mistakes, omissions and oversights are normal and common.
But, he explained, “experienced inspectors and auditors can tell or will look into whether or not observed gaps are general and/or occur systematically. This is where observations easily get raised from minor to major or even critical.”
Who’s to blame?
Both experts said the problem lies not with the operators themselves but with poor management. Rodriguez even went as far as describing an operator’s nerves being wrought by “an army of managers that are there making faces at them telling them: ‘don’t say this, don’t say that.’”
And management is often quick to blame single employees when major or critical findings are identified, Fuglsang added.
“But I can't think of any situation where I was of the impression that the employee herself/himself was a root cause. Serious gaps typically trace back to management who are not giving the necessary support - time, funding, training, equipment, environment - to their employees.”
But other problems may stem from managers “feeling above the rules and occasionally divine” or even giving deliberate orders to operators to breach certain principles to save time and money, Fuglsang said.
“It has occurred a few times that an employee is very willing to talk about topic A, B and C, but when I ask about topic D he/she suddenly has lost memory or the ability to speak English altogether. That certainly set off the alarm bells.”
In another example, Fuglsang said he had heard of a company which introduced obvious gaps in select parts of their study report and quality management system (QMS) in order to steer the inspector's focus away from what would have been a critical finding.
But some companies are aware of management issues on the facility floor and have acted to try and ensure transparency. Fresenius Kabi, for example, sacked managers and staff involved in attempting to misguide inspectors and manipulate data at an API facility in Kalyani, India in 2013.
Meanwhile, during a visit to South Korea our sister publication Biopharma-Reporter was told by biologics maker Celltrion it only employs operational staff with a proficient level of English in order for them to freely converse with English-speaking regulatory inspectors. The firm’s manufacturing site in Songdo has up to 20 inspections per year and has never had any regulatory issues.
Policing the police?
But the problem doesn’t just lie with industry, as dialogue can be hampered by auditors and inspectors too, Fuglsang said.
“If they feel their job is to police people around, dictate solutions to perceived issues, or if they are showing aggression, impatience etc. in their attitude to auditees/inspectees then that will surely and effectively kill the dialogue.
“I have witnessed this a few times, too, regrettably. I once discontinued my participation in an audit for this very reason; I felt the lead auditor was aggressive, did not leave any chance for employees to discuss and explain observations, and he basically listened only to himself and had pre-conceived opinions.”