At a recent conclave of the pharmaceutical industry, a top representative with the US Food and Drug Administration red-flagged data integrity concerns — this time, with contract research organisations (CROs).
Calling out a concerning trend with bio-availability and bio-equivalence (BA/BE) studies, Dr Patrizia Cavazzoni, Director of the Center for Drug Evaluation and Research (USFDA), said: “Since 2016, we have seen multiple data integrity issues when it comes to BA/BE studies... We have had public communications on Panexcell, Semler, Synchron, and hot off the press last week, took another action on Synapse Labs, where we uncovered more potentially broader problems.”
Looking across these cases, she said, there was good reason to believe there was submission of falsified data and widespread poor quality management procedures, among other things.
“FDA mandates quality data that is accurate, consistent and reliable,” she said, adding that “manufacturers are ultimately responsible for the conduct and quality of the work that CROs do on their behalf and so we really need manufacturers to pay attention.” Dr Cavazzoni’s remarks were part of a recorded message at the Quality Summit organised by the Indian Pharmaceutical Alliance.
While CROs are not in the limelight as much as the pharmaceutical industry, they are in a sense, its backbone. They undertake studies and clinical trials for companies on drugs or medical products. And it’s on the merit of these trials that regulatory authorities in different countries evaluate a product and green-light it — if the data establishes the product to be safe and efficacious for human/animal consumption, as the case may be.
And for that reason, the pharmaceutical companies and CROs they work with are paying heed to this alarm bell sounded by the regulatory authority.
Dr Sanish Davis, President, Indian Society for Clinical Research, says, India is at an inflection point, of being an enterprise supplier, and there is an effort across the wider ecosystem — of companies and the Indian regulator — to bring in a “quality-by-design mindset”. There could be “rogue elements”, he says and calling them out serves as a good lesson. But it is not the tip-of-the-iceberg, he says, refuting concerns on whether this was a widespread problem.
India has a unique position, he says, housing the largest number of USFDA-approved manufacturing plants outside the US. (These plants make products to supply this region, who in turn rely on CROs for their trial data for the approval process.)
Don’t commit ‘hara-kiri’
Quality and data integrity are critical for CROs, says Dr Kiran Marthak, Non-executive Director, Veeda Clinical Research. It is in the interest of both the CRO and the sponsor company undertaking the trials, he adds. “If someone wants to commit hara-kiri (self-destruct), that’s their choice,” says the industry veteran about those in it for a “fast-buck”. He observed that the reputational damage is huge for those who run foul of regulatory authorities, and often there is no coming back from a situation where transgressions are repeatedly pointed out.
Such incidents have been reported of global and Indian CROs, but an upcoming industry cannot afford to have companies hauled up by regulators as it brings in distrust, Marthak noted. That makes it difficult for other CROs who deal with sponsor companies, who then seek several levels of protection for themselves, adds another industry-hand.
Marthak estimates that about half the total 80-odd CROs in the country do BA/BE studies. And these studies are about half the cost in India, compared to other regions, he adds.
Not just bottomline
Outlining the impact of questionable data for pharmaceutical products in the US, Dr Cavazzoni said, they could lose their “automatic substitution designation”, purchasers could move away and this increased the risk of shortages. Manufacturers would have to redo the study, costing time, money, loss of market share, revenue and productivity, she said.
Recognising the important role of Indian drugmakers supplying to the US, she said, “We understand that there is a cost to quality, we understand there is cost in conducting BA/ BE studies, however, there is also a significant cost and a major impact in just looking at the bottomline and going to the lowest bidder of CROs,”.
But the critical message to take away was — such incidents “undermine the reputation of the generic industry” and lower confidence of patients, buyers and the public. Something patients and industry call ill afford.