In our latest post in this series, we looked at the increase in FDA BIMO inspections of sponsors in 2018/2019, and their corresponding decrease in 2020. In this post, we turn our attention to CRO inspections. Note that many CROs, especially ex-US CROs, have a wide range of capabilities that include pre-clinical and bioanalytical laboratories and clinical study management, and FDA inspection data does not provide clues as to which capability is being inspected, unless the inspection results in Voluntary Action Indicated/Official Action Indicated AND the data are included in the citations dataset. Thus, CRO inspections reflected here may include inspections of laboratory services.
With that caveat, as we look at CRO inspections compared with sponsor inspections over the same time period, we see a similar trend, although a more precipitous drop for CROs. While sponsor inspections dropped approximately 40% from FY2019 to FY202o and then held relatively steady for 2021, CRO inspections dropped over 50% from FY2019 to FY2020, with another >50% drop in 2021.
CRO inspections during this time period resulted in even fewer “Official Action Indicated” classifications – none at all until 2020 – although a staggering 3 out of 25 CRO inspections in 2020 were classified as such.
All three CROs were located outside of the US: Panexcell Clinical Laboratory and Synchron Research Services in India, and Biotrial Sas in France. All inspections took place at the end of 2019 (early in FY2020). For the Panexcell and Synchron inspections, FDA took the unusual step of alerting sponsors that bioavailability and bioequivalence studies contracted to these organizations were “unacceptable” due to data integrity concerns. No citation information was provided for the Biotrial inspection, but Biotrial has been on FDA’s radar since 2016 when one subject in a Phase 1 study died and four were injured.
Next, we were curious about what kinds of CROs get inspected. CROs could be selected for inspection based on any number of factors, but we would expect the primary driver to be conduct of registrational studies. Since bigger CROs conduct more studies overall than smaller CROs, we would expect them to be well-represented. Indeed, the large CROs, those with over 10k employees, represented over half of the inspections in the past five years. (Note that some CROs have merged in that time frame – for example, ICON and PPD, and Syneos and INC. For ease of data collection, all inspections for merged entities have been grouped under a single CRO.)
But “micro” CROs – those with fewer than 100 employees, according to publicly-available data – made up 18% of the inspections in the past five years.
That number is highly colored by five inspections at Synchron. Other small CROs inspected more than once over the past five years include Hill Top, WCCT, QPS, and Synteract, all of which had two inspections. By contrast, the big CROs with the highest number of inspections – Covance/Labcorp, IQVIA, and PPD – had eight inspections each, or four times the number of inspections of these CROs only a fraction of their size.
It would be unwise to draw broad conclusions from such limited data, but when working with CROs, it’s always helpful to understand how frequently – or relatively infrequently – the CRO has been inspected, considering its size. So when a behemoth CRO tells you, “We do this all the time, and we’ve never had an inspection finding,” their denominator may be as high as 4,000 clinical studies, but the numerator – number of inspections – may be as low as 8 over the past five years.