GCP Inspection Findings
A total of 49 common GCP inspections were conducted by EMA and FDA in support of 31 shared marketing applications from 2009 through 2015. Twenty-six of the common GCP inspections were for inspections of clinical investigators and 23 were for sponsors/contract research organizations. For the 26 clinical investigator inspections, a total of 170 and 320 findings were included in the final dataset for FDA and EMA, respectively (Fig. 1a). For the 23 sponsor/contract research organization inspections, a total of 165 and 300 findings were included in the final dataset for FDA and EMA, respectively (Fig. 1b). An analysis of the difference in the number of inspection findings between the two agencies is beyond the scope of this study.
For the clinical investigator inspections, for FDA, the most inspection findings were in the deficiency areas of Protocol Compliance (43%) and Documentation (28%); while for EMA, the most common findings were in the deficiency areas of Documentation (46%) and Protocol Compliance (34%) (Fig. 2a).
For sponsor/contract research organization inspections, for FDA, the most inspection findings were in the deficiency areas of Trial Management (45%) and Documentation (33%); while for EMA, the most common findings were in the deficiency areas of Documentation (45%) and Trial Management (40%) (Fig. 2b).
Concordance for Clinical Investigator Inspections
The concordance rates between the two agencies by site and deficiency area were calculated for each of the inspected sites (Fig. 3). Out of the 26 common clinical investigators inspected, 25 clinical investigator inspections had findings under the deficiency areas of Protocol Compliance and Documentation. Both agencies identified deficiencies related to Protocol Compliance at 22 of the 25 clinical investigator sites, a concordance rate of 88%. For the three non-concordant sites (one had findings by FDA and two had findings by EMA), 13 findings were identified, examples of which included FDA’s finding that a concomitant medication for one subject was not reported to the sponsor and EMA’s finding that an enrolled subject did not meet study eligibility criteria.
For Documentation deficiency area, both agencies identified findings at 17 of the 25 clinical investigator sites, making for concordance rate of 68%. All eight non-concordant sites had Documentation findings by EMA. The differing findings were mainly due to the following reasons: (1) FDA generally does not include sponsor responsibility related findings in its clinical investigator inspection reports  and (2) some findings reported by EMA were related to ICH-E6(R1) GCP requirements,  for which the FDA does not have parallel requirements under 21 Code of Federal Regulations. (1) (Table 3) Examples include delayed placement of qualification or training documentation in trial master file, and lack of adequate version control for essential documents .
For Human Subject Protection, 19 of the 26 sites had findings, with both agencies identifying findings at 11 of the 19 sites (concordance rate of 58%). Five of 8 non-concordant sites had findings by FDA and three had findings by EMA. One example of FDA’s findings was related to inadequate informed consent processes for two subjects . An example of EMA’s findings at the three remaining non-concordant sites was sending a protocol amendment late to the Independent Ethics Committee .
Twenty-three  sites had Study Drug findings, with both agencies identifying findings at 10 of the 23 sites (concordance rate of 43%). Nine of 13 non-concordant sites had findings by EMA. An example of EMA findings included inadequate documentation of study drug shipment and late acknowledgement of receipt of study drug . An example of FDA’s findings at the remaining 4 non-concordant sites included inadequate documentation of the amount of the study drug taken by one subject (see Table 3).
Concordance for Sponsor/Contract Research Organization Inspections
The concordance rates between the two agencies by deficiency area for the common sponsor/contract research organization are provided in Fig. 3b.
Out of the 23 common sponsor/contract research organizations inspected, 19 had findings related to Trial Management. Both agencies identified deficiencies related to Trial Management at 17 of these 19 (concordance rate of 89%). The two non-concordant sites had Trial Management findings reported by EMA. These differing findings were mostly due to EMA requirements linked to ICH-E6 with regard to timeliness of maintenance of essential documents and a delay in establishing the monitoring plan  (Table 3).
For the Documentation deficiency area, all 23 inspections had findings. Both agencies identified findings at 16 of the 23 sites (concordance rate of 70%). The seven non-concordant sites had findings by EMA. Example findings include deficiencies in completeness of documentation in trial master file, and lack of updating standard operating procedures in a timely manner.
For Protocol Compliance, of 17 sites with findings, 11 were identified by both agencies (concordance rate of 65%). Five of 6 non-concordant sites had findings by EMA, and one had findings by FDA. Examples of EMA findings included an inadequate process to collect and review protocol deviations. FDA’s finding at the remaining non-concordant site was that radiographs were taken out of the scheduled visit windows.
Eleven sites had findings related to Study Drug, and both agencies identified findings at 6 of these 11 sites (concordance rate of 55%). Four of 5 non-concordant sites had findings by EMA, and one had findings by FDA. An example of EMA findings included inadequate management and oversight of study drug shipment to clinical investigator sites. FDA’s finding at the remaining non-concordant site was that study drugs were diluted before administration.