Q. What types of records can FDA inspect during a GCP inspection?
A. You can expect that FDA will review all records that are associated with how the clinical trial was conducted. Always remember that, “if it isn’t documented, it didn’t happen” in the eyes of FDA. FDA will review the protocol, Informed consent forms, written procedures, IRB correspondence, Investigational medical product (IMP) dispensing and accountability, documentation that the IMP was shipped under labeled storage conditions, case report forms, training & qualification of personnel and raw data to verify adverse reactions, deaths, protocol deviations. This is by no means an all-inclusive listing. FDA’s authority does not extend to personal, sales and financial data.
Q. What does FDA consider to be raw data?
A. Raw data includes observations of the condition of the subjects, exposure to the IMP, concomitant medications administered and any indications of an adverse reaction. Raw data is the original documentation of an event that relates to the clinical trial. For Example, raw data for laboratory results would not be the recording of the results in the study records, instead it would be the report received from the laboratory. Raw data can be recorded directly into the case report form for some types of clinical data such as height, weight, blood pressure as long as that is the procedure for how this type of data is captured. There does not need to be a “source raw data” record created for this type of data and the practice of creating a “source raw data” record only allows for the possibility of transcription errors when entering it again into the case report form.
Q. What is the FDA’s objective when conducting a Sponsor/Monitor inspection?
A. FDA’s main goal is to protect the rights, safety and welfare of the subjects enrolled in FDA regulated clinical trials. The next objective is to verify that the clinical trial completely and accurately captured all of the clinical trial data that will be used to support a research or marketing application. In addition, many times the FDA investigator is provided with tables and listings from the FDA center that is reviewing the clinical trial report prior to the inspection. The FDA investigator will then perform a comparison of the tables and listings supplied by the center, to the raw data in the sponsor’s clinical trial master file to assure that the clinical trial report is complete and accurate.
Q. How does FDA expect sponsors to handle protocol deviations and non-compliance issues at clinical sites?
A. FDA will ensure that the sponsor has a process of identifying and dealing with protocol deviations in real time during the conduct of a clinical trial. The inspection will review monitoring procedures and the amount and type of clinical data that is reviewed during monitoring visits. Most importantly, FDA will assess the sponsor’s procedures for dealing with non-compliant sites and what escalation process is in place to assure that non-compliant site are not allowed to continue the study. FDA will also assess if the sponsor has an effective process for capturing protocol deviations for inclusion and evaluation in the clinical trial report.
Q. Is the FDA focusing on computerized systems more during Sponsor/Monitor inspections?
A. Yes, since March of 2011, FDA’s Bioresearch Monitoring Program has been focusing more on a sponsor’s computerized system since the industry best practice has been to use electronic case report forms (eCRF) to capture data generated during clinical trials. The FDA will assess the sponsor’s system for development of the eCRF, training on eCRF and how sponsors handle changes to the eCRF. In addition, the FDA will look at the interface between the eCRF and the database. Another area of focus is the qualification and contracting out of statistical analysis of the data. In general, future FDA sponsor/monitor inspections will review the qualifications of the personnel who are involved in the computer operations group that supports clinical trials, just as they have reviewed the qualifications of the clinical personnel previously.
Q. What documents from the many available on the FDA web site are most helpful in understanding and preparing for FDA GCP inspections?
A: Compliance Programs. These documents all have standardized numbers, just like company SOPs. If you put the number into the search box on the FDA web page, www.fda.gov you will receive a list that will include the Compliance Programs you need. Key ones to retrieve are Compliance Programs 7348.810 (Sponsors, Monitors and CROs) and 7348.811 (Clinical Investigators). Pay special attention to Part III titled, Inspectional and Part V titled, Regulatory in these documents to learn what to expect during an FDA GCP inspection.
For more information visit contact Tony Warchut at +1 860 432 4727 or Tony.Warchut@parexel.com