Preparing for Regulatory Inspection
As stated by Valania, M. (2006), quality of trial processes and generated data, as well as compliance with all applicable international and local regulations, should be always regarded as a continuous process. So, it is true that all participants of a clinical trial process must expect and be always prepared for any kind of inspections and/or audits, notwithstanding presence or absence of the foreseen triggers (high/low enrollment and dropout rates, unusual AE/SAE number, study risk profile, etc.).
In fact, the best strategy for CRAs to prepare themselves and their sites for any type of inspections/audits is to strictly and constantly adhere to CRO’s (Company’s) SOPs and all applicable regulatory guidelines. If you want something to be fulfilled, you must control and measure it (Franck, L.S. et al., 2004, p.244). If it is not being done underway, there is no sense to do major preparations within a week or two before an audit – it will be evident for an experienced auditor/inspector after all.
So, whether the study process was appropriately monitored or not, a CRO/Pharmaceutical company and a concerned site have certain time to review their operations. The scope of preparations depends, of course, on the areas that are usually checked during the inspections (and audits) and on the specific SOPs of the Sponsor/CRO. In the case of the regulatory inspection the following aspects will be reviewed and verified, as specified by:
(Holford, S., 2003)
- Site’s procedures and study conduct and whether these correspond to what was stated in the clinical trial application
- Whether submitted data reflect actually occurred events
- Whether study has been conducted according to GCP and other regulatory requirements
(Kurdziel, T.J., 2008)
- Sponsor’s/CRO’s/Site’s SOPs.
- Local guidelines.
- Adherence to the study protocol.
- Results of previous inspections if any.
Of course, specific actions will vary from one Company’s SOPs to another, but the common actions of a CRA and subsequent research team’s activities would be:
– Prompt notification of the project team and the Sponsor about the upcoming inspection details and timelines,
– Review of all site-specific monitoring visits reports for any systematic findings, incompliance, actions that require follow-up, etc.,
– Scheduling and conduct of an internal audit by the Sponsor’s/CRO’s auditor together with the CRA (as an alternative, this may be a co-monitoring visit with the study team leader),
– Review of the study Trial Master File for any missing essential documents from the site and creation of a check list for follow-up during the audit/co-monitoring,
- At the time of on-site preparation (UK Medical Research Council Clinical Trials Toolkit, 2006):
– Check of study logs (especially drug accountability, delegation of responsibilities, screening/enrollment),
– Staff’s qualification and training documents availability,
– Discussion and check of protocol-specific procedures and roles with the staff,
– Review of site facilities (especially places where patients are seen, drug and study documents are stored, procedures are performed),
– Review of EDC systems specifications,
– Availability of all patients’ charts, CRFs and ICFs.
Generally, it is better to ensure that site staff has all documents ready and in place and will be present during the inspection. I would also instruct them not to devise anything and tell the truth. Even if something is missing it is better to document the list of pending/missing documents then to re-write lost logs /charts (whatever) over the period of time before the inspection.
- Franck, L.S. et al. (2004) ‘Quality assurance for clinical research: challenges in implementing research governance in UK hospitals’, International Journal of Health Care Quality Assurance, 17(5), pp. 239-248.
- Holford, S. (2003) ‘Keeping an eye on the incubators’, PharmaFocus, July [Online]. Available from: http://www.inpharm.com/news/keeping-eye-incubators.
- Kurdziel, T.J. (2008) Regulatory Authority Inspections – Lessons Learned, New Zealand Clinical Research Conference, August, Auckland, New Zealand.
- UK Medical Research Council Clinical Trials Toolkit (2006) How to prepare for an inspection for Good Clinical Practice by the Medicines and Healthcare products Regulatory Agency (MHRA): a guide for NHS organisations that sponsor or host clinical trials of medicinal products .
- Valania, M. (2006) ‘Quality Control and Assurance in Clinical Research – A system of checks and examinations that helps ensure the quality of clinical trials’, Applied Clinical Trials.
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