Good Clinical Practice: A Question and Answer Guide2024/2025 Edition - 9

GCP Regulations, Standards, and Guidelines for Clinical Research
* Inadequate and/or inaccurate case history records; inadequate study records
* Inadequate accountability and/or control of the investigational product
* Safety reporting; failure to report and/or record adverse events
* Inadequate subject protection; informed consent issues
The top Sponsor/CRO Inspectional observations are as follows:
* Failure to ensure proper monitoring of the study and ensure the study is conducted in accordance with the
protocol and/or investigational plan
* Failure to meet the abbreviated requirements for investigational device exemptions (IDEs)
* Failure to maintain and/or retain adequate records in accordance with 21CFR312.57; accountability for the
investigational product; Investigator Statement (Form FDA 1572); Financial disclosures
* Failure to submit an FDA Investigational New Drug (IND) application; FDA IND safety report
* Failure to submit current list of all participating investigators to FDA at six-month intervals after FDA
approval of the study
B. In terms of the European Medicines Agency (EMA Inspections); inspectors want to understand and follow
the process that was utilized for the clinical study. They will inspect the documentation trail supporting the
organization's compliance with the organization's documented and approved processes. They want to be
trained on all eSystems (e.g., eTMF, CAPA System, etc.) so they may review these electronic repositories of
data on their own. They typically begin with a few clinical sites and then follow the threads to contracted
service providers and the Sponsor's location to complete the triangulation of the data lifecycle, including
how these data were maintained intact and with high degree of integrity.
C. The experience level of Regulatory Agency or Member State Inspectors/Investigators has increased, and
we are seeing more experienced inspectors reviewing GCP compliance, use ICH guidelines and check to see
if the Sponsors have followed all approved plans.
1.8
Q. Describe the typical challenges surrounding source documentation during a regulatory inspection?
A. Findings surrounding source documentation are very common during inspections - the ICH E6 (R2) addendum
changes related to source documents have addressed these findings by requiring sites to use 'certified' copies (ICH
E6 (R2) Section 1.63); copies of original records are verified by a dated signature or generated validated process to
have same information, including data that describe the context, content, and structure of the original. ALCOA++
requires source data to be Attributable, Legible, Contemporaneous, Accurate, Original and Complete.
* ICH E6 (R2) section 4.9.0 has driven good documentation practices by formalizing these requirements and
adding 'Complete' (ALCOA+) to source documents and trial records. To meet these requirements and to
ensure source documents and trial records are compliant, the following should be considered:
* Document who made the entry; e.g., signature or identifiable initials
* Include the date the entry was made; e.g., actual date the documentation occurred
* Ensure that the entry is legible and understandable; e.g., clearly written and that it is understandable by
a person unfamiliar with the organization's site or company acronyms
* Maintain the original recorded information location; e.g., not photocopied or transcribed from another
document
* Include a clear description of what exactly occurred and when, including all pertinent details to 'tell the
story' of what happened and when
* If changes are made to documents and trial records, there must be an audit trail showing what and when
changes were made
* Site to record location of documents - This is another area that has shown up during inspections and/or
audits; location of essential study documentation and source documents should be clearly documented.
* Sponsor Oversight of Vendors - The Sponsor should ensure appropriate oversight of trial-related
services, duties and functions performed and subcontracted services performed on behalf of the Sponsor
and documented.
* Quality Management - As one of the largest areas of proposed change; this section may include Critical
Process and Data Identification, Risk Identification, Risk Evaluation, Risk Control, Risk Communication,
Risk Review and Reporting.
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Good Clinical Practice: A Question and Answer Guide2024/2025 Edition

Table of Contents for the Digital Edition of Good Clinical Practice: A Question and Answer Guide2024/2025 Edition
