Section 3.11 on Quality Assurance and Quality Control, which includes monitoring activities, adds a few more references to risk, helping raise the number of appearances of this word from 74 in the May 2023 draft to a whopping 89 in the January 2025 final. Bonus - we have a fun new drinking game to play at SQA this year.
- Step 3.11.1 on Quality Assurance now includes the bolded text: "Quality assurance should be applied throughout the clinical trial and includes implementing risk-based strategies to identify potential or actual causes of serious noncompliance...." Drink!
- Step 3.12.1 on Audits modifies the statement, "The purpose of a sponsor's audit, which is independent of and separate from routine monitoring or quality control functions, is to evaluate whether the processes put in place to manage and conduct the trial are effective and compliant" by replacing the italicized text with "appropriate to ensure compliance wiht the protocol, GCP and the applicable regulatory requirements." Still no Oxford comma, but this is an important change. Clinical trial participants often perceive audits as guarantees of compliance - in other words, the number of findings in an audit is an indicator of how compliant or non-compliant the study is. This rewording emphasizes the fact that the purpose of the audit is to give feedback on the adequacy of the processes to detect and respond to non-compliance. If an auditor identifies a weak process, that's less than ideal even if no instances of non-compliance were identified.
- Step 3.11.2.2 (d) on the practice of regulatory authorities' requesting audit reports now states that regulatory authorities may request audit reports when the "evidence or suspicion" of serious GCP noncompliance exists." Previously, this statement restricted these requests to cases where there was "evidence" of serious GCP noncompliance.
- Step 3.11.3 on Quality Control adds a reference to risk, as follows: "Quality control should be applied using a risk-based approach to each stage of the data handling to ensure that data are reliable and have been processed correctly." Drink!
- Step 3.11.4.5.2 (d) on Investigator Site Selection, Initiation, Management and Close-out corrects the statement that site monitoring should confirm that informed consent was obtained before participation in the trial for "all enrolled participants" to "trial participants," so there is no confusion about the fact that informed consent must be verified for both screened and enrolled participants.
- Step 3.11.4.5.3 (a) (i) regarding IMP management notes that site monitors will verify that storage considitions are acceptable per requirements in the "protocol or other relevant documents," in recognition of the role the pharmacy manual or package insert may play in defining storage conditions.
- Step 3.11.4.5.3 (a) (v) regarding monitoring of IMP now specifies that site monitors will verify "that the receipt, storage, use, handling, return and destruction or alternative disposition of the investigational product(s) are controlled and documented adequately." The bolded words have been added, addressing a gap in this statement (still no Oxford comma after "return," though).
- Step 3.11.4.5.4 (b) on monitoring of clinical trial data now includes the bolded text: "The sample size and the types of data or records may need adjustment based on previous monitoring results or other indications of insufficient data quality."
