Clinical Data Interchange Standards Consortium (CDISC)
August 22, 2024
No Comments
In the regulatory framework, following standard operating procedures (SOPs) can serve two chief purposes, i.e., compliance with regulatory guidelines and generating quality outputs from a big-budgeted clinical trial. However, negligence in following these SOPs can lead to fallbacks during FDA inspections. It has been observed from a cross-sectional analysis that the FDA inspections found significant evidence for problems with adverse events reporting, failure to follow the investigational plan, inadequate or inaccurate recordkeeping, failure to protect the safety, rights, and welfare of patients, or issues with informed consent.1 All these problems could have been avoided if the SOPs were followed.
A well-experienced Project Manager of a clinical trial will know the value of following SOPs in the regulatory framework. Therefore, we present all the critical information related to SOPs in this blog that you can implement during clinical trial conduct.
Standard operating procedures are utilized at every stage before, during, and after clinical trial conduct. The primary importance of SOPs in the regulatory framework is that SOPs provide a mode of compliance with various regulatory guidelines. Some of the below given regulatory guidelines clearly state the use of standards in clinical activities:
One of the GLP principles states that “the test facility should ensure that appropriate and technically valid SOPs are established and followed, and approve all original and revised SOPs.”2 Therefore, as the nonclinical laboratory studies are executed to support research as well as marketing approval of products from the FDA, these studies have to be conducted in compliance with GLP (as per 21 CFR Part 58),3 these should be executed based on valid SOPs.
One of the GLP principles states that “the test facility should ensure that appropriate and technically valid SOPs are established and followed, and approve all original and revised SOPs.”2 Therefore, as the nonclinical laboratory studies are executed to support research as well as marketing approval of products from the FDA, these studies have to be conducted in compliance with GLP (as per 21 CFR Part 58),3 these should be executed based on valid SOPs.
One of the GCP principles states that “systems with procedures that assure the quality of every aspect of the trial should be implemented.” According to the ICH E6(R1) guideline (which is based on GCP principles):6
Some parts of Title 21 of the CFR describe the requirements of SOPs in regulatory processes. These include:
Besides the primary importance, SOPs help to provide consistent workflow at the clinical trial site. As every staff member follows the standard process defined in the SOP, a consistent workflow is certain. It also helps to generate consistent data from different studies conducted under the same sponsor’s roof.
As per the ICH E6(R1) guideline, “The SOPs should cover system setup, installation, and use. The SOPs should describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. The responsibilities of the sponsor, investigator, and other parties with respect to the use of these computerized systems should be clear, and the users should be provided with training in their use.”6
Considering the above guideline, an SOP should have detailed information about who will execute a specific process, how this process will be executed, and when this process will be executed for each clinical trial activity.
The U.S. Environmental Protection Agency (EPA) provided a very clear guidance document for preparing SOPs.7 Concisely written, step-by-step, and easy-to-read SOPs are more understandable by users. The information presented should not be overly complicated.
Implementation of SOPs in clinical study activities is a crucial step. The errors found during the FDA inspections are mostly due to non-compliance with SOPs. Therefore, a strong system that keeps an eye on the implementation of SOPs is a necessity. Below are steps that can be followed to implement SOPs:
To keep the SOPs updated, a review process is required. It is a systematic way of evaluating and revising SOPs on a regular basis. It involves checking SOPs for accuracy, clarity, completeness, and alignment with the latest regulatory processes.
For doing so, review criteria need to be defined first. This criteria can include steps that will be used to assess the relevance, accuracy, clarity, completeness, and compliance of SOPs with regulatory processes. During the review of SOPs, self-review, peer-review, or audits can be planned.
This review process is documented (date of review, reviewer, steps involved, feedback, and actions taken) along with the documentation involving updates in the SOP after review (updating SOP date,number, and version, updating reviewed procedure, and updating signature for approval of changes). The updated SOP comes into action and is archived simultaneously according to the sponsor’s retention and disposal policies.
Standard operating procedures are valuable documents in the regulatory framework. Conducting each process that is related to the approval of drugs for human use in compliance with SOPs can generate quality data. This data can ultimately help the regulatory authorities make fair decisions for the approval of drugs. Therefore, the preparation, implementation, management, review, and updating SOPs should be given more significance than ever.
Supporting Healthcare and Pharmaceutical Industries Across Internal, External, and Regulatory Communications. Delivering Top-Tier Support for Our Client’s Success.
Supporting Healthcare and Pharmaceutical Industries Across Internal, External, and Regulatory Communications. Delivering Top-Tier Support for Our Client’s Success.