The new article outlines certain specific aspects related to the existing legal framework, such as packaging, shipping, safety monitoring, as well as the use of electronic systems.
Table of content
The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to conducting clinical trials with decentralized elements. The document provides an overview of the applicable regulatory requirements, as well as additional clarifications and recommendations to be taken into consideration by the parties responsible for clinical investigations (study sponsors) in order to ensure the accuracy and reliability of the results, as well as the safety of study participants.
At the same time, provisions of the guidance are non-binding in their legal nature, nor are they intended to introduce new rules or impose new obligations. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the relevant legislation and has been agreed with the authority in advance.
Packaging and Shipping of Investigational Products
In accordance with the applicable regulatory requirements, in decentralized clinical trials (DCTs), investigational products (IPs) may be directly distributed to trial participants or local healthcare providers (HCPs) rather than being administered exclusively at traditional trial sites. This flexibility requires careful planning and documentation to ensure product safety, integrity, and compliance with regulations.
The FDA further outlines specific responsibilities and considerations for both sponsors and investigators involved in handling, packaging, and shipping IPs in DCTs.
Investigators remain accountable for overseeing the distribution of IPs, whether they are shipped to participants’ homes or local HCPs.
Key responsibilities include:
- Authorization of IP Release: The investigator must authorize the release of IPs by the distributor and ensure that the IP is received by the intended recipient (participant or local HCP) according to established procedures.
- Documentation and Tracking: Investigators must document all aspects of IP handling, including the release, receipt, and any return or disposal of unused products, as directed by the sponsor. This process should be conducted according to the investigational plan or other trial-related documents.
- Training for Trial Personnel: All personnel involved in packaging, shipping, and handling IPs should be trained on proper procedures, documentation requirements, and maintaining the physical integrity and stability of the IP during transportation.
Sponsors should ensure that trial-related documents include detailed plans for maintaining IP integrity during shipment.
Key considerations include:
- Packaging and Stability: The IP’s packaging must preserve its stability, with appropriate materials and methods (e.g., temperature control) to prevent degradation during transport. Clear instructions for handling and storage should be provided to recipients.
- Tracking and Documentation: Sponsors should establish processes for tracking and documenting the receipt and return of IPs, whether distributed to participants or local HCPs. These processes should include procedures for the secure disposal of unused IPs.
- Participant Instructions: When IPs are shipped directly to participants, they should receive clear instructions on how to properly use, store, and return the product.
In such a way, by ensuring the integrity and proper documentation of IP distribution, sponsors and investigators can maintain compliance with FDA requirements and protect the safety of trial participants.
Safety Monitoring in DCTs
As further explained by the FDA, safety monitoring constitutes a critical component of any clinical trial, and it becomes even more complex in a DCT setting due to the decentralized nature of trial activities. The FDA outlines specific recommendations for implementing a robust safety monitoring plan that accounts for remote and decentralized elements.
Investigational Products in a DCT
The administration and management of investigational products (IPs) in DCTs depend on the nature of the product, its safety profile, and the required level of supervision. The FDA provides guidance for both drugs and biological products, as well as medical devices, to ensure that trial participants are appropriately monitored and that safety concerns are adequately addressed.
Developing a Safety Monitoring Plan
The safety monitoring plan should be tailored to the specific decentralized aspects of the trial and must include procedures for capturing, reporting, and managing adverse events.
According to the guidance, key elements of the plan include:
– Adverse Event Reporting by Local HCPs: Local HCPs involved in trial-related activities may become aware of adverse events during routine assessments. The safety monitoring plan should include clear instructions for these HCPs on how to report such findings.
- Participant Instructions for Reporting Adverse Events: Participants should be given comprehensive instructions on how to report adverse events, including whom to contact and where to seek local medical assistance if needed. The plan should also provide guidance for accessing follow-up care in case of emergency.
- Use of Digital Health Technologies (DHTs): If DHTs are used for remote data collection (e.g., wearable devices or monitoring apps), the plan should specify what types of data will be collected, how these data will be monitored, and what actions participants or personnel should take in response to abnormal readings or alerts.
Managing Safety Risks
If significant safety risks emerge (e.g., due to remote administration of an IP), the sponsor must take immediate action to mitigate these risks, including potentially discontinuing the trial or modifying trial procedures. All relevant parties, including the FDA, the Institutional Review Board (IRB), and investigators, should be notified promptly.
Routine Safety Monitoring by Local Facilities
Routine safety monitoring activities, such as laboratory tests or imaging, may be conducted at local clinical facilities close to the participant’s location. Investigators should ensure that results from these local facilities are promptly reviewed and incorporated into the overall safety assessment.
Electronic Systems Used in DCTs
As it is mentioned in the guidance, Electronic systems are vitally important to the successful implementation of DCTs, providing a centralized platform for managing trial data, coordinating activities, and ensuring compliance with FDA regulations. In particular, the FDA outlines the roles and functionalities of electronic systems in DCTs, emphasizing the importance of data integrity, security, and privacy.
According to the document, electronic systems in DCTs may serve multiple purposes, such as:
- Electronic Informed Consent Management: Maintaining approved versions of informed consent forms, documenting IRB approvals, and archiving signed consent forms.
- Data Collection and Reporting: Capturing and storing reports from remote trial personnel, local HCPs, and clinical laboratory facilities. These systems also support the management of electronic case report forms (eCRFs) and syncing data from DHTs.
- IP Tracking: Monitoring the distribution and receipt of IPs shipped directly to trial participants.
- Scheduling and Communication: Coordinating trial visits and activities, and facilitating communication between trial personnel and participants.
Training and Data Management
All personnel using these systems, including local HCPs and trial participants, should receive adequate training to ensure proper use and data entry. Sponsors must implement procedures to validate the data entered into electronic systems and ensure compliance with 21 CFR part 11, which governs the use of electronic records and electronic signatures.
Data Security and Privacy
The FDA requires that electronic systems used to generate or process trial records meet stringent criteria for data security, privacy, and confidentiality. Systems must be designed to prevent unauthorized access and ensure the reliability and integrity of trial data.
Real-Time Video and Audio Interactions
The FDA distinguishes real-time video and audio interactions, such as telehealth consultations, from traditional electronic records. Although these interactions are not subject to 21 CFR part 11, documentation of the visit, such as written notes or summaries, must be handled according to electronic record-keeping standards.
Conclusion
In summary, the present guidance document issued by the FDA outlines the aspects related to packaging, shipping, safety monitoring, and electronic systems in DCTs, and also highlights the need for meticulous planning, rigorous training, and strict compliance with the relevant regulatory requirements to ensure participant safety and data integrity. According to the document, implementation of these guidelines will enable the successful integration of decentralized elements into clinical research, enhancing the flexibility and reach of modern clinical trials.
How Can RegDesk Help?
RegDesk is an AI-powered Regulatory Information Management System that provides medical device companies with regulatory intelligence for over 120 markets worldwide. It can help you prepare and publish global applications, manage standards, run change assessments, and obtain real-time alerts on regulatory changes through a centralized platform. Global expansion has never been this simple.
