Updated Guidance on the Management of Clinical Trials during COVID-19

Recommendation

5-7 November 2024
Hamburg, Germany

GMP meets Development
GMP and FDA Compliance in Pharmaceutical Development and IMP Manufacturing

Pragmatic procedures (e.g. for IMP distribution) are currently required to ensure the flexibility needed to maintain the integrity of clinical trials during the COVID-19 pandemic. Therefore, the European Medicines Agency (EMA), the Heads of Medicines Agency (HMA) and the European Commission (EC) published a joint guidance on the management of clinical trials during the coronavirus pandemic. The guidance has been revised in February (Version 4) to include details on remote source data verification.

Changes in investigational medicinal product (IMP) distribution

According to the document changes in IMP distribution may include the following:

• Larger amounts of IMP can be provided to the trial participants and it is appropriate that stock is maintained to ensure treatment in case of distribution failure.
• Re-distribution between sites in accordance with EU GMP Annex 13 should follow a written procedure established in cooperation with the Qualified Person (QP) or the person responsible for IMP distribution. Transfer documentation needs to be included in the investigators´and the sponsor´s trial master file (TMF / eTMF).
• Direct shipment to trial participants:
  - IMP delivery directly to participants is possible (further education / training of the participants may be necessary for IMP receipt, handling and self administration). The delivery should be done from trial sites to participants.
  - The IMP may as an exception be shipped to the participants by a distributor (a contract between the sponsor and the distributor and an agreement with the investigator is then needed). The agreement and the procedure should be recorded in the investigator site file and should protect blinding and ensure compliance with the randomization.
  - The shipment should be done under conditions that ensure the integrity of the IMP and temperature records should be maintained during shipment for temperature-sensitive products.
  - Procedures for the accountability of the IMP must be in place (among others for compliance monitoring).
  - Records of shipment from the trial site / from the distributor should be kept in the investigator site file (incl. documentation of receipt by the trial participant).
  - Participants should retain unused IMP / packaging and return them to the investigator when they next have a visit to the investigator site.

Remote source data verification (SDV)

According to the Agencies, remote SDV should focus on the quality control of critical data such as primary efficacy data and important safety data. The sponsor should determine the extent and nature of remote SDV that they consider needed for each trial and should carefully weigh it against the extra burden that introduction of any alternative measures would put on site staff.

The following has to be considered for remote SDV:

• Remote SDV should not be carried out if adequate data protection is not ensured. 
• Site staff and monitors should be trained on the remote SDV process.
• It should not be possible to make local copies of trial participants' health records.
• Users should be aware of the automatic creation of temporary files on their computer when reviewing participant data, and should securely delete such files immediately after each SDV session.
• Remote SDV should be described in the initial protocol application (and informed consent form). In case of ongoing trials the use of remote SDV should be submitted via a substantial amendment.
• Remote SDV can be carried out only in agreement with the investigators.

For more information please see the Guidance on the management of clinical trials during the COVID-19 Pandemic.