Bioequivalence studies during the COVID-19 pandemic. Russian experience.

Despite the current epidemiological situation in the world, approved plans for the clinical development of drugs do not lose their validity. According to the Association of Clinical Trials Organizations (ACTO), in 2019 more than half of the clinical trials in the Russian Federation were bioequivalence studies. The question arises about safety measures for study participants, research center personnel, and CRO representatives when organizing and conducting bioequivalence studies. What kind of measures need to be implemented by early-phase research sites? The X7 Research team offers its vision of the ideal research site.

Due to Resolution No. 15 of the Chief State Sanitary Physician of the Russian Federation of 22.05.2020 “On Approval of Sanitary and Epidemiological Rules SP 3.1.3597-20 “Prevention of New Coronavirus Infection (COVID-19)”, prevention of COVID-19 spread requires compliance with measures aimed at “breaking” the transmission mechanism of the infection.

Specifically: “the observance by all individuals of the rules of personal hygiene (handwashing, use of antiseptics, medical masks, gloves), the observance of a social distance of 1.5 to 2 meters”.

To maintain social distance, the research site must have sufficient space with the ability to separate the flow of volunteers and other visitors to the site. At the entrance to the research site, it is necessary to conduct interviews with clinical research subjects and other visitors to the site about COVID-19, providing detailed information about the main symptoms of the disease and preventive measures, including an explanation of the rules of wearing masks to protect the respiratory organs, the use of disinfectants, including personal antiseptics. To maintain personal hygiene measures, it is recommended that the site have a supply of antiseptics, medical masks, and gloves not only for staff and ensure control over the timely change of personal hygiene products. It is also necessary to ensure that all visitors to the site are thermometrically tested and that appropriate records are made in the logbook. Medical examinations for signs of SARS  should be arranged for all employees of the site before the beginning of the working day.

Observing social distancing and other preventive measures is equally important when performing Study Protocol procedures. To this end, it is recommended that:

• Establish and adhere to a strict schedule of volunteer visits: while during “normal times” screening for all volunteers is scheduled, for example, from 09:00 to 11:00, during an epidemic it is better to invite each volunteer for screening at specific time intervals. For example, the first volunteer is invited to be screened from 09:00 to 09:30, the next from 09:30 to 10:00, and so on. A similar schedule should apply to volunteer hospitalizations, study drug dispensing, pharmacokinetic testing, and other Protocol procedures.
• Limit as much as possible the number of persons present in the procedure room during the dispensing of study drugs, collection of biological samples, and other Protocol procedures.
• Place volunteers no more than two persons per room and arrange meals in pairs to maintain social distance and reduce the number of persons in one room.
• For routine disinfection of rooms, work surfaces, and furniture, use disinfectants approved for use in the presence of people.
• Treat the air in the presence of people using ultraviolet radiation equipment.
• Due to the introduction of restrictions in some regions of the Russian Federation on the employment of part-time medical personnel and the increased time interval for ambulance arrivals during epidemics, it is recommended that the site have its intensive care physician, registered at this site not part-time, but at the main place of work.

Ensuring the safety of CRO representatives and customers is also one of the important tasks of the research site. To prevent the spread of COVID-19, the research site team needs to plan the visits of CRO representatives, customers, and auditors more carefully. Specifically:

• Before the visit, it is recommended that visitors be notified via phone call and e-mail of the preventive measures observed at the site and the need to observe personal hygiene (handwashing, wearing gloves and masks) and social distancing when on the site premises.
• It is recommended to place no more than one project team in a room so that the team members can observe the social distance of 1.5 – 2 meters.
• If it is necessary to check the protocol procedures by the Customer or visits the premises of the site, it is also recommended to provide the possibility of social distance in the offices of the site.
• To minimize casual contacts on the territory of the site, it is recommended to organize coffee breaks and meals for representatives of the CRO, customers, and auditors in the room for monitoring.
• It is recommended to provide representatives of the CRO, customers, and auditors with a separate bathroom to minimize accidental contacts in the site.
• If there is more than one monitoring room in the site and it is possible to organize visits of more than one project team at the same time, it is recommended to avoid “overlapping” of members of different teams at the entrance and in other rooms of the site.

In times of increased epidemiological danger, the work of the physician-epidemiologist at the site is extremely important, as his task is to draw up a plan of preventive measures and monitor compliance with these measures. This requires the physician-epidemiologist and other persons in charge of the site (executive director, chief medical officer, head nurse, director of quality assurance) to draw up orders and/or SOPs for additional measures to prevent the introduction and spread of the new coronavirus infection COVID-19 into the institution and to ensure that all employees of the research site are familiar with these documents. This will help ensure a high level of compliance with all preventive measures, quality control of compliance measures, and will satisfy CRO representatives, customers, and auditors in case of questions about what measures the site are taking to keep its employees, volunteers, and other visitors to the site safe.

In this way, we see that preventing the spread of COVID-19 internally at the research site is a comprehensive system of measures to ensure the safety of subjects, employees, and visitors to the site. Employees of the site need to constantly monitor the epidemiological situation and update the regulatory documents of the Russian Ministry of Health and other governing bodies. X7 Research is always ready to conduct an independent audit of the site, to prepare site documents in a dynamically changing environment.