The SID&GP under the auspices of the Ministry of Industry and Trade of the Russian Federation conducted the first online inspection of Roche’s manufacturing site

On May 29, 2020 the Chairman of the Government of the Russian Federation, Mikhail Mishustin signed the Government Decree No. 789 according to which the rules of organizing and conducting inspections of pharmaceutical manufacturers in terms of their compliance with the GMP rules requirements, as well as the rules of issuing GMP-certificates to pharmaceutical manufacturers are amended. Already at the end of May 2020, the State Institute of Drugs and Good Practices under the auspices of the Ministry of Industry and Trade of the Russian Federation (hereinafter – SID&GP) conducted an online inspection of the Roche site’s manufacturing and support areas in Basel (Switzerland).

The Roche’s manufacturing site specializes in the manufacturing of solid dosage forms. It produces a number of medicines already supplied to the Russian market, as well as medicines being in the registration process. Among them are: antitumor drug “Kotellik” (INN Cobimetinib) (the dosage form is “film-coated tablets”), approved for use in the treatment of melanoma, “Risdyplam” a drug planned for the treatment of spinal muscular atrophy, in the dosage form of a powder to prepare a solution for oral administration (in the process of registration, it is supplied to Russia within the framework of the program of pre-registration access and clinical trials) and a medicinal product “Xofluza” (INN baloxavir marboxil) for the treatment of influenza, in a form of granules for suspension preparation for ingestion (in the process of registration, it is supplied within the framework of the clinical trials program).

Taking into account the products demand, as well as the world situation that poses a threat to the spread of diseases and lesions, as a result of adverse biological factors at which the inspection of the manufacturer to be inspected is not possible. Therefore, the inspection team and the SID&GP group of inspectors authorized by the Ministry of Industry and Trade of the Russian Federation decided to use technical means in the organization of the inspection process, to carry out an inspection of the manufacturing site in a format of online live stream. The use of this approach in the inspection was applied for the first time. The decision of the inspection team of the SID&GP about the possibility of a new, remote format of inspections was based on the results of materials evaluation presented by Roche. The online format was agreed with the authorized representative of the company’s manufacturer in Russia and site management. Inspection on the site was carried out with the help of special communications equipment in the Roche Moscow office.

As usual, the inspection was conducted by two inspectors with the participation of Roche representatives. In two of the five days of the inspection, an online inspection of the manufacturing areas was carried out in accordance with the manufacturing site plan and the inspection plan. The manufacturer demonstrated manufacturing areas, areas of storage of pharmaceutical substances, finished medicinal products, raw materials dispensing areas, laboratory of internal manufacturing control and control of microbial enumeration test of drugs, areas of engineering systems and support areas (water and air

treatment). Materials on functioning and maintenance of engineering systems were also presented.

Evaluating the new format of GMP-inspections, Vladislav Shestakov, Director of the SID&GP, noted the advantages of online inspections: “When a visit to a manufacturing site by the inspection team is not possible, the use of modern technologies and modern equipment allows to communicate with employees of the company and observe the technological operations in real time without physical presence at the manufacturing site. Specialists with the necessary expertise who could answer the inspectors’ questions, Roche’s staff were in direct contact and could explain or answer questions to the inspector at any time during the online inspection of the manufacturing site”. The manufacturer’s real-time responses to the inspectors’ questions reduce the amount of documents requested (and their translation), which is also facilitated by online discussions and more detailed explanations by site staff to the inspectors on various topics related to the functioning of the pharmaceutical quality system, manufacturing facilities, processes and other aspects of the enterprise.

At the same time, the Inspectorate of the SID&GP is convinced that online inspection is a temporary measure and will not be able to completely replace on-site inspections in the future. This requirement is stated in all recommendations of international regulators, in particular, in the recommendation of the European Medicines Agency EMA/572454/2014 Rev 17 Compliance and Inspection Compilation of Community Procedures on Inspections and Exchange of Information, PIC/S PI 048-1 1 June 2018 GMP INSPECTION RELIANCE.

For Roche, this “visit” of the Russian State GMP Inspectorate was the eighth in 2020 and the first one using virtual technologies. Natalia Nazarova, Head of the Department for registration and quality assurance of medicines at Roche –Moscow stated: “By the time of receiving the official request for online inspection by the SID&GP, we have already had the experience of two remote desk-top inspections and we thought about possible ways to improve the process. Undoubtedly, the virtual inspection required a thorough evaluation of technical means and the training of all involved parties. Carrying out online inspection in the current situation allows us to get as close as possible to the format of on-site inspection”.