Issue link: https://www.e-digitaleditions.com/i/1462272
www.biopharminternational.com Quality and Regulatory Sourcebook eBook March 2022 BioPharm International 13 "Remote inspection: An inspection in which the inspector is not physically present at the site(s) where the activities subject to the assessment take or have taken place. Remote inspections may take several forms, including desktop, virtual, and hybrid." "Desktop inspection: A t y pe of remote inspection in which documen- tation (e.g., f iling commitments, site description, and key procedures) is requested by the inspecting body that is not physically present at the site(s). Requests and responses to questions are shared in written form (e.g., via email or on a document-sharing platform). There can be several iterations of the request and review of documentation, questions, and answers. Phone calls or videoconferences take place only rarely to provide clarification about the docu- ments requested or provided." "Virtual inspection: In addition to sharing documentation as in any other remote inspection, virtual inspections utilize technologies such as live or real-time streaming video technol- ogy, screen sharing, or other means of real-time communication. Virtual inspections may include virtual tours of aspects of the inspected site. These inspections may also be referred to as distant assessments or remote interac- tive evaluations." "Hybrid inspection: An inspection that is conducted remotely in part and also includes an in-person presence and on-site visit by the inspecting body. The remote and on-site aspects may be concurrent or at different times (e.g., a portion of the inspection is performed virtually or desktop, followed by a sec- ond portion on-site). The combina- tion of remote and on-site components may be captured in a single inspection report or in separate reports." Though the inspectorates have per- formed many remote inspections (e.g., by March 2021, the United Kingdom's Medicines and Healthcare products Regulatory Agency [MHRA] had con- ducted more than 750 remote inspec- tions [3]), little has been reported about industry experience and lessons learned. This article presents some cases to help fill this gap. SELECT AGENCY EXPERIENCE In the United States, FDA first sus- pended travel for inspections except for those deemed mission critical and began requesting records to assess company compliance. The agency issued sev- eral warning letters to companies based solely on the review of the requested records (4). Industry was not happy that FDA was making decisions without any opportunity for companies to explain or defend their practices. FDA published guidance and implemented a new form, Form FDA 4003, FDA Inspection Records Request, to guide industry on what to expect (5, 6). As beneficial as the availability of this guidance is, it still leaves many ques- tions as to how this plays out in practice. The following are therefore some exam- ples that provide some helpful insights. Case number one The management of an oral solids plant in Asia, holding several abbre- viated new drug application (ANDA) and new dr ug application (NDA) licenses, had first-hand experience with this new FDA approach. This facility received a Form FDA 4003 request- ing an extensive number of records that would normally also be reviewed in a routine surveillance inspection. The company, located outside of the US, needed to translate the requested doc- uments. The Form FDA 4003 asked for the names and qualifications of the person(s) performing the translation. The company specifically asked FDA whether this request was in lieu of, or in addition to, an on-site inspection. FDA never answered this question and never made any additional requests of information to the company. FDA conf irmed receipt of the records in November 2020. The company was left wondering if this desktop audit would serve as their inspection, or whether the agency would still schedule an on-site inspection once travel restric- tions began to lift. The company asked FDA about their status. In June 2021, FDA replied that an Assessment Issue Letter (AIL) will not be sent, and the document review has been completed. The agency stated it would contact the company when it planned to begin on-site inspections again. Case number two The management of an aseptic man- ufacturing facility in Western Europe was subject to a remote inspection by the Federal Drug Control Service of the Russian Federation (FSKN). The Russian regulatory authorities' remote inspection approach consisted of a records request, a video tour, and daily video conferences with subject mat- ter experts (SMEs). What the com- pany experienced was a very thorough inspection as each evening the regu- latory authorities would review all the records with an unknown number of auditors and then attend the video con- ferences with well-prepared questions. The inspection resulted in a few obser- vations equivalent to what US FDA inspectors would classify as Voluntary Action Indicated (VAI). Russian inspectors typically perform a two-day document review in the com- pany's Moscow office before the remote inspection. During the virtual tour of the facility, the inspectors asked the person with the camera to go outside and access Google maps for the position so that they could confirm the location before commencing the mobile video tour under direction of the inspectors, following a map of the facility. The company utilized Microsoft TEAMS to host the remote audit. The audit took five days, three of which included the video conferences for less than four hours each day. The remaining two days included email discussions. The videoconference audit was con- ducted during company business hours Quality and Regulatory Sourcebook Regulations: Inspections