BioPharm International - March 2022

BioPharm International March 2022

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14 BioPharm International Quality and Regulatory Sourcebook eBook March 2022 acceptable to the regulatory auditors. An agenda was provided, and the com- pany paid for translators to participate in the videoconferences and translate the requested documents into English. Case number three The management of an aseptic man- ufacturing facility in Asia submitted a biological license application (BLA) to FDA for a combination product with the drug substance (DS) manu- factured on site, but the drug product produced by a contract manufactur- ing organization (CMO). The com- pany received a Form F DA 4 0 03, Inspect ion Records Request. T he company asked if this would serve in lieu of, or in addition to, an on-site inspection and needed to translate the documents. The Form FDA 4003 records request included a request to con f ir m t he specif ic roles a nd responsibilities of the various compa- nies involved in this application and focused on the DS production at the applicant site. After a few weeks, the company received a second Form FDA 4003 requesting additional, focused doc- uments relating to the new product application. The second request asked for complete translations of some doc- uments that had only been summa- rized in the first request. In between the two records requests, FDA issued guidance on how it intended to con- t inue inspec t ing du r ing t he pa n- demic. The guidance says that FDA may make use of the information in inspection reports issued by other reg- ulatory authorities, for which mutual re c og n it ion a g re ement s ( M R A s) exist. Furthermore, the new Form FDA 4003 was updated to clarify if the request is an Inspection Records Request with or without an interactive assessment or in lieu of or in addition to an (on-site) inspection. As of the writing of this article, FDA had not informed the company if they intend to either conduct an interactive assess- ment or an (on-site) inspection, leav- ing the company in limbo. Case number four A company in Western Europe was remotely inspected by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Over three months, the agency requested nearly 600 doc- uments in several installments. Every document had to be translated in its entirety and annotated. The annota- tions are necessary to provide context, which would normally be provided by company staff when handing the documents to inspectors on site (e.g., specific pieces of information may be difficult to find within a document and attaching pointers is sensible). PMDA insisted on email communication and would not agree to video conferences or phone calls with the site. LESSONS LEARNED Though regulators have published var- ious guidance documents on remote inspections, much of the actual details, such as structure, length, etc. remain unclear. Even though the inspectors have every intention to resume on-site inspect ions, t his w i l l not happen quickly, especially when it comes to overseas inspections. Thus, industry must be prepared for remote inspec- tions for some time to come. Being prepared means having the procedures and processes in place to respond to documentation requests and to host virtual inspections. T he COV I D -19 pa ndem ic ha s c h a n g e d t h e w o r l d w e l i v e i n . Regulatory authorities responded to the challenge by implementing alter- native means of evaluating company compliance. Challenges for the regu- lated industry remain, such as: • Acc u rate t ra nslat ion of t he requested documents with a short time frame for response • Not knowing if the records request will be followed by an interactive assessment or inspection • More thorough review of docu- ments as many more documents are requested and reviewed • MRAs have not been utilized as envisaged by industry (i.e., there has not been a significant reduc- tion in inspection requests) • Regulator y authorities do not have an inspection trip time- frame limiting them • Technical challenges of setting up the SME inter views using v ideo conferencing soft ware, conducting virtual site tours • Potential delay in approval of new products due to delayed pre-approval inspections. As noted from the case studies pro- vided, learning from the experience of others is one of the best ways of understanding and preparing for the challenges of remote inspections. REFERENCES 1. EC, Directive 2011/62/EU of The European Parliament And Of The Council of 8 June 2011 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use, as regards the prevention of the entry into the legal supply chain of falsified medicinal product. 2. PDA, Points to Consider in Remote and Hybrid GMP/GDP Inspections, May 2021. 3. MHRA Inspectorate blog, Inspectors Grounded–A Year of Innovation, March 26, 2021. 4. J. S. Eglovitch, "FDA's Document-based Inspections Prompt Warning Letters for GMP Violations," R, April 13, 2021. 5. FDA, Staff Manual Guides, Volume IV - Agency Program Directives, General Or Multidiscipline, Policy And Procedures For Requesting Records In Advance Of Or In Lieu Of A Drug Inspection, Staff Manual Guide 9004.1, 6. FDA, Inspection Records Request Form 4003. BP Quality and Regulatory Sourcebook Regulations: Inspections

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