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electronic submission staff (contact information provided below) for technical assistance, rather than submitting a waiver request, as described in Section III.E of FDA’s guidance for industry Providing Regulatory Submissions in Electronic Format—Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (February 2020, Revision 7): FDA may grant temporary waivers of the requirement for eCTD submission if one or more of the following events or circumstances exist: • Extraordinary events or circumstances occur that are beyond the control of the submitter that justify a waiver, including but not limited to, natural disasters that impact computer operations. • An unplanned long-term Internet disruption or other unplanned event occurs that would preclude the sponsor from submitting in eCTD format (e.g., malware attacks). • The sponsor intends to request a withdrawal of an application that has not yet converted to eCTD format. 41 See 21 CFR 312.62 and 812.140(a) Contains Nonbinding Recommendations 25 • The sponsor submitted a request for withdrawal and has not yet received FDA’s acknowledgement of the withdrawal.42 The guidance also states: The sponsor or applicant’s request to waive the eCTD electronic format requirement must include all of the following as supporting documentation to justify the waiver: (a) A description of the circumstances or event–including the anticipated duration of the circumstance or event–giving rise to the need for a waiver (b) The requested duration of the waiver (c) A description of the proposed alternative submission format the sponsor or applicant will be using for the duration of the waiver The request should reference all products that are to be covered by the waiver. The waiver request should be clearly titled “WAIVER REQUEST–eCTD REQUIREMENTS” in bold capital letters at the top of the first page of the submission.43 Waiver requests for new drug applications (NDAs), biologics license applications (BLAs), abbreviated new drug applications (ANDAs), drug master files (DMFs), and commercial INDs may be sent to FDA electronic submission staff via email to CDER (esub@fda.hhs.gov) or CBER (esubprep@cber.fda.gov). If a waiver is granted, FDA intends to provide information in the response letter on how to transmit the submission. FDA intends to encourage sponsors and applicants to send submissions electronically in an alternative electronic format (e.g., PDF files following the eCTD structure). Q17. During the COVID-19 public health emergency, certain patients may no longer be able to travel to a central location for protocol-based treatment that is scheduled on a recurring basis. Can the investigational product intended for infusion be shipped to a local health care provider who is not a sub-investigator to administer the infusion to a patient while still maintaining integrity of the trial? If so, what else would be needed regarding trial monitoring and institutional review board (IRB) oversight? Specific circumstances for a given clinical trial would affect the feasibility and appropriateness of shipping investigational products (IP) to locations other than clinical trial sites as specified under an IND, as well as administering the IP. If the IPs being evaluated in the trial are administered by infusion, then it would be important that any alternative infusion center have appropriately trained personnel and oversight by physicians with sufficient experience regarding 42 See the guidance for industry Providing Regulatory Submissions in Electronic Format—Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (February 2020, Revision 7), available on the FDA guidance web page. To the extent that the guidance provides criteria for waivers and exemptions from the eCTD reporting requirements under section 745A(a) of the FD&C Act, it has binding effect pursuant to statute. 43 Ibid. Contains Nonbinding Recommendations 26 the class of products involved to assure trial participant safety comparable to administration at a trial site. For the purposes of this guidance, local health care providers (HCPs) who are administering drugs in a manner that does not differ from their normal clinical practices would not be considered sub-investigators and need not be listed on Form FDA 1572.44 FDA recommends that these HCPs be listed in site records, such as a log of activities delegated by the investigator. Any changes to a trial protocol to permit an HCP to administer the investigational drug generally must be reviewed and approved by an IRB. 45 The above paragraph described administration of the investigational product by local HCPs who are practicing medicine within their scope of practice. In contrast, if a sponsor will be asking local HCPs to perform study-specific research procedures or assessments that represent a direct and significant contribution to the clinical data for the study (e.g., assessing drug response for a patient or performing a procedure unique to the study and not part of routine medical care), these HCPs would be considered sub-investigators and should be listed on Form FDA 1572. IP may be shipped from a central distribution site directly to an HCP, provided that such shipping is done under the supervision of the investigator using procedures that 

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