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Jul 16, 2020

In section 745A(b) of the FD&C Act, Congress granted explicit statutory authorization to the FDA to specify guidance for the electronic submissions requirement by providing standards, criteria for waivers and exemptions, and a timetable for such submissions.

This document provides guidance on FDA’s interpretation of the statutory requirement for submission in electronic format; this document also contains guidance on additional submission types for which submission in electronic format is anticipated to be recommended.

In order to standardize the clinical trials of drugs during COVID-19 pandemic in China and provide effective safety management measures, under the deployment and approval of the National Medical Products Administration (NMPA), the NMPA Drug Review Center has issued the draft guidance, which is in effect on the date of release.

This guidance is one in a series that provides recommendations regarding eligibility criteria for clinical trials of drugs or biological products regulated by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) for the treatment of cancer. Specifically, this guidance includes recommendations regarding the inclusion of pediatric patients (i.e., children and adolescents) when appropriate. This guidance is intended to assist stakeholders, including sponsors and institutional review boards (IRBs), responsible for the development and oversight of clinical trials.

The purpose of this technical notice is to remind sponsors of clinical trials conducted in the EU Member States, of the legal situation applicable after the end of the transition period on 31 December 2020, as described in the Commission Brexit readiness notice regarding Clinical Trials.

According to Article 13(2) of Directive 2001/20/EC, the qualified person has to be established in the EU/EEA. Investigational medicinal products used in clinical trials can be imported only after their batch-release has been certified by a qualified person in the EU. According to Article 19 of Directive 2001/20/EC, the sponsor of a clinical trial or a legal representative must be established in the EU.

In addition, for trials authorised in at least one Member State where the sponsor is established in a third-country and with a legal representative in the UK, the sponsor needs to establish its legal representative in the EU by the end of the transition period. At the end of the transition period, the sponsor or its legal representative has to be established in the EU for all ongoing trials. Failure to meet this requirement will be a breach of Directive 2001/20/EC and could trigger a request for corrective actions by Member State competent authorities.

This guidance covers the information and procedures applicable to orphan designated products:

• incentives
• annual reports
• transfer of sponsorship
• change of sponsor’s name or address
• amendment of designated condition
• marketing authorisation application
• review of the maintenance of orphan medicinal product designation at the time of marketing authorisation application
• review of the maintenance of orphan medicinal product designation at the time of extending the therapeutic indication post-authorisation
• withdrawal of orphan designation

A total of 255 pharmacovigilance inspections were conducted for human medicinal products in 2018 in EU/EEA. Of these, 47 human pharmacovigilance inspections were requested in 2018 in the context of supervisory authority inspections of marketing authorisation holders (MAHs) with centrally authorised products (CAPs).

A total of 175 findings, 18 critical (10,3%) and 157 major (89,7%), were identified during the supervisory authority inspections conducted in 2018 (period covering 01/01/2018 to 31/12/2018). These numbers include both supervisory authority inspections of MAHs with CAPs requested by the Committee for Medicinal Products for Human Use (CHMP) and supervisory authority inspections that were conducted under national inspection programmes.

The three most common areas with findings were:

• Management and reporting of ICSRs;
• Quality assurance;
• Signal management.

There were no critical or major findings related to local qualified persons responsible for pharmacovigilance (QPPV).

FDA issued this guidance to provide general considerations to assist sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice (GCP), and minimizing risks to trial integrity for the duration of the COVID-19 public health emergency. The appendix to this guidance further explains those general considerations by providing answers to questions that the Agency has received about conducting clinical trials during the COVID-19 public health emergency. A new Q&A (#12) section has been added about the alternative process to obtain informed consent when electronic and paper forms cannot be provided.

This guidance describes FDA’s intention regarding enforcement of these requirements for class I and unclassified devices.

This guidance also describes FDA’s direct marking compliance policy for class III, LS/LS, and class II devices that are non-sterile, that are manufactured and labeled prior to their applicable direct marking compliance date, and that remain in inventory, as well as for class I and unclassified devices that are not LS/LS devices, that are non-sterile, that are manufactured and labeled prior to September 24, 2022, and that remain in inventory.