that help to facilitate subject voluntary compliance?9 Overheard:They ask a lot of questions just for curiosity and I don't know all that is in the consent form anyway.Investigator delegate who instructed a college student who volunteered as a healthy research subject to swallow the study medication (capsules) per the appointed clock time just as the subject was about to ask a question about the study. Beds for study subjects for the phase 1 first‐in human study were lined up side by side in the research facility. A clock above each bed was used to record the time of the study procedure. A nurse took the subject's vital signs, followed by another who drew blood, and the subinvestigator physician followed with the cup of water and study dose to research subject.Comment and discuss:Were any of the subject's rights violated in this scenario?Are there any issues with investigator delegation of responsibility at this site?
Reference
1 1 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Integrated Addendum to ICH E6(R1):Guideline for Good Clinical Practice, E6(R2) (2016). Current Step 4 version dated 9 November 2016. https://www.ich.org/page/efficacy‐guidelines
11 Regulatory Authority – Roles and Responsibilities
P. Michael Dubinsky
GCP Key Point
Regulatory Authorities are part of the ICH team that draft ICH Guidance documents. They work to ensure that the guidance reflects the current regulatory expectations. Understanding their role is important.
11.1 Introduction
Among the players in the clinical trial endeavor, the regulatory authority has a unique and highly visible role. Understanding the roles of the regulatory authority whether it is as a gatekeeper approving a trial application or an inspector following up on a complaint, the regulatory authority is in a unique position of control and influence. Placing the roles and responsibilities of the regulatory authority in perspective is therefore meaningful.
11.2 Objectives
In this chapter, you will be introduced to the primary roles and responsibilities of the Regulatory Authority (or Competent Authority) in terms of those functions which are highlighted in the GCP framework. The primary roles, i.e. functions, of the regulator are:
Reviewing and making decisions on clinical trial applications.
Oversight and inspection of the other players involved in the clinical trial endeavor to ensure conformance with GCP, investigational plans, and applicable regulations.
As noted in the Players and Interactions topic, the regulator performs these functions through interactions with sponsors, investigator sites, and IRBs/IECs.
In addition, you will gain insight into why the regulator has responsibility for these functions and is therefore accountable for implementing them.
11.3 Definition and Overview
When one reviews the ICH E6(R2), the number of references to the regulatory authorities (regulators) is limited and there is no specific section devoted to delineating roles or responsibilities for this important player in the clinical trial process. Regulatory authorities are of course mentioned several times in the body of the ICH E6(R2) guideline. Examples include Section 5.10 Notification/Submission to Regulatory Authority (ies) and Section 5.20.2 – Noncompliance – which speaks to the need for regulatory authorities to be notified if an investigator is terminated from participation in a trial. Therefore, one needs to look elsewhere to fully frame out and define the roles and responsibilities of the regulatory authority from a GCP standpoint.
The ICH E6(R2) guideline does, however, include a definition of a regulatory authority and it is useful to reflect on it because it sets the stage for how these entities fit, from a GCP standpoint into the clinical trial arena. The definition reads in part: Regulatory Authorities: Bodies having the power to regulate. In the ICH E6(R2) guidance, the expression “Regulatory Authorities” includes the authorities that review submitted clinical data and those that conduct inspections (see Section 1.29). These bodies are sometimes referred to as competent authorities. Note: The terms Regulatory Authority, regulator, and competent authority all are used in this topic write up interchangeably.
The roles of regulatory authorities in the oversight of clinical trials have been an evolutionary process often driven by tragic events. As noted in Chapter 1 History, the topic the birth defects caused by the product Thalidomide in many newborns was instrumental in moving legislative bodies worldwide to require substantial evidence of safety and effectiveness before allowing a new drug product on the market. Such events and the failure of industry or professional groups to self‐regulate in an effective manner have all too often been the match that lit the fire of regulatory change.
The regulator’s clinical trial responsibilities are assigned and founded in the laws, statutes, regulations, and directives that are put in place by a country or region’s legislative bodies. Well‐known examples of such laws are the USA’s Federal Food Drug and Cosmetic Act and the EU’s Clinical Trial Directive 2001/20/EC and the EU’s Clinical Trial Regulation 536/2014 which supersede the Directive.
This chapter’s discussion of the regulatory authority will focus on how they intersect with the other key players in performing their roles in the conduct and implementation of the clinical trial process as well as the underlying responsibilities for which they are held accountable.
Figure 11.1 depicts the Regulatory Authority’s interaction with the other players in the clinical trial arena.
11.4 Trial Approval – Submission of Applications
The scheme for undertaking a clinical trial process begins with a sponsor who has developed and prepared, in the form of a clinical trial plan including a scientifically sound protocol, an approach to conducting human research to gather data demonstrating that an investigational product is safe and effective for a specified indication. In all countries and regions with established regulatory authorities, the sponsor must obtain the agreement of the regulatory authority before activating that clinical trial plan and protocol for pharmaceutical drug product clinical trials.
The agreement of the regulatory authority is usually given in the form of an approval or permission to proceed. In the United States, the U.S. Food and Drug Administration implements this permission pursuant to the regulations governing Investigational New Drug Applications (IND) – 21 CFR 312. In the EU, the competent authority for each of the 27 member State implements the permission as part of their Clinical Trial Authorization (CTA) process. Under the EU CTR 536, the trial authorization process has been harmonized to increase efficiency. In these and in most similar situations, the regulatory authority is the decision maker. Therefore, it is up to the applicant or sponsor to submit a complete and convincing submission requesting permission to undertake the clinical trial investigation and providing the information and data specified by the regulations governing the application process. The sponsor or applicant is the primary point of contact for the regulator in the application submission process since that entity, be it a firm,
