The Fundamentals of Clinical Research. P. Michael Dubinsky

with all parties who need to know. It should not be assumed that every sponsor will have an SOP describing the process of documenting communications via phone (or otherwise) with representatives of a regulatory authority. Such procedures will usually be accompanied by a blank form to be used for documenting the specific of the call, meeting, etc. In times past, such records were made in pen and ink on three part carbonless forms which accommodated distributing the record, archiving it, and maintaining a personal copy. The blank form provided the user with places to record the basic elements of a communication such as names, titles, times, contact numbers, and substance of the communication. E‐mail or a memo to the files would likely be used today but the parameters are the same. In order for the record, whether made in writing or electronically, to be in conformance with GCP, it must be legible, contemporaneous, original, complete, accurate, and clear as to who the author is. There is nothing more problematic than having an inspector from a regulatory authority, who is reviewing records of adverse experiences, find one with the word YIKES written across it in red ink! Try explaining that entry. The record must also be permanent so that any additions, changes or versions are clearly identified. In the case of meeting with or communicating with a regulatory authority it is sometimes appropriate to share the record of meeting with them. Doing so does not mean they consider it the only record or the “official” one but at least they will know you created a record and its content. This type of record keeping guidance and explanation will be mentioned in several places in the text and it is appropriate to do so because it is a fundamental requirement of applying GCP principles.

5.6 Meetings – When and How They fit‐GCP

      Meetings with regulatory authorities are encouraged for the Clinical Trial Sponsor at trial milestones. Those times are often just before submission of an application to conduct the trial and before embarking on each of the applicable phases. During such meetings topics such as complexities in the protocol, approach to compliance with elements of GCP can be on the agenda as well as the science of the IP and trial approach. After a trial a meeting may be scheduled to clarify outcomes prior to the submission of any marketing application. Regulatory authorities agree that meetings are useful. For example the US FDA includes specific references to meetings during the conduct of a clinical investigation in the controlling regulations.

      In most situations the topics discussed are instrumental in the performance of clinical trial activities so documenting all outcomes, agreements, decisions, and follow‐up steps via a meeting record is important. ICH E6(R2) section 8.3.11 serves as a catch all in the TMF for the written record of such meeting minutes.

      Face‐to‐face meetings are usually the most effective forum for ensuring that there is clarity between parties on all aspects of an endeavor such as a clinical trial. Conformance with one or more aspects of GCP can and is on the agenda of many meetings between sponsor and regulatory authority as well as between the parties performing steps in the trial. Therefore, the records of meetings and all forms of communications are vital. An often overlooked benefit of well‐documented communications is that they engender trust among the parties involved. Trust between parties goes a long way when issues arise and explanation must be made for decisions that impact a trial‐related matter.

5.7 Applications

      This text is not meant to serve as specific training for the regulatory affairs personnel in terms of application preparation and submission. Many other reference texts describe the ins and outs of that task. It is however useful to reflect on the importance of GCP when noncompliance with it can have a significant impact on the review and processing of applications.

All of the regulatory authorities who receive and process applications have established internal instructions regarding the evaluation of noncompliance with regulatory requirements. Serious deficiencies are evaluated for their impact on the continued review and evaluation of an application as well as whether the trial should continue to be conducted at a site(s) or be placed on hold. Any decision to place a trial on hold would be based on a risk‐benefit evaluation to determine whether the risk factor may have changed due to the deficiencies. If, for example, adverse experience reports had not been made in a timely manner or at all, then the risk of the non‐reporting will be weighed by the competent authority. Many such deficiencies are identified during inspections of sponsors and/or sites. Regulatory authorities also receive reports from sponsors of situations, e.g. in the UK a serious breach of the requirements impacting the safety of subjects must be reported.

5.8 Summary

      The clinical development pathway which is navigated by a sponsor’s regulatory affairs group is not a silo in terms of conformance with and adherence to GCP. The reach of GCP requirements runs throughout a sponsor’s organization if they are involved and participating in some aspect of a clinical trial activity. Interactions with regulatory authorities via any communication mechanism must be appropriately documented, shared to the extent necessary and available for review as part of the evidence that the overall trial was conducted in conformance with GCP.

      Knowledge Check Questions

      1 Competent authorities prefer to have at least ten points of contact should there need to be communications between they and the sponsor about some aspect of a clinical trial. True or False?

      2 The ICH E6(R2) Guideline calls for records of meeting and other relevant communications about a clinical trial to be maintained in section 5 6 8 9 (Circle the correct section)

      3 Regulatory authorities support and encourage meetings to discuss issues which arise with clinical investigations. The US FDA reserves every Friday for such meetings. True or False?

      4 Face‐to‐face meetings are a sound approach to discussing/communicating aspects of the conduct of a clinical trial with a regulatory authority. Such meetings also can build __?___ between the parties.

      5 Nonconformance with GCP can be a rationale for placing a clinical trial or an investigational application on hold. True or False?

References

      1 1 ICH. Website link for the international council for harmonization of technical requirements for pharmaceuticals for human use (ICH), https://www.ich.org/home.html (accessed 27 January 2020)

      2 2 FDA (December 2017). Best practices for communication between IND sponsors and FDA during drug development. https://www.fda.gov/regulatory‐information/search‐fda‐guidance‐documents/best‐practices‐communication‐between‐ind‐sponsors‐and‐fda‐during‐drug‐development (accessed 27 January 2020)

      3 3 Bargaje, C. (2011). Good documentation practice in clinical research. Perspectives in Clinical Research 2 (2): 59–63. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121265/?report=printable (accessed 27 January 2020).

Part III Good Clinical Practice

6 GCP Definition and Principles

       Karen A. Henry

      GCP Key Point

       GCP and its principles are the foundational filters for performing any clinical trial activity or making any clinical trial‐related decision.

6.1 Introduction

      Experiments with and outright distribution and sale of products for the diagnosis, treatment,