Good Clinical Practice: A Question and Answer Guide2024/2025 Edition - 13

GCP Regulations, Standards, and Guidelines for Clinical Research
conducted in accordance with GCP. For purposes of this section, GCP would be defined as a standard for the
design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials in a way
that provides assurance that the data and reported results are credible and accurate and that the rights, safety, and
well-being of trial subjects are protected. It is interesting to note that the proposed regulation mentions " several
notable documents " that define GCP, including the ICH E6 GCP guidance document. This document was written
and developed for use in drug and biologic studies and is not directly applicable to device studies, although it is
widely used as a GCP reference in device clinical trials. The rule also references the ISO 14155 Document on
medical device clinical trials. This document is accepted in most other countries as the standard for GCP conduct
of medical device clinical trials.
It is important to note that the investigational new drug regulations in part 312 address FDA acceptance of foreign
clinical studies not conducted under an investigational new drug application (IND) as support for an FDA IND
or marketing application for a drug or biological product. In the past, the IND regulations referred to conducting
studies outside of the US according to the ethical principles. Since October 2008 foreign clinical studies not
conducted under an FDA IND are now required to be conducted in accordance with GCP as defined in § 312.120.
This change provides greater consistency with the regulations for drugs and biological products regarding FDA
acceptance of foreign clinical studies.
1.15 Q. For a device clinical trial, is an investigator's brochure (IB) as defined for drugs and biologics required
documentation regarding the investigational product?
A. The FDA regulations on medical device investigations (21 CFR 812) do not use the term " Investigator Brochure "
but do require that, " A sponsor shall supply all investigators participating in the investigation with copies of the
investigational plan and the report of prior investigations of the device " (see 21 CFR 812.45). The regulations
do provide descriptions of the " investigational plan " and " report of prior investigations " at 21 CFR 812.25 and
812.27, respectively. The confusion regarding language and the use of the term IB may be in part a result of the
recent update to the ISO document for medical device clinical trials (ISO 14155), used in Europe, Canada, and
many other countries as the standard for the conduct of device clinical trials. In this document, it uses the phrase
" investigator brochure " in section 5.5. The purpose of the IB is defined " to provide the principal investigator with
sufficient safety or performance data from pre-clinical investigations or clinical investigations to justify human
exposure to the investigational device specified in the clinical investigational plan (CIP) or the protocol. " This
really serves the same purpose and definition in 21 CFR 812.27 on the report of prior investigations and that this
information be provided to all participating investigators (21 CFR 812.45).
1.16 Q. In all of its various guidance documents, including those that comprise essential elements of GCP
standards and even in the ICH GCP guideline itself, the FDA clearly states that the guidances " do not
establish legally enforceable responsibilities, " that they should be viewed " only as recommendations, "
and that alternative approaches are acceptable, provided that they are consistent with applicable statutes
and regulations. Yet, in GCP as in other areas, are there persuasive arguments as to why guidance
documents should be followed in the same way as regulatory requirements?
A. Given that FDA guidance documents " describe the Agency's current thinking " and provide agency
" recommendations, " there is certainly a strong incentive to follow their provisions, unless there are specific and
appropriate grounds for choosing an alternate approach. In its current and standard " disclaimer " statement provided
with all new guidance documents, the agency even seems to encourage companies considering approaches that
deviate from guidance documents to contact the agency first - " If you want to discuss an alternative approach,
contact the FDA staff responsible for implementing this guidance. "
As noted above and throughout this text, however, FDA GCP clinical trial compliance efforts focus on compliance
with FDA regulations and not guidance documents (FDA or ICH). Although FDA inspectors may note deviations
from guidance documents and even highlight such deviations in inspection-related communications, the agency's
formal enforcement efforts will focus solely on deviations from federal regulations.
Most in industry treat the FDA guidance documents as industry best practice. During an inspection one would
need to provide justification for why they are not complying with FDA guidance documents as they are important
resources to help establish overall regulatory compliance.
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Good Clinical Practice: A Question and Answer Guide2024/2025 Edition

Table of Contents for the Digital Edition of Good Clinical Practice: A Question and Answer Guide2024/2025 Edition