China’s recent drug regulatory reform has
emphasized that clinical trial data must be authentic and
reliable. However, the legal consequences for breaching data
integrity requirements in clinical trials remain ambiguous. On
August 24, 2016, the China FDA (“CFDA”) issued a
draft Guideline for Handling Issues Identified in Clinical
Trial Data Inspections (“Draft Guideline”). The
Draft Guideline aims to clarify what constitutes data forgery and
the legal consequences of noncompliance in clinical trials for
different stakeholders. The CFDA is currently seeking public
comments on the Draft Guideline.
Previously, the CFDA issued on July 22, 2015, a circular
requiring all applicants of 1,622 pending drug registration
applications to self-inspect their clinical trial data and
compliance with the Good Clinical Practices (GCP). The circular
highlighted several priority areas for the self-inspection, such as
consistency of the final data for analysis with the original raw
data, documentation of changes, compliance in handling of samples
and investigational products, management of subject screening,
inclusion and exclusion, keeping track of protocol deviations and
reporting of adverse events. Upon self-inspection, applicants
voluntarily withdrew around 80% of the pending applications,
including domestic and imported drug applications. Based on the
submitted self-inspection results, since early 2016 the CFDA has
initiated five rounds of onsite inspections over selected clinical
trials, including some Phase I to III trials and some BE studies.
Among the first three batches of completed inspections, 30 drug
applications were rejected, in most instances based on findings of
false clinical data.
To provide more guidance on the legal consequences of these
CFDA-led inspections, the newly issued Draft Guideline mainly
addresses the following:
Division of liability between
applicants/sponsors, clinical trial institutions/sites, and
clinical research organizations (CROs). While sites and
CROs shall bear liability for those data integrity issues, they are
directly responsible for, the sponsors ultimately bear all the
legal liabilities for the submitted clinical data and drug
Types of GCP breaches that
constitute data forgery. The Draft Guideline gave a
specific list of violations of relevant sections of GCP that
constitute data forgery. Among others, hiding certain trial data or
not presenting the complete data set is considered data forgery,
which can lead to CFDA’s ban on the applicant’s future
applications (see the bullet below).
Ban on future
applications. Companies that have forged clinical trial
data are banned from refiling an application for the same product
with the CFDA for the next three years. In particular, if data
forgery is found to have occurred after November 11, 2015, the CFDA
will directly reject the current application under review, and the
applicant will be banned from filing any applications for any drug
products for one year.
blacklist. Based on the Draft Guideline, blacklisting will
apply not only to the sponsors, sites and CROs involved in data
forgery, but also to the responsible individuals within these
Suspension of studies at
study sites. If study sites are found to be involved in
data forgery, or to have committed other serious GCP violations
that threaten subject safety or data integrity, the sites must
immediately suspend subject enrollment, rectify the misbehavior,
and refrain from undertaking any new trials.
Discretion in imposing
penalties. Applicants can be exempted from penalties if
they voluntarily report all identified issues through
self-inspection and withdraw the questionable applications. There
will be leniency in penalties if applicants fully cooperate with
the investigation and timely explain and correct the identified
noncompliance. On the other hand, applicants who decline, deter, or
avoid inspections can face higher penalties.
We encourage life sciences companies to arrange necessary audits
of ongoing clinical trials, evaluate the level of GCP compliance,
and develop corrective action plans accordingly.
The content of this article is intended to provide a general
guide to the subject matter. Specialist advice should be sought
about your specific circumstances.
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