Gilead Sciences Inc.
Instruction for Business Improvement and Corrective Measures Pertaining to the Delays
in Reporting Overseas Post Marketing Safety Information on Investigational Drugs
Gilead Sciences, Inc. (headquartered in Foster City, California, hereafter “Gilead”) received a
business improvement instruction from Japan’s Ministry of Health, Labor and Welfare (MHLW) on
Feb 13, 2015 under Article 80-2, Paragraph 9 of the Act on Securing the Quality, Efficacy and Safety
of Pharmaceuticals and Medical Devices Act (Act No. 145 of 1960) for violating Article 80-2,
Paragraph 6 of the same act, due to delays in reporting post marketing safety information collected
for three investigational drugs; sofosbuvir, sofosbuvir/ledipasvir and idelalisib outside Japan.
Following identification of occurrence of non-compliance, Gilead reported a total of 735 cases for the
3 investigational drugs, to the Minister of MHLW, the Pharmaceuticals and Medical Devices Agency
(PMDA). Gilead has submitted an internal investigation report covering the root cause analysis,
course of the events, as well as the outline of corrective measures to the MHLW on February 9,
2015. Additionally, in response to the instruction for business improvement, Gilead will promptly
submit a plan outlining the corrective and future preventive measures to the MHLW.
None of the delayed post marketing safety reports contained information that would change the
known safety profile for the products involved.
Gilead would like to offer its sincere apologies for any inconveniences the company may have
caused to patients and their families, medical personnel who participated in the clinical trials, and
the public.
We take this business improvement instruction very seriously, and will assure thorough regulatory
compliance and appropriate remedial actions to prevent future recurrences and strive to regain
public trust.
Situation Overview
1. Delays in reporting the post marketing safety information collected outside Japan while clinical
trials were being conducted in Japan
Gilead Sciences, Inc. has conducted global clinical trials of the hepatitis C therapies sofosbuvir
and the single tablet regimen of ledipasvir and sofosbuvir, and the blood cancer treatment
idelalisib, as part of its global development programs that included clinical trial sites in Japan. In
Japan, regulations require post marketing safety information collected in other countries to be
reported to the PMDA, to the physicians responsible for the clinical trials, and to the heads of
the medical trial institutions in Japan. However, Gilead discovered that it delayed the reporting
of the post marketing safety information for investigational drugs described above during the
period clinical trials were being conducted in Japan.
Gilead informed this issue to the MHLW and the PMDA in December 2014. The MHLW and the
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PMDA instructed Gilead to provide to the PMDA the overseas post marketing safety information,
which should have been reported to the physicians responsible for the clinical trials and to the
heads of investigational sites and to the IRBs for all clinical trial(s); then obtain the assessment
of the IRB(s), and report back to the MHLW and the PMDA. The reporting of the delayed post
marketing safety information to PMDA has been completed. Furthermore, all IRBs responsible
for the clinical trials are evaluating whether the delayed safety information has any impacts on
their trials. Post marketing safety information collected outside Japan undergoes medical
examination on a regular basis at Gilead. Gilead concluded that there was no safety information
that would require that the package insert for these drugs be revised in the U.S. and other
countries.
The table below describes the number of delayed cases and the dates on which the company
should have started reporting post marketing information collected outside Japan.
Name of
Investigational Drugs
Status of clinical
trial
sofosbuvir
Single tablet regimen
of ledipasvir and
sofosbuvir
idelalisib
Completed
Open
(Documentation
phase)
Open
2.
Date on which reporting the
post marketing information
collected outside of Japan
to PMDA should have
started
(Approval Date)
December 6, 2013(USA）
Number of post
marketing safety cases
unreportedas of
January 29, 2015
674
October 10, 2014(USA)
3
July 23, 2014 (USA)
58
Content of the business improvement instruction
The business improvement instruction requires Gilead to:
1) Take necessary measures by ensuring an accurate reporting system, revising procedures
and conducting training so that the post marketing information collected outside of Japan is
reported consistently and on time in accordance with regulations in Japan. Collaborate
closely with the In-Country Care taker to take the necessary measures to obtain and share
the required information in a timely manner for the appropriate execution of the clinical
trials.
2) Take necessary measures to ensure that all Gilead personnel obtain and understand
precise information on Japanese regulations upon sponsoring clinical trials.
3) Submit a plan to the MHLW outlining the improvement plan for corrective and preventive
measures.
3.
Root causes and preventive measures
As for the root cause of the delay, internal and third party investigations determined that the
company fell short in thoroughly understanding the reporting obligations for post marketing safety
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information collected outside Japan to relevant organizations, and that the coordination between the
US Headquarters and the Japan affiliate was suboptimal. Gilead takes this matter caused by lack
of understanding about reporting regulations on safety information in Japan very seriously and will
ensure not to make this happen again by implementing corrective and preventive actions. In
particular, both Gilead Sciences, Inc. and its Japanese affiliate will make sure to have full
understanding of applicable Japanese regulations, to review safety information reporting process, to
conduct comprehensive training and to increase the number of staff handling safety information so
as to strengthen the safety reporting system within the organization.
Gilead has submitted an internal investigation report covering the root cause analysis, course of
the events, as well as the outline of corrective measures to the MHLW on February 9, 2015.
Additionally, in response to the instruction for business improvement, Gilead will promptly
submit a plan outlining the corrective and future preventive measures to the MHLW.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative
therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients
suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has
operations in North and South America, Europe and Asia Pacific.
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