Int. J. Pharm. Sci. Rev. Res., 61(2), March - April 2020; Article No.

10, Pages: 45-49 ISSN 0976 – 044X

Review Article

Audit Finding’s on GCP Violations and it’s Prevention

Chandaka Saranya1, C.S. Mujeebuddin2

1. Intern at Clinosol Research Private Limited, 48-7-53, Rama Talkies Rd, Srinagar, Rama Talkies, Dwaraka Nagar, Visakhapatnam, Andhra
Pradesh 530016, India.
2. Founder and CEO of Clinosol Research Private Limited, 48-7-53, Rama Talkies Rd, Srinagar, Rama Talkies, Dwaraka Nagar,
Visakhapatnam, Andhra Pradesh 530016, India.
*Corresponding author’s E-mail:

Received: 10-02-2020; Revised: 18-03-2020; Accepted: 25-03-2020.

ABSTRACT
This article summarizes regarding audit findings on GCP violations or on it’s noncompliance and what are the aspects that a
regulatory authority would find during an audit of clinical trial on violation of GCP and what are the measures to be taken in
preventing them by the investigator, sponsor, clinical trial related staff and all others. if the GCP violations are not prevented it
would ultimately lead to termination of clinical trial and imposition of fines/penalties by the regulatory authorities.
Keywords: Inspect, conduct, audit, report, compliance.

INTRODUCTION o They would inspect whether study staff is qualified

A s we all know ICH-GCP guidelines are the most enough to obtain ICF.2
important guidelines in a clinical research industry o They would inspect whether legally accepted
and all the clinical trials conducted globally should representative present is valid or invalid.
have their compliance with ICH GCP. 1 o They would inspect if the given ICF has been approved
The most common audit findings on GCP violation are as by IRB/IEC.
follows…. o They inspect whether the patient has signed full ICF.
➢ Informed consent form o They inspect if ICF has amendments and if they have
➢ Institutional review board/ independent ethics their approval/favorable opinion by IRB/IEC.
committee o They inspect whether the consent has been
➢ Protocol adherence. conducted in conductive environment.

➢ Reporting of SAE o If ICF has been translated into preferred language of

the subject by the translator, the regulatory authority
Findings of Informed Consent form would inspect if the translator is qualified enough or
Informed consent form is defined as voluntary consent not.
given by the subject after listening to all the trial related o They also inspect if substantial amendment to ICF is
risks and benefits of participation into the trail by the approved.
investigator. whICH is to be signed and dated by subject.
o They would inspect if translated consent signed and
Informed consent form should contain all relevant dated by a non-English speaking patient/study
information of objectives, methods of study, drug product, registration/enlistment and also check if it contains
treatment regimen, available alternative treatment and all required signatures.
possible complications and discomforts, which may arise
from participation in study. o They would also inspect if consent used was the
current IRB/IEC version at time of patient registration
Informed consent form is the responsibility of the or not and if outdated consent was used
investigator, who should prepare and get prior approval
from IRB/IEC. o They would inspect If reconsent not obtained as
required consent of ancillary/advanced imaging
Informed consent form is used by the subject/legally studies not executed.
accepted representative/impartial witness.
o They would inspect If consent of ancillary/advanced
Regulatory authority would inspect if subject has obtained imaging studies is not executed.
ICF prior to the participation of trail.

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Int. J. Pharm. Sci. Rev. Res., 61(2), March - April 2020; Article No. 10, Pages: 45-49 ISSN 0976 – 044X

Quality Control findings of Informed Consent Form ➢ They would inspect if any of them are missing in the
composition.3
They would inspect for various quality control findings of
informed consent form such as if consent form has been ➢ They inspect if work has been taking place according
signed by participant but signature of investigator or to the written procedures like sop and if sop’s are
witness is not dated. available or not.
They would inspect if whiteout is used to correct an error ➢ They also inspect if all the submitted reports like
on consent form. serious and unexpected and related have been taken
care or neglected.
Findings of Institutional Review Board/Independent
Ethics Committee ➢ They also inspect for presence of relevant records
which should be retained for at least 3 years.
As per ICH GCP guidelines, right, safety and well being of
trial subjects are the most important considerations and ➢ They would inspect if there is any documentation is
should prevail over the interests of science and society. missing.
As we need an external person to review independently ➢ They would inspect for reapproval of expedited
whether ICH GCP guidelines has been followed or not reporting.
which has to be performed by IRB/IEC.
➢ They would inspect if there are any major changes for
IRB/IEC should be independent of investigator and approved protocol that would increase the risk to
sponsor. subjects were given expedited approval only.
They inspect the following…. ➢ They would also inspect expedited reapproval for
situations other than approved exceptions.
➢ If information requested by regulatory authority
regarding written procedures (sop) and membership Findings of Protocol Adherence
lists is been refused or accepted.
➢ Protocol is a document that describes the objective,
➢ If they meet minimum eligible criteria of composition design, methodology, statistical considerations and
as we are aware that it is about 5 members. Which organization of a trial.
includes the following….
➢ The protocol usually also gives the background and
Physician rationale for the trail, but these could be provided in
other protocol referred documents throughout the
Physician should be the first person in ethics committee.
ICH-GCP guidelines.
The clinical trial which has been designed if it is relevant
➢ A written description of changes to formal
and if meets all the applicable requirements or not is been
classification of a protocol is called protocol
checked by the physician.
amendment.
Pharmaceutical Scientist
➢ Protocol is prepared by the sponsor.
Pharmaceutical scientist is responsible for reviewing of
➢ Investigator/institution should conduct the trail in
drug products.
compliance with protocol.
Social Activist
➢ Adherence to study protocol is the most critical.
He/she is the person who is works for society and well because any deviation to the protocol is considered as
being of society. non-compliance or violation of protocol irrespective
of study sponsor’s acceptance on deviation.6
They would talk about the benefit of society.
➢ So a regulatory authority would inspect the
Retired Judge
following…
He/she would review for any of those legal obligations on
Omission
conduction of clinical trial.
If they have met the requirements in the protocol or not.
Laymen
Addition: They inspect if we perform an activity which is
Persons who does’nt involve in review of clinical trial
not specified in the protocol.
are not responsible for review of clinical trial.
Deviation: They inspect if there is any change in particular
They would review regarding compensation of subjects.
procedure as specified in the protocol.
All the 5 members are responsible for voting and give
❖ They would inspect if amendment is documented,
approval only when clinical trials are performed based on
dated, and if maintained with the protocol.
ethics.

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❖ They would also inspect if any change to the protocol ➢ We should never perform any study assessments
has been performed by investigator and if it is been before obtaining informed consent form from
reported to the sponsor by investigator or not. potential participants.
❖ They would also inspect if the amendment is been ➢ We should always review study and consent form
approved by IRB/IEC and regulatory authority prior to with the participant as soon as the failure is
implementation. identified.
❖ Auditor would firstly find evidence for deviation from ➢ We should document all steps to correct the
protocol and review the following….. situation and attach them to the signed ICF and notify
our supervisor immediately.
❖ They would inspect what are the reasons for
deviation. ➢ We should conduct consent interviews in a quiet,
separate room.
❖ They would inspect if the patient fails to complete
scheduled visits as required by the protocol. ➢ While reviewing a consent form with a participant,
we need to focus on that task instead of distractions.
❖ They would inspect if list in final study report
matched the protocol deviation log for the site. ➢ The person who obtains a participant’s consent must
be present when consent form is signed. having the
FINDINGS OF REPORTING OF SAE
investigator sign the consent form later is
Serious Adverse Event (SAE) unacceptable. We should never backdate a consent
form.
Any noxious, unintended event which falls under the
following criteria.. ➢ We should create and use check list in order to
ensure every detail in ICF process is obtained.
➢ fatal/death.
➢ life threatening. ➢ By following good documentation practices, if an
error takes place during it’s completion. good clinical
➢ inpatient hospitalization/prolongation of inpatient
practice or good medical record correction
hospitalization.
techniques can be used to correct it.
➢ congenital animalia or birth defect.
➢ We need to cross out the error without obstructing
➢ persistent disability.
original entry, initial, date, and crossing out and enter
➢ other medically insignificant event. correct information.
➢ All grades, types, duration of SAE should be accurately
➢ When issues are identified, we should reconsent the
recorded.5
participant using appropriate informed consent form
➢ We should obtain the required protocol baseline and attach a memo identifying the issue and the
studies needed to effectively assess toxicity. corrective action to new consent form.
➢ reporting of SAE plays an important role in ICH GCP as
➢ When a new consent form is required to check on
the safety and well being of trial subjects are the most
each participant of next visit to ensure that he/she
important considerations.
has signed the new form.
➢ they inspect if SAE have been reported at correct time
or not as it is very critical. ➢ We need to device a system for flagging the files of
participates who have not yet signed new consent
➢ they inspect documents related to SAE’S.
forms.
➢ they inspect 1) charges
➢ We should use a tracking spreadsheet.
2) study notes1
➢ they inspect for any laboratory abnormalities. ➢ We must ensure documentation of consent form is in
source notes.
Prevention of GCP violations
Prevention of Institutional Review Board/Independent
GCP violations can be prevented by following the below Ethics Committee violation:
considerations. if these preventive measures are not taken
the clinical trial would most likely be terminated and fines ➢ in order to prevent GCP violations in IRB/IEC may need
are imposed by the regulatory authority. to follow a few appeal of determinations which are as
follows…
Prevention of informed consent form violations
➢ no overrule should be permitted.9
➢ We should always check if participant’s informed
consent documentation is completed before ➢ it should not allow a committee or a official to set aside
beginning study procedure.8 or overrule a determination by IRB/IEC to disapprove
modifications recommended by IRB/IEC .

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Int. J. Pharm. Sci. Rev. Res., 61(2), March - April 2020; Article No. 10, Pages: 45-49 ISSN 0976 – 044X

➢ IRB/IEC should provide notice to investigator on ➢ We can prevent most of the deviations by performing
disapproval. it should provide research investigator study required procedures and visits within the
with a written statement of its reasons regarding its required window.
opinion of modification/ modification in proposed
➢ Because of large number of out of window
research and must give investigator an opportunity to
procedures/visits may indicate poor
respond in person or in writing.
scheduling/planning.
➢ it should conduct ongoing monitoring, initiatives.
During Navigation
➢ the IRB/IEC should be responsible for reviewing of all
We have to make sure eligibility criteria are clear and there
audit findings or other reports.
is no subject to interpretation.
➢ it should evaluate and determine whether if it requires
➢ predicting all the possible deviations during navigation
corrective action or not.
itself and prior to IRB/IEC submission and creating
➢ IRB/IEC should conduct self-assessments and contingency plans in the protocol would be more
monitoring. appropriate and advantageous.
➢ it also should conduct regular meetings to identify ➢ regular internal monitoring would also be favorable for
areas of review and operations whICH may require preventing deviations.
further enhancement and strengthening.
➢ we should be careful during reviewal of amendments.
➢ whICH includes an evaluation of membership
➢ We should use correct version of the protocol.
&composition of IRB’s to ensure appropriate expertise
relative for the portfolio of research conducted. ➢ the clinical trial should be conducted in accordance
with protocol that has been prepared by the sponsor
➢ IRB/IEC should review and approve research utilizing
which have also received prior approval from IRB/IEC
expedited procedures in accordance with regulatory
and regulatory authorities.
authorities.
➢ no deviations should be implemented by the
➢ It should conduct meetings in an orderly manner.
investigator without consulting or having agreement
➢ It should appoint qualified IRB/IEC members to review with sponsor and also without approval/ favourable
and approve research utilizing expedited procedures in opinion of sponsor.
accordance with the regulatory authorities.
➢ except in conditions such as…
➢ during audit, all documents like written procedures,
❖ immediate hazards to subjects
membership lists, requested by regulatory authorities
should be given. ❖ when subjects involves only logistical or
administrative aspects of trail like..
➢ documents should be maintained appropriately.
❖ if monitors are changed
➢ works should be carried out according to written
procedures like sop, and sop should be maintained ❖ telephone numbers are changed
properly.
➢ any deviation that has been implemented by
➢ the reports like serious and unexpected submitted to investigator/ person designated by the investigator
IRB/IEC should be checked and relevant action should should be able to give proper explanation on
be taken. deviation.
Prevention of Protocol Adherence Violation ➢ violations occur due to human errors.
➢ we need to have thorough review and understanding ➢ if we intend to correct the violations such that
of the protocol.10 explaining the cause of situation of violence. it is
mandatory to document them and take their
➢ We should crosscheck and identify any procedures in
approval/favourable opinion from IRB/IEC.
the protocol that differ from standard practice at our
establishment. Prevention of Reporting of SAE violation
➢ It would be much better to conduct regulation ➢ It should conduct follow up studies which are necessary
initiation meetings and give relevant training to staff to assess if AE is performed or not.
members.
➢ There should be no delayed reporting of AE that would
➢ To implement and use a well-designed study specific require filing an expedited AE report.
forms for documentation including checklists.
➢ There should be no recurrent under or overreporting of
AE.5
➢ AE should be substantiated.

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Source of Support: Nil, Conflict of Interest: None.

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