Prospects related to GCP inspections

1.

Scientific Center
for Expert Evaluation
of Medicinal Products
Prospects related to GCP
inspections
Alla Arkadyevna Trapkova
Deputy Director General
Federal State Budgetary Institution
"Scientific Center for Expert Evaluation of Medicinal Products"
of the Ministry of Health of the Russian Federation

2.

Scientific Center
for Expert Evaluation
of Medicinal Products
Requirements for clinical studies
36. During the process of drug product authorization, the reports on performed clinical studies included into Module 5 of
its registration dossier shall be reviewed in the framework of the expertise, provided one of the following conditions is met:
Clinical studies have been performed according to the legislation of the Member States and in their territory before January 1, 2016
(according to the date of the last visit of the last patient (volunteer)) or were ongoing as of January 1, 2016 (with completed patients
(volunteers) enrolment);
Clinical studies have been performed in part or in full in the territories of the Member Countries of the International Council for
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) before January 1, 2016 (according to the date of the
last visit of the last patient (volunteer)),
based on which the medicinal product was authorized in the territories of the ICH countries;
Clinical studies initiated after January 2016 have been performed according to the international treaties and acts constituting the Law of
the Union, and at least one of the clinical studies has been carried out in full or
in part (in terms of the data obtained from the study subjects) in the territory of the Union.
If the requirements stated in the second to fourth paragraphs of the present clause are not fulfilled, prior to applying for the drug
product authorization, the Applicant shall perform clinical studies (at least one study at the discretion of the Applicant and according
to the approval by the authorized body) in full or in part in the territory of the Union, or during the expertise of the registration
dossier, an extraordinary inspection of one of the clinical centers, where the study has been carried out, shall be appointed based on
the decision of the authorized body.

3.

Scientific Center
for Expert Evaluation
of Medicinal Products
EEC Documents
for Pharmaceutical
Inspectorate and Pharmaceutical Inspections
Decision of the
Council of the EAEU
No. 83 dated November 3,
2016
approval
of the Rules of conducting pharmaceutical inspections"
amended on February 8, 2021)
Decision of the
Council of the EAEU
No. 91dated November 3,
of the procedure for performing
joint pharmaceutical
“On
(as
2016
“On adoption
inspections”
Decision of the Council of the EAEU No. 82 dated November 3, 2016 “On approval of common
requirements for quality systems of the Pharmaceutical Inspectorates in the Member States of the
Eurasian Economic Union"
Decision of the Council of the EAEU No. 90 dated November 3, 2016 “On approval of the procedure of
creating and keeping a register of pharmaceutical inspectors of the Eurasian Economic Union"

4.

Scientific Center
for Expert Evaluation
of Medicinal Products
Principles of Development of the Rules for
Pharmaceutical Inspections for Compliance with the
GCP Requirements
Commission Implementing Regulation (EU) 2017/556 dated March 24, 2017 on the detailed
arrangements for the Good Clinical Practice inspection procedures pursuant to Regulation (EU) No
536/2014 of the European Parliament and of the Council
March 28, 2017 EMA/INS/GCP/158549/2016 Rev. 1 Committee for Medicinal Products for Human Use;
Procedure for reporting of GCP inspections requested by the Committee for Medicinal Products for
Human Use (CHMP)
September 20, 2007 EMEA/INS/GCP/197228/2005 Procedure for preparing GCP inspections requested
by the EMEA March 25, 2014 EMA/INS/GCP/55482/2013 Procedure for coordinating GCP inspections
requested by the CHMP
February 1, 2017 EMA/745861/2016 Guidance on triggers for inspections of bioequivalence trials

5.

Scientific Center
for Expert Evaluation
of Medicinal Products
Rules for Pharmaceutical Inspections
for Compliance with the GCP Requirements
General
requirements
The EAEU GCP inspection shall be carried out in order to verify the observance of the Rules of Good
Clinical Practice of the EAEU, including protection of rights and well-being of the clinical study subjects, as
well as quality and accuracy of the data obtained in the clinical study and ethical aspects.
The present Rules may be applied to the following inspections:
Those focused on the clinical studies performed in the Union, including the study centers
related to such studies, but located outside the Union;
Those focused on the clinical studies stated in the applications for a permission to perform a
clinical study;
Those focused on the clinical studies performed in the third countries and stated in the
applications for drug products authorization in the Union.
The inspections are allowed in the following cases:
• Before, during and after the completion of the clinical study;
• During the expertise of the applications for the drug product authorization;
• As follow-up measures after the drug product authorization.

6.

Scientific Center
for Expert Evaluation
of Medicinal Products
Rules for Pharmaceutical Inspections
for compliance with the GCP Requirements
General requirements
The inspections my be scheduled and extraordinary. The scheduled inspections can be performed based
on the Inspectorate plan, including those within five years following the drug product authorization
according to the EAEU Rules for Registration and Expert Evaluation of Medicinal Products for Human Use
approved by the Decision of the Council of the EEC No. 78 dated November 3, 2016. Planning of the
inspections may be carried out based on the risk management principles.
According to the decision of the Pharmaceutical Inspectorate, it is allowed to perform pharmaceutical
inspections using the means of remote collaboration (for example, via audio or video
communication) in the following cases:
a) A threat of the emergence, occurrence and elimination of an emergency situation and/or
evolution of a threat of the spread of epidemic diseases that pose a danger to others, diseases and
injuries resulting from exposure
to adverse chemical, biological, radiation factors;
b) In the event of force-majeure circumstances or circumstances beyond the control of the parties that
pose a threat of injury or disease to the inspectors (for example, due to political, medical or other
reasons).

7.

Scientific Center
for Expert Evaluation
of Medicinal Products
Rules for Pharmaceutical Inspections for compliance
with the GCP Requirements Inspection
procedure
Inspecting subjects of all types:
Appendix No. 5: Inspection of the study center;
Appendix No. 6: Inspection of clinical laboratories;
Appendix No. 7: Inspection of the sponsor and/or contract research
organizations (CROs);
Appendix No. 8: Bioanalytical part, pharmacokinetic and statistical
analyses of the bioequivalence studies.

8.

Scientific Center
for Expert Evaluation
of Medicinal Products
Rules for Pharmaceutical Inspections
for Compliance with the GCP Requirements
Noncompliances
Critical non-compliances — non-compliances while conducting clinical studies that call into question
quality and integrity of the clinical study data and may result in partial or complete uncertainty of the
study data, as well as over-valuation of the benefit-to-risk ratio for the drug product, or negatively affect
the rights, safety or well-being of the subjects.
Major non-compliances — non-compliances that cannot be classified as critical, but indicate a significant
deviation from the requirements of the Rules of Good Clinical Practice of the Eurasian Economic Union, or
point to a major deviation from the requirements of other legal acts within the medicines circulation
sphere;
Minor (other)non-compliances — non-compliances that cannot be classified as critical or major, but
indicate a deviation from the requirements of the Rules of Good Clinical Practice approved by the
Eurasian Economic Commission.

9.

Scientific Center
for Expert Evaluation
of Medicinal Products
Critical
Possible
consequences
Note
Major
Possible
consequences
Note
Rules for Pharmaceutical Inspections
for Compliance with the GCP Requirements
Non-compliances
Conditions, practices or processes negatively affecting rights, safety or
well-being of the subjects and/or quality and integrity of the data.
Critical non-compliances are unacceptable.
Deviation of the data and/or required legal measures.
The non-compliances classified as critical may include a number of
deviations classified as significant, data of poor quality and/or lack of primary documents.
This group encompasses manipulations and
intentional data garbling.
Conditions, practices or processes that may negatively affect rights,
safety or well-being of the subjects and/or quality and integrity of the data.
Major non-compliances are serious deficiencies and
directly violate the GCP principles.
The data may be rejected and/or legal measures are required.
The non-compliances classified as major may include a number of
deviations and/or numerous insignificant discrepancies.

10.

Scientific Center
for Expert Evaluation
of Medicinal Products
Rules for Pharmaceutical Inspections
for compliance with the GCP Requirements
REPORT AND CAPA
In case of inspections associated with the drug product authorization or completed studies, it is necessary
to give a recommendation whether the quality of the submitted data allows their use while assessing the
application for the drug product authorization.
At the same time, the report should
cover the non-compliances that may directly affect the evaluation of the benefit-to-risk ratio of the drug
product, as well as those having no such effects, but which have been identified as systemic deficiencies
(for example, standard operating procedures and processes), i.e. related to the GCP systems.
When during the inspection any critical and/or major non-compliances have been identified, the
inspected object shall send a response to the Inspectorate within 20 working days from the date of the
report receipt attaching a corrective and preventive actions (CAPA) plan, a report on its fulfillment or data
testifying to elimination of the detected non-compliances (if applicable).

11.

Scientific Center
for Expert Evaluation
of Medicinal Products
Rules for Inspections for Compliance with
the EAEU GCP Requirements
Performing an extraordinary inspection
If the decision on initiation of an extraordinary pharmaceutical inspection is taken, the authorized body (expert
institution) of the Reference Member State shall send to the Applicant the decision (request) on required inspection
of the clinical study (indicating the subject to be inspected and the reasons for initiation of such inspection taking into
account the assessment of risks and with references to the acts of the Union authorities) not later than 5 days after
such decision.
After the receipt of the decision (request), the Applicant of the drug product authorization/marketing authorization
holder shall file an application for a EAEU GCP inspection to the Pharmaceutical Inspectorate of the Reference
Member State authorized to carry out the EAEU GCP inspections not later that in 15 working days.
In the event of a documented refusal of the Pharmaceutical Inspectorate of the Reference Member State to carry
out the EAEU GCP inspection, the Applicant shall be entitled to apply to the authorized body (institution) of other
Member State with a request for such inspection.
After the receipt of the application for the EAEU GCP inspection, within 20 working days
the Pharmaceutical Inspectorate shall agree on the inspection dates with the Applicant, include the inspection into
the plan of inspections,
and inform the authorized body of the scheduled
EAEU GCP inspection completion date.

12.

Scientific Center
for Expert Evaluation
of Medicinal Products
Rules for Inspections for Compliance with
the EAEU GCP Requirements
Performing an extraordinary inspection
The extraordinary pharmaceutical inspection should be performed within the period not exceeding
the period of the drug product expertise.
The drug product expertise
shall not be suspended in case of the taken decision on
the
pharmaceutical
inspection for
compliance
Union Good Clinical Practice.
initiation of
with the
At the same time, if the expert institution
of the Reference Member State does not receive the data of the inspection report before the preparation of the
expert report on the drug product evaluation, i.e. within 100 days from the expertise initiation, it shall send a request
to the Applicant for submission of the inspection results. Starting from the sending date of such request to the
Applicant, further expertise shall be suspended.
The Applicant shall be given not more than 180 working days not included into the expertise period to present the
response to the stated request.
When the Applicant does not submit the inspection results requested by the authorized body (expert institution)
within the established period, the expertise and authorization of the drug product shall be cancelled. The authorized
body (expert institution) shall notify the Applicant and the competent authorities (expert institutions) of the Member
States, if applicable, in a written form and/or via electronic means within 14 working days from the date of such
decision.

13.

Scientific Center
for Expert Evaluation
of Medicinal Products
Rules for Inspections for Compliance with
the EAEU GCP requirements
Performing a scheduled inspection
Scheduled EAEU GCP inspections with respect to a clinical study, including bioequivalence studies, shall be carried out
based on the decision of the reference authorized body according to the documents submitted by the Applicant
during the authorization, as well as the information taking into account the assessment of possible risks for the first
three years following the drug product authorization pursuant to paragraphs 36—39 of the Rules for Registration and
Expert Evaluation of Medicinal Products for Human Use approved by the Decision
of the Council of the EEC No. 78 dated November 3, 2016 or an inspection plan (if applicable).
The necessity of the scheduled inspection within 3 years after the drug product authorization shall be defined by the
authorized body of the Reference Member State of the Union as a post-marketing requirement according to the
provisions of Chapter VII.I of the Rules.
Initiation of the scheduled inspection after the drug product authorization by the Applicant shall be realized within
the period determined by the established requirements according to the expert report after the drug product
authorization, but not later than 3 years after the authorization.
The results of the scheduled inspection shall be submitted by the Applicant to the authorized body according to the
Rules for Registration and Expert Evaluation of Medicinal Products for Human Use approved by the Decision of the
Council of the EEC No. 78 dated November 3, 2016.
The received inspection report shall be considered by the authorized body of the Reference Member State while
revising the expert report on the drug product evaluation, as well as while establishing any additional measures or
restrictions associated with this drug product circulation.

14.

Scientific Center
for Expert Evaluation
of Medicinal Products
Rules for Inspections for Compliance with
the EAEU GCP requirements
TIMING AND REPORTS
In the event the authorized body (expert institution) has requested the extraordinary inspection within the
framework of the drug product authorization, the period of the GCP inspection shall not exceed 40 working days from
the date of application for the GCP inspection filed by the Applicant.
A leading inspector shall prepare a report in a duly established format not later than 20 days after the end of the
inspection and send it to the inspected subject.
When during the inspection any critical and/or major non-compliances have been identified, the inspected object
shall send a response to the Inspectorate within 20 working days from the date of the report receipt attaching a
corrective and preventive actions (CAPA) plan, a report on its fulfillment or data testifying to elimination of the
detected non-compliances (if applicable).
The inspection team shall assess the information contained in the response and prepare a final version of the report
within 15 working days.

15.

Scientific Center
for Expert Evaluation
of Medicinal Products
Grounds for GCP and GLP Inspections in the
Russian Federation
Decree of the Government of the Russian Federation No. 1255 dated July 14, 2022 "On amending some acts of the
Government of the Russian Federation related to implementation of the decisions of the Council of the Eurasian
Economic Commission within the sphere of circulation of medicinal products for human use"
A variation has been made to the List of Services that are obligatory and mandatory for rendering by the federal
executive bodies approved by the Decree of the Government of the Russian Federation No. 352 dated May 6, 2011
and Regulations on the Ministry of Health of the Russian Federation and the Federal Service for Surveillance in
Healthcare.
The Federal Service for Surveillance in Healthcare is empowered to:
Perform pre-marketing inspections of the pharmacovigilance system according to the Rules for
Good Pharmacovigilance Practice of the Eurasian Economic Union approved by the Decision of the Council of the
Eurasian Economic Commission No. 87 dated November 3, 2016 "On approval of the Rules of Good
Pharmacovigilance Practice of the Eurasian Economic Union".

16.

Scientific Center
for Expert Evaluation
of Medicinal Products
Grounds for GCP and GLP Inspections in the
Russian Federation
The Ministry of Health of the Russian Federation is empowered to:
arrange and/or perform the inspections (examinations) of the clinical studies with the medicinal products for human use
for compliance with the requirments of the Rules of Good Clinical Practice of the Eurasian
Economic Union approved by the Decision of the Council of the Eurasian Economic Commission No. 79 dated November 3, 2016
"On approval of the Rules of Good Clinical Practice of the Eurasian Economic Union";
arrange and/or perform the pharmaceutical inspections for compliance with the Rules of Good Clinical Practice of the
Eurasian Economic Union approved by the Decision of the Council of the Eurasian Economic Commission No. 79 dated
November 3, 2016
"On approval of the Rules of Good Clinical Practice of the Eurasian Economic Union" and with the Rules of Good Laboratory
Practice of the Eurasian Economic Union within the sphere of circulation of medicines approved by the Decision of the
Council of the Eurasian Economic Commission No. 81 dated November 3, 2016 "On approval of the Rules of Good
Laboratory Practice of the
Eurasian Economic Union within the sphere of circulation of medicines" during the period of the drug product authorization
according to the Rules for Registration and Expert Evaluation of Medicinal Products for Human Use
approved by the Decision of the Council of the Eurasian Economic Commission No. 78 dated November 3, 2016 "On the
Rules for Registration and Expert Evaluation of Medicinal Products for Human Use".

17.

Scientific Center
for Expert Evaluation
of Medicinal Products
Grounds for GCP and GLP Inspections in the
Russian Federation
The Ministry of Health of the Russian Federation has prepared a draft Order of the Ministry of Health of Russia:
"On approval of the method to determine the amount of payment for services related to inspections (examinations)
of clinical studies with medicinal products for human use for compliance with the requirements of the Rules of Good Clinical Practice
of the Eurasian Economic Union approved by the Decision of the Council
of the Eurasian Economic Commission No. 79 dated November 3, 2016 "On approval of the Rules of Good Clinical Practice of the
Eurasian Economic Union", method to determine the amount of payment for services related to pharmaceutical inspections for
compliance with the requirements of the Rules of Good Clinical Practice of the Eurasian Economic Union approved by the Decision
of the Council of the Eurasian Economic Commission No. 79 dated November 3, 2016 "On approval of the Rules for Good Clinical
Practice of the Eurasian Economic Union", and the Rules of Good Laboratory Practice of the Eurasian Economic Union within the
sphere of circulation of medicines approved by the Decision of the Council of the
Eurasian Economic Commission No. 81 dated November 3, 2016 "On approval of Good Laboratory Practice
of the Eurasian Economic Union within the sphere of circulation of medicines" during the drug product authorization period
according to the Rules for Registration and Expert Evaluation of Medicinal Products for Human Use approved by the Decision of the
Council of the Eurasian Economic Commission No. 78 dated November 3, 2016 "On the Rules for Registration and Expert Evaluation of
Medicinal Products for Human Use" and the limits of the stated
payments".
The Order provides for empowering the Federal State Budgetary Institution "Scientific Center
for Expert Evaluation of Medicinal Products" of the Ministry of Health of the Russian Federation to perform the abovementioned inspections.

18.

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Scientific Center
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