SPECIAL EDITION
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MINISTRY OF PUBLIC HEALTH
MINISTERIAL AGREEMENT No. 0075-2017
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EXPAND THE REGULATIONS FOR THE APPROVAL, DEVELOPMENT, SURVEILLANCE AND CONTROL OF CLINICAL TRIALS
2 - Friday, June 30, 2017 Special Edition No. 23 - Registration
Official
No. 0075-2017
THE MINISTER OF PUBLIC HEALTH
Considering:
That, the Constitution of the Republic of Ecuador mandates: “Art. 57.- Communes are recognized and guaranteed,
indigenous communities, peoples and nationalities, in accordance with the Constitution and with the pacts,
conventions, declarations and other international human rights instruments, the following rights
groups: (…)
12. Maintain, protect and develop collective knowledge; their sciences, technologies and knowledge
ancestral; genetic resources that contain biological diversity and agro-bio-diversity;
its medicines and traditional medicine practices, including the right to recover, promote
and protect ritual and sacred places, as well as plants, animals, minerals and ecosystems within their
territories; and knowledge of the resources and properties of fauna and flora. (…) ”;
That, the Constitution of the Republic of Ecuador in subparagraph d), numeral 3, of article 66, prohibits
the use of genetic material and scientific experimentation that threaten human rights;
That, article 350 of the Constitution of the Republic of Ecuador states that the Higher Education System
Its purpose is academic and professional training with a scientific and humanistic vision; the investigation
scientific and technological; innovation, promotion, development and dissemination of knowledge and
cultures; the construction of solutions for the country's problems, in relation to the objectives of the
development;
rectory functions in health; as well as the responsibility for the application, control and monitoring of compliance with
this law; and, the norms that it dictates for its full validity will be obligatory. ”;
That, the aforementioned Organic Health Law, in its article 6, orders:
“It is the responsibility of the Ministry of Public Health: (…)
32. Participate, in coordination with the competent national body, in the research and development of science
and health technology, safeguarding the validity of human rights, under bioethical principles; (…). ”;
That, every person, without discrimination for any reason, has in relation to health the right not to be subject to
tests, clinical, laboratory or research trials, without your prior written knowledge and consent,
nor be subjected to diagnostic tests or exams, except when expressly determined by law or in case
of emergency or urgency in which your life is in danger, as determined by article 7, literal l) of the Law
Organic Health;
That, the Organic Health Law, in article 207, prescribes that scientific research in health as well as
the use and development of biotechnology, will be oriented to priorities and needs na
Regional, subject to bioethical principles, with multi-cultural, rights and gender foundations, incorporated
l s traditional and alternative medicines;
Q e, as established in article 208 of the Ibid Law, scientific scientific research in
health will be regulated and controlled by the National Health Authority, in coordination with the agencies
competent, subject to bioethical rights and rights, prior
That, the aforementioned Constitution of the Republic of the United States provides, in article 361, that the State shall exercise the
Rectory of the National Health System through the National Health Authority, which will be responsible
to formulate the national health policy, and to regulate, regulate and control all activities related to
health, as well as the functioning of the entities of the sector;
That, the Constitution of the Republic of Ecuador, in its article 387, numeral 2, indicates that it is
State responsibility to promote the generation and production of knowledge, promote
scientific and technological research, and enhance ancestral knowledge, in order to contribute to the
realization of good living, to sumak kawsay;
That, the Universal Declaration on Bioethics and Human Rights approved by the General Conference of the
UNESCO in 2005, in its article 19, urges countries to create, promote and support committees of
independent, multidisciplinary and pluralistic ethics with a view to assessing ethical, legal,
relevant scientific and social, raised by research projects relating to human beings;
to provide advice on ethical problems in clinical contexts; and to evaluate the progress of the
science and technology;
That, the Organic Health Law provides: “Art. 4. The national health authority is the Ministry of
Public Health, entity to which the exercise of the
informed and in writing, respecting confidentiality;
That, the Code of Children and Adolescents, in the article
20 prescribes: “Right to life.- Children and adolescents have the right to life from their
conception. It is the obligation of the State, society and the family to ensure, by all means at their disposal, their
Survival and development Medical and genetic experiments and manipulations are prohibited from fertilization of
ovum until the birth of children and adolescents; and the use of any technique or practice that
endanger your life or affect your integrity or integral development. ”;
That, the Helsinki Declaration of the World Medical Association - Ethical Principles for
Medical Research in Human Beings, in its article 8, indicates that in medical research in beings
human, the rights of the person participating in the investigation must always have the primacy over all
other interests; and that for such research a prior evaluation and approval by a
independent ethics committee;
That, the International Ethical Guidelines for Biomedical Research in Human Beings, prepared by the Council of
International Medical Sciences Organizations (CIOMS), in collaboration with the World Organization of
Health, establishes among its articles that all proposals for research in humans
Official Registry - Special Edition Nº 23
they must be submitted to a scientific and ethical evaluation committee; and emphasize the importance of
individual informed consent in all biomedical research;
That, is the attribution and responsibility of the National Agency for Regulation, Control and Surveillance
Sanitaria- ARCSA, “approve clinical trials of medications, medical devices. Natural products for use
medicinal products and other products subject to registration and sanitary control based on regulations issued by the
Ministry of Public Health ”, as indicated in article 10, number 8, of the Decree
Executive No. 1290 published in the Supplement to Official Registry No. 788 of September 13, 2012;
That, by Executive Decree No. 1293 published in the Supplement of the Official Registry No. 934 of January 31
In 2017, the Constitutional President of the Republic of Ecuador appointed Dr. María Verónica Espinosa
Serrano as Minister of Public Health;
That, through Ministerial Agreement No. 00004889 of June 10, 2014, published in the Supplement
of Official Registry No. 279 of July 1, 2014, was issued
Friday, June 30, 2017 - 3
Art. 2.- Scope.- This Regulation applies at the national level for all natural or legal persons,
public or private, national or foreign, that carry out the activities provided for in article 1 of
This instrument
CHAPTER II
OF THE AUTHORIZATION FOR THE PERFORMANCE OF CLINICAL TRIALS
Art. 3.- The approval for the realization of the clinical trials object of this Regulation is the responsibility of
the National Agency for Regulation, Control and Health Surveillance - ARCSA, an instance to exercise
This attribution must strictly comply with the provisions of the Constitution of the Republic, regulations
international, the Organic Law of Health and other norms related to the subject.
The ARCSA will also be guided by the guidelines of the Helsinki Declaration of the
World Medical Association; of the Pan American Network for the Harmonization of Pharmaceutical Regulation (Network
PARF); International Ethical Guidelines for Biomedical Research
the Regulations for the approval and monitoring of
in Human Beings of the Council of
Organizations
Research Ethics Committees in Human Beings
Science Internationals
Medical (CIOMS); Y,
(CEISH) and of the Ethical Committees of Assistance for
Good Clinical Practices
(both of the Conference
Health (CEAS); and, International of
Harmonization like those of the Parf Network),
as well as the succinct declarations and revisions that
That, there are universal regulatory bodies related to the generation of safety conditions,
well-being, respect and dignity of human beings in the
update the referred documents; or others of which is equal to the Ecuadorian State
conducting scientific research, which is why it is necessary for Ecuador to have an instrument
Art. 4.- The conditions qu
clinical trials will be conducted under ensure respect for dignity
which based on ethical and scientific fundamentals
all
human
human rights, autonomy, consent
activities related to clinical trials in humans.
info mado, precautionary principle, personal integrity, privacy, confidentiality, equality, justice,
equity, non-discrimination, cultural diversity and welfare of
IN EXCERCISE
OF THE ATTRIBU
IONS
persons.
CONFERED PO
THE ARTICLES
151 Y
154, NUMBER 1,
OF THE CONSTITUTION
Art. 5.- In clinical trials, rights, security
OF THE REPUBLIC AND BY ARTICLE 17 and welfare of persons and of society,
prevail
OF THE STATUTE
OF THE LEGAL REGIME AND
on scientific and economic interests. Will be evaluated
ADMINISTRATIVE OF THE EXECUTIVE FUNCTION
Agree:
ISSUE THE REGULATIONS FOR THE APPROVAL, DEVELOPMENT, SURVEILLANCE AND CONTROL OF CLINICAL TRIALS
CHAPTER I
PURPOSE AND SCOPE
Art. 1.- Purpose.- The purpose of this Regulation is to regulate the approval, execution, monitoring,
surveillance and control of clinical trials in Ecuador, which are carried out with medications,
biological products and processed natural products for medicinal use.
For the purposes of this Regulation, the terms "trial" and "study" shall be used interchangeably.
mainly the therapeutic benefits and the risks and inconveniences for the test subject and
for public health.
Art. 6.- For the realization of a clinical trial in Ecuador it is required that every natural person or
legal, public, private, national or foreign that is sponsor of the realization of the essay, request the
prior approval to the National Agency for Regulation, Control and Health Surveillance - ARCSA.
Art. 7.- The ARCSA will verify and inspect compliance with legal, ethical and
methodologies for the development of the clinical trial in the country, before, during and after it
perform, as well as all aspects related to research technology.
Art. 8.- To authorize a clinical trial, ARCSA will request the sponsor of the study to
presentation, at least of the following documentation:
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a) A descriptive sheet of the clinical trial (Annex 1.)
b) The approval of the clinical trial protocol by a Research Ethics Committee in Beings
Humans (CEISH), officially recognized by the Ministry of Public Health.
c) In the cases that apply, the delegation of the sponsor for the development of the trial
clinical in the country to a single Contract Research Organization, through a contract or agreement legalized in
the one that states the obligations of each of the parties.
d) The research protocol.
e) The researcher's manual, as established in the Good Clinical Practices.
f) The corresponding informed consent form to which the
version of the research protocol presented, which has been previously approved by a Committee of
Research Ethics in Human Beings.
g) The pharmacological report on the marketing approval of the product under investigation
issued by the ARCSA, if it were the case of post-marketing studies.
h) The letters of declaration of institutional interest and
to show experience in the specialty being studied; and, development training of
clinical trials, Good Clinical Practices and related subjects.
m) The schedule of the study to be carried out in the country.
n) A certificate of the quality management system of the clinical laboratory or of the institution in the
that is the clinical laboratory that will participate in the study.
o) The detail of the product under investigation and other medicines to be used in the test,
according to the model in Annex 2 of these Regulations, as well as the label of the product under investigation
and packing.
p) Health risk assessment reports in the previous phases of the studies (Phase I, II and III), for
that the ARCSA establish the risk-benefit balance of the product under investigation.
q) Certification of Good Manufacturing Practices of the drug manufacturing plant
in research.
r) The batch certification of the investigational drug, with stability and expiration date.
s) The general budget of the trial, according to the model that
availability of the health establishment for the
It appears in Annex 3 of this
Regulation.
clinical trial, issued by the maximum
authority of the establishments that are proposed
t) Co ia del
contract concluded between the researcher
as clinical research centers.
i) The commitment letter signed by the researcher
Principals and the promoter.
u) In cases where clinical research centers
principal of
each center
clinical research
are located in health facilities of
participant in the clinical trial, in which it is indicated that he will participate as a researcher in the study, which has
been trained on the research protocol and therefore knows it and is in compliance with it, the
monetary value that you will receive for your services, as well as the determination of your responsibilities in the study.
j) The list of the clinical research center or centers, which includes the details of all researchers and their
work team by center, who would participate in the trial in the country, specifying the type of
health establishment, professional titles of each member and their role in the study.
k) Enrollment of the principal investigators of the study, in the database of the Ministry of
Public Health by the National Directorate of Health Intelligence, or who exercises their powers, as long as
the National Secretariat of Higher Education, Science, Technology and Research - SENESCYT develop this
tool and coordinate with the Ministry of Public Health the existence of a unique database of
researchers.
l) The resume of the principal investigator and his collaborators for each research center
clinic
the Comprehensive Public Health Network, a copy of the agreement between the health establishment and the
promoter.
v) The list of supplies necessary for the development of the clinical trial.
w) The data collection notebook.
x) The flowchart of handling adverse events and adverse reactions.
and) The notification form of suspicion of unexpected serious adverse reactions and / or serious adverse event of the
clinical trial
z) The sponsor's sworn commitment to deliver the final report of the essay to the ARCSA.
aa) Copy of the civil liability insurance policy issued by an established insurance company
in Ecuador, empowered for this purpose. The policy will cover the responsibilities of all those involved in the
research, as well as those of the clinical research center where the clinical trial is conducted. The
coverage should cover the execution of the clinical trial
Official Registry - Special Edition Nº 23
and it will be extended at least one (1) year after its completion, in order to cover the consequences that are demonstrated to be
derived from the clinical trial in question. After passing an essay, if it lasts more than one (1) year, the
promoter will present to the ARCSA a commitment to renew the policy, at least three (3) months of
anticipation of its expiration; and present the renewed policy once it is issued.
The civil liability policy must be subject to the provisions of the Monetary Organic Code and
Financial, Book III General Insurance Law, Commercial Code and other regulations in force on the subject; Y
It will contain at least the following: the title of the study, duration of the study, coverage of care
required, types of insured risks, covered clinical tests, limit value of coverage to the insured by
event and the amount of the policy, which will be determined according to the risk of the clinical investigation that appears in the
approved protocol.
Art. 9.- For the approval of the clinical trial, the ARCSA will request that all documents be presented in
Spanish language. Documents prepared in another language must be submitted with an official translation,
duly apostilled or legalized, as appropriate, in the country of origin. Additionally, the ARCSA
You may request some documents in your original language for translation review or for the purposes that
The Agency deems pertinent.
Friday, June 30, 2017 - 5
of the five (5) days after receipt of the documentation, so that within thirty (30)
days counted from the receipt of the notification, correct the observations made. Of not existing
Answer will be automatically terminated.
Art. 13.- All modifications presented within a clinical trial must be authorized.
by the ARCSA. Those amendments related to the Protocol, the Investigator Manual and the Consent
Informed, they must be previously approved by the Research Ethics Committee on Human Beings that approved the
research protocol.
Art. 14.- Requests for modifications to authorized clinical trials will receive a response.
favorable or unfavorable of the ARCSA in a term of forty-five (45) days, counted from
the presentation of the procedure. In exceptional cases, if the sponsor justifies with documentation of
adequate support that the clinical trial modification will imply a benefit for the patient, the time of
ARCSA analysis for said modification will be a maximum of fifteen (5) days.
Art. 15.- The ARCSA does not increase amendments that modify the product under investigation, the
treatment time, nor the objectives of the study. As long as a change or requested is not approved, it
it cannot be implemented and the study must follow its execution
join the conditions with which he was authorized, always
Art. 10.- Once the ARCSA verifies that the request
and when it does not imply damage to the health or life of the subjects
and the documentation presented c mplen with all l s
In est gación.
requirements established in this Regulation or, will prepare the corresponding technical report, regardless of
whether or not it is favorable to the approval of the proposed study. This report will be sent by the Agency to the Technical Committee
Clinical Research Advisor, an instance created in this instrument, to support specifically
and specialized in the evaluation process of a clinical trial.
Art. 11.- The ARCSA will have sixty (60) term days from the date the procedure was admitted,
for the issuance of the evaluation report of the research protocol and will communicate to the applicants, through
its Executive Director, the approval, non-approval or request for further information regarding the clinical trial
In analysis. Only in case of phase IV clinical trials, the report will be issued in forty-five (45) days
term, counted from the date it was admitted for processing.
Nonprofit clinical trials and those sponsored by state entities, or by the
alliance between a public institution and a private institution will have priority attention times,
this is forty five
(45) days after receiving all the documentation requested by the ARCSA, for phase I, phase II and phase tests
III.
Art. 12.- In the event that the documentation presented does not meet the requirements for approval
of the clinical trial, the ARCSA will notify the applicant within
Art. 16.- To authorize an amendment to the clinical documents, the ARCSA will analyze at least the following:
a) The protocol, the investigator's manual and the informed consent that include and
highlight the changes, in relation to the approved version.
b) The justification and technical argumentation of the changes made.
c) The approval of the changes by the Research Ethics Committee in Human Beings that approved the
clinical trial protocol, where applicable.
Art. 17.- If the ARCSA needs to clarify information or complete documentation in a process of modification of
a clinical trial, the applicant must respond within thirty (30) days, counted from
Received the notification in which you are required to submit the documentation. In case of not getting an answer
The process will be terminated automatically. If a proposed change was not duly justified, and
ARCSA issued a negative response on two (2) occasions, no further modification requests may be made
About that change.
Art. 18.- The approval of a clinical trial will be valid for the period that lasts the same, unless the ARCSA
Justifiably revoke such approval.
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Art. 19.- The ARCSA may carry out inspections of the establishments or review the documentation.
related to a clinical trial in execution, when there is any request for modification to it, which
It could cause the response to that request to be conditional on the results of the inspection.
Art. 20.- In order to protect the rights and well-being of the subjects under investigation, the ARCSA will carry out
inspections to any instance related to the execution of an approved clinical trial in the country, the
times that it considers pertinent, before, during or after the execution of the same, with or without notice
prior, according to the type of inspection performed; and, in order to verify compliance with
the Standards of Good Manufacturing Practices, Good Clinical Practices and Good Practices
Laboratory practices.
Art. 21.- Inspections may be carried out at the clinical research center, at the place of manufacture of the
product under investigation, to the facilities of the sponsor, to the facilities of the Organization of
Contract Research or the Research Ethics Committee on Human Beings that approved the protocol. The
ARCSA will define the particular conditions under which inspections will be carried out.
Art. 22.- The inspectors of the ARCSA, in forty-five (45) days after the completion of the
inspection, submit a report to the sponsor of the clinical trial and the inspected place on the
Conformities or disagreements found in relation to Good Clinical Practices (PCB), which determines whether or not
The continuity of the clinical study.
Art. 23.- In case of non-compliance of the BPCs that attempt against the safety and well-being of
participant in the investigation, the corresponding clinical research center, or if applicable, the
clinical study, will be suspended. The sponsor will establish a plan of measures to be taken to correct the
nonconformities, which will be sent through a written report to the ARCSA, within a term of forty-five
(45) days, as of the receipt of the communication of non-compliance of said Regulatory Agency.
Art. 24.- If after an inspection it is verified that there are no circumstances that threaten the
Research participant safety, the study will continue its course. However, in a term of forty and
five (45) days from the receipt of the ARCSA report, the sponsor must correct the
observations.
Art. 25.- After the inspection, if the ARCSA finds that there are circumstances that put at risk
The integrity of the participant will apply corrective measures, including:
a) Provide for the separation of researchers from the execution of the clinical trial, if they do not comply with the PCBs in
the study.
b) Suspend a clinical research center as executor of a clinical trial, if it does not comply
with
Good Clinical Practices and attentive to the safety of research participants.
c) Demand training in BPC from professionals and staff participating in the trials, when considered
necessary.
d) Establish deadlines for compliance with the plans to solve the nonconformities detected by the
ARCSA during the inspections you perform.
e) Temporarily or definitively suspend the start / execution of a clinical trial, according to
corresponding, due to the lack of guarantees for the security of the subject under investigation.
f) Revoke the approval of a clinical trial at any stage, if there is no security for
Research participants
g) Others deemed necessary.
Art. 26.- The ARCSA will suspend or cancel a clinical trial that is being carried out in the country and will revoke the
approval granted, depending on the severity of the case, for the following causes:
a) Prevent by any person related to the clinical trial, the actions of the inspectors of the
ARCSA
b) Use a product under investigation in humans for approval of the clinical trial protocol
by the ARCSA.
c) R alizar the clinical trial without adjusting to the content of the protocols on the basis of which
granted approval or modifications to the research protocol authorized for the trial
clinical or make amendments to it, without prior authorization from the ARCSA.
d) Failure to comply with the obligation to timely inform the ARCSA and the Research Ethics Committee in Beings
Corresponding human, serious adverse events and unexpected serious adverse reactions of the product in
investigation.
e) Disseminate information to identify the subject under investigation, except when said information has been
requested by the National Health Authority or by judicial means to investigate a human rights violation.
f) Carry out promotion or advertising of the product in the investigation phase.
g) Breach of the BPC, which puts the security of the subject under investigation at risk.
h) Perform the clinical trial without the informed consent of the subject in
investigation or, where appropriate, of the person empowered to grant it.
Official Registry - Special Edition Nº 23
i) Sign the informed consent with the participants in the investigation, after
Started the execution of the clinical trial.
j) Adulterate or falsify the information required in this Regulation or related data
With the essay.
k) Not guarantee the protection, benefits, rights and security of the subjects participating in the
clinical research.
l) Failure to comply with the provisions established in this Regulation.
Art. 27.- In the event that the ARCSA detects and verifies the conduct and conduct of a clinical trial without
the corresponding approval will provide both the cancellation of the study and the execution of measures that protect
the subjects under investigation, in addition to applying the sanctions to which it may take place.
CHAPTER III
Friday, June 30, 2017 - 7
both the mother and the newborn of presenting subsequent damages produced during pregnancy or
would have caused the newborn due to the execution of the investigation.
Art. 32.- Persons with disabilities may be subject to investigation, provided that the Committee on
Research Ethics in Human Beings that evaluate the clinical trial, establish compliance with the
following conditions:
a) That the research responds to the health needs and priorities of the population with disabilities and
cannot be done in other groups;
b) That the research is designed to minimize the risks of the condition you suffer and that the benefits are
exceeding the risks inherent in the study; Y,
c) That in cases of mental disability, in the process of obtaining informed consent,
people have received information from the clinical study adapted to their ability to understand, guaranteeing their
participation to the extent of its possibilities and
OF THE SUBJECTS IN CLINICAL RESEARCH
Art. 28.- The persons who investigate
That the informed consent is legal representative.
granted by his
voluntarily participate in a clinical trial, who Art. 33.- In clinical studies
made in villages
must be previously informed about it,
and nationality
d l Ecuador, in addition to consent
which must be recorded in an individual informed consent document, must be
make an enquiry
informed. These people may be healthy or suffer
common taria
prior, which should be favorable to the
diseases. The research product will be supplied to the research subjects, or the product used
as a control, once your informed consent or that of your legal representative has been obtained, in the
If applicable.
conduct of the study; and obtain additional approval from the community authorities involved in the case.
This approval must be recorded in a document duly signed by these authorities, whose copy will be attached to
the approval request procedures for the realization of
clinical trial No clinical trials may be conducted in
Art. 29.- Clinical trials carried out in older adults, people with disabilities, private persons d
freedom and those who suffer from catastrophic diseases and high complexity, because they are considered groups
of priority or vulnerable attention, should be of specific interest and limited to those whose
nature can only be done in this population group.
Art. 30.- In women of reproductive age who have agreed to participate in a clinical study, prior to
At the beginning of the confirmation will be made that the participant is not pregnant.
Access to and use of an effective contraceptive method during development should be ensured
of the clinical trial, which will be provided at no cost by the study sponsor, during the entire time of your
participation in it, including subjects in male research.
Art. 31.- In case of pregnancy during the clinical trial, the woman will be
excluded as subject in investigation; In addition, the study sponsor will monitor the
patient and newborn until he has reached at least two (2) years of age. The sponsor
must compensate
people in voluntary isolation (not contacted).
In these clinical studies, sponsors and researchers must develop forms and
culturally appropriate means with anthropologists, sociologists and translators, to communicate to
Participants in the investigation, all the necessary information regarding the trial and fulfill the
standard required in the informed consent process. In addition, in the research protocol
the procedure they plan to use to communicate the information to should be described and justified
the subjects under investigation.
CHAPTER IV
OF INFORMED CONSENT IN CLINICAL RESEARCH
Art. 34.- Informed consent is the communication process that ends in a dated document
and signed by the principal investigator and the participant of a clinical study or its legal representative,
when appropriate, who should be able to express their opinion freely and without coercion. The
Participant or his legal representative, through informed consent, will express their willingness to be part of the
I study with full
8 - Friday June 30, 2017 Special Edition No. 23 - Registration
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knowledge of its purpose, the procedures, benefits and risks to which it will be submitted, the
possible treatment alternatives and the grounds for exclusion from the investigation, being able to revoke
Your consent at any time.
The withdrawal of the informed consent of the participant will be accepted at any time, ensuring that
their disengagement from the study does not affect or endanger the health of the subject under investigation.
If a conflict of opinion arises between the subject under investigation and his legal representative, regarding his
Participation in the clinical trial, at any time during or before the study, will exclude
subject provided that such exclusion does not jeopardize your health.
In any case of exclusion of a participant from a clinical trial, the investigator and the
Sponsor will guarantee the monitoring of the subject for at least two (2) years.
Art. 35.- The principal investigator or a delegate thereof who is part of the research team,
inform in writing and verbally the subject under investigation or his legal representative, when
appropriate, regarding the risks, discomforts and possible benefits of the study in which it is raised
your participation, using simple, clear and warm terms.
Art. 36.- In the case of illiterate persons, their fingerprint will be registered in the document of
consent
d) Selection criteria, exclusion and number of subjects under investigation.
e) Duration, side effects, direct benefits of participation in the clinical trial, the expected risks
for the subject, including possible adverse reactions, risks to the health and well-being of the couple or
spouse. Possible benefits for the community or society.
f) Alternative treatments that could be beneficial for the subject under investigation.
g) Point out that the participation of the subject in the clinical trial is voluntary and that their decision to participate
or not the study will not influence in any way the health care process that the subject requires in
investigation.
h) Information about the product or products under investigation.
i) Causes that could cause the suspension of the subject's participation in the study.
j) Point out the potential risks in case of pregnancy and the importance of using
an effective contraceptive method, if the subjects that are part of the study are of age
reproductive
k) The responsibilities of the research team.
informed and will sign as witnesses two people who e
l) L li ertad que the subject in investigation of
study participant choose, as long as they have no conflict of interest with the research that was developed
It will be linked and not linked in any way with the research team.
Art. 37.- The consent document informs or any other informative material, that in relation
to the study be provided to the subjects under investigation must be previously reviewed and approved by a
Committee of Research Ethics in Human Beings, recognized by the Ministry of Public Health.
Art. 38.- The informed consent document may not contain any expression that gives rise to
that the subject who consents to it, exempts the sponsor, researcher or his or her responsibility
representatives before any responsibility for negligence, or for risks derived from the clinical trial.
Art. 39.- The informed consent document for clinical research must contain the following (Annex 4):
a) Clear information that the participant will be part of a study that may or may not have
positive results.
b) The justification and objective of the clinical trial.
c) All procedures to be performed, clearly specifying the aspects that
Be experimental and your purpose.
revoke your mind at any time and stop participating in the study, for which the researcher
it must ensure the proper process for the exclusion of the participant while preserving their safety, and without affecting their
access to the medical care you require.
m) The measures to be taken to guarantee the privacy and confidentiality of the
information of the subjects under investigation.
n) If biological samples are required as part of the research protocol, it must be specified
that they will serve exclusively for the essay for which the subject gives his consent.
Additional express consent will be required, in the case of consulting the participant about their consent
for the future use of these samples, for other investigations defined as priorities for the Authority
National Health. This last document should indicate how long the samples will be stored, where and
under what custodian This new investigation must comply with all the requirements to carry out a
health research, and obtain the approval of a CEISH and the National Health Authority prior to its
execution.
o) The obligation of the investigator to inform the subject under investigation in due course and timely
the product under investigation, although the information could affect your decision to continue participating in the
clinical trial
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p) The free delivery of the product under investigation, the time during which the
same, the complementary exams that are required for research purposes and the
standardized procedure, which according to the study protocol, research subjects should receive.
q) The participant's right to obtain additional information, through the researcher, on
any aspect of the study, if required.
r) The availability of medical treatment and the compensation legally entitled to
subject under investigation, according to the insurance policy of the study contracted by the promoter, to cover possible damages
caused directly or indirectly by the product under investigation.
s) The contact information of the principal investigator and the clinical research center to which the
subject under investigation, if there were any health effects related to the clinical study.
t) The obligation of the investigator to inform, in verbal and written form, the subjects in
investigation or its legal representative, when applicable, any new information or changes
in the study protocol that could affect the participant's safety or his decision to continue in
the study. In these cases the need to obtain a new consent will be evaluated.
u) The obligation to communicate the results of the investigation to the subjects under investigation.
v) Data on the Research Ethics Committee in Human Beings that approved the protocol and the possibility
to contact the same Committee in case of doubts regarding your right as a participant in the study.
Friday, June 30, 2017 - 9
CHAPTER V
OF THE RESEARCH PRODUCTS
Art. 41.- For the purposes of applying this Regulation, the product shall be understood as
research, for phase I, II and III studies, drugs in general, biological products and products
Natural processed medicinal products, that is, a pharmaceutical form of an active ingredient or placebo
which is being tested or used as a reference in a clinical study. For phase IV studies, it will be understood as
product under investigation to those indicated above and that have a sanitary registration in Ecuador;
when they are used or conditioned in a therapeutic indication or in a manner other than those authorized in the country; when
used in combination with other medicines than those authorized; or, in cases where
conduct post-marketing studies.
Art. 42.- The manufacture or import of the product under investigation, for use in a test
clinical, will be authorized by the ARCSA and will be subject to the standards of Good Manufacturing Practices and other standards that
This Agency determines for this purpose.
Art. 43.- For the manufacture or delivery of a product under investigation, the sponsor shall
request the authorization of importation from the ARCSA, specifying at least the type and characteristics
Product statistics, place of manufacture, certificate of quality of the lot to be imported, labeling,
traceability and transport of the same and must attach the requirements established in the instructions that the
ARCSA issues for the purpose.
Art. 44.- The sponsor shall submit to the ARCSA the certifications of the product under investigation issued by
the department of quality of the pharmaceutical company do de said product is being produced, so
such as batch releases with their stability and the extent of
w) Report that a
once finished
the investigation,
Stability, if applicable.
After data analysis, the promoter will deliver the product under investigation for free in the
following cases: if its effectiveness is demonstrated; and, when its suspension jeopardizes the safety of the
subject under investigation and there is no therapeutic option that can replace the study treatment
in the market and until the product is marketed in the country.
Art. 40.- In cases where the use of placebo is authorized in a clinical study, prior to obtaining the
informed consent of the participants, they will be informed with sufficient time and clearly in what
This process consists.
The use of placebo should be considered in cases where there is no therapy, intervention,
medication or procedure of proven efficacy for the problem investigated; and in others it must be analyzed
on a case-by-case basis by the CEISH and by the ARCSA, in order to minimize risks and not affect the safety of
subjects under investigation, ensuring that they do not run additional risks, serious adverse effects or damages
irreversible as a result of not receiving the best proven intervention.
Art. 45.- In the event that the product under investigation is manufactured in the country, the ARCSA will carry out inspections.
to verify the manufacturing process.
Art. 46.- The laboratory manufacturing the product under investigation must comply with the Standards of
Good Manufacturing Practices established by national regulations for the elaboration of a product
pharmacological, presenting the different quality and stability certifications in the product file
of the drug.
The product under investigation must be properly labeled on the primary container with ink
indelible in Spanish language, indicating at least the data that identify the sponsor, to the clinical trial
and to the product under investigation and its expiration date, protocol code, product code,
lot number, number of units and dosage form, route of administration, storage conditions,
conservation and use thereof. Additionally, the labeling must specify the phrases “Prohibited its
sale ”and“ product for exclusive research use ”. In the case of primary packaging
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that because of its space they do not allow to establish this information, it will be printed in a secondary container.
Art. 47.- In the review of the clinical trial, the ARCSA will analyze how the management of the
product under investigation, according to the Standards of Good Manufacturing Practices and studying, between
Other points, control of records, packaging, labeling and coding, procedure for
dispensing, storage and location thereof.
Art. 48.- Surplus and / or expired research products at the conclusion or suspension of the trial
clinical, should be destroyed by the sponsor or his delegate, according to the procedure established in the
corresponding regulations.
Leftover reagents not used in the investigation that are in good condition may be
donated, in accordance with current regulations.
Art. 49.- It may be exempted from the destruction referred to in the previous article to the products in
investigation, prior authorization of the ARCSA, in the following cases:
a) When the product is not expired and can be used for exceptional cases in patients whose
Life is at risk.
Art. 52.- The sponsor will keep a detailed record of all adverse events that the investigator will
notify. In the event of an unexpected serious adverse reaction or a serious adverse event,
the sponsor or the Contract Research Organization contracted, must notify the ARCSA, in both
(2) following days of known, by any means of communication, using the format defined for this purpose
(Annex 5)
Art. 53- After the notification of a serious adverse event or a suspicion of an unexpected serious adverse reaction, in the
within seven (7) days as of the fact known, the investigator must send a partial report to the
ARCSA and within fifteen (15) days, will send the corresponding full report.
Art. 54.- From the beginning of the clinical study, the sponsor will present annually to the ARCSA,
During the study, a report on the safety of the medicines used in their trials
clinical, which also includes each medication in unregistered research and the placebo, if this is
used.
Art. 55.- The ARCSA will maintain a pharmacovigilance system to monitor the
reports of serious adverse events and about unexpected serious adverse reactions. A clinical assistant can
be suspended by the ARCSA justifiably, after the analysis of the
b) When delivered in donation, by means of an agreement
number, graveda
and frequency
of adverse events, the
between the sponsor and the beneficiary institution of the
type of study and population of
test, and inspection
donation, only e
the cases in which the product
corresponding, in order to precautionary the security of
have a sanitary record and the purpose of the gift
the subject
del es udio, d
compliance with regulations
be your employment, according to the conditions of us in the sanitary registry.
CHAPTER VI
approves
that for the effect or issue the ARCSA.
CHAPTER VII
ON THE USE OF MEDICINES IN
OF THE NOTIFICATION OF E
ADVERSE BETWEEN
CLINICAL RESEARCH
AND REACTIONS ADVE SAS
Art. 50.- The principal investigator must notify the ARCSA, the sponsor or the Organization of
Contract Research and the corresponding Research Ethics Committee in Human Beings, all
serious adverse events and all suspicions of unexpected serious adverse reactions that occur during
the clinical study, in a period not exceeding twenty-four (24) hours after the event was known, as well
such as abnormal laboratory results that the protocol considers determinants and that may influence the
safety assessment, within the periods specified in said protocol. It is also the obligation of
Principal investigator send to the sponsor or the Contract Research Organization, to the ARCSA and
to the corresponding Research Ethics Committee in Human Beings, a follow-up report and
Causality assessment on suspicions of unexpected serious adverse reactions occurred.
Art. 51.- In the case of a relevant safety problem in the development of the clinical trial, the
Principal investigator is obliged to immediately notify the acquaintance, the ARCSA and the sponsor.
Art. 56.- For the ARCSA to authorize the use of an investigational drug, which could be understood as
extended use of this medicine, to treat patients in conditions in which their lives are in danger,
will consider the following:
a) Clinical report in which the attending physician justifies the use of the medicine, determining
that there is no therapeutic alternative available for the patient's disease and that the risk for
person is not older than the one faced by the disease he suffers.
b) The informed consent of the patient or his legal representative, when applicable.
c) That the producer of the medicine agrees with the free endowment of the drug, after the evaluation
Case clinic and consultation of the attending physician
Art. 57.- The doctor responsible for applying the medication under the conditions of this Chapter shall notify the
ARCSA the results of it.
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Art. 58.- The use in exceptional conditions of a drug under investigation, to treat
patients in conditions in which their lives are in danger, it is a process that does not correspond to a clinical trial of
investigational medications, and will be performed when a doctor, under your responsibility,
justify with a clinical report the use of the medicine because it considers its
use. The ARCSA must authorize the use of any investigational medication under exceptional conditions.
CHAPTER VIII
OF THE REGISTRATION AND PUBLICATION BASE OF CLINICAL TRIALS
Art. 59.- The ARCSA will create and maintain the National Registry of Clinical Trials, observing the requirements of the
Primary Registry of the World Health Organization. This record will be a publicly accessible database. The
Agency will provide access to this registry and additional information that the Ministry of Public Health requires
for the purpose of monitoring and control of the investigation.
Art. 60.- In the case of publication of results of a clinical trial developed in Ecuador in
national or international scientific journals, the researcher will send a mandatory
copy of said publication to the ARCSA and the Ministry of Public Health. Such publications in any case
will contain identification data of the study subjects.
Friday, June 30, 2017 - 11
Art. 63.- CEISH members must prove knowledge and experience in relation to ethical aspects,
methodological and legal clinical research, good clinical practices and clinical practice
welfare. They must excuse their participation in the evaluation of research projects in which they could have
interest conflict.
Art. 64.- The CEISH shall be governed by conventions, declarations, instruments and norms.
internationals related to biomedical and bioethical research, due to sanitary regulations
specific current and the regulations issued by the National Health Authority.
SPONSOR CHAPTER X
Art. 65.- The sponsor is the individual, company, institution or organization, including
academics, with legal representation in the country, responsible for financing, administration,
initiation, development, monitoring and closure of a clinical trial.
Art. 66.- In cases in which the insurance policy does not cover all damages, it will be the sponsor who solvent
the expenses for the damage that the subjects under investigation have on their health. In addition, the sponsor will be
responsible for the economic damages arising as a result of the clinical trial.
Art. 67 - If the sponsor is an individual who investigates
CHAPTER IX ba or with time with the academy, this will be the one that
hire
the insurance policy for the risks arising from the
OF THE RESEARCH ETHICS COMMITTEES IN HUMAN BEINGS
research qu
perform.
Art. 61.-
The
Committees of
Ethics of
Research on
Art. 6 .- All sponsors, without prejudice to their responsibility, may delegate a part or the
totality of
Human Beings, CEISH, are organs linked to a
its functions to a single Research Organization by
public or private institution, responsible for approving
Contract registered in the ARCSA.
the investigations involving human beings
or that use biological samples. Any clinical trial protocol carried out in the country, before
If it begins its execution, it must first be approved by a Research Ethics Committee on Human Beings and
then it will be submitted to the approval of the ARCSA.
Art. 62.- Within their functions, the CEISH will carry out the ethical, methodological and legal evaluation
of clinical research in order to ensure the protection of rights, security and
welfare of the subjects under investigation. The CEISH must evaluate the clinical research protocol and
Other study documents such as informed consent, research product manual, manual
of the researcher and ensure the follow-up of the studies approved during its development, through the
Implementation of monitoring mechanisms according to the inherent risk of clinical research.
The ethical evaluation carried out by the CEISH of the clinical trial protocols should be oriented, between
others, for the principles of transparency and impartiality and must be expressed in a report justifying the
evaluation carried out
Art. 69.- If the sponsor does not have its headquarters in Ecuador, it must necessarily have a representative
Legal domiciled in the country, which must be a Contract Research Organization registered in the
ARCSA The Contract Research Organization must additionally fulfill the functions that are
delegates by the sponsor in the contract signed for this purpose.
Art. 70.- The sponsor must guarantee the confidentiality of the data obtained from the subjects under investigation and
the protection and security of the participants in it, through the implementation of a system of
Safety monitoring and reports of adverse reactions that are disseminated worldwide.
Art. 71.- In addition to the insurance policy that each clinical trial must have, the sponsor
guarantee the provision of free medical care, until the resolution of health problems that may arise
appear in the subjects under investigation, if these problems arise as a result of their
Participation in the study.
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Art. 72.- The sponsor of a clinical trial will be responsible for guaranteeing the
implementation of a quality assurance and control system, through operational procedures
standard, to ensure that studies are carried out in compliance with Good Clinical Practices. These
Procedures must be documented.
Art. 73.- The sponsor will verify that all the documentation corresponding to the essay
clinic is properly detailed, ensuring that the data generated is correctly
communicated to the ARCSA, in the corresponding cases or when required by the Agency. Shall
guarantee access to all documentation requested by ARCSA in relation to clinical trials under
your responsibility
Art. 74.- The sponsor's functions in relation to a clinical trial, in addition to those described above, are
the following:
a) Select and hire qualified researchers for their training, training and / or experience
to participate in a clinical trial, as well as select clinical research centers
that have all the necessary resources for the clinical trial to be developed, following the
Good Clinical Practices and guaranteeing the safety of the subject under investigation.
i) Timely inform the participants of the trial, the researchers, the Committee of
Research Ethics in Human Beings and ARCSA on new findings and updated information regarding the
product or products under investigation.
j) Notify ARCSA of suspected serious adverse reactions or events
serious adverse effects that may affect the benefit-risk ratio of the clinical trial, taking urgent measures to
security to protect test subjects.
k) Provide free of charge to the study participants the product under investigation and the
auxiliary medications, and provide coverage for the complementary exams that are required during the
clinical trial development.
l) Designate a national monitor that will monitor the development of the clinical trial and have a
appropriate monitoring system.
m) Send timely monitoring reports to the clinical trial to the ARCSA.
n) Submit a progress report to ARCSA at least once a year and when required by said Agency
on and unfolding the clinical trial, as well as
b) Verify that the investigated
principal has obtained the
the final report of it.
Approval of the protocol for the development of the clinical trial by a Research Ethics Committee in
Human Beings approved by the Ministry of Public Health.
c) Request ARCSA approval for the start and development of the clinical trial, attaching the requirements
established for this purpose. In the event that the sponsor is a foreigner, the request will be made
the Contract Investigation Organization that legally represents you in Ecuador.
d) Verify that all documentation and procedures comply with the requirements of Good
Clinical Practices and regulations related to the subject.
e) Contract an insurance policy in favor of the subjects under investigation and deliver the
corresponding financial compensation, if any damage is demonstrated and its causal relationship with
The product under investigation.
f) Provide the researcher with the “Investigator Manual”.
g) Ensure strict compliance with the protocol through the clinical study monitoring.
h) Record, process, manage and keep the clinical trial information in order to communicate, interpret and
accurately verify the results of the investigation, ensuring the confidentiality of medical records and
the personal data of the test subjects.
o) Ensure that the products under investigation have been developed in compliance with the Good Practices Standards of Man
fa tur and the regulations established by the ARC A, and that are provided with a label that
Identify as “Prohibited its sale” and “product for exclusive use in research”.
p) Keep a main file of the clinical trial with all the documentation related to its realization.
This file will be kept and will be available to the ARCSA and the Ministry of Public Health when
request, during the following seven (7) years after the end of the investigation in the country.
Art. 75.- Once the investigation is finished, in the cases in which the effectiveness and
medication safety, after analysis of study data, the sponsor will be responsible for
Provide the research product free of charge to the research subjects, when the
interruption of life-threatening treatment or seriously affect the patient's condition, or there is no
another therapeutic option marketed in the country that can replace the product under study.
Art. 76.- The sponsor of the clinical trial will not offer any incentive or economic stimulus to the
subject under investigation who suffers from any disease, or his legal representative. When applicable,
will compensate the subject under investigation with the expenses inherent in transportation, accommodation, food and loss
of productivity derived from their participation in the study. These expenses must be
considered in the budget of the
Official Registry - Special Edition Nº 23
investigation and explicitly indicated in the informed consent document. The remuneration must have a
reasonable amount, at the discretion of the Research Ethics Committee on Human Beings and the ARCSA, so that
does not influence the informed consent of the subject under investigation.
Art. 77.- Healthy volunteers participating in studies may receive incentives from the sponsor
clinical. These incentives must be detailed in the informed consent document. A
Healthy volunteer may not be recruited, or participate repeatedly in the development of clinical trials.
CHAPTER XI
OF CONTRACT RESEARCH ORGANIZATIONS
Art. 78.- A Contract Research Organization is a public or private company,
national or foreign, legally domiciled in the country, to which the sponsor officially transfers
in writing some or all of its functions and / or obligations related to a research study
by contract signed by both parties; however, the final responsibility for the execution of the protocol
of research, of the results and of the clinical trial, in its entirety, is of the sponsor.
Art. 79.- Contract Research Organizations
Friday, June 30, 2017 - 13
Art. 82.- Contract Research Organizations must implement a process of assurance and control of
quality, documented in standard operating procedures. These procedures must be in writing,
before the start of a clinical trial.
Art. 83.- The sponsor of the clinical trial must specify through a contract or agreement
legalized, the activity and function related to the study that are delegated to an Organization of
Contract Research. Investigation procedures that are not specifically transferred to
The Contract Research Organization must be performed by the sponsor.
Art. 84.- Among the functions of the Research Organizations by Contract for the
The development of a clinical trial, other than those delegated by the sponsor, may be carried out
following:
a) Select and evaluate research centers in clinical trials and researchers, to
Develop the clinical trial.
b) Ensure, through monitoring visits, that clinical trials are carried out according to
ethical standards and methodology established in Good Clinical Practices, ensuring compliance with the
Authenticated protocol.
they must develop actions in the field of health and
c) An liza
the data obtained during the process of
have technical personnel trained in Good Clinical Practices or with experience to carry out the functions
to be legally delegated by the sponsor for the development of clinical trials.
research, generating partial and final results of the project.
d) Forward to ARCSA and the Research Ethics Committee in Human Beings the updates
of the
Art. 80.-
The
Research Organizations by
Researcher's Manual, immediately produced
Contract, to start and develop their activities, must be registered in the National Registry of
Contract Research Organizations in charge of ARCSA and for this purpose they will present:
a) Registration request addressed to the ARCSA.
b) Copy of the constitution document of the Contract Research Organization.
c) Structural organization chart.
d) Standard operating procedures.
e) List of personnel and specific functions assigned to each one.
f) Updated resumes of the organization's officers.
Art. 81.- Contract Research Organizations must have researchers duly registered in the
database of the Ministry of Public Health, until the Ministry of Higher Education, Science, Technology and
Research - SENESCYT develop the tool for such registration.
these updates.
CHAPTER XII OF THE MONITOR
Art. 85.- Monitor is the health professional with experience in biomedical or clinical research,
designated by the sponsor or by the Contract Research Organization to follow up
direct from the execution of the trial, who acts as a link between the sponsor and the researcher
principal. Monitors must have an academic degree related to health and / or biomedical sciences, accredit
experience to monitor a clinical trial and have training certificates in Good Clinical Practices and
in Ethics of Clinical Research.
Art. 86.- The responsibilities of the monitor in relation to clinical trials are the following:
a) Verify that the clinical trial being carried out is authorized by the ARCSA.
b) Verify the protection, exercise of the rights and well-being of the subjects under investigation.
14 - Friday June 30, 2017 Special Edition No. 23 - Registration
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c) Verify that the research team is correctly informed and trained
on the content of the protocol and the responsibility of the researchers in the clinical trial.
d) Verify that the research team and the health establishment where the trial is carried out
clinical, meet the requirements for the development of the research, as well as the functions
specific assigned to each one.
e) Verify the process and availability of informed consents of all
subjects involved in the clinical trial, before inclusion in the study.
f) Verify, according to the Good Cynical Practices, the update of the documents for the
conduct of a clinical trial, if they are complete, legible and consistent with the information
contained in the data collection notebooks and with the investigation.
g) Verify the implementation of a system that guarantees the confidentiality of the information of the subjects in
investigation.
h) Maintain permanent contact with the research team of each clinical research center.
q) Document the monitoring visits made to clinical research centers, as well as
issue the respective report for the knowledge of the sponsor or the Research Organization by
Contract, as applicable.
CHAPTER XIII
OF THE CLINICAL RESEARCH CENTERS
Art. 87.- The clinical research centers are units located within a health facility, legally
constituted in the country, where clinical trials are developed, which must comply with the
infrastructure, human talent and management requirements established by the ARCSA, which allow the correct
study execution These centers must be registered in the National Registry of Centers of
ARCSA Clinical Research.
Art. 88.- The clinical research centers are responsible for the safety of the subject that
Participate in a clinical trial. They will be evaluated before, during and after the clinical trial, by
ARCSA inspections to ensure compliance with Good Clinical Practices. Prior to
After the start of the clinical trial, the ARCSA will carry out an inspection at the research centers
cynical that will participate in the study, to ensure that the conditions of the center
i) Perform random verifications of the data registered in the clinical research center.
j) Develop a clinical trial monitoring plan and
meet the requirements to develop the type of study proposed.
Art. 89 - The Research Ethics Committee in Beings
verify that this s
development in compliance with
Hum nos and AR
SA must analyze that the center of
protocol and its approved modifications
in ca o of
clinical research count on qualified researchers,
have them, as well as the requirements
inados by
equipment and
appropriate means for development
the Research Ethics Committee in Hu Beings
years
del est gave, among them, suitable conditions for
by the National Health Authority and Good Clinical Practices
k) Review the investigator's file making sure it is complete and up to date and identify errors in
case of presenting
l) Verify that the backups of all types of resources are recorded in the investigator's file
adverse events and reactions, during the development of the clinical trial.
m) Review the handling of the product under investigation, its provision and storage conditions, in order to
verify if the established in the investigation protocol is fulfilled.
n) Verify the existence and application of the procedure for receiving, using and returning the
products under investigation in clinical research centers.
o) Verify if the correct instructions on research subjects have been provided
the use, handling, storage and return of the products under investigation.
p) Inform the investigator in writing of errors and deviations from the application of the protocol, in case of
have them, as well as the measures that must be implemented to prevent them from recurring.
product research soul according to its characteristics; appropriate conditions for
consultation and training; guarantee of immediate attention before a potential emergency-medical emergency. From
there is no capacity to attend emergencies / emergencies in the clinical research center itself, its
benefit must be duly guaranteed by means of a contract or agreement with another health facility, without
restriction of any type of attention for the study subjects.
CHAPTER XIV
FROM THE MAIN RESEARCHER
Art. 90.- The principal investigator is the professional responsible for conducting the test.
clinician in a clinical research center and who leads the research team. According to
complexity of the study determined by the ARCSA, the principal investigator must be a health professional
with a fourth level degree, related to the area to investigate. These titles must be registered in the
National Secretary of Higher Education, Science, Technology and Innovation (SENESCYT) and before the Ministry of
Public health.
The principal investigator must prove that they have participated in at least one previous clinical trial and
have certificates with academic endorsement of training in Good Clinical Practices and Ethics of the
Investigation.
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Art. 91.- The responsibilities of the principal investigator in the clinical trial are:
a) Know in detail the research protocol and all available information about the product
in research.
b) Know and comply with Good Clinical Practices and applicable national health regulations.
c) Obtain, prior to the start of the clinical trial, the letter of declaration of institutional interest of
execution of the study, signed by the legal representative of the health establishment in which
will develop the same.
d) Obtain the informed consent of the subjects participating in the study.
e) Obtain the approval of the protocol, of the informed consent, of the Manual of
Researcher and other documents described in Good Clinical Practices, by a
Research Ethics Committee on Human Beings approved by the Ministry of Public Health, prior to
Start of clinical trial.
f) Select the personnel involved in the clinical trial and verify that it is properly
informed and trained regarding the study.
g) Clearly establish the procedures to follow
Friday, June 30, 2017 - 15
during the development of the clinical trial to the ARCSA, the sponsor or the Research Organization
by Contract, as appropriate and to the Research Ethics Committee on Human Beings that approved the protocol
of investigation, observing the established reporting periods, according to the severity of the event or the
adverse reaction.
o) Ensure that the informed consent complies with the provisions of this Regulation.
p) Take the necessary measures to guarantee the protection of the confidentiality of the information
of the subject under investigation and the data obtained in the clinical trial.
q) Facilitate the inspection visits of the sponsor, of the monitor, of the Ethics Committee of Research in Beings
Human or ARCSA before, during or at the end of the clinical trial.
r) Present the partial reports and the final report to the sponsor, as well as other reports that
are requested by the ARCSA, in relation to the development of the clinical trial based on the protocol d
Authorized investigation
s) Prepare a progress report of the clinical trial, at least once a year, to deliver it to the
sponsor, to the Research Ethics Committee in Human Beings
in the event of any situation that may arise and the functions that may be delegated to the members of the
and to the A
CSA
research team, among others, storage t) Dedicate, according to the complexity of the
research and the
of the product in
research and the
management
subject number
in research, the necessary time
documentation. to cum lir with him
role of principal investigator.
h) Ensure that the study is carried out according to the authorized research protocol and that the
Product under investigation is stored, dispensed and used as established in said protocol.
i) Take the necessary measures so that the recruitment process of the participants in the
investigation, be carried out in accordance with the provisions of the authorized research protocol.
j) Ensure the safety of the subjects under investigation and adequately monitor the treatment to which
undergo, in order to identify possible adverse reactions and adverse events that could
alter your health conditions.
k) Take responsibility for the medical decisions taken with the subjects under investigation, in
relationship with the clinical trial and, in case of presenting any possible adverse event, ensure that
Research subjects receive appropriate medical attention.
l) Take responsibility for the custody and handling of the product under investigation.
m) Keep all records and documents corresponding to the clinical trial updated.
n) Submit safety reports, including reports of serious adverse events and suspicions
of unexpected serious adverse reactions that occur
CHAPTER XV
OF THE TECHNICAL ADVISORY COMMITTEE ON CLINICAL RESEARCH
Art. 92.- The Technical Advisory Committee on Clinical Research will support the National Agency of
Regulation, Control and Health Surveillance - ARCSA in the process of evaluation and initial authorization, prior to the
conduct of a clinical trial in the country. The Committee will not meet for approval of amendments or
modifications.
Art. 93.- The Technical Advisory Committee on Clinical Research will consist of five members with voice and
vote, same that will be:
By the Ministry of Public Health,
- A delegate of the Vice Ministry of Governance and Health Surveillance, who will preside;
- A delegate of the General Coordination of Strategic Health Development;
- A delegate of the National Health Control Directorate;
An Academy professional with experience in clinical research; Y,
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An Academy professional with proven experience in the area of ​​the proposed clinical study.
The proposal of professional academic experts will be made by the members of the
Committee belonging to the Ministry of Public Health, with seven (7) days in advance of the day of
the meeting, by written communication addressed to the Vice Ministry of Governance and Surveillance of the
Health. The profile of the proposed professional academic expert must be justified.
The meetings of the Committee shall participate with voice and without vote: the General Certification Technical Coordinator
of the National Agency for Regulation, Control and Health Surveillance - ARCSA, who will act as secretary;
the technician who evaluated the clinical study at the ARCSA; and, a delegate of the Research Ethics Committee in Beings
Humans who evaluated the study previously.
Art. 94.- The Technical Advisory Committee on Clinical Research will meet with a minimum of four of
The five members with voice and vote. The members of the Committee and those who participate with voice in these
meetings, they will be obliged to keep absolute discretion and confidentiality about the file being evaluated.
Once the Committee is formed, the members must sign a confidentiality document and not present
interest conflict.
established in the Organic Law of Health and other regulations in force on the subject, notwithstanding the
civil or criminal penalties where applicable.
CHAPTER XVII GLOSSARY OF TERMS
Art. 98.- For the purposes of this Regulation, it is understood as:
• Good manufacturing practices (GMP): set of rules and procedures to ensure that
medicines, medical devices and food are constantly produced and controlled by standards
of quality, from the entry of the materials until their release as a finished product.
• Good clinical practice (BPC): standard for design, conduction, performance, monitoring, audit,
registration, analysis and report of clinical studies that provides a guarantee that the data and
the reported results are credible and accurate and that the rights, integrity and
confidentiality of study subjects.
• Good Laboratory Practices o: set of rules and procedures or erati os that guarantee that
Art. 95.- The delegate of the Vice Ministry of Governance
the data generated by e
control laboratory
and Health Surveillance, through the secretary, will summon the members of the Committee for its formation, each
Once the ARCSA requests it, for the evaluation of a new clinical investigation, with at least ten (10) days term
from
Quality are complete quality.
•       Interest conflict
reliable, reproducible and of
yes ua ion in which the trial
anticipation of the day of the meeting, which will be held at the ARCSA facilities. Attached to the call
de ind viduo -c ncerniente to your primary interest-
and the integri ad of an action tend to be
The technical evaluation report of the study, prepared by the ARCSA, will be included.
Art. 96.- The secretary shall prepare the Minutes of the meeting itself, which must contain the analysis of the report.
technician that summarizes the methodological, ethical and legal considerations of the exp criteria; the
Committee agreements; and, if there is, the argumentative criterion that is contrary to the approach of the
Committee majority. The Minutes must be signed by the members. It will be an annexed part of the Minutes, the declarations
of confidentiality and non-existence of conflict of interest of the members of the Committee.
Each meeting of the Committee will have the following procedure: presentation of the technical report issued by the ARCSA,
contributions from the corresponding CEISH, contributions from professional academic experts, space for questions
and clarifications by members; Committee deliberation and recommendation. Recommendations
of the Committee are not binding on the ARCSA.
Both the ARCSA and the Technical Advisory Committee on Clinical Research must ensure compliance
with the deadlines established in these regulations to issue the response regarding an approval request
of clinical trials.
CHAPTER XVI OF SANCTIONS
Art. 97.- Failure to comply with the provisions of this Regulation shall be sanctioned in accordance
to what
unduly influenced by a secondary interest of
type generally economic or personal.
• Data Collection Notebook (CRD): manual or electronic record designed to record all
the information required in the protocol and be reported to the sponsor about each subject participating in the
study.
• Essential Documents: documents that individually and collectively allow an evaluation of the
Conducting a study and the quality of general data.
• Source Documents: are original documents, data and records among which
include: hospital records, clinical sheets, laboratory notes, memos, diaries of
subjects or evaluation checklists, pharmacy delivery records, data
Registered automated instruments, copies or certified transcripts after verifying that they are
exact copies, microfiche, photographic negatives, magnetic media or microfilm, x-rays, records of
subjects and records kept in the pharmacy, in laboratories and in medical-technical departments
involved in the clinical study.
• Amendment: written description of the change or changes to the research protocol to the researcher's manual
and / or informed consent, which does not modify the objectives, the time of treatment and the product in
investigation.
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• Clinical Trial: is any investigation that is carried out in humans with the intention of
discover or verify the clinical, pharmacological and / or any other pharmacodynamic effects of
product (s) under investigation and / or identify any adverse reaction to research product (s)
and / or to study the absorption, distribution, metabolism and excretion of product (s) under investigation, with
The purpose of checking its safety and / or effectiveness. In these Regulations the terms are used interchangeably
"Essay" and "study", without there being, for the purpose of this instrument, any difference in its meaning and scope.
• Adverse event (EA): any adverse health incident that occurs in a
subject or participant in clinical research, to whom a research product has been administered,
although it does not necessarily have a causal relationship with the product under study. An adverse event can be, by
therefore, any unfavorable and unintended sign (including an abnormal laboratory finding),
symptom or illness temporarily associated with the use of a drug or product under investigation, whether or not
related to it.
• Serious Adverse Event: any event that occurs in the context of a clinical trial, without
it is necessarily related to causality with the product under investigation, and that produces: the death of the subject in
investigation, put the subject's life at risk, make the subject's hospitalization necessary or prolong his
stay, produce permanent or significant disability or disability, or place a
Friday, June 30, 2017 - 17
commercialization; provide additional information on efficacy, effectiveness and long-term safety (risk-
benefit). They are performed under conditions of usual medical practice and in large numbers of subjects during a
prolonged period Also known as post-marketing, post-registration or
Pharmacovigilance
• Inspection: for the purposes of this regulation, the verification or revision action is understood as such
developed by the National Health Authority through the National Agency for Regulation, Control and
Health Surveillance (ARCSA), to documents, facilities, files, quality assurance systems and
Any other resource that ARCSA considers is related to a clinical study.
• Nonprofit clinical research: research conducted by researchers without the
Participation of the pharmaceutical or pharmaceutical industry that meets the following requirements: 1)
Sponsor is the academy, a public hospital, a public research institute or entities
public; 2) the ownership of the research data belongs to the sponsor from the first moment of the
study;
3) there are no agreements between the sponsor and third parties that allow the use of the data for uses that
generate an in ustrial property; 4) design, implementation, recruitment, data collection and
the dissemination of research results is kept under the control of the sponsor; and, 4) for their
characteristic, these studies cannot be part
from a development program for an authorization of
congenital anomaly or malformation.
• Phase I: research in humans where a substance, new drug, is first used
or new formulation to provide preliminary information on product safety and establish the
tolerability and feasibility thereof. They are usually performed in healthy volunteers or in
Some specific cases in patients. They comprise trials of pharmacokinetics and pharmacodynamics.
They guide the most appropriate administration schedule for more advanced clinical trials.
• Phase II: research in humans where dose / response relationships and the
pharmacological effect of new drugs and new therapeutic regimens are identified.
Its main objective is to provide preliminary information on the effectiveness of the product and expand the
safety data obtained in previous studies. They are performed on patients affected by a certain
disease or pathological condition under strict monitoring.
• Phase III: research in human beings aimed at assessing the efficacy and safety of
experimental treatment, trying to reproduce the usual conditions of use and considering the
therapeutic alternatives available in the indication studied. They are controlled and randomized and ideally to
triple blind They constitute the gold standard to evaluate new therapeutic alternatives.
• Phase IV: investigations in human beings that are carried out once the product in
investigation has obtained the sanitary record authorizing its
Productization of a product.
• Stigner's manual: it is a compilation of the clinical and non-clinical data of the
product under investigation, which are relevant for the study of it in humans. Your goal is
provide researchers and other people involved in the study with the information to
facilitate the understanding of the foundation and the fulfillment of several important characteristics of the
protocol, such as dose, frequency / dose range, administration methods and monitoring procedures for
security.
• Monitor: Qualified person to follow up the process of a clinical study and ensure that it
be conducted, recorded and reported in accordance with the protocol, standard operating procedures, Good
Clinical Practices and applicable regulatory requirements.
• Placebo: Product with pharmaceutical form, which contains a pharmacologically inert substance that
acts as a comparator in a clinical study, without it having specific pharmacological activity for
condition studied.
• Standard Operating Procedures (SOPs): Detailed and written instructions for
achieve uniformity in the execution of a specific function.
• Serious adverse reaction: Any adverse reaction that at any dose causes death threatens the
life of the subject under investigation, produces permanent or substantial disability, requires hospitalization
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or prolongs hospitalization time, causes anomaly or congenital malformation.
• Serious and unexpected adverse reaction: Reaction whose nature, severity or outcome are not consistent
with the reference safety information of the product under investigation.
GENERAL DISPOSITION
FIRST.- The National Agency for Regulation, Control and Health Surveillance - ARCSA will verify in
the entire national territory, compliance with the suspension or cancellation of trials
clinicians that run in the country and if necessary will request support from their Zonal Coordinations.
SECOND.- If necessary, within the approval, control and surveillance processes of a clinical trial, the
ARCSA will request additional information from the sponsor described in this instrument.
THIRD.- In the case of import and / or export of biological samples for the purpose of
investigation, the sponsor must request the corresponding authorization from the ARCSA, which will issue it
verifying compliance with the constitutional provisions regarding the protection of
genetic resources In order to avoid the loss of quality of the samples that need to be
analyzed immediately and that need to be processed outside the country, said sponsor will start
the authorization process with at least twenty days before taking the samples. The ARCSA
shall
national legislation in force.
SEVENTH.- The ARCSA must meet all information requirements made by the Ministry of Public Health on
clinical trials
EIGHTH.- It will be the responsibility of the ARCSA to keep the records of a clinical trial that rest in
said Agency, therefore, when the members of the Technical Advisory Committee on Clinical Research, require
analyze the files, they will have access to them in the facilities of the ARCSA.
TRANSITORY DISPOSITIONS
FIRST.- Within one hundred and twenty (120) days, counted from the publication of this
Ministerial Agreement in the Official Registry, the National Agency for Regulation, Control and Surveillance
Healthcare - ARCSA will prepare the “Guide of procedures for conducting clinical trials in Ecuador”
and other technical and administrative instructions necessary for the application of this Regulation, including
the instructions for the import and export of biological samples for research purposes and
health care
SECOND.- Within a term of one hundred eighty (180) days, as of the publication of this Agreement
Ministerial in the Registry Office, the National Registry of Research Organizations will be created by
Contract, which will be in charge of the ARCSA, for which it will coordinate with the National Directorate of Health Intelligence
of the Ministry of Public Health.
respond to the requirement within twenty (20) days,
THIRD RA.- Within one hundred eighty (180) days,
counted from the date you receive the request.
FOUR.- In the health establishments of the Comprehensive Public Health Network in which they perform
clinical trials, direct and indirect costs generated by l
counted from the publication of this Ministerial Agreement in the Official Register, the ARCSA
will create the National Registry of Clinical Research Centers, which will be subject to the requirements
that this Agency
Realization of the essay will be covered in full by the sponsor of the same.
It was close to the effect.
FOUR.- Within one hundred eighty (180) days,
All hospital care that is carried out in a public health facility, in
the phases of recruitment, execution, and possible complications that occur during or after
Once completed, they will be covered by the sponsor of the essay in accordance with the Tariff of Benefits
l National Health System in force.
These individuals must be included in the agreement signed between the promoter and the health establishment of the Network
Comprehensive Public Health.
FIFTH.- The incentives received by researchers working in establishments of the Integral Public Network of
Health (RPIS) for its services provided, in the execution of a clinical trial, which are developed in a
Establishment of this type, outside their working day, must be recorded in the agreement signed by the promoter and the
health establishment of the Comprehensive Public Health Network.
In the agreement, additionally the authorization of the health establishment for the researcher
you can use the facilities of the establishment for the purposes of the clinical trial, outside your working day
labor.
SIXTH.- Concerning clinical trials in pregnant women and minors will be subject to
a specific regulation based on the content of the
counted from the publication of this Ministerial Agreement in the Official Register, the ARCSA
will create the National Registry of Clinical Trials, which will be subject to the requirements established by the Agency for
The effect.
FIFTH.- In the term of one hundred eighty (180) days, counted from the publication of this
Ministerial Agreement in the Official Registry, the Ministry of Public Health will create the National Repository of
Health Research (RENISA).
FINAL DISPOSITION
On the execution of this Ministerial Agreement that will come into effect as of its publication in the Registry
Official, entrust yourself to the National Agency for Regulation, Control and Health Surveillance ARCSA and the Ministry of Health
Public
Given in the Metropolitan District of Quito on May 19, 2017.
f.) Dr. María Verónica Espinosa Serrano, Minister of Public Health.
It is a faithful copy of the document that appears in the file of the National Directorate of the General Secretariat, to which I refer
if necessary.- I certify it.- Quito a, May 23, 2017.- f.) Illegible, General Secretariat, Ministry of
Public health.
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