GENERAL TECHNICAL STANDARD ON - Ó É É Ó
NATIONAL PHARMACOVIGILANCE SYSTEM OF PHARMACEUTICAL PRODUCTS FOR HUMAN USE
TITLE I: GENERAL PROVISIONS
Article 1: The provisions of this General Technical Standard shall apply to the activities of
Pharmacovigilance carried out within the National System of Health Services, which
collaborate in the formation of the National Pharmacovigilance System led by the Institute of
Public Health of Chile (ISP), in its role as authority in charge of sanitary control of products
pharmacists; system to which also converge the estates of the private area, in application of
the duties and obligations established in the National Regulation of Control of Pharmaceutical Products of
Human Use, approved by Supreme Decree NO 3 of 2010, of the Ministry of Health. The system
National Pharmacovigilance has the purpose of identifying, quantifying, evaluating and preventing risks
associated with the use of medicines, such as vaccines, biological products, biotechnology and
other pharmaceutical products contemplated in said regulation.
Article 2: In accordance with the provisions of the National Regulation of Control of Pharmaceutical Products of
Human Use, the Institute of Public Health of Chile is the entity in charge throughout the national territory
surveillance of the safety of pharmaceutical specialties and those products that do not
being registered they have been authorized for use in scientific research. For these purposes, said
entity has created the National Pharmacovigilance Program and is the entity in charge
to coordinate Pharmacovigilance activities throughout the national territory and to ensure
for the correct fulfillment of the dispositions that on the matter are contained in the
regulations that regulate it and in this Technical Standard.
Article 3: Pharmacovigilance is a health control activity that must be shared by the
competent authorities, holders of health records for medicines, professionals
of health, institutions providing health services, both public and private, and the
General population. Pursuant to this, the entities previously indicated must execute the
Pharmacovigilance actions that are indicated below for each case and that are based on regulation
in force, especially that contained in Supreme Decree No. 3, of the Ministry of Health, referred
precedent.
Article 4: Pharmacovigilance (FV) is defined according to the provisions of the
D.S. MINSAL N 3/2010, as a set of activities related to detection, evaluation,
understanding and preventing the adverse effects associated with the use of medications.
For the purposes of Pharmacovigilance practice, the following definitions complement those already
contained in DS MINSAL N 3 of 2010:
a) National Pharmacovigilance Center: Corresponds to the section of the Health Institute
Public of Chile responsible for coordinating the National Pharmacovigilance Program, instituted through
resolution of said entity.
b) Type of adverse drug reactions (types of ADR): Refers to the classification of
RAM t according to the way in which they occur, which is used for analysis purposes
executed by the National Center for Medicines and is broken down as follows:
b.1 Type A Adverse Reactions (drug reactions): These are those that are due to the effects
pharmacological (increased); are relatively common (> 1%), dose dependent, can be prevented, and
they can be reproduced experimentally. They are prevented using more appropriate doses for each
individual patient.
b.2 Type B Adverse Reactions (patient reactions): Not related to the effects
pharmacological. They are rare, infrequent, and occur in a very low proportion of patients (<
1%) are not dose related, unpredictable, can be serious and sometimes fatal, their
causality is uncertain. They can be immunological or non-immunological reactions and cannot be
prevent, except for exposure to risk.
b.3 Type C Adverse Reactions: These refer to situations in which the use of the drug
the frequency of a "spontaneous" disease increases, often for unknown reasons. These effects
can be severe and frequent, may be related to prolonged effects, there is no
suggestive time sequence and it can be difficult to prove the association with the drug, its mechanism is
unknown and are difficult to detect as individual cases.
b.4 Other adverse reactions: Those whose mechanism does not allow to classify them in the
previous types; among them, delayed appearance, lack of efficacy and RAPi due to suspension of the
treatment.
c) Causality: It is the association relation between the administered medicine and the observed adverse event.
To assess each adverse event according to its causality, the ISP uses the causality method
established by the World Health Organization (WHO), known as the "WHO Causalida Method".
d) Confidentiality: Maintaining the privacy of patients, healthcare professionals
health and institutions, including people's identity and all personal medical information. The
scope of confidentiality in VF practice includes the patient, the notifier, the center
, the ISP and the holder of the health registry or any entity involved in a suspicion of
RAM.
e) Side Effect: Any unwanted effect of a drug that occurs at doses
normally used in man, which is related to the pharmacological properties of the drug.
f) Notification Form: Official Form for reporting suspected reactions
Adverse, both paper and electronic, made publicly available on the website of the
ISP and approved by resolution of the latter.
g) Periodic Safety Update Report (IPS):
Document prepared by the holder of the Sanitary Registry, whose purpose is to update the information of
safety of a medicine and that, among other elements, contains information on suspicions
of adverse reactions of which he was aware in the reference period, as well as a
updated scientific evaluation of the benefit-risk balance of the drug.
h) Spontaneous notification: Corresponds to the PV method used by the National Program of
Pharmacovigilance, which consists of communication to the ISP by a health professional or
other entity, of suspected adverse drug reactions of which it is aware, including
dependency, abuse, misuse and ineffectiveness, in a form expressly created for
such an end.
i) Notifier: Health professional or other entity that has suspected a
adverse reaction and has reported it to the ISP.
j) Risk management plan: Document in which the applicant or owner of a Registry
Health specifies the relevant risks of the medicine and establishes a plan for the realization
of the PV activities necessary to identify, characterize, quantify them and, in case
necessary, submit them to a specific program to prevent or minimize these risks.
k) National Pharmacovigilance Program: It is the set of activities carried out by the Health Institute
Public in relation to collecting data, evaluating and preparing information on adverse drug reactions,
from all over the country and the execution of the actions derived from it.
I) Benefit / risk ratio of a medicine: It is the ratio between the expected benefit and
the documented or expected risk that may result from a given therapeutic intervention that
involves a medication.
m) Temporal Relationship: Time elapsed between the appearance of the adverse reaction.
and the
n) Signal: Information communicated about a possible causal relationship between an adverse event and a
medication, said relationship being previously unknown or incompletely documented. Usually
More than one report is needed to generate a signal, depending on the severity of the event and the
Quality of the information.
ñ) Verification: The procedures carried out in FV to ensure that the data contained
in a notification they coincide with the original observations.
TITLE II: THE NATIONAL PHARMACOVIGILANCE SYSTEM
Article 5: The National Pharmacovigilance System for medicines from
human use is made up of:
a) The Institute of Public Health, which is the entity responsible for the National Program of
Pharmacovigilance.
b) The Ministerial Health Programs established by resolution (Immunizations,
Tuberculosis, HIV-AIDS, among others) and those others that the Ministry of Health determines.
c) Public and private hospitals, public and municipal clinics, private clinics and
all healthcare establishments in the country, all of them in application of the provisions of article
217 of Supreme Decree No. 3 of 2010, of the Ministry of Health.
d) Health professionals, who work in public and private areas, by virtue of
the application of article 217 of Supreme Decree NO 3 of 2010, of the Ministry of Health.
e) The Holders of Sanitary Registries, in application of articles 2180 and
219 of the Supreme Decree N 3 of 2010, of the Ministry of Health, and understood as such any person
natural or legal, national or foreign, domiciled in Chile, whose name contains a health record,
including importers and distributors who have had to obtain a sanitary registration in Chile under license or
agreement, of a natural or legal person, national or foreign, in compliance with the
provided in article 102O of the Sanitary Code.
The National Pharmacovigilance System, led by the Chilean Institute of Public Health, is
will manage on the basis of the adverse reaction reporting system provided by the
entities and people mentioned above; the information issued by health entities and organizations,
international or foreign; and voluntary notifications received regarding misuse and lack of
efficacy of medications, situations of abuse or dependency and cases of acute poisoning and
chronicle. Notifications will be made on special forms that for such purposes
established a public health institute in Chile.
Article
6: Actions to be carried out by the Institute of Public Health in
Pharmacovigilance matter.
a) Plan, coordinate, promote, evaluate and develop the National Program of
Pharmacovigilance, coordinating with the units or professionals in charge of Pharmacovigilance
in public and private hospitals in the country, and in the Pharmaceutical Industry, as well as holders of
Health Register.
b) Receive notifications about suspected serious adverse reactions that have occurred
in the country, of medicines, such as vaccines, biological products, biotechnology and other products
Pharmaceuticals contemplated in the Regulation of the National System of Control of Pharmaceutical Products of
Human use.
Receive, evaluate and record suspected adverse drug reactions received on the sheet
notification of suspected adverse drug reactions.
d) Administer and manage the database of the National Pharmacovigilance Program of
medications, ensuring their availability, updating and integrity in the transfer of information;
monitoring the security and guaranteeing the confidentiality of the data.
e) Identify health alert situations related to the profile of
drug safety and recommend regulatory measures to reduce health risk
identified.
f) Establish the appropriate measures for the management of
identified risk situations, with the ultimate aim of minimizing or preventing them.
g) Resolve the regulatory measures aimed at reducing the identified health risk in relation to the use of
a medicine.
h) Communicate medication safety alerts to health professionals, through
of the diffusion network of the Institute of Public Health.
Promote education or training in Pharmacovigilance, through collaboration with study centers,
public departments and scientific societies, through conferences, courses, talks or workshops,
and provide updated information on drug safety.
j) Establish a communication network on drug safety
With the Public and Private Network of healthcare establishments, with universities, scientific societies
and professional associations of the country, which allows to collect and disseminate in an expeditious and official way
information related to drug safety from anywhere in the national territory.
k) Act as a benchmark in Pharmacovigilance for the country and before the International Program of
Pharmacovigilance of the World Health Organization.
l) Periodically send to the Organization's Adverse Reactions Monitoring Center
World Health, in Sweden (Uppsala Monitoring Center -UMC), reaction notifications
adverse drugs received, properly evaluated and coded and participate in
meetings organized by the World Health Organization and other international entities
on Pharmacovigilance issues.
m) Establish a communication channel with the health record holders to
ensure, in a timely and complete manner, the availability of all relevant information
about the balance between the benefit and the risk of any of your products.
- n) Evaluate the risk management plans presented by the holders of the
health records, for all products that require it or that the regulatory authority indicates.
Article 7: Actions to be carried out by health professionals.
a) Health professionals have a duty to report any suspected adverse reaction of
those that have knowledge during their habitual practice and send it in the notification form of
adverse drug reactions, electronically or in print, prioritizing reactions
adverse to serious and unexpected drugs of any drug and to all of drugs of
recent commercialization in the country. These notifications must be sent to the Health Institute
Public within the terms established in the Regulations of the National Product Control System
Pharmaceuticals for human use, for which you must adhere to the procedures established in the
institution in which it works.
b) Likewise, health professionals must keep clinical documentation of suspicions
of adverse drug reactions in order to complete or monitor the event, if
necessary.
c) Collaborate with the professionals of the Institute of Public Health, providing the
necessary information that they request in order to complete or expand the information on the
suspected adverse drug reactions.
Article 8: Actions to be taken by the technical directors of pharmacy with recipes
magistrales and prescriptores of magisterial and officinal formulations.
a) Regarding pharmaceutical preparations, the prescribers of formulations
magistrates, as well as the technical directors of master recipes, are required to report
any adverse effect, derived from the use of these products, to the Regional Ministerial Secretaries
of Health (SEREMI) competent.
b) The SEREMI must notify the ISP of any report they are aware of, both
those that receive according to those established in the preceding letter, such as those that take
knowledge in the development of their usual tasks.
Article 9: Actions to be carried out by those in charge of clinical drug studies during
its execution:
a) Serious adverse reactions seen in the scientific investigation of a medicine must be
informed by the researchers to the Scientific Ethics Committee and to the Director of the establishment where
conduct such research; the latter being the one who must report them to the Institute of Public Health,
according to the provisions of s-articles 216 and 217 of the D.S. No. 3 of 2010, already cited.
Article IO: Actions that must or can be carried out by the institutions providing services of
health, public and private, and other related entities.
a) To comply with the obligations established in the Regulations of the National System of
Control of Pharmaceutical Products for Human Use, the Technical Directors of the healthcare centers,
both public and private, such as hospitals, surgeries and clinics, will be responsible for
Pharmacovigilance activities, taking care of:
i. Collect and send notifications of suspected adverse reactions that occur in
the establishment, within the terms established in the National System Regulation
of Control of Pharmaceutical Products for human use and keep a record of the cases detected in the
establishment.
ii. Receive and disseminate, to the extent possible, information on drug safety
sent from the Institute of Public Health or obtained from other authorized sources.
iii. Be available to be contacted from the Institute of Public Health before the eventual
need to complete information regarding a case notified from the establishment.
These healthcare centers may have a health professional in charge of the functions of
Pharmacovigilance in said center, previously described, designation to be made by the Director
Technician of the establishment, which does not affect or avoid the responsibility of said Technical Director.
b) The professionals in charge of the ministerial health programs must notify the
Institute of Public Health any suspicion of adverse drug reaction.
c) Other related entities that use medications in their activities may
voluntarily collaborate with the "National Pharmacovigilance System", communicating to the Institute of
Public Health any suspicion of an adverse event to medications of which they become aware. So too,
Universities, drug and toxicology information centers, scientific associations
and professional associations, the entities that administer health plans, may provide the
collaboration that is within their possibilities and adjusted to current legislation, that is
requested by the Institute of Public Health, for example, about disseminating content of general interest
relating to the safety of medicines, to educate in the concepts related to the
Pharmacovigilance, or to provide information that is requested from the Institute of Public Health
regarding prescription and / or drug use profiles, obtainable from their databases.
. TITLE III: OF THE HEADLINES OF THE SANITARY REGISTRIES
Article 11: Actions to be carried out by the Pharmaceutical Industry, as holder of health records and others
entities that are also.
a) Holders of health registration are ultimately responsible for safety and efficacy
of their medications and must implement and maintain, in accordance with the provisions of the Regulations
National Control of Pharmaceutical Products for Human Use, a documented system that allows the
collection and treatment of suspected adverse drug reactions and information from
security generated from its products, including that from importers and
dealers.
b) Any holder of sanitary registration of medicines for human use, depending on the
exposed, you must have a pharmacovigilance system, own or externalized, in charge of your
Technical Director or, failing that, a Technical Advisor, who may be a professional in the health area,
personnel whose designation must be notified to the Institute of Public Health.
cl The person in charge or the professional in charge of the Pharmacovigilance System will have at least the following
functions:
• Maintain a Pharmacovigilance System that allows the collection and evaluation of information on reactions
adverse to medicines notified to the holder of the sanitary registry, in order to send them
opportunely to the Institute of Public Health, in the forms authorized for this purpose, always
in Spanish language and for medicines that are sold in the country.
• Prepare and send to the Institute of Public Health periodic safety reports for those
active principles indicated by the Institute of Public Health through resolution.
• Present the risk management plans and develop the possible actions that
indicate the Institute of Public Health by means of a founded resolution.
• Give an immediate response to any information request from the Health Institute
Public that allows evaluating the benefits and risks of medicines, in the terms that
entity has, which will establish in accordance with the general provisions contained
in Law 19,880, law on the bases of administrative procedures that govern the acts of
organs of the state administration.
0 • Keep the respective documentation of suspected
adverse drug reactions to complete or follow up if necessary.
• Conduct a continuous evaluation of the benefit-risk ratio of medications during the
post-marketing period and immediately notify the competent authority of any
information that could mean a change in said relationship.
• Collect the safety information from post-marketing studies.
• Inform regarding the effectiveness of the risk minimization measures contemplated in the
risk management.
d) Individual reports must be sent within the deadlines established in the Regulations of the
National Control System for Pharmaceutical Products for Human Use.
e) The Institute of Public Health, in qualified cases and by founded resolution, will establish
the periodicity of presentation of the Periodic Safety Reports and the products to which
This requirement will be applied to them based on their nature and according to the provisions of the subsection
end of article 2180, of DS MINSAL N 3 of 2010. In the case of innovative products,
In response to the need to strengthen their security data, it will be available to them in
the resolution that grants the respective sanitary registry, the periodicity of presentation of the Reports
Security Newspapers, in the following scheme: during the first two years, every 6 months as
maximum; for the following 3 years, annually at most; thereafter, every 5 years as
maximum.
Article 12: Medications that require Risk Planning plans
a) The Institute of Public Health will request, in qualified cases and by means of a founded resolution,
risk management plans, among several, for products corresponding to introduced molecules
for the first time on the market, biotech products and product-like products
innovators who already have risk management plans. In these cases, the applicant or holder of the
sanitary registry must propose a risk management plan, which may be accepted or returned for
modification.
b) The risk management plans for products of biological origin must pay special attention to
immunogenicity risk, characteristic of this type of products.
• TITLE IV: ON MEDICAL SAFETY
Article 13: t4odifications of sanitary registration authorizations of
the drugs.
a) The Institute of Public Health will resolve when, in accordance with the
• evaluation of national or international pharmacovigilance data and in use of the
Powers established in the National Regulation of Control of Pharmaceutical Products of
Human use, it is considered necessary for reasons of public health security, modify the registry
health of a medicine its condition of sale, graphic label, medical and / or patient brochure or
proceed with the suspension or revocation of the authorization of the respective health registry.
b) Any holder of sanitary registration of pharmaceutical products must notify the Institute
of Public Health, any information that affects the safety of medications and request
the corresponding modification in accordance with the provisions of the Regulations of the National System of
Control of Pharmaceutical Products for Human Use.
TITLE V: CONFIDENTIALITY.
Article 13: The treatment of the data obtained and the result of the notifications and
communications referred to in this technical standard, which are made in order to protect the health of
people, will be governed by the regulations of Law N 19.628, on protection of privacy, maintaining the
due protection by the officials who have access to this information, the
professional secrecy, an obligation that does not cease for having finished its activities in that field.