drug approval system of chile
TRANSCRIPT
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Abbreviation and Regulatory Terms
Spanish English
Agencia nacional de medicamentos
(ANAMED) National Drug Agency Department
Instituto Bacteriológico Bacteriologic Institute
Instituto de Higiene Institute of Hygiene
Instituto de Salud Pública (ISP) Institute of Public Health
Ministerio de Bienestar Social Ministry of Social Welfare
Ministerio de Salud Ministry of Health
Secretarias Regionales Ministeriales de
Salud (SEREMI) Regional Health Department
Subsecretaría de Salud Pública Department of Public Health
Major Terms in the REGULATIONS OF THE NATIONAL SYSTEM CONTROL OF
PHARMACEUTICAL PRODUCTS FOR HUMAN USE
Actividad biológica Biological Activity
Administración Administration
Aseguramiento de la calidad Quality Assurance
Biodisponibilidad Bioavailability
Buenas Prácticas de Laboratorio (BPL) Good Laboratory Practices (GLP)
Buenas Prácticas de Manufactura (BPM) Good Manufacturing Practices (GMP)
Calidad de un medicamento Quality of a medicine
Certificado de registro sanitario Marketing Authorization Certificate
Control de calidad Quality Control
Control de estantería Shelf Control
Clave Code
Contramuestra Counter Sample
Cuarentena Quarantine
Dispensación Dispensing
Distribución Distribution
Dosificación Dosage
Dosis Dose
Droga vegetal o material vegetal Herbal drug or material
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Eficacia Efficacy
Encarte Insert
Ensayos de disolución Dissolution Tests
Envase dispensador Dispenser
Envase primario Primary Packaging
Envase secundario Secondary Packaging
Envases clínicos Clinical Packaging
Equivalentes farmacéuticos Pharmaceutical Equivalents
Equivalentes terapéuticos Therapeutical Equivalents
Especialidad farmacéutica Pharmaceutical Product
E p i i io n Specification
Estabilidad Stability
Estado de producción Production State
Estudio de equivalencia terapéutica Therapeutical Equivalence Study
Estudio de estabilidad a tiempo real Real-time Stability Study
Estudio de estabilidad acelerado Accelerated Stability Study
Estudio de estabilidad Stability Study
Estudios de biodisponibilidad Bioavailability Study
Estudios farmacocinéticos Pharmacokinetics Study
Evaluación de un producto farmacéutico Pharmaceutical product evaluation
Excipiente Excipient
Expendio Retailing
Farmacovigilancia Pharmacovigilance
Fecha de expiración, vencimiento o
caducidad Expiration, due or expiry date
Forma farmacéutica Pharmaceutical form
Fórmula patrón o fórmula maestra Master Pattern or Formula
Importación Importing
Impurezas Impurities
Internación Admission
Licencia License
Marcadores vegetales Herbal markers
Márgenes de tolerancia Margin of tolerance
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Materia prima Raw material
Material de envase Packaging material
Monografía Monograph
Muestra médica Medical sample
Muestras de referencia o muestras de
retención Reference sample or retention sample
Muestra o Contramuestra legal Legal sample or Legal counter sample
Nombre genérico de un producto
farmacéutico Generic name of a pharmaceutical product
País de procedencia Country of origin
País de producción Country of production
Período de eficacia Effective period
Potencia Potency
Preparación vegetal Plant preparation
Principio activo Active ingredient
Procedimiento operativo estándar (POE) Standard Operating Procedure (SOP)
Producto a granel Bulk product
Producto farmacéutico de asociación Associated pharmaceutical product
Producto farmacéutico de combinación Combined pharmaceutical product
Producto farmacéutico de referencia o
comparador
Pharmaceutical product of reference or
comparison
Producto semielaborado Semielaborated product
Producto semiterminado Semifinished product
Producto terminado Finished product
Producción, Proceso de producción,
Fabricación, Manufactura o
Faena/Production
Production process, Fabrication,
Manufacturing, Work
Reacción adversa a medicamento (RAM) Adverse drug reaction (ADR)
Reacción adversa seria Serious adverse reaction
Reacción adversa inesperada Unexpected adverse reaction
Receta médica Prescription
Registro sanitario Marketing Authorization
Rotulado gráfico Graphic labeling
Serie o Lote Batch or Lot
Subserie o Sublote Sub-batch or Sub-lot
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Tenencia Possession
Titular de Registro sanitario Marketing Authorization Holder
Trazabilidad de datos analíticos Traceability of analytical data
Trazabilidad de un producto Product traceability
Unidad de venta Sales unit
Validación Validation
Notice
1. Due to the purpose of this document, most of the information was quoted directly
from the website or related guidelines of each ountry’ drug r gul tory g n i ,
and reviewed by the agencies.
2. This document is limited only to pharmaceutical products, not applicable to
biological and herbal products.
3. When referring to the contents of this document, check the up-to-date
information including related laws and regulations, and revision of guidelines.
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Table of Contents
I. Drug Regulatory Agency ·································································· 8
1. Institute of Public Health (Instituto de Salud Pública)································· 8
1.1 Organization·········································································· 8
1.2 Task···················································································· 9
1.3 Website················································································ 9
II. Related Laws and Regulations························································· 10
1. Approval Regulations of the National System Control of Pharmaceutical Products
for Human Use············································································· 10
1.1 Overview············································································· 10
III. Classification of Pharmaceutical Products ········································ 11
1. Classification by regulation ····························································· 11
IV. Drug Approval System ································································· 12
1. Investigational new drug application ··················································· 12
1.1 Clinical trial application ····························································· 12
1.2 Authorization process of clinical trials ············································ 13
1.3 Priority review ········································································ 13
1.4 Review period ········································································ 13
1.5 Required dossiers ···································································· 14
2. New Drug Application approval························································· 14
2.1 Procedure ·············································································· 14
2.2 Rejection and procedures for appeal··············································· 15
2.3 Priority review ········································································ 16
2.4 Review period ········································································ 16
2.5 Required dossiers ···································································· 16
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3. Generic drug approval application ····················································· 27
3.1 Procedure ··············································································27
3.2 Priority review ········································································ 28
3.3 Review period ········································································ 28
3.4 Required dossiers ···································································· 28
4. Orphan drugs ·············································································· 28
5. Priority review ············································································· 28
5.1 Short Registration Procedure ······················································· 28
5.2 Simplified Registration Procedure ················································· 28
V. Others ······················································································· 31
1. Good Manufacturing Practices ·························································· 31
2. Drug Master File ·········································································· 31
3. Labeling and package inserts···························································· 31
4. Certificate of a Pharmaceutical Product ··············································· 35
5. Manufacturing Licenses ································································· 35
6. Fees ························································································· 35
VI. References ················································································ 36
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List of Figures
Figure 1. Organization Chart of Ministry of Health
Figure 2. Organization Chart of ANAMED
Figure 3. Clinical Trials Section
Figure 4. Personnel and Roles
Figure 5. Authorization Process
List of Appendix
Appendix 1. List of Drugs that Requires Bioequivalence Tests
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I. Drug Regulatory Agency1
1. Institute of Public Health (Instituto de Salud Pública)
1.1. Organization
The central government organization, which manages overall issues regarding the public
and private health/sanitary services in Chile, is the Ministry of Health of Chile (Ministerio de
Salud de Chile).
The Ministry of Health plays a guiding and regulatory role in the field of pharmaceutical
products by implementing national drug policies and issuing technical and administrative
standards to be met by public and private entities engaging in the activities, such as
registering, importing, exporting, manufacturing, storing, possessing, and distributing
pharmaceutical products, advertising and/or supplying information about them, through the
Department of Public Health. The organization called Regional Health Department
(Secretarias Regionales Ministeriales de Salud, SEREMI) under the Department of Public
Health is responsible for authorizing the admission of pharmaceutical products.
Figure 1. Organization Chart of Ministry of Health
The Institute of Public Health (Instituto de Salud Pública, ISP) under the Ministry of
Health is the national health authority responsible for the sanitary surveillance of
pharmaceutical products and for ensuring compliance with the provisions regarding the
Regulations of the National System Control of Pharmaceutical Products for Human Use, the
Sanitary Code and its supplementary regulations, and other laws on the subject, and
authorizes the marketing registration for pharmaceutical products by issuing the final
resolutions.
The current Institute of Public Health of Chile (ISP) traces its historical roots back to
September 15th of 1892 when the law of the Institute of Hygiene (Instituto de Higiene) was
established. The work of Institute of Hygiene continued to 1924 until the military junta took
power and closed the institute between November and December of that year. In 1929, the
Bacteriologic Institute (Instituto Bacteriológico) was established, as a part of Ministry of
Social Welfare (Ministerio de Bienestar Social), by the Law No. 4,457 dated January 29th of
1 http://www.leychile.cl/Navegar?idNorma=1026879&idVersion=
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that year, and was responsible for public health and sanitary until 1980. When the Supreme
Decree No. 79 was newly enacted on April 1st, 1980, today’s Institute of Public Health of
Chile was established.
Among other organizations under the Institute of Public Health of Chile (ISP), the
National Drug Agency Department (Agencia nacional de medicamentos, ANAMED) is
responsible for ensuring the efficacy, safety, and quality of pharmaceutical products subject
to sanitary control used in Chile. This Department consists of 8 sub-departments as shown
inFigure 2.2
Figure 2. Organization Chart of ANAMED
1.2. Task
The major tasks of ISP are:
verifying the quality of pharmaceutical products in any of the stages including
registering, importing, exporting, manufacturing, storing, possessing, and distributing
authorizing the establishment and operation of pharmaceutical laboratories
licensing and registering pharmaceutical products and other products subject to
regulations for pharmaceutical products
supervising conditions for import, admission, export, manufacturing, and distribution
of pharmaceutical products, advertising and providing information regarding these
products
controlling narcotic drugs and pharmaceutical products that cause addiction, and
other psychotropic substances likely to have a similar effect, in relation to the import,
export, and lawful use thereof in the preparation of pharmaceutical products
monitoring and ensuring compliance with the provisions stated in the Regulations of
the National System Control of Pharmaceutical Products for Human Use and other
regulations governing such matters.
1.3. Website
http://www.ispch.cl/
2 http://www.ispch.cl/quienes_somos/organigrama
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II. Related Laws and Regulations3
1. Approval Regulations of the National System Control of Pharmaceutical
Products for Human Use (Apruebase Reglamento del Sistema Nacional
de Control de los Productos Farmaceuticos de Uso Humano)
1.1 Overview
The Approval Regulations of the National System Control of Pharmaceutical Products for
Human Use is a decree signed and issued by the President of Chile. The date of promulgation
of this decree is January 25th, 2010; the publication date is June 25th, 2011, and recently
modified on August 28th, 2015.
The decree was established, having regard to the provisions of the fourth and sixth books
and other relevant provisions of Decree-Law No. 725 issued by the Ministry of Health in
1967 approving the Sanitary Code. The purpose of this decree is to update, organize, and
complete existing rules regarding the matter, and by doing so, technical and administrative
standards and other terms or requirements to be met for registering, importing, exporting,
admission, manufacturing, storing, possessing, and distributing pharmaceutical products;
advertising and/or supplying information about them; and for their use for scientific research.
The Regulations of the National System Control of Pharmaceutical Products for Human
Use consists of 12 titles in total including provisional article, as well as preliminary title.
Preliminary Title
Title I Pharmaceutical Products
Title II Marketing Authorization of Pharmaceutical Products and Other Products
Title III Packaging and Labeling
Title IV Import and Admission of Pharmaceutical Products
Title V Export of Pharmaceutical Products
Title VI Pharmaceutical Laboratories
Title VII Quality
Title VIII Distribution
Title IX Advertising and Information
Title X Sanitary Surveillance
Title XI Administrative Procedure, Penalties and Appeals
Provisional Article
3 http://www.leychile.cl/Navegar?idNorma=1026879&idVersion=
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III. Classification of Pharmaceutical Products4
1. Classification by regulation
According to the Ministry of Health of Chile, pharmaceutical or medicinal product is
defined as any natural or synthetic substance, or mixture of those substances, which is
intended for use in cure, mitigation, treatment, prevention or diagnosis of diseases or
symptoms, and for physiological systems or mental state of the person to whom it is
administered to be modified5.
There is no specific definition of new drugs, bio-similar drugs, or orphan drugs in the
regulation regarding pharmaceutical products for human use stated in the above section.
Instead, Article 10 in the regulation classifies the pharmaceutical products into 7 categories
according to their nature.
However, the term "Therapeutic equivalents" is defined as pharmaceutical equivalents
meeting the same or similar quality specifications and producing essentially the same effects
upon administration under conditions described in their labels in terms of effectiveness and
safety which are determined by appropriate tests which are considered as generic drugs used
in South Korea.
Chemical or chemical synthesis products are drugs that are compromised of one or
more purified and identified active ingredients obtained from a chemical synthesis or
extraction process.
Biological products are obtained from and/or produced by living organisms and their
fluids or tissues, and includes vaccines, Serum, blood products, hormones,
biotechnological or recombinant drugs, antibiotics, allergen, and gene therapy
products.
Radiopharmaceuticals are products or formulations labelled with radionuclides or
radioisotopes for use in the diagnosis or treatment of diseases, regardless of the route
of administration.
Phytopharmaceuticals are pharmaceutical drugs that are compromised of properly
standardized active ingredients originated from the part above the root or root part of
plants or other plant materials.
Homeopathic products are pharmaceutical drugs that are compromised of
homeopathic substances originated from plant, animal, mineral or chemical raw
materials, and are prepared in accordance with a homeopathic manufacturing
procedure described in official regulations approved by the Ministry of Health.
Medical gases are pharmaceutical drugs made of one or more gaseous components
with known concentration and impurities within the specified range, and are intended
for administration to humans.
Other pharmaceutical drugs not listed above include any other products having
therapeutic properties as indicated in the label, advertised or attributed by any means
with intention for use in cure, mitigation, treatment, diagnosis or prevention of
diseases or symptoms, and for physiological systems or mental state of the person to
whom it is administered to be modified.
4 http://www.leychile.cl/Navegar?idNorma=1026879&idVersion=
5 http://www.ispch.cl/anamed/subdeptoregistro/definicion_medicamentos
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IV. Drug Approval System
1. Investigational New Drug application
1.1 Clinical trial application
The unit called Clinical Trials section of the sub-department of Sanitary Registration and
Authorization of ANAMED under the Institute of Public Health of Chile (ISP) is responsible
for evaluating the use of pharmaceutical products without national marketing authorization.
This unit also evaluates the modifications that are required in connection with the
authorization of use of pharmaceutical products in clinical research and follows up on the
activities of the centers and laboratories that conduct such studies in humans6.
Figure 3. Clinical Trials Section
Seven people work in this unit and their roles are shown in Fig 47.
Figure 4. Personnel and Roles
According to the Decree called “Approval Regulations of the National System Control of
Pharmaceutical Products for Human Use”, the phase I, II, and III clinical trials demonstrating
6http://www.ispch.cl/sites/default/files/Instructivo%20procedimiento%20de%20registro%20de%20productos%2
0farmaceuticos.pdf 7 http://www.ispch.cl/sites/default/files/regulacion_estudios_clinicos.pdf
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the safety and efficacy of the pharmaceutical products intended for marketing authorization
should be included when applying for the registration. For the pharmaceutical products
comprising active ingredients which need to prove the bioavailability or therapeutic
equivalence however, the studies demonstrating those properties should be submitted when
applying for the registration.
1.2 Authorization process of clinical trials8
Figure 5. Authorization Process
The authorization and registration procedures can be processed manually or electronically
through GICONA (https://gicona.ispch.cl/giconaweb), an online information management
system of ISP. If a person or company that will apply for registration/authorization currently
is not a user of this online system, subscription is required to be granted a password for login
to the system. When the GICONA is used, payment is also made through the online system9.
It seems that the approval of authorization is highly dependent on the opinion or discretion
of the reviewer of Institute of Public Health (ISP).
1.3 Priority review
Not specified in the regulation.
1.4 Review period
Not specified in the regulation.
8 http://www.ispch.cl/sites/default/files/regulacion_estudios_clinicos.pdf
9 http://www.ispch.cl/sistema-informatico-de-tramitacion-en-linea
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1.5 Required dossiers10
The requirements to apply for import and use of investigational drugs are:
Approval letter written by Ethics Committee (Comité de É tica) which is corresponding
to the area where the research center is located
Letter of the Director of Service (Director del Servicio) to another Committee (if
applicable)
ICF (Informed Consent Form) dated, signed and stamped by the Ethics Committee
Protocol in English and Castilian
Investigator's Brochure in English and Castilian
Current Certificate of GMP (Good Manufacturing Practices) of the manufacturer
Summary of the manufacturing process (if biological products)
A copy of the letter to the PNI (National Immunization Program) (If vaccines)
Delegation of functions of the sponsor (if applicable)
Simple statement of the applicant stating that the information submitted are true
Proposed labeling
2. New Drug Application11
approval
2.1 Procedure
All pharmaceutical products, whether imported or domestically manufactured, should be
distributed or used with proper marketing authorization. The application for marketing
authorization and any required information depending on the type of pharmaceutical product
must be submitted to the Institute of Public Health (ISP) using the approved forms upon
payment of the corresponding fee.
Anapplication must be kept on a written or electronic file which includes documents
submitted by applicants, stating the time and date of presentation with a reference number for
reference and tracking purposes, upon payment of the fee corresponding to the first
admissibility phase of the application.
The ISP reviews the application form and the information submitted and delivers a
statement on its admissibility within 10 working days. Upon acceptance of the application for
further evaluation, the applicant will receive the notice of this decision to proceed with the
payment of fees corresponding to the next phase of the procedure.
Upon admission of the registration procedure, the application will be forwarded to
appropriate department for the separate analysis for the technical and administrative
information. The administrative records, including the legal documents prepared in Castilian
or translated versions signed by the legal representative, an appointed professional or the
chief technical officer of the company will be checked primarily by the legal consultancy
department. The technical records concerning requirements in relation to the technical
information, pharmaceutical quality, safety and efficacy of the pharmaceutical product, as
10
http://www.leychile.cl/Navegar?idNorma=1026879&idVersion= 11
http://www.leychile.cl/Navegar?idNorma=1026879&idVersion=
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well as any other particular records as required by the type of product will be separated and
forwarded to specialized technical offices for evaluation.
If the evaluation results are positive, the requested registration will be granted by the
enactment of a resolution notified to the applicant within 6 months from the date of payment
of the corresponding fee.
The proper marketing authorization of a pharmaceutical product contains at least the
following information:
Name and address of the marketing authorization holder
Name and address of the manufacturer, importer, manufacturing or packaging
pharmaceutical laboratory, quality control laboratory, distributor, and licensor, if
applicable
Registration number
Name of the pharmaceutical product
Full qualitative and quantitative composition
Pharmaceutical form
Therapeutic group
Storage conditions and effectiveness period
Packaging and presentations
Authorized therapeutic indications
Prescribing and retail conditions pursuant to regulations of Ministry of Health
Whether the product is subject to legal control, batch control or others with
information regarding the situation
Authorization restrictions concerning the validity of the registered product and the
need to supervise the use thereof
Specific obligations of the holder
Obligation to inform about the first batch of production or import for distribution in
any shape or form
Other relevant information depending on the nature and specific composition of each
pharmaceutical product and relating to the production, import, quality control, storage,
distribution or delivery of the product, and the protection of undisclosed data.
Authorized graphic labeling, the patient information sheet or insert, the healthcare
professional information leaflet, and the specifications and testing methodology of the
finished product must be included in one or several stamped attachments, which are
considered to be a part of the registration certificate.
2.2 Rejection and procedures for appeal
An application may be rejected in the absence of compliance with the requirements stated
above and any supplementary regulations, according to the type of pharmaceutical product,
and the ISP will inform the applicant of any missing information required to fulfill the
authorization processes. The applicant must submit within 5 working days, upon which the
ISP proceeds to further assessment or rejects the applicant finally.
The application for marketing authorization may be rejected under the following
circumstances:
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Incidental issues: upon notification, the applicant must make any submissions as
deemed appropriate within 15 working days, after which the ISP issues the final
resolution.
Inadequate tests or insufficient information: upon notification, the applicant must
provide further information within 30 working days, and the marketing
authorization will be granted if such information is sufficient to fulfill the
conditions listed above.
If such additional information is not submitted within the specified period of time, or if
such information is submitted within the period, but once again, it is determined to be
insufficient, the ISP requests the Ministry of Health to order the rejection of the registration.
Then, the Ministry of Health issues a report on the rejection of the registration within 10
working days and forwards it to the ISP. Based on this, the ISP passes the resolution which
will be notified to the applicant.
2.3 Priority review
Not specified in the regulation.
2.4 Review period
Within 6 months from the date of payment of the corresponding fee
2.5 Required dossiers
2.5.1 Administrative Requirements
An application for marketing authorization should meet the following general
administrative requirements and include the following information:
Identification and address of the applicant, and legal representative in the case of legal
entities.
Name of the chief technical officer in charge of the entity requesting the registration or,
if not applicable, of the professional responsible for the technical information provided.
Name of the pharmaceutical product including:
- trade name, generic or common international name, or otherwise the pharmacopoeial
or chemical name;
- pharmaceutical form;
- unit dose per pharmaceutical form; and
- route of administration
Class or therapeutic group, further indicating the corresponding anatomical-therapeutic
classification.
Manufacturing system, including:
- domestic manufacture, for products manufactured in a legally and technically
qualified pharmaceutical laboratory, whether it is made at its own premises or by
third parties
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- imported products, including:
imported finished products manufactured abroad, whether imported directly
or by authorized third parties
imported semi-finished products in their final primary packaging to be fitted
in Chile, either directly or by authorized third parties
imported bulk products in their final pharmaceutical form to be packed in
Chile, either directly or by authorized third parties
imported semi-manufactured products to engage in other subsequent
manufacturing activities in Chile necessary to obtain a finished product,
either directly or by authorized third parties
Identification of the licensor under the name appearing on the license, if the license is
used for prosecution of the registration.
Name and address of the domestic or foreign manufacturing facility.
Product presentation describing the contents of different packages, retail, clinical
packages and/or medical samples, including elements or devices used for the
administration thereof.
Physical description of the packaging material, indicating the type of primary and
secondary packaging materials and other elements or devices used for administration, if
applicable.
Legal documents in Spanish or translated versions there of signed by the legal
representative, an appointed professional or the chief technical officer of the company
including the following:
- For products imported during any stage of the production process:
Marketing authorization certificate, pharmaceutical product certificate,
marketing authorization certificate or official certification recommended by
the World Health Organization, issued by the authorities of the country of
origin and duly legalized, certifying that the manufacturing facilities meet
the requirements established in the marketing legislation of their country,
that the product is registered in the country according to current regulations
(stating the approved formula in full), and whether the sale of the product is
subject to a restrictive regime or special marketing supervision, if
applicable.
Legalized manufacturing agreement signed by the applicant and the foreign
manufacturing pharmaceutical laboratory.
Legalized license, if applicable.
Official certificate issued by the competent health authority of the country
where the manufacturing facilities are located certifying that the foreign
manufacturer is duly authorized in their country and follows Good
Manufacturing Practices in accordance with WHO recommendations,
indicating production areas or types of products authorized for manufacture,
unless such information is included in the document mentioned in e.i herein.
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Legalized import agreement executed before a notary public, if applicable.
Manufacturing and/or domestic distribution agreement executed before a
notary public, attaching the corresponding sanitary authorization for each
facility.
Quality control agreement entered into with a pharmaceutical laboratory
authorized by the Institute and executed before a notary public, if
applicable.
- For domestically manufactured products:
Manufacturing and/or domestic distribution agreement executed before a
notary public, attaching the corresponding marketing authorization for each
facility.
Legalized license, if applicable.
Quality control agreement entered into with a pharmaceutical laboratory
authorized by the Institute and executed before a notary public, if
applicable.
2.5.2 Technical information requirements
The application for marketing authorization is required to meet the following general
conditions in relation to the technical information of the pharmaceutical product:
Clinical and pharmacological monograph prepared in Spanish signed by the chief
technical officer or technical adviser
Draft of graphic labeling prepared in Spanish intended for retail, clinical sales and
medical samples
Draft of the healthcare professional information leaflet endorsed by relevant scientific
data. The results of bioavailability and therapeutic equivalence studies are required if
the pharmaceutical products comprise active ingredients that are subject to this
requirement.
Draft of the patient information sheet endorsed by relevant scientific data
2.5.3 Pharmaceutical Quality Requirements
The application for marketing authorization is required to meet the following general
conditions to certify the pharmaceutical quality of the product:
Qualitative and quantitative composition of the pharmaceutical product in the
following order:
- Quali-quantitative statement for each active ingredient
- Quali-quantitative statement for each excipient
- Qualitative statement of any excipient used and removed during the manufacturing
process, if applicable.
- Quali-quantitative composition expressed in metric system units of mass or volume,
or units of biological activity. Whenever possible, the biological activity must be
indicated per unit of mass or volume.
- Active ingredients and excipients must be designated by their INN (International
Non-proprietary Names) or by the existing pharmacopoeial names. For non-
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pharmacopoeial substances, the chemical name in Spanish must be used. No
abbreviations or marks can be used for designating active ingredients.
- Any colorants in the product must be designated by their generic names or by their
chemical name. Other names with authorized colorants indexes in accordance with
the relevant national technical standard approved by the Ministry of Heath also can
be used to designate the colorants. The same provision applies when colored
capsules are used.
With respect to the active ingredients used in the manufacture of pharmaceutical
products, the following information must be submitted:
- Specifications and quality control methods, conforming to the requirements listed
in official texts, pharmacopoeias or in pharmacopoeial monographs, currently valid
in Chile
- Supplier and manufacturer of the active ingredients, including an analysis report
detailing all the characterizing parameters of the active ingredient
- Origin of the primary reference standard, including the corresponding certificate of
analysis indicating at least its origin, potency, traceability and other relevant
characterizing tests
- Spectrogram or chromatogram of the active ingredient and the standard obtained
by any instrumental method, if applicable.
- Storage conditions of the active ingredient used as raw material.
Specifications and control methods for every excipient, conforming to the
requirements listed in official texts, pharmacopoeias or in pharmacopoeial
monographs, currently valid in Chile
Analytical methodology in Castilian signed by the professional preparing the
application and by the quality control manager of the pharmaceutical laboratory or the
contracted supplier
- The analytical methodology must characterize the pharmaceutical product and
include controls as necessary to guarantee its quality, depending on the
manufactured pharmaceutical form.
- The analytical methodology of all pharmaceutical products must include the
following general test methods: sensory description (appearance, size, shape, color,
odor, etc.); selective identification of active ingredients; titration, performance or
activity of active ingredients; identification of impurities if applicable; and
description of the type and material of both primary and secondary packaging.
- Specific test methods according to the pharmaceutical form must be prepared
according to current additional technical standards issued by the ISP.
- The methodology must be validated, if not described in officially recognized
pharmacopoeias.
Special tests:
- Modified-release pharmaceutical forms, such as delayed-release or enteric
prolonged-release forms and others, must be indicated as such and endorsed by
pharmacokinetic, dissolution or dissemination tests, or other studies.
- Therapeutic equivalence and bioavailability studies, in the case of pharmaceutical
products comprising active ingredients subject to this requirement.
- 20 -
Fact sheet including analytical parameters and acceptance criteria characterizing the
product which, upon being made official, must be the specifications that the finished
product should meet throughout its effectiveness period.
Proposed effectiveness period and storage and packaging conditions for both the
pharmaceutical product and the reconstituted product, if applicable, endorsed by the
corresponding stability tests, including the following:
- Stability information, including at least: identification of the manufacturer and an
entity or individual responsible for conducting the stability test; temperature and
humidity conditions, packaging material and batches (minimum 3 batches); test
design and analytical procedures; and specifications of the finished product; all of
the above in accordance with the Guide of Stability of Pharmaceutical Products
(Guía de Estabilidad de Productos Farmacéuticos), a technical standard approved
by the Ministry of Health at the proposal of the ISP.
- When the product requires dilution prior to administration, stability data for the
formulation, the solvent (if included in the presentation) and reconstituted product
should be attached. In the event of the product requiring dilution and the solvent
not being included in the package, there must be an indication as to the
recommended solvents; stability tests for the formulation and the reconstituted
product must be additionally submitted.
- If the product requires dilution for immediate administration, only a compatibility
study for the corresponding diluents must be submitted.
- In the case of an active ingredient that is not part of the authorized formula of a
registered pharmaceutical drug, the results of forced degradation studies under
stress conditions, as well as the requirements stated above.
Technical information relating to the manufacturing process and the code for the
product, quality control, and physical-chemical data, presented in a record sheet
including flow charts and controls along the process.
For the purposes of determining the identity, potency, purity, stability, and other
physical, chemical, microbiological and bio-pharmaceutical requirements for drugs
for which a registration is sought, the ISP will observe the relevant rules in the
following pharmacopoeias and their supplements:
a) Chilean Pharmacopoeia.
b) International Pharmacopoeia.
c) European Pharmacopoeia.
d) United States Pharmacopoeia and the National Formulary.
e) British Pharmacopoeia.
f) French Pharmacopoeia.
g) German Pharmacopoeia.
h) German Homeopathic Pharmacopoeia.
i) Wilmar Schwabe Pharmacopoeia.
j) US Homeopathic Pharmacopoeia.
k) Mexican Homeopathic Pharmacopoeia.
l) Japanese Pharmacopoeia.
m) Spanish Pharmacopoeia.
n) Mexican Pharmacopoeia.
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In addition, the technical reports of the World Health Organization Expert Committee
on biological, biotechnological, chemical, radioactive, and similar standards, and the
provi ion o titl 21 o th Unit d St t “Cod o F d r l R gul tion ” (CFR),
Section 1.1, will be used for the purposes mentioned above. In the case of a
pharmaceutical product that is not listed in any of the foregoing official documents,
the ISP can accept or reject, either totally or in part, the technical information supplied
by the applicant with proper reasons. If those official texts do not specify the
tolerances or other specifications, these specifications must be included in the
application for registration so that the Institute can decide about their adequacy.
Due to the nature, diversity and extent of the general requirements for the
pharmaceutical quality of products, they may be listed in additional technical
standards approved by the Ministry of Health at the proposal of the ISP.
2.5.4 Safety and Efficacy Requirements
The application for marketing authorization is required to include information on the
safety and efficacy of the product:
Studies on the development of the pharmaceutical product, including chemical,
pharmaceutical, and biological tests as appropriate for the proposed formulation and
their rationale.
Preclinical trials such as those conducted in vitro with experimental animals usually
designed to gather further information as to whether more extensive studies should be
carried out in humans without exposing them to undue risk.
Selective pharmacological studies in animals.
Toxicological studies in animals, including acute and chronic toxicity, teratogenicity,
embryotoxicity, fertility, mutagenesis, and carcinogenesis tests, as well as any other
assays necessary for a proper evaluation of the safety and tolerance of a
pharmaceutical product.
Phase I, II, and III clinical trials endorsing the safety and efficacy of a pharmaceutical
product to be registered. Trials of products that do not correspond to the formula
intended for registration may be submitted, provided that their pharmaceutical and
therapeutic equivalence has been established by the corresponding studies.
Pharmacokinetic tests, if applicable.
Studies proving the bioavailability or therapeutic equivalence of a pharmaceutical
product to be registered, if the products comprise active ingredients that are subject to
this requirement.
A chemical, pharmaceutical, and biological report, including analytical, chemical,
physical, chemical, biological or microbiological tests to determine if the product
intended for registration is in conformity with the stated composition and has the
appropriate quality, and whether the proposed control methods are in accordance with
the state of scientific knowledge, the formulation and pharmaceutical form are
suitable for their intended purposes, and the container is suitable for proper
preservation.
A toxicological and pharmacologic report, including preclinical trials reporting the
toxicity of the product and its proven pharmacological properties.
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A clinical report prepared by independent experts evaluating the tests submitted by
the applicant with regard to the product having an adequate tolerance, the
recommended dosage being correct, and any eventual contraindications or side effects.
Registration Details and Conditions for Certain Pharmaceutical Drugs
The following conditions must be met for the registration of pharmaceutical products
comprising a combination of fixed-dose active ingredients:
1) Each active ingredient is required to contribute to the therapeutic effect of the
product, and the combination should contribute to improving patient compliance
with the treatment.
2) The dose of each component, the frequency of administration, and duration of the
treatment must grant safety and efficacy to the combination, and avoid the
potentiation of adverse reactions.
3) The ingredients including excipients used in the combination are required to be
chemically, pharmacologically, pharmacokinetically, and biopharmaceutically
compatible, either in vitro or in vivo, as appropriate.
4) Toxic or side effects should be at the same or less than those found in each of the
active ingredients separately.
Notwithstanding the foregoing, applications for the registration of pharmaceutical
products comprising a combination of fixed-dose active ingredients will be rejected
under the following circumstances:
1) Natural course of the product’s indication (disease or symptom) is different from
the one described in the registration for each of its active ingredients unless
proven otherwise.
2) Clinical, pharmacological or other tests subject to evaluation are not available for
any of the components.
For combined pharmaceutical products, the applicant applying for marketing
authorization must provide evidence of their product's safety and efficacy when used
at the same time. In addition, the applicant must submit further evidence as to the
following:
1) Each pharmaceutical product should contribute to the therapeutic effect of the
combined product.
2) The dose of each pharmaceutical product, the frequency of administration, and
duration of the treatment must grant safety and efficacy to the combination, and
avoid the potentiation of adverse reactions.
3) The ingredients used in each pharmaceutical product, including excipients, are
required to be chemically, pharmacologically, pharmacokinetically, and
biopharmaceutically compatible, both in vitro and in vivo as appropriate.
4) Toxic or side effects should be the same or less than those found in each of the
pharmaceutical products separately.
Given the nature of phytopharmaceutical products, the following considerations must
be taken into account for their registration:
1) To prove safety, results of pre-clinical trials, toxicity studies, and phase I clinical
studies, with the results of by phase II and III clinical trials for the proof of
efficacy should be submitted. If aforementioned information can be found from
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the official documents published by international organizations or foreign
agencies like WHO, FDA or EMEA, it can be used when requesting the
marketing authorization.
2) Applications must comply with the provisions stated in the general registration
requirements, including the following special rules:
- Therapeutic equivalence studies are not required at the time of registration or
when requesting any subsequent modifications.
- The description of the manufacturing process is required.
- The generic name must correspond to the taxonomic botanic denomination of
the plant providing the active ingredients.
- The quali-quantitative formula must include the type of plant preparation
used for the product, such as dry or fluid extracts, soft extracts, powder or
others, followed by the plant or parts thereof that have been employed in the
preparation, plus their scientific name, concentration and its equivalent plant
marker, if applicable.
- No narcotic or psychotropic substances or allopathic medicines is allowed in
the preparation.
- The identity and purity of the ingredients are determined in accordance with
foreign or international pharmacopoeias or sources of information, and are
required for validating the proposed analytical methodology.
- The analytical methodology for evaluating the finished product and the raw
materials should appear in any of the pharmacopoeias officially accepted in
Chile or in foreign sources of scientific information, if not, the corresponding
validation of the proposed analytical methodology is required.
- Finished product specifications must be in accordance with the
pharmaceutical form of the product. Notwithstanding the foregoing, the
titration of active ingredients in the finished product may be replaced with
the titration of specific plant marker.
- Products comprising isolated or synthetic active ingredients are not
considered to be phytopharmaceuticals, even if prepared from plant raw
materials.
Given the nature of homeopathic products, the following considerations will be taken
into account for their registration:
1) Regarding information on the pharmaceutical quality of the product:
- Generic names of active ingredients are required to be prepared in Latin as
specified in the recognized pharmacopoeias.
- In quali-quantitative formulas, each homeopathic substance must be prepared
in Latin, followed by the final dilution (i.e. in the finished product) and
concentration.
- A clear and complete description of the starting raw materials used in the
preparation of the homeopathic substance is required, in addition to their
characterization, method of preparation, and any physicochemical controls to
which they have been submitted.
- A description of the manufacturing methods used for preparing the finished
product.
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- Homeopathic pharmaceutical products must meet the finished product
specifications according to the pharmaceutical form in which they are
presented, like any other drugs, except for the titration of the active
ingredients in the finished product.
- When homeopathic products are administered as conventional tablets,
disintegration tests are required instead of dissolution tests.
2) With respect to information endorsing the efficacy and safety of the product, in
addition to the texts particularly mentioned in article 33, the use of other
pharmacopoeias, documents issued by WHO expert committees, or other
references acknowledged by decree of the Ministry of Health may be authorized
und r th ormul “By ord r o th Pr id nt o th R publi ” (Por ord n d l
Presidente de la República) at the proposal of the ISP.
In addition to meeting general product registration requirements, applications for the
marketing authorization of biological products must include the following information:
1) Name of the product, in the following order:
- Trade name or otherwise the generic (INN) or pharmacopoeial name.
Vaccines must be designated with a Latin name after the disease against for
which they provide protection.
- The manufacturing process when the active ingredients are living or dead
mi roorg ni m , r rring to th pro “living”, “ tt nu t d,”
onjug t d”, “in tiv t d” or oth r .
- The manufacturing method, in the case of active ingredients produced by a
living organism that has been genetically modified, referring to the process as
“r ombin nt”
- Pharmaceutical form and dosage, if appropriate.
2) Quali-quantitative composition in the following order:
- Quali-quantitative statement for each active ingredient.
- Quali-quantitative statement for each of excipient.
- Quali-quantitative statement for any adjuvant or adsorbing agent in the
product, if applicable.
- Quali-quantitative composition is required to be stated (if applicable) in units
of mass or volume in the metric system. The protein content or units of
biological activity is required to be stated in units of mass or volume, or
alternatively in international units.
- In the case of products for active immunization, the quali-quantitative
composition must be preferably stated in unit doses.
- Active ingredients and excipients should be designated by their international
non-proprietary names (INN) or by existing pharmacopoeial names.
Substances not included in the pharmacopoeia must be named after their
chemical or biological denomination, and as for vaccines Latin names must
be used according to the name of disease prevented by the vaccine used. No
abbreviations or marks may be used for designation.
- The taxonomic designation of microorganisms should be stated in short,
including the strain, serotype or other subspecies information when
appropriate.
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- The nature of any cellular system used for manufacturing biological products
must be disclosed, as well as the use of recombinant DNA or RNA
technology.
- When including living microorganism as part of active ingredient, the
chemical compound used in the chemical inactivation method should also be
disclosed.
- Should the quali-quantitative statement include adsorbing agents such as
aluminum, the quantitative statement must be per dose base.
- Preservatives must be quantitatively detailed at the end of the formula, if
present, which must include qualitative details of antibiotic residues and
antimicrobial agents used in the manufacturing process that may potentially
trigger allergic reactions in certain individuals.
- Any colorings in the product must be designated by their generic names or
by their chemical names. Other names with authorized coloring indexes in
accordance with the relevant national technical standard approved by the
Ministry of Heath also can be used to designate the colorings.
3) Active ingredient requirements, including quality and purity specifications, and
control methods:
- Manufacturer and supplier of the active ingredient.
- Supplier and traceability (if applicable) of the reference standard used for
describing the active ingredient.
- Storage conditions of the active ingredient, including temperature, humidity
and quality of the package.
- Description of other desired elements and related compounds, including their
properties and characteristics, structure, biological activity or others.
- When describing active ingredients obtained from human blood or blood
products, the following information is required to further indicate the
procedures followed to guarantee to the fullest extent the absence of
potentially pathogenic agents that may be transmitted:
Donor selection protocols.
Plasma fractionation method.
Testing of the plasma before and during the process, including the
determination of hepatitis B virus (HBV) surface antigens and antibodies
to Human Immunodeficiency Virus (HIV) and Hepatitis C virus (HCV),
as well as others as appropriate.
Storage temperature of the active ingredient and monitoring method.
Validity and expiry date.
Methods of inactivating infectious contaminants that the starting material
may contain, as well as intermediate and final products.
4) Manufacturing method:
- Description of the manufacturing method, including process controls and
tolerance.
- Description of the manufacturing process, including raw materials, critical
steps and reprocessing if applicable, as well as an indication as to how
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routine monitoring methods have been selected for controlling the finished
product.
- Description of source and starting materials for the production of the
biological active ingredient.
- Description of actions taken to prevent or control contamination by both viral
and non-viral adventitious agents such as HIV, HSV, HCV, transmissible
spongiform encephalopathy (TSE), bacteria, mycoplasma or fungi.
- Description and information about the validation process.
5) Control of excipients:
- Quality and purity specifications, as well as methods of controlling
excipients used in the formulation pursuant to the requirements set forth in
official documents authorized hereunder or otherwise in their monographs.
- A certification attesting to the absence of raw materials from animal species
affected by TSE and other transmissible diseases.
6) Control of finished products:
- At least the following information should be included:
Description and appearance (shape, color, odor and clarity if applicable).
Selective identification of active ingredients.
Titration, potency or activity of active ingredients.
Determination of impurities, if applicable.
Description of the nature and type of both primary and secondary
packaging material and accessories, in the event of the latter being in
contact with the pharmaceutical product.
Any other information as required by the Institute according to the
nature and composition of the biological product.
- Indication of acceptance criteria and minimum and maximum values if
considered to be deciding factors.
- Fact sheet, including laboratory parameters and acceptance criteria
characterizing the biological product which, upon being made official, should
be the specifications that the finished product must meet throughout its
effectiveness period.
7) Packaging material:
- Description of the nature and type of both primary and secondary packaging
material and accessories, in the event of the latter being in contact with the
pharmaceutical product.
- Information regarding the choice of primary packaging materials in view of
the protection against light and moisture, and their compatibility with the
pharmaceutical form and its administration.
- When the dosage form is sterile, information on the integrity of the package
sealing system used to prevent microbial contamination is required.
8) Stability tests for formulation, solvent and reconstituted product, as appropriate:
- The information on the stability of the product should include at least the
following:
Formula subject to study.
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Information of the person in charge of the stability test and the
manufacturer.
Temperature and humidity conditions, packaging material and batches
(minimum 3 batches), test design and analytical procedures, and
specifications of the finished product must be in accordance with the
Guidance of the Stability of Pharmaceutical Products (Guía de
Estabilidad de Productos Farmacéuticos), which is the technical standard
approved by the Ministry of Health at the proposal of the ISP.
- In the event of a biological product containing a new active ingredient in the
field of medicine in Chile, the information should include the results of
studies on forced degradation stability and stress conditions.
- As for effectiveness period and storage precautions proposed on the basis of
the corresponding stability test, effectiveness period for reconstituted product
(if necessary) should be included.
- In the event of the product requiring dilution prior to administration, the
information should include compatibility and stability tests with adequate
diluents, as appropriate.
9) Efficacy and safety requirements
- In the case of biotechnological products, a technical standard will be
approved by order of the Ministry of Health at the proposal of the ISP to
determine active ingredients and their presentation. And then, abridged
clinical studies endorsing the efficacy and safety of the product will be
accepted based on the existence of another registered biotechnological
product comprising the same active ingredients, unit dose, pharmaceutical
product and route of administration.
- Notwithstanding the foregoing, the applicant must submit comparative
studies including the reference product for each indicated active ingredient in
order to properly characterize the product and provide evidence as to the
similarity in their nature.
3. Generic drug approval application
3.1 Procedure
The marketing authorization of generic drugs can be according to the ordinary approval
pro (“N w Drug Appli tion” in thi do um nt), the simplified approval process
(“Simpli i d R gi tr tion Pro dur ” in thi do um nt), or th bbr vi t d pprov l pro
(“Short R gi tr tion Pro dur ” in thi do um nt). Th r gi tration procedure will depend on
the pharmaceutical product (NDA for new active ingredients, new doses or new routes of
administration; Simplified procedure if there are any products already approved with the
same ingredients in the same dose and with the same route of administration; and Short
procedure if the Ministry of Health requests it either for the implementation of public health
plans and programmes, or if the active ingredient is added to the National Formulary).
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3.2 Priority review
Not specified in the regulation.
3.3 Review period
Within 6 months from the date of payment of application fees
3.4 Required dossiers
All pharmaceutical products which require marketing authorization should meet the
same requirements depending on their nature and type. As for the generic drugs, refer to
the various requirements stated in the previous section.
Refer to Appendix 1 for the list of drugs that require bioequivalence evaluation.
4. Orphan drugs
The Resolution 411 of 2015 sets forth recommendations for the marketing authorization of
orphan drugs. This resolution states that the procedures in the Supreme Decree 3 of 2010
must be followed, but in the application the applicant must provide the justification for the
orphan drug designation, and will be able to present evidence of safety and efficacy with a
lower number of patients.
This resolution can be found in the following link:
http://www.ispch.cl/sites/default/files/res_exenta_411_05022015.pdf
5. Priority review12
5.1. Short Registration Procedure
Priority review is applicable for medicines for the following cases:
For serious diseases and life threatening conditions, and when medicines are apparently
expected to contribute to the improvement of quality of healthcare based on overall
evaluation of the seriousness of the target disease and medical usefulness.
When application is submitted for marketing approval and consideration is made based
on the opinions of the external experts.
5.2. Simplified Registration Procedure
The regular registration procedure may be simplified upon the interested party's request
by leaving out certain information as indicated below:
- In the case of pharmaceutical products comprising the same active ingredient, in
the same amounts, pharmaceutical form and route of administration as another
registered product whose registration has not been cancelled by the ISP due to
public health reasons, information on safety and efficacy may not be submitted,
unless the ISP determines the need for some or all of such information by means of
12
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a substantiated decision. In the case of a non-standard release pharmaceutical
product, the corresponding therapeutic equivalence studies should be submitted.
- In the case of widely recognized active ingredients which have been the subject of
ample experimentation so that their efficacy, safety of use and adverse reactions
are widely reviewed in the scientific literature, information on pre-clinical trials
may be replaced with the relevant bibliography. In addition, scientific information
relating to the efficacy and safety of the product intended for registration may also
be partially omitted, in which case the Institute will review the application and
reasonably require all the necessary information.
- In the event of a pharmaceutical product being pharmaceutically equivalent to a
registered product and listed under active ingredients for which evidence of
therapeutic equivalence has been required, the corresponding studies should be
submitted pursuant to specific regulations.
- In the event of a product having been manufactured in Chile for the sole purpose of
export, while it is considered to be a pharmaceutical product under Chilean
regulations and a food product in the country of destination as certified by the
relevant health authorities, the information on safety and efficacy may be omitted
unless the Institute by means of a substantiated decision determines the need for
some or all of such information.
The simplified marketing authorization procedure will not be applicable in the
following cases:
- The pharmaceutical product to be registered appears to have the active ingredient
that is used first time in the field of medicine in Chile, except for the active
ingredients widely known.
- The pharmaceutical product to be registered comprises the same active ingredient
as another registered product, and the disclosure of information about such product
is protected under the provisions of section 2, Title VIII of law no. 19,939.
- The pharmaceutical product to be registered is concerned with a new therapeutic
use, dosage schedule, extension of a previously approved route of administration,
or age group.
- The pharmaceutical product to be registered presents a change in the composition
and concentration of active ingredients over a registered formula, or contains new
salts, esters, complexes or isoforms of the active ingredients in a registered
pharmaceutical product, or comprises combinations of separately registered or
unregistered fixed-dose active ingredients.
- In the event of the pharmaceutical product to be registered being in a different
pharmaceutical form and wherein the release of active ingredients has been
modified.
- In the case of a combined pharmaceutical product to be registered for the first time.
- When requesting the registration of a biological product.
The registration procedure of homoeopathic pharmaceutical products may only be
simplified upon meeting all of the following conditions:
- The route of administration is oral or external.
- Absence of specific therapeutic indications in the graphic labeling or in healthcare
professional and patient information sheets.
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- The product comprises a single homoeopathic substance to a degree of dilution that
guarantees the safety of the drug.
- The homoeopathic substance making up the pharmaceutical product is obtained
from a plant, animal, mineral or chemical substances and raw materials described
in officially recognized pharmacopoeias in accordance with homoeopathic
manufacturing procedures also described in such texts.
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V. Others13
1. Good Manufacturing Practices
Good Manufacturing Practices (GMP) (Buenas Prácticas de Manufactura, BPM) is the
minimum technical standards established for all procedures with a view to ensure a consistent
and satisfactory quality in pharmaceutical products within statutory limits currently in force.
This standard will be approved by order of the Ministry of Health at the proposal of the ISP.
Both GMP and Good Laboratory Practices (GLP) standards will be applied to the
manufacture, quality control and storage of products for export. All pharmaceutical
laboratories should observe GMP and GLP standards as appropriate depending on the
activities for which they are authorized
Also, the manufacturing or packaging agreement relating to pharmaceutical products in
any stage of production should include the technical aspects of corresponding stage in
accordance with GMP.
The ISP inspects the facilities to supervise operating conditions in accordance with GMP
and GLP standards as well as the provisions stated in REGULATIONS OF THE
NATIONAL SYSTEM CONTROL OF PHARMACEUTICAL PRODUCTS FOR HUMAN
USE.
2. Drug Master File
Not specified in the regulation.
3. Labeling and package inserts
The label of the secondary packaging must be written in Castilian, in clearly visible
letters, and should include at least the following information without any advertising
or promotional texts.
- Name of the pharmaceutical drug.
- Pharmaceutical form and dosage unit in the case of monodrugs.
- Unconventional release pharmaceutical forms should be indicated as such on the
packaging material, as stated in the corresponding registration.
- Number of dosage units.
- Formula composition: quantitative and qualitative list of active ingredients and
excipients.
- Name and address of the holder and the manufacturing laboratory, packer or
importer, as appropriate.
- Route of administration.
- Approved retail conditions indicated with the appropriate abbreviation or full text.
- Expiry date. Furthermore, the included or recommended solvent should also be
indicated in the case of extemporaneous preparations, as well as the effectiveness
period after reconstitution, if applicable.
13
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- Registration number given by the Institute, preceded by the following acronym
“R g. I.S.P.” (In titut o Publi H lth r gi tr tion).
- Product code: Imported finished products must keep the original code.
- Storage and conservation conditions.
- Incorporation o th ption “M yor in orm ión n www.i p h. l" (Mor
information at www.ispch.cl) and other information, if applicable.
- Any other information specially and additionally required hereunder or deemed
necessary by the Institute upon registration or later.
The labeling of the primary packaging should include at least name of the
pharmaceutical drug; pharmaceutical form and dosage unit in the case of monodrugs;
route of administration; expiry date, expiry date of included or recommended solvent
in the case of extemporaneous preparations, as well as the effectiveness period after
reconstitution, if applicable; registration number given by the ISP, preceded by the
ollowing ronym “R g. I.S.P.” (In titut o Publi H lth registration), product code
(Imported finished products must keep the original code).
Pharmaceutical products packed as medical samples should include the caption
“MUESTRA MEDICA PROHIBIDA SU VENTAX” (Medical Sample. Prohibited
from Selling) in both the primary and the secondary packages in indelible ink, in a
clear and visible manner.
The labels must be printed or adhered to the outer surface of the package without
being in contact with its contents. Arial or other similar straight fonts should be used
for labeling purposes, in a minimum size of 6. The graphic labeling of imported
finished pharmaceutical products may exceptionally contain texts in other languages
apart from Castilian, provided that the text authorized by the ISP is not modified.
Under their sole responsibility, marketing authorization holders may include in the
labels industrial property information as required by law to exercise the rights arising
therefrom. Graphic labeling and healthcare professional and patient information
leaflets submitted upon applying for a marketing authorization must conform to their
final text once authorized, without prejudice to any amendments introduced by the
ISP. The font type and size for the secondary packaging stated above paragraph are
applied to the patient information leaflets. The same requirements should be applied
to the subsequent amendments of the graphic labeling and healthcare professional
leaflets and patient information sheets.
In addition to the information described in the above, pharmaceutical drugs intended
for direct sale should include the following details:
- Regular dosing instructions for each indication as authorized in the corresponding
registration.
- Any warnings as deemed necessary for safe and effective use of the product,
indicating contraindications, interactions and adverse reactions if applicable as
determined by the Institute upon granting the marketing authorization.
These products may be presented in dispensers provided that each blister or strip is
placed within an insert or other unit disclosing the full text of the caption approved for
the secondary packaging and the patient information sheet, if not enclosed.
A pharmaceutical product must be designated after its generic or trade name.
Notwithstanding the foregoing, if a pharmaceutical product is not being identified by
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its generic name and comprising a single active ingredient, the ingredient should be
identified by its generic name printed in legible characters under the following
conditions:
- The name should be located on the bottom line right after the authorized
denomination.
- The color of letters and the background of the authorized designation must be the
same.
- The font size should not be greater than fifty percent of the size of the product
name or less than the minimum of 6.
- The name should be printed in capital letters.
A pharmaceutical drug may not be designated with a trade name in the following
cases:
- The name is the same with or similar to an international non-proprietary name or
its own chemical or generic name, or other than a name referring to active
ingredients composing the product.
- It could cause confusion because the name is the same with or similar to the name
of another registered product with different active ingredients or therapeutic
properties.
- The name has been used to identify a product whose registration is cancelled or
expired, unless 10 years or more have elapsed in the case of products intended for
direct sales and 5 years or more in other cases, with different therapeutic properties,
or unless evidence is provided that the product has never been marketed in Chile.
- The name includes or is similar to the name of a food item, a cosmetic product or
any other product under marketing control.
- The name encourages misuse and self-medication.
Notwithstanding the foregoing, the holder of a registration may use the same trade
name for a number of registered pharmaceutical drugs provided that their
compositions comprise at least one active ingredient in common producing the main
therapeutic action and that they are intended for direct sale.
The containers of all parenteral solutions of 100 ml or more should include label
indicating the date, month and year of manufacture in a clear, visible and indelible
manner, and a warning to discard the product in case of turbidity or precipitate, unless
such conditions are deemed to be particular specifications of the finished product and
have been authorized in the corresponding registration. In addition to this, if the
parenteral solutions comprise electrolytes in a single drug, this must be indicated on
the label in letters of a particular color or otherwise different from the corresponding
color. The ISP will determine the colors for each cation of the active ingredient in the
respective solutions.
The amount of pharmaceutical product must be indicated by weight, volume or unit,
as appropriate. In the case of blisters or vials, each should have the indications for
primary packaging and the amount of active ingredient, unless that in view of the size
of the packaging, the ISP may issue a resolution relevant to waive in whole or part
some of these requirements.
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The composition of the product should be indicated by its active ingredients as
authorized upon granting of the registration and should indicate the equivalence of
active ingredients with the parent drug and the qualitative list of all excipients.
The composition of the formula should be indicated in percentages and in the
corresponding unit dose in the case of syrups, solutions, emulsions, powders,
ointments, creams, gels and other formulations of similar nature.
In the case of vials, capsules, tablets, pills, pessaries and suppositories, the
composition of the formula should be indicated by each unit dose. Solid or diluted
pharmaceutical forms that are not presented in units such as tablets, lozenges,
pessaries or the like should indicate the active ingredients in the current or usual
administration measures.
Labels must highlight the following captions as appropriate:
- “SUJETO A CONTROL DE ESTUPEFACIENTES" (SUBJECT TO CONTROL
OF NARCOTIC SUBSTANCES)
- "SUJETO A CONTROL DE PSICOTRÓ PICOS" (SUBJECT TO CONTROL OF
PSYCHOTROPIC SUBSTANCES)
- "FORMULARIO NACIONAL" (NATIONAL FORMULARY)
- "ENVASE CLÍNICO SÓ LO PARA ESTABLECIMIENTOS MÉDICO-
ASISTENCIALES" (CLINICAL PACKAGING FOR MEDICAL CARE
FACILITIES ONLY)
- "ENVASE CLÍNICO PARA VENTA EN ESTABLECIMIENTOS
FARMACÉUTICOS AUTORIZADOS" (CLINICAL PACKAGING FOR SALE
IN LICENSED PHARMACIES)
- "USO EXTERNO" (EXTERNAL USE)
- "USO BAJO SUPERVISIÓ N MÉDICA" (USE UNDER MEDICAL
SUPERVISION)
- "MUESTRA MÉDICA PROHIBIDA SU VENTA" (MEDICAL SAMPLE NOT
FOR SALE)
- R = Receta Simple, Simple Prescription, RR = Receta Retenida, Withheld
Prescription, RCH = Receta Cheque, Controlled prescription, VD = Venta Directa,
Non-prescription product
Any batch or sub-batch of a pharmaceutical product should be identified by a code
that will enable tracking at any stage from manufacturing to retail or use. The codes
should be indicated on the labels of primary and secondary packages containing the
pharmaceutical drug. The code must consist of numbers or combinations of letters and
numbers, and indicate the month and year of manufacture and the batch number in
sequential and chronological order. In other cases, any alphanumeric combination will
be accepted as a code, but it should indicate the month and year of manufacturing on
all labels and comply with general labeling requirements. In the case of imported
finished pharmaceutical products, the holder must submit the code of the country of
origin upon applying for registration and indicate how it should be interpreted. If a
pharmaceutical product from a single batch should be go through in discontinuous
steps until being finished, each step will be considered to be a sub-batch and must be
identified by an addition to the original serial number.
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4. Certificate of a Pharmaceutical Product
Certificate is for those products imported during any stage of the production process,
issued by the corresponding health authority of the country where the manufacturing facilities
are located certifying that the foreign manufacturer is duly authorized in their country and
follows Good Manufacturing Practices in accordance with WHO recommendations. It also
indicates that production areas or types of products are authorized for manufacturing, unless
such information is included in the document such as marketing authorization certificate,
pharmaceutical product certificate, marketing authorization certificate or official certification
recommended by the World Health Organization issued by the authorities of the country of
origin and duly legalized.
5. Manufacturing Licenses
Manufacturing and/or domestic distribution agreements notarized by notary public are
submitted with marketing authorization for each manufacturing facility.
6. Fees
The specified fees and charges for registration are as below:
4112126 General approval of pharmaceutical products $279,125
4112127 General registration of pharmaceutical products $837,375
4112124 Approval of simplified application of pharmaceutical products $216,195
4112125 Simplified registration of pharmaceutical products $646,555
4112137 General approval of phytodrug or other pharmaceutical products (Art. 53) $216,195
4112138 General registration of phytodrug or other pharmaceutical products (Art.
53) $646,555
4112139 Approval of simplified application of pharmaceutical products or other
phytodrug (Art. 52) $194,492
4112140 Simplified registration of pharmaceutical product or other phytodrug (Art,
52) $571,480
4112141 General approval of of homeopathic pharmaceutical product (Art. 53) $114,970
4112142 General registration of homeopathic pharmaceutical product $343,495
4112143 Approval of simplified application of homeopathic pharmaceutical product
(Art. 54) $20,358
4112144 Simplified registration of homeopathic pharmaceutical product (Art. 54) $94,758
4112128 Abbreviated application of pharmaceutical product registration $216,195
4112129 Short pharmaceutical product registration $646,555
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VII. References
Website
1. Institute of Public Health (Instituto de Salud Pública):
http://www.ispch.cl/
2. Library of the National Congress of Chile (Biblioteca del Congreso Nacional de Chile):
http://www.leychile.cl/
3. Ministry of Health of Chile (Ministerio de Salud de Chile):
http://web.minsal.cl/
Journal
1. Health Industry Brief - Medical Device/IT Health Vol.33, Information on market trend of
medical devices in Chile, Issued by Korean Health Industry Development Institute
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Appendix 1. List of Drugs that Requires Bioequivalence Tests14
14
http://www.ispch.cl/sites/default/files/uso_tratamiento.pdf