National Health Surveillance Agency
Dr. TEJAL MEHTA
SEM 1 (M-PHARM)
• ANVISA is regulatory body of BRAZIL. Brazil is biggest
country of South America. Some of the small countries
nearby Brazil are following the rules according to
• ANVISA means “Agencia Nacional de Vigilancia
Sanitaria”. This abbreviation is in Portuguese language.
In English, it means “National Health Surveillance
Agency” or sometimes it is written as “Brazilian Health
ANVISA is established on 26th January, 1999. Thus it
does not have long historical backgrounds.
• To get information about ANVISA, one has to open the
website www.anvisa.gov.br. The website will open in
Portuguese language first.
• The National Health Surveillance Agency was established in
1999 by president Fernando Henrique Cardoso. Linked to the
Ministry of Health, the agency coordinates:
– The National Sanitary Surveillance System
– The National Program of Blood and Blood Products
– The National Program of Prevention and Control of
• Anvisa's Mission
– "To protect and promote health, ensuring the hygiene
and safety of products and services and taking part in
developing access to it."
– Knowledge (as a springboard for action)
– To be an agent for transformation of the decentralized
sanitary surveillance system, within a network, holding
a distinct position, legitimized by the population, as
regulator and promotor of social well-being.
• ANVISA is responsible for
– monitoring drug prices
– prices of medical devices
– control and inspection of smoking products
– technical support in granting of patents by the National
Institute of Industrial Property.
– protection of the health of the population by exercising
sanitary control over production
– marketing of products and services subject to sanitary
surveillance, controlling ports, airports and borders
– linked to the Brazilian Ministry of Foreign Affairs and foreign
institutions over matters concerning international aspects of
ANVISA is a part of NSSS
• National System of Sanitary Surveillance (NSSS) is an organization
of Brazil whose responsibility is
– To keep a watch over certain professional activities
– To put a stop to charlatanism
– To inspect ships, cemeteries and places where food was on sale
to the public.
• The federal, state and municipal units of this sanitary surveillance
– National Agency for Sanitary Surveillance (ANVISA)
– The National Council of State Health Secretaries (CONASS)
– The National Council of Municipal Health Secretaries
– The State, Federal District and Municipal Sanitary Surveillance
– The Central Public Health Laboratories (LACENS)
– The National Institute for Quality Control in Health (INCQS)
– The Oswaldo Cruz Foundation (FIOCRUZ)
– The State, District and Municipal Health Councils
HIGHLIGHTS OF ANVISA
National System of Sanitary Surveillance
• In this section, you will find the addresses (in portuguese) of
the federal, state and municipal units of sanitary surveillance
that make up the National System of Sanitary Surveillance.
• FAQs section
• Industry –
– In this section, industry professionals can obtain
information about Brazil's Generic Drugs Policy.
– If your company wishes to apply for registration of a
generic drug, whose reference drug has not yet been
informed by ANVISA, please make a formal request to the
Office of Generic Drugs.
– Pharmaceutical equivalence and bioequivalence tests
needed for registering generic drugs can only be carried
out by reference centers duly authorized by ANVISA.
• Legislation – Rules and documents related to regulation and
registration of drugs in Brazil. Various Guidelines different
categories are given.
Medicine Bioavailability Bioequivalence
Application Forms for BA/BE centers
Certification for Medicine Bioavailability/Bioequivalence Centers
Renewal of Certification for Medicine BA/BE centers
Centers for carrying out BA/BE shall observe the rules and
technical regulations in force.
• BA/BE Good Practices Manual is given in two volumes
• This section is covered under a specific part of ANVISA related
to Airport and Border regulation. Any new visitor of Brazil has
to take Vaccine against YELLOW FEVER at least 10 days before
his arrival to Brazil. And on arrival he has to show
“International Certificate of Vaccination (ICV)”.
• If he had taken Vaccine against yellow fever, before 10 years,
then he has to take it again a booster dose.
• Anvisa's Public Health Care Centers and Vaccination Rooms (in
Portuguese) are ready to provide the vaccine and to issue the
International Certificate of Vaccination (ICV), which is yellow.
• Every person vaccinated in one of the Sanitary Units of the
Unified Health System (SUS) receives the National Certificate
of Vaccination, which is white and accepted in the whole
• If, after that, you need the ICV, you should go to a Public
Health Care Center or to a Vaccination Room of ANVISA to
copy the National Certificate data to the International one.
Severe Acute Respiratory Syndrome
• In Brazil, there may be probability of getting Severe
Acute Respiratory Syndrome (SARS) disease, similar to
yellow fever. Thus, ANVISA had provided information on
website for it. They had provided WHO website link for
OFFICES OF ANVISA
Office of Ombudsman
• It monitors and follows up the development of activities
carried out by ANVISA. Council comprise of Representatives
– Public Administration Institutions
– Organized Civil Society
– Scientific Community
• The main function of advisory council is to provide
information upon request by any citizen, patient, industrialist
or health professional on any topics. Unlike other well known
regulatory bodies, ANVISA does not have specific offices for
each topic to provide specific information only. It has a
general functioning common Advisory council.
OFFICE OF OMBUDSMAN
• It is an independent body for direct communication of Citizens
or Institutes to attend the Complaints.
• It is characterized by impartiality and transparency.
• It has no direct or indirect linking with ANVISA. It is regulated
directly under the Brazilian ministry of health.
• It Start action against complaints within 2 days, if appropriate.
Regulations by ANVISA
Blood and blood products
Ports, airports and borders
REBLAS – Brazilian network of Analytical Laboratory
ANVISA - GUIDELINES
REGISTRATION OF NEW DRUG
• Registration procedure of new drug is divided in mainly 3
parts as follows…
1. Pre-registration measures
• Protocol for Clinical study
• Documents to be submitted
• Protocol for the new drug
• Protocol for import of new drug
• Alteration in Registration, Renewal of Registration
Thus, these three parts can be considered similar to IND, NDA
and Supplementary NDA as per US FDA.
I. Pre-registration measures
• In case of a new national drug product, the protocols of the
clinical studies and the results or current status of the studies
in compliance with the legislation in force has to be
• In case of a new imported drug product that will undergo
phase III clinical studies in Brazil, the study protocol and the
results or current status of the studies in compliance with the
legislation in force has to be submitted.
• Whenever phase III will take place with a new product
manufactured in the country, pre-notification for the
production of pilot batch according to the GUIDE FOR THE
NOTIFICATION OF PILOT BATCHES OF MEDICINES has to be
1. Documents to be submitted
Registration petition forms
Proof of payment of Sanitary Surveillance Inspection
copy of the company’s Operation License
Technical Responsibility Certificate by the Regional Pharmacy
• Copy of the notification protocol of pilot batch production
• Good Manufacturing Practices certificate (GMP) emitted by
2. Protocol for the new drug
• General data: package insert text, label etc…
• Expiry date by Stability studies
• All Toxicity study reports
• Clinical trial data with statistical treatments
• For Combination – Maximum 3 is allowed for oral or injectable
preparations. Four combinations are allowed only if the fourth
ingredient is caffeine.
• Retail Price: if the product is available in other market then
applicator has to submit retail price of product to consumer. If
product is not available anywhere, and first time registered in
Brazil, then has to submit the Proposed retail cost of new drug
• Physico-Chemical parameters of drug
• Synthesis route (all reagent, solvent, condition)
• Pharmacodynamic parameters
• Pharmacokinetic parameters
• Production Report(Batch size ,methods and equipments used)
• Q.C. of raw material and finished products
3. Protocol for the import of new drug
GMP of importing country or Inspection by ANVISA.
Documentation is allowed in Portuguese, English or
Label, Package Insert must be in Portuguese (Brazilian)
Official Documents like certificates given by importing
country, if it is in foreign language that must be translated
with Legal translator only.
In some cases, applicator wants to import Bulk drug from
foreign and then Pack the product in Brazil. In such cases,
Expiry Date must be counted from Manufacturing date in
foreign, and not the packaging date in Brazil
Additionally all document should be submitted in CD
III. Post-registration measures
• Any registration changes shall follow the procedures specified
in the GUIDE FOR MAKING POST-REGISTRATION ALTERATIONS
AND INCLUSIONS IN MEDICINES.
• ANVISA may undertake a control analysis of commercialized
batches in official laboratories in order to monitor the quality
and conformity of the drug with the drug registered.
Whenever necessary, ANVISA may request that the
companies train their technicians in order to enable them to
undertake this monitoring.
TECHNICAL REGULATION OF GENERIC
• Generic drug product is similar to a reference or innovator
product, expected to be interchangeable with latter, usually
produce after expiration or waiver of patent protection or of
other exclusive rights, and its effectiveness, safety and quality
had been already proven.
• Registration procedure for Generic drug is similar to new drug
– Pre registration measures
– Post registration
Additional Requirements in registration includes…
• Pharmaceutical Equivalence : Generic and Reference
• If anyone of Generic or Reference is Coated tablet, prove that
coating does not present Gastro-protection
• Bioequivalence study in Laboratories duly authorized by
• Exemption of Bioequivalence study
– Based on comparison of dissolution profile
– For BCS Class I product – High solubility & permeability
Medicines NOT accepted as GENERIC
• Parenteral that don’t contain API like WFI, glucose solution,
NaCl solution, electrolytes solution etc.
• Biological products: Blood, Plasma products
• Products obtained through Biotech except antibiotics
• Herbal drug products
• Vitamins &/or Mineral salts
• Antiseptics for Hospital use
• Endogenous Hormones of oral use
• Products with Diagnostic purpose and Radiological contrasts
• Some of OTC products
• Similar drugs are similar to Reference Drug product. It has
Administration, Strength ,Therapeutic action, but it only
Differs in Size, Form of product, Packaging, Labeling, Expiry
date, Excipients, Vehicles, and it is mainly identified by Trade
Mark / Brand Name.
• The advantage of similar drug is that it can be Dispense in
place of Reference drug, unless denied by Doctor in written
How to identify the types of drugs in the Brazilian market:
generic and branded?
• Generic drug package / box contain phrase“ Generic Drug Law
• Generic will be identified in blue large letter “ G “ printed
over a yellow emblem located in the lower part of the
package which carry the product.
Harmonisation of already registered drugs
• ANVISA had introduced some modification in Registration
procedures and Documents after 1st December 2004.
• Drugs Registered before this date, has to submit information
or data or documents related to drug, for harmonization with
Newer Registered drug products
• Registration of Homeopathic drugs is valid upto 5 years.
• For Injectables Homeopathic medicines, applicator has to
submit Risk/Benefit compared with oral presentation of same
• Combination of any synthetic/ semi-synthetic/ biological
product/ vitamins/ mineral salts/ herbal along with
homeopathic is forbidden.
Registration EXEMPTED for…
• Simple drug product (Single Ingredient)
• Without trademark or brand name
• Manufacturing as per Brazilian Homeopathic Pharmacopoeia
• Or in official compendia recognized by ANVISA
Registration REQUIRED for…
• Simple or Compound (2 or more Ingredient)
• With trademark and brand name
• whose formulation is composed of substances of verified
therapeutic action described in the homeopathic drug
product literature, official compendia, clinical studies or
indexed journals and manufacturing procedures are as per
Brazilian Homeopathic Pharmacopoeia
GITE :List of specified therapeutic group and
Drugs described in GITE can be sold OTC
Parentrals can not sold OTC (can not sell without Prescription)
Drugs not listed in GITE can not sell without PRESCRIPTION.
Any NEW DRUG, not to be sold under GITE
If New Drug has minimum 5 years experience in USA or
European market (with FDA or EMEA approval), and if it
comes under GITE list, applicator may request to classify it as
In-vitro Diagnostic product
ANVISA had classified in vitro diagnostic product into 4 classes as
Group A - Materials, devices, accessories & inputs for support of in
vitro diagnostic products.
Group B - for diagnosis of non-transmissible diseases.
Group C - for diagnosis of infectious-contagious diseases, except those
classified in Group D.
Group D - for diagnosis of infectious-contagious diseases, sexually
transmissible diseases or diseases spread by blood and blood
products, as well as identification of blood groups, transfusion or
preparation of blood products.
Documents required for Registration…
• Application form, Fee payment receipt
• Copy of License or Permit for Manufacturing.
• Label on the package of product, Instruction for Use
• Technical Report
• If imported, proof of Registration at competent health agency of
Level of Risk
Level 1 - Products with minimum risk
Level 2 - Products with potential risk
• ANVISA is more conscious about cosmetics and thus a
stringent rules and conditions are observed for cosmetics.
• ANVISA gives a List of Allowed PRESERVATIVES (56
preservatives) with the following details of preservatives
Maximum Allowable Concentration
Condition of Use and Warning
• Similar to preservatives, ANVISA also gives List of Allowed
SUNSCREEN AGENTS (23) with similar details
• Similarly, List of Allowed COLORING AGENT also given by
ANVISA with following information…
Name or Number of Coloring Agent
Field of Application : 1 / 2 / 3 / 4
Other Limitation or Requirements
• Field of Application is important to write for coloring agent.
Permitted for All Cosmetics
For All Cosmetics, Except EYE Area
In Cosmetic which don’t come in contact with Mucosa
In Cosmetic which come in contact with Skin & Hair only
List of RESTRICTIVE SUBSTANCES is also given by ANVISA.
• Restrictive substances can be used with some established
conditions and a specific warning for each individual
restrictive substance should be printed on Label as per
requirement. For such restrictive substance ANVISA had given
• Ref. No.
• Substance Name, Field of application or use
• Maximum Allowable Concentration
• Limitations and Requirements
• Condition of Use and Warning
List of PROHIBITED SUBSTANCE (412) is also given which cannot
be used in cosmetic products.
For Registration of Cosmetic, one has to enter the CODES in the
application form given in guideline.
• Codes are given for…
Cosmetic Product Group i.e. Toothpaste, Beauty cream
For Physical form i.e. Cream, Powder, Aerosol, Gel
Primary Packaging i.e. Al tube, film, vial, jar
External Packaging i.e. plastic bag, cloth bag, case, jar
• As per the latest updates of “GMP Guide for Pharmaceutical
Industry” approved by WHO’s World Health Assembly – WHA.
• For Import of Drug in Brazil from country which is not
included in MERCOSUL group requires Inspection of Drug
Manufacturing unit by ANVISA.
• MERCOSUL = Mercado Commun del Sul means “South
Common Market” includes Argentina, Brazil, Chile, Paraguay &
Uruguay (Group of Countries of South America)
• All documents should be submitted in Portuguese language
and Certified by the Brazilian Consulate, of the Country,
where the Drug for Importation in Brazil is manufactured
• GMP Certificate is Valid upto 1 year only.
Three stages of testing
• Clinical Stage
• Follow clinical studies as per Brazilian Pharmacopoeia
• There should be not more than 5% difference in amount of
Test and Reference API
• Clinical researcher has to Quantify Unchanged API and
• Interval before 2nd dose – atleast 7 t1/2 of API
• Weight of Volunteer should be +/- 15% of Normal Wt.
• If t1/2 > 24 hrs. – Collect sample upto 72 hrs
• Modified Release DF – Add Study with FOOD
• Protocol approved & licensed by National Committee of Ethics
• As per GCP, GLP ; using SOPs
• Use Enough Std. for Calibration Curve
• Chromatographic Methods are recommended
• NMT 20% samples are Re-analyzed.
• Loss of Samples shall be Justified
• Results below LQL (Lower Quantification Limit) are considered
as ZERO for statistical calculation.
• Calculate ASC, Cmax, Tmax. (ASC in Portuguese means AUC in
• For Multiple doses…
– Average Conc. In Steady state
– Fluctuation Rate in Steady state
• Submit – ANOVA, SSR, DF, F value, p value…
• Necessary to build 90% Confidence Interval (CI)
• For Low therapeutic Range API – 95% CI
• Information about Software Program used.
BA – BE GOOD PRACTICE MANUAL
Module 1. Clinical Step
Module 2. Analytical Step
Module 3. Statistical Step
Module 1. Micropipettes
Module 2. Water for Chemical Analysis
Module 3. Analytical Instrumentations
OTHER FUNCTIONS OF ANVISA:
REBLAS - Brazilian Network of Analytical Laboratories. It is the
laboratory network and every analysis and clinical studies
must be performing at any one of the REBLAS center
approved by ANVISA.
• Along with Drugs and Cosmetics, ANVISA have also regulation
– Medical devices
– Tobacco products
– Toxic products
RECENT TRENDS OF ANVISA:
• Launched the project to prevent the resistance against Antibiotic drugs
• The site is among the ten best in two categories of the iBest
Awards. ANVISA’s site is among the ten finalists in two
categories i.e. “Government” and “Health and Well-being”
• Launched the project to prevent the resistance against Antibiotic drugs.
INDIAN PHARMA IN BRAZILIAN MARKET:
Prominent product exporters:
• Zydus Cadila
• Torrent Pharmaceuticals
• Dr. Reddys Labs
• Ranbaxy Pharmaceuticals
• Intas Pharmaceuticals
• Sun Pharmaceuticals
ANVISA approved CROs in Ahmedabad:
BioArc Research Labs
Zydus Research Center (ZRC)
Torrent Research Center (TRC)
Lambda Research Center
Veeda Research Center
Synchron Research Labs