ANVISA

ANVISA

(Agencia Nacional de Vigilancia Sanitaria)

( Brazilian Health Surveillance Agency )

• Guided By:-Dr. R. K. Parikh

Mrs. Devarshi Shah

• Prepared By :-

Karishma Halatwala

Contents

• Introduction• Attributes of ANVISA• Regulation by ANVISA• Recent trends of ANVISA• Indian pharmacy in Brazilian market• Study questions• References

Anvisa's Mission

"To protect and promote health, ensuring the hygiene and safety of products and servicesand taking part in developing access to it.“

Values:-Transparency Knowledge (as a springboard for action) Co-operation

Vision

• The National Health Surveillance Agency was established by Law 9.782, of January 26, 1999. The Agency is designated an autonomous agency operating under a special regime.

• This means that ANVISA is an independently administered, financially-autonomous regulatory agency, with security of tenure for its directors during the period of their mandates. The Agency is managed by a Collegiate Board of Directors, comprised of five members.

• Within the structure of Federal Public Administration, the Agency is linked to the Ministry of Health, under a Management Contract. The agency incorporated additional attributions:

• Coordination of the National Sanitary Surveillance System (SNVS), the National Program of Blood and Blood Products and the National Program of Prevention and Control of Hospital.

• Infections; monitoring of drug prices and prices of medical devices; attributions pertaining to regulation, control and inspection of smoking products; technical support in granting of patents by the National Institute of Industrial Property.

INTERNATIONAL RELATIONSPRINCIPLES AND GUIDELINES

• Brazilian Foreign Policy• Unified System of Health (SUS)• Transparency (WTO)• National treatment(WTO)• Non discrimination (WTO)

Food Cosmetics Sanitizing Products

Tobacco Toxicology (pesticides) Health services

Drugs Medical Devices Blood and blood products

Post-market surveillance

Market regulation international

Blood, Tissues, and Organs

To assure the quality of treatments based on the use of blood, other tissues, cells, and human organs, Anvisa formulates technical rules, inspects services, and monitors the occurrence of adverse reactions caused by technologies available in Brazil. Blood transfusion, as well as tissues and organs implants are always risky for the receptors. Products and processes that don’t follow quality standards may be harmful and cause the transmission of diseases such as AIDS, and Hepatitis B and C. For that reason, the Brazilian Health Surveillance Agency works to diminish or to avoid completely those risks.

• Anvisa is the government body responsible for surveilling

the marketing of hygiene products, cosmetics, and

perfumes.

•To guarantee the quality of those products Anvisa works at

registration, notification, and inspection.

•The agency also creates norms and rules applicable to

the production processes, the techniques, the methods and

the use of those products by consumers.

Cosmetics

Drugs

Anvisa is responsible for drug registration and licenses to pharmaceutical

laboratories and to other companies inside the pharmaceutical production

flow. The agency is also responsible for establishing regulations applicable to

clinical trials and drug pricing.

Together with states and municipalities, the agency inspects factories,

monitors the quality of drugs, exercises post-marketing surveillance, takes

pharmacovigilance actions, and regulates drug promotion and marketing.

Moreover, Anvisa is in charge of analyzing patent requests related to

pharmaceutical processes and products, in partnership with the National

Industrial Property Institute (INPI).

Registration OF New Drug

• Registration procedure of new drug is divided in mainly 3 parts as follows…

1. Pre-registration measures -Protocol for Clinical study2.Registration

– Documents to be submitted– Protocol for the new drug– Protocol for import of new drug

3.Post-registration -Alteration in Registration, Renewal of Registration

Protocol for the import of new drug

• GMP of importing country or Inspection by ANVISA.

• Documentation is allowed in Portuguese, English or Spanish language.

• Label, Package Insert must be in Portuguese (Brazilian) language

• 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

FoodAnvisa coordinates, supervises, and controls activities regarding

registration, information, inspection, risk control, and rulemaking

to assure health surveillance over food, beverages, water,

ingredients, packages, technologies, contamination limits, and

veterinary residues.

This work is done in cooperation with other governmental

bodies, such as the Ministry of Agriculture, Livestock and Food

Supply and the state and municipal health offices, which take

part of the National Health Surveillance System.

Health Related services

• Health care quality is inextricably related to risk monitoring.

For that reason, health related services surveillance is a necessary task, for it

improves the quality of health services, by means of instruments that enable

health provision betterment.

• Anvisa coordinates nationwide health related services surveillance actions,

which are carried out by states, municipalities, and the Federal District.

• Besides, the agency formulates and enforces rules, establishes controlling

mechanisms, and assesses risks and adverse events regarding health provision

in hospitals, clinics, and health posts.

Cont…

Health related products is a huge area comprised of different levels of complexity, including infrared lamps, magnetic resonance equipment,

gauze compress, hip prosthesis, culture medium, and HIV test kit. Those products are used in medical, dental, and physiotherapeuticprocedures, as well as in diagnosis, treatment, rehabilitation and patient monitoring.

Laboratories

• According to Law 9782/1999, Anvisa is responsible for

coordinating health surveillance actions of laboratories that

take part of the official health quality control laboratory net. In

2004, Administrative Rule 2031/2004, creates the Public Health

Laboratories National System , to help improve the effectiveness of

health surveillance actions. This system is formed by four nets, among

which the Health Surveillance Laboratories Net is set, structured in

specific sub-nets, specified according to kinds of product, services, and

programs.

Cont…

• The Health Surveillance Laboratories Net performs analysis of products

and services such as food, drugs, cosmetics, sanitizing products,

immunobiologicals, blood products, toxic substances, biological and

non-biological contaminants, health materials and equipment. Those

analyses include areas of ports, airports, and frontiers.

• The base of this net is formed by the National Institute for Quality

Control in Health (INCQS), the State Health Public Laboratories (LACEN),

and other laboratories determined by current legislation

Medicine Bioavailability/ Bioequivalence Centers

• The International CROs that intend to be certificated by Anvisa,

must contact a national company to represent them at ANVISA.

• The selected national company will be responsible for the

submission of specific application forms for first certification or

certification renewal.

• It is recommended that the application form for certification

renewal be submitted at least 90 days before the expire date.

• Application form

• Renewal form

Pesticides and Toxicology

• Anvisa is responsible for assessing, regulating, controlling and

inspecting products and services that pose health risks, including pesticides,

pesticides components, and other chemical substances studied by toxicology.

• The agency carries out toxicological analysis for new pesticides registration

and for the reevaluation of molecules that have already been registered.

Anvisa also formulates norms, technical rules, and monographs of active

ingredients used in pesticides. Besides, the agency coordinates the National

System for Toxicology Surveillance, the Food Pesticide Residues Analysis

Program, and the National Wet of Centers for Toxicological Information.

Pharmaceutical Ingredients

• The pharmaceutical ingredients are the beginning of the

pharmaceutical industry production flow. To assure the quality of

drug production, Anvisa issues working licenses and exerts health

control over pharmaceutical ingredients, by means of health

inspection and rulemaking. To improve control, Anvisa has

developed a net system, that should be used by industries,

containing all pharmaceutical ingredients.

• Anvisa is also responsible for investigating notifications on quality

control deviation.

Ports, Airports and Borders

• According to its role as a governmental body, Anvisa is committed

to assuring the health control of ports, airports, and borders. This is

an important task, since it protects the health of travelers, and

guaranties the safety of means of transport and services in those

areas.

• This work involves environments, processes, product registration

and approval, including ingredients and technologies. Therefore,

Anvisa enforces national and international law such as the WHO

International Health Regulations (IHR), and other international acts

signed by Brazil.

Cont…

• Travelers information

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.

Sanitizing Products

Sanitizing products are largely used for cleansing and protecting

environments such as houses, offices, shops, and hospitals. To assure the

efficacy of those products, Anvisa makes their registration and notification,

observing all quality standards.

On the other hand, to enable quality improvement , the agency draws up

rules and standards, helps organizing information about adverse events

caused by sanitizing products, undertakes constant risk assessment,

monitors scientific and technological development, and adopts corrective

procedures to eliminate, avoid or diminish the hazards related to sanitizing

products.

Tobacco Products

• Anvisa is responsible for health surveillance and inspection of tobacco products. That includes rulemaking and law enforcement. To diminish tobacco use. • The agency has develop many actions: obliged the use of health warnings on cigarette packages and in cigarette advertising, prohibited tobacco advertising outside tobacco shops as well as food production that simulate

tobacco products.

Cont…

• All the procedures for tobacco registration, marketing, and promotion

are established by the agency. To help improve enforcing those rules,

Anvisa works in collaboration with other national and international

institutions, agencies, and governmental bodies involved in tobacco

control. This collaboration aims specially at: controlling the different

ways of tobacco promotion and dissemination, specially among young

people; reducing gradually public exposure to tobacco substances; and

reducing tobacco addiction.

Advertising Monitoring• Anvisa promotes public education and monitors advertising that

may pose public health hazards. Both kinds of work have been

developed to reduce public exposure to misleading and abusive

advertising and to help prevent problems such as self-medication,

intoxication, inadequate use of drugs and food.

• This way, Anvisa aims at diminishing hazards to health, supporting

legislation improvement, and fostering policies towards health

education.

Post Marketing Surveillances

Market Regulation

• Anvisa monitors drug prices and gives technical support for the

definition of drug prices. One of the agency’s attributions is the

Executive Secretariat of the Drug Market Regulation Chamber

(CMED), an inter ministerial body responsible for drug market

regulation and for establishing criteria of drug prices definition

and adjusting.

• Besides its role in CMED, the agency monitors health market so

that economic information may be observed in drug registration.

Pharmacovigilance

• Pharmacovigilance monitors drugs in the market. This kind of

post-marketing surveillance is put into practice by Anvisa, in

cooperation with states, municipalities and the Federal District.

• Although drugs are produced to prevent, alleviate or cure

diseases, they may cause undesirable and harmful effects. This

duality, sometimes tragic, is very significant to public health and

makes pharmacovigilance essential to health surveillance in any

country. Pharmacovigilance protects people from harm by

previously identifying risks and timely acting.

Technovigilance

• Technovigilance is a system created for monitoring after-marketing

adverse events and technical complaints about health products.

• The system aims at providing recommendations and adopting

measures that assure public promotion and protection against

hazards caused by products such as health equipment, health

materials, medical devices, in vitro diagnostic products, and

implants.

New drug labeling guide for the Health Ministry

• According to Dirceu Barbano, among the novelties of the new labeling rules is the valorization of the drug active ingredient name rather than its trade name, in a way to stimulate prescribers to use the products’ technical names. Highlighting the active ingredient name also aims at facilitating the identification of the drugs, avoiding mistakes in delivery or the use of such products. “This measure seeks to comfort the citizens, so they may verify it is a drug distributed by the public system, as well as accurately identify the drug and its way of use”, Barbano explained.

Cont…

• The manufacturers of such drugs will have 180 days from the publication of the norm to alter the products’ packages. The adequacy of the new packages will be checked by Anvisa during the process of authorization renewal and post-registration analysis.

vAnvisa approves the withdrawal of flavored cigarettes

• The Brazilian Health Surveillance Agency (Anvisa) published

on Friday 16 March a resolution that restricts the use of

additives in tobacco products marketed in Brazil. In

accordance with Anvisa Resolution RDC 14/2012, flavored

cigarettes will be withdrawn from the Brazilian market in up

to two years.

• As those additives’ main goal is to make tobacco products

more attractive to children and adolescents”

Cont…

• Substances that give a sweet flavour and enhance the

action of nicotine in the organism, such as levulinic

acid, theobromine, gama-valerolactone, and

ammonia will also be banished.

• “Scientific evidence shows that many of those

additives enhance nicotine power, making cigarettes

more addictive”,

ANVISA - GUIDELINES

1. REGISTRATION OF NEW DRUG2. TECHNICAL REGULATION OF GENEERIC DRUGS3. HARMONIZATION OF ALREADY REGISTERED

DRUGS4. GITE: List of Specified Therapeutic Group &

Indication5. HOMEOPATHIC DRUGS6. IN VITRO DIAGNOSTIC PRODUCT7. COSMETICS

1. REGISTRATION OF NEW DRUG• Registration procedure of new drug is divided in mainly 3

parts as follows…•

• Pre-registration measures• Protocol for Clinical study•

• Registration– Documents to be submitted– Protocol for the new drug– Protocol for import of new drug

•

• Post-registration• Alteration in Registration, Renewal of Registration

• II. Registration • 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 Council• Copy of the notification protocol of pilot batch production• Good Manufacturing Practices certificate (GMP) emitted

by ANVISA

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.– For Combination drugs’ application, one has to carry out

“Controlled Clinical Trial studies”. By this study the applicator has to prove the after combination of drugs that only final therapeutic action increases and there is no increase in risk or side-effects.

HARMONIZATION OF ALREADY REGISTERED DRUGS

(Resolution - RDC nº 134 of 29 May 2003)

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

GITE: List of Specified Therapeutic Group & Indication

(Resolution - RDC nº 138 of 29 May 2003)

• 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 OTC product.

HOMEOPATHIC DRUGS(Resolution - RDC nº 139 of 29 May 2003)

• 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 product

• Combination of any synthetic/ semi-synthetic/ biological product/ vitamins/ mineral salts/ herbal alongwith Homeopathic is FORBIDDEN.

IN VITRO DIAGNOSTIC PRODUCT(Administrative Order n. 8/MS/SVS, of

January 23, 1996)

• ANVISA had classified in vitro diagnostic product into 4 classes as follows…

• 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.

PACKAGE INSERT(Resolution - RDC nº 140 of 29 May 2003)

• Package Insert for Health Professionals• Package Insert for Patients• Medicine Package Insert Compendium (CBM)

– Yearly publication edited by ANVISA – Set of Package Inserts of Marketed drug products

• Therapeutic Memento :-– Information by Official Laboratories for health

professionals.

COSMETICS(Resolution 335 of July 22, 1999)

• Four Categories– Hygiene Product - Soap, Shampoo, Tooth paste…– Cosmetic – Lipstick, Beauty Creams, Hair dye, Talc,

Eye cosmetics, Nail cosmetics, Sunscreens, Oils…– Perfume– Children’s Product

TECHNICAL REGULATION OF GENEERIC DRUGS

(Resolution - RDC nº 135 of 29 May 2003)•

• Definition: • 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 registration. – Pre registration measures– Registration– Post registration

• 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 product.

• Physico-Chemical parameters of drug• Synthesis route (all reagent, solvent, condition)• Pharmacodynamic parameters• Pharmacokinetic parameters• Production Report

– Batch size (minimum to maximum)– Method and Equipment 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 Spanish

language.– Label, Package Insert must be in Portuguese (Brazilian)

language– 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

• Annexo I• Technical Procedures for Sanitary Inspection of

Palm Hearts Producers Based Abroad• Form requesting a sanitary inspection of premises

producing preserved palm heart• located abroad• Annex II• Instructions for Completion of Brazilian Sanitary

Surveillance Agency Remittance voucher.

• Technical procedures• Annex I• INFORMATION ABOUT IMPORTING COMPANY• Company Name: |_|_|_|_|_|_|_|_|_|_|_|_|

_|_|_|_|• CNPJ: | _|_|_|_|_|_|_|_|_|_|_|_|_|_|• Address:|_|_|_|_|_|_|_|_|_|_|_|_|_|• CITY:|_|_|_|_|_|_|_|_|_|_|_|_|_|_|_|_|_|_|

• STATE:|_|_| CEP:|_|_|_|_|_|_|_|_|• e-mail: |_|_|_|_|_|_|_• Telephone:_|_|_|_|_| • FAX: (__)|_|_|_|_|_|_|_|_|• IMPORTED PRODUCTS• roduct Name:• 1__________________________• 2__________________________• 3__________________________

• INFORMATION ON PRESERVED PALM HEART PRODUCING COMPANY

• COMPANY name:-• Address:-

Indian pharma in Brazilian market

• Many Indian Pharmaceutical companies are exporting pharmaceutical

products to Brazil and hence follows ANVISA

• Prominent among them are:

Zydus Cadila

Torrent Pharmaceuticals

Ranbaxy Pharmaceuticals

Intas Pharmaceuticals

Sun Pharmaceuticals

The major drugs exported are:

• Losartan Potassium

• Zolpidem tartarate

• Alprazolam

• Enalapril Maleate

• Nortryptiline

• Carbamazepine

• Clonazepam

• Fluconazole

• Fluoxetine, etc.

ANVISA approved CROs in Ahmedabad:

• Zydus Research Center (ZRC)

• Torrent Research Center (TRC)

• Cadila Pharma

• Lambda Research Center

• Veeda Research Center

• Synchron Research Labs

Questions…

• What is ANVISA. Give its attributes• Give information about the website of ANVISA• Enlist the areas of action of ANVISA• Describe in detail the guidelines of ANVISA• Give a brief introduction of ANVISA. And

comment about the Indian pharmaceutical market in Brazil.

References

www.anvisa.gov.br

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