General overview of Brazilian Health regulation Brazilian ...

General overview of Brazilian Health regulation

Brazilian Health Surveillance Agency (Anvisa)

Victor Gomes Pereira

Regulation and Health Surveillance Specialist

April, 2016

K-Pharma Academy 2016

General overview of Brazilian Health regulation

1. Presentation on Brazilian Healthcare Regulation (Pharmaceutical, Medical Devices)

2. Healthcare policy tendencies.

3. Brazilian essential drug products list and drugs procurement process

Presentation on Brazilian Healthcare Regulation (Pharmaceutical, Medical

Devices)

The Brazilian Health Surveillance Agency (Anvisa)

Regulatory Agency: Administrative Independence and financial autonomy

• 16 years since its creation (Law 9.782/1999)

• Linked to the Ministry of Health

• Management Contract (indicators and targets)

• Stability of the Directors (mandate)

• Board of Directors – 5 Directors named by the President of Republic, for a mandate of 3 years, renewed once for another 3 years.

National Health Surveillance System (SNVS)

• Brazilian Constitution (1988)

• Integrates the National Health

System (SUS)

• Integrated by the Federal, State

and Local level

• Coordinated by Anvisa

• Characteristic: articulation and

decentralization

Federal Ministry of HealthANVISANational Institute for Quality Control in Health

Municipal LevelLocal Secretary of HealthLocal Health Surveillance

State LevelState Secretary of HealthState Health SurveillanceLaboratories of Public Health - LACEN

Anvisa Regulation Fields

Medicines Medical devices

PesticidesCosmetics Tobacco

Advertisement Ports, airports and borders

Laboratórios

International affairs SNVS coordination

Sanitizer

Official Laboratories

Foods

Health Service

Pharmacovigilance

Blood, Tissues and

e organs

Brazilian Legal Framework

• Anvisa has competency to edit

legislation related to health

surveillance subjects – Resolution

of the Board of Directors (RDC)

• RDC – elaborated following the

Good Regulatory Practices

Process

• Regulatory Agenda – annual

prevision of priority themes to be

regulated

• Transparency: legislation is

published on the Official

Newspaper (Diário Oficial da

União) and is on ANVISA’s

website

Federal Law and Decrees

• Law 6360/76 (beyond other purposes, gives legal provision for productregistration);

• Law 6437/77 (sets violations of federal health legislation andestablishes their respective sanctions);

• Law 8080/90 (defines the Unique Health System);

• Law 9782/99 (establishes Anvisa’s roles and responsibilities, definesthe National Health Surveillance System);

• Law 8077/13 (has replaced Decree 79094/77 - gives interpretation ofAct 6360/76).

Marketing Authorization / Registration: drug productsand medical devices

• Premarket Activities

Company Authorization (AFE)

GMP Certification

Registration/Notification

• Post-market Activities

Post-aprovall changes

Renewal (each 5 years)

Monitoring Programs

Postmarket surveillance

Drug product Registration

• In Brazil, drug products need to be registered.

• The registration must be renewed every five years.

• Categories of Drug Products registered in Brazil:

“New” drugs (innovative and others)

Synthetic and semi-synthetic drugs

Biologicals (includes biossimilars)

Herbal medicines

“Copies” (Synthetic and semi-synthetic drugs)

Generic Drugs

Similar Drug products (“brand generic”)

Drug Products Registration – Category of medicines

CATEGORY OF DRUGS

NEW DRUGS

BIOLOGICALS

HERBAL MEDICINES

GENERIC DRUGS

HOMEOPHATICS

NOTIFIED

SPECIFIC DRUGS

SIMILAR

Drug Registration – legislation

Registration Resolution

Synthetic and semi-synthetic drugs (news, generics and similars)

RDC Nº. 60/2014

Homeopathic Drug RDC Nº. 26/2007

Herbal Medicines RDC Nº. 26/2014

Biological Drug RDC Nº. 55/2010

Specific Drugs RDC Nº 24/2011

Notified RDC Nº 199/2006

Post-Registation Resolution

Drug Post Registration RDC Nº 73/2016

Drug Post Registration for biologicals RDC Nº 24/2013

http://portal.anvisa.gov.br/wps/content/Anvisa+Portal/Anvisa/regulacao

+sanitaria/Assuntos+de+interesse/Legislacao+Sanitaria

GGMED’s flow chart

General Office of Drug products and biologicalproducts (GGMED)

Office ofadministrative

Appeal

Coordination ofprescribing information

and labelling

Office of Safety andEfficacy Evaluation

Office of registrationevaluation

Office of post-approvalchanges evaluation

Office of biologicalproducts

Office of specific, notified andherbal drugs, homeopathy and

medicinal gases

Drug Products Registration – main requirements

• Company Authorization (AFE)

• Good Manufacturing Practices (GMP certificates)

• Information about API used – drug master file

• Production Report (quanti/qualitative formula, role of each excipient, productiondetails, summarized validation report)

• Quality Control Report

• Analytical Method Validation

• Stability studies of 3 pilot batches (Zone IVb)

• Pharmaceutical equivalence and bioequivalence for “copies” (Center Certified byAnvisa)

• Clinical trials for “news”

Drug Products Registration – main complementary legislation

Subject Resolution

Bovine spongiform encephalopathy (BSE) RDC Nº 305/2002 and RDC Nº 68/2003

List of Groups and Specific Therapeutic Indication RDC nº 138/2003

Analytical and Bioanalytical Validation Guideline RE Nº 899/2003 and RDC Nº 27/2012

Stability studies guideline RE Nº 1/2005

Leaflets RDC Nº 47/2009

Labeling RDC Nº 71/2009

Pharmaceutical equivalence and dissolution profile RDC Nº 31/2010

BE/BA studies exemption guideline RDC Nº 37/2011

Stability studies for biological products RDC Nº. 50/2011

Drug Products Registration – GMP legislation

Subject Resolution RDC

GMP guide for Drug Products RDC Nº 17/2010

GMP guide for APIs RDC Nº 69/2014

GMP Certificate RDC Nº 39/2013

Medical Devices

Medical Devices Registration – Classification

• For regulatory purposes MD are separated into:

Non IVD: e.g. equipment, software, articles, and materials.

IVD: e.g. reagents, calibrators, standards and controls.

Each of them have their specific legislations and requirements,

including classification.

GGTPS´s flow chart

• General Office of Medical Device (GGTPS )

Office ofEquipment

Office ofMaterials

Office of Products used for in vitro

diagnosis

Coordination of of Ortopedic materials

Coordination ofclinical trials for medical devices

Non IVD Classification

Established by RDC 185/2001:

• Four Classes:

– Class I: low risk;

– Class II: medium risk;

– Class III: high risk;

– Class IV: maximum risk.

18 Rules are used to classify the device according to the duration of

contact with the patient, the degree of invasiveness and the body part

affected by the use of the device.

IVD Classification

• Four Classes according to RDC 26/2015:

– Class I - low risk devices to the individual and low risk to public health (e.g. sample

collection receptacles, culture media);

– Class II - medium risk devices to the individual and/or low risk to public health (e.g.

cholesterol quantitative test);

– Class III - high risk devices to the individual and/or medium risk to public health

(e.g. syphilis test); and

– Class IV - high-risk devices to the individual and high risk to public health (e.g. HIV

1/2 Ab assay).

Medical Device Registration

• There are two types of premarket applications:

– Registration: Classes III and IV

– Simplified registration: Classes I and II

• The registration is valid for 5 years and must be renewed after this

period.

Medical Device Registration– main requirements


• GMP Certification

• Requests a comprehensive documentation, including all technical data and tests about the device, and for some types of devices, clinical data are also requested.

• Requirements defined by RDC 185/01 (nIVD) and RDC 206/06 (IVD).

Medical Device Simplified registration– main requirements


• Does not request GMP certification. However the manufacturer shall

comply with GMP requirements and may the subject to a regulatory

inspection at anytime.

• Requests only summarized documentation and specific forms;

Medical Device – main legislation

Subject Resolution

Premarket technical review for device and family of devices (non IVDs)

RDC Nº 185/2001

Premarket technical review for device and family of devices (IVDs)

RDC Nº 206/2006

Essential Requirements of Safety and Effectiveness RDC Nº 56/2001

MD Notification (nIVDs) RDC Nº 20/2015

Good Manufacturing Practices Requirements for MD RDC Nº 16/2013

GMP certificate as requirement for product registration RDC Nº 15/2014

There are other RDCs which defines additional requirements for specifics devices.

Healthcare policy tendencies

Productive Development Partnership (PDP)

• Defined by a Ministry of Health Decree ( Portaria n° 2.531/2014);

• List of SUS strategic products (APIs, Drugproducts, vaccines, softwares...)

• Encouraging Technology Transfer and use the purchasing power of the State.

Productive Development Partnership (PDP)Steps of the PDP

• 1) Proposal of a PDP project -submission and evaluation ofthe project;

• 2) Implementation of PDP approved project- commitmentagreement ;

• 3) Execution of the PDP -Acquisition contract;

• 4) Technology Transfer;

Holder oftechnology

PublicLaboratory

NationalLaboratory

Federal Government

The holder is responsiblefor the technology transferand to supply the productfor the Public Lab

Acquisition of theproduct exclusivelyfrom the holder oftechnology

Technology receiver; Responsible for the manufacturingof the product atthe end of theprocess

When the public Lab isnot capable to

manufacture the API or critical component

a National lab mayparticipate

RDC N° 37/2014

• Over 1000 submissions waiting for analysis in generic/similar products queue;

• Approximately 700 days for thefirst evaluation;

• Lots of different submissions for the same API.

RDC N° 37/2014

API N° of submissions N° of products alreadyregistered

Ibuprofen 16 27

Rivastigmine 14 9

Escitalopram 12 17

Montelukast 12 5

Sildenafil 12 35

Pregabalin 12 17

Pemetrexed 10 9

Oxiplatin 10 15

Trometamol 10 10

Meropenem 9 11

RDC N° 37/2014

• Determination ofprioritization criteria;

• The submissions are scored;

• Determination of a deadline for theevaluation

RDC N° 37/2014

• First generic ou similar product;

• One of the components of the Brazilianessential drug products list;

• Used for a negleted disease;

• Inovation manufactured in Brazil;

• API manufactured in Brazil.

Brazilian essential drugs list and drugs procurement process

Brazilian essential drugs list (RENAME)

• Brazilian’s first essential drugslist was elaborated in 1964

• The national policy for drugproducts was stablished only in 1998.

• The law 12.401/2011 states the integral therapeutic assistance

• All drug products used in theSUS must be described in RENAME

• Law 8666/93 states theacquisition process for PublicBodies.


There are 3 components of thePharmaceutical Assistance

• Basic Component

• Strategic Component

• Specialized Component


Basic Component

• The basic component is composed by the drug substances used in thebasic assistance

• Insulin, hypertension medications, birth control pills...

• The financing of this program is shared by the 3 levels of the Government: Federal, states and local.


Stratategic Component

• The Strategic component is composed by the drug substances used in thetreatment of endemic diseases, with epidemiological importance, economicimpact or diseases affecting vulnerable people

• The acquisition is made by the Minstry of Health .

• Examples of Strategic Programs: Control of tuberculosis and Hansen’sdisease, AIDS, Quit smoking programs ...


Stratategic Component – Institutional responsabilities

Ministryof Health

Municipaldistrict

States

Treatment protocols;Planning;

Financing and acquisition;Distribution to states and

municipal district fdr

Storage; Distribuition to theMunicipal district;Planning

Storage; Distribution to the local

Health units; Planning;

Dispensingdr


Specialized Component

• The Specialized component was stablished by a regulation of Ministry ofHealth GM/MS N° 2.981/2009 and this component is divided in 3 groups

Group3

Group2

Group1

Increasing of complexity


Group 3- Funded by the 3 levels of the Government

Group 2- Funded by States

Group 1 – Funded exclusively by the Federal Government

Specialized Component-Acquisition


• Law 8666/93 determines the acquisiton rules for the Public Bodies;

• Low Price Acquisition;

• Generic products

Acquisition process

THANK YOU!

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Obrigado!

Contacts

Agência Nacional de Vigilância Sanitária - Anvisa

SIA Trecho 5 - Área especial 57 - Lote 200

Zip code: 71205-050

Brasília - DF

Phone: + 55 61 3462 6000

www.anvisa.gov.br

www.twitter.com/anvisa_oficial

Anvisa Atende: 0800-642-9782

[email protected]

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