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
• Company Authorization (AFE)
• 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
• Company Authorization (AFE)
• 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.
Brazilian essential drugs list (RENAME)
There are 3 components of thePharmaceutical Assistance
• Basic Component
• Strategic Component
• Specialized Component
Brazilian essential drugs list (RENAME)
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.
Brazilian essential drugs list (RENAME)
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 ...
Brazilian essential drugs list (RENAME)
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
Brazilian essential drugs list (RENAME)
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
Brazilian essential drugs list (RENAME)
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
Brazilian essential drugs list (RENAME)
• Law 8666/93 determines the acquisiton rules for the Public Bodies;
• Low Price Acquisition;
• Generic products
Acquisition process
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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