Transcript II Workshop on Medicines Regulation in the Caribbean Region Regulatory Function of DRUG REGISTRATION Celeste Sánchez González, PhD. Adviser.

II Workshop on Medicines
Regulation in the Caribbean
Region
Regulatory Function
of
DRUG REGISTRATION
Celeste Sánchez González, PhD.
Adviser. CECMED/Cuba
[email protected]/[email protected]
II Workshop on Medicines Regulation
Caribbean Region
th in the th
Barbados, September 8 and 9 , 2009
Barbados, September
Se 8th and 9th , 2009
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Content of the Presentation
1. Drug registration as a regulatory function
2. What does drug registration is?
3. Regulatory requirements for drug
registration
4. Ways to implement registration
5. Steps of the registration process
6. Drug registration requirements according to
the Pan American Network for Drug
Regulation Harmonization (PANDRH)
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An approach of Regulatory Functions of Medicines
National Regulatory Authorities (1)
Administrative Elements
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Policy, legislation, regulations
Human resources
Finance
Infrastructure
Regulatory Functions
Technical
elements
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Standards
Specifications
Guidelines
Procedures
Regulation level
Licensing of
premises,
practices &
persons
Inspection of
manufacturers
&
distributors
Product
assessment
& registration
Monitoring
quality of
drugs
Control of
drug
promotion &
advertising
Adverse drug
reaction
monitoring


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Central
State/province
District
Community
(1) Ratanawijitrasin S. & Wondemagegnehu E. Effective drug regulation. A multicountry study.
WHO, 2002
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Another approach of Regulatory Functions of
Medicines National Regulatory Authorities (2)
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2
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Regulatory System
Licenses: For medicines -vaccines- (Registration)
Licenses: For Companies (manufacturing, importing,
exporting, distributing)
Post-marketing surveillance
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5
6
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Lot Release
Access to Laboratory (for quality controls)
Regulatory Inspections: GMP and distribution channels
Regulatory overview to clinical trials
(2) Milstein J. Belgharbi L. Regulatory pathways for vaccines for developing countries. WHO.
Bulletin of the World Health Organization, February 2004
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Drug Registration
An important task for a Drug National
Regulatory Authority (NRA) is to institute a
system which subjects all pharmaceutical
products to:
•Pre marketing evaluation;
•Marketing authorization (registration);
•Postmarketing review
To ensure that they conform to required
standards of quality, safety and efficacy
(3) Guiding Principles for small national drug regulatory authorities. Quality Assurance of
pharmaceuticals:a compendium of gudelines and related materials, Vol. Geneva, WHO, 1997:18-30.
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Drug Registration
Drug registration a function of regulation and control
within NRAs that deals with this objectives interrelated
with the other regulatory functions
It has been defined as: “a system that subjects all
pharmaceutical products (under the scope of the
NRA) to pre-marketing evaluation, marketing
authorization (registration), and post-marketing review
to ensure that they conform to required standards of
quality, safety and efficacy established by NRA” (4).
(4) How to implement Computer-Assisted Drug Registration. Annex 2. Regulatory Support Series, No.
2. Geneva, WHO/MSH, 1998.
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Drug Registration Results
The outcome of the drug registration process is the
issuance or denial of a pharmaceutical product
marketing authorization or license (registry) The registry
holder is obliges the registry holder to commercialize the
product for the therapeutic conditions indicated, with the
specifications, pharmaceutical form, presentations,
manufacturer, storage conditions,etc.
Information for patients, health professionals are also
results of this regulatory function
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Drug Registration
•Registration
•Variations
•Renewals
Manufacturer
Pharmaceutical Product
GMP
Requirements
Quality
Safety
Efficacy
Laboratory
Information
Inspections and
Establishment Licenses
Rational Use/Promotion
and Advertising
Post Marketing Controls
and Surveillance
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Drug Registration Requirements in
Terms of Regulation for a NRA
• Legal Bases
• Guidelines
• Assessment procedures
• Human resources and others
• Records
• Availability of the information
(5) WHO DATA COLLECTION TOOL (To be used jointly with the Guidance for the
assessment of Drug Regulatory Systems). WHO, 2009
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Drug Registration Assessment and
Requirement Characteristics
BASIS OF REGISTRATION
OWN
ASSESSMENT
RELY ON EXPORTING
COUNTRY´S NRA
RELY ON REPORTS OF
ASSESSMENT FRON
ANOTHER NRA
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REGISTRATION. RELY ON EXPORTING CONTRY´S NRA
Does Product have Registry in Exporting Country?
Yes
No
Is the Product the same as
in exporting country?
Yes
OWN ASSESSMENT
No
No
Are differences acceptable?
Yes
• Check whether analytical methods for finished product can be applied at NQC laboratory
• Check if stability studies were conducted including the national climatic zone requirements
• Review, (adapt if necessary) labelling and product information/ Assess interchangeability, if required
(5) WHO. Marketing Authorization. A manual for Drug Regulatory Authorities…..
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Drug Registration. Phases for the Assessment
Reception
(Checking the formal validity of the Application)
Assessment
Quality: (Product design/Manufacturing GMP profile)
Product Information: (Labels, Information for patients information for
health professionals)
Interchangeability/Safety and efficacy
Follow-up
Post-marketing activities
(Update stability data, variations of the product/specifications/manufacturing
process, update product information, marketing status, control of promotional
activities, pharmacoepidemiological studies, monitor adverse drug reactions)
(4) How to implement Computer-Assisted Drug Registration. Regulatory Support Series, No. 2. Geneva, WHO/MSH, 1998:50.
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Drug Registration Requirements
OWN ASSESSMENT. DIFFERENT PARTS OF THE
INFORMATION
LEGAL AND ADMINISTRATIVE INFORMATION
PRODUCT INFORMATION
QUALITY
INTERCHANGEABILITY
SAFETY AND EFFICACY
(6) PAHO. PANDRH. Working Group for Drug Registration. Proposal of Harmonized Drug
Registration Requirements in the Americas Region. 2009.
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PANDRH* DRUG REGISTRATION REQUIREMENTS
LEGAL AND ADMINISTRATIVE INFORMATION
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•
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Trademark
INN (7) or generic name
Concentration or strength
Pharmaceutical form
Technical Director
Country Legal Representative
International License Holder.
Manufacturer of Active Pharmaceutical Ingredient (s) (API): Name,
address, telephone, fax, mail
Manufacturer (s) of the Finished Pharmaceutical Product (FPP):
Name, address, telephone, fax, mail
Another manufacturers of the FPP: Name, address, telephone, fax,
mail of other manufacturers in case they participate in any stage of the
FPP. For freeze dried products also should be declared the manufacturer
of diluents
Commercial presentation (Primary container)
Route of Administration
(7) WHO Guidelines on the Use of International Nonproprietary Names (INNs) for Pharmaceutical
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Substances, 1997, WHO MD. Available at:
http://www.who.int/druginformation/general/innlists-shtml.
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PANDRH REGISTRATION REQUIREMENTS
LEGAL AND ADMINISTRATIVE INFORMATION
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•
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•
•
•
•
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Shelf life and storage conditions
Dispensing category
Quali-quantitative formulation per dosage unite and %.
Legal documentation for:
Technical Director
Representative
Certificate of a Pharmaceutical Product (CPP)
Certificate of GMP for manufacturers taking part in
any step of the FPP (including activities authorized)
Trade mark certificate
Information of the product:.
Labelling (inner container and secondary package)
Insert
Information for health professionals
Samples or Mock ups of the final package for marketing
(including accessories)
Samples of the finished products
Quality Analysis Certificate (corresponding to the bath of the
samples)
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PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR INNER
CONTAINERS
Trademark
INN or generic name
Pharmaceutical form
Concentration or strength
Content/Volume
Number of dosages per vial (for multidose presentations)
Route of Administration
Storage conditions (if container size is big enough)
Warnings
Batch number
Expiry date
Manufacturer
Registration Number (according to the country legislation/container size)
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PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR SECONDARY
PACKAGE
Distribution level (according
Trademark
to country legislation)
INN or generic name
Special signals (according to
Pharmaceutical form
country legislation)
Concentration or strength
Batch number
Content/Volume
Expiry date
Number of dosages per vial
Name and address of the
(for multidose
manufacturing of the FPP
presentations)
Name and address of the
Composition
packer of the FPP (if
Declaration of excipients
different)
(according to country
Name of the Technical
legislation)
Responsible (according to
Storage conditions
country legislation)
Route of Administration
Registration Number
Instructions for preparation
country
Instructions
for use
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Warnings (according to the
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PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR INSERTS
Trademark
INN or generic name
Pharmaceutical form
Concentration or strength
Content/Volume
Number of dosages per vial
(for multidose
presentations)
Composition
Declaration of excipients
Route of Administration
Indications
Instructions for use
Dosage/ Posology
Maximal dosage in 24 hours
Precautions
Warnings
Contraindications
Over dosage
Use in pregnancy and
lactation
Shelf life and storage
conditions
Name and address of the
manufacturing of the FPP
Name and address of the
packer of the FPP (if
different)
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PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR QUALITY
Active Pharmaceutical Ingredient (s):
•
•
•
Chemical name (WHO/Relevant Pharmacopoeia)
Manufacturer (s): (According to country legislation). Note: For fixed drug
combinations (FDC), this information applies for each API
Characteristics:
Complete description (odor, taste, flavor, etc.)
Physical
Chemical
Specifications of API
Analytical Method:
Validation of the Analytical method (According to country
legislation).
Validity period
For New Molecular Entities:
Structural and molecular formula/ Molecular weight/ Synthesis/
Source
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PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR QUALITY
Finished Pharmaceutical Product:
•
•
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Description and composition:
Full description of the FPP, detailing API (s), preservatives,
stabilizers and other excipients and their function,
For freeze dried products should be included description and
close-container system for dissolvent.
Pharmaceutical development: Studies for establishing the
pharmaceutical form, formulation, manufacturing process and
close-container system
Manufacturing of the FPP:
Batch formula (List of all components according country
legislation)
Manufacturing process (Flow with critical steps, in
process controls, intermediate products and FPP)
Physical and chemical characteristics for excipients (according
country legislation)
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PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR QUALITY
FPP Control
• Specifications
• Analytical Methods
• Validation of analytical methods of the FPP including
experimental data
• Standards and reference materials information
• Description of the close-container system (including
specifications of component materials)
• Stability studies (according to the country legislation and
climatic zones):
Protocols and results of stability studies justifying validity
period: (According to country legislation including:
study protocol, specifications, analytical methods,
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PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR QUALITY
FPP Control
description of close-container system,
storage conditions (temperature and humidity)
results of 3 batches minimal manufactured with 3 different batches of API,
conclusions and proposed validity period).
For freeze dried products should be demonstrated compatibility between
lyophilized and diluents
•
Program of stability studies post registration: Program or commitment
including number of batches to be included annually and analytical tests to be
performed. Each NRA will establish mechanisms for checking updating of this
information
•
Validity Period and storage conditions
•
Description of procedures for assuring cold chain: For products to be
refrigerated detailed measures for assuring adequate temperature and humidity
trough storage and distribution chain indicating controls
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PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR
INTERCHANGEABILITY
Biopharmaceutical Information
– In Vitro Equivalence Studies (dissolution profiles/SBC
System)
– In Vivo Equivalence Studies (Pharmacokinetics
studies, Bioequivalence studies; Pharmacodinamic
studies, Clinical trials)
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PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR
NON CLINICAL STUDIES
Applicable for New Molecular Entities
• Pharmacodinamics studies
• Pharmacokinetics studies
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PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR
NON CLINICAL STUDIES
Applicable for New Molecular Entities
• Pharmacodinamic studies
• Pharmacokinetics studies
• Toxicology studies
General Toxicology
Special toxicology
• New Fixed Dose Combinations: According WHO Technical Report
Series Nº 929, Annex 5
• For New excipients, new administration routes and FDCs are
necessary appropriate toxicological studies
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PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR
CLINICAL STUDIES
Applicable for New Molecular Entities
Summary of Clinical Studies
• Phase I studies (also apply for new concentration/strengths)
• Phase II studies
• Phase III studies (also apply for new concentration/strengths,
new combinations, new formulations)
• Phase IV studies (Pharmacovigilance Plan)
• Studies in special populations
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II Workshop on Medicines
Regulation
in the Caribbean Region
THANK YOU
VERY MUCH
MUCHAS
GRACIAS
Barbados,
September
8th and 9th , 2009
Se
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