II Workshop on Medicines

Regulation in the Caribbean

Region

Regulatory Function
of
DRUG REGISTRATION
Celeste Sánchez González, PhD.
Adviser. CECMED/Cuba
sanchez.celeste@gmail.com/evareg@cecmed.sld.cu

II Workshop on Medicines Regulationthin the Caribbean Region

Barbados, September 8 and 9 , 2009 th

Barbados, September
Se 8th and 9th , 2009 1
 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)

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 2
 An approach of Regulatory Functions of Medicines
National Regulatory Authorities (1)
Administrative Elements

 Policy, legislation, regulations

 Human resources


Finance
Infrastructure
Regulatory Functions

Technical
elements Regulation level

Licensing of Inspection of Product Monitoring Control of Adverse drug

 Standards premises, manufacturers assessment quality of drug reaction  Central
 Specifications practices & & & registration drugs promotion & monitoring  State/province
 Guidelines persons distributors advertising  District
 Procedures  Community

(1) Ratanawijitrasin S. & Wondemagegnehu E. Effective drug regulation. A multicountry study.

WHO, 2002

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 3
 Another approach of Regulatory Functions of
Medicines National Regulatory Authorities (2)
1 Regulatory System
2 Licenses: For medicines -vaccines- (Registration)
Licenses: For Companies (manufacturing, importing,
exporting, distributing)
3 Post-marketing surveillance
4 Lot Release
5 Access to Laboratory (for quality controls)
6 Regulatory Inspections: GMP and distribution channels
7 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
II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 4
 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.

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 5
 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.

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 6
 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

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 7
 Drug Registration
•Registration
•Variations

Manufacturer •Renewals

Pharmaceutical Product

Quality
GMP Safety
Requirements Information Efficacy
Laboratory
Inspections and Rational Use/Promotion
Post Marketing Controls
Establishment Licenses and Advertising
and Surveillance
II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 8
 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

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 9
Drug Registration Assessment and
Requirement Characteristics

BASIS OF REGISTRATION

OWN RELY ON EXPORTING

ASSESSMENT COUNTRY´S NRA

RELY ON REPORTS OF
ASSESSMENT FRON
ANOTHER NRA

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 10
 REGISTRATION. RELY ON EXPORTING CONTRY´S NRA

Does Product have Registry in Exporting Country?

Yes No

Is the Product the same as OWN ASSESSMENT

in exporting country?

Yes 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…..

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 11
 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.

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 12
 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.
II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 13
 PANDRH* DRUG REGISTRATION REQUIREMENTS
LEGAL AND ADMINISTRATIVE INFORMATION
• 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
II Workshop on Medicines Regulation in the Caribbean Region
Substances, 1997, WHO MD. Available at:
http://www.who.int/druginformation/general/innlists-shtml.
Barbados, September
Se 8th and 9th , 2009 14
 PANDRH REGISTRATION REQUIREMENTS
LEGAL AND ADMINISTRATIVE INFORMATION
• 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)
II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 15
 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)

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 16
 PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR SECONDARY
PACKAGE
Trademark Distribution level (according
INN or generic name to country legislation)
Pharmaceutical form Special signals (according to
Concentration or strength country legislation)
Content/Volume Batch number
Number of dosages per vial Expiry date
(for multidose Name and address of the
presentations) manufacturing of the FPP
Composition Name and address of the
Declaration of excipients packer of the FPP (if
(according to country different)
legislation) Name of the Technical
Storage conditions Responsible (according to
Route of Administration country legislation)
Instructions for preparation Registration Number
Instructions (according
for use on Medicines Regulation in the Caribbean
II Workshop to country
Region
Warnings (according to the legislation)
package size) Barbados, September
Se 8th and 9th , 2009 17
 PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR INSERTS

Trademark Precautions
INN or generic name Warnings
Pharmaceutical form Contraindications
Concentration or strength Over dosage
Content/Volume Use in pregnancy and
Number of dosages per vial lactation
(for multidose Shelf life and storage
presentations) conditions
Composition Name and address of the
Declaration of excipients manufacturing of the FPP
Route of Administration Name and address of the
Indications packer of the FPP (if
Instructions for use different)
Dosage/ Posology
Maximal dosage in 24 hours

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 18
 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
II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 19
PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR QUALITY
Finished Pharmaceutical Product:
• 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)

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 20
 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,

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 21
 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
II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 22
 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)

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 23
 PANDRH REGISTRATION REQUIREMENTS
BASIC INFORMATION FOR
NON CLINICAL STUDIES

Applicable for New Molecular Entities

• Pharmacodinamics studies

• Pharmacokinetics studies

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 24
 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
II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 25
 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

II Workshop on Medicines Regulation in the Caribbean Region

Barbados, September
Se 8th and 9th , 2009 26
 THANK
II Workshop on YOU
Medicines VERY inMUCH
Regulation the Caribbean Region

MUCHAS
Barbados, GRACIAS
September
Se 8th and 9th , 2009 27