Comparative Dossier Filling Procedure in The Asean, Cis and The GCC Region

Sneh lata et al.
/ AJPSR volume 2 issue 6, June, 2012

Available online at www.ordonearresearchlibrary.com
ISSN 2249-4898
Review Article
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES AND RESEARCH

COMPARATIVE DOSSIER FILLING PROCEDURE IN THE ASEAN, CIS AND THE GCC REGION
Sneh lata*, Rajendra songara.
Jaipur National University, Jagatpura, Jaipur (Rajasthan), India
Received: 23 May 2012; Revised: 4 June 2012; Accepted: 21 June 2012; Available online: 5 July. 2012
ABSTRACT
Dossier is a file document submitted based on the requirement of the drug approval process. It is a comprehensive
scientific document used to obtained worldwide licensing approval of a drug by diverse health authorities. Its
creations, processing, compilation & dispatch to the field by a regulatory affairs department, is dependent upon
many interrelated activities the filling process in the emerging markets will be depends upon the region .In the
Asean region A-CTD filling procedure in GCC region CTD format and CIS countries will be NeeS filling
procedure will be follow. After compilation 1 copy of the dossier will be submitted to the regulatory authorities
for the registration of the drug product.
Keyword: CTD-Common Technical Document. DMF-Drug Master File ICH-International Conference on
Harmonisation. Dossier File Submission.
INTRODUCTION
The registration procedure is different in every region .some will follow the ICH guidelines, WHO guidelines
for the registration of the drug product .But some region have the country specific guidelines for the registration
of the FPP. Drug regulatory affairs in pharma industries have mandated two types of dossier namely CTD
(Common Technical Dossier) and ACTD (Asean Common Technical Dossier). Regulated pharma markets
(eg.USA, Europe) markets require submission of dossier in CTD format which has to provide clinical trial and
bioequivalence studies. As against this, semi-regulated pharma markets (South East Asian) require ACTD
format which does not require exhaustive details like CTD. All of these guidelines will be considered the safety,
quality and efficacy of the FP product
Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

CTD (common Technical Documents)
The agreement to assemble all the Quality, Safety and Efficacy information in a common format (called CTD Common Technical Document ) has revolutionised the regulatory review processes, led to harmonised
electronic submission that, in turn, enabled implementation of good review practices. For industries, it has
eliminated the need to reformat the information for submission to the different ICH regulatory authorities.
The CTD is organised into five modules. Module 1 is region specific and Modules 2, 3, 4 and 5 are intended to
be common for all regions. In July 2003, the CTD became the mandatory format for new drug applications in
the EU and Japan, and the strongly recommended format of choice for NDAs submitted to the FDA.
The CTD is organized into five modules
Module 1. Administrative Information and Prescribing Information
This module contains documents specific for each region specified by the
Relevant regulatory authorities.
- Application forms
- Proposed label for use in this region
Module 2. Common Technical Document Summaries
10

CTD Table of Contents
CTD Introduction
Quality Overall Summary
Nonclinical Overview
Clinical Overview
Nonclinical Written and Tabulated Summaries
Clinical Summary
Module 3. Quality
Information on quality should be presented in the structured format described in
the guidance,
M4Q
Module 4. Nonclinical Study Reports

The Nonclinical Study Reports should be presented in the order described in the
Guidance M4S
Module 5. Clinical Study Reports
The modules that comprise the CTD are modules 2-5 of the submission and contain the
scientific data and summaries .Modules 1 of any submission is not part of the CTD and
contain region specific administrative information .the organization of the data in to
modules and nodes is referred to as the granulatory of the submission
Asean ACTD format
11

. The Association of Southeast Asian Nations (ASEAN) has mandated the filing of an
ASEAN Common Technology Dossier (ACTD) as the only regulatory filing for
pharmaceutical companies to get approval for their drugs in the 10-member states of
Singapore, Malaysia, Indonesia, Philippines, Thailand, Vietnam, Brunei, Myanmar,
Cambodia and Laos, with effect from 2012.
A-CTD have been organize in to 4 modules
Module 1- Administrative & prescribing information

-
Table of Contents
Application Form
Letter of Authorisation (where applicable)
Certifications
Labelling
Product Information
Module 2- Quality
Table of Contents
A table of contents for the filed application should be provided.
Section C: Body of Data
S
S1
DRUG SUBSTANCE
General Information
S 1.1 Nomenclature
International nonproprietary name (INN)
Compendial name if relevant
Registry number of chemical abstract service (CAS)
Laboratory code (if applicable)
Chemical name(s)
S 1.2 Structural formula

12

The structural, including relative and absolute stereochemistry, the molecular formula, and the relative
molecular mass should be provided.
S 1.3 General Properties
A list should be provided of physicochemical and other relevant properties of the drug substance.
Reference ICH Guidelines: Q6A
S2
Manufacture
S 2.1 Manufacturer(s)
Name and full addresses including the city and country of the manufacturer of active ingredient.
S 2.2 Description of Manufacturing Process and Process Controls
The description of the drug substances manufacturing process represents the applicants commitment for the
manufacture of drug substances. The following information should be provided to adequately describe the
manufacturing process and process controls:
A schematic flow diagram of the synthetic process(es) should be provided
that includes molecular
formulae, weights and yields, chemical structures of starting materials, intermediates, reagents and drug
substance reflecting stereochemistry, and identifies operating conditions and solvents.
A sequential procedural narrative of the manufacturing process that provides quantities of raw materials,
solvent, catalysts and reagent reflecting the representative batch scale, and includes process controls,
equipment and operating conditions, such as temperature, pressure, pH, time etc
Alternative process should be explained and described with the same level of details as the primary process.
Reprocessing steps should be identified and justified
S 2.3 Control of Materials

Material used in the manufacture of the drug substance (e.g., raw materials, starting materials, solvents,
reagents, catalysts) should be listed identifying where each material is used in the process. Information on the
quality and control of these materials should be provided. Information demonstrating that materials (including
biologically-sourced materials, e.g., media components, monoclonal antibodies, enzymes) meet standards
appropriate for their intended use (including the clearance or control of adventitious agents) should be provided,
13

as appropriate. For biologically-sourced materials, this can include information regarding the source,
manufacture, and characterization.
Reference ICH Guidelines : Q6A
S 2.4 Controls of critical steps and intermediates

Critical steps: Tests and acceptance criteria, with justification including experimental data, performed at critical
steps of the manufacturing process to ensure that the process is controlled.
Intermediates: Specifications and analytical procedure, if any, for intermediates isolated during the process.
S 2.5 Process Validation and/or Evaluation

Process validation or evaluation studies for aseptic processing and sterilization
S 2.6 Manufacturing Process Development

Description and discussion of significant changes made to the manufacturing process or manufacturing site of
the drug substance used in producing non-clinical, clinical scale-up, pilot and if available, production scale
batches.
S 3 Characterization
S 3.1 Elucidation of Structure and Characteristic

Confirmation of structure based on e.g. synthetic route and spectral analysis. Information on the potential
for isomerism, the identification of stereochemistry, or the potential for forming polymorph should also be
included.
S 3.2 Impurities
Information on impurities should be provided.
Reference ICH guidelines : Q3A, Q3C, and Q6A
14
S 4 Control of Drug Substance

Specification and justification of specification (s).
Summary of analytical procedure and validation.
S 4.1 Specification
Detailed specification, tests and acceptance criteria
for the drug substance should be provided.
Compendia specification are adequate. Indicate clearly whether the drug substance is purchased based on
specification with a certificate of analysis, or tested by applicant.
Reference ICH Guidelines Q6A
S 4.2 Analytical Procedures
The analytical procedure used for testing the drug substance should be provided in sufficient detail to enable
reproducible testing by another laboratory.
S 4.4 Batch Analyses
Description of batches and results of batch analyses should be provided
Reference ICH Guidelines : Q3A, Q3C and Q6A
S 4.5 Justification of Specification

Justification for the drug substance specification should be provided.
S 5 Reference Standards or Materials
Quality information of Reference standard or material used for testing of substance should be provided.
S 6 Container Closure System
A descriptions of the container closure systems should be provided, including the identity of materials of
construction of each primary packaging component, and each specifications. The specifications should include
15

description and identification (and critical dimensions with drawings where appropriate). Non-compendial
methods (with validations) should be included where appropriate.
For non-functional secondary packaging components (e.g. those that do not provide additional protection nor
serve to deliver the product), only a brief description should be provided. For functional secondary packaging
components, additional information should be provided.
The suitability should be discussed with respect to, for example, choice of materials, protection from moisture
and light, compatibility of the materials of construction with the drug substance, including sorption to container
and leaching, and/or safety of materials of construction.
Stability Summary and Conclusion
The types of studies conducted, protocols used, and the results of the studies should be summarized. The
summary should include results, for example, from forced degradation studies and stress conditions, as well as
conclusions with respect to storage conditions and retest date or shelf-life, as appropriate.
Reference ICH Guidelines : Q1A (R2), Q1B
Post-approval Stability Protocol and Stability Commitment
The post-approval stability protocol and stability commitment should be provided.
Reference ICH Guidelines : Q1A (R2)
Stability Data
Results of the stability studies (e.g. forced degradation studies and stress conditions) should be presented in an
appropriate format such as tabular, graphical, or narrative. Information on the analytical procedures used to
generate the data and validation of these procedures should be included. Manufacturer stability data or
equivalent information for generic drug
Reference ICH Guidelines : Q1A (R2), Q1B, Q2A, Q2B,
P
DRUG PRODUCT
P1
Description and Composition
A description of the drug product and its composition should be provided. The information provided should
include, for example :
16
Description of the dosage form;
Composition, i.e., list of all components of the dosage form, and their amount on a per-unit basis
(including overages, if any) the function of the components, and a reference to their quality standards
(e.g., compendial monographs or manufacturers specifications)
Description of accompanying reconstitution diluent(s); and
Type of container and closure used for the dosage form and accompanying reconstitution diluent, if
applicable.

2.Pharmaceutical Development
P 2.1 Information on Development Studies
The section of Pharmaceutical Development presents information and data on the development studies
conducted to establish that the dosage form, the formulation manufacturing process, container closure system,
microbiological attributes and usages instruction are appropriate for the purpose specified in the application.
The studies described here are distinguished from routine control tests conducted according to specifications.
Additionally, this section should identify and describe the formulation and process attributes (clinical
parameters) that may influence batch reproducibility, product performance and drug product quality. Supportive
data and result from specific studies or published literature may be included within or attached to the
Pharmaceutical Development Section. Additional supportive data may be referenced to the relevant non-clinical
sections of the application.
Reference ICH Guidelines : Q8(R2)
P 2.2 Component of Drug Product
P P.2.2.1 Active Ingredients:
The compatibility of the drug substances with excipients listed in Item 2.1 should be discussed.
Additionally, key physicochemical characteristics (e.g. Water content, solubility, particle size distribution,
polymorphic or solid state form) of the drug substance, which may influence the performance of the drug
product should be discussed.
17

For generic drug Literature data is sufficient.
P 2.2.2 Excipients
The choice of excipients listed in Item P 1, their concentration and characteristics which influence the drug
product performance should be discussed relative to their respective function.
P 2.3 Finished Product

P 2.3.1 Formulation Development
A brief summary describing the development of the drug product should be provided, taking into consideration
the proposed route of administration and usage. The differences between clinical formulations and the
formulation (i.e. Composition) described in Item P 1 and P 2 should be discussed. Results from comparative in
vitro studies (e.g. dissolution) or comparative in vivo studies (e.g., bioequivalence) should be discussed when
appropriate.
P 2.3.2 Overages
Any overages in the formulation(s) described in Item P 1 should be justified.
P 2.3.3 Physicochemical and Biological Properties

Parameters relevant to the performance of the drug product such as pH, ionic strength, dissolution, redispersion,
reconstitution, particle size distribution, aggregation, polymorphism, rheological properties, biological activity
or potency and immunological activity should be addressed
P 2.4 Manufacturing Process Development

The selection and optimization of the manufacturing process described in Item P 3.2, in particular its critical
aspects, should be explained. Where relevant, the method of sterilization should be explained and justified.
Differences between the manufacturing process(es) used to produce pivotal clinical batches and the process
described in Item P 3.2 that can influence the performance of the product should be discussed.
P 2.5 Container Closure System

The suitability of the container closure system used for the storage, transportation (shipping) and use of the drug
product should be discussed as necessary. This discussion should consider e.g. choice of materials, protection
18

from moisture and light, compatibility of the materials of construction with the dosage form including sorption
to container and leaching safety of materials of contraction, and performance such as reproducibility of the dose
delivery from the device when present as part the drug product.
P 2.6 Microbiological Attributes

Where appropriate, the microbiological attributes of the dosage form should be discussed including the rationale
for not performing microbial limits testing for non-sterile products, and the selection and effectiveness of
preservatives systems in product containing anti microbial preservatives. For sterile products, the integrity of
the container closure system to prevent microbial contamination should be addressed.
P 2.7 Compatibility
The compatibility of the drug product or reconstitution diluents(s) or dosage devices, e.g. precipitation of drug
substance in solution, sorption on injection vessels and stability should be addressed to provide appropriate and
supportive information for the labeling.
reference
P3
Manufacture
P 3.1 Batch Formula

The formula with name and quantities of all ingredients (active and otherwise) including substance(s) which are
removed in the course of manufacture should be included:
The actual quantities (g, kg, liters) etc. of ingredient should be stated.
Overage: Supporting data and the reason for including the overage shall be enclosed.
The total number of dosage unit per batch must stated.
A description of all stages involved in the manufacture of the dosage form is required.
P 3.2 Manufacturing Process and Process Control

A flow diagram should be presented giving the steps of the process and showing where materials enter the
process. The critical steps and points at which process controls, intermediate tests or final product controls are
conducted should be identified.
19
The full description of manufacturing process must sufficient details to cover the essential point of each

stage of manufacture.
For sterile product the description includes preparation and sterilization of components (i.e. Containers,
closures, etc).
P 3.3 Controls of Critical Steps and Intermediates

Critical steps: Tests and acceptance criteria should be provided (with justification, including experimental data)
performed at the critical steps identified P3.3 of the manufacturing process, to ensure that the process is
controlled.
Intermediates: information on the quality and control of intermediates isolated during the process should be
provided.
Reference ICH Guidelines : Q2A and Q6A
P 3.4 Process Validation and/or Evaluation

Description, documentation, and result of the validation studies should be provided from critical steps or critical
assays used in the manufacturing process.
(e.g. Validation of the sterilization process or aseptic processing or filling).
Reference : Q6A or Asean guidelines for Process validation
P4
Control of Excipients
P 4.1 Specification
The specification for the excipients should be provided.
P 4.2 Analytical Procedures
The analytical procedure used for the testing of critical excipients i.e. substances which
affect stability and bioavailability of
finished product (e.g. preservative, buffer
components, dissolution enhancer)should be provided.

Reference ICH Guidelines : NCE : Q2A and Q5A
P 4.3. Excipients of Human and Animal Origin
For excipients of human or animal origin, provide information of sources (e.g gelatin, enzyme, etc),
specifications,
20
description,
viral safety data)
regarding
adventitious agents (e.g., TSE,
viruses,

mycoplasma).Reference ICH Guidelines : NCE : Q5A, Q5D ;
P 4.4 Novel Excipients
For excipient(s) used for the first time in a drug product or by a new route of administration, full details of
manufacture, characterization and controls, with cross references to supporting safety data (nonclinical or
clinical) should be provided
P 5 Control of Finished Product
Specification and justification of the specification, summary of the analytical procedure and validation, and
characterization of impurities.
P 5.1 Specification
The specification for the finished product should be provided.
Reference ICH Guidelines : NCE : Q6A;
P 5.2 Analytical Procedures.
The analytical procedures use for the testing the finished product should be provided.
Reference ICH Guidelines : NCE : Q2A
P 5.3 Validation of Analytical Procedures
Analytical validation information, including experimental data for the analytical procedures use for the testing
the finished product should be provided.
ReferenceICH Guidelines : NCE : Q2A and Q2B
Reference : ASEAN Guideline
P 5.4 Batch analyses
Description (including size, origin and use) and test result of all relevant batches e.g pre-clinical, clinical pilot,
scale-up, and if available production-scale batches) used to
establish specification and evaluate consistency
in manufacturing should be provided.

Reference ICH Guidelines : NCE : Q3A, Q3C, and Q6A
21

P 5.5 Characterization of Impurities
Information on the characterization of impurities should be provided, if not previously provided in Item 1.3.2
Impurities.
Reference ICH Guidelines : NCE : Q3B and Q6A
P 5.6 Justification of Specification
Justification for the proposed finished product should be provided
Reference ICH Guidelines : NCE : Q3B and Q6A
P 6 Reference Standards or Materials
Requirement : Quality information and tabulated presentation of Reference standard or materials used for
testing of drug product should be included.
P 7 Container closure system
A descriptions of the container closure systems should be provided, including the identity of materials of
construction of each primary and secondary packaging component, and each specifications. The specifications
should include description and identification (and critical dimensions with drawings where appropriate). Noncompendial methods (with validations) should be included where appropriate.
For non-functional secondary packaging components (e.g. those that do not provide additional protection nor
serve to deliver the product), only a brief description should be provided. For functional secondary packaging
components, additional information should be provided.
Suitability information should be located in P 2
P 8 Product Stability
Evidence is required to demonstrate that product is stable, meets the finished product specifications throughout
its proposed shelf-life, that toxic decomposition products are not produced in significant amount during this
period, and that potency, efficacy of preservative etc. are maintained.
Stability Summary and Conclusion:
22

All criteria under ICH Guidelines are acceptable with the exception of real time storage conditions which
should be 300C, 70% RH. Provision of moisture protection of the packaging should be taken into
consideration.
Reference ICH Guidelines: Q1A (R2), Q1B, Q2A, Q2B and Q5C
ASEAN Guideline on Stability Study
Post-approval stability protocol and stability commitment
the post-approval stability protocol and stability commitment should be provided.
References ICH Guidelines : NCE,
ASEAN Guideline on Stability Study
Stability Data
Results of the stability studies should be presented in an appropriate format (e.g. tabular, graphical, narrative).
Information on the analytical procedures used to generate the data and validation of these procedures should be
included.
reference : ASEAN Guideline on Stability Study, ASEAN Guideline on Validation of Analytical Procedure
P 9 Product Interchange ability
The type of studies conducted, protocol used and the result of the studies should be presented in the study
report.
Type of studies conducted should refer to ASEAN (proposed) Bioavailability and Bioequivalence requirement,
Guideline for Bioavailability and Bioequivalence Studies or WHO Manual for Drug Regulatory Authority.
Reference: - WHO, Regulatory Support Series No 5,"Bioequivalence Studies in Humans."
- ASEAN Guideline on Bioequivalence Study
Section D: Key Literature References
Key literature references should be provided, if applicable.
Module 3-Non clinical study report

Module 4- clinical study report
23
GCC- CTD registration procedure
The data requirements for each application will differ, depending on the drug
submission type. However, all the required data should be in accordance with the
CTD structure.
Section
Requirements
Module 1
Regional Administrative Information
1.0
Cover letter
1.1
Comprehensive Table of content
1.2
Application Form
1.3
Product Information
1.3.1
Summary of Product Characteristics (SPC)
1.3.2
Labeling
24

1.3.3
Package Leaflet
1.3.3.1
Arabic leaflet
1.3.3.2
English leaflet /French leaflet
1.3.4
Artwork (Mock-ups)
1.3.5
Samples
1.4
Information About The Expert
1.4.1
Quality
1.4.2
Non-Clinical
1.4.3
Clinical
1.5
1.5.1
Non-Genetically Modified Organism (Non-GMO)
1.5.2
GMO
1.6
Pharmacovigilance
1.6.1
Pharmacovigilance System
1.6.2
Risk Management Plan
1.7
Administrative information
1.7.1
GMP Certificate
1.7.2
CPP or Free-sales
1.7.3
Certificate of analysis Drug Substance
1.7.4
Certificate of analysis Excipients
1.7.5
Alcohol-free declaration
1.7.6
Pork-free declaration
1.7.7
Certificate of suitability for TSE
1.7.8
The diluents and coloring agents in the product formula
1.7.9
Patent Information
1.7.10
Letter of access or acknowledgment to DMF
1.8
Pricing
1.8.1
Price certificate
1.8.2
Other documents related Pricing list
1.9
25
Environmental Risk Assessment
Responses to questions

Module 2*
Common Technical Document Summaries
2.1
Table of Contents of Module 2-5
2.2
Introduction
2.3
Quality Overall Summary
Introduction
2.3.S
2.3.S.1
General Information
2.3.S.2
Manufacture
2.3.S.3
Characterization
2.3.S.4
Control of Drug Substance
2.3.S.5
Reference Standards or Materials
2.3.S.6
Container/Closure System
2.3.S.7
Stability
2.3.P
Drug Product
2.3.P.1
Description and Composition of the Drug Product
2.3.P.2
Pharmaceutical Development
2.3.P.3
Manufacture
2.3.P.4
2.3.P.5
Control of Drug Product
2.3.P.6
2.3.P.7
2.3.P.8
Stability
2.3.A
Appendices
2.3.A.1
Facilities and Equipment
2.3.A.2
Adventitious Agents Safety Evaluation
2.3.A.3
Novel Excipients
2.3.R
2.4
Drug substance
Regional Information
Nonclinical Overview
FOR ORIGINATORS
ONLY
2.5
26
Overview of the Nonclinical Testing Strategy


2.5.1
Product Development Rationale
2.5.2
Overview of Biopharmaceutics
2.5.3
Overview of Clinical Pharmacology
2.5.4
Overview of Efficacy
2.5.5
Overview of Safety
2.5.6
Benefits and Risks Conclusions
2.5.7
References
2.6
Non clinical written and tabulated summaries: Pharmacology,

pharmacokinetics Toxicology FOR ORIGINATOR ONLY
2.6.1
Introduction
2.6.2
Pharmacology Written Summary
2.6.2.1
Brief Summary
2.6.2.2
Primary Pharmacodynamics
2.6.2.3
Secondary Pharmacodynamics
2.6.2.4
Safety Pharmacology
2.6.2.5
Pharmacodynamic Drug Interactions
2.6.2.6
Discussion and Conclusions
Section
2.6.2.7
Requirements
Tables and Figures
2.6.3
Pharmacology Tabulated Summary
2.6.4
Pharmacokinetics Written Summary
27
2.6.4.1
Brief Summary
2.6.4.2
Methods of Analysis
2.6.4.3
Absorption
2.6.4.4
Distribution
2.6.4.5
Metabolism (interspecies comparison)
2.6.4.6
Excretion
2.6.4.7
Pharmacokinetic Drug Interactions
2.6.4.8
Other Pharmacokinetic Studies
2.6.4.9


2.6.4.10
Tables and Figures
2.6.5
Pharmacokinetics Tabulated Summary
2.6.6
Toxicology Written Summary
2.6.6.1
Brief Summary
2.6.6.2
Single-Dose Toxicity
2.6.6.3
Repeat-Dose Toxicity
2.6.6.4
Genotoxicity
2.6.6.5
Carcinogenicity
2.6.6.6
Reproductive and Developmental Toxicity
2.6.6.7
Local Tolerance
2.6.6.8
Other Toxicity Studies (if available)
2.6.6.9
2.6.6.10
References
2.6.7
2.7
Toxicology Tabulated Summary

Clinical Summary
2.7.1
Summary of Biopharmaceutic and Associated Analytical

Methods
2.7.1.1
Background and Overview
2.7.1.2
Summary of Results of Individual Studies
2.7.1.3
Comparison and Analyses of Results Across Studies
2.7.1.4
Appendix
2.7.2
2.7.2.1
Background and Overview
2.7.2.2
2.7.2.3
2.7.2.4
Special Studies
2.7.2.5
Appendix
2.7.3
28
Summary of Clinical Pharmacology Studies
Summary of Clinical Efficacy
2.7.3.1
Background and Overview of Clinical Efficacy
2.7.3.2

2.7.3.3
2.7.3.3.1
Study Populations
2.7.3.3.2
Comparison of Efficacy Results Across All Studies
2.7.3.3.3
Comparison of Results in Sub-Populations
2.7.3.4
Analysis
of
Clinical
Information
Relevant
to
Dosing
Recommendations
2.7.3.5
Persistence of Efficacy and/or Tolerance Effects
2.7.3.6
Appendix
Section
2.7.4
2.7.4.1
Requirements
Summary of Clinical Safety

Exposure to the Drug
2.7.4.1.1
Overall Safety Evaluation Plan and Narratives of Safety Studies
2.7.4.1.2
Overall Extent of Exposure
2.7.4.1.3
Demographic and Other Characteristics of Study Population
2.7.4.2
Adverse Events
2.7.4.2.1
Analysis of Adverse Events by Organ System or Syndrome
2.7.4.2.2
Narratives
2.7.4.3
Clinical Laboratory Evaluations
2.7.4.4
Vital Signs, Physical Findings, Observations Related to Safety
2.7.4.5
Safety in Special Groups and Situations
2.7.4.5.1
Intrinsic Factors
2.7.4.5.2
Extrinsic Factors
2.7.4.5.3
Drug Interactions
2.7.4.5.4
Use in Pregnancy and Lactation
2.7.4.5.5
Overdose
2.7.4.5.6
Drug Abuse
2.7.4.5.7
Withdrawal and Rebound
2.7.4.5.8
Effects on Ability to Drive or Operate Machinery or Impairment

of Mental Ability
2.7.4.6
29
Post-Marketing Data

2.7.4.7
Appendix
2.7.5
References
2.7.6
Synopses of Individual Studies
Module 3
Quality
Section
Requirements
3.1
Table of Contents of Module 3
3.2
Body of data
3.2.S
3.2.S.1
General Information
3.2.S.1.1
Nomenclature
3.2.S.1.2
Structure
3.2.S.1.3
General Properties
3.2.S.2
Manufacture
3.2.S.2.1
Manufacturer(s)
3.2.S.2.2
Description of Process and Process Controls
3.2.S.2.3
Control of Materials
3.2.S.2.4
Control of Critical Steps and Intermediates
3.2.S.2.5
Process Validation and/or Evaluation
3.2.S.2.6
Manufacturing Process Development
3.2.S.3
Characterization
3.2.S.3.1
Elucidation of Structure and Other Characteristics
3.2.S.3.2
Impurities
3.2.S.4
30
Drug Substance
3.2.S.4.1
Specifications
3.2.S.4.2
Analytical Procedures
3.2.S.4.3
Validation of Analytical Procedures
3.2.S.4.4
Batch Analyses
3.2.S.4.5
Justification of Specification
3.2.S.5
3.2.S.6
Container/Closure Systems

3.2.S.7
Stability
3.2.S.7.1
Stability Summary and Conclusions
3.2.S.7.2
Post-approval Stability Protocol and Commitment
3.2.S.7.3
Stability Data
3.2.P
Drug Product
3.2.P.1
3.2.P.2
3.2.P.2.1
Components of the Drug Product

Drug substance
Excipients
3.2.P.2.1.1
3.2.P.2.1.2
3.2.P.2.2
Drug Product
Formulation Development
Overages
Physiochemical and Biological Properties
3.2.P.2.3
3.2.P.2.4
Container Closure System
3.2.P.2.5
Microbiological Attributes
3.2.P.2.6
Compatibility
3.2.P.2.2.1
3.2.P.2.2.2
3.2.P.2.2.3
3.2.P.3
3.2.P.3.1
Manufacturer(s)
3.2.P.3.2
Batch Formula
3.2.P.3.3
Description of Manufacturing Process and Process Controls
3.2.P.3.4
Controls of Critical Steps and Intermediates
3.2.P.3.5
3.2.P.4
31
Manufacture

3.2.P.4.1
Specifications
3.2.P.4.2
Section
Requirements
3.2.P.4.3
3.2.P.4.4
Justification of Specifications
3.2.P.4.5
Excipients of Human or Animal Origin
3.2.P.4.6
Novel Excipients
3.2.P.5
3.2.P.5.1
Specifications
3.2.P.5.2
3.2.P.5.3
3.2.P.5.4
Batch Analyses
3.2.P.5.5
Characterization of Impurities
3.2.P.5.6
3.2.P.6
3.2.P.7
3.2.P.8
Stability
3.2.P.8.1
3.2.P.8.2
Post-Approval Stability Protocol and Stability Commitments
3.2.P.8.3
Stability Data
3.2.A
32
Appendices
3.2.A.1
3.2.A.2
3.2.A.3
Excipients
3.2.R
3.3
Regional Information
3.2.R.1
Alcohol Content Declaration
3.2.R.2
Porcine/Pork content/origin
3.2.R.3

Literature References
R
Modules 4 is not required for the Gucc country for the registration of the generic drug.
Section
Requirements
Module 5
Clinical study report
5.1
Tabular listing of all clinical studies
5.2
5.3
Clinical study reports
5.3.1
Report of biopharmaceutical studies
5.3.1.1
Bioavailability(BA) study report
NR
5.3.1.2
Comparative bioequivalence(BE) and BA study report
5.3.1.3
In vitro in vivo correlation study report
NR
5.3.1.4
Report of Bioanalytical and Analytical Method
NR
5.3.2
Report of studies pertinent to pharmacokinetic using human NR

Biomaterials
5.3.3
Report of human pharmacokinetic (PK )studies
NR
5.3.4
Report of human pharmacodynamic (PD )studies
NR
5.3.5.
Report of Efficacy and safety study
NR
5.3.6
Report of post marketing Experiences
NR
5.3.7
5.4
Case report forms and individuals patients listings

Key literature references
NR
CIS-NeeS format
33
REGISTRATION CHART IN RUSSIA COUNTRY
34
REGISTRATION CHART IN BELARUS COUNTRY
35

REGISTRATION CHART IN KAZAKHASTAN COUNTRY
Registration file (or dossier) represents the documents submitted to State Regulatory Authority for registration.
Russian registration file consists from 6 parts:
Administrative documents
Description of pharmaceutical properties
Data about manufacturing of pharmaceutical product
Data about quality control of the finished pharmaceutical product
Data about PRE-CLINICAL pharmacological and toxicological studies of pharmaceutical product
Data about CLINICAL studies of pharmaceutical product
European registration file consists from 5 modules. The structure of Russian and European registration files is
very similar. If manufacturer has European registration file it is not necessary to prepare separated docs for
Russia. All data required for Russian dossier are available in European file. Russian registration file must be
presented to State Regulatory Authorities in Russian language.
The country will follow the CTD format for the registration of the drug product
1. Module 1 Administrative part
2. Common technical document Summaries
36

3. Quality
4. Non Clinical Report
5. Clinical Report
Modules 4 is not required in the filling of the Drug product in the Ukraine
Section
Requirements
Module 1
Regional Administrative Information
1.1
Table Of Content
1.2
Application Form
1.3
Product Information
1.3.1
Summary of Product Characteristics (SPC)
1.3.2
Labeling
1.3.3
Package leaflet
NR
1.3.3.1
English leaflet /French leaflet
1.3.4
Artwork (Mock-ups)
1.4
Information About the Experts
1.4.1
Quality
1.4.2
Non-Clinical
1.4.3
Clinical
1.5
1.6
1.7
Specific
Requirement
For
Different
Applications
Environment Risk Management Plan
Types Of
R
R
Administrative Information
1.7.1
GMP Certificate
1.7.2
CPP or Free-sales
1.7.3
Manufacturing License
1.7.4
Patent Information
37

Modules 2 Requirement is same as in the GCC countries.
Module 3
Quality
Section
Requirements
3.1
Table of Contents of Module 3
3.2
Body of data
3.2.S
Drug Substance
3.2.S.1
General Information
3.2.S.1.1
Nomenclature
3.2.S.1.2
Structure
3.2.S.1.3
General Properties
3.2.S.2
Manufacture
3.2.S.2.1
Manufacturer(s)
3.2.S.2.2
Description of Process and Process Controls
3.2.S.2.3
Control of Materials
3.2.S.2.4
Control of Critical Steps and Intermediates
3.2.S.2.5
3.2.S.2.6
3.2.S.3
Characterization
3.2.S.3.1
Elucidation of Structure and Other Characteristics
3.2.S.3.2
Impurities
3.2.S.4
3.2.S.4.1
Specifications
3.2.S.4.2
3.2.S.4.3
3.2.S.4.4
Batch Analyses
3.2.S.4.5
Justification of Specification
3.2.S.5
3.2.S.6
Container/Closure Systems
3.2.S.7
Stability
38

3.2.S.7.1
3.2.S.7.2
Post-approval Stability Protocol and Commitment
3.2.S.7.3
Stability Data
3.2.P
Drug Product
3.2.P.1
3.2.P.2
3.2.P.2.1
Components of the Drug Product
3.2.P.2.1.1
Drug substance
3.2.P.2.1.2
Excipients
3.2.P.2.2
Drug Product
3.2.P.2.2.1
Formulation Development
3.2.P.2.2.2
Overages
3.2.P.2.2.3
Physiochemical and Biological Properties
3.2.P.2.3
3.2.P.2.4
Container Closure System
3.2.P.2.5
Microbiological Attributes
3.2.P.2.6
Compatibility
3.2.P.3
Manufacture
3.2.P.3.1
Manufacturer(s)
3.2.P.3.2
Batch Formula
3.2.P.3.3
Description of Manufacturing Process and Process Controls
3.2.P.3.4
Controls of Critical Steps and Intermediates
3.2.P.3.5
3.2.P.4
3.2.P.4.1
Specifications
3.2.P.4.2
Section
Requirements
3.2.P.4.3
3.2.P.4.4
3.2.P.4.5
Excipients of Human or Animal Origin
39

3.2.P.4.6
Novel Excipients
3.2.P.5
3.2.P.5.1
Specifications
3.2.P.5.2
3.2.P.5.3
3.2.P.5.4
Batch Analyses
3.2.P.5.5
Characterization of Impurities
3.2.P.5.6
3.2.P.6
3.2.P.7
3.2.P.8.1
3.2.P.8.2
Post-Approval Stability Protocol and Stability Commitments R
3.2.P.8.3
Stability Data
3.2.P.8
3.2.A
3.2.A.1
NR
3.2.A.2
NR
3.2.A.3
Excipients
NR
3.2.R.1
Alcohol Content Declaration
NR
3.2.R.2
Porcine/Pork content/origin
NR
3.2.R.3
NR
3.3
Literature References
3.2.R
Section
Requirements
Module 5
Clinical study report
5.1
Tabular listing of all clinical studies
5.2
5.3
Clinical study reports
5.3.1
Report of biopharmaceutical studies
40

5.3.1.1
NR
Bioavailability(BA) study report
5.3.1.2
Comparative bioequivalence(BE) and BA study report
5.3.1.3
In vitro in vivo correlation study report
NR
5.3.1.4
Report of Bioanalytical and Analytical Method
NR
5.3.2
Report of studies pertinent to pharmacokinetic using human Biomaterials
NR
5.3.3
Report of human pharmacokinetic (PK )studies
NR
5.3.4
Report of human pharmacodynamic (PD )studies
NR
5.3.5.
Report of Efficacy and safety study
NR
5.3.6
Report of post marketing Experiences
NR
5.3.7
NR
Case report forms and individuals patients listings
5.4
Key literature references
Comparative study in Asean ,GCC and CIS country
Filling Procedure
Approval timeline
Asean
GCC
CIS
A-CTD
CTD
NeeS
140 working days
It will be differ from the
110 working days
country to country
Russia-210 working days
Belarus-180 working days
Kazakhstan-227 days
Administrative Data
NOT REQUIRED
NOT REQUIRED
Not required
Required
required
and Not required
Required
required
(LETTER
REQUIRED
OF
AUTHORIZATION)
Pharmacovigilance
Mock
up
speciman
Package leaflet
Required(English)
Required(Arabic/En Not required

glish)
41

Information about the Not required
Not required
required
overall Not required
Required
required
studies 300C2/755%RH
300C2/755%RH
300C2/655%RH
experts
Quality
summary
Stability
(condition)
Conclusion:From the above point we have concluded the registration procedure will be differ in minor variation there is
further needs for harmonization so the applicant does not modify the individual format & the information will
be become unambiguous and the transparent to facilitate the review and help a reviewer to become quickly
oriented
References
1. http://reg-info.com/ctd-guidelines
2. http://www.ich.org/products/ctd.html
3. www.ich.org/about/organisation-of-ich/coopgroup/asean.html
4. http://www.moh.gov.bn/pharmacyservices/download/ASEAN%20Common%20Technical%20Docume
nt%20(ACTD).pdf
5. http://www.ectdblog.com/2008/05/asean-ctd-actd.html
6. www.ich.org/about/organisation-of-ich/coopgroup/gcc.html.
7. www.fda.gov/cder/regulatory/application/ind_page_1html
8. www.nccmerp.org
9.
www.ismp.org
10. http://estri.ich.org/eCTD/eCTD_Specification_v3_2_2.pdf
11. http://aspe.hhs.gov/sp/reports/2010/GenericDrugs/ib.shtml
12. www.jyoungpharm.in/article.asp?issn=0975-1483;year...
42

13. http://www.ipapharma.org/Regulations.aspx
14. http://leavefreedom.blogspot.in/2010/01/asean-harmonises-drug-registration.html
43

Comparative Dossier Filling Procedure in The Asean, Cis and The GCC Region

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Sneh lata et al.

/ AJPSR volume 2 issue 6, June, 2012

ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES AND RESEARCH

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Module 4. Nonclinical Study Reports

Asean ACTD format

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Module 1- Administrative & prescribing information

Letter of Authorisation (where applicable)

International nonproprietary name (INN)

Compendial name if relevant

Registry number of chemical abstract service (CAS)

Laboratory code (if applicable)

S 1.2 Structural formula

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

A schematic flow diagram of the synthetic process(es) should be provided

that includes molecular

S 2.3 Control of Materials

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Reference ICH Guidelines : Q6A

S 2.4 Controls of critical steps and intermediates

S 2.5 Process Validation and/or Evaluation

S 2.6 Manufacturing Process Development

S 3.1 Elucidation of Structure and Characteristic

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

S 4 Control of Drug Substance

for the drug substance should be provided.

S 4.5 Justification of Specification

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Description and Composition

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Description of the dosage form;

Description of accompanying reconstitution diluent(s); and

Reference ICH Guidelines : Q6A

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

P 2.3 Finished Product

P 2.3.3 Physicochemical and Biological Properties

P 2.4 Manufacturing Process Development

P 2.5 Container Closure System

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

P 2.6 Microbiological Attributes

P 3.1 Batch Formula

The total number of dosage unit per batch must stated.

P 3.2 Manufacturing Process and Process Control

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012

P 3.3 Controls of Critical Steps and Intermediates

P 3.4 Process Validation and/or Evaluation

finished product (e.g. preservative, buffer

components, dissolution enhancer)should be provided.

viral safety data)

adventitious agents (e.g., TSE,

Sneh lata et al. / AJPSR volume 2 issue 6, June, 2012