AJPSR41

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

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

Available online at www.ordonearresearchlibrary.com ISSN 2249-4898

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

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

Review Article

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.

http://www.ordonearresearchlibrary.com/



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



• 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



. 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 DRUG SUBSTANCE

S 1 General Information

S 1.1 Nomenclature

International non–proprietary 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



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

S 2 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 applicant’s 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,



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



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



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

P 1 Description and Composition

A description of the drug product and its composition should be provided. The information provided should

include, for example :



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 manufacturer’s 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.



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



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

P 3 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.

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

P 4 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, 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



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). 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.

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:



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



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 G

Module 1 Regional Administrative Information

1.0 Cover letter R

1.1 Comprehensive Table of content R

1.2 Application Form R

1.3 Product Information

1.3.1 Summary of Product Characteristics (SPC) R

1.3.2 Labeling R



1.3.3 Package Leaflet

1.3.3.1 Arabic leaflet R

1.3.3.2 English leaflet /French leaflet R

1.3.4 Artwork (Mock-ups) R

1.3.5 Samples R

1.4 Information About The Expert

1.4.1 Quality O

1.4.2 Non-Clinical O

1.4.3 Clinical O

1.5 Environmental Risk Assessment

1.5.1 Non-Genetically Modified Organism (Non-GMO) O

1.5.2 GMO O

1.6 Pharmacovigilance

1.6.1 Pharmacovigilance System R

1.6.2 Risk Management Plan O

1.7 Administrative information

1.7.1 GMP Certificate R

1.7.2 CPP or Free-sales R

1.7.3 Certificate of analysis – Drug Substance R

1.7.4 Certificate of analysis – Excipients R

1.7.5 Alcohol-free declaration R

1.7.6 Pork-free declaration R

1.7.7 Certificate of suitability for TSE R

1.7.8 The diluents and coloring agents in the product formula R

1.7.9 Patent Information O

1.7.10 Letter of access or acknowledgment to DMF R

1.8 Pricing

1.8.1 Price certificate R

1.8.2 Other documents related – Pricing list O

1.9 Responses to questions O



Module 2* Common Technical Document Summaries

2.1 Table of Contents of Module 2-5 R

2.2 Introduction R

2.3 Quality Overall Summary R

Introduction

2.3.S Drug substance

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 Control of Excipients

2.3.P.5 Control of Drug Product

2.3.P.6 Reference Standards or Materials

2.3.P.7 Container/Closure System

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 Regional Information

2.4 Nonclinical Overview FOR ORIGINATORS

ONLY

2.5 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


2.6.2.7 Tables and Figures

2.6.3 Pharmacology Tabulated Summary

2.6.4 Pharmacokinetics Written 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




2.6.4.10 Tables and Figures

2.6.5 Pharmacokinetics Tabulated Summary

2.6.6 Toxicology Written 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)


2.6.6.10 References

2.6.7 Toxicology Tabulated Summary

2.7 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 Summary of Clinical Pharmacology Studies

2.7.2.1 Background and Overview



2.7.2.4 Special Studies

2.7.2.5 Appendix

2.7.3 Summary of Clinical Efficacy

2.7.3.1 Background and Overview of Clinical Efficacy





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


2.7.4 Summary of Clinical Safety

2.7.4.1 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 Post-Marketing Data



2.7.4.7 Appendix

2.7.5 References

2.7.6 Synopses of Individual Studies

Module 3 Quality


3.1 Table of Contents of Module 3 R

3.2 Body of data

3.2.S Drug Substance


3.2.S.1.1 Nomenclature R

3.2.S.1.2 Structure R

3.2.S.1.3 General Properties R

3.2.S.2 Manufacture

3.2.S.2.1 Manufacturer(s) R

3.2.S.2.2 Description of Process and Process Controls R

3.2.S.2.3 Control of Materials R

3.2.S.2.4 Control of Critical Steps and Intermediates R

3.2.S.2.5 Process Validation and/or Evaluation R

3.2.S.2.6 Manufacturing Process Development R


3.2.S.3.1 Elucidation of Structure and Other Characteristics R

3.2.S.3.2 Impurities R


3.2.S.4.1 Specifications R

3.2.S.4.2 Analytical Procedures R

3.2.S.4.3 Validation of Analytical Procedures R

3.2.S.4.4 Batch Analyses R

3.2.S.4.5 Justification of Specification R

3.2.S.5 Reference Standards or Materials R

3.2.S.6 Container/Closure Systems R



3.2.S.7 Stability

3.2.S.7.1 Stability Summary and Conclusions R

3.2.S.7.2 Post-approval Stability Protocol and Commitment R

3.2.S.7.3 Stability Data R

3.2.P Drug Product

3.2.P.1 Description and Composition of the Drug Product R


3.2.P.2.1 Components of the Drug Product

3.2.P.2.1.1

Drug substance R

3.2.P.2.1.2

Excipients R

3.2.P.2.2 Drug Product

3.2.P.2.2.1

Formulation Development O

3.2.P.2.2.2

Overages R

3.2.P.2.2.3

Physiochemical and Biological Properties R

3.2.P.2.3 Manufacturing Process Development R

3.2.P.2.4 Container Closure System R

3.2.P.2.5 Microbiological Attributes R

3.2.P.2.6 Compatibility O

3.2.P.3 Manufacture

3.2.P.3.1 Manufacturer(s) R

3.2.P.3.2 Batch Formula R

3.2.P.3.3 Description of Manufacturing Process and Process Controls R

3.2.P.3.4 Controls of Critical Steps and Intermediates R

3.2.P.3.5 Process Validation and/or Evaluation R




3.2.P.4.1 Specifications R

3.2.P.4.2 Analytical Procedures R


3.2.P.4.3 Validation of Analytical Procedures R

3.2.P.4.4 Justification of Specifications R

3.2.P.4.5 Excipients of Human or Animal Origin R

3.2.P.4.6 Novel Excipients R





3.2.P.5.4 Batch Analyses R

3.2.P.5.5 Characterization of Impurities R


3.2.P.6 Reference Standards or Materials R

3.2.P.7 Container/Closure System R

3.2.P.8 Stability

3.2.P.8.1 Stability Summary and Conclusions R

3.2.P.8.2 Post-Approval Stability Protocol and Stability Commitments R

3.2.P.8.3 Stability Data R

3.2.A Appendices

3.2.A.1 Facilities and Equipment O

3.2.A.2 Adventitious Agents Safety Evaluation O

3.2.A.3 Excipients R

3.2.R Regional Information

3.2.R.1 Alcohol Content Declaration R

3.2.R.2 Porcine/Pork – content/origin R

3.2.R.3 The diluents and coloring agents in the product formula

3.3 Literature References R



Modules 4 is not required for the Gucc country for the registration of the generic drug.


Module 5 Clinical study report

5.1 Tabular listing of all clinical studies R


5.3 Clinical study reports R

5.3.1 Report of biopharmaceutical studies R

5.3.1.1 Bioavailability(BA) study report NR

5.3.1.2 Comparative bioequivalence(BE) and BA study report R

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

Case report forms and individuals patients listings

NR

5.4 Key literature references R

CIS-NeeS format



REGISTRATION CHART IN RUSSIA COUNTRY



REGISTRATION CHART IN BELARUS COUNTRY



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



3. Quality

4. Non Clinical Report

5. Clinical Report

Modules 4 is not required in the filling of the Drug product in the Ukraine


Module 1 Regional Administrative Information

1.1 Table Of Content R

1.2 Application Form R

1.3 Product Information R

1.3.1 Summary of Product Characteristics (SPC) R

1.3.2 Labeling R

1.3.3 Package leaflet NR

1.3.3.1 English leaflet /French leaflet R

1.3.4 Artwork (Mock-ups) R

1.4 Information About the Experts

1.4.1 Quality R

1.4.2 Non-Clinical R

1.4.3 Clinical R

1.5 Specific Requirement For Different Types Of

Applications R

1.6 Environment Risk Management Plan R

1.7 Administrative Information

1.7.1 GMP Certificate R

1.7.2 CPP or Free-sales R

1.7.3 Manufacturing License R

1.7.4 Patent Information R



Modules 2 Requirement is same as in the GCC countries.

Module 3 Quality


3.1 Table of Contents of Module 3 R

3.2 Body of data

3.2.S Drug Substance


3.2.S.1.1 Nomenclature R

3.2.S.1.2 Structure R

3.2.S.1.3 General Properties R

3.2.S.2 Manufacture

3.2.S.2.1 Manufacturer(s) R

3.2.S.2.2 Description of Process and Process Controls R

3.2.S.2.3 Control of Materials R

3.2.S.2.4 Control of Critical Steps and Intermediates R

3.2.S.2.5 Process Validation and/or Evaluation R

3.2.S.2.6 Manufacturing Process Development R


3.2.S.3.1 Elucidation of Structure and Other Characteristics R

3.2.S.3.2 Impurities R


3.2.S.4.1 Specifications R

3.2.S.4.2 Analytical Procedures R

3.2.S.4.3 Validation of Analytical Procedures R

3.2.S.4.4 Batch Analyses R

3.2.S.4.5 Justification of Specification R

3.2.S.5 Reference Standards or Materials R

3.2.S.6 Container/Closure Systems R

3.2.S.7 Stability



3.2.S.7.1 Stability Summary and Conclusions R

3.2.S.7.2 Post-approval Stability Protocol and Commitment R

3.2.S.7.3 Stability Data R

3.2.P Drug Product

3.2.P.1 Description and Composition of the Drug Product R


3.2.P.2.1 Components of the Drug Product

3.2.P.2.1.1 Drug substance R

3.2.P.2.1.2 Excipients R

3.2.P.2.2 Drug Product

3.2.P.2.2.1 Formulation Development O

3.2.P.2.2.2 Overages R

3.2.P.2.2.3 Physiochemical and Biological Properties R

3.2.P.2.3 Manufacturing Process Development R

3.2.P.2.4 Container Closure System R

3.2.P.2.5 Microbiological Attributes R

3.2.P.2.6 Compatibility O

3.2.P.3 Manufacture

3.2.P.3.1 Manufacturer(s) R

3.2.P.3.2 Batch Formula R

3.2.P.3.3 Description of Manufacturing Process and Process Controls R

3.2.P.3.4 Controls of Critical Steps and Intermediates R

3.2.P.3.5 Process Validation and/or Evaluation R







3.2.P.4.5 Excipients of Human or Animal Origin R



3.2.P.4.6 Novel Excipients R





3.2.P.5.4 Batch Analyses R

3.2.P.5.5 Characterization of Impurities R


3.2.P.6 Reference Standards or Materials R

3.2.P.7 Container/Closure System R

3.2.P.8

3.2.P.8.1 Stability Summary and Conclusions R

3.2.P.8.2 Post-Approval Stability Protocol and Stability Commitments R

3.2.P.8.3 Stability Data R

3.2.A

3.2.A.1 Facilities and Equipment NR

3.2.A.2 Adventitious Agents Safety Evaluation NR

3.2.A.3 Excipients NR

3.2.R

3.2.R.1 Alcohol Content Declaration NR

3.2.R.2 Porcine/Pork – content/origin NR

3.2.R.3 The diluents and coloring agents in the product formula NR

3.3 Literature References R


Module 5 Clinical study report

5.1 Tabular listing of all clinical studies R


5.3 Clinical study reports R

5.3.1 Report of biopharmaceutical studies R



5.3.1.1 Bioavailability(BA) study report NR

5.3.1.2 Comparative bioequivalence(BE) and BA study report R

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

Case report forms and individuals patients listings

NR

5.4 Key literature references R

Comparative study in Asean ,GCC and CIS country

Asean GCC CIS

Filling Procedure A-CTD CTD NeeS

Approval timeline 110 working days 140 working days It will be differ from the

country to country

Russia-210 working days

Belarus-180 working days

Kazakhstan-227 days

Administrative Data

(LETTER OF

AUTHORIZATION)

REQUIRED NOT REQUIRED NOT REQUIRED

Pharmacovigilance Not required Required required

Mock –up and

speciman

Not required Required required

Package leaflet Required(English) Required(Arabic/En

glish)

Not required



Information about the

experts

Not required Not required required

Quality overall

summary

Not required Required required

Stability studies

(condition)

300C±2/75±5%RH 300C±2/75±5%RH 300C±2/65±5%RH

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...

http://reg-info.com/ctd-guidelines

http://www.ich.org/products/ctd.html

http://www.moh.gov.bn/pharmacyservices/download/ASEAN Common Technical Document (ACTD).pdf

http://www.moh.gov.bn/pharmacyservices/download/ASEAN Common Technical Document (ACTD).pdf

http://www.ich.org/about/organisation-of-ich/coopgroup/gcc.html

http://www.fda.gov/cder/regulatory/application/ind_page_1html

http://www.nccmerp.org/

http://www.ismp.org/

http://estri.ich.org/eCTD/eCTD_Specification_v3_2_2.pdf

http://aspe.hhs.gov/sp/reports/2010/GenericDrugs/ib.shtml



13. http://www.ipapharma.org/Regulations.aspx

14. http://leavefreedom.blogspot.in/2010/01/asean-harmonises-drug-registration.html

http://www.ipapharma.org/Regulations.aspx

http://leavefreedom.blogspot.in/2010/01/asean-harmonises-drug-registration.html

AJPSR41

Documents

Transcript of AJPSR41