A STUDY OF PROCEDURES FOR DOSSIER PREPARATION AND THEIR MARKETING AUTHORISATION IN DIFFERENT COUNTRIES OF SELECTED DRUG(S)

 

 

The registration procedure is differs from region to region. Thus some follow the ICH guidelines and some WHO guidelines for the registration of the drug product. But some regions have the country specific guidelines for registration of the FPP. Drug regulatory affairs in pharmaceutical industries have mandated two types of dossier namely CTD (Common Technical Dossier) and ACTD (ASEAN Common Technical Dossier). Regulated pharmaceutical markets (eg. USA, Europe) require submission of dossier in CTD format which require clinical trial and bioequivalence studies. As against this, semi-regulated pharmaceutical markets (South East Asian) require ACTD format which does not require exhaustive details like CTD. All of these guidelines will consider the safety, quality and efficacy of  Finished Pharmaceutical Product (FPP).

ORGANIZATION OF ICH-CTD FORMAT [14-18]
The CTD is organized into five modules. Module 1 is region-specific. Modules 2, 3, 4 and 5 are be common for all regions. Conformance with ICH guidelines should ensure that these four modules are provided in a format acceptable to WHO and regulatory authorities. An overview of module contents for a multisource product in greater details.
The five Modules are:
- Module 1: Administrative and prescribing information 
- Module 2: Overview and summary of module 3 to 5
- Module 3: Quality (Pharmaceutical documentation)
- Module 4: Safety (Toxicology/ Non-clinical studies)
- Module 5: Efficacy (Clinical studies)
The diagram below represents the above information as a modular structure which is known as CTD Triangle.
The modular structure of ICH-CTD shows that Module 1 is not a part of CTD, it contain only the regional information or administrative information of the one who right to file  the dossier for getting market authorization.
The modular structure is detailed with the help of technical data of common technical document (CTD) which is mentioned in all module as module of contents.

Fig 2 : Modular Structure of ICH CTD

This format is explained with an examples of two selected countries Zimbabwe and Australia from different continents which follow the ICH-CTD format for dossier preparation for selected drug(s) Regorafenib and Roflumilast respectively.

CATEGORIES OF PHARMACEUTICAL PRODUCT THAT CAN BE SUBMITTED AS A CTD REGISTRATION FILE
Most categories of product can be submitted in all of the ICH regions as a CTD registration file. This includes the following:
- New drug substance (NCE) products
- New biological/biopharmaceutical products
- Radiopharmaceuticals
- Phytopharmaceuticals (herbal medicines)

In the case of the United States, CTD registration files may also be submitted for generic and OTC products and this format would be obligatory in the European Union for these products.

DIFFERENCES IN CTD CONTENT BETWEEN THE ICH REGIONS
As mentioned in the Preface, the CTD is a harmonized format for registration files; however, the content is not yet completely harmonized. There are still national or regional differences in the content of submissions—not only in Module 1 but also in other parts of the dossier. These arise from differences in regulatory practice and procedures, differences in practices of medicine and pharmacy, and differences in access to diagnostic and therapeutic procedures. What are the major differences in content and how can companies cope with them to make filings in the major developed world markets?

Module 1 Differences
Although the ICH CTD refers to Module 1 as comprising “Regional Administrative  Information” (such as the application form, labeling, text of prescriber, and patient information), in practice there are other differences and some of key ones are summarized in table 2. It is usual for companies to prepare a common Core Data Sheet for information to health practitioners that could then be used to prepare draft Prescribing Information and Patient Information for the United States, the Summary of Product Characteristics (SmPC), and Patient Information Leaflet for the European Union.

Nation/region

Key differences

European Union

 1.4 Information about the Experts (who sign the Module 2 Summaries)

1.5 Specific Requirements for Different Kinds of Application (summaries to support
generics, hybrid applications, bibliographic applications, extended market exclusivity
applications, conditional marketing authorizations, etc.)

1.6 Environmental Risk Assessment

1.7 Information relating to Orphan Market Exclusivity

 1.8 Information relating to Pharmacovigilance

1.9 Information relating to Clinical Trials

United States

1.3.5 Patent and exclusivity information

1.9 Pediatric administrative information

1.16 Risk management plans

Japan

Patent status

Background of origin, discovery, and development

List of related products

Data for review of designation as poisons, deleterious substances, etc.

Draft of basic protocol for postmarketing surveillance

Canada

1.2.4 Patent information

1.4 Health Canada Summaries
1.4.1 Certified Product Information Document (CPID)
1.4.2 Comprehensive Summary of BE

1.5 Environmental Assessment Statement

Australia

1.4.1 Information about the Experts (who sign the Module 2 Summaries)

1.5 Specific requirements about different types of application (literature based,
orphan drug products, genetically modified organisms, comarketed medicines, etc.)

1.6 Drug and Plasma Master Files and Ph Eur Certificates of Suitability

GMP clearance letters

Summary Biopharmaceutic Studies

Pediatric Development Program

Environmental Risk for non-GMOs containing medicines

Antibiotic resistance data

CPID: This is a condensed summary of current and specific chemistry and manufacturing information attested by the manufacturer and sponsor. There is no requirement for Expert signatures for the Module 2 Summaries in registration filings in the United States, Japan, and Canada.

Module 2 Differences
Although the formal ICH requirements for the Module 2 Summaries are identical in all ICH
and other countries, there are likely to be national or regional differences particularly in elation to the contents of the Module 3: Quality and Module 5: Clinical Studies modular files, and these will be reflected in these high-level summaries. For example, where a pharmacopoeial drug is the subject of a DMF, there will be just a reference to the DMF in Module 2 of a U.S. or Japanese dossier, whereas in the European Union there will be a summary of the Open Part of the European Union Active Substance Master File (DMF).

Module 3 Differences
Some of the key national or regional differences in content of Module 3 in relation to the drug substance and drug product are summarized in Table 3 and Table 4.
In addition, there are the 3.2.R Regional Differences. Examples quoted in the ICH CTD
are as follows:
- Executed Batch Records for Drug Substance and Drug Product (the United States only): Copies of records with equipment specified, manufacturing conditions, packaging records, and batch reconciliation information (theoretical yield, actual yield, and packaged yield).
- Method validation package for drug substance and drug product (the United States only)
- Comparability protocols (the United States only)
- Process validation scheme (the European Union only), including a process validation protocol where validation studies on the manufacturing process for the drug product are not complete
- Medical device used in combination with the drug product (the European Union only)

In addition, highly abbreviated documentation (a “lite” document) on the manufacture of the drug substance in 3.2.S.2.2 Description of the Manufacturing Process and on 3.2.P.3.3 Description of the Manufacturing Process and Process Controls for the drug product may need to be supplied in countries where regulatory agencies do not always respect the confidentiality of data.

There may also be differences in marketing needs for different countries. Thus, blister or foil packs are usually the packaging material of choice for tablets or capsules in the European Union whereas in the United States high-density polyethylene (HDPE) bottles are much more commonly used. In such a case, 3.2.P.7 Container Closure will include different information and also the primary stability data in 3.2.P.8 Stability for the European Union will be in blister or foil packs and in the United States it will be in HDPE bottles.

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