CTD to TRD Related To Pharmaceutical Packaging

COMMON TECHNICAL DOCUMENT (CTD)

OVERVIEW:

•       The agreement to assemble all the Quality, Safety and Efficacy information in a common format and incorporates ICH guidelines.

•       It includes set of specifications for the submission of regulatory data in the application to market pharmaceutical product.

•       It is organized into 5 modules.

•       The order in which documents must appear so they are grouped logically and can be easily located.

CTD TRIANGLE

CTD format consists of 5 modules

•       Module 1:- Administrative and prescribing information

•       Module 2:- Summaries and overview

•       Module 3:- Information on product quality

•       Module 4:- Nonclinical study reports

•       Module 5:- Clinical study reports

 

The CTD should be organized according to the following general outline:

Module 1: Administrative Information and Prescribing Information

1.1 Table of Contents of the Submission Including Module 1

1.2 Documents Specific to Each Region (for example, application forms, prescribing information)

Module 2: Common Technical Document Summaries

2.1 CTD Table of Contents:

2.2 CTD Introduction

2.3 Quality Overall Summary

2.4 Nonclinical Overview

2.5 Clinical Overview

2.6 Nonclinical Written and Tabulated Summary

       Pharmacology

       Pharmacokinetics

       Toxicology

2.7 Clinical Summary

       Biopharmaceutics and Associated Analytical Methods

       Clinical Pharmacology Studies

       Clinical Efficacy

       Clinical Safety

       Synopses of Individual Studies

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.P.9	Product interchangeability
2.3.R	Regional Information

Module 3: Quality

3.1 Module 3 Table of Contents

3.2 Body of Data - Includes the data regarding the packaging material used in the production of Pharmaceutical drug substances and the drug product.

3.3 Literature References

Module 4: Nonclinical Study Reports

4.1 Module 4 Table of Contents

4.2 Study Reports

4.3 Literature References

Module 5: Clinical Study Reports

5.1 Module 5 Table of Contents

5.2 Tabular Listing of All Clinical Studies

5.3 Clinical Study Reports

5.4 Literature References

Section 3.2 Quality

BODY OF DATA

3.2.S	Drug Substance
3.2.S.1	General Information
3.2.S.2	Manufacture
3.2.S.3	Characterization
3.2.S.4	Control of Drug Substance
3.2.S.5	Reference Standards or Materials
3.2.S.6	Container/Closure Systems
3.2.S.7	Stability
3.2.P	Drug Product
3.2.P.1	Description and Composition of the Drug Product
3.2.P.2	Pharmaceutical Development
3.2.P.3	Manufacture
3.2.P.4	Control of Excipients
3.2.P.S	Control of Drug Product
3.2.P.6	Reference Standards or Materials
3.2.P.7	Container/Closure System
3.2.P.8	Stability
3.2.P.9	Product interchangeability

Container closure system refers to the sum of packaging components that together contain and protect the dosage form.

This includes primary packaging components and secondary packaging components, if the latter are intended to provide additional protection to the drug product.

•       A brief description of the container closure systems listed in P.7

•       If an NDA is submitted for a new plastic that will be used for blood component storage, adequate information on the plastic should be submitted.

•       Including the identification of the leachables such as plasticizers since plasticizers are more readily leached into a lipid such as blood than an aqueous solution.

Requirements which needs to be included:

•       The identity of materials of construction of each primary packaging component, and their specifications.

•       The specifications should include description and identification (and critical dimensions with drawings, where appropriate).

•       Noncompendial methods (with validation) should be included.

•       For nonfunctional secondary packaging components (e.g., those that do not provide additional protection), only a brief description should be provided.

•       For functional secondary packaging components, additional information should be provided.

Suitability information

•       Should be located in 3.2.P.2

•       The suitability of materials should be discussed with respect to drugs.

•       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 also safety of materials of construction.

•       The suitability of the container closure system (described in 3.2.P.7) for the storage, transportation (shipping), and use of the drug product should be discussed.

•       Suitability of the container closure system to protect from light

•       e.g., light transmission data should be discussed in 3.2.P.2.4.

•       Photo-stability data should be provided in 3.2.P.8.3

Importance of suitability studies:

•       The results of suitability studies can form the basis for inclusion, or omission, of specific tests on the finished product, container closure system, or individual packaging components. For example, when suitability studies and stability data demonstrate that leachables from the container closure systems used for products such as ophthalmic solutions or large volume parenterals (LVPs) are consistently below agreed upon levels, routine testing of the finished product for leachables would not be necessary.

Performance

Reproducibility of the dose delivery from the device presented as part of the drug product.

•       Information on performance of the container closure system should be included in 3.2.P.2.4 (e.g., priming and re-priming studies for metered dose inhalers).

•       Information on cleaning of metered dose inhalers should be included in 3.2.P.2.4.

Leachable

•       Information on leachables should also be included in 3.2.P.5.1 and 3.2.P.5.5.

•       Also, if leachables are confirmed through shelf-life as part of the formal stability studies, the results would be reported in 3.2.P.8.3.

Multiple Containers:

•       When there are two containers (e.g., PVC blister and PE bottle) for one drug product, the documents for the drug product part in Module 3 should generally be common.

•       In this case, one set of documentation, 3.2.P.1 through 3.2.P.8, should be provided.

•       The information for the blister and the bottle should be presented in the corresponding sections of the single drug product part in Module 3 (e.g., 3.2.P.7, 3.2.P.8), divided by subsections for each type of container and identified by the type of container.

Translation to technical regulatory documents (TRD)

•       The technical documentation it is more a set of documents that are written “automatically” during the development process.

•       Ensures the smooth transition for all the electronic submission's and avoids disruptions with review.

•       Technical Regulation shall establish requirements, which are mandatory for application for packaging (closures) and requirements related thereto for the processes of storage, transportation, and disposal.

Importance:

•       Ensuring Compliance

•       Safety Requirements

•       Requirements for Marking of Packaging (Closures)

Marking shall contain information required for identification of material from which the packaging (closures) is made, and information about the possibility of recycling.

Content of documentation files

•       File 1 of 3: Manufacturer Documentation

•       File 2 of 3 - Section one: FPP, API and excipients Documentation

•       File 2 of 3 - Section two: Packaging, Container/closure system(s)

•       File 3 of 3: Documents to accompany samples

File 2 of 3 - Section two: Packaging, Container/closure system(s)

1. Description and composition of the primary packaging.

2. Description and composition of the container/closure systems.

3. Description and composition of the liner/wadding/padding system.

4. Description and composition of secondary and any other packaging.

5. Evidence of conformance

6. Evidence of compliance with the requirement for packaging to be suitable for delivery and use.