1. CTD
Module 3 : Quality
Presented by
Ekant Taywade
Designation
Assistant Professor
Dr. Rajendra Gode Institute of Pharmacy, Amravati
2. SCOPE OF THE GUIDELINE
• The purpose of this document is to offer instructions on how to structure a
registration application for drug substances and the accompanying drug products
that are covered by ICH Guidelines Q 6 A ("NCE") and Q 6 B. ("Biotech"). For several
additional product categories, this approach might also be applicable. Applicants
should contact with the relevant regulatory authorities to determine whether this
format is applicable for a particular kind of product.
• The text following the section titles is intended to be explanatory and illustrative
only.
3.1. TABLE OF CONTENTS OF MODULE 3
A Table of Contents for the filed application should be provided
3.2. BODY OF DATA
3.2.S DRUG SUBSTANCE1 (NAME, MANUFACTURER)
3.2.S.1 General Information (name, manufacturer)
3. 3.2.S.1.1 Nomenclature (name, manufacturer)
Information on the nomenclature of the drug substance should be provided. For
example:
• Recommended International Nonproprietary Name (INN);
• Compendial name if relevant;
• Chemical name(s);
• Company or laboratory code;
• Other non-proprietary name(s), e.g., national name, United States Adopted Name
• (USAN), Japanese Accepted Name (JAN); British Approved Name (BAN), and
• Chemical Abstracts Service (CAS) registry number
3.2.S.1.2 Structure (name, manufacturer)
NCE:
It is necessary to presented the structural formula, including the absolute and relative
stereochemistry, the molecular formula, and the relative molecular mass.
Boitech:
As necessary, a schematic amino acid sequence indicating glycosylation sites or other
post-translational modifications should be included.
4. 3.2.S.1.3 General Properties (name, manufacturer)
Physicochemical and other pertinent characteristics of the drug material, such as biological
activity for Biotech, should be mentioned.
Reference ICH Guidelines: Q6A and Q6B
3.2.S.2 Manufacture (name, manufacturer)
3.2.S.2.1 Manufacturer(s) (name, manufacturer)
Each proposed production site or facility involved in manufacturing and testing should be
identified with the name, address, and responsibility of each manufacturer, including
contractors.
3.2.S.2.2 Description of Manufacturing Process and Process Controls (name,
manufacturer)
The applicant’s dedication to producing the drug substance is represented in the process
description for the manufacturing of the drug substance. The production process and process
controls should be adequately described in the information provided.
NCE:
• Molecular formulae, weight ranges, chemical structures of starting materials, intermediates,
reagents, and drug substances reflecting stereochemistry, as well as operating parameters and
solvents, should be included in a flow diagram of the synthetic process.
5. • A sequential procedural narrative of the manufacturing process should be submitted
such as quantities of raw materials, solvents, catalysts and reagents reflecting the
representative batch scale for commercial manufacture, identification of critical steps,
process controls.
• Alternate processes should be explained and described with the same level of detail as
the primary process.
• Any data to
• support this justification should be either referenced or filed in 3.2.S.2.5
Biotech
Batch(es) and scale definition
An explanation of the batch numbering system, including information regarding any
pooling of harvests or intermediates and batch size or scale should be provided.
Cell culture and harvest
Flow diagram of manufacturing route from original incolum . In diagram should include
all steps and intermediate and relevant information of each steps . Critical steps and
critical intermediates for which specifications are established (as mentioned in 3.2.S.2.4)
should be identified.
6. Purification and modification reactions
• The flow diagram of purification steps from crude harvest upto Step preceding filling of the
drug subtance and reletaed information of all steps and intermediate.Critical steps for which
specifications are established as mentioned in 3.2.S.2.4 should be identified.
• Description of eache steps. In description contain information about scale, reagent (details
provided in 3.2.S.2.3, major equipment (details provided in 3.2.A.1), and materials. For
material like membrane, cromatograpy resin information and conditions of use should be
included(Equipment details in 3.2.A.1; validation studies for the reuse and regeneration of
columns and membranes in 3.2.S.2.5.)
• Reprocessing procedures with criteria for reprocessing of any intermediate or the drug
substance should be described. (Details should be given in 3.2.S.2.5.)
• Information on procedures used to transfer material between steps, equipment, areas, and
buildings, as appropriate, and shipping and storage conditions should be provided (details on
shipping and storage provided in 3.2.S.2.4.).
Filling, storage and transportation (shipping)
Details about filling procedure of drug subtance process control and acceptance criteria must be
provided (Details in 3.2.S.2.4.) also the container closer system used for storage of drug subtance
(details in 3.2.S.6.) and storage and shipping condition also described.
7. 3.2.S.2.3 Control of Materials (name, manufacturer)
List of all material used in manufacturing of drug subtance with sources also quality and control
data must be provided
Reference ICH Guidelines: Q6A and Q6B
Biotech:
• Control of Source and Starting Materials of Biological Origin.
• Source, history, and generation of the cell substrate.
• Cell banking system, characterisation, and testing
Reference ICH Guidelines: Q5A, Q5B, Q5C and Q5D
3.2.S.2.4 Controls of Critical Steps and Intermediates (name, manufacturer)
Critical Steps: Tests and acceptance criteria ( performed at critical steps identified in 3.2.S.2.2 of
the manufacturing process to ensure that the process is controlled should be provided.
Intermediates: Information on the quality and control of intermediates isolated during the
process should be provided.
Reference ICH Guidelines: Q6A and Q6B
Additionally for Biotech: Stability data supporting storage conditions should be provided.
Reference ICH Guideline: Q5C
8. 3.2.S.2.5 Process Validation and/or Evaluation (name, manufacturer)
Biotech: manufacturing process is appropriate for its intended use and to support the choice of
critical process controls and their limitations for critical manufacturing processes, sufficient
information should be provided on validation and evaluation studies.
The analytical procedures and corresponding validation should be cross-referenced.
3.2.S.2.6 Manufacturing Process Development (name, manufacturer)
NCE:For producing nonclinical, clinical, scale-up, pilot, and, if available, production scale batches,
the drug substance’s manufacturing process and/or manufacturing location should have been
described and discussed.
Biotech:
• The developmental history of the manufacturing process, as described in 3.2.S.2.2,
should be provided.
• The description of change(s) made to the manufacture of drug substance batches used in
support of the marketing application.
• Changes to the process or to critical equipment. The reason for the change should be
explained.
• Relevant information on drug substance batches manufactured during development, such as
the batch nnumber, manufacturing scale, and use
9. • Data from comparative analytical testing on relevant drug substance batches should be
provided for manufacturing changes that are considered major in order to determine the
impact on drug substance quality.
Reference should be made to the drug substance data provided in section 3.2.S.4.4.
Reference ICH Guideline: Q6B
3.2.S.3 Characterisation (name, manufacturer)
3.2.S.3.1 Elucidation of Structure and other Characteristics (name, manufacturer)
NCE: It is essential to provide structural confirmation using methods like synthetic route and
spectral analysis. Include details about stereochemistry, the possibility of isomerism, and the
capacity to create polymorphs, among other things.
Biotech:Details on primary, secondary, and higher-order structure, post-translational forms,
biological activity, purity, and immunochemical properties should be included for the target
product and compounds related to it, as appropriate.
3.2.S.3.2 Impurities (name, manufacturer)
Information on impurities should be provided.
Reference ICH Guidelines: Q3A, Q3C, Q5C, Q6A, and Q6B
10. 3.2.S.4 Control of Drug Substance (name, manufacturer)
3.2.S.4.1 Specification (name, manufacturer)
The specification for the drug substance should be provided.
Reference ICH Guidelines: Q6A and Q6B
3.2.S.4.2 Analytical Procedures (name, manufacturer)
The analytical procedures used for testing the drug substance should be provided.
Reference ICH Guidelines: Q2A and Q6B
3.2.S.4.3 Validation of Analytical Procedures (name, manufacturer)
Analytical validation information, including experimental data for the analytical
procedures used for testing the drug substance, should be provided.
Reference ICH Guidelines: Q2A, Q2B, and Q6B
3.2.S.4.4 Batch Analyses (name, manufacturer)
Description of batches and results of batch analyses should be provided.
Reference ICH Guidelines: Q3A, Q3C, Q6A, and Q6B
3.2.S.4.5 Justification of Specification (name, manufacturer)
Justification for the drug substance specification should be provided.
Reference ICH Guidelines: Q3A, Q3C, Q6A and Q6B
11. 3.2.S.5 Reference Standards or Materials (name, manufacturer)
Information on the reference standards or reference materials used for testing of the drug
substance should be provided.
Reference ICH Guidelines: Q6A and Q6B
3.2.S.6 Container Closure System (name, manufacturer)
• Detail of container closure system should be provided. In the detail Also includes identify of
material of construction of each primary packaging components and their specifications. It
also include dwaing and critical dimension.
• Brief information about secondary packaging.
• Detail about compatibility of material of construction with drug substance.
3.2.S.7 Stability (name, manufacturer)
3.2.S.7.1 Stability Summary and Conclusions (name, manufacturer)
summarized data of types of study , protocol used , result of study (forced degradation
studies and stress conditions, shelf-life).
Reference ICH Guidelines: Q1A, Q1B, and Q5C
3.2.S.7.2 Post-approval Stability Protocol and Stability Commitment (name, manufacturer)
The post-approval stability protocol and stability commitment should be provided.
Reference ICH Guidelines: Q1A and Q5C
12. 3.2.S.7.3 Stability Data (name, manufacturer)
The stability studies’ results (such as those involving forced degradation and stress conditions)
should be presented in a suitable format, such as tabular, graphical, or narrative. It should
provide information on the analytical techniques used to produce the data and the verification
of those techniques.
Reference ICH Guidelines: Q1A, Q1B, Q2A, Q2B, and Q5C
