THE ASEAN COMMON TECHNICAL DOSSIER (ACTD) FOR THE

REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE

QUALITY

Table of Contents

Scope of The Guideline . . . . . . . . . . . . . . . . . . . . . . . . . .10

Section A: Table of Contents . . . . . . . . . . . . . . . . . . . . . . . 10

Section B: Quality Overall Summary . . . . . . . . . . . . . . . . . . . 10

Section C: Body of Data . . . . . . . . . . . . . . . . . . . . . . . . . .16

1. Drug Substance . . . . . . . . . . . . . . . . . . . . . . .16
2. Drug Product . . . . . . . . . . . . . . . . . . . . . . . . .25

Section D: Key Literature References . . . . . . . . . . . . . . . . . . .34

ACTD 9
Scope of The Guideline
This document is intended to provide guidance on the format of a registration
application for drug products regarding ASEAN CTR. This format is
appropriate for NCE (New Chemical Entity), Biotech (Biotechnological
Products), MaV (Major Variations), MiV (Minor Variations) and G (Generics).
To determine the applicability of this format for a particular type of product,
applicant should consult with the appropriate National Regulatory
Authorities. The “Body of Data” in this guideline merely indicates where
the information should be located. Neither the type nor extent of specific
supporting data has been addressed in this guideline and both may depend
upon national guidance and or accepted leading international references
(pharmacopoeias).
For NCE and Biotech requirements please refer to the relevant ICH
Guidelines.

Section A: Table of Contents

A table of contents for the filed application should be provided.

Section B: Quality Overall Summary (QOS)

REQUIREMENTS
No. PARAMETERS COMPONENTS
NCE BIOTECH MaV MiV G

S DRUG SUBSTANCE
S1 General Information
1.1. Nomenclature − Information from the S1   * 
1.2. Structure − Structural formula, including relative and  
absolute stereochemistry, the molecular
formula, and the relative molecular
mass.
− Schematic amino acid sequence 
indicating glycosylation sites or other
post- translational modifications and
relative molecular mass as appropriate.
1.3. General Properties − Physico chemical characteristics and   * 
other relevant properties including
biological activity for biotech.

10 ACTD
 REQUIREMENTS
No. PARAMETERS COMPONENTS
NCE BIOTECH MaV MiV G
S2 Manufacture
2.1. Manufacturer(s) Name and address of the manufacturer (s).   
2.2. Description of − The description of the drug substance  
Manufacturing Process manufacturing process and process
and Process Controls control that represents the applicant's
commitment for the manufacture of the
drug substances.
− Information on the manufacturing 
process, which typically starts with a
vial(s) of the cell bank, and includes
cell culture, harvest(s), purification and
modification reaction, filling, storage and
shipping conditions.
2.3. Control of Materials − Starting materials, solvents, reagents,  
catalysts, and any other materials used in
the manufacture of the drugs substance
indicating where each material is used
in the process. Tests and acceptance
criteria of these materials.
− Control of source and starting materials 
of biological origin.
− Source, history and generation of the cell 
substrate.
− Cell banking system, characterisation 
and testing.
− Viral safety evaluation. 
2.4. Controls of Critical Steps − Critical steps: Tests and acceptance  
and Intermediates 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.
− Stability data supporting storage 
conditions.
2.5. Process Validation and/ Process validation and/or evaluation  
or Evaluation studies for aseptic processing and
sterilization.
2.6. Manufacturing Process − Description and discussion of significant 
Development changes made to the manufacturing
process and/or manufacturing site of
the drug substance used in producing
non- clinical, clinical, scale-up, pilot and
if available, production scale batches.
− The development history of the 
manufacturing process as described in
S 2.2
S3 Characterisation
3.1. Elucidation of Structure − Confirmation of structure based on e.g. 
and other characteristics synthetic route and spectral analyses.
− Compendial requirements or appropriate 
information from the manufacturer

ACTD 11
 REQUIREMENTS
No. PARAMETERS COMPONENTS
NCE BIOTECH MaV MiV G
− Details on primary, secondary and 
higher- order structure and information
on biological activity, purity and
immunochemical properties (when
relevant).
3.2. Impurities − Summary of impurities monitored or  
tested for during and after manufacture
of drug substance
− Compendial requirements or appropriate 
information from the manufacturer
S4 Control of Drug Substance
4.1. Specification − Detailed specification, tests and  
acceptance criteria.
− Compendial specification or appropriate 
information from the manufacturer
− Specify source, including as appropriate 
species of animal, type of microorganism
etc.
4.2. Analytical Procedures − The analytical procedures used for  
testing of drug substance.
− Compendial methods or appropriate 
information from the manufacturer
4.3. Validation of Analytical − Analytical validation information,  
Procedures including experimental data for the
analytical procedures used for testing
the drug substance
− Non-compendial methods 

4.4. Batch Analyses − Description of batches and results of the  

analysis to establish the specification.
4.5. Justification of − Justification for drug substance  
Specification specification.
S5 Reference Standards or − Information on the reference standards  
Materials or reference materials used for testing of
the drug substance .
− Compendial reference standard. * 

S6 Container Closure System − Descriptions of the container closure  

systems.
S7 Stability − Stability report.  
− Literature data . * 

P DRUG PRODUCT

P1 Description and Composition − Description   * * 

− Dosage form and characteristics.

− Accompanying reconstitution diluent (s)

if any.
− Type of container and closure used
for the dosage form and reconstitution
diluent (s), if applicable.
Composition   * * 
Name, quantity stated in metric weight or
measures, function and quality standard
reference.

12 ACTD
 REQUIREMENTS
No. PARAMETERS COMPONENTS
NCE BIOTECH MaV MiV G
P2 Pharmaceutical Development

2.1 Information on − Data on the development studies  

Development Studies conducted to establish that the dosage
form, formulation, manufacturing
process, container closure system,
microbiological attributes and usage
instruction are appropriate for the
purpose specified in the application.
2.2. Components of the Drug − Active ingredient
Product
• Justification of the compatibility of the  
active ingredient with excipients listed
in P1
• In case of combination products,
justification of the compatibility of
active ingredients with each other.
− Literature data. * 

− Excipients  
Justification of the choice of excipients
listed in P1, which may influence the
drug product performance.
2.3. Finished Product − Formulation Development   

A brief summary describing the

development of the finished product,
(taking into consideration the proposed
route of administration and usage for
NCE and Biotech).
− Overages   

Justification of any overage in the

formulation(s) described in P1 .
− Physicochemical and Biological   
Properties Parameters relevant to the
performance of the finished product e.g
pH, dissolution.
2.4. Manufacturing Process − Selection and optimisation of the  
Development manufacturing process
− Differences between the manufacturing  
process (es) used to produce pivotal
clinical batches and the process
described in P.3.2, if applicable
2.5. Container Closure Suitability of the container closure system   
System used for the storage, transportation
(shipping) and use of the finished product.
2.6. Microbiological Attributes Microbiological attributes of the dosage   * 
form, where appropriate
2.7. Compatibility Compatibility of the finished product with   *
reconstitution diluent(s) or dosage devices.
Literature data 

ACTD 13
 REQUIREMENTS
No. PARAMETERS COMPONENTS
NCE BIOTECH MaV MiV G
P3 Manufacture

3.1. Batch Formula Name and quantities of all ingredients   * 

3.2. Manufacturing Process Description of manufacturing process   * * 
and Process Control and process control
3.3. Control of Critical Steps Tests and acceptance criteria   
and Intermediates
3.4. Process Validation and/ Description, documentation, and results of   
or Evaluation the validation and/or evaluation studies for
critical steps or critical assays used in the
manufacturing process.
P4 Control of excipients

4.1. Specifications − Specifications for excipients  

Compendial requirements or appropriate * 

information from the manufacturer
4.2. Analytical Procedures − Analytical procedures used for testing  
excipients where appropriate.
Compendial requirements or appropriate * * 
information from the manufacturer
4.3. Excipient of Human or − Information regarding sources and or  
Animal Origin adventitious agents.
Compendial requirements or appropriate * * 
information from the manufacturer
4.4. Novel Excipients − For excipient(s) used for the first  
time in a finished product or by a new
route of administration, full details
of manufacture, charcterization and
controls, with cross reference to
supporting safety data (non- clinical or
clinical)
P5 Control of Finished Product

5.1. Specification − The specification(s) for the finished   * * 

product.
5.2. Analytical Procedures − Analytical procedures used for testing   * * 
the finished product
5.3. Validation of Analytical − Information including experimental data,  
Procedures for the analytical procedure used for
testing the finished product
Non-compendial method   * * 

Verification of compendial method * * 

applicability - precision & accuracy
5.4. Batch Analyses − Description and test results of all  
relevant batches.
5.5. Characterisation of − Information on the characterisation of  
Impurities impurities
Compendial requirements or appropriate * 
information from the manufacturer
5.6. Justification of − Justification of the proposed finished  
Specification(s) product specification(s).
Compendial requirements or appropriate * 
information from the manufacturer

14 ACTD
 REQUIREMENTS
No. PARAMETERS COMPONENTS
NCE BIOTECH MaV MiV G
P6 Reference Standards or − Information on the reference standards  
Materials or reference materials used for testing of
the finished product.
Compendial requirements or appropriate * 
information from the manufacturer
P7 Container Closure System − Specification and control of primary and   * * 
secondary packaging material, type of
packaging and the package size, details
of packaging inclusion (e.g. desiccant,
etc)
P8 Stability Stability report: data demonstrating that   * 
product is stable through its proposed
shelf life.
Commitment on post approval stability
monitoring
P9 Product Interchangeability

Equivalence evidence − In Vitro * 

Comparative dissolution study as

required
− In Vivo * 

Bioequivalence study as required

remarks : * if required
NCE : New Chemical Entity
Biotech : Biotechnological Products
MaV : Major Variation
MiV : Minor Variation
G : Generics

ACTD 15
 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

NCE:
The structural, including relative and absolute stereochemistry,
the molecular formula, and the relative molecular mass should be
provided.
Biotech:
The schematic amino acid sequence indicating glycosylation sites
or other post-translational modifications and relative molecular mass
should be provided, as appropriate.
Generic:
Compendial requirement or equivalent information from the
manufacturer.

S 1.3 General Properties

A list should be provided of physicochemical and other relevant
properties of the drug substance, including biological activity for
Biotech.
Reference ICH Guidelines: NCE: Q6A, Biotech: Q6B

16 ACTD
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:
NCE:
• 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.
Biotech:
• Information on the manufacturing process, which typically starts
with a vial(s) of the cell bank and includes cell culture, harvest(s),
purification and modification reaction, filling storage and shipping
conditions.
Reference ICH Guidelines: Q5A, Q5B and Q6B.

ACTD 17
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: NCE: Q6A; Biotech: Q6B
Biotech:
• Control of source and starting materials of biological Origin.
Summaries of viral safety information for biologically -sourced
materials should be provided.
• Source, history and generation of the cell substrate.
Information of the source of the cell substrate and analysis of
the expression construct used to genetically modify cells and
incorporated in the initial cell clone used to develop the Master
Cell Bank should be provided as described in Q5B and Q5D.
• Cell banking system, characterization and testing.
Information on the cell banking system; quality control activities
and cell line stability during production and storage (including
procedures used to generate the Master and Working Cell
Bank(s)) should be provided as described in Q5B and Q5D.
Reference ICH Guidelines: Q5A, Q5B, Q5C, and Q5D

18 ACTD
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.
Reference ICH Guidelines: Q6A, Q6B,
Additionally for Biotech: Stability data supporting storage conditions.
Reference ICH Guidelines: Q5C

S 2.5 Process Validation and/or Evaluation

Process validation or evaluation studies for aseptic processing and
sterilization.
Biotech
Sufficient information on validation and evaluation studies to
demonstrate that the manufacturing process (including reprocessing
steps) is suitable for its intended purpose and to substantiated
selection of critical process controls (operational parameters and in-
process test) and their limits for critical manufacturing steps (e.g. cell
culture, harvesting, purification, and modification).
Information should include a description of the plan for conducting
the study and the results, analysis and conclusions from the executed
study(ies). The validation of corresponding assay and analytical
methods should be cross-referenced or provided as part of justifying
the selection of critical process controls and limits.
For manufacturing steps, intended to remove or inactive viral
contaminants, the information from evaluation studies should be
provided
Reference ICH Guidelines Q5A, Q5D, and Q6B

ACTD 19
S 2.6 Manufacturing Process Development
NCE
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.
Reference ICH Guidelines: Q3A
Biotech
The developmental history of the manufacturing process, as
described in 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 (e.g. non-clinical or clinical studies)
including for example, changes to the process or critical equipment.
The reason for the change should be explained. Relevant information
on drug substance batches manufactured during development, such
as the batch number, manufacturing scale and use (e.g. stability, non
clinical reference material) in relation to the change.
The significance of change should be assessed by evaluating
its potential to impact the quality of the drug substance (and/or
intermediate, if appropriate). For manufacturing changes that are
considered significant, data from comparative analytical testing
on relevant drug substance. A discussion of the data including
a justification for selection of the test and assessment of results,
should be included.
Testing used to assess the impact of manufacturing changes on
the drug substance(s) and the corresponding drug product(s) may
also include non-clinical and clinical studies in other modules of the
submission should be included.
Reference ICH Guidelines: Q6B

20 ACTD
S 3 Characterization

S 3.1 Elucidation of Structure and Characteristic

NCE:
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.
Reference ICH Guidelines: Q6A
Biotech:
Details on primary, secondary and higher-order structure and
information on biological activity, purity and immunochemical
properties (when relevant).
Reference ICH Guidelines: Q6B
MaV, MiV, G:
Compendial requirement or equivalent information from the
manufacturer.

S 3.2 Impurities
Information on impurities should be provided.
Reference ICH guidelines: Q3A, Q3C, Q5C, Q6A and Q6B
Generic:
Compendial requirement or equivalent information from the
manufacturer.

ACTD 21
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.
Reference ICH Guidelines NCE: Q6A
Biotech:
Specify source, including as appropriate species of animal, type of
microorganism, etc.
Reference ICH Guidelines: Q6B
MaV, MiV, G:
Compendia specification are adequate. Indicate clearly whether the
drug substance is purchased based on specification with a certificate
of analysis, or tested by applicant.

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.
Reference ICH Guidelines: NCE: Q2A ; Biotech: Q6B

MaV, MiV, G:
Compendial requirement or equivalent information from the
manufacturer

S 4.3 Validation of Analytical Procedures

Analytical validation information, including experimental data for
the analytical procedure used for testing the drug substance should
be provided. Typical validation characteristics to be considered

22 ACTD
 are selectivity, precision (repeatability, intermediate precision and
reproducibility), accuracy, linearity, range, limit of quantitation, limit
of detection, robustness, and system suitability.
Reference ICH Guidelines: NCE: Q2A and Q2B ; Biotech: Q6B
MaV, MiV, G:
Required for non-compendial method only
Reference ASEAN Guideline for Validation of Analytical Procedure

S 4.4 Batch Analyses

Description of batches and results of batch analyses should be
provided
Reference ICH Guidelines: NCE: Q3A, Q3C and Q6A ; Biotech: Q6B

S 4.5 Justification of Specification

Justification for the drug substance specification should be provided.
Reference ICH Guidelines: NCE: Q6A ; Biotech: Q6B

S 5 Reference Standards or Materials

Quality information of Reference standard or material used for
testing of substance should be provided.
Reference ICH Guidelines: NCE: Q6A ; Biotech: Q6B
MaV, MiV, G:
Compendial requirement or equivalent information from the
manufacturer

S 6 Container Closure System

NCE and Biotech:
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

ACTD 23
 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.

S 7 Stability
Stability Summary and Conclusion
The types os 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, and Q5C
Post-approval Stability Protocol and Stability Commitment
The post-approval stability protocol and stability commitment should
be provided.
Reference ICH Guidelines: Q1A (R2) and Q5C
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.

24 ACTD
 Reference ICH Guidelines: Q1A (R2), Q1B, Q2A, Q2B, and Q5C
MaV, MiV, G:
Manufacturer stability data or equivalent information

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.
Reference ICH Guidelines: NCE: Q6A ; Biotech: Q6B

P 2 Pharmaceutical Development

P 2.1 Information on Development Studies

NCE and Biotech:
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

ACTD 25
 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: NCE: Q6A; Biotech: Q6B

P 2.2 Component of Drug Product

P 2.2.1 Active Ingredients

NCE and Biotech:
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.
MaV, MiV, G:
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

26 ACTD
 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.
Generics: refer to P.3.2.

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

ACTD 27
 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
from 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.
MaV, MiV, G:
Literature data are acceptable

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 be stated.
• A description of all stages involved in the manufacture of the
dosage form is required. Reference ICH Guidelines: Biotech: Q6B

28 ACTD
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, Q2B, Q6A and Q6B

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: NCE: Q6B, Biotech: Q6B
MaV, MiV, G:
ASEAN Guideline on process validation

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P 4 Control of Excipients

P 4.1 Specification
The specification for the excipients should be provided. Reference
ICH Guidelines: NCE: Q6A ; Biotech: Q6B
MaV, MiV, G:
Compendial requirements or equivalent information from the
manufacturer

P 4.2 Analytical Procedures

The analytical procedures used for the testing the excipient
should be provided, where appropriate.
Reference ICH Guidelines: NCE: Q2A ; Biotech: Q6B
MaV, MiV, G:
Compendial requirements or equivalent information from the
manufacturer.

P 4.3. Excipients of Human and Animal Origin

For excipients of human or animal origin, information should be
provided regarding advenitious agents(e.g. sources, specifications,
description of the testing performed, viral safety data).
(Reference ICH Guidelines: NCE: Q5A, Q5D ; Biotech: Q6B)

MaV, G:
Use compendial requirements if available, otherwise the same
requirements apply.

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

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 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; Biotech: Q6B

P 5.2 Analytical Procedures.

The analytical procedures use for the testing the finished product
should be provided.
Reference ICH Guidelines: NCE: Q2A ; Biotech: Q6B

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.
Reference ICH Guidelines: NCE: Q2A and Q2B; Biotech: Q6B
MaV, MiV. G:
Required for non-compendial method only however, verification for
the applicability of compendial method used is required.
Reference: ASEAN Guideline for validation of analytical procedure.

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.

ACTD 31
 Reference ICH Guidelines: NCE: Q3A, Q3C, and Q6A; Biotech:
Q6B.
Generics: refer to P.3.4.
MaV, MiV, G:
A tabulated summary of the batch analyses, with graphical
representation where appropriate, should be provided.

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; Biotech: Q6B
MaV, MiV, G:
Compendial requirements or appropriate information from the
manufacture.

P 5.6 Justification of Specification

Justification for the proposed finished product should be provided
Reference ICH Guidelines: NCE: Q3B and Q6A; Biotech: Q6B
MaV, MiV, G:
Compendial requirements or equivalent information from the
manufacture.

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.
Reference: NCE: Q6A, Biotech: Q6B
MaV , MiV, G:
Compendial requirements or equivalent information from the
manufacture.

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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
NCE and Biotech:
All criteria under ICH Guidelines are acceptable with the exception
of real time storage conditions which should be 300C, 75% RH.
Provision of moisture protection of the packaging should be taken
into consideration.
Reference ICH Guidelines: Q1A (R2), Q1B, Q2A, Q2B and Q5C
MaV, G:
ASEAN Guideline on Stability Study of Drug Product

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 Post-approval stability protocol and stability commitment
The post-approval stability protocol and stability commitment should
be provided.
References ICH Guidelines: NCE, Biotech: Q1A (R2) and Q5C
Generic:
ASEAN Guideline on Stability Study of Drug Product
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 of Drug Product,
ASEAN Guideline on Validation of Analytical Procedure

P 9 Product Interchangeability
This requirement applies to MaV, G.
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.

34 ACTD