SFDA

Data Requirements for Human Drugs
Submission
Content of the Dossier
Version 3.0
Date of issue 22 June 2011
Date of implementation 22 September 2011
DS-REQ-002-V03/110622
Data Requirements for Human Drugs
Submission
Content of the Dossier
Version 3.0
Saudi Food & Drug Authority

Drug Sector
For Inquiries [email protected]

For Comments [email protected]
Please visit SFDA’s website at

https://www.sfda.gov.sa/en/regulations?tags=2
for the latest update

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Saudi Food and Drug Authority
Vision and Mission
Vision
To be a leading international science-based regulator to protect and promote public

health
Mission
Protecting the community through regulations and effective controls to ensure the
safety of food, drugs, medical devices, cosmetics, pesticides and feed
DS-REQ-002-V03/110622
Document Control
Version Author Date Comments
Executive Directorate of Product

1.0 22 June 2011 Draft
Evaluation and Standards Setting

1.1 24 June 2013 Updated

1.2 12 April 2014 Updated

1.3 15 July 2014 Updated
2.0 Drug Sector 9 March 2017 Updated
2.1 Drug Sector 24 October 2017 Updated

Update
Executive Department of
3.0 13 October 2022 (Next page shows the
Regulatory Affairs updated details)
DS-REQ-002-V03/110622
What is New in version No. 3.0?
The following table shows the update to the previous version:
Section Description of change
Update:
Introduction - In case of Generic Products:
Introduction: Module 1: Regional Add:
Administrative Information - Patents information
Update:
1.2 Application Form
- The eSDR link
1.3.4 Artwork (Mock-ups) Updated
1.6.1 Pharmacovigilance System Updated
1.7.5 Alcohol-content declaration Updated
Add:
1.7.10 Letter of access or - The drug substance information.
acknowledgment to DMF - Attach the confirmation email of DMF/ASMF
submission.
Add:
1.8 Pricing - Price list
- Other documents related
1.9 Responses to questions Add:
– Additional Data: - Documents related to abridge and verification.
Update:
Module 2
- Quality Overall Summary
Addition:
3.2.S Drug Substance
- DMF submissions and correspondence and attach the
- 2 Drug Master File (DMF):
confirmation email of DMF/ASMF submission.
Update
- 3.2.S.2.1 Manufacturer(s)
- 3.2.S.2.2 Description of Process and Process Controls
- 3.2.S.2.3 Control of Materials
- 3.2. S.2.4 Control of Critical Steps and Intermediates
3.2.S.2 Manufacturer
- 3.2. S.2.5 Process Validation and/or Evaluation
- 3.2.S.2.6 Manufacturing Process Development
- 3.2.S.3.1 Elucidation of Structure and Other Characteristics
- For Biotech
- 3.2.S.3.2 Impurities
Addition:
3.2.P.3.1 Manufacturer(s) This section should also include all the proposed QC testing site(s)
intended to be approved in Saudi Arabia.
3.2.P.3.5 Process Validation and/or
Updated
Evaluation
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Table of Contents
ACRONYMS AND ABBREVIATIONS ....................................................................................... 7

INTRODUCTION .......................................................................................................................... 8
TABLE 1: THE eCTD STRUCTURE FOR HUMAN DRUGS SUBMISSION ......................... 13
MODULE 1 REGIONAL ADMINISTRATIVE INFORMATION ........................................ 21
MODULE 2 COMMON TECHNICAL DOCUMENT SUMMARIES ................................... 30
MODULE 3 QUALITY ............................................................................................................ 40
MODULE 4 NON-CLINICAL STUDY REPORTS ................................................................ 97
MODULE 5 CLINICAL STUDY REPORTS ........................................................................ 102
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ACRONYMS AND ABBREVIATIONS
BA Bioavailability
BE Bioequivalence
BP British Pharmacopoeia
BSE Bovine Spongiform Encephalopathy
CEP Certificates of Suitability
COO Country of Origin
CPP Certificate of Pharmaceutical Product
CRFs Case Report Forms
eCTD Common Technical Document
DMF Drug Master File
EU European Union
GCC Gulf Cooperation Council
GCP Good Clinical Practice
GLP Good Laboratory Practice
GMO Genetically Modified Organism
GMP Good Manufacturing Practice
ICH International Conference on Harmonisation
IV/IVC In vitro/In vivo Correlation
NCE New Chemical Entity
Non-GMO Non-Genetically Modified Organism
PD Pharmacodynamics
Ph. Eur. European Pharmacopoeia
PIL Patient Information Leaflet
PK Pharmacokinetics
QOS Quality Overall Summary
RMP Risk Management Plan
SDR Saudi Drug Registration System
SFDA Saudi Food and Drug Authority
SPC Summary of Product Characteristics
TSE Transmissible Spongiform Encephalopathy
US FDA Food and Drug Administration of the United States
USP United States Pharmacopoeia
WHO World Health Organization
DS-REQ-002-V03/110622
INTRODUCTION
The information presented in this guidance is based on recommendations of the:
− WHO, as described in the "Guideline on Submission of Documentation for a Multisource

(Generic) Finished Pharmaceutical Product (FPP): Quality Part (2010)”;
− ICH, as described in the “M4Q (R1), M4S(R2), and “M4E(R1) (2002)”; and
− EU, as described in the “Notice to Applicants, Volume 2B: Presentation and content of the
dossier (2006)”.
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 eCTD structure (i.e. applicants
should not modify the overall organization of the eCTD as outlined in this guideline):
a) In case of New Chemical Entity (NCE), Biologicals and Biosimilars ALL the eCTD
Modules are required.
b) In case of Generic Products:
In preparing the dossier for generic products, it is acknowledged that certain modules or
sections of the eCTD would generally not be applicable and should be marked as such (and
not to be deleted).
Please note that for applications of generic drug of a non-SFDA registered reference product
should include in addition to the bioequivalence requirements, a comprehensive literature
review of the active substance to support the generic product registration. The literature review
should be submitted in module 2.5 clinical overview and covers the following aspects:
▪ The search should be as extensive and relevant as possible
▪ The rationale for the development of the active substance as well as the
generic product. The search should support the efficacy and safety of the
active ingredient in each proposed indication.
▪ Bioequivalence and bioavailability data of the generic product.
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▪ Safety and efficacy of the active substance in each of the proposed
indications.
▪ Methodology of the search used should be stated in detail (database used,

keywords used, and filters applied as well as date and time the search was
carried on).
▪ Provide a tabular listing of the identified literature with their citations and
arrange the studies according to the following:
- Start with the key clinical studies (e.g. confirmatory studies).
- Well-designed, adequately powered, and preferably multicenter studies.
- Studies that have registered protocol or registered in clinical trials

registries (provide registration status).
- Evidence from non-randomized controlled trials should be located in a

separate section of the table.
- Post marketing safety studies.
- If possible, provide study reports for each identified study.
Summarize serious adverse events related to the product (from randomized controlled trials
and observational studies as well as periodic safety update reports (PSUR) of the reference
product).
− Module 1: Regional Administrative Information
This Module is required to be submitted. It should contain documents specific to SFDA;

e.g., application form, proposed labelling, alcohol-content declaration, patents information
... etc. The content and format of this module is further illustrated in this guideline.
− Module 2: Common Technical Document Summaries
The following sections are required to be submitted under Module 2:
- 2.1 Table of Contents of Module 2-5.

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- 2.2 Introduction:
This section should begin with a general introduction to the pharmaceutical, including
its pharmacologic class, mode of action, and proposed clinical use. In general, the
introduction should not exceed one page.
- 2.3 Quality Overall Summary:
The whole section is required and should reflects the information provided in Module
3.
- 2.5 Clinical Overview:
2.5.2 “Overview of Biopharmaceutics”: The summary of the comparative

bioequivalence/bioavailability study reports should be provided under this section. In
addition, critical analysis of any important issues related to bioavailability that might
affect efficacy and/or safety of the to-be-marketed formulation(s) (e.g., dosage
form/strength proportionality and influence of food on exposure) should be provided
under this section.
− Module 3: Quality
The whole section is required and the information should be presented according to the
structured format described in this guideline.
− Module 4: Non-Clinical Study Reports
Generally not applicable for generic products, however some exceptions may apply.
− Module 5: Clinical Study Reports
It is anticipated that only the following relevant sections of Module 5 will normally be
required.
- 5.1 Table of contents for Module 5
- 5.2 Tabular listing of all clinical studies
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- 5.3 Clinical study reports
o 5.3.1 Reports of biopharmaceutical studies
− 5.3.1.2 Comparative BA & BE Study Reports
The comparative bioavailability/bioequivalence study reports should be

presented in Module 5 under section 5.3.1.2 “Comparative BA & BE Study
Reports”.
− 5.3.1.3 In vitro/In vivo Correlation (IV/IVC) study reports: if available
− 5.3.1.4 Reports of Bioanalytical and Analytical Methods for Human studies:

Bioanalytical or analytical methods for BA/BE or in vitro dissolution
studies should ordinarily be provided in the clinical study reports. However,
where a method is used in multiple studies, the method and its validation
should only be included once in section 5.3.1.4 and referenced in the
appropriate individual clinical study reports.
− 5.3.7 Case Report Forms and Individual Patient Listings: only Case Report
Forms (CRFs) for subjects who experienced serious adverse events should
be included. All CRFs should be available upon request.
− 5.4 Literature references
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The following are recommendations for the presentation of the information in the Quality
Module for different scenarios that may be encountered:
− For a drug product containing more than one drug substance: one complete “3.2.S”
section should be provided for one drug substance, followed by other complete “3.2.S” sections
for each drug substance.
− For a drug substance from multiple manufacturers: one complete “3.2.S” section should
be provided for the drug substance from one manufacturer, followed by other complete “3.2.S”
sections for each drug substance manufacturer.
− For a drug product with multiple strengths: one complete “3.2.P” section should be
provided with the information for the different strengths provided within the subsections. One
complete copy of the dossier should be provided for each strength.
− For a drug product with multiple container closure systems (e.g. bottles and unit dose
blisters): one complete “3.2.P” section should be provided with the information for the
different presentations provided within the subsections.
− For multiple drug products (e.g. tablets and a parenteral product): a separate dossier is
required for each drug product.
− For a drug product supplied with reconstitution diluent(s), the information on the diluent
should be provided in a separate part “3.2.P” if the diluent is co-packaged with the drug
product. However, if the diluent is not co-packaged with the drug product, the compatibility of
the diluent with the drug product should be discussed in 3.2.P.2.6.
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TABLE 1: THE eCTD STRUCTURE FOR HUMAN DRUGS SUBMISSION
Section Requirements
Module 1 Regional Administrative Information
1.0 Cover letter
1.2 Application Form
1.3 Product Information
1.3.1 Summary of Product Characteristics (SPC)
1.3.2 Labeling
1.3.3 Patient information leaflet (PIL)
1.3.3.1 Arabic leaflet
1.3.3.2 English leaflet
1.3.4 Artwork (Mock-ups)
1.3.5 Samples
1.4 Information on the experts
1.4.1 Quality
1.4.2 Non-clinical
1.4.3 Clinical
1.5 Environmental Risk Assessment
1.5.1 Non-Genetically Modified Organism (Non-GMO)
1.5.2 GMO
1.6 Pharmacovigilance
1.6.1 Pharmacovigilance System
1.6.2 Risk Management Plan
1.7 Certificates and Documents
1.7.1 GMP Certificate
1.7.2 CPP or Free-sales
1.7.3 Certificate of analysis – Drug Substance / Finished Product
1.7.4 Certificate of analysis – Excipients
1.7.5 Alcohol-content declaration
1.7.6 Pork- content declaration
1.7.7 Certificate of suitability for TSE
1.7.8 The diluents and coloring agents in the product formula
1.7.9 Patents Information
1.7.10 Letter of access or acknowledgment to DMF
1.8 Pricing
1.8.1 Price list
1.8.2 Other documents related
1.9 Responses to questions
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Module 21 Common Technical Document Summaries
2.1 Table of Contents of Module 2-5
2.2 Introduction
2.3 Quality Overall Summary
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
2.5 Clinical Overview
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
2.6.1 Introduction
2.6.2 Pharmacology Written Summary
2.6.2.1 Brief Summary
2.6.2.2 Primary Pharmacodynamics
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Module 2 should reflect the information provided in modules 3, 4 and 5.
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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
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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
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Module 3 Quality
3.1 Table of Contents of Module 3
3.2 Body of data
3.2.S.1.1 Nomenclature
3.2.S.1.2 Structure
3.2.S.1.3 General Properties
3.2.S.2 Manufacture
3.2.S.2.1 Manufacturer(s)
3.2.S.2.2 Description of Process and Process Controls
3.2.S.2.3 Control of Materials
3.2.S.2.4 Control of Critical Steps and Intermediates
3.2.S.2.5 Process Validation and/or Evaluation
3.2.S.2.6 Manufacturing Process Development
3.2.S.3.1 Elucidation of Structure and Other Characteristics
3.2.S.3.2 Impurities
3.2.S.4.1 Specifications
3.2.S.4.2 Analytical Procedures
3.2.S.4.3 Validation of Analytical Procedures
3.2.S.4.4 Batch Analyses
3.2.S.4.5 Justification of Specification
3.2.S.6 Container/Closure Systems
3.2.S.7 Stability
3.2.S.7.1 Stability Summary and Conclusions
3.2.S.7.2 Post-approval Stability Protocol and Commitment
3.2.S.7.3 Stability Data
3.2.P Drug Product
3.2.P.2.1 Components of the Drug Product
3.2.P.2.1.1 Drug substance
3.2.P.2.1.2 Excipients
3.2.P.2.2 Drug Product
3.2.P.2.2.1 Formulation Development
3.2.P.2.2.2 Overages
3.2.P.2.2.3 Physiochemical and Biological Properties
3.2.P.2.3 Manufacturing Process Development
3.2.P.2.4 Container Closure System
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3.2.P.2.5 Microbiological Attributes
3.2.P.2.6 Compatibility
3.2.P.3 Manufacture
3.2.P.3.1 Manufacturer(s)
3.2.P.3.2 Batch Formula
3.2.P.3.3 Description of Manufacturing Process and Process Controls
3.2.P.3.4 Controls of Critical Steps and Intermediates
3.2.P.3.5 Process Validation and/or Evaluation
3.2.P.4.1 Specifications
3.2.P.4.2 Analytical Procedures
3.2.P.4.3 Validation of Analytical Procedures
3.2.P.4.4 Justification of Specifications
3.2.P.4.5 Excipients of Human or Animal Origin
3.2.P.4.6 Novel Excipients
3.2.P.5.4 Batch Analyses
3.2.P.5.5 Characterization of Impurities
3.2.P.8 Stability
3.2.P.8.1 Stability Summary and Conclusions
3.2.P.8.2 Post-Approval Stability Protocol and Stability Commitments
3.2.P.8.3 Stability Data
3.2.A Appendices
3.2.A.3 Excipients
3.3 Literature References
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Module 4 Non-Clinical Study Reports
4.2 Study Reports
4.2.1 Pharmacology
4.2.2 Pharmacokinetics
4.2.2.1 Analytical Methods and Validation Reports
4.2.2.2 Absorption
4.2.2.4 Metabolism
4.2.2.5 Excretion
4.2.3 Toxicology
4.2.3.3.1 In vitro Studies
4.2.3.3.2 In vivo Studies
4.2.3.4.1 Long Term Studies
4.2.3.4.2 Short or medium term studies
4.2.3.4.3 Other studies
4.2.3.5 Reproductive and Development Toxicity
4.2.3.5.1 Fertility and Embryonic Development
4.2.3.5.2 Embryo-Fetal Development
4.2.3.5.3 Pre- and Post-natal Development & Maternal Function
4.2.3.5.4 Offspring, Juvenile, Second & Third-Generation Studies
4.2.3.7 Other Toxicity Studies
4.2.3.7.1 Antigenicity
4.2.3.7.2 Immunogenicity
4.2.3.7.3 Mechanistic Studies (not included elsewhere)
4.2.3.7.4 Dependence
4.2.3.7.5 Metabolites
4.2.3.7.6 Impurities
4.2.3.7.7 Other
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Module 5 Clinical Study Reports
5.2 Tabular Listing of All Clinical Studies
5.3 Clinical Study Reports
5.3.1 Reports of Biopharmaceutic Studies
5.3.1.1 Bioavailability (BA) Study Reports
5.3.1.2 Comparative BA & BE Study Reports
5.3.1.3 In vitro/In vivo Correlation (IV/IVC) study reports
5.3.1.4 Reports of Bioanalytical and Analytical Methods for Human studies
5.3.2 Reports of Studies Pertinent to Pharmacokinetics using Human Biomaterials
5.3.2.1 Plasma Protein Binding Study Reports
5.3.2.2 Reports of Hepatic Metabolism and Drug Interactions studies
5.3.2.3 Reports of Studies Using other Human Biomaterials
5.3.3 Reports of Human Pharmacokinetic Studies
5.3.3.1 Healthy Subject PK and Tolerability
5.3.3.2 Patient PK and Initial Tolerability
5.3.3.3 Intrinsic Factor PK Study Reports
5.3.3.4 Extrinsic Factor PK Study Reports
5.3.3.5 Population PK Study Reports
5.3.4 Reports of Human Pharmacodynamic (PD) Studies
5.3.4.1 Healthy Subject PD and PK/PD Study Reports
5.3.4.2 Patient PD and PK/PD Study Reports
5.3.5 Reports of Efficacy and Safety Studies
5.3.5.1 Study reports of Controlled Clinical Studies pertinent to the claimed
Indication
5.3.5.2 Study reports of Uncontrolled Clinical Studies
5.3.5.3 Reports of Analyses of Data from More than One Study
5.3.5.4 Other Study Reports
5.3.6 Reports of Post-Marketing Experience
5.3.7 Case Report Forms and Individual Patient Listings
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MODULE 1 REGIONAL ADMINISTRATIVE INFORMATION
1. Cover letter
The applicant shall include a cover letter for each submission. A template is provided in the
SFDA Guidance for Submission.
1.2. Application Form
The completed application form printed out from the Saudi Drug Registration (SDR) system
(https://esdr.sfda.gov.sa) should be presented in this section.
1.3. Product Information
This section contains the Summary of Product Characteristics (SPC), Labeling, Patient
Information Leaflet (PIL) in Arabic and English, Artwork and the Samples.
1.3.1. Summary of Product Characteristics (SPC)
The SPC should include the name of the product, strength, pharmaceutical form, quantity of active
ingredients, posology, method of administration, indications, contraindications, excipients, shelf-
life and any special warnings and precautions for use … etc.
Refer to the GCC Guidance for Presenting the SPC, PIL and Labeling Information.
1.3.2. Labeling
The labeling forms part of the authorization of the product and must therefore be approved by the
SFDA. The text of the labeling must be in compliance with the SPC.
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1.3.3. Patient Information Leaflet (PIL)
1.3.3.1. Arabic leaflet
1.3.3.2. English leaflet
The Patient Information Leaflet (PIL) forms part of the authorization of the product and must
therefore be approved by the SFDA. The text of the PIL must be in compliance with the SPC. The
application for a marketing authorization must include a draft for the PIL.
1.3.4. Artwork (Mock-ups)
A mock-up is a flat artwork design in full color, presented so that, following cutting and folding,
where necessary, it provides a full size replica of both the outer and immediate packaging so that
the two dimensional presentation of the label text is clear.
The application for a marketing authorization must include 4 mock-ups as following:
1. The non-contrast photo of flat outer pack.
2. The on shelf photo of outer pack.
3. The photo of internal product.
4. The photo of dosage form.
1.3.5. Samples
A number of samples should be provided in order to perform complete testing. The required
quantities of samples is further described in the SFDA Guidance for Submission .The submitted
samples must represent the final finished product to be marketed in Saudi Arabia.
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1.4. Information on the experts
1.4.1. Quality
1.4.2. Non-Clinical
1.4.3. Clinical
It is important to emphasize that well prepared expert reports greatly facilitate the task of the SFDA
in evaluating the dossier and contribute towards the speedy processing of applications.
Authors of expert reports must be chosen on the basis of their relevant qualifications and their
recognized expertise in the field concerned. The experts should preferably not have been
personally involved in the conduct of the tests included in the dossier.
Each expert report should consist of:
• An abbreviated product profile;

• A critical evaluation of the dossier;
• The opinion of the expert as to whether sufficient guarantees have been provided as to the
suitability of the product for its proposed use;
• A summary of all the important data;
• The signature of the expert and the place and date of the report’s issue;
• The expert’s curriculum vitae and a declaration of the expert’s professional relationship to the
applicant.
It is essential to note that the expert reports must include a critical discussion of the properties of
the product as demonstrated by the contents of the dossier. The expert is expected to take and
defend a clear position on the final product, in the light of current scientific knowledge. A simple
factual summary of the information contained in the application is not sufficient and the expert
reports must not be a repetition of other parts of the dossier, although important data will need to
be summarized in the expert report in some form. Both expert reports and summaries must contain
precise references to the information contained in the main documentation. If experts wish to
supplement their report by reference to additional literature, they must indicate clearly that the
applicant has not included this information in the relevant part of the dossier.
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1.5. Environmental Risk Assessment
1.5.1. Non-Genetically Modified Organism (Non-GMO)
1.5.2. GMO
The applicant shall include an evaluation for any potential risks of the product to the environment.
This should include risks to the environment arising from use, storage and disposal of products
and not for risks arising from the synthesis or manufacture of products.
1.6. Pharmacovigilance
1.6.1. Pharmacovigilance System
A summary description of the pharmacovigilance system used by the marketing authorization

holder and by the SFDA to fulfil the tasks and responsibilities listed in the published guideline on
good pharmacovigilance practices which is designed to monitor the safety of authorized medicinal
products and detect any change to their risk-benefit balance.
For further information, refer to Guideline on Good Pharmacovigilance Practices.
1.6.2. Risk Management Plan
A detailed description of the risk management system.
To this end, it must identify or characterize the safety profile of the medicinal product(s)
concerned, indicate how to characterize further the safety profile of the medicinal product(s)
concerned, document measures to prevent or minimize the risks associated with the medicinal
product, including an assessment of the effectiveness of those interventions and document post-
authorization obligations that have been imposed as a condition of the marketing authorization.
For further information, refer to Guideline on Good Pharmacovigilance Practices.
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1.7. Certificates and Documents
1.7.1. GMP Certificate
A valid GMP Certificate should be submitted.
1.7.2. CPP or Free-sales
The CPP should be in accordance with WHO guidelines. However, if the CPP is not available, a
marketing authorization (or free sales certificate) from the country of origin (COO) should be
submitted. Marketing authorization (or free sales certificate) should include the following:
1. Product trade name in the COO.
2. Number and date of marketing authorization in the COO.
3. Name of active and inactive substances with their concentrations.
4. A statement that certifies the product is marketed in the COO. If not, please specify the reasons
and provide a marketing authorization showing that the product is marketed in one of the
countries approved by SFDA (reference member state in EU, USA, Canada, Switzerland,
Australia and Japan).
5. Provide official document demonstrating that the product has been registered for no less than
one year in the COO.
6. Provide the Summary of Product Characteristics (SPC).
7. Provide a copy of the patient information leaflet (PIL).
1.7.3. Certificate of analysis – Drug Substance/Finished Product
− Certificates of analysis for more than one batch of the drug substance should be submitted
from the supplier (drug substance manufacturer).
− Certificates of analysis for the drug substance should be submitted from the finished product
manufacturer.
− Certificates of analysis for more than one batch of the finished product should be submitted.
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The information on drug substance batch analyses is recommended to be presented as
follows:
Batch Batch Batch Site(s) of: Date(s) of:

number size type Manufacturing Analysis Manufacturing Analysis
The information on finished product batch analyses is recommended to be presented as

follows:
Batch Batch Batch Site(s) of: Date(s) of: API

number size type Manufacturing Analysis Manufacturing Analysis manufacturer
1.7.4. Certificate of analysis – Excipients
− Certificates of analysis for more than one batch of the excipients may be submitted to support
the application.
1.7.5. Alcohol-content declaration
This section should contain a declaration letter, in an official company letterhead, stating that the
finished product is free from alcohol. In the case of alcohol come into existence in the finished
product, a pre-approval from the authority is required along with the justification to make it
possible for the authority to evaluate the request and send the respond to the applicant.
1.7.6. Pork-content declaration
This section should contain a declaration letter in an official company letterhead stating that the
product is free from any materials of pork/porcine source.
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1.7.7. Certificate of suitability for TSE
This section should contain a valid TSE Certificate of Suitability issued by the European
Directorate for the Quality of Medicines (EDQM), which conforms the compliance of a substance
to the relevant monograph of the European Pharmacopoeia.
1.7.8. The diluents and coloring agents in the product formula
This section should contain a declaration letter in an official company letterhead stating the
diluents and coloring agents used in the product formula.
1.7.9. Patent Information
This section should contain a declaration letter in an official company letterhead stating the patent
status of the product.
1.7.10. Letter of access or acknowledgment to DMF
The DMF owner should specify which of the following options is chosen to present the drug
substance information:
• Certificate of suitability (CEP); or

• Drug master file (DMF); or
• Complete information on the “3.2.S drug substance” sections.
A letter written by the DMF owner or authorized Agent permitting SFDA to reference information
in the DMF on behalf of the Applicant.
The letter of access should include the following information on DMF:

• Name of the holder:
• Applicant’s part:
− DMF Version number:
− DMF Date (yyyy-mm-dd):
• Restricted part:
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• If no changes were made within the last five years, a letter indicating that the DMF remains
current.
• In regards to the restricted part, has it been submitted to the SFDA:
 Yes  No
If yes, please attach the confirmation email of DMF/ASMF submission.
If the applicant has already a Certificate of Suitability (CEP), the following should be
submitted:
• A valid Certificate of Suitability (CEP) (including any annexes) where the declaration of
access for the CEP should be duly filled out by the CEP holder.
• A written assurance that no significant changes in the manufacturing method have taken place
following the granting of certificate or its last revision.
For more information about the certificates that must be authenticated refer to the SFDA Guidance
for Submission.
1.8. Pricing
The applicant shall include the price of the product in countries listed in the SFDA Guidance for
Submission.
1.8.1. Price List:
Price list (Form 16) containing of all marketed countries of the product as detailed in the
pharmaceutical pricing rules
1.8.2. Other documents related:
• Pricing Application Form (found in the pharmaceutical pricing rules)

• Clinical studies overview (including: approved indication, guidelines, and comparative safety
and efficacy studies)
• Economic studies summaries
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1.9. Responses to questions
The response document should follow the same presentation as the initial dossier.
The applicant should include in this section a document which lists the questions with the
corresponding narrative text response for each question. This section will not be used for
supporting technical documentation, which will be included to the relevant Modules. Each
question should be followed by the name of section, page number and a hyperlink where the
answer can be found in the concerned Module.
Additional Data:
In this section the applicant/sponsor should submit the following:
• The Bioequivalence Study Summary Template2.
• Excel file for the tabulated plasma concentrations for the test and reference products along
with the randomization plan in the bioequivalence study.
• Addition documents related to abridge and verification, if applicable.
2
The template can be found in Guidelines for Bioequivalence - Annex 1 and also available as a soft copy
in the SFDA website Forms Section.
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MODULE 2 COMMON TECHNICAL DOCUMENT SUMMARIES
Table of Contents of Module 2-5
The table of content should list all documents included in Modules 2 to 5.
Quality Overall Summary
The Quality Overall Summary (QOS) is a summary that follows the scope and the outline of the
Body of Data in Module 3. The QOS should not include information, data or justification that was
not already included in Module 3 or in other parts of the eCTD. The QOS should include sufficient
information from each section to provide the Quality reviewer with an overview of Module 3. The
QOS should include a discussion of key issues that integrates information from sections in the
Quality Module and supporting information from other Modules (e.g. qualification of impurities
via toxicological studies discussed under module 4), including cross-referencing to volume and
page number in other Modules, the following requirements should be submitted under this module
if applicable:
2.3 Introduction to the Quality Overall Summary
Proprietary Name of Drug Product

Non-Proprietary Name of Drug Product
Non-Proprietary Name of Drug Substance
Company Name
Dosage Form
Strength(s)
Route of Administration
Proposed Indication(s)
2.3. S DRUG SUBSTANCE
• 2.3.S.1 General Information
What are the nomenclature, molecular structure, molecular formula, and molecular weight?
What are the physicochemical properties including physical description, pKa, polymorphism,
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aqueous solubility (as function of pH), hygroscopicity, melting points, and partition coefficient?
For Biologics:
Identity , physical prosperity and Biological activity.
• 2.3.S.2 Manufacture
Who manufactures the drug substance?

How do the manufacturing processes and controls ensure consistent production of drug
substance?
• 2.3.S.3 Characterization
How was the drug substance structure elucidated and characterized?

How were potential impurities identified and characterized?
• 2.3.S.4 Control of Drug Substance
What is the drug substance specification? Does it include all the critical drug substance attributes
that affect the manufacturing and quality of the drug product?
For each test in the specification, is the analytical method(s) suitable for its intended use and, if
necessary, validated? What is the justification for the acceptance criterion?
• 2.3.S.5 Reference Standards
How were the primary reference standards certified?

For biologics:
Brief on characterization and stability of the primary standard and protocol for generating
working standards
• 2.3.S.6 Container Closure System
What container closure system is used for packaging and storage of the drug substance?
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• 2.3.S.7 Stability
What drug substance stability studies support the retest or expiration date and storage conditions
for the drug substance?
2.3. P DRUG PRODUCT
2.3. P.1 Description and Composition
What are the components and composition of the final product? What is the function(s) of each
excipient?
Does any excipient exceed the IIG limit for this route of administration?
Do the differences between this formulation and the RLD present potential concerns with respect
to therapeutic equivalence?
2.3.P.2.1 Components of the Product
2.3.P.2.1.1 Drug Substance
Which properties or physical chemical characteristics of the drug substance affect drug product
development, manufacture, or performance?
What evidence supports compatibility between the excipients and the drug substance?
What attributes should the drug product possess?

How was the drug product designed to have these attributes?
Were alternative formulations or mechanisms investigated?
How were the excipients and their grades selected?
How was the final formulation optimized?
(If applicable for example: Non-Simple Dosage Form)

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Why was the manufacturing process described in 2.3.P.3 selected for this drug product?
How are the manufacturing steps (unit operations) related to the drug product quality?
How were the critical process parameters identified, monitored, and/or controlled?
What is the scale-up experience with the unit operations in this process?
What specific container closure attributes are necessary to ensure product performance?
2.3.P.3 Manufacture
(For All Products)

Who manufactures the drug product?
What are the unit operations in the drug product manufacturing process?
What is the reconciliation of the exhibit batch?
Does the batch formula accurately reflect the drug product composition? If not, what are the
differences and the justifications?
What are the in-process tests and controls that ensure each step is successful?
(If Product is Not a Solution)
What is the difference in size between commercial scale and exhibit batch? Does the equipment
use the same design and operating principles?
(If the Product is a NTI Drug or a Non-Simple Dosage Form)
In the proposed scale-up plan what operating parameters will be adjusted to ensure the product
meets all in-process and final product specifications?
What evidence supports the plan to scale up the process to commercial scale?
What are the specifications for the inactive ingredients and are they suitable for their intended
function?
For Biologics:
What is the function of each excipient?
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What is the drug product specification? Does it include all the critical drug product attributes?
For each test in the specification, is the analytical method(s) suitable for its intended use and, if
necessary, validated? What is the justification for the acceptance criterion?
2.3.P.6 Reference Standards and Materials
How were the primary reference standards certified?
2.3.P.7 Container Closure System
What container closure system(s) is proposed for packaging and storage of the drug product? Has
the container closure system been qualified as safe for use with this dosage form?
2.3.P.8 Stability
What are the specifications for stability studies, including justification of acceptance criteria that
differ from the drug product release specification?
What drug product stability studies support the proposed shelf life and storage conditions?
What is the post-approval stability protocol?
This QOS normally should not exceed 40 pages of text, excluding tables and figures. For biotech
products and products manufactured using more complex processes, the document could be longer
but normally should not exceed 80 pages of text (excluding tables and figures). The use of tables
to summarize the information is encouraged, where possible.
Non-Clinical Overview
The Nonclinical Overview should provide an integrated overall analysis of the information in the
eCTD. In general, the Nonclinical Overview should not exceed 30 pages.
The nonclinical testing strategy should be discussed and justified. There should be comment on
the GLP status of the studies submitted. Any association between nonclinical findings and the
quality characteristics of the human pharmaceutical, the results of clinical trials, or effects seen
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with related products should be indicated, as appropriate. Except for biotechnology-derived
products, an assessment of the impurities and degradants present in the drug substance/active
substance and product should be included along with what is known of their potential
pharmacological and toxicological effects. This assessment should form part of the justification
for proposed impurity limits in the drug substance/active substance and product, and be
appropriately cross-referenced to the quality documentation.
The implications of any differences in the chirality, chemical form, and impurity profile between
the compound used in the nonclinical studies and the product to be marketed should be discussed.
For biotechnology-derived products, comparability of material used in nonclinical studies, clinical
studies, and proposed for marketing should be assessed. If a drug product/medicinal product
includes a novel excipient, an assessment of the information regarding its safety should be
provided.
The Nonclinical Overview should be presented in the following sequence:
− Overview of the nonclinical testing strategy.
− Pharmacology.
− Pharmacokinetics.
− Toxicology.
− Integrated overview and conclusions.
− List of literature references.
Clinical Overview
The clinical overview should include:
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

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2.5.5. Overview of Safety
2.5.6. Benefits and Risks Conclusions
2.5.7. Literature References
The Clinical Overview is intended to provide a critical analysis of the clinical data in the Common
Technical Document. The Clinical Overview will refer to application data provided in the
comprehensive Clinical Summary, the individual clinical study reports (ICH E3), and other
relevant reports; but it should primarily present the conclusions and implications of those data and
should not recapitulate them. Specifically, the Clinical Summary should provide a detailed factual
summarization of the clinical information in the eCTD, and the Clinical Overview should provide
a succinct discussion and interpretation of these findings together with any other relevant
information (e.g., pertinent animal data or product quality issues that may have clinical
implications).
The Clinical Overview should:
1. Present the strengths and limitations of the development program and study results,
2. Analyze the benefits and risks of the medicinal product in its intended use, and
3. Describe how the study results support critical parts of the prescribing information.
In order to achieve these objectives the Clinical Overview should:
• Describe and explain the overall approach to the clinical development of a medicinal product,
including critical study design decisions.
• Assess the quality of the design and performance of the studies, and include a statement
regarding good clinical practice (GCP) compliance.
• Provide a brief overview of the clinical findings, including important limitations (e.g., lack of
comparisons with an especially relevant active comparator, or absence of information on some
patient populations, on pertinent endpoints, or on use in combination therapy).
• Provide an evaluation of benefits and risks based upon the conclusions of the relevant clinical
studies, including interpretation of how the efficacy and safety findings support the proposed
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dose and target indication and an evaluation of how prescribing information and other
approaches will optimize benefits and manage risks.
• Address particular efficacy or safety issues encountered in development, and how they have
been evaluated and resolved.
• Explore unresolved issues, explain why they should not be considered as barriers to approval,
and describe plans to resolve them.
• Explain the basis for important or unusual aspects of the prescribing information.
The Clinical Overview should generally be a relatively short document (about 30 pages). The
length, however, will depend on the complexity of the application. The use of graphs and concise
tables in the body of the text is encouraged for brevity and to facilitate understanding. It is not
intended that material presented fully elsewhere be repeated in the Clinical Overview; cross-
referencing to more detailed presentations provided in the Clinical Summary or in Module 5 is
encouraged.
Non-Clinical Written and Tabulated Summaries
Whenever appropriate, age- and gender-related effects should be discussed. Relevant findings with
stereoisomers and/or metabolites should be included, as appropriate. Consistent use of units
throughout the Nonclinical Written Summaries will facilitate their review. A table for converting
units might also be useful.
When available, in vitro studies should precede in vivo studies. Where multiple studies of the same
type are summarized within the Pharmacokinetics and Toxicology sections, studies should be
ordered by species, by route, and then by duration (shortest duration first).
Species should be ordered as follows:
• Mouse.
• Rat.
• Hamster.
• Other rodent.
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• Rabbit.
• Dog.
• Nonhuman primate.
• Other nonrodent mammal.
• Nonmammals.
Routes of administration should be ordered as follows:
• The intended route for human use.

• Oral.
• Intravenous.
• Intramuscular.
• Intraperitoneal.
• Subcutaneous.
• Inhalation.
• Topical.
• Other.
Although there is no formal limit to the length of the Nonclinical Written Summaries, it is
recommended that the total length of the three Nonclinical Written Summaries in general not
exceed 100-150 pages.
Clinical Summary
The Clinical Summary is intended to provide a detailed, factual summarization of all of the clinical
information in the Common Technical Document. This includes information provided in ICH E3
clinical study reports; information obtained from any meta-analyses or other cross-study analyses
for which full reports have been included in Module 5; and post-marketing data for products that
have been marketed in other regions. The comparisons and analyses of results across studies
provided in this document should focus on factual observations (In contrast, the eCTD Clinical
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Overview document should provide critical analysis of the clinical study program and its results,
including discussion and interpretation of the clinical findings and discussion of the place of the
test drug in the armamentarium).
The length of the Clinical Summary will vary substantially according to the information to be
conveyed, but it is anticipated that (excluding attached tables) the Clinical Summary will usually
be in the range of 50 to 400 pages.
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MODULE 3 QUALITY
The table of content should list all documents included in Module 3.
3.2 Body of data
The number of Active Pharmaceutical Ingredients (API) suppliers must not exceed two sources
for each API, unless reasonably justified.
The drug substance information can be submitted in one of the following options:
1. Certificate of suitability (CEP); or

2. Drug master file (DMF); or
3. Complete information on the “3.2.S drug substance” sections.
The drug substance information submitted should include the following for each of the options
used.
1. Certificate of Suitability (CEP)

The applicant should submit:
• A valid Certificate of Suitability (CEP) (including any annexes) where the declaration of
access for the CEP should be duly filled out by the CEP holder.
• A written assurance that no significant changes in the manufacturing method have taken place
following the granting of certificate or its last revision.
A complete copy of the CEP (including any annexes) should be provided in Module 1 (section
1.7.10). Along with the CEP, the applicant should submit the following:
a) 3.2.S.1.3 General properties
Discussions on any additional applicable physicochemical and other relevant drug

substance properties that are not controlled by the CEP and Ph. Eur. monograph, e.g.
solubilities and polymorphs.
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b) 3.2.S.3.1 Elucidation of structure and other characteristics
Studies to identify polymorphs (exception: where the CEP specifies a polymorphic form)
and particle size distribution, where applicable.
c) 3.2.S.4.1 Specification
The specifications of the finished product manufacturer including all tests and limits of the
CEP and Ph. Eur. monograph and any additional tests and acceptance criteria that are not
controlled in the CEP and Ph. Eur. monograph, such as polymorphs and/or particle size
distribution.
d) 3.2.S.4.2 / 3.2.S.4.3 Analytical procedures and validation
For any tests in addition to those in the CEP and Ph. Eur. monograph.
e) 3.2.S.4.4 Batch analysis
Results from three batches of at least pilot scale, demonstrating compliance with the
finished product manufacturer’s API specifications.
f) 3.2.S.5 Reference standards or materials
Information on the finished product manufacturer’s reference standards.
g) 3.2.S.6 Container closure system
The specifications including descriptions and identification of primary packaging

components should be included in this section, except where the CEP specifies a re-test
period.
h) 3.2.S.7 Stability
The stability should be included in this section, except where the CEP specifies a re-test
period that is the same as or of longer duration than the re-test period proposed by the
applicant.
In the case of sterile drug substances, data on the sterilization process of the drug substance,
including validation data, should be included in the dossier.
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2. Drug Master File (DMF)
Full details of the chemistry, manufacturing process, quality controls during manufacturing and
process validation for the drug substance may be submitted as DMF. In such cases, the Open part
needs to be included in its entirety in the dossier as an annex to 3.2.S. In addition, the
applicant/finished product manufacturer should complete the following sections:
a) General information 3.2.S.1.1 through 3.2.S.1.3

b) Manufacture 3.2.S.2
− Manufacturer(s) 3.2.S.2.1
− Description of manufacturing process and process controls 3.2.S.2.23
− Controls of critical steps and intermediates 3.2.S.2.44
c) Elucidation of structure and other characteristics 3.2.S.3.1
d) Impurities 3.2.S.3.2
e) Control of the API 3.2.S.4.1 through 3.2.S.4.5
f) Reference standards or materials 3.2.S.5
g) Container closure system 3.2.S.6
h) Stability 3.2.S.7.1 through 3.2.S.7.3
It is the responsibility of the applicant to ensure that the complete DMF (i.e. both the applicant’s
Open part and the API manufacturer's Restricted part) is supplied to SFDA directly by the API
manufacturer and that the applicant has access to the relevant information in the DMF concerning
the current manufacture of the drug substance.
DMF submissions and correspondence should be submitted as per the SFDA Drug Master File
(DMF) Guidance for Submission.
3
Flow chart and short description is regarded as sufficient, if the detailed information is presented in
the Restricted Part.
4
As far as the information is also relevant for the Applicant/MA holder.
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A copy of the letter of access should be provided in Module 1 (Section 1.7.10). The letter should
include the following information on DMF:
• Name of the holder:
• Applicant’s part:
• Restricted part:
• If no changes were made within the last five years, a letter indicating that the DMF remains
current.
• In regards to the restricted part, has it been submitted to the SFDA:
 Yes  No
If yes, please attach the confirmation email of DMF/ASMF submission.
3. Complete Information on the “3.2.S Drug Substance” Sections
Information on the 3.2.S Drug Substance sections, including full details of chemistry,
manufacturing process, quality controls during manufacturing and process validation for the drug
substance, should be submitted in the dossier as outlined in the subsequent sections of this
guideline.
3.2.S.1.1 Nomenclature
Information on the nomenclature of the drug substance(s) should be provided. For example:
• Recommended International Nonproprietary Name (INN);

• Compendial name (if relevant);
• Chemical name(s);
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• Company or laboratory code;
• Other non-proprietary name(s), e.g., National Name, United States Adopted Name (USAN),
British Approved Name (BAN), and
• Chemical Abstracts Service (CAS) registry number.
3.2.S.1.2 Structure
The structural formula, including relative and absolute stereochemistry, the molecular formula,
and the relative molecular mass should be provided. For drug substance(s) existing as salts, the
molecular mass of the free base or acid should be provided.
For Biotech:
In addition to the above, the schematic amino acid sequence indicating glycosylation sites or other
post-translational modifications and relative molecular mass should be provided, as appropriate.
3.2.S.1.3 General Properties
A list should be provided of physicochemical and other relevant properties of the drug substance.
This includes:
a) Physical description (e.g., appearance, color, physical state).
b) Physical form (e.g., polymorphic form, solvate, hydrate).
c) Solubilities (e.g., in common solvents, aqueous/nonaqueous solubility profile).
d) pH and pKa values.
e) Other (e.g., partition coefficients, melting or boiling points, optical rotation, refractive
index (for a liquid), hygroscopicity, UV absorption maxima and molar absorptivity).
For Biotech:
In addition to the above, the biological activity should be provided.
3.2.S.2 Manufacture
3.2.S.2.1 Manufacturer(s)
The name, address, and responsibility of each manufacturer, including contractors, and each
proposed production site or facility involved in manufacturing and testing should be provided. In
addition, a valid manufacturing authorization for the production of drug substance(s) and a
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certificate of GMP compliance should be provided.
This section should also include all the proposed QC testing site(s) intended to be approved in
Saudi Arabia (along with required method transfer reports).
3.2.S.2.2 Description of Process and Process Controls
The description of the drug substance manufacturing process represents the applicant’s
commitment for the manufacture of the drug substance. Information should be provided to
adequately describe the manufacturing process and process controls. For example:
• Individual unit operations and their sequence in the manufacturing process

• For levels/details of Established Conditions (ECs) for inputs (process parameters and material
attributes) and outputs of individual unit operations (ICH Q12 chapter : Identification of ECs
for the Manufacturing Processes)
• A flow diagram of the synthetic process(es) should be provided that includes molecular
formulae, weights, yield ranges, chemical structures of starting materials, intermediates,
reagents and drug substance reflecting stereochemistry, and identifies operating conditions and
solvents.
• Detailed information on the starting material(s) including the name of the
manufacturer(s)/supplier(s), route of synthesis and specifications which should be justified by
supporting data.
• A sequential procedural narrative of the manufacturing process should be submitted. The
narrative should include, for example, quantities of raw materials, solvents, catalysts and
reagents reflecting the representative batch scale for commercial manufacture, identification
of critical steps, process controls, equipment and operating conditions (e.g., temperature,
pressure, pH, time… etc).
• Alternate processes should be explained and described with the same level of detail as the
primary process. Justification should be provided for the alternate manufacturing processes.
• If applicable, reprocessing steps should be identified and justified. Any data to support this
justification should be either referenced or filed in 3.2.S.2.5.
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In case there are multiple manufacturing sites for one drug substance manufacturer, a
comprehensive list in tabular form should be provided comparing the processes at each site and
highlighting any differences.
For Biotech:
In addition to the above, information should be provided on the manufacturing process, which
typically starts with a vial(s) of the cell bank, and includes cell culture, harvest(s), purification and
modification reactions, filling, storage and shipping conditions.
− 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.
The size of a batch produced by continuous manufacturing (CM) can be defined in terms of
one of the following:
• Quantity of output material
• Quantity of input material
• Run time at a defined mass flow rate
• Other approaches to define batch size can also be considered, if scientifically justified
based on the characteristics of the CM process.
• A batch size can also be defined as a range. For example, a batch size range can be
established by defining a minimum and maximum run time
− Cell culture and harvest
A flow diagram should be provided that illustrates the manufacturing route from the original
inoculum (e.g. cells contained in one or more vials(s) of the Working Cell Bank) up to the last
harvesting operation. The diagram should include all steps (i.e., unit operations) and
intermediates. Relevant information for each stage, such as population doubling levels, cell
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concentration, volumes, pH, cultivation times, holding times, and temperature, should be
included. Critical steps and critical intermediates for which specifications are established (as
mentioned in 3.2.S.2.4) should be identified.
A description of each process step in the flow diagram should be provided. Information should
be included on, for example, scale; culture media and other additives (details provided in
3.2.S.2.3); major equipment (details provided in 3.2.A.1); and process controls, including in-
process tests and operational parameters, process steps, equipment and intermediates with
acceptance criteria (details provided in 3.2.S.2.4). 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.).
− Purification and modification reactions
A flow diagram should be provided that illustrates the purification steps (i.e., unit operations)
from the crude harvest(s) up to the step preceding filling of the drug substance. All steps and
intermediates and relevant information for each stage (e.g., volumes, pH, critical processing
time, holding times, temperatures and elution profiles and selection of fraction, storage of
intermediate, if applicable) should be included. Critical steps for which specifications are
established as mentioned in 3.2.S.2.4 should be identified.
A description of each process step (as identified in the flow diagram) should be provided. The
description should include information on, for example, scale, buffers and other reagents
(details provided in 3.2.S.2.3), major equipment (details provided in 3.2.A.1), and materials.
For materials such as membranes and chromatography resins, information for conditions of use
and reuse also should be provided (equipment details in 3.2.A.1; validation studies for the reuse
and regeneration of columns and membranes in 3.2.S.2.5.). The description should include
process controls (including in-process tests and operational parameters) with acceptance
criteria for process steps, equipment and intermediates (details in 3.2.S.2.4.).
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
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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)
A description of the filling procedure for the drug substance, process controls (including in-
process tests and operational parameters), and acceptance criteria should be provided (details
in 3.2.S.2.4.). The container closure system(s) used for storage of the drug substance (details in
3.2.S.6.) and storage and shipping conditions for the drug substance should be described.
For CM:
• Commercial manufacturing process description, including flow diagram and equipment
scheme
• Process controls and limits (e.g., input rates/mass flow rates, feeder control limits)
• Critical process parameters
• Active controls (e.g., feedforward or feedback control) and process models, if these elements
are part of the control strategy
• Criteria for product collection, including control limits and strategy for segregation and
diversion to waste.
• Description of equipment and system integration critical to the output material quality
• Overview of high-impact process models, if used.
3.2.S.2.3 Control of Materials
Materials 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. For each starting material, the name, manufacturing site, and the address of each
manufacturer should be indicated. Information on the quality and control of these materials should
be provided (including the route of synthesis, specifications, impurity profile, scientific
justification/rationale for selecting starting material(s) and certificate of analysis from each
supplier). Information demonstrating that materials (including biologically-sourced materials,
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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 (details in 3.2.A.2).
A letter should be provided confirming that the drug substance, starting materials and reagents
used to manufacture the drug substance are without risk of transmitting agents of Bovine
Spongiform Encephalopathy (BSE)/Transmissible Spongiform Encephalopathy (TSE). When
available, a CEP demonstrating TSE-compliance should be submitted. A complete copy of the
CEP (including any annexes) should be provided in Module 1 (Section 1.7.7).
For Biotech: “In addition to the above”
− Information on the development genetics including origin of the gene, description of the
gene construction, rationale behind the gene construct, genetic stability (specify state of
the recombinant gene and copy number).
− Description of the producer strain /cell line (type, origin), history of establishment and
identification. Highlight any issues related to components used during development with
potential impact on product safety (e.g. reagents of biological origin).
− Cell banks: Establishment of the MCB/WCB, adequacy of tests performed, cell bank
stability, phenotypic and genotypic characterisation, protocol for the establishment of
future WCB. (as described in Q5B and Q5D).
− For of biological materials (e.g. monoclonal antibody purification columns, blood/plasma

derivatives) used in the manufacture of the drug substance, the assessment of the source,
manufacture, characterisation and control should be provided. For biological materials (e.g.
blood/plasma derivatives such as human albumin) used in the manufacture of the drug
substance, the assessment of the source, manufacture, characterisation and control should
be provided.
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− Specifications of culture media and other additives.
− Other materials 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 with information on the quality and control of these materials.
− Information related to materials such as membranes and chromatography resins
− For plasma products such as human albumin that whenever it is used in the manufacture of
medicinal products, it should comply with the note for guidance and should have the same
documentation, including the origin of donations, the same quality and specifications as
that of albumin for therapeutic use.
− Summaries of viral safety information for biologically-sourced materials should be

provided (details in 3.2.A.2.).
3.2. S.2.4 Control of Critical Steps and Intermediates
− Critical Steps:
Tests and acceptance criteria (with justification including experimental data) 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.
For Biotech:
− List critical process steps and critical process parameters, intermediate specifications, and
in-process control acceptance criteria
− End of production / cultivation criteria if applicable
− Proposed intervals of set-point specifications and limits of In Process Control

specifications in relation to the results of process validation.
− Description of storage conditions/shelf life of intermediates.

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− Highlight any specific step aimed/validated for virus removal/inactivation (e.g. low pH
treatment).
− Stability data supporting storage conditions and holding time between steps of
manufacturing should be provided.
3.2. S.2.5 Process Validation and/or Evaluation
Process validation and/or evaluation studies for aseptic processing and sterilization should be
included.
The information on process validation and/or evaluation studies for STERILE drug
substance is recommended to be presented as follows:
Number of batches
Batch number
Batch type
Batch size
Are the submitted batches consecutive?  Yes  No
Is the process validation protocol submitted?  Yes  No
Are the process validation results submitted?  Yes  No
For Biotech:
Sufficient information should be provided on validation and evaluation studies to demonstrate that
the manufacturing process (including reprocessing steps) is suitable for its intended purpose and
to substantiate selection of critical process controls (operational parameters and in-process tests)
and their limits for critical manufacturing steps (e.g., cell culture, harvesting, purification, and
modification).
The plan for conducting the study (protocol) should be described and the results, analysis and
conclusions from the executed study(ies) should be provided. The analytical procedures and
corresponding validation should be cross-referenced (e.g., 3.2.S.2.4, 3.2.S.4.3) or provided as part
of justifying the selection of critical process controls and acceptance criteria.
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For manufacturing steps intended to remove or inactivate viral contaminants, the information from
evaluation studies should be provided in 3.2.A.2.
For continuous process, the use of a continuous process verification approach should be justified
based on the product and process understanding, system design, and overall control strategy. When
continuous process verification is used, the CM system performance and material quality should
be continuously monitored, such that the real-time data collected demonstrate the maintenance of
a state of control and production of output material with the desired quality for the run time
duration. The dossier should contain justifications to support the adequacy of a proposed control
strategy for continuous process verification.
3.2.S.2.6 Manufacturing Process Development
The developmental history of the manufacturing process, as described in 3.2.S.2.2, should be

provided. In addition, A description and discussion should be provided of the significant changes
made to the manufacturing process and/or manufacturing site of the drug substance used in
producing nonclinical, clinical, scale-up, pilot, and, if available, production scale batches.
Reference should be made to the drug substance data provided in section 3.2.S.4.4.
For 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 (e.g., nonclinical or clinical studies) should include, for
example, 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 number, manufacturing scale, and use (e.g., stability, nonclinical, reference
material) in relation to the change, should be provided.
The significance of the 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 batches
should be provided to determine the impact on quality of the drug substance (see Q6B for
additional guidance). A discussion of the data, including a justification for selection of the tests
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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) can also include nonclinical and clinical studies. Cross-reference to
the location of these studies in other modules of the submission should be included. Reference
should be made to the drug substance data provided in section 3.2.S.4.4.
For continuous manufacturing (CM)

− Summary of the overall process development, including all relevant control strategy
elements (with links to the eCTD sections that contain detailed information), for example:
o Description and justification of the system start-up, shutdown and pauses
o Description and justification of the material diversion and collection strategy
o Description of feedforward and feedback controls
− Development and justification of process models, if used
− Summary of disturbance management
3.2.S.3.1 Elucidation of Structure and Other Characteristics
Confirmation of structure based on e.g., synthetic route and spectral analyses should be provided.
This should include copies of the spectra, peak assignments and a detailed interpretation of the
data of the studies performed to elucidate and/or confirm the structure of the drug substance.
• For non-pharmacopoeial drug substance(s), these studies normally include elemental analysis,
infrared (IR), ultraviolet (UV), nuclear magnetic resonance (NMR) and mass spectra (MS)
studies. Other tests could include X-ray diffraction (XRD) and differential scanning
calorimetry (DSC).
• For pharmacopoeial drug substance(s), it is generally sufficient to provide copies of the IR

spectrum of the drug substance run concomitantly with a reference standard.
Information such as the potential for isomerism, the identification of stereochemistry, or the
potential for forming polymorphs should also be included.
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In addition, studies performed to identify the particle size distribution of the drug substance should
be included.
For Biotech:
In addition to the above, Characterization to justify classification as CQA (cross reference to

nonclinical/clinical sections if relevant) details (for the desired product and product-related
substances) should be provided on primary, secondary and higher-order structure, post-
translational forms (e.g., glycoforms), biological activity, purity, and immunochemical properties,
when relevant.
3.2.S.3.2 Impurities
Information on impurities should be provided, including a discussion on the potential and actual
impurities arising from the synthesis, manufacture, or degradation of the drug substance. This
should cover starting materials, by-products, intermediates, chiral impurities and degradation
products and should include the chemical names, structures and origins.
In addition, a specific discussion should be provided with regard to impurities with potential
genotoxicity (Refer to ICH M7 guideline: Assessment and Control of DNA Reactive (Mutagenic)
Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk).
Details on the principles for the control of impurities (e.g. reporting, identification and
qualification) are outlined in the ICH Q3A, Q3B and Q3C impurity guidelines.
The information on impurities is recommended to be presented as follows:
Drug-related
Acceptance
Impurity Structure Origin Reference
Criteria
(chemical name)
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It should be known that some solvents (e.g. acetone, toluene, ethanol, methanol, isopropanol,
xylene, hexane, petroleum ether, chloroform and dichloromethane (methylene chloride)) may be
contaminated with Class 1 solvents (e.g. benzene, carbon tetrachloride). Therefore, when these
solvents are used in the manufacturing process of the final substance, and in particular in the
purification steps, potential residues of their contaminant in an intermediate or in the final
substance should be addressed (refer to CPMP/QWP/450/03 Rev. 1, Annex I, B: Class 1 Solvents
Present as an Impurity).
According to the European “Note for Guidance on Specifications for Class 1 and Class 2 residual
solvents in active substances, annex to the CPMP/ICH/283/95 Impurities: Guideline for Residual
Solvents, three options may be used that support the absence of routine testing of the contaminant
in the final substance. When one of the three options is met and demonstrated in the application, a
routine test for Class I solvent in a suitable intermediate or in the final active substance is not
required.
3.2.S.4.1 Specifications
Copies of the drug substance specifications, dated and signed by the concerned individual(s)
should be provided, including specifications from each drug substance manufacturer as well as
those of the finished product manufacturer.
3.2.S.4.2 Analytical Procedures
The analytical procedures used for testing the drug substance should be provided. Copies of the
non-compendial analytical procedures used to generate testing results provided in the dossier, as
well as those proposed for routine testing of the drug substance by the finished product
manufacturer, should be provided. Unless modified, it is not necessary to provide copies of the
compendial analytical procedures.
Chromatographic methods (e.g., HPLC & GC) are normally considered the method of choice for
determining API-related impurities and assay. The analytical procedure submitted should be
described in sufficient detail including: Preparation of mobile phase, Chromatographic condition
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(Column: packing type (e.g., C18 or C8), dimension (length, inner diameter), particle size (10
μm, 5 μm), Detector (wavelength), Injection volume, Column Temperature, Flow rate), elution
procedure (isocratic or gradient elution), preparation of standards and samples solution, type of
reagent & materials used, operation procedure (sequence of injections), system suitability testing
(SST) and criteria and calculations (including correction factors when the API is used as an
external standard to estimate the levels of impurities and data to support their calculation for an
in-house method).
The system suitability tests (SSTs) represent an integral part of the method and are used to ensure
the satisfactory performance of the chosen chromatographic system. As a minimum, HPLC and
GC purity methods should include SSTs for resolution and repeatability. HPLC assay methods
should include SSTs for repeatability and in addition either peak asymmetry, theoretical plates or
resolution.
The information on analytical procedures is recommended to be presented as follows:
Tested parameter e.g. assay, related substances, … (one separate table for each tested
parameter).
Reference e.g. USP, BP, in-house method, …
Chromatographic Conditions:
− Column
− Flow rate
− Wavelength
− Injection volume
− Temperature
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− Run time
− Retention time
Solutions preparation:
− Mobile phase
− Buffer
− Gradient programs (if

applicable)
− Stock standard solution
− Standard solution
− Test solution
− System suitability solution
Acceptance criteria for system suitability test:
− % RSD
− Tailing factor
− No. of theoretical plates

(N)
− Resolution
GC for Residual Solvents:
− Column
− Column flow
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− Carrier
− Air flow
− H2 flow
− Split
− Detector temperature
− Load
− Injector temperature
− Makeup flow
− Stock solution(s)
− Standard preparation
− Sample Preparation
− System suitability
− % RSD
− Tailing factor
− Resolution
3.2.S.4.3 Validation of Analytical Procedures
Analytical validation information, including experimental data for the analytical procedures used
for testing the drug substance, should be provided (in accordance with ICH Q2 (R1) and Q6A).
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Copies of the validation reports for the analytical procedures used to generate testing results
provided in the dossier, as well as those proposed for routine testing of the drug substance by the
finished product manufacturer, should be provided. For in-house methods full validation are
required.
Verification of compendial methods is necessary, since the compendial methods as published are
typically validated based on an API originating from a specific manufacturer. Different sources of
the same API can contain impurities and/or degradation products that were not considered during
the development of the monograph. Therefore, the monograph and compendial method should be
demonstrated as suitable to control the impurity profile of the API from the intended source(s).
For the verification of compendial API assay methods, specificity should be demonstrated.
If compendial method is used to control API-related impurities that are not specified in the
monograph, full validation of the method is expected with respect to those impurities.
If compendial standard is claimed and an in-house method is used as an alternative method (e.g.
for assay or specified impurities), equivalence of the in-house and compendial methods should be
demonstrated. This could be accomplished by performing duplicate analyses of one sample by
both methods and providing the results from the study. For impurity methods the sample analysed
should be the API spiked with impurities at concentrations equivalent to their specification limits.
If there are identified impurities specified in an official compendial monograph that are not
controlled by the proposed routine in-house analytical procedure, a justification for their exclusion
from routine analyses should be provided. If acceptable justification cannot be provided it should
be demonstrated that the routine in-house method is capable of separating and detecting the
impurities specified in the official compendial monograph at an acceptable level (e.g. 0.10%). If
such a demonstration cannot be performed, a one-time study should be conducted applying the
pharmacopoeial method to several recent batches to demonstrate the absence of the impurities
listed in the pharmacopoeia.
Transfer of analytical methods should accommodate all the analytical testing required to
demonstrate compliance of the product to be transferred with the approved specifications.
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Analytical methods used to test pharmaceutical products, should be implemented at the testing
laboratory. The analytical methods transfer protocol should include a description of the objective,
scope and responsibilities of the SU and the RU; a specification of materials and methods; the
experimental design and acceptance criteria; documentation (including information to be supplied
with the results, and report forms to be used, if any).
The information on validation of analytical procedures is recommended to be presented as

follows:
parameter).
Specificity
− Brief summary on how it was

performed:
− Representative chromatogram(s) The chromatogram(s) can be found in page No…
Linearity
− No. of concentrations
− Specified ranges
− Parameters: Acceptance criteria Results
• Correlation coefficient
• y-intercept
• Residual sum of squares
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Accuracy

performed:
• % Recovery
• % RSD
• CI
Precision (repeatability and intermediate precision)

performed:
− Parameter: Acceptance criteria Results
• % RSD
LOQ/LOD

performed:
− LOD
− LOQ
Robustness

performed:
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Systems suitability
• % RDS
• Tailing factor
• No. of theoretical plates
• Resolution
Method transfer (if applicable):
Protocol:
− Tested Parameters: Acceptance criteria Results
3.2.S.4.4 Batch Analyses
Description of batches and results of batch analyses should be provided. The information provided
should include batch number, batch size, date and production site of relevant drug substance
batches used in comparative bioavailability or biowaiver studies, preclinical and clinical data (if
relevant), stability, pilot, scale-up and, if available, production-scale batches.
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The information on drug substance batch analyses is recommended to be presented as
follows:
Batch Batch Batch Site(s) of: Date(s) of:

number size type Manufacturing Analysis Manufacturing Analysis
Copies of the certificates of analysis from both the API manufacturer(s) and the FPP manufacturer
should be provided.
Analytical results should be provided from at least two batches of at least pilot scale from each
proposed manufacturing site of the drug substance and should include the batch(es) used in the
comparative bioavailability or biowaiver studies. A pilot-scale batch should be manufactured by a
procedure fully representative of and simulating that to be applied to a full production-scale batch.
The discussion of results should focus on observations noted for the various tests, rather than
reporting comments such as “all tests meet specifications”. For quantitative tests (e.g. assay test,
individual and total impurity tests), it should be ensured that actual numerical results are provided
rather than vague statements such as “within limits” or “conforms”.
3.2.S.4.5 Justification of Specification
Justification for the drug substance specification should be provided. This should include a
discussion on the inclusion of certain tests, evolution of tests, analytical procedures and acceptance
criteria, etc. If the compendial methods have been modified or replaced, a discussion should be
included.
The justification for certain tests, analytical procedures and acceptance criteria may have been
discussed in other sections of the dossier (e.g. impurities) and does not need to be repeated here,
although a cross-reference to their location should be provided.
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Information on the reference standards or reference materials used for testing of the drug substance
should include the following:
1. The source of reference standards or reference materials (e.g., House, USP, BP, Ph. Eur.).
2. Certificate of analysis for reference standards or reference materials .
3. Characterization and evaluation of non-official (e.g., non-compendial) reference standards or

reference materials (e.g., method of manufacture, elucidation of structure, certificate of
analysis, calibration against an official standard).
The information on reference standards/reference materials is recommended to be presented

as follows:
 Primary reference standard
Type of reference standards  Working or secondary reference standard
 Manufacturer reference standard
Information on potency ……… %
Information on calibration of
working standard with primary
reference standard
3.2.S.6 Container/Closure Systems
A description of the container closure system(s) should be provided, including 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). Non-compendial methods (with validation) should be included,
where appropriate.
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For non-functional 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.
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.
3.2.S.7 Stability
3.2.S.7.1 Stability Summary and Conclusions
The GCC guidelines for “Stability Testing of Active Pharmaceutical Ingredients (APIs) and
Finished Pharmaceutical Products (FPPs)” should be followed for recommendations on the
stability data required for the drug substance(s).
The types of studies conducted, protocols used, and the results of the studies should be
summarized. The summary should include information on storage conditions, batch number, batch
size, batch type, batch manufacturing date, container closure system and testing intervals
(completed and proposed), results, as well as conclusions with respect to storage conditions and
retest date or shelf-life, as appropriate.
The information on stability studies is recommended to be presented as follows:
Accelerated stability
Long term stability studies
studies
Storage conditions (C, % RH)
Batch number
Batch type
Batch size
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Completed (and proposed)
testing intervals
Container closure system
Manufacturing site
Manufacturing date
Stability start date
Storage conditions and the

proposed retest date or shelf-
life
reporting comments such as “all tests meet specifications”.
Where the methods used in the stability studies are different from those described in 3.2.S.4.2,
descriptions and validation of the methodology used in stability studies should be provided.
3.2.S.7.2 Post-approval Stability Protocol and Commitment
The post-approval stability protocol and if applicable stability commitment should be provided.
When the available long-term stability data on primary batches do not cover the proposed re-test
period granted at the time of assessment of the dossier, a commitment should be made to continue
the stability studies in order to firmly establish the re-test period. A written commitment (signed
and dated) to continue long-term testing over the re-test period should be included in the dossier.
Where the submission includes long-term stability data on three production batches covering the
proposed re-test period, a post-approval commitment is considered unnecessary. Otherwise one of
the following commitments should be made:
− If the submission includes data from stability studies on three production batches, a written
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commitment (signed and dated) should be made to continue these studies through the proposed
re-test period.
− If the submission includes data from stability studies on less than three production
batches, a written commitment (signed and dated) should be made to continue these studies
through the proposed re-test period and to place additional production batches, to a total of at
least three, in long-term stability studies through the proposed re-test period.
− If the submission does not include stability data on production batches, a written
commitment (signed and dated) should be made to place the first three production batches on
long term stability studies through the proposed re-test period.
The stability protocol for the commitment batches should be provided and should include, but not
be limited to, the following parameters:
• Number of batch(s) and different batch sizes, if applicable;
• Relevant physical, chemical, microbiological and biological test methods;
• Acceptance criteria;
• Reference to test methods;
• Description of the container closure system(s);
• Testing frequency;
• Description of the conditions of storage; and
• Other applicable parameters specific to the drug substance.
The stability of the drug substance should be monitored according to a continuous and appropriate
programme that will permit the detection of any stability issue (e.g. changes in levels of
degradation products). For this purpose, the ongoing stability programme should include at least
one production batch per year of drug substance (unless none is produced during that year). In
certain situations, additional batches should be included. Therefore, a written commitment (signed
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and dated) for ongoing stability studies should be included in the dossier.
Any differences in the stability protocols used for the primary batches and those proposed for the
commitment batches or ongoing batches should be scientifically justified.
3.2.S.7.3 Stability Data
Results of the stability studies should be presented in a tabular format. The results of all testing
parameters related to each batch for the entire testing period should be presented in one table (i.e.
presenting the results of one parameter of all batches in one table is not acceptable).
For quantitative tests (e.g. individual and total degradation product tests and assay tests), it should
be ensured that actual numerical results are provided rather than vague statements such as “within
limits” or “conforms”.
Information on the analytical procedures used to generate the data and validation of these
procedures should be included.
3.2.P Drug Product
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.
The pharmaceutical development section should contain information on the development studies
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conducted to establish that the dosage form, the formulation, manufacturing process, container
closure system, microbiological attributes and usage instructions 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 (critical parameters) that can influence batch reproducibility,
product performance and drug product quality. Supportive data and results from specific studies
or published literature can be included within or attached to the pharmaceutical development
section. Additional supportive data can be referenced to the relevant nonclinical or clinical sections
of the application.
3.2.P.2.1 Components of the Drug Product
3.2.P.2.1.1 Drug substance
The compatibility of the drug substance with excipients listed in 3.2.P.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 that can influence the
performance of the drug product should be discussed. For combination products, the compatibility
of drug substances with each other should be discussed.
In general, drug substance-excipient compatibility is not required to be established for specific

excipients when evidence is provided (e.g. SPC or PIL) that the excipients are present in the
comparator product.
The choice of excipients listed in 3.2.P.1, their concentration, their characteristics that can
influence the drug product performance should be discussed relative to their respective functions.
Where relevant, compatibility study results (e.g. compatibility of a primary or secondary amine
API with lactose) should be included to justify the choice of excipients. Where antioxidants are
included in the formulation, the effectiveness of the proposed concentration of the antioxidant
should be justified and verified by appropriate studies. Where relevant, the antimicrobial
preservatives should be discussed in 3.2.P.2.5.

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3.2.P.2.2.1 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 in the formulations
for the batches used the in the in vivo studies (e.g., pivotal clinical, comparative bioequivalence)
and the formulation (i.e. composition) described in 2.3.P.1 should be discussed.
Summary of the results from comparative in vitro studies (e.g., dissolution) or comparative in vivo
studies (e.g., bioequivalence) should be discussed when appropriate, including the description of
batches (e.g., batch number, strength, type of the study … etc) used in the these studies.
The discussion should include the results of studies justifying the choice of in vitro dissolution or
drug release conditions (e.g. apparatus, rotation speed, medium). Furthermore, the submitted data
should demonstrate whether the method is sensitive to changes in manufacturing processes and/or
changes in grades and/or amounts of critical excipients and particle size where relevant.
Scored Tablets
In order to ensure that the patient will receive the intended dose, the efficacy of the break-mark(s)
must be assessed during the development of the product, in respect of uniformity of mass of the
subdivided parts.
If the proposed finished product is a scored tablet or the applicant indicates that it may be divided,
the following should be submitted:
• A justification/rationale for the tablet scoring, and

• Results of the appropriate compendial tests demonstrating equivalence in
characteristics/correct dosing (i.e. results demonstrating that the proposed tablet breaks
evenly). The submitted data should include a description of the test method, individual values,
mean and relative standard deviation (RSD) of the results.
3.2.P.2.2.2 Overages
In general, use of an overage of a drug substance to compensate for degradation during
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manufacture or a product’s shelf life, or to extend shelf life, is discouraged. Any overages in the
manufacture of the drug product, whether they appear in the final formulated product or not, should
be justified considering the safety and efficacy of the product.
Information should be provided on the:

• Amount of overage,
• Reason for the overage (e.g., to compensate for expected and documented manufacturing
losses), and
• Justification for the amount of overage. The justification of an overage to compensate for loss
during manufacture should be provided, including the step(s) where the loss occurs, the reasons
for the loss and batch analysis (comparative data showing the differences in the assay test
results before and after adding the overage).
The overage should be included in the amount of drug substance listed in the batch formula
(3.2.P.3.2).
3.2.P.2.2.3 Physiochemical and Biological Properties
Parameters relevant to the performance of the drug product, such as pH, ionic strength, dissolution,
redispersion, reconstitution, particle size distribution, aggregation, refractive index,
polymorphism, rheological properties, biological activity or potency, and/or immunological
activity, should be addressed.
The scientific rationale for the selection and optimization and scale-up of the manufacturing
process described in 3.2.P.3.3, in particular its critical aspects, should be explained.
Where relevant, the method of sterilization should be explained and justified. The justification for
selecting aseptic processing or other sterilization methods over terminal sterilization should be
provided.
Differences between the manufacturing process(s) used to produce pivotal clinical batches/
comparative bioavailability batches and the process described in 3.2.P.3.3 that can influence the
performance of the product should be discussed.

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The suitability of the container closure system (described in 3.2.P.7) used for the storage,
transportation (shipping) and use of the drug product should be discussed.
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), and performance (such as reproducibility of the dose delivery from the
device when presented as part of the drug product). In case of using new packaging materials, the
discussion should include the safety of those materials, in addition to the above mentioned
requirements.
For a device accompanying a multidose container, the discussion should provide the results that
demonstrate the reproducibility of the device (e.g. consistent delivery of the intended volume),
generally at the lowest intended dose.
3.2.P.2.5 Microbiological Attributes
Where appropriate, the microbiological attributes of the dosage form should be discussed,
including, for example, the rationale for not performing microbial limits testing for non-sterile
products, the selection and effectiveness of preservative systems in products containing
antimicrobial preservatives. A single primary stability batch of the finished product should be
tested for effectiveness of the antimicrobial preservative (in addition to preservative content) at the
proposed shelf-life for verification purposes, regardless of whether there is a difference between
the release and shelf-life acceptance criteria for preservative content.
For sterile products, the integrity of the container closure system to prevent microbial
contamination should be addressed.
3.2.P.2.6 Compatibility
The compatibility of the drug product with reconstitution diluent(s) or dosage device(s) (e.g.,
precipitation of drug substance in solution, sorption on injection vessels, stability) should be
addressed to provide appropriate and supportive information for the labeling.
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Where sterile reconstituted products are to be further diluted, compatibility should be demonstrated
with all diluents over the range of dilution proposed in the labeling. These studies should preferably
be conducted on aged samples. Where the labeling does not specify the type of containers,
compatibility (with respect to parameters such as appearance, pH, assay, levels of individual and
total degradation products, sub-visible particulate matters and extractables from the packaging
components) should be demonstrated in glass, PVC and polyolefin containers. However, if one or
more containers are identified in the labeling, compatibility of admixtures needs to be
demonstrated only in the specified containers.
Where the labeling specifies co-administration with other finished products, compatibility should
be demonstrated with respect to the principal finished product as well as the co-administered
finished product (i.e. in addition to other aforementioned parameters for the mixture, the assay
and degradation levels of each co-administered finished product should be reported).
3.2.P.3 Manufacture
3.2.P.3.1 Manufacturer(s)
The name, address, and responsibility of each manufacturer, including contractors, and each
proposed production site or facility involved in manufacturing and testing should be provided.
A valid manufacturing authorization and marketing authorization should be submitted. A GMP

certificate should be submitted for each manufacturing site where the major production step(s) are
carried out, when applicable.
This section should also include all the proposed QC testing site(s) intended to be approved in
Saudi Arabia.
3.2.P.3.2 Batch Formula
A batch formula for all proposed individual batch sizes should be provided that includes a list of
all components of the dosage form to be used in the manufacturing process (including those that
may not be added to every batch [e.g. acid and alkali], those that may be removed during
processing [e.g. solvents] and any others [e.g. nitrogen, silicon for stoppers]), and their amounts
on a per batch basis, including overages. The components used in the manufacturing process
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should be declared by their proper or common names and a reference to their quality standards
(e.g. BP, USP).
In addition, an official letter indicating the expected production size range and confirming that this
range will not be changed before getting the SFDA approval.
3.2.P.3.3 Description of Manufacturing Process and Process Controls
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.
A narrative description of the manufacturing process, including packaging, that represents the
sequence of steps undertaken and the scale of production should also be provided. Novel processes
or technologies and packaging operations that directly affect product quality should be described
with a greater level of detail.
Equipment should, at least, be identified by type (e.g., tumble blender) and working capacity,
where relevant. Steps in the process should have the appropriate process parameters identified,
such as time, temperature, or pH. Associated numeric values can be presented as an expected
range. Numeric ranges for critical steps should be justified in Section 3.2.P.3.4. In certain cases,
environmental conditions (e.g., low humidity for an effervescent product) should be stated.
For the manufacture of sterile products, the class of the areas (e.g. A, B, …etc) should be stated for
each activity (e.g. compounding, filling, …etc), as well as the sterilization parameters for
equipment, container/closure, terminal sterilization …etc.
Proposals for the reprocessing of materials should be justified. Any data to support this justification
should be either referenced or filed in this section.
Detailed information on Biotech facilities and equipment should be provided in 3.2.A.1.
3.2.P.3.4 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 in 3.2.P.3.3 of the manufacturing process, to
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ensure that the process is controlled.
• Intermediates:
Information on the quality and control of intermediates isolated during the process should be
provided.
The following are examples for applicable in-process controls:
− Granulations:
Moisture (limits expressed as a range), blend uniformity (e.g. low dose tablets), bulk and
tapped densities, particle size distribution, …etc.
− Solid oral products:
Average weight, weight variation, hardness, thickness, friability, and disintegration checked
periodically throughout compression, weight gain during coating, …etc.
− Semi-solids:
Viscosity, homogeneity, pH, …etc.
− Transdermal dosage forms:
Assay of drug substance-adhesive mixture, weight per area of coated patch without backing,
…etc.
− Metered dose inhalers:
Fill weight/volume, leak testing, valve delivery, …etc.
− Dry powder inhalers:
Assay of drug substance-excipient blend, moisture, weight variation of individually contained

doses such as capsules or blisters, …etc.
− Liquids:
Specific gravity, pH, clarity of solutions, …etc.
− Parenterals:
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Appearance, clarity, fill volume/weight, pH, filter integrity tests, particulate matter, leak testing
of ampoules, …etc.
3.2.P.3.5 Process Validation and/or Evaluation
Description, documentation, and results of the validation and/or evaluation studies should be
provided for critical steps or critical assays used in the manufacturing process (e.g., validation of
the sterilization process or aseptic processing or filling). Viral safety evaluation should be
provided in 3.2.A.2, if necessary.
The controls can include parameters and attributes related to drug substance and drug product
materials and components, facility and equipment operating conditions, in-process controls,
finished product specifications, and the associated methods and frequency of monitoring and
control (ICH Q10).
The following information should be provided:
For non-sterile products:

1. A copy of the process validation protocol, specific to this finished product, that identifies the
critical equipment and process parameters that can affect the quality of the finished product
and defines testing parameters, sampling plans, analytical procedures and acceptance criteria;
2. A letter of commitment to conduct prospective validation on three consecutive production-
scale batches (Section 3.2.P.3.5) and to report immediately any out of specification (OOS)
results to the SFDA.
For sterile products:

1. Process validation on three consecutive validation batches including the sterilization process
(Section 3.2.P.3.5).
2. A letter of commitment to conduct prospective validation on three consecutive production
batches including the sterilization process (Section 3.2.P.3.5) and to report immediately any
out of specification (OOS) results to the SFDA.
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The information on process validation and/or evaluation studies for STERILE product is
recommended to be presented as follows:
Number of batches
Batch number
Batch type
Batch size
Are the submitted batches consecutive?  Yes  No
Is the process validation protocol submitted?  Yes  No
Are the process validation results submitted?  Yes  No
The specifications should be provided for all excipients, including those that may not be added to
every batch (e.g. acid and alkali), those that do not appear in the finished product (e.g. solvents)
and any others used in the manufacturing process (e.g. nitrogen, silicon for stoppers).
For excipients of natural origin, microbial limit testing should be included in the specifications.
For oils of plant origin (e.g. soy bean oil, peanut oil) the absence of aflatoxins or biocides should
be demonstrated.
The colors permitted for use are limited to those listed in the EU “List of permitted food colors”
and the US FDA “Inactive ingredient guide”. For proprietary mixtures, the supplier’s product sheet
with the qualitative formulation should be submitted, in addition to the finished product
manufacturer’s specifications for the product including identification testing.
The analytical procedures used for testing the excipients should be provided. Copies of the non-
compendial analytical procedures used to generate testing results should be provided. Unless
modified, it is not necessary to provide copies of the compendial analytical procedures.
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Analytical validation information, including experimental data, for the non-compendial analytical
procedures used for testing the excipients should be provided, where appropriate.
Justification for the proposed excipient specifications should be provided, where appropriate. This
should include a discussion on the tests that are supplementary to those appearing in the
compendial monograph.
3.2.P.4.5 Excipients of Human or Animal Origin
List of excipients that are of human or animal origin (including country of origin). Summary of
the information (e.g., sources, specifications, description of the testing performed, viral safety
data) regarding adventitious agents for excipients of human or animal origin (details should be
located in 3.2.A.2).
For excipients obtained from sources that are at risk of transmitting Bovine Spongiform
Encephalopathy (BSE)/Transmissible Spongiform Encephalopathy (TSE) agents (e.g., ruminant
origin), a letter of attestation (with supporting documentation) should be provided confirming that
the material is not from a BSE/TSE affected country/area. When available, a CEP demonstrating
TSE-compliance should be submitted. A complete copy of the CEP (including any annexes) should
be provided in Module 1 (Section 1.7.7).
3.2.P.4.6 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 (Specification and each Quality Attribute on
the specification, test Method, acceptance Criteria) with cross references to supporting safety data
(nonclinical and/or clinical) should be provided according to the drug substance format (details in
3.2.A.3).
A copy of the finished product specification(s) (release and shelf-life specifications) dated and
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signed by authorized personnel (i.e. the person in charge of the quality control or quality assurance
department), should be provided.
Generally, stability indicating parameters in specifications should have tighter release limits than
shelf life.
The specification(s) sheet should include, but not be limited to, the following:
• The tests;
• The standard declared by the applicant (e.g. compendial or in-house standard);
• The specification reference number and version (e.g. revision number and/or date);
• Analytical procedures, including their type (e.g. visual, IR, HPLC …), source (e.g. Ph. Eur.,
BP, USP, in-house) and version (e.g. code number/version/date).
Specifications should include, at minimum, tests for appearance, identification, assay, purity,
pharmaceutical tests (e.g. dissolution), physical tests (e.g. loss on drying, hardness, friability,
particle size, apparent density), uniformity of dosage units, identification of coloring materials,
identification and assay of antimicrobial or chemical preservatives (e.g. antioxidants) and
microbial limit tests (refer to ICH Q6A).
The analytical procedures used for testing the drug product should be provided. Copies of the non-
compendial analytical procedures used during pharmaceutical development (if used to generate
testing results provided in the dossier) as well as those proposed for routine testing should be
provided. Unless modified, it is not necessary to provide copies of the compendial analytical
procedures.
Chromatographic methods (e.g., HPLC & GC) are normally considered the method of choice for
determining impurities and assay. The analytical procedure submitted should be described in
sufficient detail including: Preparation of mobile phase, Chromatographic condition (Column:
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packing type (e.g., C18 or C8), dimension (length, inner diameter), particle size (10 μm, 5 μm),
Detector (wavelength), Injection volume, Column Temperature, Flow rate), elution procedure
(isocratic or gradient elution), preparation of standards and samples solution, type of reagent &
materials used, operation procedure (sequence of injections), system suitability testing (SST) and
criteria and calculations (including correction factors when the API is used as an external standard
to estimate the levels of impurities and data to support their calculation for an in-house method).
The system suitability tests (SSTs) represent an integral part of the method and are used to ensure
the satisfactory performance of the chosen chromatographic system. As a minimum, HPLC and
GC purity methods should include SSTs for resolution and repeatability. HPLC assay methods
should include SSTs for repeatability and in addition either peak asymmetry, theoretical plates or
resolution.
The information on analytical procedures is recommended to be presented as follows:
parameter).
Reference e.g. USP, BP, in-house method, …
− Column
− Flow rate
− Wavelength
− Injection volume
− Temperature
− Run time
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− Retention time
− Mobile phase
− Buffer
− Gradient programs (if

applicable)
− Stock standard solution
− Standard solution
− Test solution
− System suitability solution
− % RSD
− Tailing factor
− No. of theoretical plates (N)
− Resolution
Analytical validation information, including experimental data, for the analytical procedures used
for testing the drug product, should be provided (in accordance with ICH Q2(R1) and Q6A).
Copies of the validation reports (including the acceptance criteria and representative
chromatograms) for the non-compendial analytical procedures used during pharmaceutical
development (if used to support testing results provided in the dossier) as well as those proposed
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for routine testing should be provided. For in-house methods full validation are required.
Verification of compendial methods can be necessary. The compendial methods, as published, are
typically validated based on a drug substance or a finished product originating from a specific
manufacturer. Different sources of the same drug substance or finished product can contain
impurities and/or degradation products or excipients that were not considered during the
development of the monograph. Therefore, the monograph and compendial method(s) should be
demonstrated suitable for the control of the proposed finished product.
For compendial assay methods, verification should include a demonstration of specificity,

accuracy and repeatability (method precision). If a compendial method is used to control related
substances that are not specified in the monograph, full validation of the method is expected with
respect to those related substances.
If a compendial standard is claimed and an in-house method is used in lieu of the compendial
method (e.g. for assay or related substance), equivalency of the in-house and compendial methods
should be demonstrated. This could be accomplished by performing duplicate analyses of one
sample by both methods and providing the results from the study. For related substance methods,
the sample analyzed should be the placebo spiked with related substances at concentrations
equivalent to their specification limits.
If there are identified impurities specified in an official compendial monograph that are not
controlled by the proposed routine in-house analytical procedure, a justification for their exclusion
from routine analyses should be provided. If acceptable justification cannot be provided it should
be demonstrated that the routine in-house method is capable of separating and detecting the
impurities specified in the official compendial monograph at an acceptable level (e.g. 0.10%). If
such a demonstration cannot be performed, a one-time study should be conducted applying the
pharmacopoeial method to several recent batches to demonstrate the absence of the impurities
listed in the pharmacopoeia.
Transfer of analytical methods should accommodate all the analytical testing required to
demonstrate compliance of the product to be transferred with the approved specifications.
Analytical methods used to test pharmaceutical products, should be implemented at the testing
laboratory. The analytical methods transfer protocol should include a description of the objective,
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scope and responsibilities of the sending unit (SU) and receiving unit (RU); a specification of
materials and methods; the experimental design and acceptance criteria; documentation (including
information to be supplied with the results, and report forms to be used, if any).
The information on validation of analytical procedures is recommended to be presented as

follows:
parameter).
Specificity

performed:
− Representative chromatogram(s) The chromatogram(s) can be found in page No…
Linearity
− No. of concentrations
− Specified ranges
• Correlation coefficient
• y-intercept
• Residual sum of squares
Accuracy

performed:
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• % Recovery
• % RSD
• CI
Precision (repeatability and intermediate precision)

performed:
− Parameter: Acceptance criteria Results
• % RSD
LOQ/LOD

performed:
− LOD
− LOQ
Robustness

performed:
Systems suitability
• % RDS
• Tailing factor
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• No. of theoretical plates
• Resolution
Method transfer (if applicable):
Protocol:
− Tested Parameters: Acceptance criteria Results
3.2.P.5.4 Batch Analyses
A description of batches and results of batch analyses should be provided. The information
provided should include strength, batch number, batch size, batch type, date and site of production
and API manufacturer.
The information on finished product batch analyses is recommended to be presented as

follows:
Batch Batch Batch Site(s) of: Date(s) of: API

number size type Manufacturing Analysis Manufacturing Analysis manufacturer
Analytical results tested by the company responsible for the batch release of the finished product
should be provided for not less than two batches of at least pilot scale batches. These batches
should be manufactured by a procedure fully representative of and simulating that to be applied to
a full production-scale batch.
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reporting comments such as “all tests meet specifications”. For quantitative tests it should be
ensured that actual numerical results are provided rather than vague statements such as “within
limits” or “conforms”. Dissolution results should be expressed at minimum as both the average
and range of individual results.
A discussion and justification should be provided for any incomplete analyses (e.g. results not
tested according to the proposed specification).
3.2.P.5.5 Characterization of Impurities
Information on the characterization of impurities should be provided, if not previously provided

in "3.2.S.3.2 Impurities". The discussion should be provided for all impurities that are potential
degradation products and finished product process-related impurities.
Justification for the proposed drug product specification(s) should be provided. The discussion
should be provided on the omission or inclusion of certain tests, evolution of tests, analytical
procedures and acceptance criteria, differences from the compendial standard(s), …etc. If the
compendial methods have been modified or replaced, a discussion should be included.
The justification for certain tests, analytical procedures and acceptance criteria (e.g. degradation
products) may have been discussed in other sections of the dossier and does not need to be repeated
here, although a cross-reference to their location should be provided.
Information on the reference standards or reference materials used for testing of the drug product
should include the following, if not previously provided in "3.2.S.5 Reference Standards or
Materials":
1. The source of reference standards or reference materials (e.g., House, USP, BP, Ph. Eur.).
2. Certificate of analysis for reference standards or reference materials .
3. Characterization and evaluation of non-official (e.g., non-compendial) reference standards or
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reference materials (e.g., method of manufacture, elucidation of structure, certificate of
analysis, calibration against an official standard).
The information on reference standards/reference materials is recommended to be presented

as follows:
 Primary reference standard

Type of reference standards  Working or secondary reference standard
 Manufacturer reference standard
Information on potency ……… %
Information on calibration of
working standard with primary
reference standard
A description of the container closure systems should be provided, including unit count or fill size,
container size or volume, the identity of materials of construction of each primary packaging
component, its specification and the supplier’s name and address.
The specifications should include description and identification (and critical dimensions, with
drawings where appropriate). The specifications for the primary packaging components should
include a specific test for identification (e.g. IR). Specifications for film and foil materials should
include limits for thickness or area weight. Non-compendial methods (with validation) should be
included where appropriate.
The discussion should include copies of certificate of analysis for all primary packaging
components in which the specifications are in compliance with the pharmacopoeia.
For non-functional secondary packaging components (e.g., those that neither 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 of the container closure system used for the storage, transportation (shipping) and
use of the drug product should be located in 3.2.P.2.4. Information to establish the suitability (e.g.
qualification) of the container closure system should be discussed in Section 3.2.P.2.4.
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Comparative studies may be provided for certain changes in packaging components (e.g.
comparative delivery study “droplet size” for a change in manufacturer of dropper tips).
3.2.P.8 Stability
3.2.P.8.1 Stability Summary and Conclusions
The GCC guidelines for “Stability Testing of Active Pharmaceutical Ingredients (APIs) and
Finished Pharmaceutical Products (FPPs)” should be followed for recommendations on the
stability data required for the finished product(s).
The types of studies conducted, protocols used, and the results of the studies should be
summarized. The summary should include information on storage conditions, strength, batch
number (including the drug substance batch number(s) and manufacturer(s)), batch size, batch
type, batch manufacturing date, container closure system (including where applicable the
orientation e.g. inverted) and completed (and proposed) testing intervals, results, as well as
conclusions with respect to storage conditions and shelf-life, and, if applicable, in-use storage
conditions and shelf-life.
reporting comments such as “all tests meet specifications”. For quantitative tests (e.g. individual
and total degradation product tests and assay tests), it should be ensured that actual numerical
results are provided rather than vague statements such as “within limits” or “conforms”.
Dissolution results should be expressed at minimum as both the average and range of individual
results.
Where the methods used in the stability studies are different from those described in 3.2.P.5.2,
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A summary of stability study information is recommended to be presented as follows:
Accelerated stability
Long term stability studies
studies
Storage conditions (C, % RH)
FPP batch number
Batch type
Batch size
• Drug substance batch
number(s)
• Drug substance
manufacturer(s)
Completed testing intervals
Proposed testing intervals
Container closure system
Manufacturing site
Manufacturing date
Stability starting date
Conclusions with respect to
storage conditions and
proposed shelf-life
Conclusions with respect to in-
use storage conditions and
shelf-life, if applicable
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In-use stability studies should be conducted in accordance with the GCC Guidelines for
Stability Testing on at least two batches taking into consideration the following
requirements:
• Stability protocol to be submitted including: number of batch(s), size of batch(s), tested
parameters, manufacturing date and the starting date of the in-use stability study.
• The study design simulates the use of the product in practice.
• ONE of the batches should be chosen towards the END of its shelf-life (if available).
If such results are not available:
− ONE of the batches should be tested at the FINAL POINT of the submitted stability
studies with
− A commitment to conduct in-use stability study at the END of shelf-life and to report
immediately any out of specifications to the SFDA.
reporting comments such as “all tests meet specifications”. For quantitative tests (e.g. individual
and total degradation product tests and assay tests), it should be ensured that actual numerical
results are provided rather than vague statements such as “within limits” or “conforms”.
Dissolution results should be expressed at minimum as both the average and range of individual
results.
Where the methods used in the stability studies are different from those described in 3.2.P.5.2,
The information on the in-use stability study is recommended to be presented as follows:
Number of batches
Batch numbers
Batch type
Batch size
Manufacturing date
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Starting date of the study
Tested parameters
Is the study protocol submitted?  Yes  No
The information on the compatibility study is recommended to be presented as follows:
Number of batches
Batch numbers
Batch type
Batch size
Manufacturing date
Starting date of the study
Tested parameters
Reconstitution diluent(s)
Is the study protocol submitted?  Yes  No
3.2.P.8.2 Post-Approval Stability Protocol and Stability Commitments
The post-approval stability protocol and if applicable stability commitment should be provided.
When the available long-term stability data on primary batches do not cover the proposed shelf-
life period granted at the time of assessment of the dossier, a commitment should be made to
continue the stability studies in order to firmly establish the shelf-life period. A written
commitment (signed and dated) to continue long-term testing over the shelf-life period should be
included in the dossier.
Where the submission includes long-term stability data on three production batches covering the
proposed shelf-life period, a post-approval commitment is considered unnecessary. Otherwise one
of the following commitments should be made:
− If the submission includes data from stability studies on three production batches, a written
commitment (signed and dated) should be made to continue these studies through the proposed
shelf-life period.
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− If the submission includes data from stability studies on less than three production
batches, a written commitment (signed and dated) should be made to continue these studies
through the proposed shelf-life period and to place additional production batches, to a total of
at least three, in long-term stability studies through the proposed shelf-life period.
− If the submission does not include stability data on production batches, a written
commitment (signed and dated) should be made to place the first three production batches on
long term stability studies through the proposed shelf-life period.
The stability protocol for the commitment batches should be provided and should include, but not
be limited to, the following parameters:
• Number of batch(es) and different batch sizes, if applicable;
• Relevant physical, chemical, microbiological and biological test methods;
• Reference to test methods;
• Description of the container closure system(s);
• Testing frequency; and
• Description of the conditions of storage.
The stability of the drug product should be monitored over its shelf-life to determine that the
product remains within its specifications and to detect any stability issue (e.g. changes in levels of
degradation products). For this purpose, the ongoing stability programme should include at least
one production batch per year of product manufactured in every strength and every container
closure system (unless none is produced during that year). Therefore, a written commitment
(signed and dated) for ongoing stability studies should be included in the dossier.
Any differences in the stability protocols used for the primary batches and those proposed for the
commitment batches or ongoing batches should be scientifically justified.
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3.2.P.8.3 Stability Data
Results of the stability studies should be presented in a tabular format. The results of all testing
parameters related to each batch for the entire testing period should be presented in one table (i.e.
presenting the results of one parameter of all batches in one table is not acceptable).
The actual stability results/reports used to support the proposed shelf-life should be provided in
the dossier. For quantitative tests (e.g. individual and total degradation product tests and assay
tests), it should be ensured that actual numerical results are provided rather than vague statements
such as “within limits” or “conforms”. Dissolution results should be expressed at minimum as
both the average and range of individual results.
Information on the analytical procedures used to generate the data and validation of these
procedures should be included. Information on characterization of impurities is located in
3.2.P.5.5.
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3.2.A Appendices
For Biotech:
A diagram should be provided illustrating the manufacturing flow including movement of raw
materials, personnel, waste, and intermediate(s) in and out of the manufacturing areas. Information
should be presented with respect to adjacent areas or rooms that may be of concern for maintaining
integrity of the product.
Information on all developmental or approved products manufactured or manipulated in the same

areas as the applicant's product should be included.
A summary description of product-contact equipment, and its use (dedicated or multi-use) should
be provided. Information on preparation, cleaning, sterilization, and storage of specified equipment
and materials should be included, as appropriate.
Information should be included on procedures (e.g., cleaning and production scheduling) and
design features of the facility (e.g., area classifications) to prevent contamination or cross-
contamination of areas and equipment, where operations for the preparation of cell banks and
product manufacturing are performed.
Information assessing the risk with respect to potential contamination with adventitious agents
should be provided in this section.
For non-viral adventitious agents:
Detailed information should be provided on the avoidance and control of non-viral adventitious
agents (e.g., transmissible spongiform encephalopathy agents, bacteria, mycoplasma, fungi). This
information can include, for example, certification and/or testing of raw materials and excipients,
and control of the production process, as appropriate for the material, process and agent.
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For viral adventitious agents:
Detailed information from viral safety evaluation studies should be provided in this section. Viral
evaluation studies should demonstrate that the materials used in production are considered safe,
and that the approaches used to test, evaluate, and eliminate the potential risks during
manufacturing are suitable (refer to Q5A(R1), Q5D, and Q6B).
Materials of Biological Origin
Information essential to evaluate the virological safety of materials of animal or human origin (e.g.
biological fluids, tissue, organ, cell lines) should be provided (See related information in 3.2.S.2.3,
and 3.2.P.4.5). For cell lines, information on the selection, testing, and safety assessment for
potential viral contamination of the cells and viral qualification of cell banks should also be
provided (See related information in 3.2.S.2.3).
Testing at appropriate stages of production
The selection of virological tests that are conducted during manufacturing (e.g., cell substrate,
unprocessed bulk or post viral clearance testing) should be justified. The type of test, sensitivity
and specificity of the test, if applicable, and frequency of testing should be included. Test results
to confirm, at an appropriate stage of manufacture, that the product is free from viral contamination
should be provided (See related information in 3.2.S.2.4 and 3.2.P.3.4 ).
Viral Testing of Unprocessed Bulk
In accordance with ICH Q5A(R1) and Q6B, results for viral testing of unprocessed bulk should be
included.
Viral Clearance Studies
In accordance with ICH Q5A(R1), the rationale and action plan for assessing viral clearance and
the results and evaluation of the viral clearance studies should be provided. Data can include those
that demonstrate the validity of the scaled-down model compared to the commercial scale process;
the adequacy of viral inactivation or removal procedures for manufacturing equipment and
materials; and manufacturing steps that are capable of removing or inactivating viruses (See
related information in 3.2.S.2.5 and 3.2.P.3.5).
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3.2.A.3 Excipients
Any additional information should be provided in this section. The requirements for this section is
being subjected to development and will be published soon.
A list and copies of all bibliographical references cited in support of this application should be
provided. References that have not been provided should be available upon request.
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MODULE 4 NON-CLINICAL STUDY REPORTS
A Table of Contents should be provided that lists all of the nonclinical study reports and gives the
location of each study report in the eCTD.
4.2 Study Reports
The study reports should be presented in the following order:
4.2.1 Pharmacology
This section should begin with a description of the content of the pharmacologic data package,
pointing out any notable aspects such as the inclusion/exclusion of particular data (e.g., lack of an
animal model).
Studies on primary pharmacodynamics should be provided and evaluated. Where possible, it

would be helpful to relate the pharmacology of the drug to available data (in terms of selectivity,
safety, potency, … etc.) on other drugs in the class.
Studies on secondary pharmacodynamics should be provided by organ system, where appropriate,

and evaluated in this section.
Safety pharmacology studies should be provided and evaluated in this section. In some cases,
secondary pharmacodynamic studies can contribute to the safety evaluation when they predict or
assess potential adverse effect(s) in humans. In such cases, these secondary pharmacodynamic
studies should be considered along with safety pharmacology studies.
If they have been performed, pharmacodynamic drug interaction studies should be provided in this
section.
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4.2.2 Pharmacokinetics
4.2.2.1 Analytical Methods and Validation Reports
This section should contain the methods of analysis for biological samples, including the detection
and quantification limits of an analytical procedure. If possible, validation data for the analytical
method and stability of biological samples should be discussed in this section. The potential impact
of different methods of analysis on the interpretation of the results should be discussed in the
following relevant sections.
4.2.2.2 Absorption
The following data should be provided in this section:
• Absorption (extent and rate of absorption, in vivo and in situ studies).
• Kinetic parameters, bioequivalence and/or bioavailability (serum/plasma/blood PK

studies).
• Tissue distribution studies.
• Protein binding and distribution in blood cells.
• Placental transfer studies.
4.2.2.4 Metabolism
• Chemical structures and quantities of metabolites in biological samples.
• Possible metabolic pathways.
• Pre-systemic metabolism (GI/hepatic first-pass effects).
• In vitro metabolism including P450 studies.
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• Enzyme induction and inhibition.
4.2.2.5 Excretion
• Routes and extent of excretion.
• Excretion in milk.
If they have been performed, nonclinical pharmacokinetic drug-interaction studies (in vitro and/or
in vivo) should be provided in this section.
If studies have been performed in nonclinical models of disease (e.g., renally impaired animals),
they should be provided in this section.
4.2.3 Toxicology
The single-dose data should be provided, in order by species, by route. In some cases, it may be
helpful to provide the data in the form of a table.
Studies should be provided in order by species, by route, and by duration, giving details of the
methodology and highlighting important findings (e.g., nature and severity of target organ
toxicity, dose (exposure)/response relationships, no observed adverse effect levels, …etc).
Studies should be provided in the following order:
• In vitro non-mammalian cell system.
• In vitro mammalian cell system.
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• In vivo mammalian system (including supportive toxicokinetics evaluation).
• Other systems.
The choice of the studies and the basis for the high-dose selection should be explained. Individual
studies should be provided in the following order:
4.2.3.4.1 Long-term Studies
Long-term studies should be provided in order by species; including range-finding studies that
cannot appropriately be included under repeat-dose toxicity or pharmacokinetics.
4.2.3.4.2 Short- or medium-term studies
Short- or medium-term studies should be provided including range-finding studies that cannot
appropriately be included under repeat-dose toxicity or pharmacokinetics.
4.2.3.4.3 Other studies
4.2.3.5 Reproductive and Development Toxicity
Studies should be provided in the following order, giving details of the methodology and important
findings.
4.2.3.5.1 Fertility and Embryonic Development
4.2.3.5.2 Embryo-Fetal Development
4.2.3.5.3 Pre- and Post-natal Development & Maternal Function
4.2.3.5.4 Offspring, Juvenile, Second & Third-Generation Studies
If modified study designs are used, the sub-headings should be modified accordingly.
If local tolerance studies have been performed, they should be provided in order by species, by
route, and by duration, giving details of the methodology and important findings.
4.2.3.7 Other Toxicity Studies

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If other studies have been performed they should be provided in the following order, and where
appropriate, the rationale for conducting the studies should be provided.
4.2.3.7.1 Antigenicity
4.2.3.7.2 Immunogenicity
4.2.3.7.3 Mechanistic Studies (if not reported elsewhere)
4.2.3.7.4 Dependence
4.2.3.7.5 Metabolites
4.2.3.7.6 Impurities
4.2.3.7.7 Other
A list and copies of all bibliographical references cited in support of this application should be
provided. References that have not been provided should be available upon request.
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MODULE 5 CLINICAL STUDY REPORTS
A Table of contents for the clinical study reports should be provided.
5.2 Tabular Listing of All Clinical Studies
A tabular listing of all clinical studies and related information should be provided. For each study,
this tabular listing should generally include the type of information identified in Table 5.1. Other
information can be included in this table if the applicant considers it useful. The sequence in which
the studies are listed should follow the sequence described in Section 5.3. Use of a different
sequence should be noted and explained in an introduction to the tabular listing.
5.3 Clinical Study Reports
5.3.1 Reports of Biopharmaceutic Studies
BA studies evaluate the rate and extent of release of the active substance from the medicinal
product. Comparative BA or BE studies may use PK, PD, clinical, or in vitro dissolution endpoints,
and may be either single dose or multiple dose. When the primary purpose of a study is to assess
the PK of a drug, but also includes BA information, the study report should be submitted in Section
5.3.1, and referenced in Sections 5.3.1.1 and/or 5.3.1.2.
5.3.1.1 Bioavailability (BA) Study Reports
BA studies in this section should include:
• Studies comparing the release and systemic availability of a drug substance from a solid
oral dosage form to the systemic availability of the drug substance given intravenously or
as an oral liquid dosage form,
• Dosage form proportionality studies, and
• Food-effect studies.
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Table 5.1 Listing of Clinical Studies
Study Test Product(s); Healthy

Location of Study Design
Identifier Objective(s) Dosage Regimen; Number of Subjects or Duration of Study Status; Type
Type of Study Study and Type of
of the Study Route of Subjects Diagnosis of Treatment of Report
Report Control
Administration Patients
Tablet, 50mg Complete;

Sec. No., Absolute BA Healthy
BA 001 Cross-over single dose, 20 Single dose Abbreviated
page No. IV vs Tablet Subjects
oral, 10 mg IV
Compare
clinical study Two tablet Complete;
Sec. No., Healthy Abbreviated
BE 002 and to-be- Cross-over formulations, 50 32 Single dose
page No. Subjects
marketed mg, oral
formulation
Sec. No., Tablet, 50mg Renal Single dose Complete; Full

PK 1010 Define PK Cross-over 50
page No. single dose, oral Insufficiency
Bridging
Randomized Tablet, 50mg, 24 (12 Patients with
Sec. No., study
PD 020 placebo- multiple dose, drug, 12 primary 2 weeks Complete; Interim
page No. between
controlled oral, every 8 hrs placebo) hypertension
regions
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5.3.1.2 Comparative BA & BE Study Reports
Studies in this section compare the rate and extent of release of the drug substance from similar
drug products (e.g., tablet to tablet). Comparative Bioavailability (BA) or Bioequivalence (BE)
studies may include comparisons between:
• The drug product used in clinical studies supporting effectiveness and the to-be-marketed
drug product,
• The drug product used in clinical studies supporting effectiveness and the drug product
used in stability batches, and
• Similar drug products from different manufacturers.
Biowaiver studies should be submitted in this section. For more information regarding the
biowaiver studies, kindly refer to the SFDA Guidelines for Biowaiver.
5.3.1.3 In vitro/In vivo Correlation (IV/IVC) study reports
In vitro dissolution studies that provide BA information, including studies used in seeking to
correlate in vitro data with in vivo correlations, should be submitted in this section.
Comparative in vitro dissolution profiles according to the GCC Guidelines for Bioequivalence
should be submitted in this section.
Reports of in vitro dissolution tests used for batch quality control and/or batch release should be
placed in the Quality section of the eCTD.
5.3.1.4 Reports of Bioanalytical and Analytical Methods for Human studies
Bioanalytical and/or analytical methods for biopharmaceutic studies or in vitro dissolution

studies should ordinarily be provided in individual study reports. Where a method is used in
multiple studies, the method and its validation should be included once in Section 5.3.1.4 and
referenced in the appropriate individual study reports.
5.3.2 Reports of Studies Pertinent to Pharmacokinetics using Human Biomaterials
Human biomaterials is a term used to refer to proteins, cells, tissues and related materials derived
from human sources that are used in vitro or ex vivo to assess PK properties of drug substances.
Examples include cultured human colonic cells that are used to assess permeability through
biological membranes and transport processes, and human albumin that is used to assess plasma
protein binding. Of particular importance is the use of human biomaterials such as hepatocytes
and/or hepatic microsomes to study metabolic pathways and to assess drug-drug interactions with
these pathways. Studies using biomaterials to address other properties (e.g., sterility or
pharmacodynamics) should not be placed in the Clinical Study Reports Section, but in the
Nonclinical Study Section (Module 4).
5.3.2.1 Plasma Protein Binding Study Reports
Ex vivo protein binding study reports should be provided here. Protein binding data from PK blood
and/or plasma studies should be provided in Section 5.3.3.
5.3.2.2 Reports of Hepatic Metabolism and Drug Interactions studies
Reports of hepatic metabolism and metabolic drug interaction studies with hepatic tissue should
be provided in this section.
5.3.2.3 Reports of Studies Using other Human Biomaterials
Reports of studies with other biomaterials should be provided in this section.
5.3.3 Reports of Human Pharmacokinetic Studies
Assessment of the PK of a drug in healthy subjects and/or patients is considered critical to

designing dosing strategies and titration steps, to anticipating the effects of concomitant drug use,
and to interpreting observed pharmacodynamic differences. These assessments should provide a
description of the body’s handling of a drug over time, focusing on maximum plasma
105
concentrations (peak exposure), area-under-curve (total exposure), clearance, and accumulation of
the parent drug and its metabolite(s), in particular those that have pharmacological activity.
The PK studies whose reports should be included in Sections 5.3.3.1 and 5.3.3.2 are generally
designed to:
1. Measure plasma drug and metabolite concentrations over time,

2. Measure drug and metabolite concentrations in urine or faeces when useful or necessary,
and/or
3. Measure drug and metabolite binding to protein or red blood cells.
On occasion, PK studies may include measurement of drug distribution into other body tissues,
body organs, or fluids (e.g., synovial fluid or cerebrospinal fluid), and the results of these tissue
distribution studies should be included in Section 5.3.3.1 to 5.3.3.2, as appropriate. These studies
should characterize the drug’s PK and provide information about the absorption, distribution,
metabolism, and excretion of a drug and any active metabolites in healthy subjects and/or patients.
Studies of mass balance and changes in PK related to dose (e.g., determination of dose
proportionality) or time (e.g., due to enzyme induction or formation of antibodies) are of particular
interest and should be included in Sections 5.3.3.1 and/or 5.3.3.2. Apart from describing mean PK
in normal and patient volunteers, PK studies should also describe the range of individual
variability. In the ICH E5 guideline on Ethnic Factors in the Acceptance of Foreign Data, factors
that may result in different responses to a drug in different populations are categorized as intrinsic
ethnic factors or extrinsic ethnic factors. In this document, these categories are referred to as
intrinsic factors and extrinsic factors, respectively. Additional studies can also assess differences
in systemic exposure as a result of changes in PK due to intrinsic (e.g., age, gender, racial, weight,
height, disease, genetic polymorphism, and organ dysfunction) and extrinsic (e.g., drug-drug
interactions, diet, smoking, and alcohol use) factors. Reports of PK studies examining the
influence of intrinsic and extrinsic factors on exposure should be organized in Sections 5.3.3.3 and
5.3.3.4, respectively.
106
In addition to standard multiple-sample PK studies, population PK analyses based on sparse
sampling during clinical studies can also address questions about the contributions of intrinsic and
extrinsic factors to the variability in the dose-PK-response relationship. Because the methods used
in population PK studies are substantially different from those used in standard PK studies, these
studies should be provided in Section 5.3.3.5.
5.3.3.1 Healthy Subject PK and Tolerability
Reports of PK and initial tolerability studies in healthy subjects should be placed in this section.
5.3.3.2 Patient PK and Initial Tolerability
Reports of PK and initial tolerability studies in patients should be placed in this section.
5.3.3.3 Intrinsic Factor PK Study Reports
Reports of PK studies to assess effects of intrinsic factors, should be placed in this section.
5.3.3.4 Extrinsic Factor PK Study Reports
Reports of PK studies to assess effects of extrinsic factors, should be placed in this section.
5.3.3.5 Population PK Study Reports
Reports of population PK studies based on sparse samples obtained in clinical trials including
efficacy and safety trials, should be placed in this section.
5.3.4 Reports of Human Pharmacodynamic (PD) Studies
Reports of studies with a primary objective of determining the PD effects of a drug product in
humans should be provided in this section. Reports of studies whose primary objective is to
establish efficacy or to accumulate safety data, however, should be provided in Section 5.3.5.
This section should include reports of:
1. Studies of pharmacologic properties known or thought to be related to the desired clinical

effects (biomarkers),
2. Short-term studies of the main clinical effect, and
3. PD studies of other properties not related to the desired clinical effect.
107
Because a quantitative relationship of these pharmacological effects to dose and/or plasma drug
and metabolite concentrations is usually of interest, PD information is frequently collected in dose
response studies or together with drug concentration information in PK studies (concentration-
response or PK/PD studies). Relationships between PK and PD effects that are not obtained in
well-controlled studies are often evaluated using an appropriate model and used as a basis for
designing further dose-response studies or, in some cases, for interpreting effects of concentration
differences in population subsets.
Dose-finding, PD and/or PK-PD studies can be conducted in healthy subjects and/or patients, and
can also be incorporated into the studies that evaluate safety and efficacy in a clinical indication.
Reports of dose-finding, PD and/or PK/PD studies conducted in healthy subjects should be
provided in Section 5.3.4.1, and the reports for those studies conducted in patients should be
provided in Section 5.3.4.2.
In some cases, the short-term PD, dose-finding, and/or PK-PD information found in
pharmacodynamic studies conducted in patients will provide data that contribute to assessment of
efficacy, either because they show an effect on an acceptable surrogate marker (e.g., blood
pressure) or on a clinical benefit endpoint (e.g., pain relief). Similarly, a PD study may contain
important clinical safety information. When these studies are part of the efficacy or safety
demonstration, they are considered clinical efficacy and safety studies that should be included in
Section 5.3.5, not in Section 5.3.4.
5.3.4.1 Healthy Subject PD and PK/PD Study Reports
PD and/or PK/PD studies having non-therapeutic objectives in healthy subjects should be provided
in this section.
5.3.4.2 Patient PD and PK/PD Study Reports
PD and/or PK/PD studies in patients should be provided in this section.
5.3.5 Reports of Efficacy and Safety Studies
This section should include reports of all clinical studies of efficacy and/or safety carried out with
the drug, conducted by the sponsor, or otherwise available, including all completed and all ongoing
studies of the drug in proposed and non-proposed indications. The study reports should provide
the level of detail appropriate to the study and its role in the application. ICH E3 describes the
108
contents of a full report for a study contributing evidence pertinent to both safety and efficacy.
Abbreviated reports can be provided for some studies (see ICH E3).
Within Section 5.3.5, studies should be organized by design (controlled, uncontrolled) and, within
controlled studies, by type of control. Within each section, studies should be categorized further,
ordered by whether the study report is complete or abbreviated (ICH E3), with completely reported
studies presented first. Published reports with limited or no further data available to the sponsor
should be placed last in this section.
In cases where the application includes multiple therapeutic indications, the reports should be
organized in a separate Section 5.3.5 for each indication. In such cases, if a clinical efficacy study
is relevant to only one of the indications included in the application, it should be included in the
appropriate Section 5.3.5; if a clinical efficacy study is relevant to multiple indications, the study
report should be included in the most appropriate Section 5.3.5 and referenced as necessary in
other Sections 5.3.5 (e.g., Section 5.3.5A, Section 5.3.5B).
5.3.5.1 Study reports of Controlled Clinical Studies pertinent to the claimed Indication
The controlled clinical study reports should be sequenced by type of control:

• Placebo control (could include other control groups, such as an active comparator or other
doses),
• No-treatment control,
• Dose-response (without placebo),
• Active control (without placebo),
• External (Historical) control, regardless of the control treatment.
Within each control type, where relevant to assessment of drug effect, studies should be organized
by treatment duration. Studies of indications other than the one proposed in the application, but
that provide support for efficacy in the proposed use, should be provided in this section.
Where a pharmacodynamic study contributes to evidence of efficacy, it should be provided in this

section. The sequence in which studies were conducted is not considered pertinent to their
presentation. Thus, placebo-controlled trials, whether early or late, should be placed in this section.
Controlled safety studies, including studies in conditions that are not the subject of the application,
should also be reported in this section.
109
5.3.5.2 Study reports of Uncontrolled Clinical Studies
Study reports of uncontrolled clinical studies (e.g., reports of open label safety studies) should be
included in this section. This includes studies in conditions that are not the subject of the marketing
application.
5.3.5.3 Reports of Analyses of Data from More than One Study
Many clinical issues in an application can be addressed by an analysis considering data from more
than one study. The results of such an analysis should generally be summarized in the clinical
summary documents, but a detailed description and presentation of the results of such analyses are
considered critical to their interpretation. Where the details of the analysis are too extensive to be
reported in a summary document, they should be presented in a separate report. Such reports
should be provided in this section. Examples of reports that would be found in this section include:
a report of a formal meta-analysis or extensive exploratory analysis of efficacy to determine an
overall estimate of effect size in all patients and/or in specific subpopulations, and a report of an
integrated analysis of safety that assesses such factors as the adequacy of the safety database,
estimates of event rates, and safety with respect to variables such as dose, demographics, and
concomitant medications. A report of a detailed analysis of bridging, considering formal bridging
studies, other relevant clinical studies, and other appropriate information (e.g., PK and PD
information), should be placed in this section if the analysis is too lengthy for inclusion in the
Clinical Summary.
5.3.5.4 Other Study Reports
This section can include:
• Reports of interim analyses of studies pertinent to the claimed indications.
• Reports of controlled safety studies not reported elsewhere.
• Reports of controlled or uncontrolled studies not related to the claimed indication.
• Published reports of clinical experiences with the medicinal product that are not included
in Section 5.3.5.1. However, when literature is important to the demonstration or
substantiation of efficacy, it should be included in Section 5.3.5.1.
• Reports of ongoing studies.

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5.3.6 Reports of Post-Marketing Experience
For products that are currently marketed, reports that summarize marketing experience (including
all significant safety observations) should be provided in this section.
5.3.7 Case Report Forms and Individual Patient Listings
Case report forms and individual patient data listings that are described in the ICH clinical study
report guideline, should be placed in this section when submitted, in the same order as the clinical
study reports and indexed by study.
Copies of referenced documents, including important published articles, official meeting minutes,
or other regulatory guidance or advice should be provided here. Only one copy of each reference
should be provided. Copies of references that are not included here should be immediately
available on request.
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Data Requirements for Human Drugs

Date of issue 22 June 2011

Date of implementation 22 September 2011

Saudi Food & Drug Authority

For Inquiries [email protected]

Please visit SFDA’s website at

for the latest update

Vision and Mission

To be a leading international science-based regulator to protect and promote public

Version Author Date Comments

Executive Directorate of Product

Executive Directorate of Product

Executive Directorate of Product

Executive Directorate of Product

2.0 Drug Sector 9 March 2017 Updated

2.1 Drug Sector 24 October 2017 Updated

Section Description of change

ACRONYMS AND ABBREVIATIONS ....................................................................................... 7

The information presented in this guidance is based on recommendations of the:

− WHO, as described in the "Guideline on Submission of Documentation for a Multisource

b) In case of Generic Products:

▪ The search should be as extensive and relevant as possible

▪ Bioequivalence and bioavailability data of the generic product.

▪ Methodology of the search used should be stated in detail (database used,

- Start with the key clinical studies (e.g. confirmatory studies).

- Well-designed, adequately powered, and preferably multicenter studies.

- Studies that have registered protocol or registered in clinical trials

- Evidence from non-randomized controlled trials should be located in a

- Post marketing safety studies.

- If possible, provide study reports for each identified study.

− Module 1: Regional Administrative Information

This Module is required to be submitted. It should contain documents specific to SFDA;

− Module 2: Common Technical Document Summaries

The following sections are required to be submitted under Module 2:

- 2.1 Table of Contents of Module 2-5.

- 2.3 Quality Overall Summary:

- 2.5 Clinical Overview:

2.5.2 “Overview of Biopharmaceutics”: The summary of the comparative

− Module 4: Non-Clinical Study Reports

− Module 5: Clinical Study Reports

- 5.1 Table of contents for Module 5

- 5.2 Tabular listing of all clinical studies

o 5.3.1 Reports of biopharmaceutical studies

− 5.3.1.2 Comparative BA & BE Study Reports

The comparative bioavailability/bioequivalence study reports should be

− 5.3.1.3 In vitro/In vivo Correlation (IV/IVC) study reports: if available

− 5.3.1.4 Reports of Bioanalytical and Analytical Methods for Human studies:

− 5.4 Literature references

1.2. Application Form

1.3. Product Information

1.3.1. Summary of Product Characteristics (SPC)

1.3.3.1. Arabic leaflet

1.3.3.2. English leaflet

1.3.4. Artwork (Mock-ups)

The application for a marketing authorization must include 4 mock-ups as following:

1. The non-contrast photo of flat outer pack.

2. The on shelf photo of outer pack.

3. The photo of internal product.

4. The photo of dosage form.

Each expert report should consist of: