Quality Overall Summary – Biologic Products (QOS-B)

Foreword

The Quality Overall Summary (QOS) (Module 2.3) follows the scope and the outline of the Quality Body of Data (Module 3.2). This QOS-B template can be used by sponsors to summarize the Quality information for all types of drug applications containing drug substances and their corresponding products of biologic origin that are filed with Health Canada pursuant to Part C, Division 8 of the Food and Drug Regulations. This includes New Drug Submissions (NDSs) and Supplemental New Drug Submissions (SNDSs), Notifiable Changes (NCs), Clinical Trial Applications (CTAs) and Clinical Trial Application – Amendments (CTA-As). This QOS-B template is not to be used for Chemical Entities and Radiopharmaceutical (Schedule C) drugs. Please note that the use of the Canadian QOS-B is voluntary. The use of the global QOS will continue to be accepted. However, the use of the Canadian QOS-B may result in a reduction of clarification requests during review.

This template is an HTML representation of the form and it is not meant to be completed. To request a copy of the fillable form, please contact brdd-cppic_brdd-cppci@hc-sc.gc.ca.

Module 2.3: Quality Overall Summary– Biologics (QOS-B)
- Introduction
2.3.S Drug Substance (Common name, manufacturer)
2.3.P Drug Product (Proprietary name, Dosage form)
2.3.A Appendices
2.3.R Regional Information
- 3.2.R.5 Assessment of similarity (proprietary name, dosage form)

Module 2.3: Quality Overall Summary– Biologics (QOS-B)

Introduction

(a) Summary of product information:
Proprietary (Brand) Name of Drug Product
Non-proprietary or Common Name of Drug Product
Non-proprietary or Common Name of Drug Substance (Medicinal Ingredient)
Company (Manufacturer/Sponsor) Name
Dosage Form(s)
Strength(s)
Route of Administration
Proposed Indication(s)

(b) Other Introductory information:

2.3.S Drug Substance (Common name, manufacturer)

2.3.S.1 General Information (common name, manufacturer)

2.3.S.1.1 Nomenclature (common name, manufacturer)

2.3.S.1.2 Structure (common name, manufacturer)

2.3.S.1.3 General Properties (common name, manufacturer)

2.3.S.1.3.1 Physicochemical properties

2.3.S.1.3.2 Biological activity

2.3.S.2 Manufacture (common name, manufacturer)

2.3.S.2.1 Manufacturer(s) (common name, manufacturer)

Name and address	Responsibilities
Facility A	Drug substance manufacturer In-process controls testing Release testing including all compendial methods and non-compendial methods.
Facility B	Manufacturer and storage of the Master and Working cell banks Stability testing (e.g., Appearance, SE-HPLC, SDS-PAGE)
Facility C	Stability testing (e.g., Potency, RP-HPLC) Unprocessed bulk testing

2.3.S.2.2 Description of the manufacturing process and process controls (common name, manufacturer)

2.3.S.2.2.1 Flowchart of the upstream process

2.3.S.2.2.2 Flowchart of the downstream process

2.3.S.2.2.3 Shipment

2.3.S.2.3 Control of Materials (common name, manufacturer)

Biological Raw Material	Biological Source	Country of Origin	Manufacturer	Step	Suitability for Use

[For blood products: Donor Suitability, Testing, and Screening]
TD Marker	Test	Manufacturer	Generation	Acceptance Limit	Regulatory Approval

TD Marker	Test	Manufacturer	Generation	Acceptance Limit	Regulatory Approval

TD Marker	Test	Manufacturer	Generation	Acceptance Limit	Regulatory Approval

2.3.S.2.3.1 Raw materials, media, solutions, filter materials and chromatography resins

2.3.S.2.3.2 Source, history and generation of the cell substrate

2.3.S.2.3.3 Cell bank system

2.3.3.1 Cell Bank lineage
2.3.3.2 MCB characterization
2.3.3.3 WCB characterization
2.3.3.4 End-of-production cell banks
2.3.3.5 Post-production cell bank
2.3.3.6 Genetic stability

2.3.S.2.4 Control of Critical Steps and Intermediates (common name, manufacturer)

2.3.S.2.4.1 Identification and control of critical steps

2.3.S.2.4.2 In-process data

2.3.S.2.4.3 Justification of acceptance criteria for in-process controls

2.3.S.2.4.4 Intermediates

2.3.S.2.5 Process Validation and/or Evaluation (common name, manufacturer)

2.3.S.2.5.1 Stage 1 – Process design

2.3.S.2.5.2 Stage 2 – Process qualification/validation

2.3.S.2.5.3 Stage 3 – Continued/ongoing process verification

2.3.S.2.6 Manufacturing Process Development (common name, manufacturer)

2.3.S.2.6.1 Manufacturing process history

2.3.S.2.6.2 Comparability and characterization studies

2.3.S.2.6.3 Process design

2.3.S.3 Characterization (common name, manufacturer)

2.3.S.3.1 Elucidation of Structure and other Characteristics (common name, manufacturer)

Quality Attribute	Analytical Method	Summary of Results

2.3.S.3.1.1 Introduction

2.3.S.3.1.2 Primary structure

2.3.S.3.1.3 Secondary structure

2.3.S.3.1.4 Higher-order structure

2.3.S.3.1.5 Molecular weight

2.3.S.3.1.6 Molecular size, aggregation and fragmentation

2.3.S.3.1.7 Charge isoforms

2.3.S.3.1.8 Post-translational modifications

2.3.S.3.1.9 Biological activity

2.3.S.3.1.10 Structure function relationship

2.3.S.3.2 Impurities (common name, manufacturer)

Impurity	Use of Batches and Lot Number
	Batches used in toxicological studies	Batches used in clinical studies	Proposed commercial batches

Product-Related Impurities


TOTAL
Process-Related Impurities


Residual Solvents

Process-related Impurity or residual solvent/inorganic impurity	Source of impurity (i.e. manufacturing step or raw material, solvent)	Control Strategy and Proposed Limit (i.e. monitored as IPC, controlled as a release specification, demonstration of removal)	Maximum allowable amount (if applicable)	Supporting evidence to ensure safety and/or scientific justification (if applicable)

Product-related Impurity	Control Strategy and Proposed Limit (i.e. monitored as IPC, controlled as a release specification, demonstration of removal)	Supporting evidence to ensure safety and/or scientific justification (if applicable)

2.3.S.3.2.1 Overview

2.3.S.3.2.2 Process-related impurities

2.3.S.3.2.3 Product-related substances and impurities

2.3.S.4 Control of drug substance (common name, manufacturer)

2.3.S.4.1 Specifications (common name, manufacturer)

2.3.S.4.2 Analytical procedures (common name, manufacturer)

2.3.S.4.3 Validation of analytical procedures (common name, manufacturer)

2.3.S.4.3.1 Compendial procedures used for testing of drug substance

2.3.S.4.3.2 Non-compendial procedures used for testing of drug substance

2.3.S.4.4 Batch analyses (common name, manufacturer)

Test Parameter	Range of Results for in vivo study batches (Total number of batches)	Range of results for recent production batches (Total number of batches)

2.3.S.4.5 Justification of specifications (common name, manufacturer)

2.3.S.4.5.1 Justification of the analytical package

2.3.S.4.5.2 Justification of acceptance criteria

2.3.S.5 Reference standards or materials (common name, manufacturer)

2.3.S.5.1 Current reference standards (common name, manufacturer)

2.3.S.5.2 Future reference standards (common name, manufacturer)

2.3.S.5.3 Continuous quality assessment of working reference standard (common name, manufacturer)

2.3.S.6 Container closure system (common name, manufacturer)

2.3.S.7 Stability (common name, manufacturer)

2.3.S.7.1 Stability Summary and Conclusions (common name, manufacturer)

Drug substance batch number	Batch Designation (Phase of development or Process Validation)	Batch size	Manufacturing location and process	Manufacturing date	Type of stability study	Stability data currently available

2.3.S.7.1.1 Long term stability studies

2.3.S.7.1.2 Freeze/thaw stability studies

2.3.S.7.1.3 Summary of stability results

2.3.S.7.1.4 Conclusion

2.3.S.7.2 Post-approval stability protocol and stability commitment (common name, manufacturer)

2.3.S.7.3 Stability data (common name, manufacturer)

2.3.P. Drug Product (Proprietary name, Dosage form)

2.3.P.1 Description and Composition of the Drug Product (proprietary name, dosage form)

2.3.P.1.1 Description of the dosage form (proprietary name, dosage form)

2.3.P.1.2 Composition (proprietary name, dosage form)

2.3.P.2 Pharmaceutical Development (proprietary name, dosage form)

2.3.P.2.1 Components of Drug Product (proprietary name, dosage form)

2.3.P.2.1.1 Drug Substance

2.3.P.2.1.2 Excipients

2.3.P.2.2 Drug Product (proprietary name, dosage form)

2.3.P.2.2.1 Formulation development

Composition of Formulation or Code#	Batch#(s)	Strength	Type of Study Used In

2.3.P.2.2.2 Overages for drug product

2.3.P.2.2.3 Physicochemical and biological properties

2.3.P.2.3 Manufacturing process development (proprietary name, dosage form)

2.3.P.2.3.1 Manufacturing process history

2.3.P.2.3.2 Comparability studies

2.3.P.2.3.3 Process design

2.3.P.2.4 Container closure system (proprietary name, dosage form)

2.3.P.2.4.1 Extractables and leachables

2.3.P.2.4.2 Container closure integrity testing

2.3.P.2.4.3 Biocompatibility

2.3.P.2.5 Microbiological attributes (proprietary name, dosage form)

2.3.P.2.6 Compatibility (proprietary name, dosage form)

2.3.P.3 Manufacture (proprietary name, dosage form)

2.3.P.3.1 Manufacturer(s) (proprietary name, dosage form)

Name and address	Responsibilities
Facility A	Drug product manufacturer Packaging (primary and secondary)/Labelling In-process controls testing Release testing including all compendial methods and non-compendial methods Stability testing (e.g., Potency, RP-HPLC)
Facility B	Secondary packaging/Labelling Stability testing (e.g., sterility, SE-HPLC, SDS-PAGE)
Facility C	Importer and distributor (Enzymatic activity used as identity test)

2.3.P.3.2 Batch formula (proprietary name, dosage form)

Ingredient, Test Standard	Quantity per batch	Quantity per batch
Master Formula# or Code	no data
Date Master Formula Approved	no data
Strength (Label Claim)
Batch Size (# of dosage units)

Total (where applicable)

2.3.P.3.3 Description of manufacturing process and controls (proprietary name, dosage form)

2.3.P.3.4 Controls of critical steps and intermediates (proprietary name, dosage form)

2.3.P.3.4.1 Identification and controls of critical steps

2.3.P.3.4.2 In-Process data

2.3.P.3.4.3 Justification of IPCs

2.3.P.3.4.4 Intermediates

2.3.P.3.5 Process validation and/or evaluation (proprietary name, dosage form)

2.3.P.3.5.1 Stage 1 - Process design

2.3.P.3.5.2 Stage 2 - Process qualification/validation

2.3.P.3.5.3 Stage 3 - Continued/ongoing process verification

2.3.P.4 Control of excipients (proprietary name, dosage form)

Excipient	Biological Source	Country of Origin	Manufacturer	Suitability for Use

2.3.P.5 Control of drug product (proprietary name, dosage form)

2.3.P.5.1 Specification(s) (proprietary name, dosage form)

Test	Test method	Specification(s):
Test	Test method	Release	Shelf-life

2.3.P.5.2 Analytical procedures (proprietary name, dosage form)

2.3.P.5.3 Validation of analytical procedures (proprietary name, dosage form)

2.3.P.5.3.1 Compendial analytical procedures used for testing of drug product

2.3.P.5.3.2 Non-compendial analytical procedures specific to drug product

2.3.P.5.4 Batch analyses (proprietary name, dosage form)

Test Parameter	Range of Results for in vivo study batches (Total number of batches)	Range of results for recent production batches (Total number of batches)

2.3.P.5.5 Characterization of impurities (proprietary name, dosage form)

2.3.P.5.6 Justification of specifications (proprietary name, dosage form)

2.3.P.5.6.1 Justification of the analytical package

2.3.P.5.6.2 Justification of acceptance criteria

2.3.P.6 Reference standards or materials (proprietary name, dosage form)

2.3.P.7 Container closure system (proprietary name, dosage form)

2.3.P.8 Stability (proprietary name, dosage form)

2.3.P.8.1 Stability summary and conclusion (proprietary name, dosage form)

2.3.P.8.1.1 Long term stability studies

2.3.P.8.1.2 Photostability studies

2.3.P.8.1.3 Stability studies to support additional storage at room temperature

2.3.P.8.1.4 Thermal cycling studies

2.3.P.8.1.5 In-use stability studies

2.3.P.8.1.6 Forced degradation study

2.3.P.8.1.7 Stability indicating methods

2.3.P.8.1.8 Summary of stability study results

Drug product batch number	Batch Designation (Phase of development or Process Validation)	Manufacturing location and process	Manufacturing date	Related drug substance batch number(s)	Type of stability study	Orientation tested	Stability data currently available

2.3.P.8.1.9 Conclusions

2.3.P.8.2 Post-approval stability protocol and stability commitment (proprietary name, dosage form)

2.3.P.8.3 Stability data (proprietary name, dosage form)

2.3.A Appendices

2.3.A.1 Facilities and Equipment (common/proprietary name, manufacturer)

2.3.A.2 Adventitious Agents Safety Evaluation (common name, dosage form, manufacturer)

Biological Material	Biological Source	Country of Origin	Manufacturer	Step	Suitability for Use

2.3.A.2.1 Non-viral adventitious agents (common name, dosage form, manufacturer)

2.3.A.2.1.1 Microbial adventitious agents

2.3.A.2.1.2 Transmissible spongiform encephalopathy (TSE) agents

2.3.A.2.2 Viral adventitious agents (common name, dosage form, manufacturer)

Intermediate (Step)	Log₁₀ Reduction Factor
Intermediate (Step)	Target or Model virus "A" tested	Target or Model virus "B" tested	Target or Model virus "C" tested	Target or Model virus "D" tested	Target or Model virus "E" tested


Total log₁₀ Reduction Factor

Insert a detailed calculation of the estimated retroviral-like particles /dose, where relevant. The calculation should also be expressed as "one retroviral-like particle per number of doses".

2.3.A.3 Excipients

2.3.R Regional Information

3.2.R.5 Assessment of similarity (proprietary name, dosage form)

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2024-06-04