Quality Overall Summary - Chemical Entities Clinical Trial Application - Phase I (QOS-CE (CTA - Phase I))

Contact: Office of Clinical Trials

To: [Name], Director, Office of Clinical Trials

Security - Classification HC Protected

From: [Name], Manager, Clinical Trials Quality Division, Office of Clinical Trials

Date: [Completion date of the report]

Subject Quality Overall Summary - Chemical Entities Clinical Trial Application - Phase I
QOS - CTA GRP(PQ)-01-1(v1): Date 2009/11/12

Brand (Proprietary) Name of Drug Product

Proper, Common or Non-proprietary Name of Drug Substance

Manufacturer / Sponsor

Therapeutic Classification

Dosage Form(s) and Strength(s)

Route(s) of Administration

Type of Submission / Phase of Trial CTA

For Health Canada Use Only:

Therapeutic Products Directorate Target Date

Control No. / File No.

Contact Information

Reviewer Recommendation

This submission <IS/IS NOT> recommended for clearance with respect to the Quality (Chemistry and Manufacturing) information.

Reviewer Name

Review Hours

Reviewer Signature

Completion Date

Panel / Team Leader Signature

Report Access

References

Attachments

Evaluator's Introduction / Discussion:

PROPOSED COMMENTS TO BE FORWARDED TO THE SUBMISSION SPONSOR:

Notes to the Office of Clinical Trials - Clinical Group I/II:

INTRODUCTION

(a) Excerpt from Protocol Synopsis:

Trial Title, Number, and Phase

Trial Objectives

Study Design

Study Duration

Number of Centres/Canadian

Sample Size

Drug Formulation

Dosage Regimen (and concomitant medication, if applicable)

(b) Information on the comparator product:

Proprietary (Brand) Name of Drug Product

Non-proprietary or Common Name of Drug Substance (Medicinal Ingredient)

Company Name

Dosage Form(s)

Strength(s)

Country from which the Clinical Supplies were Obtained for the Lot to be Used in this Clinical Trial (as well as the market status in that country)

(c) If the information in any section (or subsection) has previously been submitted (in its entirety, without changes), and approved by Health Canada, do not resubmit that section. Provide the following information on the cross-referenced submission(s):

Section (and subsections)

Cross-Referenced Submission Name

File Number and Control Number

Date Approved

Drug Substance

Drug Product

2.3.S DRUG SUBSTANCE (NAME, MANUFACTURER)

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

2.3.S.1.1 Nomenclature (name, manufacturer)

(a)  Recommended International Non-proprietary name (INN):

(b) Company or laboratory code:

2.3.S.1.2 Structure (name, manufacturer)

(a) Structural formula, including relative and absolute stereochemistry:

(b)  Molecular formula:

(c) Molecular mass:

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

(a) Physical description (e.g., appearance, colour, physical state):

(b) Solubilities (e.g., aqueous/nonaqueous solubility profile, tabular format, reporting in mg/mL):

(c) pH and pKa values:

(d) Other relevant information:

2.3.S.2 Manufacture (name, manufacturer)

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

(a) Name, address, and responsibility of each manufacturer, including contractors, and each proposed production site or facility involved in the manufacturing of the batches to be used in this clinical trial:

(b) List of referenced Drug Master Files (DMFs) and DMF Numbers (copies of DMF letters of access should be located in Module 1):

2.3.S.2.2 Description of Manufacturing Process and Process Controls (name, manufacturer)

(a) Flow diagram of the synthetic process(es):

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

(a) For drug substances or drug substance manufactured with reagents obtained from sources that are at risk of transmitting Bovine Spongiform Encephalopathy (BSE)/Transmissible Spongiform Encephalopathy (TSE) agents (e.g., ruminant origin), provide an attestation (with supporting documentation, if applicable) confirming that the material is free of BSE/TSE agents:

2.3.S.3 Characterisation (name, manufacturer)

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

(a) List of studies performed (e.g., IR, UV, NMR, MS, elemental analysis) and summary of the interpretation of evidence of structure:

(b) Discussion on the potential for isomerism and identification of stereochemistry (e.g., geometric isomerism, number of chiral centres and configurations):

(c) Summary of studies performed to identify potential polymorphic forms (including solvates), if available:

(d) Summary of studies performed to identify the particle size distribution of the drug substance, if available:

(e) Other characteristics:

2.3.S.3.2 Impurities (name, manufacturer)

(a) Identification of potential and actual impurities arising from the synthesis, manufacture and/or degradation:

(i) List of drug-related impurities (e.g., starting materials, by-products, intermediates, chiral impurities, degradation products, metabolites), including chemical name and origin:

Drug-related Impurity (chemical name or descriptor)

Structure

Origin

(ii) List of process-related impurities (e.g., residual solvents, reagents, catalysts), including compound name and step used in synthesis:

(b) Actual levels of impurities (e.g., drug-related and process-related) found in batches to be used in this clinical trial:

Impurity (drug-related and process-related)

Results

2.3.S.4 Control of the Drug Substance (name, manufacturer)

2.3.S.4.4 Batch Analyses (name, manufacturer)

(a) Description of the batches to be used in this clinical trial:

Batch Number

Batch Size

Date of Manufacture and Site of Production

Use (e.g., clinical)

(b) Summary of results for the batches to be used in this clinical trial (should include tests, types of analytical procedures (e.g., HPLC, GC), and actual results):

2.3.S.6 Container Closure System (name, manufacturer)

(a) Description of the container closure system(s) for the storage and shipment of the drug substance:

2.3.S.7 Stability (name, manufacturer)

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

(a) Summary of stability studies to support this clinical trial (e.g., studies conducted, protocols used, results obtained):

(b) Proposed storage conditions for the drug substance:

2.3.S.7.2 Stability Protocol and Stability Commitment (name, manufacturer)

(a) If full long term stability data is not available at the time of filing, provide a summary of the stability protocol and a commitment for the continued monitoring of the drug substance stability according to the protocol:

2.3.S.7.3 Stability Data (name, manufacturer)

(a) The actual stability results (i.e., raw data) may be found in:

2.3.P DRUG PRODUCT (NAME, DOSAGE FORM)

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

(a) Description of the dosage form:

(b) Composition of the dosage form:

i. Composition, i.e., list of all components of the dosage form, and their amounts on a per unit basis (including overages, if any):

Component and Quality Standard (and Grade, if applicable)

Function

Strength label claim

Quantity per unit

%

Quantity per unit

%

Total

(ii) Composition of all components that are mixtures (e.g., colourants, coatings, capsule shells, imprinting inks):

(c) Description of accompanying reconstitution diluent(s), if applicable:

(d) Type of container closure system used for accompanying reconstitution diluent(s), if applicable:

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

(a) For sterile, reconstituted products, summary of compatibility studies with diluents/containers:

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

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

(a) Name, address, and responsibility of each manufacturer, including contractors, and each proposed production site or facility involved in the manufacturing of the batches to be used in this clinical trial:

(b) List of referenced Drug Master Files (DMFs) and DMF Numbers (copies of DMF letters of access should be located in Module 1):

(c) Attestation that the dosage form was manufactured under Good Manufacturing Practices (GMP) conditions:

2.3.P.3.2 Batch Formula (name, dosage form)

(a) List of all components of the dosage form to be used in the manufacturing process, and their amounts on a per batch basis (including overages, if any):

Strength (label claim)

Batch Size(s) (number of dosage units)

Component and Quality Standard (and Grade, if applicable)

Quantity per batch

Total

2.3.P.3.3 Description of Manufacturing Process and Process Controls (name, dosage form)

(a) Flow diagram of the manufacturing process:

(b) For sterile products, details and conditions of sterilization and lyophilization:

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

2.3.P.4.1 Specifications (name, dosage form)

(a) Specifications for non-compendial excipients and for compendial excipients which include supplementary tests not included in the monograph(s) may be found in:

(b) Confirmation that none of the excipients which appear in the drug product are prohibited for use in drugs by the Canadian Food and Drug Regulations:

(c) List of referenced Drug Master Files (DMFs) and DMF Numbers (copies of DMF letters of access should be located in Module 1):

2.3.P.4.5 Excipients of Human or Animal Origin (name, dosage form)

(a) List of excipients that are of human or animal origin (including country of origin):

(b) 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:

(c) For excipients obtained from sources that are at risk of transmitting Bovine Spongiform Encephalopathy (BSE)/Transmissible Spongiform Encephalopathy (TSE) agents (e.g., ruminant origin), provide an attestation (with supporting documentation, if applicable) confirming that the material is free of BSE/TSE agents :

2.3.P.4.6 Novel Excipients (name, dosage form)

(a) Summary of the details on the manufacture, characterization, and controls, with cross references to supporting safety data (nonclinical and/or clinical) on novel excipients (i.e., those used for the first time in a drug product or by a new route of administration):

2.3.P.5 Control of Drug Product (name, dosage form)

2.3.P.5.4 Batch Analyses (name, dosage form)

(a) Description of the batches to be used in this clinical trial:

Strength and Batch Number

Batch Size

Date of Manufacture and Site of Production

Input Drug Substance Batch

Use (e.g., clinical)

(b) Summary of results for the batches to be used in this clinical trial (should include tests, types of analytical procedures (e.g., HPLC), and actual results):

2.3.P.5.5 Characterisation of Impurities (name, dosage form)

(a) Information on the characterization of impurities, not previously provided in 2.3.S.3.2 (e.g., summary of actual and potential degradation products):

2.3.P.7 Container Closure System (name, dosage form)

(a) Description of the container closure systems, including unit count or fill size, container size or volume:

(b) Materials of construction of each primary packaging component:

(c) For sterile products, details of washing, sterilization and depyrogenation procedures for container closures:

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

2.3.P.8.1 Stability Summary and Conclusions (name, dosage form)

(a) Summary of stability studies to support this clinical trial (e.g., studies conducted, protocols used, results obtained):

i. Description of stability study details:

Storage Conditions (°C, % RH, light)

Strength and Batch Number

Batch Size and Date of Manufacture

Container Closure System

Completed (and Proposed) Test Intervals

(ii) Summary and discussion of stability study results:

(b) Proposed storage conditions and shelf life (and in-use storage conditions and in-use period, if applicable):

2.3.P.8.2 Post-approval Stability Protocol and Stability Commitment (name, dosage form)

(a) If full long term stability data is not available at the time of filing, provide a summary of the stability protocol and a commitment that the stability of the clinical trial samples will be monitored throughout the duration of the clinical trial or proposed shelf life:

2.3.P.8.3 Stability Data (name, dosage form)

(a) The actual stability results (i.e., raw data) may be found in:

Attachments

Attachment Number

Subject