Module 2.3: Quality Overall Summary - Natural Health Products

For Viewing Purposes Only - Licence applicants must use the available WORD or PDF versions of this form when submitting it to the Natural and Non-prescription Health Products Directorate (NNHPD).

Introduction

1. Summary of investigational finished product(s) information (copy table as needed):
   
   • Proprietary (Brand) Name of Finished Natural Health Product
   • Non-proprietary or Common Name of Finished Natural Health Product
   • Non-proprietary or Common Name of Medicinal Ingredient(s)
   • Manufacturer Name
   • Dosage Form
   • Strength(s) (Quantity per dosage unit)
   • Route of Administration
   • Proposed Indication(s)
2. Excerpt from Protocol Synopsis:
   
   • Trial Title, Number, and Phase
   • Trial Objectives
   • Study Design
   • Study Duration
   • Number of Sites (inside and outside of Canada)
   • Sample Size
   • Patient Population
   • NHP Formulation
   • Dosage Regimen
3. Information on the comparator product:
   
   • Proprietary (Brand) Name of Finished Natural Health Product
   • Non-proprietary or Common Name of Medicinal Ingredient(s)
   • Manufacturer Name
   • Dosage Form
   • Strength(s) (Quantity per dosage unit)
   • Country from which the Comparator Product Was Obtained
   • Registration Number
   • Lot Number(s)
4. 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)
     • Medicinal Ingredient
     • Finished Natural Health Product
   • Cross-Referenced Submission Name File
   • Number and Control Number
   • Date Approved

Note: Based on the natural health product substances set out in Schedule 1 of the NHP Regulations, the medicinal ingredients have been divided into three categories as indicated below. To prepare the chemistry and manufacturing information for the medicinal ingredient(s) used in your study product, please select a category (from Part A) that applies to your product. If more than one category applies (e.g., in a combination product), please complete the necessary combination of categories. To prepare the chemistry and manufacturing information for the finished product, please complete Part B. The template in Part C for the Finished Natural Health Product Specifications is also required. If any specific section does not apply to your product, please indicate as "Not Applicable". Sections that are "Not applicable" should not be deleted and should be accompanied by an explanatory note describing the reasons for the inapplicability. For more detailed information on the category of ingredients and their requirements, please see the Evidence for Quality of Finished Natural Health Products Guidance Document (www.healthcanada.gc.ca/nhp).

Part A: Chemistry & Manufacturing Information of Medicinal Ingredient(s)

The following are the categories of substances from Schedule 1 of the NHP Regulations for which specific quality requirements are described in detail below.

• Category I: Plant, Plant material, Alga, Fungus, Bacterium, Non-Human Animal Material
• Category II: Isolate, Synthetic Duplicate, Non-Standardized and Standardized Extract, Amino Acid, Essential Fatty Acid, Vitamin, Minerals
• Category III: Probiotics

Category I - Plant, Plant material, Alga, Bacterium, Fungi, Non-Human Animal Material

2.3.S Medicinal Ingredient(s)

2.3.S.1 General Information

2.3.S.1.1 Nomenclature

1. Latin Binomial Name (genus and, if any, its specific epithet):
2. Common name:
3. Other (e.g., strain number for microbial cultures):

2.3.S.1.3 General Properties

1. Physical description (e.g., organoleptic, colour, shape):
2. Part of the Plant used (e.g., leaf, stem):
3. Part of the non-human animal used (e.g., cartilage):
4. Other relevant information:

2.3.S.2 Manufacturing Information

2.3.S.2.1 Manufacturer(s)

1. Name, address, and responsibility of each manufacturer, including contractors (if any) and each proposed production site or facility involved in the manufacturing of the batches to be used in this clinical trial:
2. List of referenced NHP or Drug Master Files (NHPMFs or DMFs) and NHP-MF or DMF Numbers (copies of NHP-MF or DMF letters of access should be located in Module 1):

2.3.S.2.2 Description of Manufacturing Process and Process Controls

1. Manufacturing information is not required for plant, algal, fungal, bacterial and non-human animal material and their non-standardized extracts. However, for all non-standardized extracts a list of solvents used in the extraction is required:

2.3.S.3 Characterisation

2.3.S.3.1 Identification of Medicinal Ingredient

1. List of spectroscopic methods and/or chromatographic fingerprinting studies performed (e.g., UV HPLC, TLC, and GC) (for plant, plant material, alga, bacterium and fungus):
2. If applicable, DNA fingerprinting studies and summary of the interpretation (e.g. non-human animal material)
3. Summary of studies performed to identify Foreign Matter (e.g., sand, dirt, insect parts, glass and metal) and Acid-insoluble Ash, if applicable:
4. Summary of studies performed to identify water content (for plant, plant material, and their non-standardized extracts):
5. Other identification evidence such as phenotypic and genotypic identification methods (e.g. comparison of plant sample with herbarium specimen, microscopic characterization of bacterium, DNA fingerprint):

2.3.S.3.2 Impurities

• a. Identification of potential and actual chemical impurities:
  • 
    Note: Please duplicate this table for each medicinal ingredient used in your study product

2.3.S.4 Control of the Medicinal Ingredient

2.3.S.4.1 Quantity

2.3.S.4.4 Batch Analyses

1. Description of the batches to be used in this clinical trial:
   • Batch Number
   • Batch Size
   • Date and Site of Production
   • Use (e.g., clinical)

2.3.S.6 Container Closure System

1. Description of the container closure system(s) for the storage and shipment of the medicinal substance:

2.3.S.7 Stability

2.3.S.7.1 Stability Summary and Conclusions

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

2.3.S.7.2 Post-approval Stability Protocol and Stability Commitment

1. If full long-term stability data are not available at the time of submission, provide the stability protocol, accelerated stability data and a commitment for the continued monitoring of the medicinal substance stability according to the protocol for the duration of the clinical trial (i.e., so that if the product degrades below the tolerance limit during the trial, more product can be taken out of cold storage. If a new batch needs to be used, sponsor should notify NNHPD as a notification in order to maintain the same quality and specifications):

2.3.S.7.3 Stability Data

1. The actual stability results (i.e., raw data) used to support the clinical trial:

Category II: Isolate, Synthetic Duplicate, Non-Standardized and Standardized Extract, Amino Acid, Essential Fatty Acid, Vitamin, Minerals

2.3.S. Medicinal Ingredient(s)

2.3.S.1 General Information

2.3.S.1.1 Nomenclature

1. Proper Name:
2. Common Name:
3. If an isolate or a standardized extract, proper name of source organism:
4. If an isolate or a standardized extract, common name of source organism:
5. Company or laboratory code:
6. Other non-proprietary name(s) (e.g., national name, USAN, BAN
7. Chemical Abstracts Service (CAS) registry number, if available:

2.3.S.1.2 Structure

1. Structural formula, including relative and absolute stereochemistry:
2. Molecular formula and/or molecular mass:

2.3.S.1.3 General Properties

1. Physical description (e.g., appearance, colour, taste, smell, physical state):
2. pH and pKa values:
3. Other relevant information:

2.3.S.2 Manufacturing Information

2.3.S.2.1 Manufacturer(s)

1. 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:
2. List of referenced NHP or Drug Master Files (NHP-MFs or DMFs) and NHP-MF or DMF Numbers (copies of NHP-MF or DMF letters of access should be located in Module 1):

2.3.S.2.2 Description of Manufacturing Process and Process Controls

1. Flow diagram of the extraction, isolation and/or synthetic process(es):
2. Brief narrative description of the manufacturing process(es), e.g. temperature, solvents used, and reagents:

2.3.S.2.3 Control of Materials

1. For medicinal ingredient(s) either obtained from non-human animal sources or processed using materials that present a risk of transmitting BSE/ TSE agents (e.g., ruminant origin), a completed Animal Tissue Form (ATF) must be submitted (www.healthcanada.gc.ca/nhp); see Appendix 3 of the Clinical Trials for Natural Health Products Guidance Document.

2.3.S.3 Specifications

2.3.S.3.1 Elucidation of Structure and other Characteristics

1. List of studies performed (e.g., IR, UV, NMR, MS, elemental analysis or HPLC, GC, with MS or UV-diode array detector) and summary of the interpretation of evidence of structure:
2. Discussion on the potential for isomerism and identification of stereochemistry (e.g., geometric isomerism, number of chiral centres and configurations):
3. Other characteristics (product specific):

2.3.S.3.2 Impurities

1. Identification of potential and actual impurities arising from the extraction, isolation, synthesis, manufacture, fermentation and/or degradation. If more than one batch used, complete a table for each batch:
   • Batch #:
     • Process Related Impurities
       • Starting material impurities
       • By-products
       • Intermediates
       • Chiral Impurities
       • Residual Solvents
       • Residual Reagents
       • Other
     • Chemical Name or Structure
     • Test Method (e.g. HPLC)
     • Limit of Detection (e.g. %)

Note: Please add to the above table other types of impurities if applicable.

2.3.S.4 Control of the Medicinal Ingredient

2.3.S.4.1 Specification

2.3.S.4.4 Batch Analyses

1. Description of the batches to be used in this clinical trial:
   • Batch Number
   • Batch Size
   • Date and Site of Production
   • Use (e.g., clinical)

2.3.S.6 Container Closure System

1. Description of the container closure system(s) for the storage and shipment of the medicinal substance:

2.3.S.7 Stability

2.3.S.7.1 Stability Summary and Conclusions

1. Summary of stability studies to support this clinical trial (e.g., studies conducted, protocols used, duration of test, results obtained). If not available at time of submission, provide accelerated stability data:

2.3.S.7.2 Post-approval Stability Protocol and Stability Commitment

1. If full long-term stability data are not available at the time of submission, provide the stability protocol, accelerated stability data and a commitment for the continued monitoring of the medicinal substance stability according to the protocol for the duration of the clinical trial (i.e., so that if the product degrades below the tolerance limit during the trial, more product can be taken out of cold storage. If a new batch needs to be used, sponsor should notify NNHPD as a notification in order to maintain the same quality and specifications):

2.3.S.7.3 Stability Data

1. The actual stability results (i.e., raw data) used to support the clinical trial:

Category III - Probiotics

2.3.S Medicinal Ingredient(s)

2.3.S.1 General Information

2.3.S.1.1 Nomenclature

1. Genus, specific epithet, strain:
2. Common name(s):

2.3.S.1.3 General Properties

1. Physical description (e.g., appearance, pellet, powder, colour):
2. Other relevant information:

2.3.S.2 Manufacturing Information

2.3.S.2.1 Manufacturer(s)

1. 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:
2. List of referenced NHP or Drug Master Files (NHP-MFs or DMFs) and NHP-MF or DMF Numbers (copies of NHP-MF or DMF letters of access should be located in Module 1):

2.3.S.2.2 Description of Manufacturing Process and Process Controls

1. Flow diagram of the mother culture preparation and fermentation conditions used:
2. Brief narrative description of the manufacturing process(es). In addition to this information, data provided for a medicinal ingredient produced by fermentation should include source and type of micro-organism used, composition of media, precursors, reaction conditions (e.g., time, temperature, rate of aeration etc.), name and composition of preservatives, if any:

2.3.S.2.3 Control of Materials

1. For medicinal ingredient(s) processed using materials that present a risk of transmitting BSE/ TSE agents (e.g., ruminant origin), a completed Animal Tissue Form (ATF) must be submitted (www.healthcanada.gc.ca/nhp); see Appendix 3 of the Clinical Trials for Natural Health Products Guidance Document.

2.3.S.3 Characterization

2.3.S.3.1 Characteristics of the culture

1. Phenotypic and/or genotypic identification:
2. Other characteristics:

2.3.S.3.2 Impurities

1. Identification of microbial impurities:
   
   1. List of related microbial impurities, if applicable. If more than one batch used, complete a table for each batch:
      • Microbial Contaminant(s)
      • Test Method Used
      • Medicinal Ingredient Tolerance Limits
      • NNHPD's Acceptable Tolerance Limits

2.3.S.4 Control of the Medicinal Ingredient

2.3.S.4.1 Total Viable Count

• c. Total viable count requirements for the probiotic culture(s):
  • Probiotic Culture(s)
  • Test Method Used
  • Test Limits (CFU/g or CFU/ml)
  • NNHPD's Acceptable Tolerance Limits
    • 80-300%

2.3.S.4.4 Batch Analyses (name, manufacturer, if applicable):

1. Description of each batch to be used in this clinical trial:
   • Batch Number
   • Batch Size
   • Date and Site of Production
   • Use (e.g., clinical)

2.3.S.7 Stability

2.3.S.7.1 Stability Summary and Conclusions

• b. Summary of stability studies to support this clinical trial (e.g., studies conducted, protocols used, duration of test, results obtained). If not available at time of submission, provide accelerated stability data:

2.3.S.7.2 Post-approval Stability Protocol and Stability Commitment

• a. If full long-term stability data are not available at the time of submission, provide the stability protocol, accelerated stability data and a commitment for the continued monitoring of the medicinal substance stability according to the protocol for the duration of the clinical trial (i.e., so that if the product degrades below the tolerance limit during the trial, more product can be taken out of cold storage. If a new batch needs to be used, sponsor should notify NNHPD as a notification in order to maintain the same quality and specifications):

2.3.S.7.3 Stability Data

• b. The actual stability results (i.e., raw data) used to support the clinical trial:

Part B: Chemistry & Manufacturing Information of the Finished Natural Health Product

2.3.P Finished Natural Health Product

2.3.P.1 Description and Composition of the Finished Product

1. Description of the dosage form:
2. Composition of the dosage form:
   1. Composition - list of all medicinal and non-medicinal ingredients of the dosage form, and their amounts on a per unit basis (including overages, if any):
      • Medicinal and Non-Medicinal Ingredients and Quality Standard (and grade, if applicable)
        • Medicinal Ingredients:
        • Non-Medicinal Ingredients:
        • Total
      • Intended Functions For NMIs
      • Quantity/Dosage Unit
        • Quantity per Unit
        • %
3. Description of accompanying reconstitution diluent(s), if applicable:
4. Quantitative list of the components of the placebo samples to be used in this clinical trial:
   • Name of Each Component of the Placebo
   • Quantity of Each Component in the Placebo
   • Total Amount

2.3.P.2 Formulation Development

1. For a new formulation (new combination, standardized extract, or new dosage form such as transdermal patch) provide a rationale on the development:
2. For sterile, reconstituted products, provide a summary of compatibility studies with diluents/containers:

2.3.P.3 Manufacturing Information

2.3.P.3.1 Manufacturer(s)

1. 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:
2. List of referenced NHP or Drug Master Files (NHP-MFs or DMFs) and NHP-MF or DMF Numbers (copies of NHP-MF or DMF letters of access should be located in Module 1:

2.3.P.3.2 Batch Formula

1. 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):
   • Quantity per Dosage Unit (strength)
   • Batch Size(s) (number of dosage units)
   • Date of Manufacture
   • Component and Quality Standard (and grade, if applicable)
     • Medicinal Ingredient:
     • Non-Medicinal Ingredient:
   • Quantity Per Batch
   • Total

Note: If more than one batch produced (e.g., additional lots of finished product or different strengths), duplicate table as needed.

2.3.P.3.3 Description of Manufacturing Process and Process Controls

1. Flow diagram of the manufacturing process:
2. Narrative description of the manufacturing process and process parameters:
3. For sterile/pasteurized products, details and conditions of sterilization and/or lyophilization:

2.3.P.4 Control of Non-medicinal Ingredients

1. Confirmation if the non-medicinal ingredients (NMI) used are included in the List of Acceptable Non-medicinal Ingredients (visit www.hc-sc.gc.ca/hpfb-dgpsa/nnhpd-dpsn/compendium_of_monographs_e.html for the List of Non-medicinal Ingredients):
   If not, please provide the following information:
2. List and summary of the information of NMIs that are of non-human animal origin (including country of origin):
3. For NMIs obtained from sources that are at risk of transmitting BSE/ TSE agents, a letter of attestation (with supporting documentation) should be provided confirming that the material is not from a BSE/TSE affected country/area.
4. Confirmation that none of the non-medicinal ingredients which appear in the finished product are prohibited for use in drugs by the Canadian Food and Drug Regulations:

2.3.P.4.1 Novel Non-medicinal Ingredients

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

2.3.P.5 Control of Finished Natural Health Product

2.3.P.5.1 Specification(s)

Note: In this table all information that is required to support finished product specifications should be included.

2.3.P.5.4 Batch Analyses

1. Description of the batches to be used in this clinical trial:
   • Strength (Quantity / Dosage Unit)
   • Batch Number
   • Batch Size
   • Date and Site of Production
   • Use (e.g., clinical)

2.3.P.5.5 Characterisation of Impurities

Information on the characterization of impurities derived from the processing of the finished product, interaction between medicinal and non-medicinal ingredients, and/or other medicinal ingredient related impurities.

2.3.P.7 Container Closure System

1. Description of the container closure systems, container size or volume:
2. Materials of construction of each primary packaging component:
3. For sterile products, details of washing, sterilization, pasteurization, depyrogenation procedures or other process for container closures, e.g. for ophthalmic use.

2.3.P.8 Stability

2.3.P.8.1 Stability Summary and Conclusions

1. Summary of stability studies to support this clinical trial (e.g., studies conducted, protocols used, duration of test, results obtained):
   1. Description of stability study:
      • Batch Number
      • Time Interval
      • Storage Conditions (°C, % RH, light)
      • Description of Product
      • Strength (Quantity per Dosage Unit)/Potency of Product
   2. Summary and discussion of stability study results:
2. Proposed storage conditions and shelf life:

2.3.P.8.2 Post-approval Stability Protocol and Stability Commitment

1. If full long-term stability data are not available at the time of submission, provide the stability protocol, accelerated stability data and a commitment for the continued monitoring of the medicinal substance stability according to the protocol for the duration of the clinical trial (i.e., so that if the product degrades below the tolerance limit during the trial, more product can be taken out of cold storage. If a new batch needs to be used, sponsor should notify NNHPD as a notification in order to maintain the same quality and specifications):

2.3.P.8.3 Stability Data

1. The actual stability results (i.e., raw data) used in support of this clinical trial:

Part C: Finished Natural Health Product Specification Template

Name of the Finished Product:
Name of Manufacturer of Finished Product:
Batch Number:

• Signature:
• Date:

Note: For any revisions in the product specifications, resubmit a revised copy of this template.