Finished product specifications form user guide

Policy objectives

This guide is intended to explain the new approach to submission of finished product specifications for product licence applications.

Scope and application

This guide applies to the submission of all pre-market submissions of natural health products that fall under the Natural Health Products Regulations (regulations). This document should be read along with the following guidance document:

Quality of natural health products guide

Note about user guides in general

User guides are meant to provide assistance to industry and health care professionals on how to comply with governing statutes and regulations. They also provide guidance to Health Canada on how mandates and objectives should be implemented fairly, consistently and effectively.

User guides are administrative, not legal, instruments. This means that flexibility can be applied. However, to be acceptable, alternate approaches to the principles and practices described in this document must be supported by adequate scientific justification. They should be discussed in advance with the relevant program area to avoid the possible finding that applicable statutory or regulatory requirements have not been met.

As always, Health Canada reserves the right to request information or material, or define conditions not specifically described in this guide, to help us adequately assess the safety, efficacy or quality of a natural health product. We are committed to ensuring that such requests are justifiable and that decisions are clearly documented.

This document should be read along with the relevant sections of other applicable guides or guidance documents.

Guidance for implementation

The Natural and Non-Prescription Health Products Directorate (NNHPD) has developed a new approach to the assessment of the evidence for quality of finished natural health products (NHPs) that will expedite the pre-market authorization process. This new quality assessment process is intended to ensure that specifications meet with acceptable standards. The following document consists of a finished product specifications (FPS) template and Tables 1, 2 and 3, which outline prescribed tolerance limits for each type of test required for NHPs. Test methods recognized by the NNHPD are now also available via the Controlled Vocabulary search in the Natural Health Products Ingredients Database (NHPID).

By submitting the finished product specifications information in this form, the applicant is meeting the requirements of section 5(i) of the Natural Health Products Regulations.

The testing requirements listed in the template, the limits in Tables 1 to 3 and test methods found in the NHPID are consistent with the following guidance document:

Quality of natural health products guide

The responsibility to maintain complete quality information, including full test records, remains in place, and documentation must be provided to Health Canada on request. Auditing of documentation may occur during post-market and site-licensing evaluations.

Completing the FPS form

Note: macros must be enabled in Microsoft Word in order to check the boxes on the form. If the boxes cannot be checked, a security alert should be present in yellow below the toolbar. Click on “enable content” box to enable the feature.

Brand name

The brand name must be indicated on the FPS and must match the brand name indicated on the product licence application (PLA) form.

Sections A and B

Sections A and B are intended to provide descriptive information about the product. The type of dosage form must be specified in section A, and the types of ingredients contained in the product must be identified in section B.

This information is required as it serves to assist both the applicant and the NNHPD Assessment Officer in determining what evidence will be required to support the quality of the product. For example:

If an NHP contains both a plant and an isolate, then the applicant is able to attest that microbial contamination limits meet those that pertain to the plant material (the less stringent of the 2).
If the product type does not include plants, extracts, homeopathic medicines or traditional medicines, the Assessment Officer is immediately aware that pesticides testing may not be required.

Section C

This section covers the following:

medicinal ingredients and/or standardized constituents
their quantities
quantity tolerance limits
test methods
identity testing

The quantity and potency (if applicable) of each medicinal ingredient must be included along with its tolerance limits. Three options are provided for quantification of the medicinal ingredient:

quantification by input
a finished product assay by a method found in the NHPID or an equivalent validated in-house method
an assay by a test method recorded in section E

Note that when an ingredient is not assayed at the finished product stage (for instance, the addition is verified by GMP and in-process controls), a rationale is required to justify the absence of analytical testing. It should be clear whether testing of constituents (potency) for the purpose of standardization is done at the finished product or raw material stage (or both stages) and the test method used should be either one found in the NHPID or else specified in section E of the form.

For identity testing, it must be indicated for each medicinal ingredient whether the test methods is one found in the NHPID or an equivalent validated in-house method, whether the tolerance limits meet the requirements laid out in Table 1 and whether testing occurs at the finished product or raw material stage.

Note: If additional rows are required at any time, move your cursor to the outside right of the table (beside the last row) and press enter. A new row should appear. Alternatively, you may attach separate sheets of the same form if necessary.

Section D

Section D confirms that the product is tested in accordance with the following guidance document:

Quality of natural health products guide

This section of the guidance document and is subdivided into 3 sections:

relates to general parameters which apply to all NHPs
relates to ingredient-specific testing parameters for both medicinal and non-medicinal ingredients and
relates to performance standards for specific dosage forms

The NNHPD’s prescribed limits for the parameters in subsections 1, 2 and 3 are laid out in Tables 1, 2 and 3, respectively. For each applicable test parameter, it must be indicated whether the test methods meet those set out in NHPID or an equivalent validated in house method, whether the tolerance limits meet the requirements laid out in Tables 1, 2 and 3, and whether testing occurs at the finished product or raw material stage. This can be done by checking the appropriate boxes under each column (for instance, check the box marked “yes” if limits meet the requirements or “no” if they do not meet the requirements and provide the limits in section F). If the product does not contain the specific ingredient, indicate so by checking the box under ‘Product does not contain this ingredient’. If testing is not required (for example, microbial testing in products containing >50% alcohol), indicate so by checking the box under ‘N/A’ and provide a rationale. In the list of ingredient-specific parameters in section D(2), there is space at the end of the list to declare any additional specific tests performed that are not identified in section 2. Note that the test methods and tolerance limits must be included.

Note that the absence of a check does not equate to ‘N/A’.

Section E

When it is indicated that a test method used is not on the list of test methods found in the NHPID for a specific test parameter in sections C and D, then the test method used must be listed in section E. A rationale must be provided briefly describing the test method and justifying the use of this method.

Section F

When it is indicated that the tolerance limits for the test parameter do not meet the NNHPD’s prescribed limits for the parameters outlined in section D and the relevant tables, the alternative tolerance limits are to be listed in section F. A rationale must be provided justifying the limits and the expected risk to the consumer which arises from not meeting NNHPD limits.

Section G

Rationales must be scientific, backed by appropriate data and sufficiently justify why the proposed testing will not result in a risk to the consumer. Applicants can refer to the Quality of Natural Health Products Guide for more information on acceptable rationales:

Quality of natural health products guide

If a rationale is required by checking ‘N/A’ for any test parameter, it must be indicated in this section. Absence of a rationale will result in an incomplete FPS.

Signature block

Finally, the FPS is to be signed by a Quality Assurance signatory or designated official, confirming that all records relating to the evidence for quality of the NHP are in compliance with the FPS provided.

Recognized test methods

The NNHPD has provided a list of test methods in the NHPID. Each of these test methods is suitable for use for a particular product, either as published or modified for use for specific products. However, no test methods are appropriate for all products. By selecting 1 of these test methods from the list for a test parameter, you are indicating that:

you are using this test method or an equivalent validated in-house method for assay or other determination of the test parameter and
the test method is suitable for use for your product or raw material

It is the responsibility of the applicant to determine which test methods are appropriate for the product submitted for licensing. This is not an extensive list of methods, and thus test methods for specific products may not be present on the list. Alternate test methods may be listed in section F of the finished product specifications form.

The list of test methods found in the NHPID is not a complete list. It is part of a dynamic and growing database. As such, if it is felt that a test method used for a given test parameter is widely used in industry but it is not contained in the list, then relevant feedback (including details such as test type, protocols, validation information) should be forwarded to NNHPD. Use the natural health products ingredient database issue form to indicate this test method should be considered for addition to the NHPID.

To find the test methods listed in the Natural Health Products Ingredients Database, select “Test Methods” in the Category field using the Controlled Vocabulary Search function. You can enter specific search criteria in the Search field. You can also leave the Search field blank. A complete list of test methods recognized by NNHPD will appear.

Acceptable tolerance limits for quality test parameters (Tables 1, 2 and 3)

Table 1: General limits for the quality of finished natural health products
Test parameters		Product/ingredient	Tolerance limits
Physical Identity (physical description of the finished product)		For all products (finished product stage)	Conforms to standard
Identity of Medicinal Ingredients		For all ingredients	Conforms to reference material
Identity of Medicinal Ingredients		Live microorganisms (for example, probiotics)	Phenotyping^{Footnote 1}: Conforms to reference material and genotyping^{Footnote 2}: genome sampling/sequencing through a method that is adequate for the species, demonstrating a minimum homology of 97% to an identical type strain and below 95% to non-identical ones Whole genome in-vitro sampling/ sequencing through a method that is adequate for the species, to allow independent confirmation (for example, RAPD-PCR, PFGE, ERIC-PCR, rep-PCR)
Quantity		Most ingredients	Pharmacopoeial limits or, in their absence, 80% to 120% of the label claim
		Enzymes	80% to 150% of label claim
		Vitamins, minerals	Pharmacopoeial limits or, in their absence, 80% to 120% of label claim
		Live microorganisms (for example, probiotics)	At least 80% of the label claim at the end of shelf life Upper limits for total colony-forming units (CFU) should be established according to GMPs using internationally recognized methods.
		Lutein	90% to 130% of label claim
Potency (for standardized extracts)		Most constituents	Pharmacopoeial limits or 80% to 120% of the label claim
		Enzymes (if quantity was declared by weight)	80% to 150% of label claim
		Vitamins, minerals	Pharmacopoeial limits or, in their absence, 80% to 120% of label claim
		Lutein	90% to 130% of label claim
		Zeaxanthin	90% to 260% of label claim
Purity – microbial	Microbial contaminants	Most products	USP, BP or Eur. Pharm. Limits^{Footnote 3}
	P. aeruginosa (liquids with <50% alcohol)	Non-probiotic liquid products	USP, BP or Eur. Pharm. Limits^{Footnote 3}
	P. aeruginosa (liquids with <50% alcohol)	Products containing live microorganisms (liquid preparations only)	Absent (not detected in 1 g or 1 ml)
	Total aerobic plate count^{Footnote 4}	Products containing live microorganisms/probiotics	10⁴ CFU/g or mL
	Total yeast and mould count^{Footnote 5}	Products containing live microorganisms/probiotics	10² CFU/g or mL
	Salmonella spp.	Products containing live microorganisms/probiotics	Absent (10 g or 10 mL)
	Escherichia coli	Products containing live microorganisms/probiotics	Absent (10 g or 10 mL)
	Staphylococcus aureus	Products containing live microorganisms/probiotics	Absent (1 g or 1 mL)
	Enterobacteriaceae and bile tolerant gram-negative bacteria^{Footnote 6}	Products containing live microorganisms/probiotics	10² CFU/g or mL
	Other microbial impurity testing	As required by USP, BP or EU. Pharm.	USP, BP or EU. Pharm. limits^{Footnote 3}
Purity – chemical	Total arsenic	All products (except topical)	< 0.14 µg/kg b.w./day
	Total arsenic	Topical	3 ppm
	Organic arsenic	Only if total arsenic limit is exceeded	< 20 μg/kg b.w./day
	Inorganic arsenic	Only if total arsenic limit is exceeded	< 0.03 μg/kg b.w./day
	Cadmium	All products (except topical)	< 0.09 µg/kg b.w./day
	Cadmium	Topical	3 ppm
	Lead	All products (except topical)	< 0.14 µg/kg b.w./day
	Lead	Topical	10 ppm
	Total mercury	All products (except topical)	< 0.29 µg/kg b.w./day
	Total mercury	Topical	1 ppm
	Methylmercury^{Footnote 7}	Only if total mercury limit exceeds limit for methylmercury	< 0.029 µg/kg b.w./day
	Chromium VI (if applicable)	All products (except topical)	< 0.29 µg/ kg b.w./day
	Chromium VI (if applicable)	Topical	5 ppm
	Antimony (if applicable)	Topical	5 ppm
	Solvent residues	Extracts, isolates, synthetic duplicates	ICH Q3C or pharmacopoeial limits
Stability	Stability: Enumeration testing required for probiotics and activity testing required for enzymes	For all products	Meets the requirements set out in the Good manufacturing practices guidance document Meets the requirements in specifications at the end of shelf life for purity, quantity, potency and physical characteristics
Table 1 Note 1 Phenotyping: A set of tests for sufficient confirmation of observable traits of the species, which can include gram-staining, API sugar fermentation, enzymatic activity, fatty acid profile and proteome profile. Return to table 1 note 1 referrer Table 1 Note 2 Genotyping: species identification by comparison to identical and non-identical type strains obtained from an internationally recognized culture collection (for example, ATCC NCTC) strain characterization through up-to-date complete/whole genome sequencing Return to table 1 note 2 referrer Table 1 Note 3 Tolerance limits should comply with those set out in appropriate pharmacopoeias (for example, United States Pharmacopeia, British Pharmacopeia, or European Pharmacopoeia). Return to table 1 note 3 referrer Table 1 Note 4 Not required for products containing facultative anaerobic microorganisms (that can live and grow with or without molecular oxygen). Return to table 1 note 4 referrer Table 1 Note 5 Not required for products containing fungal microorganisms. Return to table 1 note 5 referrer Table 1 Note 6 Could exceed the 10² CFU/g or mL limit for products containing non-microbial ingredients that have not undergone or have been subject to minimal processing such as an extraction. In this case, a higher limit (or complete exclusion of testing) in line with an appropriate pharmacopeia (for example, USP, BP or Ph. Eur), would be considered acceptable. Return to table 1 note 6 referrer Table 1 Note 7 Methyl mercury determination is not necessary when the content for total mercury is less than the limit for methylmercury. Return to table 1 note 7 referrer

Table 2: Ingredient-specific limits for the quality of finished natural health products
Ingredient	Test parameter	Tolerance limit
Products containing plants, plant material, fungi, algae, cyanobacteria, non-human animal material or their extracts	Pesticides	Pharmacopoeial or World Health Organization limits
Ginseng, nuts and other suspected plants, plant material and extracts	Mycotoxins (for example, aflatoxins)	Aflatoxins < 20 µg/kg (ppb) of substance
Cyanobacterial materials (blue-green algae, including Aphanizomenon flos-aquae)	Cyanobacterial toxins	0.02 µg MC-LR/kg b.w./day
Products containing extracts, isolates, synthetic duplicates	Related impurities Product and/or process related impurities, if applicable (for example, co- extracted substances, inactive isomers, degradation product, intermediate product, reagents, catalysts)	Pharmacopoeial limits
Marine oils (for example, cod liver oil, fish oil, krill oil, seal oil, squid oil)	Sum of PCDFs, PCDDs and dioxin-like PCBs	10.0 pg TEQ TEF/g of oil
	Sum of PCDFs and PCDDs	2.0 pg TEQ TEF/g of oil
	Peroxide value (PV)	Max. 5 mEq/kg
	p-Anisidine Value (AV)	Max. 20 mEq/kg
	TOTOX value	Max. 26 mEq/kg
Oils containing non-marine unsaturated fatty acids	Oxidative stability: Peroxide value (PV) and/or Anisidine value (AV) as per pharmacopeial monographs	Pharmacopoeial limits
Bee products (for example, royal jelly and honey)	Antibiotic residues	Absent
Horsetail (Equisetum arvense L.)	Thiaminase activity (horsetail)	Free of thiaminase activity
Products that may have been in contact with radioactivity	Radioactivity (when suspected)	600 Becquerels/kg of substance
Glycerin (products containing glycerin, not including glycerin in capsules)	Diethylene glycol and related compounds	0.1% of any individual impurity, not more than 1.0% of total impurities
Products containing creatine monohydrate	Dicyandiamide	< 50 ppm
	Dihydrotriazines	Not detected (detection limit of < 5 ppm)
	Creatinine	< 100 ppm
Animal materials (for example, ovaries, hypothalamus, prostate gland, mammary gland, pituitary gland, adrenal gland and oxchic gland)	Hormones (sex hormones that are regulated as prescription drugs under the Food and Drug Regulations or as controlled substances as set out in Schedule IV of the Controlled Drugs and Substances Act)	Absent
Nosodes (for homeopathic products containing nosodes)	Sterility technique in compliance with the sterility requirements in the HPUS or HAB	Complies with sterility requirements in the HPUS or HAB
Ingredient-specific	Impurities (specify impurity)	Pharmacopoeial limits if available
	Potential adulterants (specify adulterant)	Pharmacopoeial limits if available
	Other (specify)	Pharmacopoeial limits if available
Live microorganisms/ probiotics	Antibiotic/antifungal resistance: broth microdilution or other equivalent non-clinical method	Minimal inhibitory concentrations (MIC) below species limits, as published by an internationally recognized panel (for example, EFSA) Broth microdilution or other equivalent non-clinical method
	Virulence factor production:^{Footnote 1} PCR/southern blot comparison with a closely related virulent strain (positive control)	Absence of the genetic elements responsible for the production of virulence factors characteristic to the species
	Toxigenic activity:^{Footnote 1} Confirmatory published in-vitro method adequate for the species or other internationally recognized methods	Absence of toxin production known to the species (for example, enteric, emetic)
Table 2 Note 1 Testing not required in every batch Return to table 2 note 1 referrer

Table 3: Dosage form specific limits for the quality of finished natural health products
Product	Test parameter	Tolerance limit	Comments
Discrete dosage forms	Weight variation or uniformity of dosage unit	Conforms to pharmacopoeial limits	For example, capsule, tablet, lozenge
Disintegration or dissolution	Uncoated	NMT 45 min	N/A
	Plain coated	NMT 60 min	N/A
	Enteric-coated	NLT 60 min in gastric fluid NMT 60 min in simulated intestinal fluid	Enteric-coated tablets to be tested in accordance with the U.S. or European pharmacopoeias (USP or Ph.Eur.)
Dissolution	Controlled release	2-stage or multi-point testing depending on type of controlled release (refer to “delayed and extended release”)	N/A
	Delayed release	2-stage testing required	N/A
	Extended release	Multiple-point sampling should be performed	N/A
Products containing preservatives	Antimicrobial Effectiveness^{Footnote 1}	Meets pharmacopoeial requirements	For example, potassium sorbate, sodium benzoate
Other dosage forms (for example, transdermal patches, metered dosage forms)	Please specify	Meets pharmacopoeial requirements when available	N/A
Table 3 Note 1 Testing not required in every batch Return to table 2 note 1 referrer

Page details

Date modified:: 2022-12-15

Language selection

Search