Draft for consultation: Quality of natural health products guide: General information about quality

On this page

• Natural health products
• Specifications

This section provides you with a framework of general elements, including definitions and resources, related to the quality of NHPs. Knowledge of these elements will help you navigate and use the quality and controls section of this guide when establishing, maintaining and updating the specifications of your NHP.

Natural health products

An NHP is a substance set out in Schedule 1 of the regulations or a combination of substances in which all the medicinal ingredients are substances set out in Schedule 1, a homeopathic medicine or a traditional medicine, that is manufactured, sold or represented for use in:

• the diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state or its symptoms in humans
• restoring or correcting organic functions in humans or
• modifying organic functions in humans

However, an NHP does not include a substance set out in Schedule 2 of the regulations or any combination of substances that includes a substance set out in Schedule 2.

Medicinal ingredients

A medicinal ingredient is any substance listed in Schedule 1 of the regulations that is intended to provide pharmacological activity or other direct effect in:

• diagnosing, treating, mitigating or preventing a disease, disorder or abnormal physical state or its symptoms in humans
• restoring or correcting organic functions in humans
• modifying organic functions in humans

A medicinal ingredient is characterized by its physical form, its chemical attributes, its source, its preparation as well as its dose and pharmacological action.

The following is a summary of the substances included in Schedule 1 of the regulations:

1. a plant or a plant material, an alga, a bacterium, a fungus or a non-human animal material
2. an extract or isolate of a substance described in item 1 (including enzymes)
3. vitamins (including biotin, folate, niacin, pantothenic acid, riboflavin, thiamine, and vitamins A, B6, B12, C, D, E, K1 and K2)
4. an amino acid
5. an essential fatty acid
6. a synthetic duplicate of a substance described in any of items 2 to 5
7. a mineral
8. a probiotic

Refer to the glossary for more detailed descriptions of each of the Schedule 1 substances.

Homeopathic medicines

Homeopathic medicines are NHPs. They are made from a wide range of materials, such as plants, animals, minerals and chemicals. Nosodes are also a type of homeopathic medicine. To be considered a homeopathic medicine, a product must be both:

• manufactured from, or contain as medicinal ingredients, only substances referenced in a homeopathic monograph in one of the following homeopathic pharmacopoeias, as amended from time to time:
  • Homeopathic Pharmacopeia of the United States (HPUS)
  • Homöopathisches ArzneiBuch (German Homeopathic Pharmacopoeia) (HAB)
  • European Pharmacopoeia (Ph.Eur.)
  • Pharmacopée française (Ph.F.)
  • Encyclopedia of Homeopathic Pharmacopoeia and
• prepared according to the methods outlined in one of the homeopathic pharmacopoeias listed in the first point, as amended from time to time

Homeopathic medicines must also meet all of these conditions with respect to their quality:

• not include prohibited substances as explained in the guide Evidence for homeopathic medicines
• comply with the specific quality requirements described in appendix 5 of the guide Evidence for homeopathic medicines
• comply with the general quality requirements described in the quality and controls section of this guide
• be manufactured in accordance with Part 3 (GMP) of the regulations and the NHP GMP guide

Traditional medicines

Traditional medicines are defined as medicines based on the sum total of knowledge, skills and practices that are based on the theories, beliefs and experiences indigenous to different cultures. The World Health Organization (WHO) traditional medicine program recognizes traditional medicines as practices that existed before the application of modern medicine. These practices have evolved to reflect different philosophical backgrounds and cultural origins.

All ingredients in traditional medicine NHPs should be prepared based on a traditional method utilized for that medicinal ingredient. Traditional medicines must meet the requirements described in the quality and controls section of this guide, and they must be manufactured in accordance with Part 3 (GMP) of the regulations and the NHP GMP guide.

Non-medicinal ingredients

A non-medicinal ingredient is defined as any substance that is added to a product to confer suitable consistency or form to the medicinal ingredients (suitable as per dosage form and route of administration). Non-medicinal ingredients should:

• not exhibit pharmacological effects
• not exceed the minimum concentration required for the formulation
• not have any effect contradictory to the product's recommended purpose
• not adversely affect the bioavailability, pharmacological activity or safety of the medicinal ingredients
• be safe

Non-medicinal ingredients may be added to a product to facilitate the functionality or the product's chemical, physical and microbial stability. Maintain information to support the nature and presence of all non-medicinal ingredients in your product, such as their:

• purity
• identity
• specifications
• purpose in formulation
• quality standards, and
• other manufacturing information

Health Canada may request to see this information about the non-medicinal ingredients in your product.

Always consider and justify the non-medicinal ingredients you choose to use in your product, in particular when your product is indicated for pediatric and other vulnerable sub-populations.

Refer to USP General chapter <1059> Excipient performance for test methods that can help you identify the key functional categories of the non-medicinal ingredients that may need to be controlled to ensure the physical and chemical stability and functionality of your finished product.

Specifications

In accordance with section 44 of the regulations, the specifications must contain tests describing the identity, quantity and potency (if applicable) of each medicinal ingredient in the NHP, the purity of the NHP, as well as the associated method and acceptance criteria for each test.

A specification is defined as a list of tests, references to test methods (analytical methods or procedures), and appropriate acceptance criteria that are numerical limits (such as target quantities), ranges or other criteria for the tests as described. It establishes the set of criteria to which a finished product needs to conform in order to be considered acceptable for its intended use and for sale. "Conformance to specifications" means that the NHP, when examined or tested according to the listed test methods, meets the listed acceptance criteria. In this guide, we also refer to acceptance criteria as tolerance limits where appropriate.

FPS are a critical quality standard. Every NHP intended for the Canadian market must comply with Health Canada's regulatory requirements for product specifications. PL holders must ensure that their product complies with these requirements.

The QAP must verify that each product lot meets its FPS. The certificate of analysis of every batch should match the most recent FPS as approved by the QAP, who will have ensured compliance with all applicable regulatory requirements regarding changes to FPS.

• Refer to the NHP MAP for more information on product licensing, including post-licensing changes.
• Refer to the NHP GMP guide for more information on the role of the QAP.

The FPS should confirm the quality and safety of the product rather than fully characterize its medicinal ingredient(s). As such, certain quality attributes may be established during product development or as in-process control (IPC) tests. In these instances, you may omit the test from the FPS if the decision is based on a scientific rationale and is supported by relevant data.

The use of IPC test specifications helps mitigate risks to the product batch during manufacturing. IPC tests are beneficial as they are performed during manufacturing for the purpose of adjusting process parameters. Hence, you may use IPC test limits as action limits to adjust the manufacturing process parameters within an operating range to minimize inter-batch and intra-batch variabilities ensuring all batches meet the expected acceptance criteria. Use the experience and data accumulated during the development and manufacturing of a product to create the IPC and FPS test parameters. Manufacturers may evaluate and then use certain quality tests for assaying as IPC tests, including the following:

• during granulations: tests for moisture, blend uniformity, bulk and tapped densities, granule particle size distribution
• for solid oral products: tests for average weight, tablet hardness, friability, weight gain during coating
• for semi-solids: tests for viscosity, homogeneity, pH, evaluation of phase separation
• for metered-dose inhalers: tests for fill weight/volume, leak testing, valve delivery
• for dry powder inhalers: assay of moisture, blend uniformity
• for liquids dosage forms: tests for pH, specific gravity, clarity of solutions, fill volume/weight, particulate matter test
• for tablets and chewable gels (commonly called gummies): water activity

When developing the FPS for your product, start with this guide. Establish and maintain the FPS for your product in accordance with the requirements described in this guide. The quality and controls section provides specific quality parameters and assists with using the sources of information that you will need to create, maintain and update your FPS. These sources of information include:

• pharmacopoeial monographs (from Schedule B listed pharmacopoeias)
  • for example, United States Pharmacopeia (USP) – General notices and requirements
• other internationally recognized standards
  • for example, European Medicines Agency (EMA) Guideline on specifications: test procedures and acceptance criteria for herbal substances, herbal preparations and herbal medicinal products/traditional herbal medicinal products

When asked by Health Canada to submit FPS in support of a PL application or amendment application, you should ensure the following:

• the FPS must be specific to the product referenced in the application itself
  • The FPS must include a set of universal tests (for example, identity, quantification, purity) and any specific test that relates to the dosage form (for example, viscosity in semisolid dosage forms) to ensure that your product is safe and of high quality at the time of release and over its shelf life.
  • Refer to the:
    • NHP MAP for more information on submission requirements
    • NNHPD's NHP FPS form section of this guide for more information about the form
• the FPS in the application must not indicate neither a reduced testing schedule nor a rotational testing (also known as skip testing) schedule
  • Refer to the:
    • NHP GMP guide to understand how to implement a reduced testing or rotational testing schedule and when it is deemed appropriate
    • NHP GMP guide for more information on stability testing

Pharmacopoeial monographs and other international standards

A pharmacopoeia (also spelled pharmacopeia) is an official reference book or compendium that contains standards, specifications and quality requirements for ingredients and products including NHPs. It sets standards that help ensure the quality, safety and efficacy of health products. It is prepared by a recognized authority. In general, pharmacopoeias consist of the following:

• basic assumptions, definitions and default conditions to be used
• monographs with tests, assays and acceptance criteria
• validated methods/procedures and best practices

The following pharmacopoeias and international standards are currently set out in Schedule B to the Food and Drugs Act:

• European Pharmacopoeia (Ph.Eur.)
• Pharmacopée française (Ph.F.)
• Pharmacopoeia Internationalis (Ph.I.)
• The British Pharmacopoeia (B.P. or BP)
• The Canadian Formulary (C.F.)
• The National Formulary (N.F. or NF)
• The Pharmaceutical Codex: Principles and Practices of Pharmaceuticals
• The United States Pharmacopeia (U.S.P. or USP)

Pharmacopoeial monographs and international standards are continuously revised to reflect updated safety data, advances in technology, and input from industry and regulatory authorities. An older version of a pharmacopoeial monograph may no longer reflect the most up-to-date scientific knowledge and practices. Always refer to the most current version of these types of references as only the most recently published version is considered valid. Therefore, your ingredient and product specifications must meet the requirements of the most recently published version if you are following a pharmacopoeial reference. A claim of pharmacopoeial grade must be supported by evidence that the ingredient meets all parameters of the relevant pharmacopoeial monograph.

You should also take proactive measures to implement risk mitigation strategies when a risk is identified by the pharmacopoeias and related communications, such as a USP Notice of Intent. This may include determining whether you need to make changes to the FPS of your product.

Note the following about pharmacopoeial references:

• in the pharmacopoeias, quality requirements can be included in overarching general texts (such as general notices, general monographs, dosage form monographs and general chapters) and/or in individual monographs
  • requirements presented in the general texts apply to all ingredients and products claiming to meet the pharmacopoeial monograph, unless otherwise specifically stated
  • where the requirements in an individual monograph differ from the general texts, the monograph requirements apply and supersede the requirements of the general texts, whether or not the monograph explicitly states the difference

Adherence to a pharmacopoeial monograph or to another internationally recognized standard (for example, the Food Chemicals Codex (FCC)) is only acceptable if the limits and parameters required by those references do not contravene the provisions of the Food and Drugs Act and all its associated regulations, including the Prescription drug list.

Establishing, maintaining and updating your FPS using these sources depends on the medicinal and non-medicinal ingredients in your product and the finished NHP itself (such as its dosage form, intended sub-population and route of administration). For example, for ophthalmic products you may refer to USP General chapter <771> Ophthalmic products: Quality tests. The quality and controls section of this guide describes which tests are required in the specifications for different product types and specific ingredients. This includes the test parameters, test methods, target quantities, and acceptance criteria that your FPS need to contain in order to comply with Health Canada's regulatory requirements.

Product testing

Product testing is essential to determine whether the product is compliant with Health Canada's regulatory requirements. The quality and controls section of this guide expands on what you need in terms of testing, why you need to do it and when you need to do it, as well as how you need to develop and manage FPS.

The quality and controls section of this guide describes and provides detail as to what information each test being performed on a finished product needs to contain, including the test type, the test method, the target quantity and the acceptance criteria.

Table 1 provides a set of universal tests applicable to all dosage forms to help you establish the FPS for use at product release (R) and for determination of product stability (S). These quality attributes are meant to ensure that the finished product complies with the regulatory requirements. The quality and controls section of this guide provides additional information about these universal tests as well as information on specific tests.

Test types

To ensure the quality of your NHP is acceptable at release and at expiry, you must consider the necessary tests, including:

• performance
• identity
• quantity (including potency if applicable)
• purity

It is important to identify in your FPS what the test type is (for example, dissolution, medicinal ingredient identification, elemental impurities).

Methods

A test method is a qualitative or quantitative analytical procedure that provides a precise process for testing or examining a product or material to produce reliable and reproducible results. Every analytical procedure must have an associated test method. In general, your test methods should reference a Schedule B listed pharmacopoeia or another internationally recognized standard, or be appropriately developed and validated according to recognized scientific principles.

The quality and controls section of this guide provides more detail on specific test methods and related requirements.

Using pharmacopoeial specifications that include test methods, with appropriate acceptance criteria, may also be justified. When this guide does not include information for a particular test method, the limits and procedures recommended in any one of the Schedule B listed pharmacopoeias are considered suitable. We advise you to consult these pharmacopoeias for detailed information about test methods, procedures, and acceptance criteria. Where multiple pharmacopoeias provide different specifications for the same test, you should justify your selection based on the most appropriate method for your specific product and intended use.

If the FPS are based on one of the pharmacopoeias, the pharmacopoeial monograph specifications for the assay and acceptance criteria should be regarded as the minimum standards for your FPS. If you claim your product meets a pharmacopoeial monograph, clearly identify the pharmacopoeia (for example, BP, Ph.Eur., USP) and the specific monograph you are using and follow the monograph in its entirety, including all specified test methods, acceptance criteria, and procedural requirements. When referencing pharmacopoeial monographs, ensure you specify the edition and any relevant updates or revisions to maintain consistency.

• Refer to the pharmacopoeial monographs section of this guide for a reminder on how such references present quality requirements and how to use them.

When you claim a specific pharmacopoeial standard (for example, USP), it is not acceptable to apply specifications from another pharmacopoeia (for example, Ph.Eur.) unless the monographs are harmonized. You may claim a manufacturer standard if the FPS include requirements from 2 or more pharmacopoeias, as long as you clearly justify your selection of specific tests and acceptance criteria from each source and show that the combined approach ensures product quality.

If you modify a pharmacopoeial method or use a method not from a Schedule B listed pharmacopoeia, ensure that you have a scientific rationale explaining why that test method is being used instead. Base the rationale on scientific knowledge and corroborate this with data to show that the recommended pharmacopoeial method cannot be implemented as written or is not applicable to your specific product matrix or intended use. In this instance, you need to fully validate the chosen test method and demonstrate that it is fit for purpose (see method equivalency).

Some possible reasons why a test method may not be suitable or possible include:

• matrix interactions
• test method interference
• product-specific limitations
• medicinal ingredient interactions
• inadequate sensitivity or selectivity
• non-traditional ingredient considerations

You may also choose test methods from pharmacopoeial or other internationally recognized standards other than those methods named in this guide (for example, FCC, International Organization for Standardization (ISO), Association of Analytical Collaboration International (AOAC) methods) when they are more appropriate for a specific ingredient or product. When alternate pharmacopoeial methods are used for testing or examining a product, validate the chosen test method against a relevant test method from one of the Schedule B listed pharmacopoeias or from another internationally recognized standard named in this guide (see method equivalency). The use of alternate test methods must be fit for purpose and supported by appropriate validation data showing equivalent or higher performance compared to the reference method.

If there are no test methods available for your non-traditional or novel medicinal ingredient or product, you may have to develop your own specific method (sometimes also called an in-house test method). This could include an assay for the medicinal ingredient or its related impurities. If you develop your own test method, you must maintain the following:

• a rationale indicating which references were checked for appropriate test methods when no methods exist in the pharmacopoeias or internationally recognized standards named in this guide
  • if test methods are available but not appropriate for a product, your rationale should also be accompanied by evidence that no method from those sources could be used (this includes a summary of the laboratory studies performed and data demonstrating the unsuccessful efforts)
• an appropriate statistical plan, including a description of the statistical analysis method and acceptance criteria used for evaluating the performance and capability of the test method
  • Refer to the USP General chapter <1010> Analytical data - Interpretation and treatment, and USP General chapter <1210> Statistical tools for procedure validation for additional information on designing your study.
• results of a method validation or method verification, including system suitability tests for method accuracy, precision, linearity of the calibration curve, range and robustness, which demonstrate the appropriateness of the test method for your product
  • Refer to the method equivalency section for additional guidance.
• in all cases, clearly document the supporting scientific rationale and maintain records for all test methods chosen for your ingredients and products. The method details should clearly include its source (such as Ph.Eur., USP) and full name to ensure traceability and compliance with the regulatory requirements. Here are 2 examples:
  • USP <616> Bulk and Tapped Density of Powders, Method II
  • In-house Method ABCD-999

Refer also to the following for guidance on method development:

• AOAC Official methods of analysis (AOAC OMA)
• Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO)'s Codex Alimentarius - Codex committee on methods of analysis and sampling

Regularly consult recognized sources for newly published and updated test methods that you can adopt for your product and its ingredients.

If no monograph from a Schedule B listed pharmacopoeia or other internationally recognized standard exists for an ingredient, obtain a suitable primary reference standard from a reputable commercial source or prepare one from a pivotal batch that you have fully characterized using multiple analytical methods, such as:

• mass spectrometry
• infrared (IR) spectroscopy
• nuclear magnetic resonance
• ultraviolet absorption spectrometry
• high-performance liquid chromatography

When preparing your own reference standard, ensure proper documentation of the physical and chemical properties, storage conditions, stability data, and purity determination. The reference standard should be compared to or calibrated against recognized standards where possible and include a certificate of analysis.

You need to maintain sufficiently detailed results for all tests conducted, including the range, mean and relative standard deviation (where applicable) of individual quantitative results, as well as quantities of all specified and unspecified impurities for the primary reference standard. It is generally sufficient to analyze, and maintain the test results, of the ingredient samples that were run concomitantly with the primary or secondary reference standard.

Refer to the glossary for a description of the term "primary reference standard".

Method equivalency

If you use a test method other than one listed in a Schedule B listed pharmacopoeia or another internationally recognized standard, you should establish equivalency of the chosen test method with that of a published reference when one is available. For consideration during the validation or verification of analytical procedures, refer to:

• ICH guideline Q2: Validation of analytical procedures
• USP General chapter <1225> Validation of compendial procedures
• USP General chapter <1226> Verification of compendial procedures
• USP General chapter <1223> Validation of alternative microbiological methods

Method equivalency studies should include:

• a sufficient number of representative batches
• predefined statistical analyses to demonstrate that the alternative analytical procedure is equivalent (non-inferior) or superior to the reference or original procedure for its intended purpose
• an appropriate number of samples from each batch
• comparative testing on the same samples where feasible, with predefined acceptance criteria
• evaluation of accuracy, precision, specificity and robustness under the experimental conditions

A receiving laboratory should ensure it has the capability to perform a test method that originated in another laboratory (the transferring laboratory). This includes verifying equipment suitability, analyst training, and environmental conditions.

• Refer to USP General chapter <1224> Transfer of analytical procedures for information and guidance on test method transfer.

Document equivalency studies to ensure transparency and reproducibility, covering sample preparation, statistical analysis, result comparisons, acceptance criteria and method modifications.

Target quantities

All NHPs must be formulated with the intent to provide 100% of the quantity of each medicinal ingredient declared on the product label.

Overages are generally defined as the percent of a medicinal ingredient in excess of the product label claim to compensate for the loss of the ingredient. Documented and scientifically justified medicinal ingredient overages may be used to compensate for processing losses during the manufacture of an NHP. Overages cannot exceed allowable limits, such as those contained in pharmacopoeial monographs.

Health Canada recommends against the use of an overage of a medicinal ingredient to compensate for degradation during manufacture and/or storage or to extend the product's shelf life.

Ensure the amount of the medicinal ingredient(s) in your NHP meets the target quantity or potency claimed on the product label. A pharmacopoeial monograph may allow a wider upper limit for vitamins and minerals (for example, 90-160% of the amount declared on the product label for a medicinal ingredient such as chromium). This higher limit allows for manufacturing process variations, analytical assay variability, and degradation tendencies of a specific vitamin or mineral medicinal ingredient, to the extent considered acceptable under practical conditions. Thus, adding an overage to pharmacopoeial monograph limit is generally not acceptable since it already allows for variations within scientifically recognized limits.

You should minimize the need for overage in your NHP. Instead you should apply appropriate quality control measures. This may include using microencapsulated ingredients, packaging materials with good barrier properties to prevent oxidative degradation, or other risk mitigation strategies (such as a shorter shelf life for your product).

If you need to use an overage, make sure you have a scientific rationale to support it. You must document the following:

• the overage percent (for example, 5% overage of a medicinal ingredient that has a labelled claim of 100 mg: the formulation would have 105 mg of the ingredient)
• the reasoning for the overage (that is, manufacturing loss details and documentation)
• the assessment of the impact of overage on the product tolerance limit, including:
  • the safety of higher limits of the medicinal ingredient in affected sub-populations
  • the safety of elevated related degradation substances
• any additional information available to support the rationale, including adequate data available in the scientific literature for qualification of an impurity

Justifications for stability overages should address the intrinsic instability of the medicinal ingredient due to natural degradation, potential degradants, and safety and efficacy implications.

The quality and controls section of this guide provides more specific information on target quantities.

Acceptance criteria (tolerance limits)

Acceptance criteria refer to numerical limits, ranges or other measures described in specifications to which a product should conform. The FPS for your product must include the target quantity (with units of measurement) and the tolerance limits for every test being performed. For quantitative tests, ensure that actual numerical results are included rather than vague statements such as "within limits" or "conforms".

Acceptance criteria ensure uniformity or batch-to-batch consistency, and that the quality of your product conforms to its specifications. The quantity of the medicinal ingredient(s) in an NHP must always remain within the established FPS from the time of product release to the product's expiry date. When any product falls outside of the specified acceptance criteria, it is considered to be out-of-specification (OOS).

• Refer to the NHP GMP guide for more information on OOS.

Where a pharmacopoeial monograph is available for a product, the acceptance criteria must always remain within the limits set out in the monograph. For products for which a monograph or other internationally recognized standard does not exist, it is your responsibility to establish appropriate acceptance criteria based on the principles set out in this guide.

Prescription drug list limits

A product is not considered to be an NHP if its sale requires a prescription under the Food and Drug Regulations.

• Refer to subsection 2(2) of the regulations.

Therefore, the FPS for your NHP must clearly demonstrate that the quantity or potency of the medicinal ingredient(s), including their upper tolerance limit, complies with subsection 2(2) of the regulations.

Ensure the acceptance criteria for the quantity of the medicinal ingredient(s) at the maximum Prescription drug list limit do not exceed the pharmacopoeial limit or the limit specified in this guide.

• Example: For vitamin K, the maximum recommended daily dose in an oral NHP is 120 µg, which reflects the restrictions qualified by the Prescription drug list. In a multi-vitamin/mineral supplement labelled to contain 120 µg of vitamin K per capsule, the quantity of vitamin K should not exceed the USP upper limit of 165% of the labelled quantity (that is, 198 µg).

The quality and controls section of this guide provides more specific information on acceptance criteria.

Table 1: Universal tests to be considered for the quality of finished NHPs in all dosage forms^{Footnote 1}

Test type	Test description	Test methodsFootnote 2	Acceptance criteria
Physical description of the product (R, S)	Qualitative and quantitative characteristics of the finished product, including: organoleptic tests (such as colour, clarity, shape, size, texture)	Physical tests USP General chapter <755> Minimum fill (where applicable) USP General chapter <698> Deliverable volume (where applicable)	Conforms to specifications
Identification of the medicinal ingredient(s) (R)	To discriminate between compounds of closely related structure	Pharmacopoeial or internationally recognized standards USP General chapter <197> Spectroscopic identification tests USP General chapter <857> Ultraviolet-visible spectroscopy USP General chapter <858> Raman spectroscopy or an acceptable method For plants and plant materials: USP General chapter <203> High-performance thin-layer chromatography procedure for identification of articles of botanical origin USP General chapter <1064> Identification of articles of botanical origin by high-performance thin-layer chromatography procedure Ph.Eur. General chapter2.2.27. Thin-layer chromatography Ph.Eur. General chapter2.2.28. Gas chromatography Ph.Eur. General chapter2.2.29. Liquid chromatography	Conforms to a pharmacopoeial or internationally recognized standard, reference articleFootnote 8, or NNHPD monograph
Quantification by assay of medicinal ingredient(s) (quantity or potency) (R, S)	Test for the quantity of the medicinal ingredient(s) in the finished product	Pharmacopoeial or internationally recognized standards, when available USP General chapter <621> Chromatography or another acceptable method	Conforms to pharmacopoeial or internationally recognized limits; or, in the absence of those, conforms to 80-120% of labelled claim
Uniformity of product (R, S)	Weight variation (WV) / Content uniformity (CU), may include additional tests (for example test for re-suspendability in suspensions, test for homogeneity in semi solids)	For discrete single-unit dosage forms, including: hard- or soft-shell capsules plain coated, film coated or uncoated tablets caplets lozenges chewable gels (commonly called gummies) liquid (in single-unit dosage container) Pharmacopoeial or internationally recognized standards USP General chapter <905> Uniformity of dosage units USP General chapter <2091> Weight variation of dietary supplements	Conforms to pharmacopoeial limits
Medicinal ingredient related impurities (R, S)	Tests and acceptance criteria for known related substances (for example, other isomers or polymorphs of the medicinal ingredient, known impurities including enantiomers, secondary metabolites, unknown impurities, and total known and unknown impurities)Footnote 3	Pharmacopoeial or international recognized standards	Conforms to pharmacopoeial or other acceptable qualification of individual impuritiesFootnote 4 Footnote 5 Footnote 6
Impurities (R)	Elemental impurities (refer to relevant section of this guide)	Pharmacopoeial or internationally recognized standards USP General chapter <233> Elemental impurities: Procedures or another acceptable method	Conforms to USP General chapter <2232> Elemental contaminants in dietary supplements, or ICH guideline Q3D: Elemental impurities
	Residual solvents (refer to relevant section of this guide)	USP <467> Residual solvents or another acceptable method	Conforms to USP General chapter <467> Residual solvents, or ICH guideline Q3C: Impurities: Guideline for residual solvents
	Where suspected: mycotoxins, aflatoxins, pesticides, herbicides, cyanobacterial toxins, marine oil contaminants, antibiotic residues, viruses, radioactivity	Pharmacopoeial or internationally recognized standards, NNHPD monograph, or CAMFootnote 7 method when available	Conforms to pharmacopoeial or internationally recognized limits, or limits in the NNHPD monograph
	Where suspected: other adulterants including substances under Controlled Drugs and Substances Act, prohibited and restricted substances as per Cosmetic Ingredient Hotlist, scheduled drugs under Food and Drug Regulations, and cannabis substances	Pharmacopoeial or internationally recognized standards USP General chapter <2251> Screening for undeclared drugs and drug analogues	Absent, or conforms to pharmacopoeial limits or to this guide
	Acid insoluble ash (in plants, algae, and other materials as specified in USP <561> Articles of botanical origin)	Pharmacopoeial or internationally recognized standards USP General chapter <561> Articles of botanical origin	Conforms to pharmacopoeial limits
Microbiological limits of non-sterile products (R, S)	Refer to relevant section of this guide	Pharmacopoeial or internationally recognized standards USP General chapter <61> Microbiological examination of nonsterile products: Microbial enumeration tests USP General chapter <62> Microbiological examination of nonsterile products: Tests for specified microorganisms USP General chapter <2021> Microbial enumeration tests: Nutritional and dietary supplements USP General chapter <2022> Microbiological procedures for absence of specified microorganisms: Nutritional and dietary supplements Ph.Eur. General chapter 2.6.12. Microbiological examination of non-sterile products (total viable aerobic count) Ph.Eur. General chapter 2.6.13. Microbiological examination of non-sterile products (test for specified micro-organisms) Ph.Eur. General chapter 2.6.31. Microbiological examination of herbal medicinal products for oral use and extracts used in their preparation or another acceptable method	Conforms to pharmacopoeial limits
Content of critical excipients (if present) (R, S)	For example: content of antimicrobial preservative, and ingredients added for oxidative or physical stability	Pharmacopoeial or internationally recognized standards or content tests USP General chapter <51> Antimicrobial effectiveness testing Ph.Eur. General chapter 5.1.3. Efficacy of antimicrobial preservation	Conforms to pharmacopoeial limits, or conforms to specifications
Foreign matter (R, S)	Test for the absence of process-related matters including particulates from extrinsic or exogenous sources (for example, fibers, insect parts) and intrinsic or inherent sources (for example, primary packaging materials, seal, glass lamellae)	Pharmacopoeial or internationally recognized standards or visual inspections tests For ophthalmic products: USP General chapter <789> Particulate matter in ophthalmic solutions	Conforms to pharmacopeial limits, or conforms to specifications
Note: In this table, tests required at product release are denoted by R and tests required for determination of product stability are denoted by S. Footnote 1 Refer also to table 2 of this guide for more information on dosage form-specific performance tests. Return to footnote 1 referrer Footnote 2 This table presents recommended test methods, but other test methods may also be used as long as they are suitable for the product. Return to footnote 2 referrer Footnote 3 Finished product testing is not required for ingredient-specific impurities if (a) the impurities are tested at the raw material stage, and (b) there is evidence that they do not increase during manufacturing processes and storage. Return to footnote 3 referrer Footnote 4 ICH guideline Q3A: Impurities in new drug substances. Return to footnote 4 referrer Footnote 5 For identification and qualification of mutagenic impurities in synthetic and semi-synthetic medicinal ingredients, refer to ICH guideline M7: Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk. Return to footnote 5 referrer Footnote 6 For a general framework on how to assess the potential genotoxicity of botanical substances or botanical preparations, refer to the EMA Guideline on the assessment of genotoxicity of herbal substances/preparations. Return to footnote 6 referrer Footnote 7 United States Food and Drug Administration (US FDA) Foods program compendium of analytical laboratory methods: Chemical analytical manual (CAM). Return to footnote 7 referrer Footnote 8 A National Formulary (NF) reference article must comply with all requirements in its monograph, applicable general chapters, and the General Notices of the USP–NF. Return to footnote 8 referrer

NNHPD's finished product specifications form

The FPS form is a tool to assist you in complying with the quality requirements set out in the regulations, including helping you to:

• build a set of specifications for your NHP
  • refer to the specifications section of this guide for more information
• present the FPS information in your PL application and in any subsequent amendment application, when necessary

For guidance on how to complete the FPS form itself:

• refer to the Finished product specifications form user guide
  • includes guidance on how to provide a scientific rationale to support, for example, the absence of testing or setting alternative tolerance limits in the FPS of your NHP
• refer to appendix 5 of this guide, which presents the tables to be used in conjunction with the FPS form

The information included in the FPS form must match the information in your established FPS, including all test methods and acceptance criteria.

Although they contain similar information, the FPS form does not equate to the complete set of specifications that you need to have and maintain specifically for your NHP. You must always have a complete set of specifications specific to your NHP for quality purposes (that is, for quality-related activities such as product release or determination of product stability).

• Example: when a Health Canada official or inspector requests to see a copy of the specifications for your NHP in a post-market situation, you are expected to provide a copy of the actual FPS and not a copy of the FPS form.

Maintenance of records

This guide identifies specific documents and records that you should maintain. These reminders reinforce the expectation that you keep all information necessary to comply with Health Canada's regulatory requirements. Document and maintain all quality-related information, ensuring it is relevant, accurate, and sufficient to support the quality of your NHP.

It is your responsibility to maintain complete quality information, including full test records, and provide documentation to Health Canada upon request. Auditing of documentation may occur, for example, during post-market and site licensing evaluations.

For more information on related records required by the regulations, refer to the NHP GMP guide.

This guide refers to the use of scientific rationales to support certain quality-related decisions. You must base these rationales on scientific knowledge and back them with supporting data. Document and maintain the rationales and data, and provide them to Health Canada upon request.