Good manufacturing practices guide for natural health products (GUI-0158): NHP GMP guidance, sections 43 to 47

On this page

• General information
• Prohibition (section 43)
• Specifications (section 44)
• Premises (section 45)
• Equipment (section 46)
• Personnel (section 47)

General information

For each section of the guidance, we have provided the exact text from Part 3 (GMP) of the regulations for your reference. The text is followed by the intent of the regulation and our interpretation on how to comply with it.

Certain sections may also include additional information on specific topics. At the end of each section, we have given examples of evidence to demonstrate GMP (for example, written procedures (SOPs) and records). Note that those examples are not an exhaustive list.

You will also find information on how we classify GMP observations based on risk in this guide.

Prohibition (section 43)

Section 43

1. Subject to subsection (2), no person shall sell a natural health product unless it is manufactured, packaged, labelled, imported, distributed or stored, as the case may be, in accordance with this Part.
2. A person may sell a natural health product that is manufactured, packaged, labelled, imported, distributed or stored, as the case may be, in accordance with requirements that are equivalent to those set out in this Part if the natural health product is imported.

Intent

Part 3 of the regulations begins with section 43 on prohibition. It states that any NHP sold in Canada must be manufactured, packaged, labelled, imported, distributed or stored according to the requirements outlined in Part 3.

Everyone involved in the lifecycle of an NHP must adhere to the GMP requirements.

The site licence holder must:

• follow the GMP requirements for each activity they are authorized to conduct
  • includes ensuring that their QAP has the training, experience and technical knowledge to perform all necessary quality-related functions
• ensure that all activities or services contracted out are conducted in accordance with GMP requirements

Importers:

• must ensure that imported NHPs are manufactured, packaged and labelled at foreign sites that meet the regulations
• are responsible for the NHPs they bring into Canada if there are any issues about their safety, efficacy or quality
• must provide evidence that the foreign sites they import from meet Canadian GMP requirements (or an equivalent)

For information on the evidence required from importers concerning foreign sites, consult:

• Site licensing guidance document

Any person who conducts an activity or sells an NHP in contravention of the act or regulations is breaking the law. They will be subjected to compliance and enforcement actions.

For more information on compliance and enforcement activities, consult:

• Compliance and enforcement policy for health products (POL-0001)

Specifications (section 44)

Section 44

1. Every natural health product available for sale shall comply with the specifications submitted in respect of that natural health product under paragraph 5(i) and with every change to those specifications made by the product licence holder.
2. The specifications shall contain the following information:
   1. detailed information respecting the purity of the natural health product, including statements indicating its purity tolerances;
   2. for each medicinal ingredient of the natural health product, detailed information respecting its quantity per dosage unit and its identity, including statements indicating its quantity and identity tolerances;
   3. if a representation relating to the potency of a medicinal ingredient is to be shown on a label of the natural health product, detailed information respecting the potency of the medicinal ingredient, including statements indicating its potency tolerances; and
   4. a description of the methods used for testing or examining the natural health product.
3. The specifications and every change to those specifications shall be approved by a quality assurance person.

Intent

Ensuring that a product meets its specifications involves:

• establishing product specifications
• putting in place a quality system that ensures the product meets the product specifications each and every time

The testing of finished products complements the GMP controls used during the manufacturing and importing processes. Each manufacturer, packager (when applicable) and importer must have:

• accurate specifications
• an adequate quality system in place and
• suitable test methods to ensure that each NHP sold meets its established specifications

Manufacturer, importer, packager, labeller requirements

The manufacturer, importer and, when applicable, packager and labeller must make sure a product meets its specifications.

As a manufacturer or importer, you must:

• implement written specifications related to purity, quantity, identity and potency for all finished products that are manufactured, packaged (when applicable) or imported
  • in accordance with the Quality of natural health products guide
• ensure the product specifications align with the specifications submitted in the product licence application (as applicable), are maintained and revised as necessary, and the QAP has approved any changes before they are used
  • the changes to specifications defined in section 11(1)(i) of the regulations require an amendment to the product licence
    • for more information, consult the Natural health products management of applications policy
    • for reference, the changes that require an amendment are:
      • removal of a test method set out in the specifications
      • modification of a test method that widens the purity tolerances or the quantity, identity or potency tolerances of any of its medicinal ingredients
      • modification of a test method that renders it less precise, accurate, specific or sensitive
  • document QAP approval of finished product specifications, including changes
  • develop written procedures (SOPs) for finished product testing, including associated blank record templates
• follow written procedures (SOPs) that describe the tests to be conducted that will ensure the purity, quantity, identity and potency of finished products
• include potency testing or appropriate controls in your procedures if the product licence contains any potency information for any ingredients
• ensure the test methods are suitable and have been shown to provide accurate and consistent results
• if you use a method that you developed specifically for your ingredient or product (often called an in-house test method), demonstration of consistency should include an acceptable analytical evaluation of parameters such as accuracy, precision and linearity for multiple tests of samples with known properties
• assess each lot for compliance with its product specifications and Health Canada's regulatory requirements before releasing the product in Canada

As an importer, you must also:

• confirm the imported products meet the specifications and Health Canada's regulatory requirements before releasing them in Canada
• review the supplier's certificate of analysis submitted with each lot received to ensure the product meets its specifications
• all required testing has been done
• tests not completed by the foreign site are conducted by you or a third-party laboratory
• review batch records when a medicinal ingredient of a product is quantified by input
• processes, documents and demonstrations outlined in the quantification by input section of this guide are acceptable and maintained
• when importing from buildings inspected by a regulatory authority under a mutual recognition agreement (MRA) or under the Pharmaceutical Inspection Co-operation Scheme (PIC/S), the batch certificate can replace the batch record and the review of the raw material certificates of analysis
• review label information or have a label control process in place to ensure that all imported products align with their product licence
• all imported products must meet the Guidance document: Labelling of natural health products

As a packager, you must keep records of the:

• testing or evaluation conducted by you or your packaging supplier on materials used for primary packaging the product
• if microbial contamination can be introduced during packaging, microbiological testing that confirms the environmental or sanitation controls implemented during the packaging process and microbiological testing on the finished product
  • if a third-party laboratory conducts the testing for you, a certificate of analysis will suffice as a record of testing

 As a packager, you must also:

• ensure that your polymer-based packaging materials, if used, are acceptable
• consult the Lists of acceptable polymers for use in food packaging applications for a list of generally accepted polymers

 When placing product into primary packaging, you must make sure the processes do not introduce the risk of microbial contamination. This is especially important when packaging liquid-based products. To properly monitor this risk, implement microbial controls throughout the packaging process and on finished products.

As a labeller, you must:

• ensure a product's label information aligns with its product licence and specifications
• product labels must align with the master production document
• for more information on labelling, consult:
• Guidance document: Labelling of natural health products

For all testing methods and requirements, consult:

• Quality of natural health products guide

Confirmatory testing

A confirmatory testing program is encouraged. Although it is optional, confirmatory testing provides added assurance of a product's quality, especially if manufactured by a new supplier or one that has a history of quality-related problems.

To perform confirmatory testing, an independent laboratory conducts tests to confirm the analyses of another facility and that the results already obtained for the same lot are valid.

Your confirmatory testing program should be independent of the manufacturer's testing. This will provide added assurance of a product's quality when it's manufactured or tested by a supplier.

The following is an example of a confirmatory testing program:

• Conduct full testing of the product against its specifications for the first lot received from each supplier for each product and then for each subsequent lot received:
• review the certificate of analysis showing actual test results and verify the product meets its specifications before releasing it
• take precautions to ensure that transportation conditions do not adversely affect product quality
• different products have different requirements (for example, sterile products or refrigerated products)
• verify that storage conditions do not adversely affect product quality
• conduct confirmatory testing on at least 1 lot per dosage form per supplier per year
• Have a different laboratory (as opposed to the original) perform the confirmatory testing
  • original laboratory may perform the test in exceptional circumstances, such as when test methods are very specialized

If you do confirmatory testing, you do not need to test for:

• sterility (if the method is validated and the laboratory is accredited)
• particulate matter

You may release a product for sale while undergoing confirmatory testing as long as the original analyses of the other facility are within specifications and your QAP has provided their approval. However, note that there is an increased risk of having to conduct product recalls if an out-of-specification (OOS) is identified subsequently during confirmatory testing.

Investigate the extent of the non-compliance for all products received from the facility if periodic confirmatory test results do not conform to a product's specifications.

Along with the items outlined in the section on QA, you may need to:

• assess the impact of the testing failure on:
  • the batch if your QAP released it before receiving the confirmatory test results
  • the reliability and accuracy of other results from the affected facility
• reassess and retest all products from the affected facility
• re-evaluate the affected facility's GMP compliance
• conduct additional confirmatory testing

Reduced testing

Reduced testing approaches can be a reasonable way to gain efficiencies in the quality control (QC) of NHPs. However, the choice of tests to perform and the justification for choosing those tests are key elements of operating a compliant reduced testing program that is also scientifically sound.

Microbial contaminants: Reduced testing

Some products have a low risk of microbial contamination because of their method of manufacture, low water activity and dosage form. When justified, a reduced microbiological testing strategy may be appropriate. In this case, use efficient manufacturing control processes and risk management strategies. These are defined in the section on QA.

You may implement a reduced testing procedure for microbial contaminants if you, as the manufacturer or importer, maintain records showing that:

• the product is in an acceptable dosage form (such as tablets, lip balms or topical ointments)
• water activity is controlled before the product is released and throughout its shelf life, and product yields an acceptable low water activity
  • defined by a recognized pharmacopoeial standard, such as the USP <1112> Application of water activity determination to nonsterile pharmaceutical products
• the product's antimicrobial properties are monitored throughout its shelf life, if required
  • defined by a recognized pharmacopoeial standard, such as the USP <51> Antimicrobial effectiveness testing
• the effectiveness of the product's microbial contamination controls is demonstrated, including:
• raw materials
• water used within the facility (for cleaning and rinsing equipment, for example)
• cleaning and manufacturing processes
• product formulation
• packaging system
• historical testing and stability studies show a low microbial load, demonstrated by either of the following:
• an analysis of at least 10 lots of the product, which may include:
• finished product lots
• pilot lots
• any related lot types
• a statistical analysis of:
• an adequate quantity of historical test data
• the statistical confidence in the controls during the manufacturing process to monitor or control micro contaminants

If these items are met, you may use the reduced testing approaches suggested by a recognized pharmacopoeia. Re-evaluate your reduced testing approach if you change manufacturing processes or manufacturers.

Note that a reduced microbiological testing approach is not acceptable for products containing live microorganisms (probiotics). For more information, consult the Quality of natural health products guide.

Remember that you cannot use water activity measurements alone to justify the elimination of all microbial content testing for product release, as NHPs may contain non-synthetic ingredients (for example, plants). Proper controls throughout the facility are always needed as some microorganisms, such as Salmonella spp. or filamentous fungi, may persist within or on the product without proliferating.

Microbial contaminants: Composite testing

Compositing refers to the process of pooling multiple samples for testing. Refer to the glossary for a more detailed description.

Composite testing alone is not acceptable for testing finished products, unless sample compositing is required by a sampling methodology described in a recognized pharmacopoeia.

Using individual samples instead of composite (pooled) samples provides a higher level of assurance in microbiological testing results. A compositing approach is not recommended as it may:

• mask or dilute contaminants
• reduce the sensitivity of the analysis
• reduce your ability to identify the contamination source
• increase the risk of releasing products that do not meet their specifications

Chemical contaminants: Exemption to product testing before release

As the manufacturer or importer, you do not need to test certain chemical contaminants if you can meet the following requirements:

• Heavy metal contaminant testing is not necessary if:
• raw materials are of synthetic origin or of pharmacopoeial grade
  • those that aren't of synthetic origin or of pharmacopoeial grade are tested and the results verified by the QAP
• the total daily exposure in the finished product is calculated (using USP <2232> Elemental contaminants in dietary supplements, for example), with the calculations based on the:
• quantity of each ingredient in the product
• maximum potential contamination given the proposed limits for each raw material
• daily dose of the product
• Residual solvent contaminant testing is not necessary if:
• the ingredients have been tested for residual solvents, untested ingredients are documented to be of pharmacopoeial grade, or a written confirmation is available from the supplier stating that no solvents are used during ingredient preparation
• solvents, other than water, are not used to manufacture the finished product and a written confirmation from the manufacturer is available
• Residual pesticide contaminant testing may not be necessary if:
• all botanical ingredients are shown to be organic, evidence of an acceptable organic certification from 1 of the certification bodies under the Canada Organic Regime is maintained, and all ingredients not identified as organic are tested for pesticides at the raw material stage
• the product has a certified organic content that is equal to or greater than 95%
• all the ingredients are synthetic or meet pharmacopoeial standards that have no pesticide residue limits
• the supplier is qualified to implement a reduced pesticide testing approach
• although it is optional, qualifying suppliers is encouraged as it provides added assurance of quality and permits reduced pesticide testing. To qualify a supplier, you must:
• confirm that they have a documented process they actively follow to manage quality
• evaluate their quality systems (focus on their processes to control and monitor pesticides)
• reevaluate regularly, on a defined schedule, the supplier's quality systems
• monitor the supplier for changes in their process (for example, a new source of raw materials) that may adversely affect product quality
• once a supplier is qualified, a reduced testing approach for pesticides could be implemented by:
• confirming that the first 3 lots are tested (by you or the supplier) for pesticides and that the results are acceptable
• if the results are acceptable, reduce testing to every 5 lots
• once confidence levels are high, reduce testing to every 10 lots with a minimum of 1 lot per year
• if a product fails to meet acceptable pesticide levels, you should disqualify the supplier, test all further lots for pesticides and initiate an investigation to identify the root cause
• remember to evaluate the previous lots during your investigation, because they were not tested

You must maintain supporting documents (for example, the certificate of analysis from your supplier) that demonstrate the acceptability of not testing for these contaminants prior to release.

Medicinal ingredients: Rotational testing

Based on process validation (if implemented) or in-process controls and statistical confidence, a rotational testing program (also known as skip testing) is an alternative to fully testing every lot of finished product. Even when using a rotational testing program (for example, for a product containing several medicinal ingredients, such as a multi-vitamin supplement), the medicinal ingredients not being tested must meet their acceptance criteria. At least 1 medicinal ingredient must be quantified per lot.

To implement an acceptable rotational testing program for medicinal ingredients, as a manufacturer or an importer, you must:

• establish testing levels that describe which tests on the product specifications are conducted on a lot in what order
• remember: controls need to be maintained during manufacturing to ensure that the quantity per dosage unit meets their acceptance criteria
• ensure testing of each ingredient on the product's specifications is done at least once every 3 lots or once a year if fewer than 3 lots are manufactured or imported annually
• identify tests for key potential contaminants and conduct them for every lot if required
• ensure critical tests are conducted for every lot if required. This should include tests when ingredients:
• are used to demonstrate batch homogeneity
• may degrade during the manufacturing process
• are deemed critical for the labelled health claims
• have potency limits that are not controlled at the raw material stage

As rotational testing does not fully test for each medicinal ingredient in every lot, it must be:

• scientifically supported and justified prior to implementation
• implemented after a product licence is issued using the GMP guidelines outlined in this guide

If there is a testing failure, such as OOS results, you must:

• ensure the QAP investigation includes the previous 2 lots that were not tested for the affected ingredient
• this process should be described in your written procedure (SOP) for OOS investigation
• evaluate the need for a recall for the previous 2 lots that were not tested for the affected ingredient
• remove the affected medicinal ingredient from the rotational schedule
• should be tested on the next 3 lots before being re-introduced into the rotational testing program
• evaluate the need to restore regular testing of the product

Importing from buildings inspected by a regulatory authority under an MRA or PIC/S

The MRA and PIC/S approaches are an effective way for Canada to enhance international regulatory cooperation. They help to:

• develop closer and stronger relationships among regulatory authorities
• maintain high standards of product safety and quality for its GMP compliance program, while helping to reduce the regulatory burden for industries

Canada participates in PIC/S and several MRAs that cover drug and medicinal products GMP compliance programs. Although MRA and PIC/S programs do not cover NHPs, regulated parties may use the GMP compliance information obtained under these programs and extend it to NHPs as long as the NHP complies with the regulations.

If you import an NHP that is manufactured, packaged and labelled in buildings that are inspected and authorized by a recognized regulatory authority under an MRA or PIC/S (including US FDA's dietary supplement inspections), you must:

• maintain a copy of the certificate of compliance for the foreign site
• certificates are valid for a period of 3 years from the date of the inspection

For each lot or batch of the product received, you may have a batch certificate in the format agreed upon in the International harmonized requirements for batch certification. This certificate can replace having the batch record to show the product meets its finished product specifications.

Before release, you are still required to review the documentation to ensure that:

• each NHP sold meets its specifications
• the NHP sold meets Canada's regulatory requirements

For products with medicinal ingredients that are quantified by input:

• the master production document must have been reviewed and approved by your QAP
  • remain informed of and approve any changes to the master production document as manufacturing and packaging processes may change over time
• a completed batch record from a lot imported must be reviewed periodically, such as once a year, to monitor that the quantification by input process is acceptable and under control by the manufacturer at the foreign site

Also, as an importer, you must still control testing reduction and exemptions or quantification by input (if used), as outlined in this guide.

If any licensable activity such as manufacturing, packaging or labelling is performed in a building not inspected by an MRA or PIC/S regulatory authority or the certificate is expired, the controls and testing requirements revert to those outlined in this guide once the product is received in Canada.

Quantification by input

Quantification by input means the quantity of a medicinal ingredient in the finished product is estimated from the amount that is added to a batch during manufacturing. The medicinal ingredient is not assayed (that is, it is not tested to confirm quantity) at the finished product stage.

Exemptions to testing a medicinal ingredient at the finished product stage may be acceptable if the manufacturer or importer can meet certain requirements. Refer to the Quality of natural health products guide for additional information on quantification by input.

As a manufacturer or an importer, regarding all your products with any ingredient being quantified by input, you must ensure that your QAP:

• for medicinal ingredients quantified by input:
  • has comprehensive raw material specifications to ensure adequate control of the medicinal ingredient's identity and quality before manufacturing
  • maintains and compares the certificates of analysis of raw materials to their specifications before use
• if more than 1 medicinal ingredient or if the medicinal ingredient is mixed with non-medicinal ingredients:
  • documents and describes how the batch homogeneity process is controlled

As a manufacturer or an importer, you must have batch records that include:

• objective evidence that the correct quantity of each ingredient is added to the finished product
• a description and calculation of the ingredient amounts in the finished product
• the target quantity for the medicinal ingredient (100% of the label claim)
• controls on weight variation or uniformity of the dosage units that can happen during tabletting, encapsulation or molding
  • when using average weight, a 5% variation from the target for individual dosage units (such as tablets, capsules or chewable gels) is generally acceptable
  • the variation may be higher if supported by a recognized pharmacopoeia (for example, USP <2091> Weight variation of dietary supplements allows higher variation for smaller dosage units and soft or hard shell capsules)
  • individual dosage weight variation or uniformity of dosage units does not apply to liquids and powders

You must also:

• document the controls in place during manufacturing to ensure the correct amount of each ingredient is added to achieve the labelled quantity per dosage unit
• ensure critical tests are conducted for every lot if required, such as for ingredients used to demonstrate batch homogeneity

GMP evidence

You must demonstrate GMP compliance for specifications with supporting evidence. The type of GMP evidence for specifications may vary. Examples of evidence include the following:

• relevant written procedures (SOPs) and associated blank record templates for finished product testing and specifications, including an assessment of the following:
  • raw materials against specifications
  • packaging or labelling materials against specifications
  • finished products against specifications, including a description of:
    • how finished product specifications are tested or controlled (for example, testing is product-specific, frequency of testing)
    • how to handle OOS results (including steps for when a product is tested on a rotational or reduced testing basis)
• written finished product specifications for all products to be manufactured, packaged, labelled or imported
  • all finished product specifications must be verified and approved by the QAP
  • changes to a finished product specification must be recorded and approved by the QAP
• certificate of analysis for each lot that demonstrates the product meets its specifications according to the requirements outlined in the Quality of natural health products guide, including:
  • certificate shows the same medicinal ingredients, including quantity and potency (when applicable), as the product licence
• documentation that products are tested according to their finished product specifications, including testing methods and acceptance criteria, where documentation (when applicable) is as outlined in these sections:
  • Microbial contaminants: Reduced testing
  • Chemical contaminants: Exemption to product testing before release
  • Medicinal ingredients: Rotational testing
  • Quantification by input
• finished product specification change control log
• evidence that testing is done at a suitable laboratory that adheres to good laboratory practices (GLP) or other comparable quality standards (the International Organization for Standardization (ISO), for example)

Premises (section 45)

Section 45

1. Every natural health product shall be manufactured, packaged, labelled and stored in premises that are designed, constructed and maintained in a manner that permits the activity to be conducted under sanitary conditions, and in particular that
   1. permits the premises to be kept clean and orderly;
   2. permits the effective cleaning of all surfaces in the premises;
   3. permits the natural health product to be stored or processed appropriately;
   4. prevents the contamination of the natural health product; and
   5. prevents the addition of an extraneous substance to the natural health product.
2. Every natural health product shall be stored under conditions that will maintain the quality and safety of the natural health product.

Intent

The premises where you manufacture, package, label and store NHPs must be designed and constructed to permit cleanliness and orderliness. Regular maintenance is required to prevent deterioration of the premises and to ensure products do not become contaminated through unsanitary conditions.

Manufacturer, packager, labeller, importer, distributor requirements

Depending on your activities, at every site, you must:

• ensure that all buildings are of adequate size and are designed and built to facilitate:
• maintenance, cleaning and sanitary operations
• prevention of entry of insects and other animals
• waste treatment and disposal
• designate separate production and non-production areas, as needed, to prevent cross-contamination
• clearly identify and segregate individual manufacturing, packaging, storage and testing areas
• ensure production areas are designed in a logical order, corresponding to the sequence of operations and to the requisite cleanliness level
• ensure production areas have a process flow that will prevent the finished product from becoming contaminated with raw materials
• ensure that effective controls are in place to minimize the potential for mix-ups or the chance that raw materials, packaging materials, and in-process and finished products can be adulterated
• protect raw materials, packaging materials, and in-process and finished products against physical, chemical and microbial contamination

Dried plants need to be stored properly to prevent fermentation or mould growth and prevent cross-contamination. Separate enclosed areas are recommended to quarantine incoming plants or herbals.

To prevent ingredient, product and container mix-ups (for example, transferring between the manufacturer and the labeller) and to minimize the risk to quality, you should:

• clearly mark (either physically or by using a controlled electronic system) and restrict access to authorized personnel in the following areas:
• quarantine or hold
• release
• destruction
• recall or return
• restrict, during production, the use of doors giving direct access from manufacturing and packaging areas to the outdoors and from non-production areas
• ensure that doors, windows, walls, ceilings and floors contain no holes, cracks or gaps, except those that are part of the design
• take measures to prevent contamination in all areas where raw materials, primary packaging materials, in-process products or finished products are exposed (to the extent required)
• ensure that floors, walls and ceilings permit cleaning, that all surfaces are smooth and made of non-porous materials, and that surfaces do not shed particles and permit effective and repetitive cleaning
• examples of porous materials are exposed wood or drywall, unsealed cement block or brick
• seal surfaces and joints to prevent product contamination and permit effective and repetitive cleaning
• ensure that floor drains are screened and trapped and the drains do not cause water to pool
• provide adequate ventilation and filtration to reduce dust and the potential for cross-contamination of components, in-process and finished products, and contact surfaces
• provide adequate lighting in all areas where production materials are examined, processed or held, or where contact surfaces are cleaned
• use shatter-resistant bulbs and fixtures to avoid contamination from broken glass
• control humidity and temperature, where required, to protect materials and products
• production and storage areas that have monitors or probes ensure that environmental controls accurately represent all areas and can identify where excursions may take place (for example, near a hot air or air conditioner outlet)
• an automated data monitoring system would alert you when environmental controls deviate

The various recognized pharmacopoeias (such as the USP) and other international standards provide definitions and descriptions of storage temperature terminology. This includes ambient temperature, room temperature and cold chain.

You should also:

• take appropriate measures to control, remove and prevent pests from entering the premises:
  • ensure doors and windows are adequately sealed
  • collect data on both crawling and flying pests found in your area
    • use appropriate pest control devices
    • perform a visual inspection of the premises
  • have a pest control professional review your pest control program to ensure that pest control devices and procedures are appropriate and adequate
  • install refuse receptacles and follow waste disposal practices that protect against contamination and don't attract pests
• dispose of sewage, refuse and waste in and out of buildings and the immediate surrounding area in a safe, timely and sanitary manner
• separate the break or rest areas, change rooms, washup and toilet facilities from production areas
  • these areas should have enough space to accommodate the activities performed, be well-ventilated and permit good hygiene practices
• ensure plumbing is appropriately designed and sized that it does not drip, leak or create condensation, and thus potentially adulterate products or contaminate water supplies or equipment
• ensure the water supply is of potable quality for processing and cleaning
  • refer to the water supply section
• identify any outlets for liquids and gases used in production
• maintain the grounds around the manufacturing buildings and keep areas in and around the buildings tidy
• limit pesticide use to non-production areas
  • take precaution to prevent contamination when rodenticides, insecticides and fumigation agents are used

Water supply

Use potable water that is supplied at a suitable temperature and, as needed, pressure. Your plumbing system must be in a good state to protect against contamination or undesirable chemical reactions.

The water supply must meet at least 1 of the following guidelines:

• Canadian drinking water guidelines
• Guidelines for drinking-water quality set by the World Health Organization (WHO)
• standard specified by the regulatory agency governing the manufacturer

When purified water is required for cleaning, use calibrated water purification, storage and distribution equipment.

Always assess if water is a component in an NHP (for example, when water contacts components, in-process and finished products or any contact surface). If it does, ensure the water quality will not negatively affect the quality of the NHP over its designated shelf life.

For water used in the manufacturing process that is treated by the manufacturer to achieve a defined quality, use appropriate criteria to qualify and monitor the treatment process.

Water from a private source that may be used in the NHP must comply with any provincial and municipal requirements, and not contaminate the product. To satisfy this requirement, you may have to perform appropriate water treatment procedures, including filtration, sedimentation and chlorination.

Municipal and public water distribution systems

Establishments often use water from locally or municipally controlled water sources. You should keep a record of the analysis results for source water from the municipality. Water that has been treated by a municipality is usually of high quality before it enters the distribution system. However, the microbial and chemical constituents of the water can vary.

Municipal and public water quality may deteriorate for many reasons. For example:

• the water is disinfected but not sterilized
• plumbing materials are not 100% inert
• cross-connections and line breaks to the piping in the distribution system or in the establishment can contaminate water
• compounds such as calcium carbonate and iron may precipitate and thus provide the conditions for organisms to grow

If a municipality's water safety or quality is unacceptable, the local public health unit or other responsible authority may issue advisories. This includes boil water or water safety alert or drinking water advisories. You should have measures in place, such as a subscription to an email or phone distribution list, for receiving notifications when there is a municipal water treatment failure and water advisory.

You are responsible for making sure the municipal water supply meets requirements once it reaches the establishment. For guidance, consult:

• Canadian guidelines for food processing during adverse water events

GMP evidence

You must demonstrate GMP compliance for the premises with supporting evidence. The type of GMP evidence for premises may vary. Examples of evidence include:

• relevant written procedures (SOPs) and associated blank record templates for maintaining premises, such as:
  • prevention of contamination and cross-contamination of NHPs
  • storage conditions of raw materials
  • storage conditions of finished products
  • pest control
• detailed floor plan of production, non-production, quarantine, packaging, labelling areas
• daily records (includes weekends and statutory holidays) noting temperature, relative humidity and light control (as needed) for storing raw materials, packaging materials, and in-process and finished products. These records serve to:
  • allow the QAP to confirm that the results of the environmental control monitoring are within all products' storage requirements (ranges should be based on, for example, valid scientific data, monographs, pharmacopoeial sources)
  • document and investigate results that deviate from the requirements, and corrective actions taken to ensure that product quality has not been impacted
  • document the maintenance and calibration for environmental control devices, when applicable
  • allow the QAP to verify the environmental control data record
• pest control inspection report (internal or third party) that includes:
  • information on where pest control devices are located (we recommend a floor plan with a legend)
  • pest control inspection schedule giving date and time of each inspection, identifying people performing the inspection, indicating trap replacements and any investigations and outcomes when pests are identified
  • pest control record and corrective actions taken by the QAP
• janitorial duty schedule and cleaning completion records for each area (for example, manufacturing, packaging, labelling, storage areas)
  • refer to the sanitation program section
• facility inspection and maintenance records (for example, wall, floor or ceiling repair, caulking replacement, door sweep installation, new drain grates)
• ventilation maintenance records (as applicable), including inspection schedule, filter replacement and periodic monitoring of pressure differentials
• water quality test records (for manufacturers and packagers)

Equipment (section 46)

Section 46

Every natural health product shall be manufactured, packaged, labelled and stored using equipment that is designed, constructed, maintained, operated and arranged in a manner that

1. permits the effective cleaning of its surfaces;
2. permits it to function in accordance with its intended use;
3. prevents it from contaminating the natural health product; and
4. prevents it from adding an extraneous substance to the natural health product.

Intent

These requirements are meant to prevent NHPs from being contaminated by:

• lubricants
• other products
• cleaning agents
• foreign materials, such as:
  • rust
  • dust
  • particles coming from the equipment

Contamination problems may arise from different sources, such as:

• poor maintenance
• equipment misuse
• use of worn-out equipment
• inadequate cleaning practices
• equipment capacity exceeded

Equipment arranged in an orderly manner permits effective cleaning and does not interfere with other processing operations. It also minimizes the circulation of personnel and optimizes the flow of materials.

Manufacturer, packager, labeller, importer, distributor requirements

Depending on your role, as applicable, you must:

• ensure production equipment and utensils that have direct contact with materials and products are constructed of smooth, non-reactive and non-toxic materials
  • should be designed for the environment in which they are used and to withstand repeated cleaning or be single-use (disposable)
• ensure production equipment is designed, constructed, installed and maintained so they can be cleaned, sanitized (if applicable) and inspected (inspection includes the surrounding area):
  • establish and follow procedures for cleaning and maintaining equipment and utensils used to manufacture products
    • clean between production runs of different products (including drug or cannabis products) or different batches of the same product for any shared equipment
    • establish processes to identify, store and protect clean equipment to avoid contamination
  • repair faulty equipment in a permanent and durable way and avoid using things like tape or carboard to make temporary repairs
  • label clearly or remove defective equipment
  • have enough distance around equipment to permit proper cleaning
  • make sure equipment is accessible to be disassembled for cleaning, maintenance or inspection
• ensure production and laboratory equipment is operated, maintained and calibrated according to its written procedure (SOP)
  • must be suitable for their intended use (“fit for purpose”)
• protect analytical instruments and associated control systems from vibration, electrical interference and contact with excessive moisture or other external factors
• avoid the possibility of foreign or maintenance materials contaminating the products by:
  • ensuring tanks, chain drives, transmission gears and other similar manufacturing equipment are enclosed or properly covered
  • locating or placing equipment to prevent cross-contamination or possible mix-ups
  • protecting in-process and finished products against contamination from lubricants and other external sources (for example, grease, oil, leaking gaskets)

Importers and companies with storage-only facilities may not use the same type of equipment as manufacturers, packagers and labellers. However, they still need to use, maintain, calibrate and clean any equipment that is critical to preserving the quality of a product, such as environmental controls, fridges, freezers and lifts.

Equipment suitability

The NHP industry uses equipment ranging from a utensil or simple apparatus to complex computerized systems. Equipment needs to be “fit for purpose”, which means it must meet the requirements of what a user expects and what it's designed for. For example, the range, precision and accuracy of a balance should be appropriate for its use, and calibration records should be maintained.

In general, the more complex the equipment or the more critical it is to assure the quality of the product, the more important it is to ensure its “fit for purpose”.

The requirements for how a piece of equipment should be used must be defined to help meet user, technical and operational needs.

Determining “fitness for purpose” can be as simple as documenting your review of the manual of a piece of equipment and making sure the equipment operates as intended.

Follow your change control (CC) process when any equipment undergoes major repairs or modifications and take steps to verify the equipment continues to operate satisfactorily. If you move equipment to another location, consider the impact of the change on the equipment and make sure it continues to operate properly.

Any repair or maintenance operations must not present any hazard that will affect the quality of the product. For example, consider the location of the repairs relative to materials and finished products.

Equipment calibration

When manufacturing, packaging, labelling or storing NHPs, use equipment as it's meant to be operated. Calibrate equipment according to written procedures (SOPs), its intended use and an established schedule. Use recognized pharmacopoeial reference standards or those traceable to certified standards, if available, when calibrating.

Even with an established calibration schedule, some equipment may require supplemental calibration. For example, a balance may need re-calibrating if it's bumped or moved during cleaning or during daily operations. An appropriate standard weight (for example, represents the weight of the materials that will be on the balance) should be used to ensure the balance is still working as expected.

Investigate deviations from approved standards of calibration on critical instruments. This will determine if there was an impact on the quality of products using this equipment since the last successful calibration. Repair or replace any equipment that cannot be adjusted to agree with the reference standard.

For guidance on equipment cleaning and sanitizing, refer to the sanitation program section for more information.

GMP evidence

You must demonstrate GMP compliance for equipment with supporting evidence. The type of GMP evidence for equipment may vary. Examples of evidence include:

• relevant written procedures (SOPs) and associated blank record templates for the functioning, maintenance and calibration of equipment
• calibration records for equipment that requires it according to its function, including automatic, mechanical, electronic and measuring devices
  • provide proof of the calibration standard or reference being used
• equipment usage, cleaning and maintenance logs
• preventive maintenance schedule or program for all equipment that includes:
  • information on where equipment requiring maintenance and calibration is located
  • instructions on how to maintain and calibrate the equipment or where to find the corresponding written procedure (SOP), including:
    • frequency of such activities
    • measures to be taken if equipment does not function as intended
    • individuals who are responsible for maintenance and calibration
    • external companies that conduct such activities, if applicable

Air ventilation and filtration systems, purified water production systems, and temperature and humidity controls are examples of equipment that must be calibrated, maintained and cleaned. However, they are often overlooked when creating processes and written procedures (SOPs).

Personnel (section 47)

Section 47

Every natural health product shall be manufactured, packaged, labelled and stored by personnel who are qualified by education, training or experience to perform their respective tasks.

Intent

Whom you hire is one of the most important elements in any NHP operation. Knowledgeable and well-trained personnel are needed to manufacture, package, label and store high-quality NHPs. Employing qualified personnel to supervise these activities is also important.

Without staff that have a quality mindset and are properly trained, it's almost impossible to make or store high-quality NHPs.

Requirements for manufacturers, packagers, labellers, storers (as well as importers, distributors responsible for storage or transportation)

Your senior or executive management is responsible for providing adequate resources (materials, personnel, facilities and equipment). As a manufacturer, packager, labeller and storer (including as an importer or distributor responsible for storage or transportation), you must:

• ensure enough personnel with the required qualifications and practical experience relevant to their responsibilities on-site
• not place so many responsibilities on any 1 person such that quality is at risk
• ensure personnel conducting GMP activities understand the written procedures (SOPs) for those activities
• ensure personnel have the authority to carry out their responsibilities
• record specific duties for all responsible staff in a written work description and maintain a list of written procedures (SOPs) for each position

A training matrix that outlines the written procedures applicable to each position can help to ensure all personnel are trained on the SOPs that affect them. The matrix can also be a quick reference to identify who needs to be re-trained when SOPs are revised.

You must also:

• follow a written training program (that is, a training SOP) and use qualified trainers to train personnel (including technical, maintenance and cleaning staff)
• ensure personnel have the education, training or practical experience to perform their assigned duties
• ensure personnel are aware of the principles of GMP, including good documentation practices, that affect them
  • they should receive initial and ongoing GMP training relevant to their job responsibilities
  • ongoing GMP training should be conducted according to an established schedule (for example, annually or bi-annually) and when changes are made to the GMP regulations or personnel require refresher training after a long leave (for example, parental leave) or performance deficiencies

Sometimes legislation, regulations or Health Canada guidance documents change. Provide your personnel with the most up-to-date training in Canadian NHP GMP requirements.

You must also:

• provide training on written procedures (SOPs) before implementing new or revised versions (for example, when changes to equipment or processes are made)
• give specific training to personnel working in areas where highly active, toxic or sensitizing materials are handled
  • they should have access to relevant information (for example, safety data sheets) and personal protective equipment (PPE)
• appoint qualified replacements to carry out their duties and functions when key personnel are absent
• maintain records of education and training for all personnel, including management, involved in handling NHPs and update the records when needed

Maintaining copies of resumés in addition to their records of GMP and SOP training helps to build a complete record of each employee's qualifications.

You must also:

• assess the effectiveness of training by reviewing personnel performance periodically
• personnel must have both initial and ongoing training to ensure they stay up to date on changes to written procedures (SOPs) and regulatory requirements
• confirm that consultants and contractors have the necessary qualifications, training and experience to complete the tasks they were hired to do
  • for example, a consultant could be hired to act as your QAP (with product release responsibilities), which means they would need to meet the qualifications laid out in this guide (section 51)
  • keep their resumé on file

Only qualified staff can supervise the manufacture of NHPs. These operations are often technical in nature and require constant vigilance, attention to detail and a high degree of competence. Products often fail to meet required standards when staff are poorly trained or do not understand the importance of production control.

The persons in charge of your QA department (your QAP) and of your production department must:

• have the education, training or practical experience to control or supervise the activities
• supervise each working shift that involves activities under their control
  • the person in charge can be off-site if they are fully accessible and have enough knowledge of the on-site operations to do their job
• delegate duties and responsibilities when needed (for example, to cover all shifts) to a person who is qualified while still being accountable for those duties and responsibilities
  • the designated person (that is, the QAP designate) must have the relevant education, training or practical experience
  • in this guide when we say QAP, it means the QAP or one of their designates
  • refer also to QAP training, experience and technical knowledge under section 51 in this guide

Companies must demonstrate how decisions made by the QAP are independent from other business decisions. A QAP who holds additional responsibilities within a company must still follow established written procedures (SOPs) and make decisions that are not influenced by their other company obligations, especially decisions that could impact financial gains. For example, when the QAP is also a company executive, a returned damaged product should be actioned as outlined in the relevant SOP. The QAP should not accept or justify the result and then return the damaged product to saleable stock.

GMP evidence

You must demonstrate GMP compliance for personnel with supporting evidence. The type of GMP evidence for personnel may vary. Examples of evidence include:

• relevant written procedures (SOPs) and associated blank record templates related to the appropriate education, training and work experience for all personnel
• job descriptions that outline the role and responsibilities of the position
• list of qualified designates
• resumé, copy of educational degrees that show the person meets their job description
• certificates of completed training that relate to the person's assigned duties and responsibilities (such as GMP training)
• employee training schedule or attendance records that demonstrate initial and on-going relevant training