Draft good manufacturing practices guide for natural health products: NHP GMP guidance, sections 48 to 50

On this page

• Sanitation program (section 48)
• Operations (section 49)
• Operations (section 50)

Sanitation program (section 48)

Section 48

Every natural health product shall be manufactured, packaged, labelled and stored in accordance with a sanitation program that sets out:

1. procedures for effectively cleaning the premises in which the activity is conducted
2. procedures for effectively cleaning the equipment used in the activity
3. procedures for handling any substance used in the activity and
4. all requirements, in respect of the health, the hygienic behaviour and the clothing of the personnel who are involved in the activity, that are necessary to ensure that the activity is conducted in sanitary conditions.

Intent

Sanitation of a building, as well as employee hygiene, influence the quality of NHPs. The GMP requirements under the regulations indicate to perform activities in areas that are free from:

• environmental contamination
• contamination by another product

A written sanitation program lays out the expectations and necessary steps to ensure sanitation is maintained. It also assures employees that levels of cleanliness in the plant are upheld.

Manufacturer, packager, labeller requirements

You must have a sanitation program for the facility and a health and hygiene program for employees as outlined in this section.

Importer, distributor responsible for storage or transportation requirements

You must have a storage area cleaning program (should include a suitable sanitation program).

Facility sanitation program

A written sanitation program that will prevent a product from being contaminated should include:

• cleaning procedures and specific cleaning activities or tasks for facilities, production and storage areas, and for processing equipment and utensils
  • consider all surfaces such as floors, walls, ceilings, work surfaces, light fixtures and ventilation filters
• a list of cleaning and sanitizing agents and pesticide chemicals
  • should be identified, used and stored to prevent contamination
• procedures for:
  • maintaining and cleaning equipment, including assigning responsibility for this
    • indicate how often equipment and lines between the production of different products or same product should be cleaned
  • verifying a production area has been sanitized before it is used and for manufacturing, packaging and labelling equipment
  • destroying and disposing of waste materials and debris
  • identifying and separating dirty and clean equipment and utensils
• provisions for:
  • protecting raw and packaging materials against contamination and cross-contamination
  • storing cleaned equipment to avoid recontamination
  • containing or ventilating dusty operations to prevent other areas from being contaminated (if applicable)

Health and hygiene program

Make sure that the following personnel follow appropriate practices to protect products against contamination:

• those who are in direct contact with raw, packaging and in-process materials and unpackaged products
• those who use processing equipment

A written health and hygiene program should indicate that you have to:

• wear:
  • intact, clean and sanitary gloves made of impermeable material when there is a potential for raw equipment, primary packaging components, in-process and finished products or equipment contamination
  • hairnets, caps, beard covers or other effective hair restraints when working with exposed materials or products
  • face masks in production and packaging areas when working with exposed materials or products
  • outer garments, including shoe coverings, that protect against contamination of products and equipment, when applicable
• remove:
  • cosmetics that may come in contact with raw, finished and packaging materials, and process equipment when working in the production area
  • unsecured jewellery, hand jewellery and other objects that might fall off, when applicable
    • hand jewellery that cannot be removed may be covered with a material that cannot move, is clean and is in sanitary condition
• maintain personal cleanliness
• wash hands thoroughly before starting work and at any other time when they may become soiled or contaminated
• store clothing or other personal effects outside of processing areas
• do not consume food and drink, chew products or smoke in manufacturing, packaging, labelling, storage and testing areas

The program should also indicate that you should:

• conduct periodic eye examinations of personnel responsible for visual inspection
• respect quarantine times imposed by public health authorities
• report to supervisors anyone who has a health condition that could adversely affect the manufacturing facility and remove anyone who has or appears to have:
  • an illness (including fever, coughing and sneezing)
  • an infection
  • an open lesion
  • any other source of microbial contamination
    • these could be contaminated materials or products
    • person should not be allowed back until the disease or hygienic condition no longer poses a risk
• take necessary precautions to protect against allergen cross-contact and contamination with microorganisms, allergens, filth, foreign substances or other extraneous materials, such as:
  • hair
  • tobacco
  • cosmetics
  • chemicals
  • perspiration
  • personal medicines

Equipment cleaning and sanitizing

Establish written procedures (SOPs) for cleaning equipment that’s used in the manufacturing of your products. Include enough details so operators can clean the equipment easily and effectively.

Include the following in your procedures:

• personnel responsible for cleaning equipment
• cleaning schedules
• sanitizing schedules (if applicable)
• full description of the methods and materials, including dilution of cleaning agents, used to clean equipment
• instructions for:
  • disassembling and reassembling each part of equipment to ensure proper cleaning (if applicable)
  • removing previous batch identification
  • protecting clean equipment from contamination before use
  • inspecting cleanliness of equipment immediately before use
  • identifying equipment reserved for handling contaminated materials or waste
• procedure for evaluating and confirming the efficacy of the equipment cleaning process

Tip: Always consider the materials used in your facility even when they don’t come directly into contact with your products. Materials should be easy to clean repeatedly. For example, use plastic or metal shelves and pallets, not wooden ones.

Clean primary contact surfaces for manufacturing and filling equipment in a way that consistently ensures there is no visible product or cleaning agent residues. Protect all equipment from contamination and keep it clean and dry. For susceptible products, you should control the level of microbial contamination and ensure there are no objectionable microorganisms.

Clean and, if applicable, sanitize all contact surfaces before use and after any interruption where there’s a possibility it may have become contaminated.

In consecutive operations:

• for batches of different NHPs, adequately clean and sanitize (if applicable) the contact surfaces to prevent cross-contamination
• for different batches of the same product, inspect and adequately clean the contact surfaces to prevent buildup and carry-over of contaminants

Also clean when necessary any surfaces that do not come into direct contact with components, in-process or finished products.

Ensure methods to detect residues or contaminants in evaluating cleaning are proven accurate and consistent:

• Demonstration of consistency should include a satisfactory analytical evaluation of parameters such as accuracy, precision and linearity for multiple tests of samples with known properties.

Use effective systems to reduce the potential of non-contact surfaces from becoming sources of contamination. For example, use floor sticky pads between different production areas and have in place a captive shoe policy. 

Make sure the cleaning status of equipment is stated on the equipment.

Contact surfaces used for manufacturing or holding low-moisture components, in-process or final products must be clean, dry and sanitary before use. For surfaces that are wet-cleaned, sanitize (if applicable) and thoroughly dry them before subsequent use. If wet processing is used during manufacturing, clean and sanitize (if applicable) all contact surfaces to protect against the introduction of microorganisms.

Store single-use (disposable) articles (such as utensils intended for one-time use, paper cups, and paper towels) in appropriate containers. Handle, dispense, use and dispose these articles in a manner that protects against contamination of components, in-process and final products or any contact surface. Clean, sanitize and store portable equipment and utensils that have contact surfaces in a manner and location that protects them from contamination.

Cleaning compounds, sanitizing agents, pesticides and other toxic materials

Cleaning compounds and sanitizing agents must be:

• suitable for their intended use
• safe under their conditions of use
• free from undesirable microorganisms

There is no guidance that indicates which cleaners you should use. However, use food-grade cleaners on any surfaces that may come in contact with raw materials and in-process and final products. The QAP should evaluate all cleaners to ensure they do not present a risk of contaminating materials and products.

All toxic materials that you purchase should have a safety data sheet and supplier’s guarantee or certification. Do not use or keep toxic materials where components, materials, in-process and final products, and contact surfaces are manufactured or exposed. The exception are materials required to:

• maintain clean and sanitary conditions
• conduct laboratory test procedures
• maintain or operate the facility or equipment used in your operations

Identify, handle and maintain toxic materials in a manner that protects against contamination of components, materials, in-process and final products, and contact surfaces. Follow all relevant federal, provincial and local government regulations for using and holding these toxic materials.

You may use pesticides, such as insecticides, fumigants, fungicides or rodenticides. Remember to:

• take precautions to protect against the contamination of components, materials, in-process and final products, and contact surfaces
• choose pesticides that are registered and use in accordance with the Pest Control Products Act
• follow provincial or territorial and municipal rules on pesticide use

Learn more:

•  Pesticides and pest management: Frequently asked questions

Substances associated with the operation of equipment (such as lubricants, heating fluids or coolants) must not come into contact with materials and in-process and final products. This would alter the quality of the materials or products beyond established specifications. If there is contact, you should evaluate any deviations to ensure the material or product can still be used.

Use food-grade lubricants and oils when there’s a risk of direct or indirect contact between a substance and an NHP material or product. An example would be the lubricants used for the tabletting press during the compression of tablets.

GMP evidence

The type of GMP evidence for a sanitation program may vary. However, all the requirements stated in this section must be supported by evidence that demonstrates GMP compliance for sanitation programs. Examples of evidence include:

• relevant written procedures (SOPs) and associated blank record templates for a sanitation program that include the following elements:
  • cleaning premises, production and storage areas, and equipment, with information on:
    • areas to be cleaned (for example, equipment, production line, rooms)
    • cleaning methods (for example, wet or dry mopping, dusting)
    • tools to be used and cleaning and maintaining the cleaning tool
    • cleaning agent to be used (including any dilution specifications) and expiration date advice
    • cleaning frequency for each task (for example, batch-specific, daily, weekly, monthly)
    • procedures to prevent cross-contamination between any equipment and utensils to be shared between NHPs and other substances (for example, pharmaceutical drugs, cannabis), if applicable
    • procedures for destroying and disposing of waste materials and debris (including expired or rejected materials and products and recalled or returned products)
  • health and hygiene program (including verification to ensure employees are correctly applying the procedures)
• approved facility cleaning schedule and cleaning completion logs that:
  • identify the personnel responsible for both cleaning and verifying the cleaning by signing and dating all log entries
  • describe what is being cleaned
  • identify the cleaning frequency for each task (for example, batch-specific, daily, weekly, monthly)
    • include an explanation when a cleaning task does not take place as per its intended frequency
  • verify the sanitation record by the QAP, with any changes that may affect the cleaning process documented
• personnel hygiene training log
• list of approved cleaning and sanitizing agents for the facility (must be suitable for their intended use and not pose a contamination risk)

Tip: Cleaning logs must reflect the procedures that are outlined in the sanitation written procedures (SOPs). Include cleaning log templates in the appropriate SOPs and the relevant parts of a sanitation log in the batch production record (for example, equipment cleaning and verification of sanitation before use).

Operations (section 49)

Section 49

Every natural health product shall be manufactured, packaged, labelled and stored in accordance with standard operating procedures that are designed to ensure that the activity is conducted in accordance with the requirements of this Part.

Intent

The regulations require that measures be taken to maintain the integrity of an NHP. This ranges from when raw materials enter the facility to the time the finished dosage form is released for sale and distributed.

Manufacturer, packager, labeller, storer and importer or distributor responsible for storage or transportation requirements

Make sure that practices and procedures are in place, as applicable, for:

• material control
• process control
• evaluating contracted parties (where applicable)

Manufacturer, packager, labeller requirements

The activities of manufacturing, packaging and labelling require controlling:

• raw materials
• in-process materials
• bulk products
• packaging and labelling materials
• manufacturing, packaging and labelling operations

Make sure that practices and written procedures (SOPs) are in place and up to date for both material and process control.

Transporting, handling and storing raw, packaging and labelling materials

Develop a written procedure (SOP) for transporting, handling and storing raw, packaging and labelling materials. Include in the SOP:

• sanitary specifications for conveying materials, including specific design specifications (for example, temperature control) and cleaning procedures
• vehicles and transportation equipment with adequate temperature control to prevent materials from becoming spoiled, contaminated or damaged during transportation and to keep out pests
• precautions to ensure frozen materials transported with dry ice do not come into contact with the dry ice, which may affect the material’s quality
• packaging or separating to protect materials from being contaminated by other articles in the same load
• a strictly controlled or electronic inventory system for materials that are quarantined and kept separate from approved goods before they are used in manufacturing
• appropriate conditions, including temperature and humidity, for storing materials to ensure they do not deteriorate or become contaminated
• competent supervisory personnel are in place to ensure that transportation and storage operations are carried out adequately
• personnel engaged in preparing products for transport (including those loading and unloading shipments) are trained in procedures designed to preserve the quality of materials during transportation
• records on transportation requirements, including agreements, procedures, maintenance, cleaning, temperature control and training records

Receiving, examining and identifying raw, packaging and labelling materials

Develop a written procedure (SOP) for receiving, examining and identifying raw, packaging and labelling materials. Include in the SOP:

• visual inspections of shipments (trucks and containers) for appropriate content, container damage or broken seals to determine if container condition has caused the materials to be contaminated or become deteriorated
• verification that the temperature of refrigerated trailers is correct before unloading
• inspections of containers of materials received for closure and physical integrity
• identification of each lot of raw, packaging or labelling material with a distinctive lot number, along with date received, name of material and status (quarantined, approved or rejected)
  • the lot can be traced to the supplier
  • differentiate the same lot of a material that is received in multiple different shipments to make it easier to trace
  • adding a sequential number to the lot number helps (for example, Lot #12345-1, Lot #12345-2)
• confirmation of the supplier’s invoice, guarantee or certification for each shipment to ensure the materials are consistent with the purchase order

Sampling, testing and approving or rejecting raw, packaging and labelling materials

Develop a written procedure (SOP) for sampling, testing and approving raw, packaging and labelling materials. Include in the SOP methods or procedures for:

• identifying and controlling each lot of materials according to its quality status (such as quarantined, approved or rejected)
• assessing each lot of material against specifications (such as appearance, identity and composition)
• setting a time limit beyond which materials that are subject to deterioration may not be used in production without additional testing
• retesting materials after they have been exposed to conditions that may affect their purity, quality or composition
  • could include temperature excursions during transportation, extended periods of time in storage or extended exposure to light or humidity
• review and approval by the QAP of the results of any tests or examinations conducted on the materials
• releasing the materials from quarantine by the QAP for use in manufacture, packaging or labelling

Tip: Water added to the product is also a raw material. Establish appropriate systems and controls to ensure that water used in production is of appropriate quality. Refer to the water supply section for more information.

Manufacturing the bulk and finished product

Develop a written procedure (SOP) for manufacturing the bulk and finished product. Include in the SOP:

• a master formula for the product to ensure that it adheres to regulatory requirements and claims
  • includes the strength and potency stated on the label and the product licence
• a master production document for each product
• batch records for each batch of product
  • must accurately reflect the master production document
  • indicate that each significant step in the manufacturing process was completed

Note: The manufacturing section of a master production document is a template for the batch record. It includes the master formula, manufacturing instructions and in-process controls, a list of equipment to be used and timelines for significant steps in manufacturing. Refer to the glossary for a full description of a master production document.

Batch records (manufacturing section)

Record the details of each batch processed at the time of its actual manufacturing in a batch record that has its own unique number. Make sure the batch record reflects the currently approved master production document.

Prepare and verify the batch record (this is a task for qualified personnel). Include the following information:

• name and batch or lot number of the product
• dates and times when manufacturing operations and any significant intermediate stages were started and completed
• a list of the raw materials and quantity required for each to achieve the expected batch size
  • document and verify the calculations made to determine required quantities
• batch number and quantity of each raw material actually weighed and dispensed
• equipment and processing lines used to produce the batch
  • give enough details to make it easy to trace the usage, maintenance and cleaning records for each piece of equipment and processing line
• name or identifier of each operator who performed each significant step of the process and the person who checked these steps
  • for manual operations, significant steps may include:
    • weighing or measuring each ingredient
    • adding the ingredient to the batch
    • recording steps requiring specific times
    • recording temperatures or speeds
    • recording any other steps critical to producing a consistent product
• results of quality checks done at appropriate stages of the process and the person who did the checks
• batch yields at appropriate stages of processing, as required, and final yield
  • explain any deviations from an expected yield
  • determine and document an acceptable range for the final yield
• notes on problems, including details of any deviation from the manufacturing instructions
  • provide written approval by qualified personnel, including the QAP
• signature of the person responsible for the processing operations

Note: If you use documents in your company that are not written in English or French, make sure that:

• processes are clear and controlled
• your staff has access to documents they can read and understand

Documents requested by Health Canada must be provided in either English or French. For more information, refer to the translation of records into English or French section.

Packaging and labelling the finished product

Develop a written procedure (SOP) for packaging and labelling the finished product. Include procedures for:

• preparing, reviewing and approving a master document (packaging order)
• completing records for each product batch to reflect the currently approved master document
  • document that each significant step in the packaging and labelling operation was completed
• identifying equipment and packaging and labelling lines
  • lines for packaging different products should be properly separated and, if necessary, dedicated
• issuing packaging materials for use only by authorized personnel and ensuring label control and reconciliation
• destroying and disposing outdated or obsolete material, unused printed packaging and rejected materials
• making sure that work areas, packaging and labelling lines, printing machines and other equipment are clear of products, materials or documents previously used if these are not required for the current operation
  • use a checklist to document the line clearance
• overseeing the printing of lot numbers and expiry dates, with special attention paid to printing done by hand
  • check it regularly
  • make sure printed and embossed information on packaging materials is distinct and will not fade or erase

Label control and reconciliation

Develop a written procedure (SOP) for label control and reconciliation. Your procedure should include the following activities:

• attach samples of the printed packaging and labelling materials used to package orders
  • include specimens that have the lot number, expiry date and any overprinting
• label right after filling and sealing
  • have measures to ensure that no mix-ups or mislabelling will occur if labelling is delayed
• destroy unused batch-coded materials and record their disposal after packaging and labelling is done
  • follow a procedure if non-coded printed materials are returned to stock
• destroy outdated or obsolete packaging and labelling materials and record their disposal
• compare the amount of printed packaging and labelling materials issued to the line with the number of units packaged during reconciliation
  • investigate and account for any discrepancy before releasing the materials
• make sure printed packaging and labelling materials are:
  • stored in an area with access restricted to designated personnel who are supervised by qualified personnel
  • withdrawn against a packaging order
  • issued and confirmed to match approved master copies by qualified personnel
  • identified in a way that makes them distinguishable during operations
• use roll-fed labels instead of cut labels to prevent mix-ups and avoid printing more than 1 type of label on a sheet of material
  • automated electronic verification can be used to preventing mix-ups
  • conduct checks to ensure that any electronic code readers, label counters or similar devices are operating properly
• take special care when using cut labels, carrying out overprinting off-line and in hand-packaging and labelling operations
  • have 1 operator conduct a full-scale check of during or after labelling operations
  • have a second operator independently verify this
• check and record the performance of any printing (such as the printing of lot numbers and expiry dates) to ensure it’s correct
• identify every package by a unique lot number and an expiry date

For information on labelling NHPs and complying with Canadian requirements, consult:

• Guidance document: Labelling of natural health products

It’s not only valuable to labellers and product licence holders, but also for importers, to evaluate product labels for compliance with Canadian requirements.

Batch records (packaging and labelling section)

Record the details of each batch processed when packaging and labelling a uniquely numbered batch record. Make sure the batch record is based on the currently approved master production document. Qualified personnel must prepare and verify the batch record.

Include the following information:

• name and batch and lot number of the product
  • include the natural product number (NPN) to help identify the product
• dates and times when packaging and labelling began and ended, and any significant intermediate stages
• quantity, lot number or analytical control number of each packaging and labelling material and bulk NHP issued
• equipment and packaging and labelling lines used
  • give enough detail so that their usage, maintenance and cleaning records can be traced
• an actual or representative label, or a cross-reference to the physical location of the actual or representative label specified in the master document
• names of the personnel who are supervising packaging and labelling operations and the withdrawal of the bulk NHP
• name of the operator who performed each significant step and the person who checked these operations:
  • verification of labels
  • line clearance
  • withdrawal of the bulk NHP
  • verification of the lot number and expiry date
  • recording of specific times, temperatures or speeds
  • label reconciliation
• checks for identity and conformity of the packaging and labelling
  • including the results of in-process controls
• verification that online printing (such as the printing of lot numbers and expiry dates) is correct
• verification of the proper functioning of line monitors, electronic imaging or vision systems
• how precautions applied to a partly packaged product are handled
• notes on any special problems, such as:
  • details of any deviation from the packaging and labelling instructions (with written approval by qualified personnel, including the QAP)
• the quantity of finished product obtained
• reconciliation of the quantity of printed packaging and labelling material and bulk NHP used, destroyed or returned to stock
• signature of the person responsible for the packaging and labelling operations

Tip: A review of completed batch records should be part of your QAP’s finished product release procedure and done when you review the finished product test results.

Importing and distributing

Although not specifically set out in this regulation, importers and distributors are often responsible for transporting and storing finished products. Manufacturers, packagers, labellers, importers and distributors are responsible for ensuring products are stored in accordance with up-to-date practices and written procedures (SOPs).

Transporting and storing finished product

Develop a written procedure (SOP) for transporting and storing the finished product.

Include information for:

• conducting transportation and storage operations according to appropriate sanitation principles
  • perform these operations in a manner that protects against adulteration and in conditions that minimize the potential for contamination
  • consider worst-case scenarios, including seasonal fluctuations
• maintaining and equipping, as necessary, conveyances to provide adequate temperature control
  • will prevent materials from becoming spoiled, contaminated or damaged during transportation and prevent the harbouring of pests
• taking precautions to ensure frozen products transported with dry ice do not come into contact with the dry ice
  • may affect the quality of the product
• assigning competent supervisory personnel to ensure that transportation and storage operations are carried out adequately
• training personnel responsible for transportation and storage in procedures that maintain the quality of products
• outlining all necessary specifications for the carrier's vehicle and transportation equipment
  • include specific design specifications (for example, temperature control or monitoring using calibrated devices) and cleaning procedures
• maintaining records on transportation requirements, including agreements, procedures, maintenance, cleaning, temperature control and training
• quarantining products from approved products
  • separated physically or through a strictly controlled physical or electronic inventory system
• storing products in appropriate conditions, including temperature and humidity, to protect against quality deterioration and contamination
• identifying all products, samples, containers and major equipment at all times regarding their contents and status
• ensuring adequate procedures are in place to:
  • prevent extraneous materials from being included in the products
  • identify, store and dispose of rejected or contaminated or adulterated products
• establishing written procedures (SOPs) for accepting or rejecting reprocessed batches
• investigating significant or unusual discrepancies observed during reconciliation of the product
• using correct labels and packaging materials
• identifying each package with a lot number and expiry date to make it easy to determine the history of the manufacture, packaging and labelling, and control of the lot
• restricting access to storage areas to authorized personnel
  • access can be restricted by locks, passcodes, alarms, guards or other means
• ensuring that activities contracted out to other sites meet the GMP requirements
  • this can be demonstrated by inspecting or evaluating the contractor

Standard operating procedures (SOPs)

Standard operating procedures (SOPs) play a major role in a company’s quality assurance system. An SOP describes in detail the steps needed to complete tasks consistently.

Ensure your company’s SOPs describe how company operations comply with the GMP requirements and are:

• available to all required personnel
• up to date and reflect all requirements and practices
• reviewed regularly by qualified personnel

Tip: Set up a regular schedule to review your SOPs (such as during annual self-inspection). Regular reviews help to identify Health Canada guidance updates, changes to internal and external contact information, and outdated practices. Keep a record of your reviews, even when the SOP does not require any updating. Also make sure to review and approve changes to SOPs, including the reasons for the revisions and ensure only current SOPs are in use.

At a minimum, a well-written SOP will contain the:

• company name
• SOP title
• document number
• version number
• page number on each page

Tip: Keep an up-to-date list of all your SOPs, including their SOP number, title and version number. When assigning SOP numbers, a coding system can be helpful. For example, the first issuance of the first SOP related to sanitation may be numbered as SAN-001-00. The “00” version number indicates this document has not yet been revised because it’s new. After its first approved revision, it would be numbered as SAN-001-01. When referencing other SOPs, refer to them without stating the version number. This way people will be using the current version.

Approval and effective dates:

• date of approval of the SOP is the date that it is approved by the QAP
  • includes their name, signature and date
• effective date is the date on which the SOP is put into use

Tip: The effective date is the date when everyone must use the new procedure. Leave enough time between the approval and effective dates so everyone who needs to use the SOP may be trained on it.

Also include in the SOP the following, as applicable:

• Scope: describes the purpose of the SOP and items that are not covered by the procedures
• Responsibilities: lists departments or job positions that must follow the SOP
• Materials: lists materials, equipment or devices needed to perform this activity
  • for example, detergents required to clean a particular piece of equipment
• Safety: any safety considerations specific to the task
  • for example, wear a mask
• Procedure: detailed steps to perform the activity in a consistent and repeatable manner, including illustrations or pictures and cross-references to other SOPs, as needed
  • for example, speeds, temperatures, measurements and time periods to be used
• List of attachments: any associated forms to be completed when an activity is performed
  • for example, equipment cleaning logs used to track cleaning details, including the personnel responsible and the date performed
• Revision history: date of revision, detail of changes and reason for revising the SOP
  • reference to related deviation reports or change control documents may also be included

Tip: Companies should create an SOP outlining how the company’s SOPs will be numbered, formatted, controlled, approved and stored. It's an SOP on SOPs.

Quality agreements (written agreements)

A quality agreement (written agreement) is a formal document between 2 or more parties outlining the specific GMP duties and responsibilities of each party involved with respect to Part 3 of the regulations. It defines the specific duties, responsibilities and expectations of each party involved in the agreement. A quality agreement between parties should include every activity or operation that is carried out when more than 1 party is involved.

You should monitor, review and assess the records and results of all your outsourced activities to ensure that all materials, products and services provided by the contracted party comply with the:

• GMP requirements
• site licence
• product licence
• quality agreement

The quality agreement that you draft for the contracted party (such as your contract manufacturing, packaging, labelling, importing, storage partner) should include a:

• description of who is responsible for:
  • writing and approving raw material, packaging material and finished product specifications
  • purchasing, sampling, testing and releasing raw materials and packaging materials
  • writing and approving the master formula
  • undertaking production, quality and in-process controls
  • conducting analytical tests
  • overseeing the stability program
  • overseeing transport and storage logistics and conditions
  • retaining lot or batch samples
  • coordinating and executing recalls
• clause stating there should be no subcontracting of any work without written authorization
• clause that allows you to audit the contracted facility
• description of how information will be communicated between contracted parties
• procedure used to ensure that each lot or batch being released for sale has been manufactured, packaged, labelled or imported in compliance with GMP and product licence requirements
• requirement to investigate any deviations and out-of-specification results that may have an impact on the quality of the products
• description of how to handle rejected raw and packaging materials, and in-process, bulk and finished products
• description of how complaints and information about potentially defective products are to be handled and investigated
• requirement for changes to be governed by a change control system and approved by the QAP
• quality agreement (written agreement) covering all testing activities if testing is done at a contract laboratory, which should:
  • permit audits of the external lab's facilities and operations
  • describe (at a minimum) who is responsible for:
    • overseeing collection, transportation and storage conditions of samples before testing
    • keeping stability samples at predetermined temperatures and humidity, if applicable
    • testing methods to be used, acceptance criteria to be applied and test method validation or suitability
    • retaining analytical results and supporting documentation

GMP evidence

The type of GMP evidence for operations may vary. However, all the requirements stated in this section must be supported by evidence that demonstrates GMP compliance for operations. Examples of evidence include:

• relevant written procedures (SOPs) and associated blank record templates for operations activities, including for:
  • maintaining SOPs for manufacturing, packaging, labelling and storing activities
  • transporting, receiving, handling, storing and distributing raw, packaging, labelling materials or finished products, as applicable
  • manufacturing (including all aspects of the production run), packaging, labelling and storing NHPs
  • an inspection program for contractors
  • creating and maintaining quality agreements (written agreements)
• master production documents, master labels and batch records or certificates of manufacture (for importers, when applicable)
• specifications, certificates of analysis and release records for all raw materials (medicinal and non-medicinal ingredients)
• product disposition, distribution, return and disposal logs and records
• records for out-of-specification results, including investigations into root causes
• product complaint logs, records and resulting action
• audit reports or completed records of pre-evaluation for approved contractors
• list of all contract manufacturers, packagers and labellers used (both internationally and in Canada)

Ensure you have a signed quality agreement (written agreement) for each contract manufacturer, packager, labeller, importer, storer, distributor and tester. The quality agreement should clearly outline the contracted party’s duties and responsibilities. Note that the regulations outline who is ultimately responsible for ensuring processes are in place to control outsourced (contracted) activities.

Operations (section 50)

Section 50

Every manufacturer, packager, labeller, importer and distributor shall establish and maintain a system of control that permits the rapid and complete recall of every lot or batch of the natural health product that has been made available for sale.

Intent

You must have a system in place for recalling a product. The system must include:

• tracking the product from manufacturing to distribution
• tracing the product from the raw material stage to when it’s released in its final form

In this document, we also provide guidance on how to comply with section 62 of the regulations.

Manufacturer, packager, labeller, importer, distributor requirements

You must:

• establish written procedures (SOPs) that outline how to initiate and undertake a product recall promptly and at any time
  • review and update these procedures regularly
• employ appropriately trained and experienced personnel who will manage complaints and investigations on defects
  • to decide measures for managing potential risks and conducting recalls
• ensure batch or product distribution records are available to the persons responsible for recalls
  • should contain 24-hour contact details, as well as identifying information on product quantity and batch or lot
• designate a storage area for recalled products prior to the approved and documented disposition action
• ensure a quality agreement (written agreement) is in place for activities contracted to other parties
  • should clearly establish and document the roles and responsibilities on recalls for each party involved in the contracted operations

You must also have a:

• system to proactively monitor foreign suppliers for issues that may require products to be recalled
  • includes recalls initiated by the foreign sites or regulatory compliance actions or warning letters issued by foreign authorities
• process for recording the progress of a recall and the issuance of a final report
  • includes the reconciliation between delivered and recovered quantities of the recalled products, and the corrective and preventive actions put in place
  • should also include effectiveness checks to ensure that everyone on the distribution list received the recall communication letter and was able to action it appropriately
• process for periodically evaluating the effectiveness of the recall system (for example, performing a mock recall)
  • will confirm it remains up to date with company procedures and current Health Canada requirements and guidance

You must also consult:

• Completing recalls using an established recall system
  • includes information to provide to Health Canada and how to test your system through mock recalls
• Drug and natural health products recall guide (GUI-0039) (a new online version of GUI-0039 will be available soon)

GMP evidence

The type of GMP evidence for recall systems may vary. However, all the requirements stated in this section must be supported by evidence that demonstrates GMP compliance for recall systems. Examples of evidence include:

• relevant written procedures (SOPs) and associated blank record templates for recall reporting, including:
  • procedures for recalling an NHP
• distribution records for all products
• signed quality agreement (written agreement) outlining recall responsibilities