Good manufacturing practices guide for natural health products (GUI-0158): Supplementary GMP for homeopathic medicines

On this page

• About homeopathic medicines
• Premises and equipment
• Personnel
• Sanitation
• Operations
• Specifications
• Stability
• Terminology

About homeopathic medicines

To be considered a homeopathic medicine, a product must be both:

• manufactured from, or contain as medicinal ingredients, only substances referenced in a homeopathic monograph in 1 of the following homeopathic pharmacopoeias, as amended from time to time:
  • Homeopathic Pharmacopeia of the United States
  • Homöopathisches ArzneiBuch (German homeopathic pharmacopoeia)
  • European Pharmacopoeia (Ph.Eur.)
  • Pharmacopée française (Ph.F.)
  • Encyclopedia of Homeopathic Pharmacopoeia and
• prepared according to the methods outlined in 1 of the homeopathic pharmacopoeias listed in the first point, as amended from time to time

Homeopathic medicines are NHPs. They are made from a wide range of materials, such as plants, animals, minerals and chemicals. Many of these can be highly toxic in the raw material form. Nosodes are also a type of homeopathic medicines (they are preparations of pathological tissues, excretions or secretions).

Manufacturers and importers must make sure to carry out the critical processes (for example, raw material identification, raw material handling, attenuations) under controlled conditions when producing homeopathic medicines.

If you are producing tinctures, also refer to ICH guideline Q7: Good manufacturing practices guide for active pharmaceutical ingredients. This is regardless of whether the tinctures are sold to consumers or used for further processing of finished products. Although NHPs are not within the scope of ICH guidelines, such references are helpful to the NHP industry and stakeholders. They may help you gain a better understanding of GMP concepts and processes that also apply to NHPs.

Note also that “potency” refers to the degree of dilution of a homeopathic product. In this section of the guide, there is more information on the terminology applied in the homeopathic context.

Premises and equipment

To meet the requirements

Due to the infinitesimal dose of active ingredients, prepare homeopathic medicines in a manner that eliminates the possibility of cross-contamination and outside contamination.

For manufacturers and packagers:

• Design your premises so that the homeopathic attenuations are prepared in rooms or workstations that:
  • have appropriate environmental controls, such as a room with filtered air under positive pressure or in a laminar airflow workstation
  • are distinctly separate from products that are volatile or have permeating odours
• Design your premises to accommodate hazardous raw material storage and processing requirements, including:
  • isolating toxic or infectious raw materials from other materials
  • handling raw materials in segregated areas with appropriate environmental controls suitable for each material
    • pharmacopoeias may provide more information on storing dangerous raw materials
• Use equipment and utensils exclusively for homeopathic preparations, which are:
  • made of materials that do not shed particles
  • cleaned and maintained using products (such as lubricants) that do not contaminate the homeopathic medicine
    • your cleaning written procedure (SOP) should include the cleaning of vessels and containers used in successive attenuations or triturations

For importers:

• Ensure the facilities that manufacture, package or label the homeopathic medicine meet the premises and equipment requirements

Personnel

To meet the requirements

For manufacturers and packagers:

• Provide training specific to the attenuation or trituration of homeopathic medicines

For manufacturers:

• Have a personnel qualification program that:
  • ensures trained personnel are observed performing the manual operations and that the materials produced meet their pre-determined acceptance criteria
  • provides training that is appropriate to the tasks being done
  • schedules annual training and reviews to ensure the production methods are not inappropriately modified over time
  • maintains supporting documents that detail the training content and completion dates
  • restricts the entry of untrained or unnecessary personnel in processing areas designated for attenuation and trituration

For importers:

• Ensure the facilities that manufacture, package or label the homeopathic medicine meet the personnel requirements

Sanitation

To meet the requirements

For manufacturers and packagers:

• Ensure the sanitation program does not contaminate the homeopathic medicine with chemical or particulate matter
• Put in place:
  • cleaning, microbial and environmental monitoring parameters for all processing areas, and focus on areas designated for attenuation and trituration
  • methods to ensure cleaning and maintenance products do not contaminate your product
  • methods to ensure there is no cross-contamination of your product, including:
    • any remaining traces of the product previously manufactured
    • any cleaning agent residue

For importers:

• Ensure the facilities that manufacture, package or label the homeopathic medicine meet the sanitation requirements

Operations

Manufacture your homeopathic medicines according to the preparation methods outlined in 1 of the 5 accepted homeopathic pharmacopoeias listed in this section of the guide.

There are several distinct manufacturing steps for homeopathic medicines. Each step involves repeating attenuation (dilution) and succussion (vigorous shaking). Source materials for these medicines are typically divided into 2 basic categories: soluble or insoluble. Insoluble source material must be triturated (ground with a soluble powder, typically milk sugar) until it can be dissolved in water.

The 3 basic manufacturing steps are:

• Source material is transformed to a mother tincture or soluble trituration.
• Mother tinctures are a relatively concentrated aqueous alcoholic extract from which subsequent attenuations are prepared.
• The tincture potency may vary depending on the soluble or insoluble nature of the source material.
• Detailed manufacturing processes are stated in the homeopathic pharmacopoeias listed in this section of the guide, and each monograph references a specific manufacturing process.
• Mother tincture is diluted to a target medicating potency, when required.
• The target medicating potency is typically used to impregnate pellets or other solid dosage forms.
• As it has a high alcohol content, it should not be sold directly to consumers.
• Targeting the medicating potency (or mother tincture) to the finished product.
• This step can be for either single or combination homeopathic products.

To meet the requirements

For manufacturers:

• Control the 3 basic manufacturing steps following GMP, which means generating up to 3 different types of manufacturing batch records:
  • record for source material to mother tincture or to a soluble trituration
  • record for the mother tincture to the target medicating potency
  • record for target medicating potency to the finished product

As you have to rely solely on production controls to ensure the product has reached its defined potency, you must document each critical step. The person performing the task and the person performing the verification must sign and initial each step.

Perform all verifications in a timely manner and at the same time as the batch production. Critical processes include measuring tasks (such as using scales, pipettes), attenuation processes (trituration or succussion methods) and impregnation.

For importers:

• Put in place proper processes to monitor the GMP of foreign manufacturers
• Include ongoing control measures to ensure each imported product meets its specifications before the product is released

For manufacturers, packagers and labellers:

• Keep separate written procedures (SOPs) for homeopathic medicines
• Carry out the following critical production processes that relate to your activity:
  • harvest or produce raw materials according to the homeopathic pharmacopoeias
    • verify and record the identity of all raw materials
    • label raw materials that are toxic or potentially infectious as to their safety status (such as allergen or toxic) or a material safety data sheet (MSDS) equivalent
• Ensure mother tincture batch records contain sufficient information, such as:
  • the duration of maceration or percolation
  • trituration duration and intensity for each type and size of apparatus
  • particle size of the raw materials in the triturate matrix
  • quality specifications and QA release
  • sterility of nosodes, such as heat processing of the first attenuation in the preparation
• Ensure the process for in-process attenuations or triturations (critical in production) is consistent, reliable and free of contaminants
• Include the following information in the master formula and batch record:
  • potency scale (X or C scale or Korsakovian)
  • written procedures (SOPs), or reference to SOPs, for each processing stage
  • number of succussions during each attenuation
  • duration of trituration, when applicable
  • disposal of unused intermediate homeopathic potencies
  • technique for impregnation, where final dosage forms are manufactured
  • in-process controls with specifications
  • a reference number unique to a particular series that differs from the batch number assigned to the product
  • attenuation or trituration number at the particular stage of preparation (for example, could be designated by potency)
  • name, dosage form, batch number and batch size of the preparation for which it’s intended
  • composition or reference to the master formula
  • an internal code and analytical control number of each raw material or mother tincture used
  • precautions to be adopted during handling ingredients, when applicable
    • schedule manufacturing to ensure continuity within the attenuation or trituration series, and avoid prolonged storage of intermediate homeopathic potencies
• Ensure the following is in place when manufacturing impregnated pellets from medicating potencies made by a separate company:
• raw material identity testing and a batch record showing that the raw material was added during manufacturing
• studies showing the impregnation procedure is adequate
• written procedures (SOPs), or reference to SOPs, for washing, drying and, when applicable, sterilizing packaging materials
• stability studies or challenge studies showing that the procedures and materials used ensure there is no microbial contamination until expiry
• Ensure your QAP documents the release between the different manufacturing steps (unless performed as 1 continuous process from source material to finished product)
• Ensure your batch records document the critical steps and the person performing the task and the person performing the verification must sign or initial the records
• verifications are done in a timely manner and at the same time as batch production
• critical processes include measuring, attenuation processes and impregnation

Specifications

Specifications of homeopathic medicines must meet the requirements set out in homeopathic pharmacopoeias. Consult the list of homeopathic pharmacopoeias provided in this section of the guide.

Manufacturers and importers must:

• identify the source material used to make the homeopathic medicine
• have evidence of identification (defined in 1 of the recognized homeopathic pharmacopoeias)

For homeopathic medicines, testing for identity can only be performed on the source material. To do so, use the methods and criteria set out in the homeopathic pharmacopoeias.

Manufacturers and importers must keep evidence of identity testing of the source material of homeopathic medicines. The quality of homeopathic products can only be assured by strictly controlling starting materials and diluents and using a thorough QC system.

Health Canada has monographs specific for nosodes and organotherapy, which include criteria for identification, sterilization and GMP. Manufacturers and importers must keep the information and records mentioned in these monographs, when applicable.

To meet the requirements

For manufacturer and importers:

• Keep written specifications that describe the homeopathic medicine and the required test methods

For specifications pertaining to identity, purity, quantity, potency and tolerances, consult:

• Evidence for homeopathic medicines

This guidance document also lists the conventional testing protocols for the dosage form, for example:

• tablets: uniformity of weight, hardness and disintegration
• liquids: alcohol type and percentage
• ointments or syrups: viscosity or rheology

For manufacturers:

• Keep records and evidence of identity testing of the source material of homeopathic products

For importers:

• Keep records and evidence of identity testing of the source material of homeopathic products or
• Have access to the records and evidence of identity testing
  • if you receive a certificate of manufacture or batch certificate that meets the requirements outlined in this guide

For manufacturers and importers:

• Ensure that identification, sterilization and GMP criteria from the monographs specific for nosodes and organotherapy are met when those apply

Stability

To meet the requirements

For manufacturers and importers:

• Develop and maintain written procedures (SOPs) that confirm the stability of homeopathic medicines
• Keep records of ongoing purity testing as outlined in Evidence for homeopathic medicines
  • due to the unique nature of homeopathic medicines, stability evidence focuses on:
    • microbial contamination
    • non-medicinal ingredients (for example, alcohol concentration, hardness of granules or tablets and disintegration stay consistent)
    • packaging materials, such as bottles and caps, do not contaminate the product or leak
    • labels do not fade or peel from the packaging

Terminology

Inconsistent or different interpretation of terminology used in homeopathic medicines manufacturing can make it difficult to demonstrate a sound GMP process. Definitions cannot be substituted for novel manufacturing practices or to avoid maintaining critical documents required to demonstrate GMP.

Terminology must be consistent with either:

• the definitions listed in Evidence for homeopathic medicines
• 1 of the 5 homeopathic pharmacopoeias listed in this section of the guide

Review the definitions to make sure you understand them. Generally recognized definitions of terms used in the homeopathic field include:

• Attenuation: Material prepared by dissolving 1 part of the soluble basic substance in a sufficient quantity of purified water or other appropriate menstruum, specified in the recognized monograph, to produce (X) parts by volume of liquid attenuation (such as 1X, 1CH).
• Finished product: A product that has undergone all stages of production, including packaging in its final container and labelling. The final potency of a homeopathic medicine is in the final packaging that is to be sold to consumers.
• Maceration: Processing method using unheated solvent (cold or room temperature water, alcohol or other organic solvent) to extract medicinal properties from a raw material.
• Medicating potency: The final liquid potency of a homeopathic medicine. This potency is typically used to impregnate pellets or other solid dosage form, as it has a high alcohol content and is not expected to be sold directly to consumers.
• Mother tincture: A relatively concentrated aqueous alcoholic extract from which subsequent attenuations are prepared. Synonyms are mother liquor, stock solution and starting solution. The actual tincture potency may vary depending on the soluble or insoluble nature of the source material. Detailed manufacturing processes are stated in the homeopathic pharmacopoeias and each homeopathic medicine monograph references the specific manufacturing process (also called class).
• Nosodes: These are:
  • attenuations of pathological organs or tissues
  • causative agents such as bacteria, fungi, ova, parasites, virus particles and yeast
  • disease products
  • excretions or secretions
• Percolation: A method used to extract dried substances that have been reduced to the proper degree of fineness.
• Potency: The degree of dilution of a homeopathic product.
• Source material: Substances referenced in a monograph in a homeopathic pharmacopoeia and is the undiluted, physical form of the substance. Additional clarification on source materials can be found in the section on source information in Evidence for homeopathic medicines.
• Starting material: The active ingredient used at the beginning of the manufacturing stage. Ingredient may be the source material, mother tincture or medicating potency, for example, depending on the manufacturing phase of the product.
• Succussion: The agitation step of attenuation (also known as dynamization or potentization). Vigorous agitation is obtained by a rapid bi-directional movement of the container, with each movement or stroke abruptly interrupted to create significant turbulence throughout the liquid. Rotation movements (stirring) alone cannot achieve the degree of turbulence required.
• Trituration: Attenuations of solid substances are prepared by trituration of the crude substance with lactose.