34 Sourcing Compound Ingredients, Materials, Equipment and Supplies

In the compounding process, the selection and sourcing of high-quality components, materials, equipment, and supplies are essential to ensuring the safety, efficacy, and stability of compounded preparations. The NAPRA Model Standards for Pharmacy Compounding of Non-Sterile Preparations and its associated Guidance Document outline the expectations and best practices for sourcing these components. Adherence to these standards guarantees that compounding personnel use only the most reliable and compliant ingredients, tools, and protective measures. In this section, we will review the processes for identifying, sourcing, and maintaining appropriate supplies and equipment, emphasizing the importance of traceability, regulatory compliance, and risk management in maintaining a high standard of compounding practice.

1. Ingredients (Both Active and Inactive):

• Quality:
  • Use ingredients that are pharmacopeial grade (e.g., USP, NF, BP) or approved for pharmaceutical use. (e.g. contains a specified amount of substance between 98-102%)
  • When pharmacopeial-grade ingredients are not available, substances must come with a certificate of analysis to verify their quality, purity, and suitability for compounding.
  • Any drug withdrawn from the market ca not be used/compounded.
• Source
  • Source from Health Canada–licensed suppliers.
  • Bulk ingredients should come from reputable manufacturers that comply with Good Manufacturing Practices (GMP).
• Stability and Compatibility:
  • Confirm chemical and physical stability with other components in the formulation.
  • Check for incompatibilities (e.g., pH, reactivity).
• Storage Conditions:
  • Ensure proper storage (e.g., light protection, refrigeration) per monographs or supplier instructions.
• Expiry Dates:
  • Check expiry dates every time you make a compound.
  • Assign beyond-use dates (BUDs) based on ingredients, storage using NAPRA guidelines.
• Records and Documentation:
  • Lot numbers, expiry dates, supplier information, and certificates of analysis must be documented and kept on file to ensure full traceability (per NAPRA, Section 5.1 and GD-5.5.1).
• Other considerations:
  • Cost, availability, compatibility with drug, process, packaging
  • Choice of Salt:
    •  Metronidazole free base is a very unpleasant bitter taste
    •  Metronidazole benzoate is tasteless
      • Benzoate moiety contributes a large percentage of the molecular weight
      • Metronidazole benzoate 400 mg = metronidazole 250 mg
      • 1.6 gram of metronidazole benzoate = 1 gram of metronidazole

Quality and Storage of Ingredients for Non-Sterile Compounding

Ensuring Purity and Safety

To maintain the integrity of compounded preparations, reasonable measures must be taken to verify the purity and safety of all ingredients. This can be achieved by analyzing batch data, confirming the reputation of the manufacturer, and ensuring the reliability of the supplier. Any ingredient requiring special handling or storage precautions should be properly identified. Ingredients and raw materials must be stored under conditions that preserve their quality and purity, as specified by the manufacturer or in accordance with recognized pharmacopeial monographs.

Selection of Ingredients

When choosing active or inactive ingredients for compounding, the following factors must be considered:

• • Physicochemical properties
  • Efficacy
  • Stability
  • Compatibility
  • Toxicity
  • Patient-specific considerations, including allergies and disease state
  • Prescriber’s therapeutic intent
  • Potential interactions
  • Treatment duration
  • Route and frequency of administration
  • For any formulation requiring water, only purified water (e.g., distilled or deionized water) or water of equivalent or superior quality (e.g., sterile irrigation water) must be used.
    • Bottled water dispensers, whether programmed or unprogrammed, are not recommended due to insufficient data on water quality maintenance.
    • Tap water is unsuitable for compounding and must not be used.

Sources of Ingredients

Compounding ingredients must be sourced from recognized and reputable suppliers. Non-sterile preparations should utilize approved ingredients that:

• • Have been assigned a Drug Identification Number (DIN) for use in Canada, or
  • Meet the standards outlined in pharmacopeial monographs from recognized sources such as the United States Pharmacopeia (USP), European Pharmacopoeia, British Pharmacopoeia, National Formulary of the United States, or Schedule B of the Food and Drugs Act.

When compendial-grade ingredients are unavailable, high-quality alternatives such as those listed in the Food Chemicals Codex, analytical reagent-grade substances, or materials certified by the American Chemical Society (ACS) may be used. However, caution must be exercised, as these materials are not assessed for safety in human or veterinary applications.

Quality Control of Ingredients

Only high-quality ingredients that meet identity and purity standards should be used in non-sterile compounding. Supporting documentation, such as Certificates of Analysis (COAs), should be obtained and retained. The pharmacy must keep detailed records of ingredient sources, including:

• • Lot numbers
  • Expiry dates
  • Date of receipt

If an ingredient is not sourced from a recognized supplier, it must be analyzed by a qualified laboratory to confirm its identity, purity, and compliance with pharmacopeial standards. Analytical results and supporting certificates should be documented in an ingredients log.

Ingredients that have been recalled or withdrawn from the market for safety reasons must not be used. Health Canada maintains an up-to-date list of recalled drugs on its website. If using ingredients derived from ruminant animals (e.g., bovine, caprine, ovine), the supplier must provide written confirmation of compliance with federal regulations governing their processing, use, and importation.

Storage and Handling of Ingredients

Ingredients should be stored in their original containers under appropriate conditions to prevent degradation. Key considerations include:

• • Limiting exposure to environmental factors that could impact stability.
  • Ensuring material withdrawals are conducted by trained personnel.
  • Properly labeling transferred ingredients to another storage container with:
    • Name of the ingredient
    • Original supplier
    • Lot/control number
    • Date of transfer
    • Expiry date

For ingredients lacking a manufacturer-assigned expiry date, a conservative in-house expiry should be assigned, not exceeding three years from the date of receipt, based on the ingredient type, storage conditions, and container integrity. All ingredients must be inspected before use to detect any signs of deterioration.

Safety Data Sheets (SDS)

Suppliers must provide Safety Data Sheets (SDS), previously known as Material Safety Data Sheets (MSDS), as required by the Hazardous Products Act. These documents outline:

• • Risks associated with the ingredient
  • Preventative measures
  • Recommended storage conditions

SDS documents must be readily accessible to all personnel involved in non-sterile compounding. Pharmacies should maintain an updated collection of these documents and ensure they are reviewed regularly, as suppliers update them every three years.

2. Packaging and Containers:

• Container Integrity:
  • Use containers that prevent contamination, moisture, and degradation (e.g., tight, light-resistant, child-resistant).

    Remember your dosing device!

  • Containers and closures must be appropriate for the compounded preparation to maintain stability and prevent contamination.
• Compatibility:
  • Ensure materials do not react with the compounded preparation (e.g., avoid plastics that leach chemicals).
  • Must be sourced from suppliers providing containers suitable for pharmaceutical use, ensuring materials do not interact with the compounded product.
• Labelling Space:
  • Ensure enough room for required labels and auxiliary warnings.
• Reuse Restrictions:
  • Use single-use containers where required.
  • Clean reusable containers appropriately.

3. Equipment and Devices:

• Suitability:
  • Equipment must be appropriate for the type and complexity of compounding being performed (e.g., balances, mixers, grinders, etc.).
  • Precision and accuracy must be verifiable, particularly for scales and measurement devices (per NAPRA, Section 5.4.2 and GD-5.4.2.1).
• Calibration and Maintenance:
  • Equipment must be regularly calibrated, maintained, and cleaned according to a documented schedule (Section 5.4.2; maintenance logs required).
  • Must be easy to clean and sanitize between uses; smooth, non-porous surfaces are preferred
• Procurement Sources:
  • Equipment should be obtained from suppliers specializing in pharmaceutical or laboratory-grade devices.
• Dedicated Equipment:
  • Use dedicated or properly cleaned/validated equipment for hazardous or sensitizing compounds.

4. Personal Protective Equipment (PPE):

• Risk of Compounding:
  • PPE (e.g., gloves, gowns, masks) must meet the protective requirements appropriate to the risk level of the compounded preparation (Level A, B, or C).

• Barrier Protection:
  • Use PPE that protects personnel and prevents contamination of the product (e.g., gloves, gowns, masks, hair covers).
• Compliance with Standards:
  • Ensure PPE meets safety and regulatory requirements (e.g., CSA, NIOSH for hazardous materials).
  • PPE suppliers must provide products that comply with occupational health and safety standards (e.g., CSA, NIOSH standards).
• Training:
  • Ensure staff are trained on donning, doffing, and disposal of PPE.

5. Supplies for Cleaning and Decontamination:

• Effectiveness:
  • Use cleaning agents proven to remove residue and disinfect surfaces (e.g., alcohol, quaternary ammonium compounds).
• Residue-Free:
  • Avoid cleaners that leave residues that may contaminate preparations.
• Surface Compatibility:
  • Ensure cleaning products are safe for the surfaces used in compounding areas.
• Safety and Storage:
  • Store cleaning agents safely and label them clearly; use PPE when handling concentrated solutions
• Supplies such as lint-free cloths, approved disinfectants, and cleaning tools must be procured from specialized suppliers.

Additional Notes for Sourcing:

• Supplier Qualification:
  Pharmacies should establish a list of pre-approved suppliers, verified through a qualification process that may include:
  • Reviewing the supplier’s GMP compliance.
  • Checking references or reviews from other healthcare institutions.
  • Confirming appropriate licenses and certifications.
• Ongoing Monitoring:
  Suppliers should be re-evaluated periodically to ensure continued compliance with quality expectations (aligned with NAPRA QA requirements).
• Risk-Based Decision-Making:
  Especially for higher-risk or complex compounding (Level B and Level C), sourcing decisions must consider the risk of contamination or instability introduced by poor-quality components or equipment.

To meet the regulatory and quality standards for non-sterile compounding, it is important to source ingredients, materials, equipment, and supplies from reputable suppliers who comply with industry regulations and standards. The use of pharmacopeial-grade ingredients, properly calibrated equipment, and appropriate PPE is vital in minimizing the risk of contamination and ensuring the safety and efficacy of compounded preparations. Documentation of sourcing decisions, including lot numbers, supplier certifications, and certificates of analysis, must be meticulously maintained for traceability. Additionally, a proactive approach to supplier qualification and ongoing monitoring is key to ensuring the continuous compliance and reliability of all components. By following these procedures, pharmacies can mitigate risks, comply with NAPRA standards, and provide safe, high-quality compounded medications for patients.