37 Chapter 37: Preparation of Bulk Compounds

The preparation of bulk compounds refers to the process of creating non-sterile compounded products in large quantities, rather than for individual patient use. Bulk compounding is typically used for situations where multiple doses of a particular preparation are required or where preparations are made in larger quantities to meet demand. Bulk preparations require careful attention to formulation, storage, quality control, and labeling to ensure safety, efficacy, and regulatory compliance.

Here is a breakdown of the considerations and steps involved in the preparation of bulk compounds based on the NAPRA Model Standards for Pharmacy Compounding of Non-Sterile Preparations and the associated Guidance Document:

1. Formulation Development and Risk Assessment

• Formulation: Before preparing bulk compounds, a clear and scientifically supported formulation must be established. This includes defining the correct proportions of active ingredients, excipients, and the final dosage form (e.g., tablets, capsules, creams, etc.). Master Formulation Records (MFRs) should be used to document all necessary information for reproducibility and consistency.
• Risk Assessment: A risk assessment must be performed to identify any potential hazards associated with the preparation. This includes evaluating the risk of contamination, handling of hazardous substances, and ensuring the stability of the preparation over time. Specific risks that could affect the quality of the bulk preparation should be addressed, and appropriate control measures should be implemented.

2. Equipment and Facilities

The compounding environment for bulk preparations should be suitable for the volume and complexity of the product being compounded. Larger quantities require sufficient space and equipment to prevent errors and ensure cleanliness. The following equipment and facilities considerations are crucial:

• Appropriate Equipment: Ensure that the equipment used for bulk compounding is capable of handling larger quantities of materials while maintaining the desired consistency and quality. This may include mixers, blenders, tablet presses, or other specialized devices depending on the form of the preparation.
• Designated Compounding Area: Bulk compounding should be done in a separate, specifically designated space that meets all necessary requirements for cleanliness and safety. The space should have adequate room to store equipment, ingredients, and the compounded products, and should be free from contamination risks.
• Ventilation: Depending on the ingredients and their potential hazards, proper ventilation systems (e.g., fume hoods or exhaust fans) should be in place, especially for compounds containing volatile, harmful, or hazardous substances.

3. Ingredients Sourcing and Quality Control

• Sourcing Ingredients: For bulk preparations, it is essential to ensure that ingredients are sourced from reliable and compliant suppliers. All ingredients should be inspected for quality, potency, and compliance with appropriate standards. Ingredients should be stored according to the manufacturer’s specifications, including appropriate temperature and humidity controls.
• Quality Control (QC): To ensure the quality and consistency of bulk compounds, rigorous QC procedures must be followed. This includes verifying the identity, potency, and purity of each ingredient before use. During the preparation process, random samples of the bulk compound should be tested for uniformity, content, and physical properties (e.g., weight, pH, or viscosity).
• Batch Testing: Depending on the nature of the bulk preparation, batch testing should be conducted to confirm that the compounded preparation meets the required specifications. This can include testing the homogeneity of the mixture, verifying weight or volume consistency, and checking other critical attributes of the final product.

4. Compounding Process

• Procedure: The process of bulk compounding should be clearly outlined in a Master Formulation Record (MFR), which includes step-by-step instructions for the preparation, including calculations for the quantities of active ingredients and excipients. Detailed instructions help ensure consistency and minimize human error.
• Measurement and Mixing: Accurate measurement of ingredients is critical to ensure correct dosing in each final unit. The ingredients should be carefully blended to achieve the desired uniformity and consistency. Depending on the preparation, additional processing steps, such as granulation or homogenization, may be required.
• Monitoring: The entire compounding process should be closely monitored by trained personnel, and any deviations from the standard procedures should be documented and addressed. Proper documentation of the compounding steps is essential for traceability.

5. Labeling and Storage

Labeling: Bulk compounded preparations must be appropriately labeled, including:

• The official or assigned name, strength, and dosage form.
• The Master Formulation Record reference and the Beyond-Use Date (BUD).
• The storage conditions required to maintain the integrity of the product (e.g., temperature controls, light sensitivity, humidity).
• Bulk preparations must be labeled to indicate whether the preparation is for individual patient use or for general distribution. If the preparation is for external use, clear instructions for use and handling should be included

Storage:

• Proper storage is crucial to maintaining the stability and potency of bulk compounded products.
• Bulk preparations must be stored in clearly labeled containers that protect them from contamination and degradation. This may include storage in a cool, dry environment, in temperature-controlled units, or in sealed containers to protect from light or moisture, as applicable.
• A log should be maintained for batch tracking and to ensure that stock is used within appropriate timeframes.

6. Documentation and Record Keeping

Comprehensive documentation is required for bulk compounding, which includes:

• Master Formulation Records (MFRs): As mentioned, these provide detailed instructions for preparing the compound and serve as a reference for compounding personnel.
• Compounding Records: For each batch of bulk preparation, a compounding record should be maintained to document the quantities of ingredients, the equipment used, the process followed, and the personnel involved. This ensures traceability and accountability.
• Quality Control Logs: QC tests performed on bulk preparations should be documented in QC logs. This includes testing of the final product to ensure it meets the specifications outlined in the MFR.
• Inventory and Storage Logs: Maintain records of stock levels, storage conditions, and the BUD of bulk preparations. This is important for ensuring that bulk products are used within the recommended time and are stored in compliance with regulatory guidelines

7. Compliance with Regulatory Standards

• Bulk compounding must comply with all applicable NAPRA Model Standards, provincial/territorial regulations, and federal guidelines, including USP <795> for non-sterile compounding.

The preparation of bulk compounds requires careful attention to formulation, equipment, ingredients, quality control, documentation, and storage. By following the NAPRA Model Standards and adhering to proper procedures, pharmacies can ensure the safety and efficacy of bulk compounded products. This process not only helps to maintain patient safety and product integrity but also ensures regulatory compliance and the ability to provide reliable compounded products to meet patient needs.

Examples of when bulk compounding may be done:

1. Preparing Topical Medications (e.g., creams, ointments, gels)

Example: A pharmacy may prepare large quantities of a topical corticosteroid cream or ointment for a dermatology clinic or a long-term care facility that treats multiple patients with similar conditions. Bulk compounding allows the pharmacy to supply the clinic or facility with the medication in a cost-effective and efficient manner, reducing the need to prepare individual doses for each patient.

• Why Bulk Compounding?: This method is used when a large number of patients require the same topical treatment, making it more efficient to prepare the medication in bulk and distribute it in smaller containers as needed.

2. Customizing Drug Strengths for Patients with Special Needs

Example: A pediatric or geriatric patient may require a specific dosage strength of a medication that is not commercially available (e.g., a pediatric dose of an antihypertensive medication). A pharmacy may compound the required medication in bulk, preparing it in appropriate doses for the patients and allowing them to be dispensed over time.

Why Bulk Compounding?: In cases where a specific dosage form or strength of a drug is needed, bulk compounding allows pharmacies to customize the preparation to meet the needs of the patient population, such as when the patient population requires a different formulation or strength than what is available on the market.

3. Compounding Parenteral Medications (e.g., intravenous (IV) solutions)

Example: Bulk compounding may be used for intravenous (IV) preparations, such as saline solutions, electrolytes, or parenteral nutrition (PN) solutions, where these are compounded in large quantities for use in hospitals or healthcare settings. These bulk preparations are made according to the exact specifications and stored under appropriate conditions for later use.

• Why Bulk Compounding?: Many hospitals and healthcare facilities need large volumes of IV solutions prepared for use in multiple patients. Rather than compounding individual doses for each patient, pharmacies prepare these products in bulk to meet the ongoing demand in a hospital setting.