Ten tips for quality compounding

Compounding pharmaceuticals involves the preparation of personalized medications, tailored to a patient's specific needs. This practice is essential when commercially available medications are unsuitable or unavailable. Here are some key considerations before compounding.

1. Understand legal and regulatory requirements

It is crucial for compounding pharmacists to ensure compliance, safeguard patient safety, and maintain high standards of practice. By adhering to Regulations, laws and guidelines on how compounded medications should be prepared, labelled, stored, dispensed, and monitored, compounding pharmacists can ensure they meet standards for safety, efficacy, and quality. By adhering to the legislation, guidelines, standards, essential references and ensuring proper clinical oversight, compounding can be a valuable tool for providing personalized care for patients in situations where commercial medications are insufficient or inappropriate.

• Australian Therapeutic Goods Administration (TGA): The TGA regulates pharmaceutical compounding and ensures that compounded medications meet safety standards. Pharmacists must be aware of TGA guidelines on the manufacturing and labelling of compounded medicines. The Therapeutic Goods Regulation 1990, and the associated guidance document Understanding Good Manufacturing Practice (GMP) for compounded medicines, should be referred to for guidance on the interpretation of the PIC/S GMP requirements when manufacturing compounded medicines.

• Pharmacy Board of Australia (PBA): Ensure compliance with professional standards set by the Pharmacy Board, which includes ethical practices, patient safety, and confidentiality. The PBA publishes the Guidelines on compounding of medicines. The PBA shares the Code of Conduct which applies to health practitioners.

• Australian Pharmaceutical Formulary and Handbook (APF): Refer to the official APF for standardized formulations and compounding guidelines. It provides specific instructions for preparing compounded medications safely and effectively.

• United States Pharmacopoeia – National Formulary (USP-NF): General Chapter <795> provides detailed information about Non-sterile Compounding. USP <797> is a chapter that provides procedures and requirements for compounding sterile preparations. It covers topics such as personnel training and assessment, environmental quality, equipment, storage and beyond-use dates, finished preparations release checks and tests. 

• PSA National Competency Standards Framework for Pharmacists 2016: Standard 3.4 addresses the requirements for simple and complex compounding of aseptically and non-aseptically prepared products.

2. Clinical justification 

There must be a valid clinical reason for compounding the product. Compounding is typically performed in specific situations when a commercially available medication is unsuitable or unavailable for a patient's needs. 

Medicines should not be compounded if there is a suitable commercial product that has a similar therapeutic effect and can be safely used for the intended purpose, and that can be accessed within a suitable timeframe. 

Some of the key scenarios in which compounding a pharmaceutical product is appropriate include:

1. When a commercial product is unavailable 

• Shortages: If a medication is in short supply or completely out-of-stock, compounding can be a solution to meet patient needs when no alternative commercial product is available.

• Discontinuations: If a medication is withdrawn from the Australian market for reasons other than efficacy or safety, compounding can be a solution suitable for new patients and patients well-established on the discontinued medication.

• Formulation issues: If a commercially available product doesn't come in the required dosage form (e.g., liquid instead of tablet), compounding can offer a tailored solution.

2. When a patient has an allergy or sensitivity

• Allergens or ingredients: Some patients may have allergies or sensitivities to certain ingredients in commercially available products (e.g., lactose, gluten, or dyes). Compounding allows the pharmacist to prepare a medication without those allergens.

• Sensitive ingredients: For patients who cannot tolerate certain excipients (e.g., preservatives, colorants), a compounded product can be formulated with appropriate alternatives.

3. When the dosage strength needs to be adjusted

• Customised dosage: If a patient requires a dosage strength that is not commercially available (e.g., a lower or higher dose), compounding allows for precise tailoring to the required strength.

• Paediatric or geriatric doses: Children or elderly patients often need specific dosing adjustments, such as a liquid form or a smaller dosage than what's commercially available.

• Animal doses: The required dose of medications for animals may vary depending on the species and breed.

4. For specialised dosage forms 

• Non-standard forms: Some patients may require medications in specialized forms, such as creams, gels, suppositories, lozenges, oral transmucosal films, rapid dissolving tablets, troches or transdermal patches, which may not be commercially available for every drug.

• Custom delivery methods: If a medication needs to be delivered in a specific form that isn't available in the market (e.g., topical preparations for localized conditions), compounding can address this need.

5. When a patient requires a combination of medications

• Polypill or combination therapy: Sometimes, patients need a combination of medications in a single dosage form, such as combining two or more drugs into one tablet or capsule for easier administration.

• Chronic disease management: Compounding can help manage chronic conditions by combining multiple medications into a single, more convenient formulation.

6. When a medication requires modification due to special needs

• Swallowing difficulties: Some patients, especially elderly individuals or children, may have difficulty swallowing tablets or capsules. Compounding can provide liquid or flavoured formulations that are easier to ingest.

• Patient preference: Some patients may prefer specific forms of medication (e.g., a flavoured oral suspension rather than a pill) to improve compliance and ease of use.

7. Hospice and palliative care

• End-of-life care: Compounding is often used in hospice or palliative care settings to create formulations that manage symptoms (e.g., pain relief) in a way that is more comfortable for patients, especially those who have difficulty swallowing or require a special route of administration.

8. Veterinary compounding

• Animal medications: Compounding is also common in veterinary care to provide the appropriate formulation and dosage for animals, especially when there are no commercial products available for certain species or conditions.

9. Clinical trials and research

• Trial preparations: In some research settings, compounded medications may be needed for clinical trials or investigational drugs. These medications may not yet be commercially available, but compounding ensures that participants receive the correct dosage and form.

10. Patient-specific requests

• Unique therapeutic needs: In some cases, a healthcare provider may request a compounded medication for a specific patient based on their individual medical needs, therapeutic goals, or circumstances that cannot be addressed with a standard product.

3. Follow Good Compounding Practice

Good Compounding Practice (USP GCP Chapter <1075>) is essential to ensure that compounded medications are prepared safely, accurately, and effectively for patient use It includes following established guidelines, maintaining high standards of hygiene, and utilizing appropriate techniques and equipment to deliver quality compounded products. Good compounding practice is key to minimizing errors, preventing contamination, and ensuring the safety and well-being of patients.

Good compounding practice includes: 

• Quality assurance: Follow Good Manufacturing Practice (GMP) or Good Compounding Practice (GxP) standards to ensure consistency and quality. This includes maintaining clean environments, calibrated equipment, and proper documentation.

• Personal protective equipment (PPE): Wear appropriate PPE (e.g., gloves, lab coats, face shields) to avoid contamination and ensure the safety of both the compounder and patient. 

• Storage conditions: Ensure proper storage conditions for both raw ingredients and compounded medications, which may involve temperature-controlled storage or protection from light.

• USP GCP Chapter <1075> encompasses the following guidance documents:

• Applicable definitions
• Responsibilities of the compounder
• Training
• Procedures and Documentation
• Drug compounding facilities
• Drug compounding equipment
• Component selection requirements
• Packaging and drug preparation containers
• Compounding controls 
• Labelling
• Records and reports
• Compounding for a prescribers’ office use
• Compounding veterinarian products

4. Appropriate equipment and procedures

 Compounding pharmaceutical products requires a variety of specific pharmaceutical equipment to ensure that medications are accurately prepared, mixed, and packaged. By using the appropriate equipment and following proper procedures, pharmacists can ensure that compounded medicines are prepared to the highest standards of quality, safety, and efficacy.

Consideration should be given to:

• Clean environment: Ensure that the compounding area is clean and free from contaminants, especially when preparing sterile formulations.

• Equipment maintenance and calibration: Regular verification of the calibration of weighing equipment ensures that the final product is accurate and consistent. Primary engineering controls such as powder containment cabinets, laminar airflow workstations and biological safety cabinets must be maintained as per policies and procedures.

• Standard operating procedures (SOPs): Always adhere to SOPs for each compounding step to ensure that medications are compounded safely and effectively. SOPs should include logs which document the execution of key SOPs.

5. Accurate formulation and documentation

Accurate formulation and documentation are critical elements in the compounding process to ensure the safety, quality, and efficacy of the compounded medications. Proper formulation involves using the correct ingredients, quantities, and methods to prepare medications that are safe for patients. The assigned expiry dates of compounded medicines must be referenced. Comprehensive documentation serves as a record of the entire compounding process and ensures compliance with regulatory and professional standards.

Accurate formulation and documentation includes:

• Precise measurements: Use precise and calibrated equipment when weighing and measuring ingredients to ensure accurate dosing and effectiveness.

• Compounding records: Keep detailed records of each compounded prescription, including the specific patient's details, formula used, batch numbers, and any special instructions. This documentation is crucial for patient safety and legal compliance.

• Formulas: Master formula records enable the preparation of compounded medicines which are consistent and reproducible, irrespective of the individual who prepared the medicine,

• Labelling: Properly label compounded medications with information such as the patient's name, dosage instructions, and storage conditions. This helps ensure safe and effective use. Aliquots, powder blends, liquid blends and in-process materials for future use, should also be appropriately labelled. They should include expiry dates.

6. Patient-centred approach

 A patient-centred approach in compounding focuses on tailoring medications to the individual needs of each patient, to ensure that their health outcomes are optimized. When compounding, this approach means prioritizing the patient’s specific medical conditions, preferences, and circumstances when creating a custom formulation.

A patient-centred approach considers:

• Personalised compounding: Ensure that the compounded medication meets the unique needs of the patient. This may include adjusting strength, dosage form (e.g., cream, oral liquid, or suppository), or excluding allergens. 

• Consultation: Offer thorough consultation with patients or healthcare providers to understand the requirements for compounding and clarify any questions regarding use, side effects, or dosage adjustments.

• Patient safety monitoring: Monitor for adverse reactions or effectiveness when using compounded medications and maintain communication with the patient or healthcare provider for any adjustments.

• Patient consent: Before compounding, it is essential to obtain proper consent from the patient or their caregiver, especially when making changes to their medication regimen.

7. Use of quality ingredients

To help maintain the integrity of the final product and minimize the risks associated with contamination, impurities, or ineffective formulations, the use of quality ingredients is essential. Inappropriate or poor-quality ingredients can lead to ineffective treatments, adverse effects, or even harm to patients. Using quality ingredients is fundamental to ensuring the safety, efficacy, and stability of compounded medications. From sourcing reputable suppliers to properly storing and inspecting ingredients, the quality of the ingredients used in compounding directly impacts the final product and patient outcomes. The use of quality ingredients includes consideration of:

• Pharmacopoeia-grade ingredients: Always use quality, pharmaceutical-grade ingredients sourced from reputable suppliers, manufactured under GMP. Ingredients should comply with the monograph of one of the default standards: United States Pharmacopeia (USP) or European pharmacopoeia (EP) standards, as per the Therapeutic Goods Act (1989).

• Shelf life and expiry: Be mindful of the shelf life of each ingredient and the final compounded product. Make sure to mark expiry dates clearly and educate patients on proper use within the recommended time frame. Separate expired stock, until they are appropriately discarded.

• Records: Ensure that all products are accurately records for each item, including recording expiration dates and batch numbers for each ingredient used. Regular audits should be undertaken to ensure stock is within expiration date.

8. Risk assessment and error prevention

A crucial component to ensuring the safety, efficacy, and quality of compounded medications is risk assessment and error prevention. Compounding pharmacies face numerous challenges, including the possibility of human error, contamination, and equipment failure. By identifying and managing risks, implementing comprehensive error prevention strategies, and fostering a culture of continuous improvement, compounding pharmacies can minimize the likelihood of errors, ensure regulatory compliance, and provide patients with the best possible care. Sterile medicines pose additional risks, which require a highly robust Risk Management System.

Compounder must ensure any item they are making is the right drug and right formulation for the right person at the right time. This includes verifying the following information:

• Risk assessment: All prescriptions for compounded medicines should have a risk assessment undertaken to ensure the product is appropriate for the patient at the time of compounding. This should occur regardless of whether the compounded medicine is new, or a repeat prescription.

• Cross-contamination prevention: Employ strategies to prevent cross contamination, especially when dealing with potent or hazardous drugs. This includes dedicated equipment and specific SOPs, such as protocols for cleaning workspaces and equipment.

• Double-check procedures: Implement systems for double-checking each compounded product, whether it's through peer review or additional safety protocols. Reducing human error is critical for patient safety.

• Quality verification: Implement systems to confirm that the correct ingredients were used, in the correct weights/ measurements. Digital record keeping, including the use of scanners, enables such an independent review. Validate the quality of the preparations by quantitative assessment and/or by qualitative assessment of the organoleptic properties.

• Sterile medicines: Confirm the endotoxin load of an injectable medicine is within specified limits. Monitor the physical, chemical or biological indicators of the sterilisation process such as filter passed an integrity test, temperature and pressure were within the specified ranges for the specified time during autoclaving, log reduction of biological indicator was appropriate. Monitor facilities and equipment for microbial and total particulate contamination, e.g. using particle counters, air samplers, and settle and contact plates.

9. Training and education

Training and education are fundamental components of maintaining high standards in compounding. Properly trained personnel ensure the accuracy, safety, and effectiveness of compounded medications, while also ensuring compliance with regulations and industry best practices. Ongoing education is also critical to ensure that pharmacy personnel stay updated on the latest industry practices, regulatory standards, and technological innovations, ultimately contributing to better patient outcomes and compliance with standards.

Proprietors and compounding pharmacists must ensure that all compounding staff have undertaken the following:

• Personnel certification and training: Ensure all compounding pharmacists and technicians have appropriate training in pharmaceutical compounding techniques, regulatory compliance, and patient safety, prior to commencing compounding for patients.

• Competency assessment: Evaluate whether employees are assessed for their skills and knowledge regularly, especially in handling specialized equipment or high-risk medications.

• Continual education: Pharmacists and technicians involved in compounding should regularly update their knowledge on compounding practices, new formulations, and regulations. Attending workshops, training sessions, and staying updated with relevant literature helps maintain competency. Training activities which include learning assessments are of higher value, as they provide feedback as to whether the learning objectives were met.

• Accredited programs: Participate in accredited training programs that focus on pharmaceutical compounding and the specific regulatory and safety standards within Australia, relevant to the type of compounding undertaken. • Third party potency testing: Periodicaly submit samples of frequently prepared complex or high-risk compounded medicines, to an analytical laboratory for testing. Test samples prepared by each compounding staff member.

• Sterile medicines: Validate the performance of compounding personnel, in accordance with their assigned responsibilities. These may include periodic observational audits, gloved-finger-thumb tests, aseptic process simulations (media fill program) and sterility testing of samples.

10. Self-assessment and audits

An essential component of Good Compounding Practice (GCP) is self-assessment and audits. They help ensure that the compounding process adheres to the highest standards of quality, patient safety, and regulatory compliance. Regular reviews, staff training, and adherence to SOPs are vital for maintaining high-quality standards in pharmaceutical compounding. By regularly conducting these assessments, pharmacies can identify potential risks, improve practices, and ensure that compounded medications meet the needs of their patients while reducing errors and ensuring compliance with relevant standards.

Compounding pharmacist staff must undertake regular assessment and suits to ensure:

• Improved patient safety: Regular audits help identify and correct issues before they impact patient health, ensuring compounded medications are safe and effective.

• Compliance with regulatory requirements: Staying in compliance with relevant regulations helps avoid fines, penalties, and potential legal issues while ensuring that compounded medications meet legal standards.

• Improving quality: Self-assessments allow pharmacies to continuously improve their processes by regularly reviewing their practices and comparing them to best practices, reducing errors and enhancing medication quality.

• Enhanced quality of practice: Ongoing assessments allow for continuous improvement in compounding practices, leading to better medication quality and patient outcomes.

• Increased confidence: Patients, healthcare providers, and regulatory bodies gain confidence in the pharmacy’s ability to produce high-quality, safe compounded medications.

Prepared by Tara Hehir, Professional Officer, Pharmacy Council and Patricia Ullman, Medisca Australia.