2 To Compound or not to Compound?

Non-sterile compounding is an essential service in pharmacy practice, allowing pharmacists to create customized medications when commercially available products are unsuitable or unavailable. However, this practice is tightly regulated and must always be guided by clinical, ethical, and legal standards.

Before proceeding with compounding, pharmacy personnel must assess whether it is necessary, appropriate, safe for personnel and feasible. This ensures that the preparation is in the best interest of the patient, complies with regulatory standards (e.g., NAPRA, provincial authorities), and can be performed safely within the pharmacy’s capabilities. Pharmacy personnel must also ensure the proposed compound fits within the pharmacy’s designated level of Compounding (ie Level A, B or C)

1. Assess Clinical Appropriateness

Before preparing any compound, the pharmacist must conduct a clinical assessment of the prescription. This includes:

• Evaluating the therapeutic rationale for the compounded product
• Ensuring the product is safe and effective for the intended patient
• Checking for allergies, drug interactions, or contraindications
• Assessing patient-specific factors, such as age, weight, and medical condition

Only when the prescriber’s intent is clinically justified and necessary should compounding be considered.

2. Determine Commercial Availability

Pharmacy personnel must determine if an appropriate commercially available product exists before compounding. According to regulatory guidelines, compounding must not be used as a substitute for an available approved product unless:

• The patient has an allergy or intolerance to excipients in the commercial product
• The dosage form or strength needed is not commercially available
• The patient cannot use the available form due to swallowing difficulties or adherence issues

Failure to consider commercial alternatives may violate federal regulations and lead to concerns about unauthorized manufacturing.

3. Verify the Existence of a Formulation Record

A Master Formulation Record (MFR) provides a validated recipe for the compound and is a required element of non-sterile compounding. If no recognized formulation exists, pharmacists must be cautious:

• Validated formulations can be found in reputable sources like:
  • PCCA database
  • The Hospital for Sick Children’s Compounding Guide
  • USP Compounding Compendium
  • Veterinary compounding references (for animal use)

• If no recognized formula exists, the compound may be considered experimental and should not be prepared unless the pharmacist has conducted an extensive literature review and documented the rationale.

4. Assess Risk and Determine Compounding Level

Every compound must be classified as Level A, B, or C based on a risk assessment, following NAPRA guidelines:

• Level A: Simple, non-hazardous compounds (e.g., oral solutions)
• Level B: Moderate risk (e.g., transdermal gels, capsules)
• Level C: High risk, hazardous ingredients (e.g., hormones, chemotherapy)

The risk level determines the facility, PPE, training, and procedures required.

Pharmacy personnel should refer to NAPRA’s decision-making algorithm to assign the correct risk level.

5. Assess Feasibility: Space, Equipment, and Ingredients

Even if compounding is appropriate, the pharmacy must ensure they have the infrastructure to perform it safely:

Facility Requirements

• Level A: Designated, clutter-free compounding space
• Level B: Enclosed, ventilated room
• Level C: Dedicated room with negative pressure and containment devices

Equipment and Tools

• Ointment slabs, mixers, balances, mortars and pestles, capsule machines
• Equipment should be dedicated, calibrated, and clean

Ingredient Availability

• All active and inactive ingredients must be in stock
• Expiry dates and storage conditions must be verified
• Use only compounding-grade or USP/NF-certified ingredients

6. Confirm Personnel Training and Availability

Compounding must be performed by trained and competent staff under appropriate supervision. Personnel must be:

• Assessed for competency and ongoing training
• Familiar with SOPs, risk mitigation strategies, and quality assurance
• Supervised by a compounding supervisor or designated manager
• familiar with appropriate DDC procedures (deactivation, decontamination, cleaning)

If trained staff are unavailable, compounding must not proceed.

7. Document the Decision

If compounding proceeds, all components of the decision must be documented:

• Rationale for compounding
• Source of formulation record
• Assigned risk level
• Facility and equipment used
• Staff members involved
• Any limitations or deviations

If compounding is not pursued, the rationale should still be recorded, and the patient or prescriber should be informed with appropriate alternatives suggested.

8. Know When to Refer

If the pharmacy is unable to meet any of the requirements—such as lacking the space, ingredients, or trained staff—they must refer the patient to another compounding pharmacy that can fulfill the prescription. This supports continuity of care while protecting patient safety and professional accountability.  This decision may involve several people (the compounder, prescriber, pharmacist, etc.)

Here are some examples that you can use to guide you in your own decision making process:

Example 1: 

Scenario:
A physician writes a prescription for a 5% lidocaine topical gel for a pediatric patient who is allergic to commercial topical anesthetic patches. There is no commercial preparation with only lidocaine and no preservatives.

Questions to Consider:

• Is compounding clinically appropriate? ✅ Yes – due to allergy and need for a specific formulation.
• Is there a formulation record available? ✅ Yes – a PCCA formula is available.
• What is the risk level? ✅ Moderate risk – non-sterile semi-solid with active drug.
• Does the compound fall in Level A, B or C? Does it fall within the Pharmacy’s level of compounding? ✅ Yes.
• Do we have the space and equipment? ✅ Yes – lab and ointment slab are available.
• Does this meet the pharmacy’s level of compounding? ✅ Yes.
• Are the ingredients available? ✅ Yes.
• Is trained staff available? ✅ Yes.

Decision: ✅ Proceed with compounding

Example 2:

Scenario:
A prescriber requests a flavored amoxicillin gummy preparation for a child who refuses all liquid antibiotics.

Student Questions to Consider:

• Is compounding clinically appropriate? The pharmacist must make this decision. ✅ Yes – adherence issue with standard forms.
• Is there a formulation record available? ❌ No – no recognized formula in literature or compounding databases.
• What is the risk level? ⚠️ Uncertain – novel dosage form.
  • Consider allergen potential of API- default to higher risk level due to potential cross contamination.
• Do we have the space and equipment? ⚠️ Yes, but equipment may not suit gummy prep.
• Does this meet the pharmacy’s level of compounding? ✅ Yes.
• Are the ingredients available? ✅ Yes.
• Is trained staff available? ✅ Yes.

Decision: ❌ Do not proceed without a validated formulation.
Consider contacting another compounding pharmacy or prescriber.

Example 3: 

Scenario:
A prescription for an oral suspension of spironolactone is received. The pharmacy has no oral liquid compounding tools or space for compounding.

Student Questions to Consider:

• Is compounding clinically appropriate? ✅ Yes – needed for pediatric dosing.
• Is there a formulation record available? ✅ Yes – available in Hospital for Sick Children Compounding Guide.
• What is the risk level?  High risk – oral liquid.
  • note where Spironolactone falls within NAPRA levels due to steroid and hormonal activity
  • NIOSH list of Hazardous Drugs
• Do we have the space and equipment? ❌ No.
• Does this meet the pharmacy’s level of compounding?❌ No.
• Are the ingredients available? ✅ Yes.
• Is trained staff available? ✅ Yes.

Decision: ❌ Do not proceed.
Refer the patient to a pharmacy that has appropriate facilities.

Example 4: 

Scenario:
A veterinary prescription requests a metronidazole 10 mg/mL oral suspension for a dog. The active ingredient is not in stock.

Student Questions to Consider:

• Is compounding clinically appropriate? ✅ Yes – no suitable veterinary commercial preparation.
• Is there a formulation record available? ✅ Yes – veterinary compounding references.
• What is the risk level? ✅ Simple risk.
• Do we have the space and equipment? ✅ Yes.
• Does this meet the pharmacy’s level of compounding? ✅ Yes.
• Are the ingredients available? ❌ No.
• Is trained staff available? ✅ Yes.

Decision: ❌ Do not proceed.
Order ingredients if time allows or refer the client.

Deciding whether to compound a non-sterile preparation involves more than fulfilling a prescription, it requires a systematic, risk-based assessment of patient needs, available alternatives, regulatory standards, and the pharmacy’s internal capabilities.

If any critical element—validated formula, space, equipment, ingredients, or trained personnel is missing, the compound must not be prepared. Documented, professional judgment should guide whether to proceed or refer the patient.