Sterile Compounding (IV Admixtures): A Critical Skill for Hospital Pharmacists, Understanding USP 797 Guidelines Is Non-Negotiable.

Sterile Compounding (IV Admixtures): A Critical Skill for Hospital Pharmacists, Understanding USP 797 Guidelines Is Non-Negotiable.

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Sterile compounding of IV admixtures is one of the most safety-critical tasks in hospital pharmacy. A single lapse in aseptic technique, environmental control, or labeling can seed an infection, cause emboli, or deliver the wrong drug or dose. That is why understanding and applying USP <797> is non-negotiable. The standard turns best practice into measurable, auditable steps so patients get sterile, accurate, and stable preparations every time.

Why Sterile Compounding Is High Stakes

IV drugs bypass the body’s defenses. Any microbes, endotoxins, or particulates you introduce go straight into the bloodstream. Poor technique can cause bloodstream infections, sepsis, or occluded lines. Incorrect diluent, concentration, or calcium–phosphate precipitation can injure kidneys or lungs. USP <797> exists to control these risks with consistent facilities, workflows, and verification.

What USP <797> Expects Today

Facilities and air control. Sterile compounding occurs inside a Primary Engineering Control (PEC)—for example, a laminar airflow workbench (LAFW) or biological safety cabinet (BSC)—that provides ISO 5 air. The PEC must be located either in:

  • Cleanroom suite: An ISO 7 buffer room and an ISO 7/8 ante-room with positive pressure and proper air changes; or
  • Segregated Compounding Area (SCA): A designated, low-traffic, clean space for shorter BUD preparations.

The PEC should run continuously. If it is turned off, clean and disinfect it and allow the manufacturer-specified purge time (commonly 30 minutes) before use. Certification of PEC and room airflow/pressures occurs at least every 6 months and after any relocation or major service. This matters because stable unidirectional HEPA-filtered air is the primary barrier against airborne contamination.

CSP categories and default BUDs. USP <797> classifies compounded sterile preparations (CSPs) by the compounding environment and controls:

  • Category 1: Made in an SCA or cleanroom; short BUDs. Typical defaults: up to 12 hours at room temperature or up to 24 hours refrigerated.
  • Category 2: Made in a fully compliant cleanroom suite; longer default BUDs without sterility testing. Typical defaults: up to 4 days at room temperature, 10 days refrigerated, 45 days frozen.
  • Category 3: Made in a cleanroom suite with additional controls (e.g., sterility testing, endotoxin testing, and container-closure integrity). Allows extended BUDs when all requirements are met. Use the USP tables and stability data to set specific BUDs.

These times control microbial risk. Always check chemical stability too. If the drug degrades faster than the microbial limit allows, the shorter time governs.

Personnel garbing and competency. Proper garbing and aseptic technique protect the ISO 5 environment from the largest contamination source: people. USP <797> requires documented training and competency that includes:

  • Hand hygiene and garbing technique using low-lint garments and sterile gloves.
  • Gloved fingertip and thumb sampling: Zero CFUs required for initial qualification (usually three consecutive passes) and then at least semiannually.
  • Media fill to prove aseptic technique initially and at least semiannually.
  • Competency on cleaning, disinfection, and equipment use.

These checks catch technique drift before it harms patients.

Cleaning and disinfection. Microbes accumulate on surfaces even in clean rooms. Clean and disinfect to a defined schedule with sterile agents and wipes:

  • PEC: At the start of each shift, before each batch, every 30 minutes during continuous compounding, after spills, and when contamination is suspected.
  • Counters/work surfaces: Daily.
  • Floors: Daily.
  • Walls, ceilings, doors, storage shelving: Monthly.
  • Sporicidal agent: At least monthly on appropriate surfaces to address bacterial spores.

Always clean from cleanest to dirtiest, top to bottom, and back to front. Let disinfectants (like sterile 70% IPA in the PEC) sit for full contact time. This prevents surviving organisms from colonizing your workspace.

Environmental monitoring. You must prove the environment stays in control:

  • Nonviable particle and airflow testing: During initial and 6-month certifications.
  • Viable air sampling: At least every 6 months.
  • Surface sampling: Monthly in PEC, counters, and other critical sites, after cleaning.

Trend the data and act on excursions. Any colony growth inside the PEC is a red flag and triggers investigation and corrective action. This is how you catch hidden problems like poor technique or failing HEPA filters.

Aseptic Technique That Actually Protects Patients

Technique determines whether the ISO 5 air can do its job.

  • Work inside the PEC’s first air. Do not block airflow to critical sites (vial septa, needle hubs, open IV ports).
  • Disinfect vial stoppers and ports with sterile 70% IPA using friction and allow dry time. Wet alcohol can carry microbes into the fluid path.
  • Use sterile, single-use needles and syringes. Do not pre-open components; open just before use.
  • Use a filter needle for ampules to remove glass particulates.
  • Minimize touch points. If you touch a critical site, replace or re-disinfect as appropriate.
  • Keep the PEC uncluttered. Too many items cause turbulence and block first air.
  • Label each syringe or intermediate container immediately to prevent mix-ups.

Building Safe IV Admixtures: Practical Checks

Order and calculation verification. Verify indication, dose, route, diluent, rate, allergies, and duplications. Recalculate independently. A second check must verify ingredients, lot/expiry, math, and final volume. This catches arithmetic errors that can be fatal at IV concentrations.

Compatibility and stability. A clear bag is not proof of safety. Use reliable references and watch for well-known pitfalls:

  • Calcium–phosphate precipitation in parenteral nutrition. Add phosphate first, calcium last, keep low pH and low temperature, and watch total mEq and product solubility.
  • Ceftriaxone + calcium can precipitate. Avoid co-administration in neonates and separate lines and times in others.
  • Filters: Use 0.22-micron for most aqueous solutions to remove particulates and microbes during administration; use 1.2-micron for lipid-containing admixtures (e.g., 3-in-1 PN).
  • Adsorption to PVC (e.g., nitroglycerin, insulin) can lower delivered dose; select non-PVC sets when indicated.
  • Light sensitivity (e.g., nitroprusside, amphotericin B) requires protection from light to prevent degradation or toxic byproducts.
  • Y-site incompatibilities: Check before co-infusing. Physical compatibility avoids in-line precipitation and catheter occlusion.

Osmolality and route. Peripheral IVs tolerate limited osmolality and irritants. As a practical guardrail, keep peripheral admixtures at or below about 900 mOsm/L; use central access for higher values or extremes of pH. This prevents phlebitis and tissue injury.

Sterilization approach. If you cannot terminally sterilize, you must use aseptic processing in ISO 5 with sterile components. For sterilizing a solution by filtration, use a 0.22-micron sterile filter and perform filter integrity testing when required. Terminal sterilization, when feasible and compatible, supports longer BUDs because it reduces microbial risk more reliably.

Labeling, Storage, and BUD Assignment

Your label is a safety tool, not a formality. Include:

  • Patient name and identifiers.
  • Drug name(s), strength(s), total doses, and final concentration.
  • Diluent type and final volume.
  • Route and infusion rate (or instruction: intermittent vs continuous).
  • BUD and storage conditions (e.g., refrigerate, protect from light, do not freeze).
  • Auxiliary warnings (e.g., use 0.22-micron filter).
  • Preparer and checker initials; lot numbers for traceability.

Assign the BUD based on USP category, environmental controls, sterility testing (if applicable), and drug-specific stability. If chemical stability is shorter than the microbial allowance, use the shorter period. Store as required, and quarantine doses that are pending test results when your procedure demands it.

Hazardous Drugs Require Additional Controls (USP <800>)

For antineoplastics and other hazardous drugs, compound in a negative-pressure ISO 7 room using a BSC or CACI and appropriate closed-system transfer devices when feasible. Follow a four-step surface process—deactivation, decontamination, cleaning, disinfection—with agents suitable for the drug and surface. Use chemotherapy-rated gloves and gowns, and dispose of waste in HD containers. These controls protect workers and prevent HD residue from contaminating other CSPs.

Common Failure Points and How to Fix Them

  • Insufficient disinfectant contact time: Build a visible “wet time” pause into the workflow. A 10–20 second dry time for IPA on stoppers and gloves is typical; follow your product labeling.
  • Blocking first air: Use low-profile trays, keep hands downstream of airflow, and position critical sites at the front third of the PEC.
  • Cluttered PEC: Stage only what you need for the current task. Excess items create turbulence and shed particles.
  • Worn or shedding wipes: Use sterile, low-lint wipes. Replace as soon as they become dry or soiled.
  • Unlabeled intermediates: Label syringes immediately with drug and concentration to avoid look-alike errors.
  • Poor garbing sequence: Don in correct order (shoe covers, head/facial hair cover, face mask/eye protection if used, hand hygiene, gown, sterile gloves). Any break sends you back to an earlier step.
  • Expired or improperly mixed cleaners: Date all prepared solutions and discard on schedule. Use sterile water for dilution when required.
  • Multi-dose vial misuse: Respect beyond-use dating after first puncture and discard if sterility is in doubt.

Quick, Effective Training and Competency Program

Build training around the exact tasks you expect staff to perform. Use checklists that mirror your SOPs. Teach the rationale behind each step so staff know what not to compromise under pressure. Document initial and semiannual competencies: garbing, hand hygiene, PEC use, aseptic manipulations, cleaning, gloved fingertip sampling, and media fill. When someone fails a test or shows technique drift, retrain and re-evaluate before independent work resumes. This keeps standards consistent across shifts and sites.

Responding to Environmental or Process Failures

Have a written response plan. When air or surface samples exceed action levels, or when there is visible contamination or technique failure:

  • Stop affected compounding, quarantine impacted CSPs if indicated.
  • Re-clean and disinfect, including sporicidal if appropriate.
  • Investigate root causes (technique, cleaning gaps, HVAC, increased traffic).
  • Retrain staff on specific failures.
  • Increase monitoring frequency temporarily to confirm control is restored.
  • Document findings and corrective/preventive actions.

Final Takeaways

  • USP <797> is about controlling every variable—air, surfaces, people, and time—to keep microbes and particulates out of IV admixtures.
  • Know your CSP category and apply the correct default BUDs. Do not exceed chemical stability.
  • Technique matters: protect first air, disinfect correctly, and minimize touch contamination.
  • Clean and monitor on schedule. Trend results and act on excursions right away.
  • Verify calculations, compatibility, and labels every time. Independent checks prevent rare but catastrophic errors.

Sterile compounding is a craft and a system. When pharmacists apply USP <797> with discipline and understand the “why” behind each step, patients receive IV therapy that is not only effective, but predictably safe.

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