Compounding Medications
By Sandra Jones, Ambulatory Strategies Inc.


“Our doctors were upset when I told them we had to change how we handle mixing of medications. We have mixed drugs, especially for cataract cases, for years.  Another  administrator said we cannot do this because it is compounding and nurses cannot compound.  For cataract cases, we have added a mixture to our BSS irrigation bottles.  Some doctors prefer a “cocktail” be administered while others requested we soak pledgets in a mixture. What can we do?”


Legislation about compounding and compounding pharmacies passed in 2013 to require a licensed pharmacist oversee compounding, register with the FDA as an outsourcing facility, and compound medications following nationally recognized standards such as the United States Pharmacopeia (USP). Some state pharmacy regulations specifically refer to USP 797 Standards as does the FDA.

Sterile compounding requires an International Organization for Standardization (ISO) Class 5 environment, which relies on a special type of HEPA  filter.  In addition, buffer areas for air supply control are necessary.  Hardly any surgery centers have the environment or the equipment for sterile compounding.

Compounding is mixing more than three products or using manipulation to alter products. A nurse can mix together two or three drugs.  And USP 797 Standards provides clarification for this immediate use exemption for the mixing up to three medications.

Immediate use is defined by USP 797 as emergent preparations (such as epidurals prepared by anesthesia) for immediate injection or infusion, diagnostics, short-stability medications that must be prepared immediately before administration, and any non-hazardous preparations that might cause harm due to delays in administration. The medication preparation area must be clean, uncluttered, and functionally separate to avoid contamination of medications. The administration of the mixture must be initiated within one hour of mixing and administration must be completed within 24 hours. Vancomycin when added to an IV, for example, must be initiated within one hour of mixing, but, the administration can last for up to 24 hours. The mixing process must be simple and involve the transfer of no more than three commercially available sterile, nonhazardous products from the manufacturers’ original containers.

According to the American Society of Health-System Pharmacists Guidelines for Compounding Sterile Preparations, immediate use compounded sterile preparations (CSP) do not need to be mixed in an ISO Class 5 environment and garbing and gowning are not required as long as all the following criteria are met:

  •     Hand hygiene is conducted per CDC recommendations;
  •     Aseptic technique is followed;
  •     No hazardous drugs are used;
  •     Only simple transfer of no more than three sterile, non-hazardous drugs in the manufacturer’s original containers are involved in the mixing, and no more than two entries into any one container occur;
  •     No more than 1 hour elapses from the time mixing commences to the time administration to the patient begins;
  •     No batching or storage occurs;
  •     If the mixture is not administered immediately, it must be under the continuous supervision of the person who prepared it and it must be labeled with patient identification, names and amounts of all ingredients, name or initials of preparer, and exact 1-hour BUD (beyond use date) and time;
  •     No foreign products can be added to the mixture (e.g., pledgets); and
  •     Discard mixture if administration has not started within 1-hour of mixing.

Note again that no more than three medications can be mixed for immediate use. BSS or an IV fluid would be considered one; therefore, only two more medications could be added.  Some surgery centers have changed their “cocktail” for cataract surgery patients to meet this limitation of three ingredients.  Another item of caution is that most BSS bottles now contain a label stating nothing is to be added to the BSS.  Adding a mixture to a BSS bottle would be considered using a medication off-label. Many physicians accept the risks associated with off-label use due to their extensive experience in adding medications to BSS and achieving excellent patient outcomes.  Using a compounding pharmacy may increase costs and still not assure safety as we learned from the fungal meningitis traced back to the New England Compounding Center.  With new federal regulations for compounding pharmacies in place, there are federal requirements, inspections, and required ordering and labeling that increase process complexity for a health care facility as well as the compounding pharmacy.

If you mix medications, make certain your staff is following state and federal regulations by (1)reviewing with your pharmacy consultant if your state regulations go beyond USP 797, (2) having your pharmacy consultant review your policies and procedures on mixing and administering the mixed medications to assure compliance with state and federal regulations, (3) reviewing with your physicians who order a mixture of medications, (4) providing education to your staff, and (5) auditing periodically to confirm employees are following policy.