Hospital pharmacies have faced an unprecedented number of injectable drug shortages over the last several years. The American Society of Health-System Pharmacists (ASHP) Web site currently lists more than 150 active shortages of injectables from numerous drug classes, including narcotics, anesthetics, neuromuscular blockers, electrolytes, vitamin and mineral injections used in parenteral nutrition, chemotherapy agents, anticonvulsants, antibiotics, antivirals, heart medications from various classes, 5HT3 antagonists and other antiemetics, and H2 receptor antagonists.
Health care facilities are faced with tough decisions in identifying ways to stretch available commercial product when shortages occur. Outsourcing and in-house compounding of products in short supply are options that must be carefully considered as a response to these shortages. Appropriate policies and procedures have to be created and implemented before commencing either outsourced or in-house compounding, because both options involve potential risks to patients that must be considered and addressed. Regardless of the immediate and very real pressure that shortage situations generate, patient safety must serve as the number one criterion in deciding how to address shortages appropriately.
Due Diligence Around Outsourcing Services
Ensuring the safety of any procured product is of prime importance when considering the option of outsourced compounding to meet demand caused by shortages. Due diligence is required to minimize your institution’s liability should there be a problem with an outsourced product. If you have a pre-existing relationship or if you are developing a relationship with an outsourcer, it is imperative that you verify how they are licensed and understand how they operate. The ASHP Guidelines on Outsourcing Sterile Compounding Services provides an excellent review of factors to consider (Available at: http://www.ashp.org/DocLibrary/BestPractices/MgmtGdlOutsourcingSterileComp.aspx).
Purchasing from a sterile compounding company can provide some relief from your shortage crisis, but keep in mind that the outsourcer will likely be subject to the same shortages that your facility is facing. Thus, an important question to ask is: Where is the company obtaining compounding materials? Is the outsourcing company:
Each of these processes should be well documented, with appropriate accompanying end-product testing. If the outsourcer is compounding from nonsterile ingredients, it critical to request additional information about their quality assurance processes. You must be confident that the outsourcer employs safe procedures and that quality assurance processes are in place so that steps are not missed, even—and especially—during stressful shortage situations. See Table 1 for a checklist of processes to review when choosing an outsourcer.
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Quality Practices Reduce Errors
Before addressing shortages by compounding or repackaging in-house, appropriate policies must be in place to ensure that such compounding is performed reliably and that the procedures used result in a safe final product. Batch compounding, especially from nonsterile ingredients, requires different processes than patient-specific compounding. Each employee who participates in this type of compounding should be versed in the basic principles of quality practices in order to minimize risk. There is no room in the process for error or uncertainty.
Establish internal limits for what products you will and will not compound in-house based on your facility’s level of compounding expertise and ability to confirm quality assurance of final products. For example, if you do not typically compound high-risk products, you should not attempt to do so in response to a shortage. Training, competency testing, the correct equipment, quality assurance plans, and appropriate facilities for high-risk compounding must first be in place before any such compounding can begin.
The three most common options for in-house compounding are the same as those used for outsourcers: repackaging, diluting, and compounding from nonsterile ingredients. Each of these processes must be completed in a USP <797>-compliant cleanroom by competent, trained, and tested personnel. Establishing standard procedures for each type of process and a standard quality assurance program will ensure that a safe product is made in high-pressure shortage situations. In-house compounding without pre-established safeguards is a risky proposition and should not be considered.
Repackaging without additional manipulation is the simplest process to implement. This involves taking a commercial drug from a sterile bulk container and aseptically transferring an aliquot into a smaller, sterile final container.
Manipulating a Commercial Product
This process entails dilution of a more concentrated product, followed by repackaging or preparation into the unit-of-use product. The exact method will be specific to the final preparation. Research or testing may be necessary to determine the stability of the final result.
High-risk Compounding from Nonsterile Ingredients
A high-risk process must be well documented, as you are essentially performing small-scale manufacturing from raw ingredients. The chemical stability of the drug must be investigated, and to this end, choice of diluent is important. Depending on the drug, stabilizers may be needed, and it also may be necessary to adjust the pH.
Sterilization methods also must be considered; many drugs can be sterilized by filtration. If filtration is not an option, other sterilization methods can be used, but they are more difficult and require specialized equipment. For each sterilization method, verification—such as bubble-point testing of filters—must be carried out.
See Table 2 for points to review each time that compounding occurs.
Coping with drug shortages undoubtedly presents challenges, and many times the choices available are less than ideal. As pharmacists, we must evaluate all options in order to provide the safest, most effective care for our patients. Compounding can seem like an easy solution, but if we are not properly prepared to implement it, we can put patients at risk by taking shortcuts in high-pressure situations. When compounding is the only possibility, establishing proven methods of decision-making around the process and verified procedures for developing and testing compounded products is essential for patient safety.
Angela Yaniv, PharmD, is the assistant director of pharmacy for sterile products, at Cleveland Clinic in Cleveland, Ohio.