What is Sterile Compounding?

Sterile compounding involves preparing medication in an environment free from bacteria, viruses, or any other potentially infectious microorganisms. Sterile compounding is used for preparations that will be administered either through an IV, injection, or directly into the eyes.

Medicinal compounding has its roots in ancient hunter-gatherer societies. Ingredients found in the natural environment were used to anoint the sick, perform religious ceremonies, and enhance the prowess of tribal hunters. By the Middle Ages, these practices had evolved into the spiritual pseudo-sciences of alchemy. ^[1]

The closing of the Middle Ages gave rise to the development and growing respect for the scientific method. Thus, medicinal compounding was transformed by the modern chemist and pharmacist. 

Now, the scientific community was equipped to separate fact from myth. 

One of the more amazing developments of this new way of thinking was the discovery of coal tar derivatives to create sulfa drugs. This breakthrough became the foundation of antibiotic therapy. ^[2]

Antibiotics were only the beginning. In the short span of just 150-200 years, exponential improvements in the art and science of pharmaceutical compounding have led to massive advancements in high-quality health care. 

Now, powerful pain management medications can be injected intrathecally (into the spine); parenteral nutrition keeps patients alive and speeds the healing process, and dialysis patients are prevented from being poisoned by their poorly functioning kidneys. 

Advances in evidence-based medicine with the support of regulatory standards that guide the sterile compounding of drug products make these benefits possible.

In this post, our experts at Fagron Sterile Services (FSS), a 503B Outsourcing Facility, will discuss the major components of safe, efficient, and effective sterile compounding. It is a complex process that is guided by structured regulatory procedures and adherence to sterile compounding best practices. 

The result is a consistent and reliable supply of compounded sterile preparations (CSP) to hospital pharmacies, health systems, and clinics.  

Non-sterile vs. Sterile Compounding

Non-sterile preparations are those that are prepared in an area that is clean, but not necessarily free of microorganisms. They are never injected, or used in the eyes. Examples of these are topical creams, oral medications, or suppositories. ^[3] 

Sterile products, on the other hand, must be compounded in such a way to produce as clean of a product as possible. Examples of sterile products include ophthalmic solutions, injectables, or parenteral nutrition. ^[4] Both sterile and non-sterile compounded drugs are created for patients who cannot tolerate products that may not be normally commercially available.

Sterile and non-sterile compounding share one important purpose: that is to accommodate the unique needs of patients who might benefit from drug formulations that are not otherwise commercially available. 

Some examples are patients who have allergies to certain dyes, and children or seniors might need who need different dosage forms than what is normally available.^[5]

Regulations and Best Practices

United States Pharmacopeia (USP)

USP was founded in 1820 in Washington DC. It is an independent, non-governmental volunteer organization that determines quality, purity, and strength standards for medicine, food ingredients, and dietary supplements. 

The USP has a global reach, providing valuable assistance on issues such as quality control, pharmaceutical training, and preventing the distribution of low-quality medications to the public. Many USP standards are enforceable by the US Food and Drug Administration (FDA). ^[6] The organization has a major influence on safe sterile compounding procedures.

The objective of USP General Chapter 797 – Pharmaceutical Compounding, Sterile Preparations is to describe conditions and practices that can prevent the following types of patient harm:

• Microbial contamination.
• Excessive bacterial endotoxins.
• Unacceptable variability in intended strength of ingredients.
• Unintended chemical/physical contaminants.
• Ingredients of inappropriate quality in CSPs. ^[7]

USP Chapter 797 places a strong focus on the proper training and competency of pharmacy technicians and other compounding personnel. Sterile compounding services standard operating procedures regarding the use and sanitation of cleanrooms, anterooms, buffer areas, and other spaces in which aseptic technique is performed.

Hygiene, gowning, and cleaning practices are absolutely essential in sterile preparations.[8] In fact, studies have shown that 80% of all contamination in sterile compounding comes from people. It is also interesting to note that every 24 hours, humans shed about 10 million particles. [9] Thus, it is quite apparent why USP has an extensive focus on personnel training.

The importance of verifying the sterility, accuracy, and purity of the finished CSPs is emphasized in USP 797. This requires continuous testing, monitoring, and documentation to confirm that environmental quality, aseptic manipulation practices, and sanitization protocols have occurred.

The Food and Drug Administration (FDA)

High-quality sterile compounding practices are critical in numerous types of medical therapies. Injectable and other intravenous (IV) medications, for example, must be free of microorganisms and other pathogens. 

When injected into the bloodstream, these medications bypass the body's normal defense system. If the medication contains microorganisms or other objectionable pathogens, patients are subsequently at high risk of infection. ^[10] 

In the United States, oversight of safe and effective sterile compounding by 503B outsourcing facilities falls to the FDA. The primary vehicle for compliance is Current Good Manufacturing Practices (cGMP). 

Like the standards as outlined in USP 797, FDA emphasizes quality assurance, personnel training, environmental monitoring, and continuous validation of aseptic processes. The rooms in which sterile compounding occurs must be rated at ISO level 5 or better, as documented by airflow studies, HEPA testing, and the appropriate unidirectional airflow.^[11] 

According to cGMP (as well as USP 797), CSPs must be labeled with a Beyond-Use-Date (BUD), not an expiration date. The expiration date of a pharmaceutical is determined by scientific evidence and rigorous testing. 

When determining a Beyond-Use-Date, the time for repackaging, storing, and transporting is calculated.  It should be noted that BUDs are not to exceed the expiration dates of any of the active or inactive pharmaceutical ingredients. ^[12] 

Institute for Safe Medication Practices (ISMP)[13]

The ISMP is an independent, non-profit, patient safety organization that works with health care practitioners, institutions, regulatory agencies, and consumers to continuously improve medication safety. 

Its role in sterile compounded preparations includes the adoption and communication of numerous standard operating procedures and quality standards during the compounding processes. 

Of particular note, is the ISMP recommendations regarding batches of CSPs. (503B Outsourcing Facilities manufacture compounded drugs in batches to respond to supply needs.) They emphasize the value of a Master Formulation Record that contains the following:

• Product name, strength, and dosage form.
• Identities/amounts of all ingredients.
• BUD storage requirements.
• Sterilization method used.
• Quality control procedures. 
• Appropriate container closure systems.

When choosing an outsourcing compounder for parenteral nutrition, ISMP states that only an FDA-registered 503B facility may compound non-patient-specific products.

503Bs can offer some very important patient safety assurances in that they must adhere to cGMPs and receive periodic FDA inspections. 503A sterile compounding pharmacies provide such services under the order of individual prescribers. 

Emerging Trends 

An interprofessional summit between PEW Charitable Trust, The American Society of Health-System Pharmacists (ASHP), and the American Hospital Association (AHA) revealed several emerging trends in compounded sterile preparations. 

Most notable is that many hospital pharmacies are realizing the advantages of obtaining CSPs from external sources rather than compounding in-house. These benefits include greater assurance of sterility and quality as well as immediate availability of in-demand compounded preparations. 

This is particularly advantageous for smaller rural hospitals with limited staff and other resources. Drug shortages may in some cases increase reliance on CSPs to replace pharmaceuticals that may not be available.^[14] 

The current COVID-19 pandemic has definitely increased public awareness of the possibility of drug shortages. 

Emergent challenges regarding getting compounded medications to patients and to the health care professionals who prescribe them are not lost on the Fagron Executive Leadership: 

"Fagron maintains a greater than 97 percent fulfillment rate, meaning that more than 97 percent of the time an order is placed that order is filled the same day. 

Organizations that experience recurrent unexpected delays in shipping, batch rejections that impact fulfillment rates, or frequent finished goods inventory shortages is a signal of lack of operational discipline and poor quality in operations."  Jason Winfield, Vice President of Operations, Fagron Sterile Services.

A variety of compounding technologies have been emerging onto the market that helps compounders to respond faster and more efficiently to customer needs. These include,

• Barcode verifications systems. (See Fagron's TALLMan lettering).
• Workflow systems that use barcode verification and images.
• Automated multiple ingredient compound devices for use in parenteral nutrition.
• Imaging sharing/remote video for supervisory purposes. ^[15]

Conclusion

Medicinal compounding practices may likely be as old as human society itself. Since those early endeavors, the urge to improve the quality of life and to save lives moves forward at an unrelenting pace. 

This article described multiple characteristics of state-of-the-art sterile compounding practices as conducted by 503B outsourcing facilities; and furthermore how these best practices are supported by non-profit, professional, and regulatory organizations.  

Key Takeaways

1. Although both sterile and non-sterile compounding requires a certain level of sterilization and hygienic practices, the sterile compounding aseptic technique is necessary for maximum patient safety.

2. United States Pharmacopeia (USP), as well as cGMP as designated by the United States Food and Drug Administration, provides a regulatory framework for safe and effective sterile compounded medications. 

3. FDA-registered 503B Outsourcing Facilities with a dedication to quality assurance and adherence to all standard operating procedures are well-positioned to meet the needs of hospital systems, health clinics, and pharmacies.

4. Emerging technologies and trends continue to enhance and improve sterile compounding practices.

Fagron Sterile Services is an FDA-registered 503B outsourcing facility that proudly provides sterile compounding services for anesthesia, ophthalmics, pain management, and specialty pharmaceutical solutions. To learn more about sterile compounding, call 1-877-405-8066 or speak to a rep today.