Understanding Sterile Compound Testing and Why It Matters

As a 503A compounding pharmacy, VLS Pharmacy is held to regulatory requirements by multiple governing bodies including the State Boards of Pharmacy, FDA, DEA, and credentialing agencies such as PCAB. Further, we hold ourselves accountable by subjecting our sterile drug compounds to tests that go above and beyond what is required of 503A compounding pharmacies. 

Quality Assurance or QA is a term that is often used as blanket terminology when in fact it is a very specific and actionable requirement of sterile compounding facilities in accordance with USP <71>. A key component of a QA program includes routine testing of sterile preparations. VLS Pharmacy actively tests sterile compounded products and results are available to our prescribing clinicians, upon request. Testing is nuanced and specific and understanding how and why tests are performed clarifies their importance and necessity. The below tests are performed by third-party, FDA-accredited analytical testing laboratories for the pharmaceutical industry. As a prescriber, you can rest assured that compounded medications from VLS Pharmacy have been subjected to rigorous testing by these unbiased third party experts. 

• Potency over time: A quantitative test that measures the strength (potency) of the medication over time intervals. Degradant is included. USP <1075> requires that medications are assigned a Beyond Use Date (BUD). Methods of performing this test include High-Performance Liquid Chromatography (HPLC) due to its efficiency and Titration which is based on a known chemical reaction with the drug. ²
• Stability: Measures the extent to which a product retains, within specified limits, and throughout its period of storage and use, the same properties and characteristics that it possessed at the time of compounding. A study commonly includes a stability-indicating method assay, sterility (for sterile preparations), endotoxin (for most sterile preparations), pH, visual inspection, particulate matter, preservative effectiveness, preservative quantification.¹ The method must separate the active ingredient from its degradants and impurities, as well as any other excipients in the preparation. The compound is exposed to high heat and humidity, UV radiation, an acid, a base, and a peroxide.³ It is this step that differentiates a stability-indicating test from a simple potency test. 
• Bacterial Endotoxin Testing (BET) as set forth by USP <85>: Endotoxins are remnants of bacterial cells that cannot be detected by a stability test. Bacterial endotoxins can pose health hazards, including death, if present in a sterile drug product. An endotoxin test detects toxins that are released from the cell wall of disrupted gram-negative bacteria. 
• Sterility testing detects microbial contamination. To obtain a satisfactory result, the sample must be free from contamination. Sterility testing should be performed on all drugs labeled as sterile and re-tested any time a process changes or new personnel begin compounding. This should be done in addition to testing on a regular recurring basis as part of an overall quality system.² 

Sterility testing is often conducted in two ways: 

1. Scan RDI ® Rapid Microbial Testing. See it here.
2. USP <71>: 14 day test using two-step membrane filtration. 

Sourcing and BUDs 

VLS Pharmacy sources raw materials from PCCA to ensure that the active pharmaceutical ingredients used to compound medications are free from bacteria endotoxins and to verify potency. This is an important and often overlooked decision by pharmacists-in-charge and unfortunately, it is very often tied to fiscal concerns. There are simply no shortcuts or coupon-cutting measures that replace a quality API source. 

A word about Beyond Use Date (BUD)

A specific date included on all sterile and nonsterile compounded prescription drug labels and USP defines it as: “the date after which a compounded preparation is not to be used and is determined from the date the preparation is compounded.”² The BUD must be noted and adhered to as does the multi-dose vial guidance set forth by FDA as 28 days after a vial is “opened or entered (e.g. needle puncture)”. 

Reach out to our team to learn about sterile compounding at VLS Pharmacy. 

All medications from VLS Pharmacy and New Drug Loft are prepared in a lab that follows safety and quality standards per our status as a 503A pharmacy.

Additional Reading:

• Learn more about Sterile Compounding at VLS Pharmacy. 
• Explore our compounding labs here. 
• Contact us today for all of your compounding needs. 

Sources:

1 United States Pharmacopeial Convention, Inc. United States Pharmacopeia 31–National Formulary 26. Rockville, MD: US Pharmacopeial Convention, Inc.; 2007. [In press.]  

2 https://arlok.com/laboratory-services/pharmaceuticals-testing , https://www.arlok.com/basics-sterility-testing-1 , https://www.fda.gov/media/117883/download pages 3,4

3 Kupiec TC. Dr. Kupiec’s corner: What’s in a name? Beyond use dating–101, 201,301. The Pharmacists Link. Oklahoma City, OK: Analytical Research Laboratories, Inc.; Spring, Summer, Fall 2003.