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The United States Pharmacopeial Convention, Inc. recommends within the standards of the United States Pharmacopeia that com­pounding pharmacies have staff dedicated to quality assurance and quality control to ensure patients are receiving safe medica­tions. The quality-control program must include testing. While compounding pharmacies have grown familiar with potency, ste­rility, and endotoxin testing, there are many more tests recom­mended within the United States Pharmacopeia that are critical for evaluating the quality of compounded preparations. This arti­cle discusses when a few of these tests should be utilized, how to assign acceptance criteria, and how test results are obtained.

Tests for Burkholderia cepacia Complex

USP <60>, Microbiological Examination of Nonsterile Products – Tests for Burkholderia cepacia Complex, describes a test procedure that evaluates the microbiological quality, specifically the presence of species of the genus Burkholderia, in non-sterile substances and preparations.  This is important, because Burkholderia is a potentially dangerous pathogen, especially for drugs or raw materials that are intended for inhalation use, and aqueous preparations for oral, oromucosal, cutaneous, or nasal administration. 

There are several clinical reasons why it is important to screen for this genus of microorganisms.  First, they are Gram-negative, indicating their presence will produce endotoxins, potentially triggering a pyrogenic effect in a patient.  Burkholderia is an opportunistic pathogen, commonly causing pneumonia in immunocompromised persons or those with existing lung diseases.  Lung infection from Burkholderia is dangerous, and is characterized by a steep decline in function, potentially resulting death.  According to Lyczak (2002), death rates can be nearly 5x higher in Cystic Fibrosis (CF) patients infected with Burkholderia vs non-infected CF patients.  This, combined with its ability to spread person to person via body fluids, generally results in strict isolation procedures if detected in the hospital setting.  Burkholderia are naturally resistant to many antibiotics, including aminoglycosides and polymyxin B.  Treatment generally requires a combination of several antibiotics.  Combinations of ceftazidime, doxycycline, chloramphenicol, and others have been used as successful treatment options.

What are Endotoxin Challenge Vials...

Just as crucial as the sterile production of drug products is ensuring those same products are free of dangerous pyrogens - contaminants that induce febrile reactions in patients if introduced at high levels.

Relative to patient safety, the most concerning and common pyrogen is bacterial endotoxins. Pyrogens can be removed or destroyed by depyrogenation. A common method for depyrogenation is dry heat. Largely reproducible and easily controlled, dry heat depyrogenation is dependent on temperature and time to eliminate bacterial endotoxins. The depyrogenation process can be qualified and monitored with Endotoxin Challenge Vials (ECVs).

Ophthalmic Medication and Particulate Matter

Ophthalmic medications must meet particulate matter test requirements. Particulate matter may come from foreign or product-related substances. Clinical exposure to unwanted particulate matter can cause a biological response in patients including blocking capillaries and arteries, introducing microorganisms and causing an infection, or causing an allergic reaction. 

Cleaning Validation

A cleaning validation demonstrates a pharmacy, hospital, or outsourcing facility's cleaning procedure is effective and consistent in cleaning equipment and compounding surface areas. The Food and Drug Administration (FDA) expects firms to have written procedures (SOP's) detailing the cleaning processes used for various pieces of equipment. According to the FDA, 21 CFR Part 211, "Equipment and utensils shall be cleaned, maintained, and, as appropriate for the nature of the drug, sanitized and/or sterilized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements." A cleaning validation is how one proves their cleaning SOPs are sufficient.

USP 800 Surface Wipe Sampling

According to Center for Disease Control and Prevention (CDC), over 8 million US healthcare workers are exposed to hazardous drugs (HDs) every year. Drugs classified as hazardous include cancer therapy, antiviral drugs, hormones, and bioengineered drugs.  

More than 12 billion doses of HDs are handled by US providers each year. Anyone handling HDs is at risk of exposure to acute and long-term effects including hair loss, cardiac toxicity, kidney damage, hearing loss, nausea, rashes, cancer, and infertility. 

Data Integrity

According to the FDA, ensuring data integrity is an important component of industry's responsibility to ensure the safety, efficacy, and quality of drugs. ARL Bio Pharma has GMP software that controls our laboratory's instruments and generated data. This software complies with 21CFR Part 11 as it relates to electronic records. All data is locked down and backed up so ARL can retrieve information in its native format with tracked changes and modifications. Our validated software meets FDA's expectation for GMP Compliance to provide our clients with data integrity critical to the GMP data lifecycles.

To learn more about Data Integrity and Compliance with Drug cGMP, click here

CBD Testing

Cannabidiol (CBD) is a naturally occurring compound within the cannabis plant.  It is often sold as an oil, consisting of CBD and a carrier oil such as grape seed or hemp seed oil.  The dosage of CBD within these manufactured products can vary greatly in potency depending on dosage forms including oral administration (oil) or topical use (cream).  CBD, as sourced from hemp plants, should typically contains less than 0.3% Delta-9-Tetrahydrocannabinol (THC) by weight.  Conversely, CBD as sourced from Marijuana plants may contain up to 40% of THC by weight.  To bolster consumer confidence in these products, it is critical for accurate quantification of CBD in formulated products, with corresponding demonstration of low THC content per state requirements.

ARL Bio Pharma employs High Performance Liquid Chromatography (HPLC) as our standard testing methodology for CBD quantification.  We routinely test CBD oils and creams for CBD potency.  We also offer a THC limit assay to demonstrate that THC is not present in the product formulation down to a concentration of 0.3%.  

Contact ARL at or 800-393-1595 to discuss your CBD testing requirements.

Endotoxin Limits

How are endotoxin limits calculated? How do my endotoxin test results relate to those limits?
Endotoxin limits for drug products specify the amount of endotoxin that can safely be present. Limits are based on human tolerance and generally specified in the USP monograph or if no monograph exists, calculated via USP <85> Bacterial Endotoxin Test. The testing limit calculation considers:
Route of administration
Dose of the product per kilogram of body weight (which should include the maximum bolus dose and the minimum patient weight)
Duration (time) of administration
Once a limit is determined, USP <85> allows a testing facility flexibility to determine the appropriate test dilution to reduce drug sample properties that interfere with the test. Using the endotoxin limit and the assay's sensitivity, a maximum valid dilution (MVD) is calculated. The MVD provides the maximum dilution possible to obtain a result and maintain the sensitivity necessary to determine a pass or fail. For example, if a sample is submitted with an endotoxin test limit of NMT 14 EU/mL and the MVD is determined to be 1400, then the product concentration can be diluted no further than 1:1400 and still generate a result with the appropriate sensitivity.
The test result is calculated by the assay software using the test dilution and assay sensitivity. In a case where no endotoxins are present, for example, a 1:1000 dilution was used and no presence of endotoxin was detected, a result of <10 EU/mL is reported. A result which includes a "less than" value does not indicate that the actual endotoxin value is near the number reported, only that the dilution factor used allowed for that level of sensitivity in results calculation. This means that results of <10 EU/mL and <4 EU/mL both show no presence of endotoxin at the dilution with which they were tested; and neither result offers any indication of the exact level of endotoxin present below the values reported.
If you would like to always receive the same result when endotoxins are not detected, a validation of the endotoxin test method is required.
Contact ARL at or 800-393-1595 to schedule your endotoxin test method validation.

Hand Sanitizer Guidance...

Hand sanitizers are regulated as over the counter (non-prescription) drugs by the U.S. Food and Drug Administration. The FDA has issued warnings to consumers about hand sanitizer products containing methanol. According to the CDC, Alcohol-based hand sanitizers should only contain ethanol or isopropanol, but some products have been found to contain methanol. Ethanol is a valid active ingredient, but methanol, even in small amounts, can lead to patient adverse events.