Stability failures

Quality assurance programs are essential to establishing standards for compounded preparations. One of the most important elements in a QA program is identifying the root cause of a failure and implementing a corrective action to prevent a future failure, also known as CAPA (Corrective and Preventative Action).

USP <795> states that compounders shall adhere to general principals of compounding which includes adequate procedures and records exist for investigating and correcting failures or problems in compounding, testing, or the preparation itself. 

Stability Factors

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 it possessed at the time of compounding. According to USP <1191>, pharmacists should establish and maintain compounding conditions that ensure drug stability to help prevent therapeutic failure and adverse responses.

National Drug Codes

According to the Food and Drug Administration (FDA), drugs are identified and reported using a unique, three-segment number called the National Drug Code (NDC) which serves as the FDA’s identifier for drugs. FDA publishes the listed NDC numbers in the NDC Directory which is updated daily.

Particulate Matter Testing

What is particulate matter and why is testing performed?

Particulate matter is unwanted solid material in solutions for injection. Particle counts that exceed USP limits in intravenous drug products could block blood flow inside the patient's body causing paralysis or death.  


Particulate matter testing is a good indicator of the quality of a manufacturing process and the containers used. 

OOS Investigation Part 2

ARL’s out-of-specification investigations use a hybrid approach to review data, formulations, and tests. Our data reviewers consult with ARL’s scientific directors and clients to ensure we provide a 360-view investigation and evaluate all aspects of the laboratory, data, and client and analyst trends. Typical investigations are concluded within one week or within 4 business days after the due date.  

OOS Investigation Part 1

United States Pharmacopeia monographs establish standards for identity, strength, quality, and purity of medicines. Monographs list tests and acceptance criteria (usually expressed in percentage ranges or limits). Drug substances and products should meet the acceptance criteria to be considered acceptable for its intended use. An Out of Specification (OOS) occurs when a test fails to meet acceptance criteria. An OOS Investigation follows an OOS test result and is performed to determine if there is a root cause. In this article we will look specifically at potential causes of potency OOS results of finished drug products. Understanding the factors that contributed to the potency failure allows the pharmacist and laboratory to define a strategic approach in eliminating future failures. The more specific the findings, the easier it is to properly address the cause.

Minor Chapters Major Impacts

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.

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.