Lab & Testing Services

Would your sterile compounding process pass an FDA inspection? In order to fully comply with USP <797>, a compounding pharmacy creating sterile preparations must develop its own formal quality assurance (QA) program. The characteristics of a QA program require the consideration of environmental testing and preparation verification results, with the recommended testing method outlined by USP <71>.

Because the compendial method of testing takes 14 to 18 days to complete, it is extremely limiting in the compounding industry. A sterile compound with a standard 30 day expiry will lose approximately half of its shelf life due to sterility testing. This delay may discourage compounders from developing or adhering to a QA program, leaving them at risk of failing an FDA inspection.

However, there is a faster way to comply with USP <797> and ensure your patients are receiving quality compounds. The ScanRDI Sterility Test Protocol is an FDA-accepted alternative to the official compendial sterility test method. ScanRDI rapidly detects viable microbial cells down to one microorganism without the need for growth or cell multiplication. This removes the extended incubation period included in the USP <71> test method, so results are ready in just one day.

According to USP General Notices, alternate testing methods may be used if they can be shown to provide equivalent or better results. ScanRDI uses the same sampling protocols as USP <71>, detects all of the standard USP organisms

and has been shown to provide consistent and reliable results.¹ Additionally, ScanRDI fulfills the method suitability requirement as outlined in USP <1223>. A

suitability test is performed on every unique drug formula sample submitted for ScanRDI testing. If the suitability of a compound does not pass this test, Eagle will inform the compounding pharmacist that it was incompatible with the ScanRDI method.

Want to learn more? Contact us at 800-745-8916, today.

1 Smith, R., Von Tress, M., Tubb, C., & Vanhaecke, E. (2010). Evaluation of the ScanRDI as a Rapid Alternative to the Pharmacopeial Sterility Test
Method: Comparison of the Limits of Detection. PDA Journal of Pharmaceutical Science and Technology, 64, 356-363

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Sterile articles packaged in multi-dose containers must be free of microorganisms throughout their entire shelf-life. Due to the potential for the introduction of microorganisms through the repeated withdrawal of individual doses, sterile products that are packaged in mutli-dose containers should contain an antimicrobial preservative. However, the concentration of an added antimicrobial preservative can be kept to a minimum if the ingredients of the compounded formulation possess an intrinsic antimicrobial activity. Antimicrobial effectiveness, whether inherent in the product or as a result of an antimicrobial preservative, must be demonstrated through USP <51> antimicrobial effectiveness testing. Since the antimicrobial preservative must remain effective throughout a preparation’s shelf life, it is recommended that USP <51> testing be performed at the initial and end timepoints of a stability study.

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As the presence of microorganisms in nonsterile preparations has the potential to reduce and/or inactivate therapeutic activity and adversely affect the health of patients, compounders are required to ensure that nonsterile preparations have a low bioburden that complies with established specifications for microbiological quality as outlined in USP <61>. USP <61> Microbial Enumeration tests provide a quantitative evaluation of a product’s microbial content to demonstrate compliance with established specifications.

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USP <71> outlines the compendial requirements for sterility testing that must be followed in order to be able to claim that the results of the test provide evidence that the product is sterile. As all sterile products must remain free of microbial contamination throughout their entire shelf-life, sterility is considered to be a stability characteristic. Therefore, a stability testing program should include confirmation of continuing steriliy throughout the course of the product’s shelf-life. Minimally, sterility testing should be performed at the initial and end timepoints of the stability study.

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USP <71> Method Suitability Testing (MST) must be performed prior to being able to claim that the results of a USP <71> sterility test provide evidence of a preparation’s sterility. Method Suitability Testing only needs to be completed once for each compounded formulation, and consists of two parts: i) a suitability test that confirms that the growth media used for sterility testing supports the growth of certain microorganisms and ii) a validation test that demonstrates that no components of the compounded preparation inhibit microbial growth.

Method Development:
Method development is the process of developing a stability indicating method through forced degradation studies that is appropriate for testing the potency of any given compounded formulation. Once the testing protocol is developed, method development includes method verification and method validation (see below).

Method Verification and Validation:
Method Verification is the process of testing a previously developed stability indicating assay to test the potency of a compounder’s specific formulation. Method Verification is performed to verify that no active or inactive ingredients in a compounder’s formulation are incompatible with the developed potency testing method, thus affecting the integrity of the results. This verification process also includes Method Validation, which is the process of building a statistical data package around the verified method that provides evidence of the accuracy, sensibility, specificity, and reproducibility of the testing methods used.

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 As bacterial endotoxins can pose health and safety hazards to patients, USP <85> requires bacterial endotoxin testing to detect and quantify the presence of endotoxins from Gram-negative bacteria in sterile compounds. To assure patient safety, the quantity of bacterial endotoxins may not exceed threshold limits defined in USP <85>. For each bacterial endotoxin test, inhibition validation testing is performed. This testing confirms that there are no components of the formulation that will interfere with the bacterial endotoxin test and that the testing used is sensitive enough to provide meaningful, accurate data. To provide evidence that a preparation is within endotoxin limits for the duration of its shelf-life, it is recommended that endotoxin testing be performed at the initial and end timepoints of the stability study.

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Solutions must be essentially free from observable particulate matter. Due to the small amount of material and the heterogenous composition that particulate matter represents, it cannot be quantitated by chemical analysis alone. As a result, it is recommended to perform a USP <788> particulate count test via light obscuration at every timepoint in a stability study.

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USP <1207> container-closure integrity testing demosntrates the ability of the container-closure system to maintain the integrity of its microbial barrier throughout the entire shelf-life of a product. Eagle utilizes a pressure decay to test container-closure integrity, which is one of the deterministic methods recommended by USP <1207>. As sterility is an event-related occurrence, container-closure integrity testing is performed to support the claim that the sterile containers in which the preparation is packaged are capable of maintaing the sterility of the product throughout its beyond-use-date. Container-closure testing is also recommended for nonsterile products because container-closure system failures introduce the possibility of accelerated degradation of the preparation through exposure to light, air, moisture, and humidity. It is recommended that container-closure integrity testing is performed at least at the initial and end timepoints of a stability study.

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Potency testing analyzes the active pharmaceutical ingredient(s) in preparations and measures their concentrations or amounts. When testing for potency, the concentration of active ingredient is measured using a reference standard. Eagle Analytical Services performs potency tests by using state of the art High Pressure Liquid Chromatography (HPLC) equipped to a PDA detector, Ultra High Pressure Liquid Chromatography (UHPLC) equipped to a PDA, and Corona Detector and Spectrographic instrumentation. These instrumentations are the preferred methods for pharmaceutical analysis. Protocols have been developed based on USP <621> Chromatography and USP <851> Spectrophotometry and Light-Scattering methodology.

USP Chapter <795> states: “… Compound preparations are to be prepared to ensure that each preparation shall contain not less than 90% and not more than 110% of the theoretically calculated and labeled quantity of an active ingredient.

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