Analytical OOS FAQ’s

The formulation sheet is necessary to confirm that the product was properly prepared per label claim and to evaluate other components of the formulation that could interfere with the chromatography. This includes salt forms, weights, amounts, etc. that pertain to a specific lot. The formulation sheet also provides information on sample preparation technique that the laboratory uses to examine if the OOS is due to compounding error. ARL recommends that formulation sheets also be submitted if a sub-formula is used for compounding.

• Product Formulation issues such as dose uniformity in solid dosage forms, creams, gels, etc.
• Product degradation, stability, and exposure to heat, light, moisture, etc.
• Compounder not accounting for water content of starting material
• Sample test preparation errors

Sub potent results for T3/T4 are typically due to compounding issues. T3/T4 is difficult to compound due to sticking during the mixing process.

ARL uses nonGMP and GMP methods developed specific for the active pharmaceutical ingredient tested.

• NonGMP methods are published or internally developed methods specific to the analyte of interest (typically the API). These methods follow USP system suitability guidelines, including retention time of the standard and sample, peak shape, and absence of interfering peaks in the diluent or blank chromatogram. ARL performs system suitability using one reference standard per API to verify the analytical method’s performance. Reference standards are typically secondary standards. Secondary standards are typically qualified as USP grade and obtained from reputable vendors. In some instances, reference standards may be provided by the client.
• GMP methods are either internally developed and validated or based on externally validated methods (e.g., USP) specific to the analyte of interest (typically the API). These methods follow USP and FDA guidelines for system suitability, including the ability to detect the analyte in the presence of impurities and matrix components within the drug product formulation. ARL performs system suitability using two reference standards per API to verify the analytical method’s performance. USP or other primary reference standards we used.  Each test also includes a secondary standard or a duplicate preparation of the primary standard as the quality control standard.

Yes, test specifications are based off the USP monograph or provided by the client.

Yes, ARL mixes specific sample types (creams, suspension, gels, etc.) before preparing the sample for testing. Our laboratory mixes via spatula and/or vortex and manually shakes the sample before test preparation.

Yes, ARL accounts for water or loss on drying of the standard.

We confirm reference standards by preparing a duplicate preparation of the same standard.

We typically double Out-of-Specification (OOS) turnaround time compared to the original test timeline. OOS often completed within 4 business days after the original due date for routine, non-GMP samples, but may take longer depending on client communication. OOS completion for GMP testing depends on client specifications.

Reruns are based on client history, sample preparation technique, and if other passing samples are in the sequence and/or a check standard is on the sequence. Reruns are also based on client requests. The laboratory reviewer considers multiple variables during an exhaustive OOS review process to rule out lab error.

• If we confirm failing results, we report all results along with the average.
• If we confirm mixed results, we report all results without calculating an average.
• If we invalidate a result, we report only the average of the reruns unless the client requests otherwise.
• If we invalidate a result due to a laboratory error, we do not report the invalidated result.

Our laboratory would invalidate a run if confirmed calculation error, poor methodology or a general lab error.

A second analysist performs reruns for GMP work and is at the discretion of the laboratory data review for nonGMP work.