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
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) based on USP guidelines for system suitability data such as retention time of the standard and sample, peak shape and absence of interfering peaks in the diluent / 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 often qualified as USP grade and are obtained from reputable vendors. In some instances, reference standards may be provided by the client.
- GMP methods are internally developed and validated or verified externally validated methods (e.g. USP) specific to the analyte of interest (typically the API) based on USP and FDA guidelines for system suitability data such as ability of the method to detect the analyte in the presence of impurities and matrix components in the specific 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 are used. Each test also includes a secondary standard or a duplicate preparation of the primary standard as the quality control standard.
Out of Specification turnaround time is typically doubled based on the original test turnaround time. Often OOS is completed within 4 business days of the original due date for routine, non-GMP samples and 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 results are confirmed and failing, all results plus the average are reported.
- If results are confirmed, but some passing, all results are reported with no average.
- If a result is invalidated, only the average of the reruns is reported unless otherwise requested from the client.
- If a result is invalidated due to lab error, the invalidated result is not reported.