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Out of specification investigations

An Out-of-Specification (OOS) result is a test result obtained during the analysis of any component of a drug product or related in-use materials, including raw materials, in-process materials, drug substances, or finished drug products, that falls outside established acceptance criteria defined in the applicable specification.

A specification is a defined quality standard that includes acceptance criteria such as numerical limits, ranges, or other established test requirements. These criteria establish the standards to which drug substances or drug products must conform in order to be considered acceptable for their intended use.

If an OOS result occurs, the U.S. Food and Drug Administration requires the following actions:

  1. A scientifically sound and documented justification must be established before invalidating an OOS result.
  2. A thorough investigation must be conducted to determine the root cause of the OOS result.
  3. Results from additional testing must not be averaged with the original result unless there is a scientifically justified and documented rationale supporting such averaging.

  • Client Communication

    Clients will be notified within two business days of the OOS result generated. Client communication may be verbal and/or by email.

  • Turnaround Time

    A typical OOS investigation will be closed within one week. After an OOS investigation has been opened, the investigation is completed no later than 30 calendar days.

  • Laboratory Responsibilities

    ARL Bio Pharma uses instruments meeting established specifications for sample analysis. Our analysts report potential problems that could lead to the cause of the OOS test result to ARL’s internal OOS investigator. ARL’s investigators are properly trained and thoroughly review all aspects of the OOS investigation, determine assignable cause, and follow up actions.

  • Laboratory Investigation

    ARL and its investigators thoroughly review the sample analysis:

    • Sample preparation
    • Raw data
    • Standards and Reagents
    • Standard method of analysis
    • Instrumentation and calibration settings
    • Hypothesis testing with the original sample or retained solutions
    • Trends
    • Analyst

  • Sample Re-tests

    Situations may exist in which prior knowledge is available about the sample such as trend data, client conversation of a suspect sample or physical sample observation that would indicate a high probability that the initial test result is representative of the sample. Other situations may also lead the investigator to question the validity of the OOS result and request a re-test.

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  • Investigation Reports

    ARL’s OOS investigation reports will include a summary conclusion that documents the basis for the decision, including either confirmation of the original result through scientifically justified retesting or a documented rationale for not performing a retest. If the original result cannot be confirmed and a laboratory error is identified, the original result will be invalidated and excluded from reporting in accordance with established procedures.

    For more information on OOS investigations, please contact info@arlok.com or 800-393-1595.