Understanding Analytical Instrument Qualification and Validation

If you are working in the pharmaceutical development and quality control laboratories, QC departments of API manufacturers, or Pharmaceutical contract laboratories, it is important for you to understand analytical instrument qualification and validation.

Analytical instruments should be qualified to demonstrate suitability for the intended use. You may be unsure on what exactly to qualify or re-qualify, test and document. The USP has developed a chapter that provides a framework for analytical instrument qualification (AIQ). When implemented right the standard also helps to reduce overall qualification costs. There are more reasons why the topic must be of interest to you.


    The Noncompliance Stakes are High

    Analytical instruments provide crucial scientific data regarding a manufactured product. This data in turn provides confidence that quality product is manufactured and is safe for sale to the public. It guarantees that the product is not substandard or adulterated.

    The FDA and other regulatory agencies require the analytical instruments to be under strict precision control. Manufacturing companies must display ongoing consistency, reliability, and repeatability to ensure the quality of drugs they produce. Definitive proof that the instrument qualification schedules acceptably control manufacturing, and testing processes must be produced. The FDA considers it as crucial during audits.

    If a product is deemed adulterated, it invites regulatory audits, observations, citations, 483s, recalls and even a consent decree with likely criminal prosecutions. Imagine the loss the manufacturer faces in lost revenues apart from the money to be paid out in civil suits due to harm or injury to consumers.

    Documentation and Protocols for Analytical Instrument Qualification and Validation

    A validation master plan for planning validation projects is a documented proof of what is required to execute validations. The master plan must include the following:

    • Information on the required resources
    • Input into scheduling
    • General assessment of the likely impact of the manufacturing processes
    • The equipment and analytical instruments to be qualified
    • Processes to be validated
    • Definition of products and process flows
    • Protocols and specifications
    • Methods for continuous monitoring of processes, equipment and analytical instruments

    Strict protocols must be in place for qualifying analytical instruments and manufacturing processes. The four qualification protocols required by the FDA are shown in the following figure:

    Qualification Phases

    Design Qualification (DQ)

    DQ documents all the activities that define the functional and operations specifications and the intended purpose of the instrument. It should specify the purpose of the instrument and demonstrate that the instrument is suitable for the intended purpose. It explains all requirements about safety, identity, strength, purity, and quality of the product. All details pertaining to the decisions made in selecting the suppler must be documented in the DQ.

    Installation Qualification (IQ)

    'IQ is the documented collection of activities necessary to establish that an instrument is delivered as designed and specified, is properly installed in the selected environment, and that this environment is suitable for the instrument. IQ applies to an instrument that is new or was pre-owned.' - USP Chapter <1058>

    Operational Qualification (OQ)

    The OQ is a documented proof the functions of the system satisfy design specifications. A check on each of the instrument functions are performed to ensure they meet the specifications laid out by the manufacturer of the instrument. To ensure reliable and meaningful results, the guidelines emphasize the importance of instrument qualification simulating actual testing conditions. Testing activities in the OQ phase may consist parameters that include fixed parameters, software functions, secure data storage, backup and archiving, and Instrument function tests.

    Performance Qualification (PQ)

    PQ is a to verify the acceptable performance of the instrument for its intended use. It should define the PQ plans consisting of test procedures, acceptable criteria, and frequency. In PQ consistency is crucial. PQ may include

    The 3 Kinds of Analytical Instrument Qualification

    Instrument Qualification

    Prospective Qualification

    1. Performed on new instruments, the prospective qualification is done prior to a product testing on the instrument
    2. Performed when a substantial change to the instrument or analysis that is likely to affect the analytical results has been made
    3. Performed when a new product analysis that varies from the existing product analysis is required

    Concurrent Qualification

    In the PQ phase, "Some system suitability tests or quality control checks that are performed concurrently with the test samples can be used to demonstrate that an instrument is performing suitably."

    Retrospective Qualification

    The retrospective qualification is performed on existing instrument that has not experienced a documented qualification process. It is performed after the routine production has started and is in operational use. Historical data forms the basis to provide documented proof that the instrument meets its intended purpose.

    By following the DQ/IQ/OQ/PQ protocols, a successful analytical instrument qualification plan can be implemented. Nevertheless, there is one more important step - the requalification. At periodic intervals (generally every two, three, or five years) requalification of instruments must be performed to retain trust. Critical instruments must be requalified at least once each year.

    Training programs on Analytical Instrument Qualification

    Analytical Instrument Qualification and System Validation

    Lifecycle Management of Analytical Methods and Procedures - according to new FDA and USP guidelines

    Understanding and Implementing USP <1058>: Analytical Instrument Qualification

    Analytical Instrument Qualification-Understanding the New USP draft Chapter