QC 1

• Validation is the action of proving, in accordance with the principles of Good Manufacturing Practice, that any procedure, process, equipment, material, activity or system actually and consistently leads to the expected results.
• The purpose of validation is regulatory compliance, assurance of quality, process optimization, safety, and reduction of quality costs.
• Responsibility for validation is multi-disciplinary, with the prime responsibility held by the Production and Quality Control Departments.
• The company must define the responsibilities of its personnel and external contractors in the qualification and validation program.
• A pharmaceutical company should identify what qualification and validation work is required to prove that the critical aspects of their particular operation are controlled.
• Detection Limit is the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value.
• Quantitation Limit is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy.
• Reproducibility in analytical chemistry expresses the precision between laboratories, usually applied to standardization of methodology.
• Robustness in analytical chemistry is a measure of the capacity to remain unaffected by small, but deliberate variations in method parameters which provides an indication of the reliability during normal usage.
• System suitability testing in analytical chemistry tests based on the concept that the equipment, electronics, analytical operations and samples to be analyzed constitute an integral system that can be evaluated as such.
• The key elements of a qualification and validation program should be clearly defined and documented in a validation master plan.
• The validation team consists of the General Manager, Production Manager, Plant Manager, Validation Manager, Project Manager, Engineering Manager, QA Manager, R&D Manager, and GMP Manager.
• Precision may be considered in three different levels: repeatability/intra-assay precision, intermediate precision, and laboratory precision.
• Validation reports may also contain proposals for the improvement of processes and/or equipment.
• A protocol describes the details of a comprehensive planned study to investigate the consistent operation of new system/equipment, a new procedure, or the acceptability of a new process before it is implemented.
• Analytical method validation demonstrates that an analytical procedure is suitable for its intended purpose.
• Protocols include significant background information, explain the rationale for and the objective of the study, give a full description of the procedures to be followed, set out the parameters to be measured, describe how the results will be analyzed, and provide pre-determined acceptance criteria for making conclusions.
• Accuracy/trueness expresses the closeness of agreement between the value which is accepted either as a conventional true value or an accepted reference value and the value found.
• Precision expresses the closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions.
• Specificity is the ability to assess unequivocally the analyte in the presence of components which may be expected to be present.
• Responsibilities of the validation team include identifying needs, developing protocols, conducting the validation/qualification, assessing the data generated, and approving the equipment/system/process.
• Linearity is the ability (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample.
• Intermediate precision expresses within-laboratories variations: different days, different analysts, different equipment, etc.
• Analytical performance characteristics include specificity, linearity, range, accuracy/trueness, and precision.
• The analytical method should be validated by research and development before being transferred to the quality control unit when appropriate.
• Repeatability/intra-assay precision expresses the precision under the same operating conditions over a short interval of time.
• A validation report is a document in which the records, results and evaluation of a completed validation program are assembled and summarized.
• Range is the interval between the upper and lower concentration (amounts) of analyte in the sample (including these concentrations) for which it has been demonstrated that the analytical procedure has a suitable level of precision, accuracy and linearity.
• The Validation Master Plan (VMP) is a high-level document that establishes an umbrella validation plan for the entire project and summarizes the manufacturer’s overall philosophy, intentions and approach to be used for establishing performance adequacy.
• The VMP provides information on the manufacturer’s validation work program, details of the timescales for the validation work to be performed, and responsibilities of those implementing the plan.
• Validation can be based on evidence obtained through testing (Prospective Validation) or analysis of accumulated (historical) data (Retrospective Validation).
• Prospective Validation involves establishing documented evidence that a process, procedure, system, equipment or mechanism used in manufacture does what it purports to do based on a pre-planned validation protocol.
• Concurrent Validation involves validation carried during routine production of products intended for sale.
• Retrospective Validation involves validation of a process for a product that has been marketed based upon accumulated manufacturing, testing and control batch data on the condition that composition, procedures and equipment remain unchanged.
• A validation protocol is a document describing the activities to be performed in a validation activity, including the acceptance criteria for the approval of a manufacturing process or a part thereof for routine use.
• A protocol is a written set of instructions broader in scope than a Standard Operating Procedure (SOP).
• SOPs are the detailed written instructions for procedures routinely performed in the course of any of the activities associated with pharmaceutical manufacturing.