Ascertain that suitable standards are being used (i.e. Evaluate the history of changes to programs used for calculations. Examine laboratory records and logs for vital information about the technical competence of the staff and the quality control procedures used in the laboratory. An initial content uniformity test was OOS followed by a passing retest. Evaluate the decision to release lots of product when the laboratory results indicate that the lot failed to meet specifications and determine who released them. This innovative approach is based on the application of product and process … This information may also be obtained from the supplier of the drug substance. Separate areas shall be provided each for physico-chemical, biological, microbiological or radio-isotope analysis. Review and evaluate the laboratory SOP for product failure investigations. Instead they accept unexplained peaks in chromatograms with no effort to identify them. FAILURE (OUT-OF-SPECIFICATION) LABORATORY RESULTS. Some of the tests done may differ from those done at release. Several issues must be addressed when evaluating computerized laboratory systems. In general these inspections may include. It is highly unlikely that a firm can "accurately and consistently weigh" to the same microgram. FDA Inspection Guides are based on the team inspection approach and our inspection of a laboratory is consistent with this concept. - Compliance Policy Guide 7132a.11 Computerized Drug Processing: CGMP Applicability to Hardware and Software, - Compliance Policy Guide 7132a.12 Computerized Drug Processing: Vendor Responsibility, - Compliance Policy Guide 7132a.15 Computerized Drug Processing: Source Code for Process Control Application Programs. The inquiry may vary with the object under investigation. These tests may be performed every fifteen or thirty minutes during tableting or encapsulating procedures. Evaluate raw laboratory data, laboratory procedures and methods, laboratory equipment,including maintenance and calibration, and methods validation data to determine the overall quality of the laboratory operation and the ability to comply with CGMP regulations. Cannot use a re-sample to assume a sampling or preparation error, 4. For compendial methods firms must demonstrate that the method works under the actual conditions of use. An official website of the United States government, Recalls, Market Withdrawals and Safety Alerts, Pharmaceutical Quality Control Labs (7/93). The exact cause of analyst error or mistake can be difficult to determine specifically and it is unrealistic to expect that analyst error will always be determined and documented. If a sample larger than the unit must be taken initially, aliquots which resemble the dosage size should be carefully removed for the test, retests, and reserve samples. In some cases the sponsor of ANDA's may be able to search the literature and find background data for the specificity of a particular method. This includes the preparation of the FDA 483. If this is not the case, expect to see scientific data to justify the variation. Designing a quality control laboratory requires a design process similar to that of production facilities: listening and gathering information, examining and optimizing sample analysis flows, integrating bench equipment servicing, designing for ergonomics and environmental conditions, as well as envisioning strategies for lab storage and solvent management. A significant portion of the CGMP regulations (21 CFR 211) pertain to the quality control laboratory and product testing. Determine if the firm uses an outlier test and evaluate the SOP. The use of computerized laboratory data acquisition systems is not new and is addressed in the following CGMP guidance documents: - Compliance Policy Guide 7132a.07 Computerized Drug Processing: Input/Output Checking. A stability-indicating method must be used to test the samples of the batch. The inability to identify an error's cause with confidence affects retesting procedures, not the investigation inquiry required for the initial OOS result. Expect to see consistent in-process test results within batches and between batches of the same formulation/process (including development or exhibit batches). Check for the reuse of stock solutions without assuring their stability. Laboratory errors must be determined through a failure investigation to identify the cause of the OOS. The authority to delete files and override computer systems should be thoroughly examined. The test cannot be used for chemical testing results. Once this determination is made, however, additional retesting for purposes of testing a product into compliance is not acceptable. Before sharing sensitive information, make sure you're on a federal government site. An OOS laboratory result can be overcome (invalidated) when laboratory error has been documented. - Data entries may not be deleted. Therefore, all health and safety hazards must be identified and carefully evaluated so that protective measures can be incorporated into the design. The agency has provided some basic guidance on security and authenticity issues for computerized systems: - Provision must be made so that only authorized individuals can make data entries. Examine chromatograms and spectra for evidence of impurities, poor technique, or lack of instrument calibration. Nevertheless, we expect investigators, analysts and others to work as teams and to advise management when additional expertise is required to complete a meaningful inspection. Analyst's mistakes, such as undetected calculation errors, should be specified with particularity and supported by evidence. District management makes the final decision regarding the assignment of personnel to inspections. In a recent court decision the judge used the term "out-of-specification" (OOS) laboratory result rather than the term "product failure" which is more common to FDA investigators and analysts. Analytical quality control refers to all those processes and procedures designed to ensure that the results of laboratory analysis are consistent, comparable, accurate and within specified limits. principles into pharmaceutical quality control laboratory design. Determine that a full scale inquiry has been made for multiple OOS results. Manufacturers may be required to accelerate or force degradation of a product to demonstrate that the test is stability indicating. Nevertheless, a laboratory investigation consists of more than a retest. Quality control in the medical laboratory is a statistical process used to monitor and evaluate the analytical process that produces patient results. in-date, stored properly). 18. Good manufacturing practice regulations require an active training program and the documented evaluation of the training of analysts. Labs not only monitor and control the quality of incoming APIs (active pharmaceutical ingredients), and other supplies used in the manufacturing process; QC Labs are also instrumental in the batch release process. The analyst is expected to evaluate raw laboratory data for tests performed on the test batches (biobatches and clinical batches) and to compare this raw data to the data filed in the application. Additionally, the company should consider all retest results in the context of the overall record of the product. Pharmaceutical Quality by Design: A Practical Approach outlines a new and proven approach to pharmaceutical product development which is now being rolled out across the pharmaceutical industry internationally. Content uniformity and dissolution results never should be averaged to obtain a passing value. Determine the adequacy of the firm's procedures to ensure that all valid laboratory data are considered by the firm in their determination of acceptability of components, in-process, finished product, and retained stability samples. The basic laboratory Refer to the Microbiological Inspection Guide for additional information concerning the inspection of microbiological laboratories. A selection of the best HVAC system that was most suitable for a Pharmaceutical Quality Control Laboratory was made using the design matrix. Because the initial tests are genuine, in these circumstances, additional testing alone cannot contribute to product quality. Laboratory equipment usage, maintenance, calibration logs, repair records, and maintenance SOPs also should be examined. Obviously, the initial larger sample should not be subjected to any additional mixing or manipulation prior to removing test aliquots as this may obscure non-homogeneity. Good Laboratory Practices for Pharmaceutical Quality Control Laboratories in Lebanon 2016 Edition 1 ... Design qualification (DQ) Documented collection of activities that define the functional and operational specifications of the instrument and criteria for selection of the vendor, based on the intended purpose of the instrument. Here, relying on the average figure without examining and explaining the individual OOS results is highly misleading and unacceptable. The court ruled that the use of an outlier test is inappropriate in this case.. 4. Be prepared to examine all records and worksheets for accuracy and authenticity and to verify that raw data are retained to support the conclusions found in laboratory results. Once the nature of the OOS result has been identified it can be classified into one of the three categories above. Report findings where there is substantial difference in impurity profiles and other test results. Inspection process of a laboratory involves the assessment of laboratory functions in full operation. Sponsors are not required to file all the test data because such action would require voluminous submissions and would often result in filing redundant information. Evaluate the company's retesting SOP for compliance with scientifically sound and appropriate procedures. Large countries may require several pharmaceutical … Notify me of follow-up comments by email. to release a product that has failed testing and retesting unless the failure investigation discloses evidence that the original sample is not representative or was improperly prepared. Cut charts with injections missing, deletion of files in direct data entry systems, indirect data entry without verification, and changes to computerized programs to override program features should be carefully examined. OOS results fall into three categories: - process related or manufacturing process error. This inspection guide supplements other inspectional information contained in other agency inspectional guidance documents. Investigations along with conclusions reached must be preserved with written documentation that enumerates each step of the investigation. An alternative means to invalidate an initial OOS result, provided the failure investigation proves inconclusive, is the "outlier" test. Quality control testing of pharmaceutical raw materials is critical to drug development from early-stage through to commercial batch release. Click to share on Twitter (Opens in new window), Click to share on Facebook (Opens in new window), VWR Laboratory-Online-Planning – Free online application. In addition to the general approach utilized in a drug CGMP inspection, the inspection of a laboratory requires the use of observations of the laboratory in operation and of the raw laboratory data to evaluate compliance with CGMP's and to specifically carry out the commitments in an application or DMF. It is appropriate when analyst error is documented or the review of analyst's work is "inconclusive" , but it is not appropriate for known and undisputed non-process or process related errors. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. During the inspections carried out when prequalifying laboratories, the inspectors had noticed that some of the texts of these guidelines might benefi t from additional guidance, with a special focus on microbiology. Testing areas should accommodate raw materials active phar… SOPs should be complete and adequate and the operations of the laboratories should conform to the written procedures. When conducting a comprehensive inspection of a laboratory, all aspects of the laboratory operations will be evaluated. When a diagnostic test is performed in the medical laboratory, the outcome of the test is a result. Specifically: - examine other batches of product made by the errant employee or machine, - examine other products produced by the errant process or operation, 5. Evaluate the test results from in-process tests performed in the production areas or laboratory for conformance with established sampling and testing protocols, analytical methods, and specifications. Test results should not have been transcribed without retention of the original records, nor should test results be recorded selectively. The safety and efficacy of the finished dosage form is largely dependent on the purity and quality of the bulk active drug substance. Changes must be made in the form of amendments. Pharmaceutical quality control testing is usually a matter of repetitive testing of samples of APIs or of a limited number of pharmaceutical products, whereas national quality control laboratories have to be able to deal with a much wider range of pharmaceutical substances and products and, therefore, have to apply a wider variety of test methods. Evaluate the raw data used to generate the data filed documenting that the method is stability indicating and the level of impurities. 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