A significant portion of the CGMP regulations (21 CFR 211) pertain to the quality control laboratory and product testing. When conducting a comprehensive inspection of a laboratory, all aspects of the laboratory operations will be evaluated. Multiple injections recorded should be in consecutive files with consecutive injection times recorded. - must be done on the same, not a different sample, - may be done on a second aliquot from the same portion of the sample that was the source of the first aliquot, - may be done on a portion of the same larger sample previously collected for laboratory purposes. 20. Required fields are marked *. Multiple individual blend uniformity samples taken from different areas cannot be composited. For the single OOS result the investigation should include the following steps and these inquiries must be conducted before there is a retest of the sample: - the analyst conducting the test should report the OOS result to the supervisor. because averages hide the variability among individual test results. The team should evaluate the replies to these letters to assure that the data are accurate and authentic. the specific methodology which will be used to test a new product . Determine that a full scale inquiry has been made for multiple OOS results. Examine the results of investigations using the guidance in section 5 above and evaluate the decision to release, retest, or rework products. Responsibilities for development of all reports should also be established prior to the inspection. The pharmaceutical quality control laboratory serves one of the most important functions in pharmaceutical production and control. 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. It is highly unlikely that a firm can "accurately and consistently weigh" to the same microgram. is not a product failure. These tests may be performed every fifteen or thirty minutes during tableting or encapsulating procedures. The number of retests performed before a firm concludes that an unexplained OOS result is invalid or that a product is unacceptable is a matter of scientific judgment. This includes the preparation of the FDA 483. Laboratory logs and documents when cross referenced may show that data has been discarded by company officials who decided to release the product without a satisfactory explanation of the results showing the product fails to meet the specifications. Samples will be collected on pre-approval inspections. Formal investigations extending beyond the laboratory must follow an outline with particular attention to corrective action. This information may also be obtained from the supplier of the drug substance. This phenomenon is particularly troubling if testing generates both OOS and passing individual results which when averaged are within specification. - 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. Firms cannot rely on resampling. Blend uniformity testing cannot be waived in favor of total reliance on finished product testing because finished product testing is limited. It is important, for computerized and non computerized systems, to define the universe of data that will be collected, the procedures to collect it, and the means to verify its accuracy. a complete assessment of laboratory’s conformance with GMP’s. Nevertheless, a laboratory investigation consists of more than a retest. List other batches and products possibly affected, the results of investigation of these batches and products, and any corrective action. Coordination between headquarters and the field is essential for a complete review of the application and the plant. The result may be quantitative The goal of retesting is to isolate OOS results but retesting cannot continue ad infinitum. There should be an audit trail for changes to data. Experienced investigators and analysts may contact the review chemist (with appropriate supervisory concurrence) when questions concerning specifications and standards arise. Such systems have also been accepted provided they have been defined (with raw data identified) and validated. Good manufacturing practice regulations require an active training program and the documented evaluation of the training of analysts. Most manufacturers use systems that provide for the investigation of laboratory test failures. Follow the sampling guidelines in CP 7346.832, Part III, pages 5 and 6. Review personal analytical notebooks kept by the analysts in the laboratory and compare them with the worksheets and general lab notebooks and records. Again, review the raw laboratory data and the results of testing at the various stations to determine if the data actually reported matches the data found in on site records. In general these inspections may include. Physical properties tests often require the use of unique equipment and protocols. Any other practice would blur differences in portions of the blend and defeat the object of the test. The court provided explicit limitations on the use of outlier tests and these are discussed in a later segment of this document., or overcome by retesting. Relevant sections of the NDA or ANDA should be reviewed prior to the inspection; but if the application is not available from any other source, this review will have to be conducted using the company's copy of the application. For example, in the case of content uniformity testing designed to detect variability in the blend or tablets, failing and non-failing results are not inherently inconsistent and passing results on limited retesting do not rule out the possibility that the batch is not uniform. Evaluate the history of changes to programs used for calculations. Manufacturers may be required to accelerate or force degradation of a product to demonstrate that the test is stability indicating. Once the nature of the OOS result has been identified it can be classified into one of the three categories above. Products cannot be "tested into compliance" by arbitrarily labeling out-of-specification lab results as "laboratory errors" without an investigation resulting in scientifically valid criteria. 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. Preserve the comments and signatures of all production and quality control personnel who conducted the investigation and approved any reprocessed material after additional testing. District management makes the final decision regarding the assignment of personnel to inspections. 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. Specific procedures must be followed when single and multiple OOS results are investigated. Therefore, all health and safety hazards must be identified and carefully evaluated so that protective measures can be incorporated into the design. 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. Also, evaluate the methods used to test and establish bioburdens. In the case of microbiological turbidimetric and plate assays an average is preferred by the USP. Absorbance values and calculations have even been found on desk calendars. - The data base must be made as tamperproof as possible. For drug substance labs evaluate methods validation and raw data for sterility, endotoxin testing, environmental monitoring, and filter and filtration validation. For most of those manufacturers which had duplicate sets of records or "raw data", non-numbered loose sheets of paper were employed. Documents relating to the formulation of the product, synthesis of the bulk drug substance, product specifications, analysis of the product, and others are examined during the review process in headquarters. They may accept stability test results showing an apparent increase in the assay of the drug with the passage of time with no apparent question about the result. Lucideon's pharmaceutical quality control testing and validation laboratories are fitted with state-of-the-art analytical equipment and testing facilities. There is no substitute for actually seeing the work performed and noting whether good technique is used. weak or hot spots in the blend. Testing areas should accommodate raw materials active phar… In particular, if a compendial method exists, but the firm chooses to use an alternate method instead, they must compare the two and demonstrate that the in-house method is equivalent or superior to the official procedure. Review and evaluate the laboratory SOP for product failure investigations. The Pharmaceutical Quality by Design course will provides an understanding of the challenges faced by the pharmaceutical and healthcare industries as they strive to develop new products and equips you with modern product development and manufacturing solutions that conform to current industry best practices and modern QbD principles. The review of microbiological data on applicable dosage forms is best performed by the microbiologist (analyst). Additionally, the company should consider all retest results in the context of the overall record of the product. Determine if the firm uses an outlier test and evaluate the SOP. For example, a firm may perform disintegration testing as an in-process test but dissolution testing as a release test. Examine the laboratory refrigerators for these solutions and when found check for appropriate identification. Some of the tests done may differ from those done at release. As a minimum, each pharmaceutical quality control laboratory should receive a comprehensive GMP evaluation each two years as part of the statutory inspection obligation. An official website of the United States government, Recalls, Market Withdrawals and Safety Alerts, Pharmaceutical Quality Control Labs (7/93). The company must: 1. Test dates should correspond to the dates when the sample should have been in the laboratory. The court ruled that a firm should have a predetermined testing procedure and it should consider a point at which testing ends and the product is evaluated. System suitability data alone is insufficient for and does not constitute method validation. 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. These practices raise questions about the overall quality of data. Separate areas shall be provided each for physico-chemical, biological, microbiological or radio-isotope analysis. The laboratory serves a vital function in blend testing which is necessary to increase the likelihood of detecting inferior batches. These investigations represent a key issue in deciding whether a product may be released or rejected and form the basis for retesting, and resampling. adopted in 2009 a revised version of the Good practices for pharmaceutical quality control laboratories (1). In the case of nonprocess and process-related errors, retesting is suspect. Context and challenges. Quality control testing of pharmaceutical raw materials is critical to drug development from early-stage through to commercial batch release. Laboratory errors occur when analysts make mistakes in following the method of analysis, use incorrect standards, and/or simply miscalculate the data. If there is a computer data base, determine the protocols for making changes to the data. Laboratory errors must be determined through a failure investigation to identify the cause of the OOS. Quality control in the medical laboratory is a statistical process used to monitor and evaluate the analytical process that produces patient results. As part of our effort to achieve uniformity and consistency in laboratory inspections, we expect that complex, highly technical and specialized testing equipment, procedures and data manipulations, as well as scientific laboratory operations will be evaluated by an experienced laboratory analyst with specialized knowledge in such matters. Several issues must be addressed when evaluating computerized laboratory systems. Content uniformity and dissolution results never should be averaged to obtain a passing value. Therefore, continuing to use and release product on the basis of such equipment represents a serious violation of CGMP's. 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. For example, Compliance Program 7346.832 requiring pre-approval NDA/ANDA inspections contains general instructions to conduct product specific NDA/ANDA inspection audits to measure compliance with the applications and CGMP requirements. Design – construction of a pharmaceutical laboratory and a control room Design / Project management Life Sciences France. QUALITY AND COMPLIANCE IN QUALITY CONTROL LABORATORIES Primary objectives of regulatory inspections are to (1) verify that the data measured in quality control laboratories are reliable and accurate, and (2) ensure that only safe and effective drugs are authorized for marketing and released for product shipment. http://www.manostaxx.com Find bellow some examples of Pharmaceutical Quality Control Lab: Also see: https://dadoswebaxx.w The first floor consists of chemistry and immunology laboratories for quality control testing of product and raw materials, a sample control suite, and rooms for consumables storage and waste stagin… Evaluate the justification for disregarding test results that show the product failed to meet specifications. This includes the history of the product. Provide summation of the process sequences that may have caused the problem, 3. 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. 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. 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. When the laboratory investigation is inconclusive (reason for the error is not identified) the firm: 1. 18. 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. Evidence that the method is stability indicating must be presented, even for compendial methods. principles into pharmaceutical quality control laboratory design. This client is a major pharmaceutical player specializing in pharmaceutical synthesis and specialty ingredients. Determine if the manufacturer has a program to audit the certificate of analysis of the BPC, and, if so, check the results of these tests. The court ruled that the firm must recall a batch that was released for content uniformity on the basis of averaged test results. Also, diminishing reproducibility in HPLC chromatograms appearing several hours after system suitability is established is accepted without question. 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. Determine whether equipment is being used properly. Usually, whether the methods are the same or different, the specifications may be tighter for the in-process tests. List of Standard Operating Procedures (SOPs) for Quality Control laboratories in pharmaceutical products manufacturing facilities. Data that should be reviewed include preservative effectiveness testing, bioburden data, and product specific microbiological testing and methods. However, these reviews and evaluations depend on accurate and authentic data that truly represents the product. Specifications and analytical procedures should be suitable and, as applicable, in conformance with application commitments and compendial requirements. An alternative means to invalidate an initial OOS result, provided the failure investigation proves inconclusive, is the "outlier" test. Overall management of the laboratory work, its staff, and the evaluation of the results of analysis are important elements in the evaluation of a control laboratory. Averaging can be a rational and valid approach when the object under consideration is total product assay, but as a general rule this practice should be avoided. Laboratory records and logs represent a vital source of information that allows a complete overview of the technical ability of the staff and of overall quality control procedures. The safety and efficacy of the finished dosage form is largely dependent on the purity and quality of the bulk active drug substance. Sampling area design requires an understanding of reception protocols and secure storage. Cross reference the data that has been corrected to authenticate it. Once this determination is made, however, additional retesting for purposes of testing a product into compliance is not acceptable. Periodic data comparisons would be sufficient only when such comparisons have been made over a sufficient period of time to assure that the computerized system produces consistent and valid results. 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