Out-of-Specification investigations

Out of specification investigations Customer complaints Standard Operating Proeedures... 

Case Study 3 Poor Assay Accuracy Data, an Out-of-Specification Investigation 260... 

The added attention to detail and validation of the software has given us software with far fewer problems than before the PAT initiative. Rebooting a computer at a grain elevator will not cause an out of specification investigation, merely inconvenience for the operator. This is yet another benefit of the guidance. 

Investigating Out of Specification (005) Test Results for Pharmaceutical Production, FDA Draft Guidance for Industry (J IGUIDANC 121DFT.WPD) dated 9/4/98. 

Lastly, the need for potential trouble shooting bulk samples should be agreed to facilitate any out-of-specification (OOS) investigations (Worsham, 2010). 

Samples of intermediates and finished products taken for analysis are recorded, stating the time, date, and conditions for these samples. Deviations in operating conditions and out of specification (OOS) conditions in samples are reported and investigated. Figure 9.2 shows a mechanism for production and in-process controls. 

Out-of-Specifications There are insufficient investigations to determine the root cause of problems and issues are not closed in a timely manner. Product Sterility The tests performed are superficial and not validated. Environment Monitoring Personnel are not monitored, there is inadequate monitoring, microorganisms are not monitored, there is no... 

The terms mode-selective and bond-selective dissociation refer to the control of the dissociation products in VMP. The terms are usually used as synonyms although, strictly speaking, the former should refer to selective preexcitation of a vibrational mode and the latter to the resulting selective bond cleavage. Control of the dissociation products in VMP has been extensively reviewed [28-31] and our discussion will focus on molecules studied (or continued to be smdied) after the latest comprehensive review was published [31], An exception will be a short overview on the VMP of water isotopologues since it was the extensive theoretical and experimental investigations of these molecules, in particular H2O and HOD, that opened a new era of detailed smdies of state-to-state photodissociation out of specific rovibrationally excited states of polyatomic molecules. 

Perform a laboratory technical investigation and retest the testing reagents. Repeat the test with more restrictive sampling and testing conditions. Perform investigational analysis of out-of-specification microbiological... 

Corrective actions PAT opens the door for new tools for root cause investigations and data collection in production Manufacturing Science provides the foundation for more effective approaches CGMP initiative objective f-5 Product is out of specification (OOS) or procedural deviations Crisis —immediate action needed Required by regulators... 

Through investigation of production records, auditors spot deviations or out-of-specification issues. This in turn may lead to an examination of an operator s work and qualifications for the job. The auditors may ask how or what additional training was conducted and request the records that prove training was provided. 

Instrument qualification is required to establish the functional capability and reliability of a system for its intended use in a suitable environment. Instrument qualification can be divided into three stages installation, operation, and performance qualifications. A qualification protocol that provides details about the system, the scope and constraints of the qualification, qualification tests, test procedures, and acceptance criteria should be available for review and approval before qualification begins. Sufficient time should be provided for review and approval. The protocol should also contain an exception log to record any out-of-specification results, investigation, and problem resolution. 

Whatever dimensionality the data have, they must be easily accessible and put to use. The data are imperative for product release, setting of product specifications that are based on true process variability, investigation of out-of-specification product, validation of the process, and trend analysis of production.28 A cost-estimate of the inefficient use of data for decision-making in a typical pharmaceutical plant shows the impact of such behavior on the company s costs. For a single product the annual costs are estimated as ... 

Failure to comply with cGMP requirements is just one of the areas during clinical trials that may result in compliance issues. Improperly assigned expiration dates, inadequate procedures related to the extension of expiration dates, and abreakdown in any of the steps from manufacture of a clinical trial material to its use in a clinical trial could result in compliance issues. Starting with the manufacture of clinical trial material, there must be well-designed and documented procedures that effectively involve all appropriate persons and departments to assure that only material within specifications is used in clinical trials. There must be procedures that ensure the timely availability of clinical supplies, timely and appropriate extension of expiration dates, timely investigation of out-of-specification (OOS) results and rapid notification of appropriate persons, timely recall of all OOS and expired materials, and timely resupply with fresh materials. Depending on the severity of the compliance issue, the clinical trial could be considered compromised. 

It defines anew term, OOS or out-of-specification result, which refers to a result obtained for the pharmaceutical material or drug product that does not comply with the regulatory specification for the particular test performed. Previously, FDA inspectors would prematurely term OOS laboratory results as product failures, which clearly was not established without proper laboratory and possibly more extensive investigational activities outside the laboratory environment. 

Thoroughly investigate complaints and out of specification and out of trend results. 

Provision of independent data sources for GxP records (e.g., QA monitoring and records for critical parameters, and QA investigations of out-of-specification incidents)... 

Lack of process and computer validation. Out-of-specification results inadequately investigated. Failure to investigate injury complaints. Cross-contamination due to improper equipment cleaning, particularly with APIs. 

Draft Guidances. Manufacturing, processing, or holding APIs and investigating out-of-specification (00 S) test results for pharmaceutical production. 

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