Check if samples were incorrectly prepared, diluted, injected or stored at an inappropriate. Review of recent oos related citations in warning letters. When the oos report is complete, it should be kept in the sample report and the copy should be sent to the quality manager. The first session will discuss the fda guidance for industry on oosoot investigation in details. A blog about pharmaceutical quality control, quality assurance, microbiology, production and regulatory updates provided by regulatory. The oos process is concerned with the examination of any result that falls outside established acceptance criteria. Purpose the purpose of this standard operation procedure is to establish a procedure for the routine handling of outofspecification oos laboratory results the investigation or failure investigation should where ever possible identify the cause of the oos and evaluate its impact.
These may or may not be oos atypical results are usually anomalies or unexpected results. Guidance for industry food and drug administration. Checklist to investigate the out of specification in analytical results of pharmaceutical products in qc laboratory, manufacturing and warehouse. If an oos or oot result is identified, then this must be. On coming to know about an oos result the laboratory in charge should first of all jointly conduct the initial investigations as detailed above and make a written report of the findings. How to properly investigate oos results webinar compliance. I am attaching 2 articles from the pharmaceutical technology on related subject that you might find useful.
Ensuring that this sop is understood and adhered to by all laboratory personnel. Lesson 1 dont ignore the fda schering plough was audited by the fda on several occasions and 483s were issued every time the fda returned none of the issues identified in the 483s had been addressed. How to properly investigate oos results compliance trainings. Laboratory errors, flow of investigation, phases of investigation. Both the us and the uk guidance make it clear that the investigation process to be followed should be the same for analytical results that are oos, oot or. Investigating outofspecification test results for pharmaceutical production guidance for industry october 2006. However, in case of oos of outsourced raw materials, intermediates and resampling may be performed even if there is no evidence suspected in sampling errors primarily to. Laboratory investigation outofspecification results.
Pdf out of specification oos and out of trend oot analysis in. These deals with handling of deviating analysis results. Investigating oos for finished product on the stability. Current gmps demand full understandng of outofcontrol concepts. Investigating outofspecification oos in pharmaceutical. When the oos or oot results merited following is the chart that can be used for taking quick actions before performing the investigations and must be part of.
Oot investigation shall be completed within 30 days of its detection. How to investigate out of specification oos laboratory. When the guidance was first released there was some what of a mixed reaction. Although it is less detailed, in general the mhra guideline is compatible with that of the fda and it improves upon it in some areas. Note that any decision to release a batch, in spite of an initial oos result that has not been invalidated, should come only after a full investigation has shown that the oos result does not reflect.
If the oos is confirmed the batch is rejected and if the oos is found inconclusive then qa may be able to justify and release the batch. Confirm and summarize if there are any previous stability oos or oot events for the batch andor product. Out of specification guidance update by mhra pharmalex. Oos includes all test results that fall outside specifications or acceptance criteria established by the manufacturer and or laboratory oot are results which fall out of trends. What is out of specification oos the result obtained out of defined test limit is called out of specification. Yyy stands for serial number and started from 001 for each calendar year. Mainly because the guidance is in the form of a flow chart, so it didnt look like other guidance and there was next to no focus on how much repeat testing is enough. This white paper provides an example oos investigation checklist, as well as a discussion on oos investigation, including. Laboratory investigation of outofspecification oos results. Oos procedure additionally, if a specific analytical method andor a standard operating procedure sop for a given technique has defined acceptance criteria for replication of. The investigation process flow is similar in the us and uk guides. This series will give a complete discussion on oosoot investigation practices.
The mhra first published guidance to industry on how to handle oos investigations in august 20. Investigations of out of specification oosout of trend ootatypical results have to be done in cases of. Usfda guideline investigating out of specification oos test results for pharmaceutical industry published by cder in oct 2006. Guidance on out of specification investigations, including definitions and laboratory analysis and phase i,ii and iii investigations. Management of out of specification oos for finished product. Technical management team considers and evaluates the investigating result and all the data for conclusion and report. It can be difficult to determine if the oos result is valid or if retesting is appropriate and can be justified.
Analysts must investigate for laboratory errors which can occur when analysts make analytical mistakes. The term oos out of specification, is defined as t hose results of in process or finished p roduct testing, which falling out. The objective of this webinar is to develop an understanding of how a compliant laboratory handles the investigation of outofspecification oos test results and how the laboratory interfaces with other units through the laboratory investigation process. Oos results are most often generated due to laboratory or manufacturingrelated errors, the setting of inappropriate specifications, or poor method development. Online ankur choudhary is indias first professional pharmaceutical blogger, author and founder of pharmaceutical guidelines, a widelyread pharmaceutical blog since 2008. This topic provides how to evaluate outof specification oos test results. Once an oos value is discovered, one needs to confirm if it is caused by the measurement or the manufacture. It is important to distinguish between oos and oot results. Phase 2 investigations both us fda and mhra guidances discuss the concept of phase 2 investigation. Unlike phase 1 both guidances address this concept in exactly the same manner. Nsf pb white paper out of specification and out of trend.
Batch release testing and testing of starting materials. After completing the initial investigations it is essential that documentation be completed for future reference. Oos investigations in pharmaceutical laboratory, outof. Several companies have received 483 observations requesting the development of procedures documenting how oot results will be identified and investigated.
Posted by admin comments 0 tags ooe, oos, oot, outofspecification. The regulatory agencies require that oos, outoftrend oot, or aberrant results be investigated. Quality unit should have well define sop for oos the scope of sop should be well define dr ravi. Laboratory investigations will be initiated within one 1 business day of the discovery of the oosatypical result, and will be completed within ten 10 business days, unless an extension is approved in writing by the laboratory supervisor and qa. Out of specification oos and out of trend oot analysis in pharmaceutical manufacturing investigations mir. This guidance represents the food and drug administration s fdas current thinking on this topic. Investigations of out of specification oos out of trend oot atypical results have to be done in cases of. The sop should give clear guidance on the number of retests allowed based on sound. In this video initial three parts of the guidelines are decoded those are 1. Management of out of specification oos for finished.
Out of specification investigation flowchart for laboratory stage as well as manufacturing. For the release of test batch oos investigation is mandatory. In order that laboratories can perform a meaningful investigation following an oos or oot result, it. Fda guidelinesfor out of specifications oos in industries.
The investigation of outofspecification oos results is an important part of the work undertaken by the analytical laboratory. Fda issued a oos guidance in the scientific literature and discussed at many scientific conferences about oos results. In this 90minute training on laboratory outofspecification oos investigations, you will learn what constitutes an oos observation, what is the oos investigation process described in the oos guidance and steps to be taken in the laboratory in the event of an oos observation. Since we have no opportunity to determine which test or study will become problematic, we must as a matter of course be prepared to investigate all of. Manual 058 out of specification results investigation. Remember that oot may not be oos and just off the trend. The oos will be recorded in the list of out of specification ws. Oos includes all test results that fall outside specifications or acceptance criteria established by the. Pdf on dec 15, 2018, sagar savale and others published out of specification oos and out of trend oot analysis in pharmaceutical manufacturing investigations mir. Evaluate the need for investigations where confirmed outofspecification results occur and ensuring they are completed. One way to approach this, is to conduct an oos investigation.
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