OOT (Out-of-trend) in Pharma : Identification, Investigation, Overview

OOT (Out-of-trend) in Pharma 

Identification, Investigation, Overview

Days back we have gone through a detailed post on OOS investigation. Many people have questions about Out of trend (OOT) results. Both the criteria i.e. OOS and OOT are related to analytical test results, however, both are having different meanings and identification criteria. So, in this post, we will go through differentiation between OOS (out-of-specification) and OOT (Out-of-trend) and details related to OOT.

What are out-of-trend results?

First, we will understand the concept of Out of trend. For that let's see what is trend first. Any activity which is carried out continuously in a similar manner gives some results which fall in one direction that create a trend of that observed results. whereas some time some outlier results observed other than this trend which is actually within the specification but has more difference between previous results that is called as out of trend results. 

Difference between OOS and OOT results:

Now let's see the difference between out-of-specification results and out-of-trend results with the help of an easy example. Consider Assay test having acceptance value of 95.00 % to 105.00% in the Specification. Now we are getting results like given in the following tables. Suddenly, we got the result of one of the batches is 103.60% which is different from previous results that are out of trend results because it is within specification but different from previous results. But if we get the result of one of the batches is 105.90% which is called out of specification results. These examples are well explained with the help of the following tables and graphs. 

Satisfactory Assay results
Batch Number	Assay Results in %	Lower Limit in %	Upper Limit in %	Lower Trend Limit in %	Upper Trend Limit in %
1	99.98	95	105	98	102
2	99.55	95	105	98	102
3	99.69	95	105	98	102
4	100.23	95	105	98	102
5	100.56	95	105	98	102
6	99.85	95	105	98	102
7	100.37	95	105	98	102

Assay results (OOT result)
Batch Number	Assay Results in %	Lower Limit in %	Upper Limit in %	Lower Trend Limit in %	Upper Trend Limit in %
1	99.98	95	105	98	102
2	99.55	95	105	98	102
3	99.69	95	105	98	102
4	103.6	95	105	98	102
5	100.56	95	105	98	102
6	99.85	95	105	98	102
7	100.37	95	105	98	102
8	98.2	95	105	98	102
9	100.8	95	105	98	102

Assay Result with OOS results
Batch Number	Assay Results in %	Lower Limit in %	Upper Limit in %	Lower Trend Limit in %	Upper Trend Limit in %
1	99.98	95	105	98	102
2	99.55	95	105	98	102
3	105.9	95	105	98	102
4	102.6	95	105	98	102
5	100.56	95	105	98	102
6	99.85	95	105	98	102
7	100.37	95	105	98	102
8	98.2	95	105	98	102
9	100.8	95	105	98	102

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Handling of OOT results: 

Now we are aware of the meaning of Out of trend results. Let's see how to handle it? All identified out of trend results shall be reported, documented, and investigated. We will see step by step procedure for it. There is no more difference between handling OOS and OOT. For detailed procedure for handling of OOT refer this post: OOS In the Pharmaceutical industry

• When an analyst identifies that results are out of trend then he/She shall immediately report to reporting head. Reporting head shall do the preliminary investigation of the analysis for any laboratory error or analyst error. 
• Reporting head shall store all the samples with standard preparations in a safe dedicated location till the final investigation and reporting of it. 
• Then allocation of OOT number to this event shall be carried out by dedicated person by Analytical Quality Assurance personnel. 
• Once the number is locked then laboratory investigation starts. The investigational department shall start the investigation on a laboratory basis.  If the root cause is identified in the preliminary investigation then reporting of investigation shall be done and reanalysis by the same analyst shall be done. and OOT closes here. 
• If the route cause is not identified by preliminary investigations then resampling and reanalysis are carried out. If the same results are observed this time and route cause is not identified then the investigation report is shared with production Quality Assurance. The final decision shall be taken by Quality Head on the basis of the Investigation report. 
• In the case of Raw material and packaging material, it is rejected and discussed with the vendor. 

Reporting of Out of trend results: 

Nowadays there is software to handle Out of trend results. Some are handling it manually. In software, all information regarding sample, product details including name, batch number, stage, strength, specification, and method of analysis details, analyst details are filled. then investigation report is submitted to software. 

In the case of the manual method, there are some forms according to the sample. The form includes all details of the sample, product, and checklist. After this investigation report is prepared and attached to the OOT form. 

Out of Trend is an event that is generally asked by auditors. Auditors want it to be described in a good manner as per guidelines. Handling and reporting of Out of trend results shall be done accordingly. 

Thank you for reading this post. For any queries feel free to comment below.