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Impact of SOP on Dissolution Failure

Dissolution failures often are caused by improperly written SOPs.  These failures happen when important information isn't written into the SOP or isn't properly defined.  When the method is followed by someone else (especially in a method transfer), the dissolution run will then be done differently and can cause a different result.  A dissolution method is just like a cooking recipe, and deviations can result in disasters.

The SOP should define all critical aspects of the dissolution method.  What are the conditions of the dissolution such as the agitation speed and media?  What filters are needed for the run?  How should the media be prepared and degassed?  Are sinkers needed, if so - what type and how are they made?  If there are any special concerns those should be defined as well.  Special concerns might be stability issues, robustness issues where a parameter might need to be more tightly maintained than usual, key observations to look out for.

Care should be taken when defining something in your SOP to make it specific enough so that the right item will be chosen - but not so specific that it will limit the method in the future.  One example of what I mean concerns dissolution filters.  A dissolution filter could be defined in a method as:

1) 10um filter tip filter

2) 10um UHMWPE Full Flow Cannula Tip Filter Varian p/n 17-4005

In the case of 1) the filter isn't defined well enough since the chemistry of the filter is not defined and someone could choose a PVDF or other chemistry filter instead.  In the case if 2) the filter is too tightly defined.  If this filter has it's part number changed or the company name changes than there is an issue with compliance to the SOP.  We had several labs that ran into issues with 2) when Agilent purchased Varian!

When defining something in your SOP, fully define that component but also future proof it by adding "or another validated" component to the language.  In this case, you could say "use a 10um UHMWPE Full Flow Cannula Tip Filter from Varian or another validated filter".  This both fully defines that item and allows for a substitution if needed with another component if equivalency is validated for it.

Before finishing your SOP, have another analyst walk through the SOP and ensure that all of the critical aspects of the dissolution method have been captured.  Have that SOP walked through like a rehearsal to make sure a component or step hasn't been missed.  Doing this can help limit many future dissolution failures.

Read also: Dissolution Method Development and Validation

Resource Person: Ken Boda (Dissolution Product Specialist at Agilent Technologies)

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