I read this post when it was first posted. Then I re-read today, and decided to post.
I'm retired, R&D; my employer's QA Department and my supervisor went on a big cGMP kick a decade ago. For a while, QA wanted the analytical chemistry department to confirm and standardize ALL chemicals and solutions that were to be used for anything involving cGMP. Fortunately, this was explained to QA that many new employees would need to be hired, nothing else would ever get done, and everything would need to be compared to something trusted anyway. For example, if one was trying to confirm normality of 0.1N silver nitrate, then one would first need to determine purity of the NaCl used as reference standard. Fortunately, that idea was discarded.
Economics readily showed that using new unopened containers of titrant was considerably less expensive than labor for standardizations.
I was chosen to draft an SOP for us, and I went through many back-and-forths with my pointy-haired supervisor; I don't believe such SOP was ever finalized, but I'll include here from one of my drafts.
1. All lab-prepared volumetric titrants used for GxP or ISO purposes shall be standardized according to procedures outlined in the current USP or as specified in the test procedure.
2. The procedure for standardization must be performed in triplicate.
3. If the %RSD is greater than 0.5%, continue with three additional attempts and document rationale for any %RSD over 0.5%. After three additional attempts, unless otherwise specified, consult supervision and investigate causes using laboratory investigation procedure (reference the company SOP for OOS investigations).
4. Previously unopened and unexpired containers of certified/guaranteed titrant used for GxP or ISO purposes for which normality/molarity is reported as a range must also be standardized as above upon opening to determine the actual value before use. Once opened/prepared and standardized, titrants must be restandardized before next use if more than 30 calendar days since the previous standardization.
5. Previously unopened and unexpired containers of certified/guaranteed titrant used for GxP or ISO assays for which normality/molarity is reported as an actual tested value do not need standardization before use. Once opened, such titrants must be restandardized before next use if more than 30 calendar days since the previous standardization.
6. A volumetric titrant may be prepared by dilution of more concentrated titrant meeting the conditions above.
7. An appendix details volumetric titrant restandardization and stability periods for titrants for GxP and ISO use. All volumetric titrants for GxP and ISO use, unless specified otherwise in the relevant test procedure, must be restandardized every 30 calendar days (or prior to use if the time interval has exceeded 30 days). Certain titrants, such as 0.1N silver nitrate used for cGMP testing, are subject to a daily titer check as detailed in the test procedures.
8. No titrant may be used past its expiration date even if restandardized.
