Drug Impurities

Are there any guidelines that would address lidocaine impurities in a OTC lidocaine product? Also would such impurities of lidocaine be a safety issue anymore than lidocaine itself and are there specific limits for such impurities?

3 replies
  1. Shayne Gad
    Shayne Gad says:

    Marv Are the impurities identified and quanitated? If none are mutagenic(see ICH M7(R2), then (as Bill points out), determine if they adhere to ICH Q3B or are covered by the lidocaine monograph in USP. If not, you have several options to qualify it or they.


  2. JoAnn C.L. Schuh
    JoAnn C.L. Schuh says:


    The FDA is most concerned by the formation of 2,6-xylidine from lidocaine.
    This is considered a rat carcinogen (causes nasal tumors – NTP report #278 and other monographs from US and EU). You’ll need to qualify this impurity/degradant and show that you control it to the lowest possible level in manufacturing and storage (see ICH M7). Two years ago I had the FDA ask for a carc study on a product with lidocaine concentration 10% above the maximum concentration currently marketed. Exposure was slightly less than comparators and 2,6-xylidine was minimal so the FDA backed off the requirement for a carc study this past Dec.


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