Surprise, Surprise – More New ANDA Requirements

Anyone contemplating submitting a drug-device combination product like an autoinjector, prefilled syringe, transdermal patch (yes, transdermal patch), etc., should be prepared to address some of the device regulations or you will likely get a deficiency letter.  (To be perfectly honest, if you get these deficiencies, I think you should push back on the FDA, but that is an individual decision you must make.)

FDA has been asking to address 21 CFR 820.20, Management Responsibilities, 820.30 Design Control, 820.50 Purchasing Control, and 820.100, Corrective and Preventative Action Plans in ANDA submissions for these products.  One might think that these would be cGMP issues that should be covered in an FDA inspection.  Well, that is what several people thought at the Association of Affordable Medicines (AAM) CMC Conference yesterday.  So why is FDA asking?  In response to the question “shouldn’t these issues be covered by investigators in an inspection rather than submitted in the ANDA?”, an FDA representative stated that “having that information in the ANDA will allow FDA to decide whether an inspection of the device manufacturer needs to be made.”

This seems like a bit of a stretch.  These questions certainly won’t be determinative as to whether FDA would inspect a drug manufacturer, so why would you think they would be determinative as to whether a device manufacturer would need to be inspected? The answers to these regulatory citations address cGMP issues.  Whatever happened to the separation of review of the ANDA and cGMPs?  Certainly, FDA’s Compliance teams know most of these device manufacturers and could make a determination of the compliance with these sections of the regulations based on past inspections.  If a device manufacturer is new and has never been previously inspected, FDA would likely inspect them anyway independent of an ANDA submission by another party.

These deficiencies appearing in Complete Response Letters (CRLs) or Information Requests (IRs) or Easily Correctible Deficiencies (ECD) letters seem to be relatively new informational requests and have not been asked for historically.  Request for inclusion of this information in the ANDA represents yet another example of asking ANDA sponsors to include new and additional information in its application, and seems to represent a new requirement. It is no wonder that ANDAs don’t get approved in the first cycle.

Maybe I am being too harsh, but looking for ways to streamline the review and approval process does not mean asking for additional information in the ANDA, especially cGMP information that is within the review purview of the compliance folks.  Please let me know what you think about this issue.  I can be reached at