FDAs Office of Generic Drugs (OGD) has very quietly listed a new set of tables on their 'Information for Industry'page. These tables are titled Summary Tables for the Listing and Characterization of Impurities and Justification of Limits in Drug Substance and Drug Products and apparently must be completed and submitted along with the rest of the CMC data in new ANDAs. The tables are not dated but the paragraph referring to the need to complete and submit these tables is dated 'January 2014'. The presumption is that they must be submitted now, that is for now forward.
The tables are appended and are relatively simple in that they provide for recording all of the data concerning impurities required in the ANDA. They also require calculation of the identification and qualification thresholds. In addition applicants must list the proposed acceptance criteria and justify any proposed limits over those of ICH. This information is to be separately tabulated for both drug substance and drug product.
While this information has been required, pulling it together in one set of tables will enable ANDA acceptance reviewers to quickly assess whether all impurity acceptance limits (API and Finished Product) are appropriate and justified. It appears that OGD is continuing to expand the acceptance review to assure in as far as possible that all ANDAs filed are essentially approvable when filed. Resolving any significant deficiencies prior to filing is the mechanism used to ensure that NDAs meet the PDUFA goal dates. It seems that OGD is going to follow suit and resolve as many deficiencies as possible prior to receiving an ANDA. If you don't have justified impurity acceptance criteria you run the risk of having your ANDA receival refused and losing 25% of your filing fee.
From a practical perspective, in the past many ANDA applicants have filed ANDAs with relatively wide impurity acceptance criteria based on the fact that they did not have full term stability on the Exhibit Batches which were often the first batches made at a larger scale. Accordingly they got their ANDAs filed by using wide limits which could be tightened via CMC review deficiency when much more stability data was available to justify a tighter limit. It would seem those days are over and applicants will need to either accept ICH limits or have an acceptable justification for a wider limit. In other words they will need to know enough about their new product to be confident that they can meet what will be essentially final impurity acceptance criteria at the time of filing.
