Back in November 2021, the Lachman blog brought your attention to the changes coming with the new FDA reporting requirements that were instituted under the March 2020 CARES Act (section 3112(e)) when it was reported at the AAM GRx-Biosims conference.  This new law, enacted for COVID‑19 response and relief, includes “enhanced” abilities for the FDA to better monitor the market for potential drug shortages.  Lots of confusion ensued and several industry groups have come together to request that the FDA delay this implementation.  However, at this point, no one can definitively count on that delay to happen; therefore, Lachman Consultants’ Regulatory Group has studied the two Guidances for Industry (GFIs) that the FDA issued and summarized the requirements outlined in these guidances.

Under section 510(j)(3) to the FD&C Act, any registrant in the U.S. is REQUIRED to annually report the monthly amount (ACTUAL, NOT THEORETICAL YIELDS) of listed drug “manufactured, prepared, propagated, compounded, or processed (including repacking and relabeling)” and released for commercial distribution (including repackers and relabelers) of any of the following product types:

  • API
  • Finished product (including medical gases, homeopathic products, and products marketed in accordance with requirements under section 505G of the FD&C Act (21 USC 355h), often referred to as over-the-counter monograph drugs, and animal drug products that are not approved, conditionally approved, or indexed under sections 512, 571, and 572 of the FD&C Act)
  • Unfinished drugs (defined as an API either alone or together with one or more other ingredients, but does not include finished drug products (per § 207.1))

If you have a product drug listed but did not manufacture and/or release for distribution any of the product, you must state in the annual reporting that zero was released for distribution each month that you did not manufacture/and or release product for distribution.

This requirement is not only being enacted as an annual requirement starting in 2022, but is also retroactive for the years 2020 and 2021.  Anyone who has an FDA-registered API or drug product manufacturer (as defined above) is required to report as follows:

  • The first reporting deadline (for calendar year 2020) is February 15, 2022.
  • The next reporting deadline (for calendar year 2021) is May 16, 2022.
  • The next reporting deadline (for calendar year 2022) will be February 15, 2023.

The reporting is to be submitted to the FDA via the FDA’s NexGen portal, an FDA electronic submission system for which one must register and create an account.  The data can be entered manually into the portal or uploaded as a completed .csv file using the FDA’s .csv template, which is provided in the NexGen portal (it will open as an Excel spreadsheet).  You can choose to type in your information directly on the NexGen Portal or use your own Excel spreadsheet (but beware – if you use your own, the formatting must match the .csv template to ensure that it uploads successfully).  The portal has instructions for both downloading the template and using it.  Here are some helpful hints (summarized from the GFIs) to help you in filling out the template.

GENERAL

  • The template Excel spreadsheet from the FDA has example data entered on the second tab. Note, all expected package types are listed on the third tab.
    • Hyphens need to be included in the NDC number.
    • Reporting is to be done on an annual basis, but data is to be reported by month.
    • Data is to be reported based on the amount of product released that month for distribution.

REPORTING INFORMATION

  • Reporting needs to be broken out by NDC codes, by outer package quantity (e.g., case) and innermost package quantity (e.g., bottle). (Examples are provided in the GFI Technical Conformance Guide Appendices.)
    • However, if the product is listed as a kit, the amount should only be based on the outermost layer of packaging associated with the NDC.
    • Sometimes a product could be assigned an NDC (NDC#1) on its own and also be included as a part of a kit or as an inner packaging layer for another product NDC (e.g., NDC#2). In this case, NDC#1 should only be reported as NDC#1 when it is on its own.  It would be included in the NDC#2 reporting when that accounting is reported.
  • For each NDC, you will need the following information:
    • The establishment DUNS associated for that NDC
    • The associated Business Operations (BO) for that NDC (You should select the single BO that best describes the activities that the establishment performs for that NDC.)
      • The BO is entered via a dropdown menu and only the following options are available (descriptions are available in the Technical Conformance Guide GFI):
        • MANUFACTURE
        • API MANUFACTURE
        • REPACK
        • RELABEL
        • TRANSFILL
        • POSITRON EMISSION TOMOGRAPHY DRUG PRODUCTION
      • Generally, you should NOT enter an NDC in association with more than one BO at a single establishment, though there are some exceptions (see the Technical Conformance Guide GFI for examples).
    • Private Label Distributor (PLD) requirements are specifically addressed in the guidance. Reports are by NDC number; therefore, the guidance points out that two separate reports (one for the contract manufacturer’s NDCs and one for the PLD’s NDCs) are to be submitted.  Therefore, similar to PLD NDC drug listings, PLDs and their contract manufacturers may need to collaborate and coordinate who will do the required amount reporting for the PLD’s NDCs based on their current Quality Agreements and/or release procedures.
    • Reports should NOT be done based on the number of tablets, volume, or mass of the products.
    • There is no exemption for drugs recalled or returned so these should not be subtracted from the released amounts being reported.
    • Registrants are to report even if they only distributed for a portion of the year. Data is entered for each month.
    • If a product is drug listed, even if no material was released for distribution, you must still include the NDC in the reporting; the box can be left blank or filled in with a zero, but it must be reported.

API/DRUG PRODUCT-SPECIFIC INFORMATION

  • For medical gasses, reporting should be done based on the number of units released from the establishment; see the GFI for further details.
  • For API, the reporting should list the amount of API released (not manufactured) by monthly amount for the subject year (refer to footnote 14 of the Reporting Amounts guidance for the FDA’s definition of “released”). Please note that this does not include intermediates used in the synthesis of the API.
    • The amount reported should be in the appropriate unit containers as reported in the drug listing (e.g., tanks, drums, cylinders, bags) rather than by weight, mass, or volume‑suing metric or imperial‑system units.
    • Amount reported is to be based on ACTUAL yield, NOT THEORETICAL yield.

REGULATORY INFORMATION

  • If a foreign establishment manufactures for distribution in the U.S. and other countries, it may report only the amount distributed within the U.S. However, if they are not sure how much was distributed in the U.S., they should report the total amount they distributed and indicate “market unknown.”
  • This reporting is more specific than the Annual Report distribution data required for human drugs under 314.81(b)(2)(ii)(a); for example, this data has to be reported for each establishment. Thus, you cannot use submitted Annual Report data to satisfy this requirement, but you may be able to use this data to satisfy Annual Reporting requirement under the above regulation.  The FDA has indicated that it is “unlikely that FDA will enforce the requirement to report [this] distribution data in ARs” if the data is reported under this new system.
  • Similarly, a registrant for animal drugs must also submit a separate report under this new section 510(j)(3) in addition to the annual reporting requirements under 514.80(b)(4)(i) and 514.87(b)(4)-(5).

The following FDA GFIdocuments were used to put together this summary and should be referenced for additional details:

  • “Reporting Amount of Listed Drugs and Biological Products Under Section 510(j)(3) of the FD&C Act” (here) addresses in detail what is summarized above.
  • “Reporting Amount of Listed Drugs and Biological Products Technical Conformance Guide” (here) explains the submission process and data-entry particulars needed. There are examples for each standard situation in the Appendices beginning on page 11.

On January 31, 2022, the FDA announced that it has added two webinars to help with implementation of the Reporting Amount of Listed Drugs and Biological Products required under the CARES Act.  Additionally, it has included instructions for filling out the .csv template.  These resources can be found here.

If you have any problems or questions and need support with these new requirements, please reach out to us at R.Welton@LachmanConsultants.com.