Twice a year, the FDA publishes an update of the List of Off‑Patent, Off‑Exclusivity Drugs without an Approved Generic (see here). This list is designed to generate interest from the industry in increasing competition among such products. It is made up of two parts. Part I is for drugs for which the path to approval is relatively clear cut, and Part II is for products that might have a dodgy regulatory path to approval and for which the Agency suggests that potential sponsors have in‑depth discussions with the OGD prior to proceeding on development. Some of the products in Part II of the list may not qualify for ANDA submissions; they may be more suitable for 505(b)(2) NDA submissions, and it’s best to know that as early in development as possible.
In this update, the Agency lists 376 individual products in Part I and 130 in Part II. Looking at the list, one at first might think that there are a lot of duplicate products on it; for instance, there are six products listed for CALCIUM CHLORIDE, POTASSIUM CHLORIDE, and SODIUM CHLORIDE solution and injection, but each has a difference and is the subject of a different NDA. There is also an Annex that describes products for which ANDAs have been approved since the previous update (albeit it does not indicate whether the products came off Part I or II). In the past six months, eleven products were removed from the list. In the last list update, provided in June 2022, Part I contained 364 products and Part II contained 139. Unfortunately, simple math can’t make the numbers make sense from one update to the next because the number of NDA products without ANDA approvals can also change as ANDAs are discontinued, which might make an NDA product now eligible to appear on the list.
There are also lists for over‑the‑counter (OTC) drugs that are subject to marketing through an approved application. Part I of that list has twenty‑five products and Part II contains thirty‑four products. The Part II list has drug dosage forms that present more unique filing issues, such as acetaminophen suppositories or twelve different products for chlorhexidine gluconate that encompass aerosol, sponge, solution, swab, and cloth products. One product, ibuprofen suspension/drops, is identified as having come off the list of OTC products as an ANDA was approved during the last six‑month update cycle.
While some of these products might be difficult to develop, the lists do provide some fertile targets for development. The question is really whether the commercial values of some of these products are attractive to industry.
