Mining the Bowels of the Orange Book: What Do the Data Reveal?

By Kurt R. Karst –      

There’s no two ways about it: We love data.  And it doesn’t really matter what FDA-related topic those data concern: citizen petitions (here and here), drug patent settlement agreements (here), user fees (here), orphan drugs (here), or just general FDA regulation (here).  We find it all rather interesting.  After all, data can provide an informative picture of the FDA sandbox in which we play, and data are often predictive of the future. 

As this blogger fingered through the pages of the final Cumulative Supplement to the Orange Book from December 2014 (yes, the paper version of the publication is still used!), I stopped at a section I had seen may times before, but to which I had not paid a lot of attention: Section 1.6, titled “Report Of Counts For The Prescripton Drug Product List.”  It’s buried deep in the bowels of each Orange Book Cumulative Supplement  (but is not included in each annual edition) and is probably ignored by most folks.  Here’s how that section is described in the December 2014 Orange Book Cumulative Supplement:

This report provides summary counts derived from the product information in the Prescription Drug Product List and the current Cumulative Supplement.  Products included in the counts are domestically marketed drug products approved for both safety and effectiveness under section 505 of the Federal Food, Drug, and Cosmetic Act.  Excluded are approved drug products marketed by distributors; those marketed solely abroad; and those now regarded as medical devices, biologics or foods.

The baseline column (Dec 201[3]) refers to the products in the Prescription Drug Product List.  For each three-month period, a column of quarterly data is added which incorporates counts of product activity from the previous quarter(s) with those in the baseline count.

That description sounds pretty humdrum, and the numbers provided for each category and subcategory seem just as uninteresting – at least until they’re put into historical perspective.  And that’s just what we did.  We went back to the 1987 Orange Book (7th edition) – the first year after FDA transitioned from a fiscal year to a calendar year Orange Book publication schedule – and pulled the numbers from each December from 1986-2014 for two categories of drug product information: Drug Products Listed and Number of Applicants ("NoA").  We also looked at the following subcategories under the Drug Products Listed category: Single Source, Multisource, Therapeutically Equivalent ("TE"), and Not Therapeutically Equivalent ("Not TE").  Here’s the table we put together with the information we culled: 

The numbers from the table above are even more illuminating when put into graphic format.  Below are several tables, first showing graphically the numbers for all of the categories in the table above, and then breaking out some of the categories (by number or percent).

The historical Orange Book data show some interesting trends – many of which seem self-evident.  First, the number of marketed drug products has grown significantly in nearly 30 years – increasing by more than 80%.  Second, generic penetration post-Hatch-Waxman continues to grow.  According to the IMS Institute for Healthcare Informatics and the Generic Pharmaceutical Association (here and here), 86% of prescriptions dispensed in the United States in 2013 were for generic drugs. That figure is pretty close to the 84.1% figure above for multisource drugs listed in the “active” (i.e., Prescription Drug Product List) section of the Orange Book.  Similarly, the number of therapeutically equivalent (i.e., “A-rated”) drugs continues to grow – from 65.2% in 1986 to 83.2% at the end of 2014.  Meanwhile, the number of drug products not therapeutically equivalent (i.e., “B-rated”) continues to decrease – from 10.8% in 1986 to just 0.8% in 2014.  This significant (more than 86%) decrease may be due to the fact that post-Hatch-Waxman, drug products approved under an ANDA are not “B-rated.”  Prior to Hatch-Waxman, and as a result of the Drug Efficacy Study Implementation program, FDA approved many ANDAs with a “B” therapeutic equivalence rating.  Finally, the number of applicants increased by more than 178%.  Although there’s been a lot of consolidation among companies over the past decade, and some companies may have multiple subsidiaries, that’s a pretty significant increase in the spread of companies, and seems to show the continuing development of a robust pharmaceutical industry.  

Viewed as a whole, the data convey a clear message (at least to this blogger): the Hatch-Waxman Amendments, now in their 31st year post-enactment, have been a great success.  The two competing goals of the legislation – to spur new pharmaceutical development and to encourage greater access to generic drugs – have thus far been met.  That’s an important message to keep in mind as Congress considers proposals (see here, here, and here) that some folks argue might upset the balance created back in 1984.