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

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

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

Posted: 04 Feb 2015 07:49 PM PST

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 date 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:

Year	Drug Products Listed	Single Source		Multisource		TE		Not TE		NoA
	No.	No.	%	No.	%	No.	%	No.	%	No.
1986	8957	2103	23.5	6854	76.5	5838	65.2	967	10.8	333
1987	9709	2096	21.6	7613	78.4	6691	68.9	848	8.7	349
1988	10091	1983	19.7	8108	80.3	7242	71.8	748	7.4	374
1989	10123	2030	20.1	8093	79.9	7222	71.3	752	7.4	400
1990	10123	2030	20.1	8093	79.9	7222	71.3	752	7.4	400
1991	9584	2187	22.8	7397	77.2	6580	68.7	664	6.9	430
1992	9488	2245	23.7	7243	76.3	6516	68.6	577	6.1	477
1993	9140	2144	23.5	6996	76.5	6292	68.8	527	5.8	526
1994	9141	2178	23.8	6963	76.2	6330	69.2	453	5	534
1995	9286	2217	23.9	7069	76.1	6437	69.3	440	4.7	586
1996	9392	2383	25.4	7009	74.6	6463	68.8	442	4.7	650
1997	9624	2462	25.5	7052	73.3	6673	69.3	379	4	511
1998	9923	2504	25.2	7308	73.6	6934	69.9	374	3.8	563
1999	10045	2599	25.9	7335	73	6986	69.5	349	3.5	576
2000	10360	2682	25.9	7568	73.1	7257	70	311	3	594
2001	10166	2665	26.2	7391	72.7	7105	69.9	286	2.8	574
2002	10465	2420	23.1	7939	75.9	7659	73.2	280	2.7	598
2003	10665	2423	22.7	8134	76.3	7856	73.7	278	2.6	601
2004	11082	2427	21.9	8547	77.1	8327	75.1	220	2	625
2005	11368	2428	21.4	8851	77.9	8642	76	209	1.8	628
2006	11896	2471	20.8	9336	78.5	9139	76.8	197	1.7	666
2007	12302	2483	20.2	9724	79	9571	77.8	153	1.2	693
2008	12751	2433	19.1	10229	80.2	10072	79	157	1.2	719
2009	13065	2460	18.8	10516	80.5	10367	79.3	149	1.1	718
2010	13838	2482	17.9	11267	81.4	11107	80.3	160	1.2	752
2011	14480	2451	16.9	11953	82.5	11792	81.4	161	1.1	810
2012	15343	2440	15.9	12825	83.6	12683	82.7	142	0.9	835
2013	15711	2517	16	13194	84	13055	83.1	139	0.9	866
2014	16150	2572	15.9	13578	84.1	13443	83.2	135	0.8	927

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.