jueves, 5 de febrero de 2015

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?



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).DrugReportCounts1

DrugReportCounts2

DrugReportCounts3

DrugReportCounts4

DrugReportCounts5

DrugReportCounts6

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 herehere, and here) that some folks argue might upset the balance created back in 1984. 

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