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

February 4, 2015

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: 

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.