Update to Seminal Report on Orphan Drugs Co-Authored By HP&M Attorneys Shows FDA’s Continued “Extraordinarily Reasonable Flexibility” in Approval

May 1, 2015

On April 27, 2015 the Drug Information Association journal, Therapeutic Innovation and Regulatory Science, published the findings of a study conducted by HP&M Attorneys Frank J. Sasinowski and James E. Valentine*, along with co-author, Erika B. Panico, RAC, head of U.S. Regulatory Affairs for Chiesi Pharmaceuticals Inc.  This study serves as a follow-up to a March 2012 analysis conducted by Frank J. Sasinowski that reviewed the quantum of effectiveness evidence that is required to secure FDA approval of therapies for rare diseases, or orphan drugs, from the 1983 enactment of the Orphan Drug Act through June 30, 2010.  This current study was designed to determine, over the 4 years since the original study, how frequently FDA has required marketing applications of drugs for rare diseases to provide the conventional level of proof of effectiveness that is ordinarily expected for most drugs for prevalent diseases.

This study employed methods similar to the original analysis, identifying the noncancer orphan drugs approved as new chemical entities by relying on FDA’s publicly available documents for drugs approved by FDA from July 1, 2010, to June 30, 2014. These materials were used to identify the basis for each drug’s approval, and each approval was analyzed and classified.

The results of this study show that for just over two-thirds of all noncancer orphan drugs approved between July 1, 2010, and June 30, 2014, FDA did not require the orphan drug applications to provide the conventional level of proof of effectiveness that is ordinarily expected for drugs for prevalent diseases. This is consistent with the results of the 2012 analysis (see Table below).

Table. Update to Analysis of Orphan Drug Efficacy Evidence 

Orphan Drug Efficacy Evidence


Total Flexibility


Case-by-Case Flexibility

2012 Sasinowski Analysis*

45 (33.3%)

90 (66.7%)



2014 Update**

8 (29.6%)

19 (70.4%)




53 (32.7%)

109 (67.3%)



* January 1, 1983 to June 30, 2010. ** July 1, 2010 to June 30, 2014.

The findings further support that FDA has demonstrated extraordinarily reasonable flexibility in its review of certain applications for orphan drugs and reinforce the need for FDA and drug companies to better understand and discuss the various types of flexibility.

*Admitted only in Maryland. Work supervised by the Firm while D.C. application pending.