the effect of shorter review times on drug safety
TRANSCRIPT
The Effect of Shorter Review Times on Drug Safety Information
by
Dawud N. Ellayan
Project
Submitted to the College of Health and Human Services
Eastern Michigan University
in partial fulfillment of the requirements
for the degree of
MASTER OF SCIENCE
in Clinical Research Administration
Prof. Irwin Martin
04/15/2017
Ypsilanti, Michigan
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION i
Table of Contents
Abstract .............................................................................................................................. 1
Introduction ....................................................................................................................... 3
Purpose of the study.......................................................................................................... 6
Justification and significance ........................................................................................... 6
Research question ............................................................................................................. 7
Methodology ...................................................................................................................... 8
Results .............................................................................................................................. 12
Discussion......................................................................................................................... 17
Conclusion ....................................................................................................................... 21
References ........................................................................................................................ 22
Appendix * ................................................................................................................... 27
Appendix A .................................................................................................................. 28
Appendix B .................................................................................................................. 31
Appendix C .................................................................................................................. 33
Appendix D .................................................................................................................. 63
Appendix E .................................................................................................................. 67
Appendix F ................................................................................................................... 75
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION ii
Appendix I .................................................................................................................... 77
Appendix G .................................................................................................................. 80
Appendix H ................................................................................................................ 145
Appendix J ................................................................................................................. 206
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 1
Abstract
During the review process the FDA will approve a new drug application (NDA), if a drug
is considered safe, effective and meets the minimum required standards for the suggested
indication in the desired population (Applications for FDA approval to market a new
drug, 2015). Regulations governing the FDA review process have been evolving over the
last two decades to allow for a faster review of potential lifesaving and clinical significant
products (FDA, 2014). The focus of expedited review is introducing potential lifesaving
agents to patients in conditions where the benefit to risk ratio is affected by the higher
risk that patients might be willing to accept in these conditions (FDA, 2014), however,
for patients and physicians to be able to make that decision the common risks of such
therapies should be for the most part well established through premarket studies. This
study aims to determine if faster new NDA reviews sacrifice product safety information.
From publicly available data on the FDA website database; Drugs@FDA, all new drug
applications for type 1 New Molecular Entities (NMEs-1) approved by the FDA from
January 1, 2000 through December 31, 2016 (Drugs@FDA, 2016) were identified and
then stratified to standard, priority, orphan, and accelerated reviews. Then the first three
safety labeling changes (SLC) were identified for each drug, and the type of each SLC
whether it was; boxed warning, contraindication, precaution, warning or an adverse
reaction. Furthermore, the size of the safety database and the FDA requirement of post-
marketing requirements and commitments at approval were also identified for each drug.
Afterwards, the time for each SLC time point was averaged and compared across the
standard, priority, accelerated and orphan reviews for significance using both t-tests and
z-tests. Moreover, the average size of the safety database was also compared across the
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 2
aforementioned groups and the prevalence of each type of each of the SLCs was
compared across standard and priority reviews. No significant differences were identified
in the time to first, second, and third SLC, except for a statistically significant difference
between standard and priority reviewed drugs at the third SLC time point. To clarify, the
time to the third SLC was significantly longer for the standard reviewed drugs at the time
of the third SLC compared to priority reviewed drugs. Furthermore, the prevalence of
Boxed Warnings at the time of the third SLC time point was significantly higher for
standard reviewed drugs. In conclusion, the speed of review does not affect the safety
information of approved drugs, and although this analysis might have limited clinical
application, it provides reasoning for decreasing the review time for standard drugs to 6
months provided that adequate funding is available for needed resources.
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 3
Introduction
The introduction of new medications to medical practice is governed by a variety
of regulatory agencies that differ from country to country. Thus, the Food and Drug
Administration (FDA) regulates the manufacturing, developing, and selling of such
product, whether it is a biologic or a chemical entity. The FDA reviews new drug
applications submitted by pharmaceutical companies in order to determine if they have
sufficient data to support an effective and safe use for a specific indication in a specific
population (Applications for FDA approval to market a new drug, 2015).
Regulations governing the FDA review process have been evolving over the last
two decades to allow for a faster review than the usual standard review of potential
lifesaving products (FDA, 2014). The implementation of PDUFA in 1992, which was
followed by FDAMA in 1997 and SDASIA in 2012, led to regulations of expedited
review of certain applications. These regulations were reflected into four different review
pathways; Priority review, Breakthrough therapy, Accelerated approval, and Fast track
(FDA, 2014).
During the review process the FDA will approve an NDA, if a drug is considered
safe and effective and meets the minimum required standards for the suggested indication
in the desired population (Applications for FDA approval to market a new drug, 2015).
In order to get approval, the marketing applications should in most cases be based on
studies that are adequate and well controlled (Applications for FDA approval to market a
new drug, 2015).
The FDA gives a great importance to safety concerns from the studies presented
for approval during the review process. In fact, about 70% of the time that an agent
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 4
undergoes more than one review cycle is due to safety concerns (Ross, Dzara, &
Downing, 2015). However, the majority of these studies are designed to detect statistical
significance in efficacy parameters rather than safety, limiting the toxicity data available
(Ioannidis, 2009; Seruga, Sterling, Wang, & Tannock, 2011). Furthermore, even though
The International Conference on Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH) advocates that clinical trials safety
databases should include at least 1500 patients (Food and Drug Administration, 1995), a
sample size within this range will not detect rare side effects and may possibly have
lower than the needed power to detect adverse effects that occur at prevalence as high as
1/100, a percentage that it is usually expected to achieve (Food and Drug Administration,
1995; Reed, Anstrom, Seils, Califf, & Schulman, 2008). Lasser et al. (2002)
approximated that 20% of drugs approved over a period of 25 years will be either
withdrawn or have a new black box warning, which is a warning that reflect a life
threatening risk associated with the use of that drug (FDA, 2012). Moreover, about half
the withdrawals occur during the first couple of years. Knowing that more than eighty
percent of the U.S population uses one or more prescription medication and about thirty
percent use at least five medications (Slone Epidemiology Center at Boston University,
2006), an agent that gets approved without a well-established safety database has the
possibility of negatively impacting a large portion of the population. From a post
marketing perspective, during a two year period Adverse Drug Events (ADEs)
contributed to 700,000 emergency unit encounters, 120,000 hospital admissions and $3.5
billion of extra healthcare expenditure (Budnitz , et al., 2006). Furthermore, it is logical
that the concept of a favorable benefit to risk ratio would only be achieved if most of the
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 5
common adverse effects are identified in the premarket period. Sample size is a great
contributer to this knowledge, because as many as 15000 more ADEs could be averted
using a bigger sample (Reed et al., 2008). Examining a more antibiotic focused review,
Outterson, Powers, Seoane-Vazquez, Rodriguez-Monguio and Kesselheim (2013) looked
at the development of antibiotics over the last two decades and they argued that
advocating a faster review and approval of antibiotics based on limited data may result in
drugs that have a limited effect in the desired indication as these products will be
eventually withdrawn from the market for safety and other reasons. A proper review
process is integral in bringing safe and effective drugs to the market, and any disruption
in the review process would have a negative health and financial impact on the
population.
Medications for serious and life threatening conditions are usually approved
through accelerated approval regulations (FDA, 2014; Food and Drugs, 2015). Even
though drugs that might fall under the aforementioned regulation such as antineoplastic
agents have higher risk for death and serious ADEs than usual controls (Niraula, et al.,
2012), higher risk from these potentially beneficial therapies might be acceptable for
patient and health providers (FDA, 2014). The focus of expedited review is introducing
potential lifesaving agents to patients in conditions where the benefit to risk ratio is
affected by the higher risk that patients might be willing to accept (FDA, 2014). To
clarify, the expedited review includes priority, accelerated programs. Moreover, drugs
that classify as priority review would undergo a 6-month review period rather than the
standard 10-month review period, whereas classifying under accelerated review allows
for faster review by considering surrogate end point as a basis for approval (FDA, 2014).
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 6
Furthermore, in order to increase the development of drugs for rare diseases, the orphan
drug designation was developed which provide for 6 month of marketing exclusivity for
agents developed under this designation (FDA, 2017). Nonetheless, rare diseases
inherently have smaller study population sizes which could also have an effect on the
product safety information and predictability of certain adverse events and so does the
shorter review period granted by accelerated and priority review programs. However, for
patients and physicians to be able to make that decision the common risks of such
therapies should be well established through premarket studies. This study aims to
determine if faster NDA reviews and possibly smaller study sizes would jeopardize
product safety information and decrease the ability of premarket safety data to adequately
predict future adverse events.
Purpose of the study
Determining if faster NDA reviews sacrifice product safety information.
Justification and significance
Faster NDA reviews means faster availability of clinically significant medications
to patients. Nonetheless, faster review should not be at the cost of safety information
availability. Moreover, for physicians and patients to be able to choose the most
appropriate therapeutic agent, the common risks of such therapies should be well
established through premarket studies. And so this study aims to determine if faster NDA
reviews sacrifice product safety information.
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 7
Research question
Do faster NDA reviews sacrifice products safety information?
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 8
Methodology
First of all, to determine the effect of faster review process on the safety of
approved drugs, the time for drug’s safety labeling changes (SLCs) was used as an
outcome measure for comparison between the different arms in this study, the arms
included priority, accelerated reviews and drugs with an orphan designation. Logically
having well established safety information from the premarket period, means higher
predictability of the probability of certain adverse events in the product labeling which
should reflect on the timing of change to the safety information. To clarify, a change to
the safety labeling can happen due the appearance of certain adverse events in the post
marketing period that were not observed or observed to a lesser degree, or lesser
probability in the premarketing period. And so a drug with adequate safety information
from the premarketing period would have a well-established safety labeling in the
marketed product that would in natural circumstances take longer time to require changes
to labeling because of new safety information. On the other hand, drugs that are approved
without adequate safety information from the premarketing period would have safety
labeling that is not adequate and would result in faster changes to the safety labeling after
marketing as adverse events that should have been identified through development are
readily and constantly identified in the post market period.
Construction of the research database was done through three steps.:
First of all, from publicly available information on the FDA website database,
Drugs@FDA, all the new drug applications for new molecular entities (NMEs) approved
by the FDA from January 1, 2000 through December 31, 2016 (FDA, 2016) were
identified by choosing the drug approval by month tab, and then exporting each month
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 9
into an Excel-spread sheet using the functionality provided by the FDA website.
Afterwards, the drugs approved from January 1, 2000 to December 31, 2016 were
analyzed and drugs that were classified as NME-1 and a review classification as either
standard or priority were pulled into a collective Excel spread-sheet. In this spread-sheet
drugs were stratified based on their review designation into either priority or standard
review. Duplicate entries that had the same review designation and timelines were
removed from the database and are referenced in Appendix I. This resulted in 376 drugs;
164 of which were priority reviews and 212 were standard reviews.
In the second step, each drug in the database was searched using Drugs@FDA
search function which led to the NDA application information. Next, clicking on the
“Approval Date(s) and History, Letters, Labels, Reviews for NDA” tab presents two
sections the “Original Approvals or Tentative Approvals” section and the “Supplements”
section. Respectively, the first section was used to obtain information such as, review
classification and whether the NDA was granted an orphan designation or not.
Furthermore, a link to the original drug label is provided in this section, which was used
to obtain the indication and the size of the safety database for each drug through careful
examination of each label, except for the drugs in Appendix J for which the size of the
safety database was obtained through careful reading and examination of the medical
review section of the NDA review, the medical review of the aforementioned drugs was
obtained by choosing the review hyperlink in the supplement section of the FDA website.
As for the second section it was used to track the labeling changes by examining the
supplements that were classified as labeling supplements. These supplements were used
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 10
to track the safety labeling changes dates for every drug by going through the following
step for each drug.
All letters from the FDA in regard to supplement that were classified as labeling
were read to determine if the letter was approving a safety labeling change (SLC) in one
of the following label sections; Warnings, Precautions, Adverse Reactions,
Contraindications, or Boxed Warning. Moreover, using the date of each supplement we
looked for SLC on the FDA “Medical Product Safety Information” web page for NDAs
approved after 2008 (Drug Safety Labeling Changes (SLC), 2016), and by downloading
the Medwatch SLC archive for drugs approved between 1996 – 2007 (FDA, 2009). These
two databases referenced SLCs by month and year. For every drug in the database the
first three safety labeling changes that happened over the course of the NDA were
identified in order to determine the adequacy of safety information for all drugs in our
database. Doing so enabled judgment on whether different review speeds would sacrifice
and compromise the safety information in the premarket which could result in a faster
appearance of new adverse events that were not observed before and so would result in
shorter time from approval to safety labeling changes.
The last two pieces of information used in the database were “the post marketing
requirements and commitments”, orphan, and accelerated review status of each NDA.
The latter was obtained by examining drugs in the CDER’s novel new drugs report for
each year as of September 2011 and by the comprehensive CDER drug and biologic
accelerated approvals report for all drugs before 2011 (CDER, 2011; CDER, 2012;
CDER, 2012; CDER, 2013; FDA, 2015; CDER, 2016; CDER, 2017). As for the post
marketing requirements and commitments, each drug was searched through the FDA’s
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 11
post marketing requirements and commitments database (FDA, 2017) to see if the post
marketing requirements and commitments were required at approval or not. This
information could provide further input about the adequacy of safety information in the
premarket period, which is fundamental in judging whether other factors present a
confounding factor to the research question other than the review speed.
In the third step, the average time was calculated to the first, the second and the
third safety labeling change for every drug along with the average of number of patients
in the safety database for each comparison category. Then, statistical analysis of the data
was done through Excel’s built-in capabilities using t-test and z-test to establish
significance in differences between means. Both tests were utilized to compare the
average time to first, second, and third SLC for drugs reviewed under standard review,
priority review, orphan, and accelerated approval designated drugs. Comparisons
between standard, accelerated, and orphan drugs were done in aforementioned
comparison groups with common drugs between groups and without any similarities,
which was done by removing any drug that could be categorized simultaneously in two
groups. Furthermore, the type of each SLC change was compared between standard and
priority reviews using N-1 chi-squared test for proportions through the statistical
calculator provided by Medcalc website (Medcalc, 2017). Another point of comparison is
the size of the safety database, which was compared a cross all categories for significant
differences in mean using Excels’ built-in t-test and z-test for statistical significance.
Also, the therapeutic categories of drugs were compared in a table between priority and
standard review drugs to further identify any possible confounding factors.
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 12
Results
NDAs were analyzed for class one new molecular entity (NME-1) between Jan 1,
2000 and Dec 31, 2016. This process resulted in a total of 376 drugs; 212 standard
reviewed drugs and 164 priority reviewed drugs. The distribution of drugs between the
aforementioned categories among therapeutic groups was very diverse as listed in
Appendix A. Among the 376 approvals there were 47 accelerated approvals; 7 standard
reviews, 40 priority reviews, and 102 orphan drugs (of which there were 31 standard
reviews and 71 priority reviews), refer to Appendix G and Appendix H for the entire
database. Furthermore, 52.8% of the standard reviews had post marketing requirements
and commitments whereas the latter was required by 60.3% of the priority reviewed
drugs. Moreover, the number of applications without safety labeling changes was very
similar with 42 standard reviewed drugs and 41 priority reviewed drugs. Of these drugs;
10 were standard drugs and 9 were priority drugs that which were discontinued from the
market, as presented in Appendix F. Three main analyses were done: analysis of the time
to the first SLC, time to the second SLC, and time to third SLC (Table 1).
Table 1
Review categorization, time and size of the safety database
Review 1st labeling
change (Yrs.)1
2nd labeling
change (Yrs.)2
3rd labeling
change (Yrs.)3
Size of safety database
(average number of
patients)4
Standard 2.38 4.17 5.03 2392.00
Priority a 2.33 3.59 4.20 1299.47
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 13
Accelerated b 2.07 3.41 4.47 563.42
Orphan c 2.72 4.04 4.46 652.05
1. a) Priority (z = 0.20, P = 0.83, z critical two-tail = 1.95).
b) Accelerated (z = 1.02, P = 0.30, z Critical two-tail = 1.95).
c) Orphan drugs (z = -1.24, P = 0.21, z Critical two-tail = 1.95).
2. a) Priority (z = 1.72, P = 0.08, z Critical two-tail = 1.95).
b) Accelerated (z = 1.54, P = 0.12, z Critical two-tail = 1.95).
c) Orphan drugs (z = 0.16, P = 0.86, z Critical two-tail = 1.95).
3. a) Priority (z = 2.19, P = 0.02, z Critical two-tail = 1.95).
b) Accelerated (z = 1.056, P = 0.29, z Critical two-tail = 1.95).
c) Orphan drugs (z = 0.91, P = 0.36, z Critical two-tail = 1.95).
4. a) Priority (t Stat = 4.61, P = 5.53, t Critical two-tail = 1.96).
b) Accelerated (t Stat = 9.77, P = 2.18, t Critical two-tail = 1.96).
c) Orphan drugs (t Stat = 8.88, P = 6.08, t Critical two-tail = 1.96).
Note: 95% CI was used for all calculations.
There were no statistically significant differences in the time to first SLC between
standard reviewed drugs against priority, accelerated and orphan drugs. Moreover, there
were no significant differences in the time to the second SLC between standard against
priority, accelerated and orphan drugs. However, statistically significant difference in the
time to third SLC was identified between standard and priority reviews, standard
reviewed drugs were found to take about 10 months more than priority reviewed drugs to
require a third safety labeling change. Nonetheless, the difference was not statistically
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 14
significant between standard review, accelerated review and orphan drugs. Further
confirmatory analysis is presented in Appendix C. Although the differences in times to
first, second and third SLC were not statistically significant except for the difference
between standard and priority reviewed drugs in third SLC, the difference in the size of
the safety databases was statistically significant across the comparison groups; standard,
priority, accelerated, and orphan drugs (Table1), detailed analysis is presented in
Appendix D.
Further analysis was made to determine the type of SLC across priority and
standard review drugs to determine whether there was significant difference in the type of
SLCs between the two groups across the spectrum of the three SLCs timelines which is
listed in Appendix B. Five types of SLCs were tracked over the course of the three
timelines; Boxed Warning, Contraindications, Warnings, Precautions, and Adverse
Reactions. In the first and second SLC time point there were no significant differences in
the probability of any of the aforementioned SLC types between priority and standard
reviews (Table 8). There were no significant differences in the prevalence of the five
tracked types of SLCs across standard, priority, accelerated, and orphan designations.
Finally, the only statistically significant difference identified was in the
prevalence of Boxed Warnings between standard and priority reviewed drugs at the third
SLC time point, however, for the rest of the SLC types there were no significant
differences between priority and standard reviews (Table 8). The prevalence of Boxed
Warnings at the third SLC time point in standard reviewed drugs was about 3 times more
than that of priority reviewed drugs, however, there were no significant differences in the
prevalence of other SLC types.
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 15
Table 8
Probability of different SLCs type between standard and priority review
Time point Type of first labeling
change
(probability)1
Type of second labeling
change
(probability)2
Type of third labeling
change
(probability)3
Type of change Standard Priority Standard Priority Standard Priority
Boxed warnings%
a
8.88% 8.20% 3.57% 7.22% 12.61% 4.00%
Adverse
reactions% e
54.44% 55.74% 61.43% 61.86% 70.27% 65.33%
Warnings% d 53.25% 56.56% 48.57% 50.52% 57.66% 44.00%
Precautions% c 70.41% 77.05% 72.86% 69.07% 70.27% 70.67%
contraindications%
b
14.79% 11.48% 12.86% 7.22% 13.51% 10.67%
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 16
1) a) Boxed warnings (95% CI Chi squared 0.042, DF 1, P = 0.8385).
b) Contraindications (95% CI -5.3073 to 11.3623, Chi-squared 0.667, DF 1, P = 0.4143).
c) Precautions (95% CI -4.2090 to 16.9815, Chi-squared 1.587, DF 1, P = 0.2078).
d) Warnings (95% CI -8.7442 To 15.1913, Chi-squared 0.312 DF 1, P = 0.5764).
e) Adverse reactions (95% CI -10.7299 to 13.2150, Chi-squared 0.048, DF 1, P = 0.8262).
2) a) Boxed warning (95% CI -2.5993 to 11.1349, Chi-squared 1.581, DF 1, P = 0.2086).
b) Contraindication (95% CI -3.0678 to 13.5837, Chi-squared 1.923, DF 1, P = 0.1655).
c) Precautions (95% CI -8.3530 to 16.2510, Chi-squared 0.401, DF 1, P = 0.5268).
d) Warnings (95% CI -11.4941 to 15.3296, Chi-squared 0.087, DF 1, P = 0.7683).
e) Adverse reactions (95% CI -12.7694 to 13.3724, Chi-squared 0.004, DF 1, P = 0.9468).
3) a) Boxed warnings (95% CI -0.5136 to 16.8829, Chi-squared 3.975, DF 1, P = 0.0462).
b) Contraindications (95% CI -8.0709 to 12.6442, Chi-squared 0.331, DF 1, P = 0.5649).
c) Precautions (95% CI -13.9014 to 14.1007, Chi-squared 0.003, DF 1, P = 0.9534).
d) Warnings (95% CI -1.7514 to 28.4280, Chi-squared 3.329, DF 1, P = 0.0681).
e) Adverse reactions (95% CI -9.2563 to 19.4299, Chi-squared 0.502, DF 1, P = 0.4788).
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 17
Discussion
The focus of expedited review, which priority and accelerated review programs
fall under, is introducing potential lifesaving agents to patients in conditions where the
benefit to risk ratio is affected by the higher risk that patients might be willing to accept
(FDA, 2014). However, for patients and physicians to be able to make that decision, the
common risks of such therapies should be to the most part well established through
premarket studies. This study aimed to determine if the safety information of drugs
approved under priority, accelerated review and orphan designation is not as well
established as for drugs approved under standard review. Review of the first three safety
labeling changes for every drug across the two main categories (Priority and Standard)
and the two sub categories (Accelerated and Orphan Drugs) found that there are no
significant differences in the time to the first, second, and third SLCs, except for the time
to the third SLC between priority and standard reviewed drugs, for which the analysis is
presented in Appendix E. These finding show that the size of the safety database between
the comparison groups varies significantly (as shown in Appendix D), and the therapeutic
indications vary greatly among the approved drugs between the priority and the standard.
Nonetheless, there were no significant differences in the timing of the first, second, and
third SLCs among the comparison groups except, as mentioned earlier. Moreover, there
were no significant differences in the type of SLCs across the three time points, except
for the prevalence of Boxed Warnings in the third SLC time point. Furthermore, the
number of post marketing requirements and commitments for priority and standard
review drugs were fairly close. Having no statistically significant differences in the
timing and type of SLCs for most points of comparison shows that the review type and
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 18
designations did not correlate with the safety labeling changes of new drugs. It is
noteworthy to point out that, in the database 10 standard review drugs and 9 priority
review drugs were discontinued from marketing. However, even though, the
discontinuation status was not incorporated in this study analysis, Friedman et al. (1999)
studied a surge of drug removals and found that it was not affected by the speed of
review, diminishing this factor contribution to our end point. In conclusion, even though
the comparison groups were different in indications and safety population size, there
were no significant differences between aforementioned groups in the timing and type of
SLCs except for the time of the third SLC.
The fact that the safety of drugs is well established regardless of the review
pathway suggests that it is reasonable to decrease the review time for standard review
drugs to a 6-month review. Decreasing the time to action on standard review drugs can
increase the speed with which safe and effective medicine reaches the market.
Nonetheless, consideration should be made to the fact that most drugs regardless of
review priority undergo multiple review cycles before market approvals (Ross, Dzara, &
Downing, 2015). On the other hand, appropriate review of safety is not the only factor
that affect the time of review by FDA. Other factors that come to mind is the availability
of resources to complete standard reviews with 6-month reviews. Nonetheless, these kind
of resources which may include hiring extra reviewers which is amenable by increasing
the PDUFA user fee. The fee has dropped for drugs with clinical data from $2,374,200 in
2016 to $2,038,100 in 2017 (Mezher, 2016), presenting a possibility of increase to the
user fee act to hire more reviewers to make a goal of 6 months for the FDA to action on
standard reviews very feasible considering established safety won’t be affected by shorter
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 19
review period. However, care must be taken as to the fact that efficacy of drugs is also a
very important consideration as lack of efficacy inherently means a higher risk and less
acceptable safety profile. Finally, the fact that the faster review speeds don’t in most
cases sacrifice safety information of new drugs presents a logical argument to decrease
the review times of standard review drugs, keeping in mind adequate resources and
efficacy review.
This research involved NDAs for NME-1 that were approved between 1/1/2000
and 12/31/2016 that had either a priority or a standard designation which presents a
couple of limitations to the research database. First of all, by limiting our research to the
aforementioned criteria we have excluded biologics from our analysis, as biologics are
reviewed by the Center for Biologics Evaluation and Research (CBER) and not by the
Center for Drug Evaluation and Research (CDER). Furthermore, biologics do not fall
under the same designations of priority and standard on the FDA’s Drugs@FDA
database. Another possible limitation is the broad diversity of the indications for the
drugs presented in the database for which our results are general and not based on the
specific conditions that encompasses each indication, for example, the severity of disease
and the size of the disease population. This can be seen by examining the prescribing
behavior among physicians in different specialties. For example, Huskamp et al., (2013)
studied the prescribing attitudes for second generation antipsycotic drugs and found that
physicians started prescribing those drugs after 2 or more years on average from the time
of their first approval. This two-year timespan may limit the amount of safety data
generated during the first two years of marketing for second generation antipsychotics,
which could possibly decrease the effect of the esablished safety information in the
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 20
premarketing period on the time of SLCs in that instance. However, Huskamp et al.
(2013) suggested that the delay in utilization of the second generation antipsychotics
could be a practice intentionally used by physicians to ensure patient safety. Now,
although Huskamp et al.’s (2013) data was based on a single drug family for a limited
indication, our data can offer support to such prescribing behavior as the time to the first
SLC was more than two years for all of our comparison groups. Nonetheless, endorsing
physicians prescribing behavior that limits the use of new drugs until after two years can
be counter productive as it may result in increasing the time to first SLC and decreasing
exposure to the drug. This may explain why orphan drugs have the longest time to first
SLC when compared to the rest of the comparision groups as the number of patient
exposed to the drug each year is lower due to inherently smaller population. This research
may be limited by generalizabiliy of the result among various indications that may differ
by several aspects, such as patient population and prescribing behavior among medical
practitionars in that speciality.
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 21
Conclusion
The speed of review does not affect the rate of safety labeling changes safety of
approved drugs. No significant differences were identified in the time to first, second, and
third SLC, except for a statistically significant difference between standard and priority
reviewed drugs at the third SLC time point. To elaborate, the prevalence of Boxed
Warnings at the time of the third SLC time point was significantly higher for standard
reviewed drugs. Furthermore, the time to the third SLC was significantly longer for the
standard reviewed drugs at the time of the third SLC compared to priority reviewed
drugs. In conclusion, study findings present an argument for decreasing the review time
for standard drugs to 6 months, as no correlation between the shorter review period and
the timing of safety labeling related changes was identified between a 6-month priority
and 10-month standard review. However, this is tentative, provided that adequate funding
is provided for needed resources to feasibly accommodate a faster review goal.
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 22
References
Applications for FDA approval to market a new drug. (2015). 21 C.F.R. § 314.
Budnitz , D. S., Pollock , D. A., Weidenbach, K. N., Mendelsohn , A. B., Schroeder , T.
J., & Annest , J. L. (2006). National surveillance of emergency department visits
for outpatient adverse drug events. JAMA: Journal Of The American Medical
Association, 296(15), 1858-1866.
CDER. (2012, January). 2011 Novel drug summary. Retrieved 2 11, 2017, from
www.fda.gov:
http://www.fda.gov/downloads/drugs/developmentapprovalprocess/druginnovatio
n/ucm293663.pdf
CDER. (2012, January). 2011 Novel new drugs. Retrieved 2 11, 2017, from FDA:
https://www.fda.gov/downloads/drugs/developmentapprovalprocess/druginnovati
on/ucm293663.pdf
CDER. (2013, January). 2012 Novel New Drug Summary. Retrieved from FDA:
http://www.fda.gov/downloads/drugs/developmentapprovalprocess/druginnovatio
n/ucm337830.pdf
CDER. (2016, January). 2015 Novel drug summary. Retrieved 2 11, 2017, from
www.fda.gov:
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 23
http://www.fda.gov/downloads/drugs/developmentapprovalprocess/druginnovatio
n/ucm481709.pdf
CDER. (2017, January). 2016 Novel New Drugs summary. Retrieved 2 11, 2017, from
www.FDA.gov:
https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DrugInnov
ation/UCM536693.pdf
Drug Safety Labeling Changes (SLC). (2016, november 5). Retrieved 11 5, 2016, from
FDA: http://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/
FDA. (2009, May 28). Medwatch archive 1996-2007. Retrieved 1 1, 2017, from Medical
Product Safety Information:
https://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/UCM1898
11.zip
FDA. (2012, November). Consumer health information. Retrieved April 13, 2017, from
Food and Drug administeration:
https://www.fda.gov/downloads/forconsumers/consumerupdates/ucm107976.pdf
FDA. (2014, May). Guidance for Industry Expedited Programs for Serious Conditions –
Drugs and Biologics. Retrieved November 5, 2016, from FDA:
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/
guidances/ucm358301.pdf
FDA. (2015, January). 2014 Novel drug summary. Retrieved from www.Fda.gov:
http://www.fda.gov/downloads/drugs/developmentapprovalprocess/druginnovatio
n/ucm430299.pdf
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 24
FDA. (2016, november 5). Drugs@FDA. Retrieved 11 5, 2016, from FDA:
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
FDA. (2017, March 3). Developing products for rare diseases & conditions. Retrieved
April 13, 2017, from U.S Food and Drug Administeration:
https://www.fda.gov/forindustry/developingproductsforrarediseasesconditions/uc
m2005525.htm
FDA. (2017, February 1). Postmarket Requirements and Commitments. Retrieved from
FDA: http://www.accessdata.fda.gov/scripts/cder/pmc/index.cfm
Food and Drug Administration. (1995, March). Guideline for Industry The Extent of
Population Exposure to Assess Clinical Safety: For Drugs Intended for Longterm
Treatment of Non-Life-Threatening Conditions. Retrieved 11 5, 2016, from
http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4068B1_09_ICH-E1A-
Guidelines.pdf
Friedman, M. A., Woodcock, J., Lumpkin, M. M., Shuren, J. E., Hass, A. E., &
Thompson, L. J. (1999, 5 12). The safety of newly approved medicines do recent
market removals mean there is a problem? JAMA, 1728-1734.
Huskamp, H., O’Malley, A. J., Horvitz-Lennon, M., Taub, A. L., Berndt, E., & Donohue,
J. (2013, April 1). How quickly do physicians adopt new drugs? The case of
second-generation antipsychotics. Psychiatr Serv., 64(4), 324–330.
doi:10.1176/appi.ps.201200186
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 25
Ioannidis, J. (2009). Adverse events in randomized trials: neglected, restricted, distorted,
and silenced. Archives Of Internal Medicine, 169(19), 1737-1739.
doi:10.1001/archinternmed.2009.313
Lasser, K. E., Allen , P. D., Woolhandler, S. J., Himmelstein , D. U., Wolfe, S. M., &
Bohr, D. H. (2002). Timing of new black box warnings and withdrawals for
prescription medications. JAMA: Journal of the American Medical Association,
287(17), 2215-2296.
Medcalc. (2017, February 18). Comparison of proportions calculator. Retrieved from
Medcalc: https://trac.med.umich.edu/imaging/
Mezher, M. (2016, August 1). FDA Unveils User Fee Rates for FY 2017. Retrieved from
The Regulatory Affairs Professionals Society: http://www.raps.org/Regulatory-
Focus/News/2016/08/01/25478/FDA-Unveils-User-Fee-Rates-for-FY-2017/
Niraula, S., Seruga, B., Ocana, A., Shao, T., Goldstein, R., Tannock, I. F., & Amir, E.
(2012). The price we pay for progress: A meta-Analysis of harms of newly
approved anticancer drugs. Journal of Clinical Oncology, 30(24), 3012-3019.
doi:10.1200/JCO.2011.40.3824
Outterson, K., Powers, J. H., Seoane-Vazquez, E., Rodriguez-Monguio, R., &
Kesselheim, A. S. (2013). Approval and withdrawal of new antibiotics and other
antiinfectives in the U.S., 1980-2009. Journal of Law, Medicine & Ethics, 41(3),
688-696. doi:http://dx.doi.org.ezproxy.emich.edu/10.1111/jlme.12079
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 26
Reed, S. D., Anstrom, K. J., Seils, D. M., Califf, R. M., & Schulman, K. A. (2008). Use
of larger versus smaller drug-Safety databases before regulatory approval:The
trade-Offs. Health Affairs, 27(5), w360-w370. doi:10.1377/hlthaff.27.5.w360
Ross, J. S., Dzara, K., & Downing, N. S. (2015). Efficacy and safety concerns are
important reasons why the FDA requires multiple reviews before approval of new
drugs. Health Affairs, 34(4), 681-688.
doi:http://dx.doi.org/10.1377/hlthaff.2014.1160
Ross, J. S., Dzara, K., & Downing, N. S. (2015, April 21). Efficacy and safety concerns
are important reasons why the FDA requires multiple reviews before approval of
new drugs. Health Affairs, 681-688.
doi:http://dx.doi.org/10.1377/hlthaff.2014.1160
Seruga, B., Sterling, L., Wang, L., & Tannock, I. (2011). Reporting of serious adverse
drug reactions of targeted anticancer agents in pivotal phase III clinical trials. J
CLIN ONCOL, 29(2), 174-185.
doi:http://dx.doi.org.ezproxy.emich.edu/10.1200/JCO.2010.31.9624
Slone Epidemiology Center at Boston University. (2006). Patterns of medication use in
the United States. Retrieved 11 5, 2016, from
http://www.bu.edu/slone/files/2012/11/SloneSurveyReport2006.pdf
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 27
Appendix *
Definition of terms
ADE: adverse drug reaction.
AE: adverse event.
FDA: Food and Drug administration.
FDAMA: FDA Modernization.
FDASIA: FDA Safety and Innovation Act.
NCE: New chemical entity.
NME: New molecular entity.
PDUFA: Prescription Drug User Fee Act.
SLC: Safety labeling change.
DF: Degrees of freedom
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 28
Appendix A
Therapeutic Areas Across Standard and Priority Review for NME-1 between 1/1/2000 –
12/31/2016
Table 6
Therapeutic areas across standard and priority reviewed NME-1 drugs
between 1/1/2000 – 12/31/2016
Therapeutic area Standard Priority
GU 15 2
Oncology 19 54
Endocrine 20 3
Ophthalmic 5 6
CNS 37 5
Antibiotic 11 14
Antifungal 7 3
Antiviral 6 18
Diagnostic 9 7
CVS 28 13
GI 19 9
Bone and Joint 7 0
Macular degeneration 0 1
Hypertyrosinemia 0 1
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 29
Adjuvant for injection 0 4
Gaucher disease 2 2
Muscular dystrophy 0 1
Alcohol dependence 0 1
Dermatology 1 0
Respiratory 11 4
Fibromyalgia 1 0
Enzyme replacement 0 1
Contraception 4 0
Gynecology 2 0
Hyperphenylanalinemia 0 1
Osmotic balance 3 0
Myelodysplastic disorders 2 2
Iron overload 1 1
Multiple Sclerosis 2 2
Head lice 2 0
Restless leg syndrome 1 0
Contamination & poisoning 0 3
Spinal Muscular atrophy 0 1
Keratosis 1 0
Weight management 1 0
Narcolepsy 0 1
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 30
Orotic acidurea 0 1
Smoking cessation 0 1
Pharmacologic stress agent 1 0
Total in subgroup 218 162
Overall Total 380 *
* some drugs fall under more than one indication
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 31
Appendix B
Prevalence of Safety Labeling Changes Types in Priority and Standard Reviews Across
the Three Tracked Time Points.
Table 4.2
Priority Review SLCs
Time point Type of first labeling
change
Type of second
labeling change
Type of third
labeling change
Type of change Number of
changes
Prevalenc
e
Number
of
changes
Prevalenc
e
Number
of
changes
Prevalenc
e
Boxed Warnings 10 8.20% 7 7.22% 3 4.00%
Adverse
reactions
68 55.74% 60 61.86% 49 65.33%
Warnings 69 56.56% 49 50.52% 33 44.00%
Precautions 94 77.05% 67 69.07% 53 70.67%
Contraindication
s
14 11.48% 7 7.22% 8 10.67%
Drugs with no
SLCs
41 67 89
Number of drugs
with SLCs
122 97 75
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 32
Total Number of
SLCs
255 190 146
Table 4.1
Standard review SLCs type
Type of change Type of first
labeling change
Type of second
labeling change
Type of third
labeling change
Type of change Number
of
changes
Prevalenc
e
Number
of
changes
Prevalenc
e
Number
of
changes
Prevalenc
e
Boxed Warnings 15 8.88% 5 3.57% 14 12.61%
Adverse reactions 92 54.44% 86 61.43% 78 70.27%
Warnings 90 53.25% 68 48.57% 64 57.66%
Precautions 119 70.41% 102 72.86% 78 70.27%
Contraindications 25 14.79% 18 12.86% 15 13.51%
No change 42 72 101
Number of drugs
with SLCs
169 140 111
Total Number of
changes
341 279 249
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 33
Appendix C
Time to Safety Labeling Changes Across Standard, Priority, Accelerated, Orphan drugs
(95% CI used in all calculations)
Table 1.1.1
t-Test: Two-Sample assuming unequal variances for comparison of the time to safety
labeling changes across standard and priority reviews.
Standard vs Priority Standard Priority
Mean 869.5029586 852.8278689
Variance 293576.3705 601404.8875
Observations 169 122
Hypothesized Mean Difference 0
Degrees of freedom 203
t Stat 0.204227002
P(T<=t) one-tail 0.419190357
t Critical one-tail 1.65239446
P(T<=t) two-tail 0.838380713
t Critical two-tail 1.971718848
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 34
Table 1.1.2
z-Test: Two Sample for Means for comparison of the time to safety labeling changes
across standard and priority reviews.
Standard vs Priority Standard Priority
Mean (days) 869.5029586 852.8278689
Known Variance 293576.3705 601404.8875
Observations 169 122
Hypothesized Mean Difference 0
z 0.204227002
P(Z<=z) one-tail 0.419088056
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.838176112
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 35
Table 1.2.1
t-Test: Two-Sample assuming unequal variances for comparison of time to safety
labeling changes across standard and accelerated reviews.
Standard vs accelerated Standard accelerated
Mean (days) 869.5029586 756.7948718
Variance 293576.3705 376349.0621
Observations 169 39
Hypothesized Mean Difference 0
Degrees of freedom 53
t Stat 1.056205048
P(T<=t) one-tail 0.147832675
t Critical one-tail 1.674116237
P(T<=t) two-tail 0.29566535
t Critical two-tail 2.005745995
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 36
Table 1.2.2
z-Test: Two Sample for Means for comparison of time to safety labeling changes
across standard and accelerated reviews.
Standard vs accelerated Standard accelerated
Mean (days) 869.5029586 756.7948718
Known Variance 293576.3705 376349.0621
Observations 169 39
Hypothesized Mean Difference 0
z 1.056205048
P(Z<=z) one-tail 0.145437272
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.290874545
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 37
Table 1.2.3
t-Test: Two-Sample Assuming Unequal Variances for comparison of time to safety
labeling changes across standard and accelerated reviews.
Standard vs accelerated (without similarities) Standard accelerated
Mean (days) 864.7310345 738.3030303
Variance 292955.0174 437488.8428
Observations 145 33
Hypothesized Mean Difference 0
Degrees of freedom 42
t Stat 1.022858295
P(T<=t) one-tail 0.156115245
t Critical one-tail 1.681952357
P(T<=t) two-tail 0.31223049
t Critical two-tail 2.018081703
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 38
Table 1.2.3
z-Test: Two sample for means for comparison of time to safety labeling changes
across standard and accelerated reviews.
Standard vs accelerated (without
similarities)
Standard accelerated
Mean (days) 864.7310345 738.3030303
Known Variance 292955.0174 437488.8428
Observations 145 33
Hypothesized Mean Difference 0
z 1.022858295
P(Z<=z) one-tail 0.153187425
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.30637485
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 39
Table: 1.3.1
t-Test: Two-Sample assuming unequal variances for comparison of time to safety
labeling changes across standard and orphan reviews.
Standard vs Orphan Standard Orphan
Mean (days) 869.5029586 994.1927711
Variance 293576.3705 764166.0843
Observations 169 83
Hypothesized Mean Difference 0
Degrees of freedom 114
t Stat -1.191910791
P(T<=t) one-tail 0.11788578
t Critical one-tail 1.658329969
P(T<=t) two-tail 0.23577156
t Critical two-tail 1.980992298
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 40
Table 1.3.2
z-Test: Two sample for means for comparison of time to safety labeling changes
across standard and orphan reviews.
Standard vs Orphan in the first
SLC
Standard Orphan
Mean (days) 869.5029586 994.1927711
Known Variance 293576.3705 764166.0843
Observations 169 83
Hypothesized Mean Difference 0
z -1.191910791
P(Z<=z) one-tail 0.116648113
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.233296227
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 41
Table 1.3.3
t-Test: Two-Sample assuming unequal variances for comparison of time to safety
labeling changes across standard and orphan reviews.
Standard vs Orphan (similarities removed) Standard Orphan
Mean (days) 864.7310345 1033.186441
Variance 292955.0174 952401.9819
Observations 145 59
Hypothesized Mean Difference 0
Degrees of freedom 73
t Stat -1.24995311
P(T<=t) one-tail 0.107654521
t Critical one-tail 1.665996224
P(T<=t) two-tail 0.215309041
t Critical two-tail 1.992997126
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 42
Table 1.3.4
z-Test: Two sample for means for comparison of time to safety labeling changes
across standard and orphan reviews.
Standard vs Orphan (similarities removed) Standard Orphan
Mean (days) 864.7310345 1033.186441
Known Variance 292955.0174 952401.9819
Observations 145 59
Hypothesized Mean Difference 0
z -1.24995311
P(Z<=z) one-tail 0.105658338
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.211316677
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 43
Table 2.1.1
t-Test: Two-Sample assuming unequal variances for comparison of time to safety
labeling changes across standard and priority reviews.
Second SLC for standard vs priority standard priority
Mean (days) 1522.057143 1312.247423
Variance 757627.7233 913533.6881
Observations 140 97
Hypothesized Mean Difference 0
Degrees of freedom 194
t Stat 1.722909062
P(T<=t) one-tail 0.043249219
t Critical one-tail 1.652745977
P(T<=t) two-tail 0.086498438
t Critical two-tail 1.972267533
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 44
Table 2.1.2
z-Test: Two sample for means for comparison of time to safety labeling changes across
standard and priority reviews.
Second SLC for standard vs priority standard priority
Mean (days) 1522.057143 1312.247423
Known Variance 757627.7233 913533.6881
Observations 140 97
Hypothesized Mean Difference 0
z 1.722909062
P(Z<=z) one-tail 0.042452486
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.084904971
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 45
Table 2.2.1
t-Test: Two-Sample assuming unequal variances for comparison of time to safety
labeling changes across standard and accelerated reviews.
Second SLC for standard vs accelerated Standard Accelerated
Mean (days) 1522.057143 1248.09375
Variance 757627.7233 636867.5071
Observations 140 32
Hypothesized Mean Difference 0
Degrees of freedom 49
t Stat 1.721925713
P(T<=t) one-tail 0.045695434
t Critical one-tail 1.676550893
P(T<=t) two-tail 0.091390869
t Critical two-tail 2.009575237
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 46
Table 2.2.2
z-Test: Two sample for means for comparison of time to safety labeling changes across
standard and accelerated reviews.
Second for standard vs accelerated Standard Accelerated
Mean (days) 1522.057143 1248.09375
Known Variance 757627.7233 636867.5071
Observations 140 32
Hypothesized Mean Difference 0
z 1.721925712
P(Z<=z) one-tail 0.042541488
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.085082976
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 47
Table 2.2.3
t-Test: Two-Sample assuming unequal variances for comparison of the time to safety
labeling changes across standard and orphan reviews.
Second SLC for standard vs accelerated (without
similarities)
Standard Accelerated
Mean (days) 1539.918033 1262.821429
Variance 776854.8858 727108.078
Observations 122 28
Hypothesized Mean Difference 0
Degrees of freedom 41
t Stat 1.540952815
P(T<=t) one-tail 0.065505891
t Critical one-tail 1.682878002
P(T<=t) two-tail 0.131011783
t Critical two-tail 2.01954097
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 48
Table 2.2.4
z-Test: two sample for means for comparison of time to safety labeling changes across
standard and accelerated reviews.
Second SLC for standard vs accelerated
(without similarities)
Standard Accelerated
Mean (days) 1539.918033 1262.821429
Known Variance 776854.8858 727108.078
Observations 122 28
Hypothesized Mean Difference 0
z 1.540952815
P(Z<=z) one-tail 0.061664135
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.12332827
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 49
Table 2.3.1
t-Test: Two-Sample assuming unequal variances for comparison of the time to safety
labeling changes across standard and orphan reviews.
Second SLC for standard vs orphan Standard Orphan
Mean (days) 1522.057143 1476.534483
Variance 757627.7233 898993.2356
Observations 140 58
Hypothesized Mean Difference 0
Degrees of freedom 99
t Stat 0.314800153
P(T<=t) one-tail 0.376787957
t Critical one-tail 1.660391156
P(T<=t) two-tail 0.753575915
t Critical two-tail 1.984216952
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 50
Table 2.3.2
z-Test: Two sample for means for comparison of the time to second safety labeling
changes across standard and orphan reviews.
Second SLC for standard vs orphan Standard Orphan
Mean (days) 1522.057143 1476.534483
Known Variance 757627.7233 898993.2356
Observations 140 58
Hypothesized Mean Difference 0
z 0.314800153
P(Z<=z) one-tail 0.376456698
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.752913395
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 51
Table 2.3.3
t-Test: Two-Sample assuming unequal variances for comparison of the time to second
safety labeling changes across standard and orphan reviews.
Second for standard vs orphan (without
similarities)
Standard Orphan
Mean (days) 1539.918033 1510.525
Variance 776854.8858 1027835.794
Observations 122 40
Hypothesized Mean Difference 0
Degrees of freedom 60
t Stat 0.164149114
P(T<=t) one-tail 0.435082741
t Critical one-tail 1.670648865
P(T<=t) two-tail 0.870165483
t Critical two-tail 2.000297822
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 52
Table 2.3.4
z-Test: Two sample for means for comparison of the time to second safety labeling
changes across standard and orphan reviews.
Second SLC for standard vs orphan
(without similarities)
Standard Orphan
Mean (days) 1539.918033 1510.525
Known Variance 776854.8858 1027835.794
Observations 122 40
Hypothesized Mean Difference 0
z 0.164149114
P(Z<=z) one-tail 0.434806879
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.869613759
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 53
Table 3.1.1
t-Test: Two-Sample assuming unequal variances for comparison of the time to the third
safety labeling changes across standard and priority reviews.
Third SLC for standard vs priority Standard Priority
Mean (days) 1837.09009 1533.533333
Variance 1091882.519 690950.009
Observations 111 75
Hypothesized Mean Difference 0
Degrees of freedom 179
t Stat 2.199372175
P(T<=t) one-tail 0.014566407
t Critical one-tail 1.6534108
P(T<=t) two-tail 0.029132814
t Critical two-tail 1.973305434
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 54
Table: 3.1.2
z-Test: Two sample for means for comparison of the time to the third safety labeling
changes across standard and priority reviews.
Third SLC for standard vs priority Standard Priority
Mean (days) 1837.09009 1533.533333
Known Variance 1091882.519 690950.009
Observations 111 75
Hypothesized Mean Difference 0
z 2.199372175
P(Z<=z) one-tail 0.013925735
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.027851469
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 55
Table 3.2.1
t-Test: Two-Sample assuming unequal variances for comparison of the time to the third
safety labeling changes across standard and accelerated reviews.
Third SLC for standard vs accelerated Standard Accelerated
Mean (days) 1837.09009 1633.115385
Variance 1091882.519 622116.1862
Observations 111 26
Hypothesized Mean Difference 0
Degrees of freedom 48
t Stat 1.110062108
P(T<=t) one-tail 0.136251248
t Critical one-tail 1.677224196
P(T<=t) two-tail 0.272502497
t Critical two-tail 2.010634758
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 56
Table 3.2.2
z-Test: Two sample for means for comparison of the time to the third safety
labeling changes across standard and accelerated reviews.
Third SLC for standard vs
accelerated
Standard Accelerated
Mean (days) 1837.09009 1633.115385
Known Variance 1091882.519 622116.1862
Observations 111 26
Hypothesized Mean Difference 0
z 1.110062108
P(Z<=z) one-tail 0.133486132
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.266972264
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 57
Table 3.2.3
t-Test: Two-Sample assuming unequal variances for comparison of the time to the third
safety labeling changes across standard and accelerated reviews without similarities.
Third SLC for standard vs accelerated (without
similarities)
standard accelerated
Mean (days) 1883.757576 1667.043478
Variance 1178982.124 693792.3162
Observations 99 23
Hypothesized Mean Difference 0
Degrees of freedom 41
t Stat 1.056528769
P(T<=t) one-tail 0.148456268
t Critical one-tail 1.682878002
P(T<=t) two-tail 0.296912536
t Critical two-tail 2.01954097
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 58
Table 3.2.4: z-Test
Two sample for means for comparison of the time to the third safety labeling changes
across standard and accelerated reviews without similarities.
Third SLC for standard vs accelerated (without
similarities)
Standard accelerated
Mean (days) 1883.757576 1667.04347
8
Known Variance 1178982.124 693792.316
2
Observations 99 23
Hypothesized Mean Difference 0
z 1.056528769
P(Z<=z) one-tail 0.145363352
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.290726704
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 59
Table 3.3.1
t-Test: Two-Sample assuming unequal variances for comparison of the time to the
third safety labeling changes across standard and orphan reviews.
Third SLC for standard vs orphan Standard Orphan
Mean (days) 1837.09009 1630.658537
Variance 1091882.519 619246.7805
Observations 111 41
Hypothesized Mean Difference 0
Degrees of freedom 94
t Stat 1.307147891
P(T<=t) one-tail 0.097175503
t Critical one-tail 1.661225855
P(T<=t) two-tail 0.194351007
t Critical two-tail 1.985523442
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 60
Table 3.3.2
z-Test: Two sample for means for comparison of the time to the third safety
labeling changes across standard and orphan reviews
Third SLC for standard vs orphan Standard Orphan
Mean (days) 1837.09009 1630.658537
Known Variance 1091882.519 619246.7805
Observations 111 41
Hypothesized Mean Difference 0
z 1.307147891
P(Z<=z) one-tail 0.095581244
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.191162489
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 61
Table 3.3.3
t-Test: Two-Sample assuming unequal variances for comparison of the time to the third
safety labeling changes across standard and orphan reviews without similarities.
Third SLC for standard vs orphan (without
similarities)
Standard Orphan
Mean (days) 1883.757576 1704.551724
Variance 1178982.124 773442.7562
Observations 99 29
Hypothesized Mean Difference 0
Degrees of freedom 55
t Stat 0.912377848
P(T<=t) one-tail 0.182775924
t Critical one-tail 1.673033965
P(T<=t) two-tail 0.365551847
t Critical two-tail 2.004044783
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 62
Table 3.3.4
z-Test: Two sample for means for comparison of the time to the third safety labeling
changes across standard and orphan reviews without similarities.
Third SLC for standard vs orphan (without
similarities)
Standard Orphan
Mean (days) 1883.757576 1704.551724
Known Variance 1178982.124 773442.7562
Observations 99 29
Hypothesized Mean Difference 0
z 0.912377848
P(Z<=z) one-tail 0.180784923
z Critical one-tail 1.644853627
P(Z<=z) two-tail 0.361569847
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 63
Appendix D
Comparison of Size of the Safety Database Across Standard, Priority, Accelerated, and
Orphan drugs
Table 5.1
t-Test: Two-Sample assuming unequal variances for comparison of size of the
safety database across standard and priority drugs
Standard vs Priority Standard Priority
Mean (number of patients) 2392.004739 1299.471698
Variance 6267061.224 4201541.263
Observations 211 159
Hypothesized Mean Difference 0
Degrees of freedom 365
t Stat 4.611589063
P(T<=t) one-tail 2.76826E-06
t Critical one-tail 1.649039017
P(T<=t) two-tail 5.53652E-06
t Critical two-tail 1.966484596
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 64
Table 5.2
z-Test: two sample for means for comparison of size of the safety database
across standard and priority drugs
Standard vs Priority Standard Priority
Mean (number of patients) 2392.004739 1299.471698
Known Variance 6267061.224 4201541.263
Observations 211 159
Hypothesized Mean Difference 0
z 4.611589063
P(Z<=z) one-tail 1.99801E-06
z Critical one-tail 1.644853627
P(Z<=z) two-tail 3.99602E-06
z Critical two-tail 1.959963985
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 65
Table 5.3
t-Test: Two-Sample Assuming Unequal Variances for comparison of size of
the safety database across standard and accelerated review drugs
Standard vs Accelerated Standard Accelerated
Mean (number of patients) 2392.004739 563.4255319
Variance 6267061.224 247201.2063
Observations 211 47
Hypothesized Mean Difference 0
Degrees of freedom 255
t Stat 9.77957351
P(T<=t) one-tail 1.09385E-19
t Critical one-tail 1.650851092
P(T<=t) two-tail 2.1877E-19
t Critical two-tail 1.96931057
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 66
Table 5.4
t-Test: Two-Sample assuming unequal variances for comparison of size of the
safety database across standard and orphan reviewed drugs
Standard vs Orphan Standard Orphan
Mean (days) 2392.004739 652.0588235
Variance 6267061.224 878261.8975
Observations 211 102
Hypothesized Mean Difference 0
Degrees of freedom 297
t Stat 8.8893016
P(T<=t) one-tail 3.04205E-17
t Critical one-tail 1.650000301
P(T<=t) two-tail 6.08411E-17
t Critical two-tail 1.967983525
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 67
Appendix E
Prevalence of SLCS Types
Table 7.1.1
Boxed warnings in the first
SLC
Standard Priority
Prevalence 8.88% 8.20%
Sample size 169 122
Difference 0.68%
95% CI -6.7424 to 7.4732
Chi-squared 0.042
Degrees of freedom 1
Significance level P = 0.8385
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 68
Table 7.1.2
Boxed warnings in the
second SLC
Standard Priority
Prevalence 3.57% 7.22%
Sample size 140 97
Difference 3.65%
95% CI -
2.5993 to 11.1349
Chi-squared 1.581
Degrees of freedom 1
Significance level P = 0.2086
Table 7.1.3
Boxed warnings in the
third SLC
Standard Priority
Prevalence 12.61% 4.00%
Sample size 111 75
Difference 8.61%
95% CI -0.5136 to 16.8829
Chi-squared 3.975
Degrees of freedom 1
Significance level P = 0.0462
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 69
Table 7.2.1
contraindications in the
first SLC
Standard Priority
Prevalence 14.79% 11.48%
Sample size 169 122
Difference 3.31%
95% CI -5.3073 to 11.3623
Chi-squared 0.667
Degrees of freedom 1
Significance level P = 0.4143
Table 7.2.2
contraindications in the
second SLC
Standard Priority
Prevalence 12.86% 7.22%
Sample size 140 97
Difference 5.64%
95% CI -3.0678 to 13.5837
Chi-squared 1.923
Degrees of freedom 1
Significance level P = 0.1655
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 70
Table 7.2.3
Contraindications in the
third SLC
Standard Priority
Prevalence 13.51% 10.67%
Sample size 111 75
Difference 2.84%
95% CI -8.0709 to 12.6442
Chi-squared 0.331
Degrees of freedom 1
Significance level P = 0.5649
Table 7.3.1
warnings in the first SLC Standard Priority
Prevalence 53.25% 56.56%
Sample size 169 122
Difference 3.31%
95% CI -8.7442 to 15.1913
Chi-squared 0.312
Degrees of freedom 1
Significance level P = 0.5764
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 71
Table 7.3.2
warnings in the second SLC Standard Priority
Prevalence 48.57% 50.52%
Sample size 140 97
Difference 1.95%
95% CI -11.4941 to 15.3296
Chi-squared 0.087
Degrees of freedom 1
Significance level P = 0.7683
Table 7.3.3
warnings in the third SLC Standard Priority
Prevalence 57.66% 44.00%
Sample size 111 75
Difference 13.66%
95% CI -1.7514 to 28.4280
Chi-squared 3.329
DEGREES OF FREEDOM 1
Significance level P = 0.0681
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 72
Table 7.4.1
precautions in the first SLC Standard Priority
Prevalence 70.41% 77.05%
Sample size 169 122
Difference 6.64%
95% CI -4.2090 to 16.9815
Chi-squared 1.587
DEGREES OF FREEDOM 1
Significance level P = 0.2078
Table 7.4.2
precautions in the second SLC Standard Priority
Prevalence 72.86% 69.07%
Sample size 140 97
Difference 3.79%
95% CI -8.3530 to 16.2510
Chi-squared 0.401
DEGREES OF FREEDOM 1
Significance level P = 0.5268
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 73
Table 7.4.3
precautions in the third SLC Standard Priority
Prevalence 70.27% 70.67%
Sample size 111 75
Difference 0.40%
95% CI -13.9014 to 14.1007
Chi-squared 0.003
DEGREES OF FREEDOM 1
Significance level P = 0.9534
Table 7.5.1
1st for Adverse reactions Standard Priority
Prevalence 54.44% 55.74%
Sample size 169 122
Difference 1.30%
95% CI -10.7299 to 13.2150
Chi-squared 0.048
DEGREES OF FREEDOM 1
Significance level P = 0.8262
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 74
Table 7.5.2
2nd for Adverse reactions Standard Priority
Prevalence 61.43% 61.86%
Sample size 140 97
Difference 0.43%
95% CI -12.7694 to 13.3724
Chi-squared 0.004
DEGREES OF FREEDOM 1
Significance level P = 0.9468
Table 7.5.3
adverse reaction in the third
SLC
Standard Priority
Prevalence 70.27% 65.33%
Sample size 111 75
Difference 4.94%
95% CI -
9.2563 to 19.4299
Chi-squared 0.502
DEGREES OF FREEDOM 1
Significance level P = 0.4788
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 75
Appendix F
Summary of Drugs Characteristics in the Database
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 76
Table 10 Standard Priority
Total Number of drugs 376 212 164
Number of accelerated approval 7 40
Number of orphan drugs 31 72
Number of drugs without SLCs 42 41
Number of drugs with no Safety database size information 1 5
Priority requiring post marketing commitments and
requirements
112 99
Number of discontinued drugs 10 9
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 77
Appendix I
NDAs Removed from The Database
Date approved Name NDA# Review type Reason
04/20/2000 LANTUS
SOLOSTAR
NDA
#021081
Standard Duplicate
06/07/2000 NOVOLOG
FLEXPEN
NDA
#020986
Standard Duplicate
06/07/2000 NOVOLOG
FLEXTOUCH
NDA
#020986
Standard Duplicate
06/07/2000 NOVOLOG
INNOLET
NDA
#020986
Standard Duplicate
06/07/2000 NOVOLOG
PENFILL
NDA
#020986
Standard Duplicate
07/25/2000 ABREVA NDA
#020941
Standard OTC
06/20/2014 SIVEXTRO NDA
#205436
Priority Duplicate
03/06/2015 CRESEMBA NDA #207501 Priority Duplicate
02/18/2016 BRIVIACT NDA
#205837
Standard Duplicate
02/18/2016 BRIVIACT NDA
#205838
Standard Duplicate
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 78
09/12/2003 CUBICIN RF NDA
#021572
Priority Duplicate
04/16/2004 APIDRA
SOLOSTAR
NDA
#021629
Standard Duplicate
03/27/2012 OMONTYS
PRESERVATIVE
FREE
NDA
#202799
Standard Duplicate
12/29/2005
VAPRISOL IN
5% DEXTROSE
IN PLASTIC
CONTAINER
NDA
#021697
Standard Duplicate
11/22/2004
EPIVIR NDA
#020564
Original
approval 1995
06/16/2005 LEVEMIR
FLEXPEN
NDA
#021536
Standard Duplicate
06/16/2005 LEVEMIR
FLEXTOUCH
NDA
#021536
Standard Duplicate
06/16/2005 LEVEMIR
INNOLET
NDA
#021536
Standard Duplicate
06/16/2005 LEVEMIR
PENFILL
NDA
#021536
Standard Duplicate
08/03/2000 RESCULA NDA
#021214
Priority
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 80
Appendix G
Database of NME-1 Approved from 01/01/2000 – 12/31/2016
Date
approved
Drug name Review
Type
Size of safety
database
Therapeutic category post marketing
requirements and
commitments
Notes Day
Accessed
01/11/2000 EVOXAC
NDA #020989
Standard 1777 GI NO
12/25/2016
01/14/2000 TRILEPTAL
NDA #021014
Standard 2139 CNS NO
12/25/2016
02/02/2000 PROTONIX
NDA #020987
Standard 11,100 GI yes
12/25/2016
02/09/2000 LOTRONEX
NDA #021107
Priority 11,874 GI NO
12/25/2016
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 81
03/27/2000 ZONEGRAN
NDA #020789
Standard 1,598 CNS NO
12/25/2016
04/12/2000 VISUDYNE
NDA #021119
Priority 402 ophthalmic NO
12/25/2016
04/13/2000 MOBIC NDA
#020938
Standard 13627 osteoarthritis NO
12/25/2016
04/18/2000 ZYVOX NDA
#021130
Priority 2046 Antibiotic NO
12/25/2016
04/20/2000 LANTUS
NDA #021081
Standard 4239 endocrine NO
12/25/2016
04/21/2000 EXELON
NDA #020823
Standard 5297 CNS NO
12/25/2016
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 82
05/17/2000 MYLOTARG
NDA #021174
Priority 348 Cancer NO D/C -
accelerated
12/25/2016
05/26/2000 WELCHOL
NDA #021176
Standard 1400 CVS yes
12/25/2016
06/07/2000 NOVOLOG
NDA #020986
Standard 1357 endocrine NO
12/25/2016
06/15/2000 TRELSTAR
NDA #020715
Standard 140 Cancer NO
12/25/2016
06/30/2000 ARGATROBAN
NDA #020883
Standard 1127 CVS NO
12/25/2016
07/14/2000 INNOHEP
NDA #020484
Standard 4000 CVS NO D/C 12/25/2016
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 83
07/18/2000 COLAZAL
NDA #020610
Standard 1000 GI yes
12/25/2016
08/11/2000 CETROTIDE
NDA #021197
Standard 949 GU NO
12/26/2016
09/25/2000 TRISENOX
NDA #021248
Priority 52 Cancer NO Orphan 12/26/2016
09/28/2000 MIFEPREX
NDA #020687
Priority 2659 GU NO Accelerated
approval
12/26/2016
12/15/2000 ANGIOMAX
NDA #020873
Standard 2161 CVS NO
12/26/2016
12/22/2000 STARLIX
NDA #021204
Standard 2400 endocrine NO
12/26/2016
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 84
01/26/2001 CANCIDAS
NDA #021227
Priority 623 Antibiotic yes
12/26/2016
02/28/2001 RAZADYNE
NDA #021169
Standard 1040 CNS NO
12/26/2016
02/16/2001 FORADIL
NDA #020831
Standard 5824 Respiratory Yes
12/26/2016
02/05/2001 GEODON
NDA #020825
Standard 5400 psychiatric yes
12/26/2016
03/16/2001 TRAVATAN
NDA #021257
Priority ophthalmic NO D/C 12/26/2016
03/16/2001 LUMIGAN
NDA #021275
Priority 1219 ophthalmic NO D/C 12/26/2016
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 85
05/07/2001 AXERT NDA
#021001
Standard 1840 CNS NO
12/26/2016
05/10/2001 GLEEVEC
NDA #021335
Priority 1027 cancer YES Accelerated
approval
12/26/2016
07/05/2001 REMODULIN
NDA #021272
Priority 236 CVS NO Orphan -
Accelerated
12/26/2016
07/31/2001 DEFINITY
NDA #021064
Standard 1716 CVS NO
12/26/2016
08/10/2001 NATRECOR
NDA #020920
Standard 941 CVS NO
12/28/2016
08/20/2001 ZOMETA
NDA #021223
Priority 86 Cancer symptoms no Orphan 12/28/2016
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 86
08/29/2001 SPECTRACEF
NDA #021222
Standard 4299 Antibiotic NO D/C 12/28/2016
10/03/2001 NUVARING
NDA #021187
Standard 2501 contraception NO
12/28/2016
10/26/2001 VIREAD
NDA #021356
Priority 1000 antiviral Yes Accelerated
approval
12/28/2016
11/08/2001 FROVA NDA
#021006
Standard 1554 CNS NO
12/28/2016
11/16/2001 BEXTRA
NDA #021341
Standard 5349 osteoarthritis,
Rheumatoid arthritis,
Dysmenorrhea
NO D/C 12/28/2016
11/20/2001 TRACLEER
NDA #021290
Standard 777 CVS Yes Orphan -
Accelerated
12/28/2016
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 87
11/20/2001 AVODART
NDA #021319
Standard 2166 GU NO
12/28/2016
11/21/2001 INVANZ
NDA #021337
Standard 1954 Antibiotic NO
12/28/2016
12/07/2001 ARIXTRA
NDA #021345
Priority 4823 CVS Yes
12/28/2016
12/13/2001 ELIDEL NDA
#021302
Standard 1171 Dermatology Yes
1/1/2017
12/21/2001 CLARINEX
NDA #021165
Standard 1838 Respiratory NO
1/1/2017
01/18/2002 ORFADIN
NDA #021232
Priority 207 tyrosinemia NO Orphan 1/1/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 88
04/25/2002 BENICAR
NDA #021286
Standard 3825 CVS NO
1/1/2017
04/25/2002 FASLODEX
NDA #021344
Standard 1277 Cancer NO
1/1/2017
05/24/2002 VFEND NDA
#021266
Standard 1493 antifungal Yes
1/1/2017
05/31/2002 IMAGENT
NDA #021191
Standard 777 CVS NO D/C 1/1/2017
07/17/2002 XYREM NDA
#021196
Priority 448 narcolepsy Yes Orphan -
Accelerated
1/1/2017
07/24/2002 ZELNORM
NDA #021200
Priority 2632 GI Yes D/C 1/1/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 89
08/09/2002 ELOXATIN
NDA #021492
Priority 1500 cancer NO D/C -
accelerated
1/1/2017
09/20/2002 HEPSERA
NDA #021449
Priority 294 antiviral NO
1/1/2017
10/25/2002 ZETIA NDA
#021445
Standard 4700 CVS No
1/1/2017
11/15/2002 ABILIFY
NDA #021436
Standard 5592 psychiatric Yes Orphan 1/1/2017
11/22/2002 ALINIA NDA
#021498
Priority 613 antibiotic no Orphan 1/1/2017
11/26/2002 STRATTERA
NDA #021411
Standard 2067 CNS no
1/1/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 90
12/20/2002 EXTRANEAL
NDA #021321
Standard 493 GU yes Orphan 1/1/2017
12/26/2002 RELPAX
NDA #021016
Standard 4597 CNS NO
1/1/2017
03/13/2003 FUZEON
NDA #021481
Priority 1188 antiviral no Accelerated
approval
1/1/2017
03/25/2003 SOMAVERT
NDA #021106
Priority 80 endocrine
(Acromegaly)
NO Orphan 1/1/2017
03/26/2003 EMEND NDA
#021549
Priority 3300 N/V (GI) with cancer Yes
1/1/2017
04/04/2003 FACTIVE
NDA #021158
Standard 6775 antibiotic NO
1/1/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 91
05/05/2003 IRESSA NDA
#021399
Priority 941 cancer no D/C -
accelerated
1/1/2017
05/13/2003 VELCADE
NDA #021602
Priority 228 cancer NO Orphan -
Accelerated
1/1/2017
05/16/2003 BONIVA
NDA #021455
Standard 3900 Osteoporosis NO
1/1/2017
06/12/2003 UROXATRAL
NDA #021287
Standard 1608 GU NO
1/1/2017
06/20/2003 REYATAZ
NDA #021567
Priority 1597 antiviral NO
1/1/2017
07/02/2003 EMTRIVA
NDA #021500
Standard 2000 antiviral NO
1/1/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 92
07/25/2003 ALOXI NDA
#021372
Standard 1374 N/V (GI) with cancer Yes
1/1/2017
07/31/2003 ZAVESCA
NDA #021348
Standard 80 Gaucher disease NO Orphan 1/1/2017
08/12/2003 CRESTOR
NDA #021366
Standard 10275 CVS NO
1/2/2017
08/19/2003 LEVITRA
NDA #021400
Standard 4430 Erectile dysfunction NO
1/2/2017
09/12/2003 CUBICIN
NDA #021572
Priority 1409 antibiotic yes
1/2/2017
10/02/2003 RADIOGARDASE
(PRUSSIAN
Priority 106 contamination with
Radioactive
Yes Orphan 1/2/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 93
BLUE) NDA
#021626
cesium/non radioactive
lethium
10/16/2003 NAMENDA
NDA #021487
Standard 1350 CNS NO
1/2/2017
10/16/2003 ELESTAT
NDA #021565
Standard 800 ophthalmic NO
1/2/2017
11/21/2003 CIALIS NDA
#021368
Standard 5700 Erectile dysfunction NO
1/2/2017
11/25/2003 PLENAXIS
NDA #021320
Priority 81 CANCER Yes D/C –
accelerated
1/2/2017
12/10/2003 ERTACZO
NDA #021385
Standard 297 antifungal NO
1/2/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 94
01/30/2004 SPIRIVA
NDA #021395
Standard 1308 Respiratory Yes
1/2/2017
02/04/2004 ALIMTA
NDA #021462
Priority 226 Cancer no Orphan 1/2/2017
03/08/2004 SENSIPAR
NDA #021688
Priority 656 Endocrine/GU NO Orphan 1/2/2017
04/01/2004 KETEK NDA
#021144
Standard 4780 antibiotic NO D/C 1/2/2017
04/09/2004 CHIRHOSTIM
NDA #021256
Priority 584 GI NO
1/2/2017
04/16/2004 APIDRA NDA
#021629
Standard 1833 Endocrine No
1/2/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 95
04/20/2004 APOKYN
NDA #021264
Priority 550 CNS yes Orphan 1/2/2017
05/05/2004 VITRASE
NDA #021640
Priority adjuvant to increase the
absorption and
dispersion of other
injected drugs -
adjuvant injection
NO 1/2/2017
05/17/2004 TINDAMAX
NDA #021618
Standard 3669 Antifungal NO Orphan 1/2/2017
05/19/2004 VIDAZA
NDA #050794
Priority 268 Cancer/myelodysplastic
disorders
NO Orphan 1/2/2017
05/25/2004 XIFAXAN
NDA #021361
Standard 320 antibiotic yes Orphan 1/2/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 96
05/28/2004 SANCTURA
NDA #021595
Standard 1673 GU NO D/C 1/2/2017
06/10/2004 NUTRESTORE
NDA #021667
Standard 41 GI NO Orphan 1/2/2017
07/29/2004 CAMPRAL
NDA #021431
Priority 7000 alcohol dependence NO
1/2/2017
08/03/2004 CYMBALTA
NDA #021427
Standard 2418 psychiatric Yes
1/2/2017
08/11/2004 PENTETATE
CALCIUM
TRISODIUM
NDA #021749
Priority 646 known or suspected
internal contamination
with plutonium
yes Orphan 1/2/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 97
08/11/2004 PENTETATE
ZINC
TRISODIUM
NDA #021751
Priority 646 known or suspected
internal contamination
with plutonium
Yes Orphan 1/2/2017
09/17/2004 MACUGEN
NDA #021756
Priority 892 age-related macular
degeneration
yes
1/2/2017
10/26/2004 FOSRENOL
NDA #021468
Standard 1215 GU NO
1/3/2017
10/26/2004 AMPHADASE
NDA #021665
Priority an adjuvant to increase
the absorption and
dispersion of other
injected drugs -
Adjuvant inection
NO 1/3/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 98
11/10/2004 LOVAZA
NDA #021654
Standard 226 reduce triglycerides -
CVS
NO
1/3/2017
11/18/2004 TARCEVA
NDA #021743
Priority 2084 Cancer Yes
1/3/2017
11/19/2004 VESICARE
NDA #021518
Standard 1811 GU Yes
1/3/2017
11/23/2004 MULTIHANCE
NDA #021357
Standard 2982 Diagnostic No
1/3/2017
12/15/2004 LUNESTA
NDA #021476
Standard 1950 CNS no
1/3/2017
12/16/2004 VISIONBLUE
NDA #021670
Priority an aid in ophthalmic
surgery
no
1/3/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 99
12/22/2004 ENABLEX
NDA #021513
Standard 8830 GU no
1/8/2017
12/28/2004 PRIALT NDA
#021060
Priority 1254 Pain NO
1/8/2017
12/28/2004 CLOLAR
NDA #021673
Priority 113 Cancer yes Orphan -
Accelerated
1/8/2017
12/29/2004 VENTAVIS
NDA #021779
Priority 215 CVS no Orphan 1/8/2017
12/30/2004 LYRICA NDA
#021446
Priority 10000 Pain yes
1/8/2017
03/16/2005 SYMLIN
NDA #021332
Standard 5325 Endocrine NO
1/8/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 100
03/16/2005 MYCAMINE
NDA #021506
Priority 2402 antifungal no
1/8/2017
03/29/2005 BARACLUDE
NDA #021797
Priority 1720 antiviral yes
1/8/2017
04/28/2005 BYETTA
NDA #021773
Standard 1857 endocrine yes
1/8/2017
06/15/2005 TYGACIL
NDA #021821
Priority 2167 Antibiotic yes
1/8/2017
06/16/2005 LEVEMIR
NDA #021536
Standard 6004 endocrine NO
1/8/2017
06/22/2005 APTIVUS
NDA #021814
Priority 1854 antiviral NO Accelerated
approval
1/8/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 101
07/07/2005 EXJADE
NDA #021882
Priority 700 chronic iron overload yes Orphan -
Accelerated
1/8/2017
07/22/2005 ROZEREM
NDA #021782
Standard 4251 CNS NO
1/8/2017
08/19/2005 NEVANAC
NDA #021862
Priority 536 ophthalmic NO
1/8/2017
08/30/2005 INCRELEX
NDA #021839
Priority 71 endocrine NO Orphan 1/8/2017
10/25/2005 HYDASE
NDA #021716
Priority 100 NO D/C 1/8/2017
10/28/2005 ARRANON
NDA #021877
Priority 459 Cancer yes Orphan -
Accelerated
1/8/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 102
12/01/2005 NEXAVAR
NDA #021923
Priority 1286 Cancer yes Orphan 1/8/2017
12/02/2005 HYLENEX
RECOMBINANT
NDA #021859
Priority an adjuvant to increase
the absorption and
dispersion of other
injected drugs -
Adjuvant inection
NO
1/8/2017
12/27/2005 REVLIMID
NDA #021880
Priority 148 myelodysplastic yes Orphan -
Accelerated
1/8/2017
12/29/2005 VAPRISOL
NDA #021697
Standard 183 euvolemic
hyponatremia
yes
1/8/2017
01/26/2006 SUTENT
NDA #021938
Priority 450 Cancer yes
1/8/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 103
01/27/2006 RANEXA
NDA #021526
Standard 2018 CVS NO
1/8/2017
01/31/2006 AMITIZA
NDA #021908
Standard 1429 GI yes
1/8/2017
02/17/2006 ERAXIS NDA
#021632
Standard 929 Antifungal yes
1/8/2017
05/02/2006 DACOGEN
NDA #021790
Standard 240 myelodysplastic
syndromes
NO Orphan 1/8/2017
05/10/2006 CHANTIX
NDA #021928
Priority 4500 Smoking cessation yes
1/8/2017
05/16/2006 AZILECT
NDA #021641
Standard 1361 CNS yes
1/8/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 104
06/23/2006 PREZISTA
NDA #021976
Priority 415 antiviral No Accelerated
approval
1/8/2017
06/28/2006 SPRYCEL
NDA #021986
Priority 911 cancer NO Orphan -
Accelerated
1/8/2017
09/15/2006 NOXAFIL
NDA #022003
Priority 1844 Antifungal yes
1/8/2017
10/06/2006 ZOLINZA
NDA #021991
Priority 107 cancer NO Orphan 1/8/2017
10/16/2006 JANUVIA
NDA #021995
Standard 2316 Endocrine yes
1/8/2017
10/20/2006 OMNARIS
NDA #022004
Standard 1524 Respiratory NO
1/8/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 105
10/25/2006 TYZEKA
NDA #022011
Standard 760 antiviral yes
1/8/2017
10/31/2006 VEREGEN
NDA #021902
Standard 915 Topical antibiotic NO
1/8/2017
12/19/2006 INVEGA
NDA #021999
Standard 2720 CNS NO
1/8/2017
02/23/2007 VYVANSE
NDA #021977
Standard 404 CNS yes
1/14/2017
03/05/2007 TEKTURNA
NDA #021985
Standard 6460 CVS yes
1/14/2017
03/13/2007 TYKERB
NDA #022059
Priority 3500 cancer yes
1/14/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 106
04/12/2007 ALTABAX
NDA #022055
Standard 2115 Antibiotic NO
1/14/2017
05/09/2007 NEUPRO
NDA #021829
Standard 649 CNS yes
1/14/2017
05/30/2007 TORISEL
NDA #022088
Priority 1080 cancer NO
1/14/2017
06/15/2007 LETAIRIS
NDA #022081
Priority 483 CVS yes Orphan -
Accelerated
1/14/2017
08/06/2007 SELZENTRY
NDA #022128
Priority 840 antiviral yes Accelerated
approval
1/14/2017
08/23/2007 AMMONIA N 13
NDA #022119
Standard Diagnostic No
1/14/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 107
08/30/2007 SOMATULINE
DEPOT NDA
#022074
Standard 416 acromegaly (endocrine) No Orphan 1/14/2017
10/12/2007 DORIBAX
NDA #022106
Standard 853 Antibiotic yes
1/14/2017
10/12/2007 ISENTRESS
NDA #022145
Priority 507 antiviral yes Accelerated
approval
1/14/2017
10/16/2007 IXEMPRA KIT
NDA #022065
Priority 1323 cancer no
1/14/2017
10/29/2007 TASIGNA
NDA #022068
Standard 438 cancer NO Orphan -
Accel
1/14/2017
12/13/2007 KUVAN NDA
#022181
Priority 579 hyperphenylalaninemia yes
1/14/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 108
12/17/2007 BYSTOLIC
NDA #021742
Standard 6545 CVS no
1/14/2017
01/18/2008 INTELENCE
NDA #022187
Priority 1203 antiviral yes Accelerated
approval
1/14/2017
02/29/2008 PRISTIQ
NDA #021992
Standard 1834 psychiatric yes
1/14/2017
03/20/2008 TREANDA
NDA #022249
Priority 153 cancer YES Orphan 1/14/2017
04/10/2008 LEXISCAN
NDA #022161
Standard 1651 pharmacologic stress
agent
NO
1/14/2017
04/24/2008 RELISTOR
NDA #021964
Standard 165 GI yes
1/14/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 109
05/20/2008 ENTEREG
NDA #021775
Standard 1650 GI yes
1/14/2017
06/23/2008 DUREZOL
NDA #022212
Priority 314 ophthalmic NO Orphan 1/14/2017
07/03/2008 EOVIST NDA
#022090
Standard 1755 Diagnostic NO
1/14/2017
08/01/2008 CLEVIPREX
NDA #022156
Standard 1406 CVS yes
1/14/2017
08/15/2008 XENAZINE
NDA #021894
Priority 773 chorea associated with
Huntington’s disease
(HD). Cancer
yes Orphan 1/14/2017
09/19/2008 ADREVIEW
NDA #022290
Priority 251 Diagnostic Cancer NO Orphan 1/14/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 110
10/08/2008 RAPAFLO
NDA #022206
Standard 897 BPH, GU NO
1/14/2017
10/28/2008 VIMPAT
NDA #022253
Standard 1327 CNS yes
1/14/2017
10/31/2008 TOVIAZ NDA
#022030
Standard 2288 GU yes
1/14/2017
11/14/2008 BANZEL
NDA #021911
Standard 1978 CNS NO Orphan 1/14/2017
11/20/2008 PROMACTA
NDA #022291
Priority 313 Thrompocytopenia NO Orphan -
Accel
1/14/2017
11/20/2008 NUCYNTA
NDA #022304
Standard 2178 Pain yes
1/14/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 111
12/12/2008 LUSEDRA
NDA #022244
Standard 332 Sedative-Hypnotic
CNS
YES D/C 1/14/2017
12/15/2008 MOZOBIL
NDA #022311
Priority 543 Hematologic NO Orphan 1/14/2017
12/22/2008 ABLAVAR
NDA #021711
Standard 1676 Diagnostic NO D/C 1/14/2017
12/24/2008 FIRMAGON
NDA #022201
Standard 1325 Cancer NO
1/14/2017
01/14/2009 SAVELLA
NDA #022256
Standard 1557 Fibromylagia yes
1/15/2017
02/13/2009 ULORIC NDA
#021856
Standard 2757 Gout yes
1/15/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 112
03/30/2009 AFINITOR
NDA #022334
Priority 274 cancer yes
1/15/2017
04/07/2009 COARTEM
NDA #022268
Priority 1979 Antibiotic yes Orphan 1/15/2017
04/09/2009 ULESFIA
NDA #022129
Standard 1199 Head Lice No
1/15/2017
05/06/2009 FANAPT
NDA #022192
Standard 2070 psychiatric yes
1/15/2017
05/19/2009 SAMSCA
NDA #022275
Standard 607 hyponatremia yes
1/15/2017
05/28/2009 BESIVANCE
NDA #022308
Standard 1000 ophthalmic, Antibiotic NO
1/15/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 113
07/01/2009 MULTAQ
NDA #022425
Priority 6285 CVS NO
1/15/2017
07/10/2009 EFFIENT
NDA #022307
Priority 6741 CVS NO
1/15/2017
07/31/2009 ONGLYZA
NDA #022350
Standard 4148 Endocrine yes
1/15/2017
08/03/2009 LIVALO NDA
#022363
Standard 3291 CVS, lipid lowering no
1/15/2017
08/13/2009 SAPHRIS
NDA #022117
Standard 3350 psychiatric yes
1/15/2017
08/21/2009 SABRIL NDA
#020427
Standard 4079 CNS yes Orphan 1/15/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 114
08/21/2009 SABRIL NDA
#022006
Priority 4079 CNS yes Orphan 1/15/2017
09/08/2009 BEPREVE
NDA #022288
Standard 861 Anti-histamine-itching-
ophthalmic
NO
1/15/2017
09/11/2009 VIBATIV
NDA #022110
Standard 929 Antibiotic yes
1/15/2017
09/24/2009 FOLOTYN
NDA #022468
Priority 111 cancer yes Orphan,
Accel
1/15/2017
11/05/2009 ISTODAX
NDA #022393
Standard 185 cancer yes Orphan 1/15/2017
11/16/2009 QUTENZA
NDA #022395
Standard 1600 Pain No Orphan 1/15/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 115
01/22/2010 AMPYRA
NDA #022250
Priority 400 Multiple Sclerosis No Orphan 1/15/2017
01/25/2010 VICTOZA
NDA #022341
Standard 3978 endocrine yes
1/15/2017
02/26/2010 VPRIV NDA
#022575
Priority 94 Gaucher disease no Orphan 1/15/2017
03/18/2010 CARBAGLU
NDA #022562
Priority 30 yes Orphan 1/15/2017
03/30/2010 ASCLERA
NDA #021201
Standard 401 varicose veins CVS no
1/15/2017
05/06/2010 NATAZIA
NDA #022252
Standard 2131 contraception yes
1/16/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 116
06/17/2010 JEVTANA KIT
NDA #201023
Priority 371 Cancer yes
1/16/2017
07/28/2010 LASTACAFT
NDA #022134
Standard 909 ophthalmic no
1/16/2017
08/13/2010 ELLA NDA
#022474
Standard 2637 contraception yes
1/16/2017
09/21/2010 GILENYA
NDA #022527
Priority 1703 Multiple Sclerosis yes
1/16/2017
10/19/2010 PRADAXA
NDA #022512
Priority 12042 CVS yes
1/16/2017
10/28/2010 LATUDA
NDA #200603
Standard 2096 psychiatric yes
1/16/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 117
10/29/2010 TEFLARO
NDA #200327
Standard 1300 Antibiotic yes
1/16/2017
11/10/2010 EGRIFTA
NDA #022505
Standard 740 endocrine, HIV yes
1/16/2017
11/15/2010 HALAVEN
NDA #201532
Priority 1222 Cancer NO
1/21/2017
12/09/2010 SUCRAID
NDA #020772
Priority 34 Enzyme replacement NO Orphan 1/21/2017
01/14/2011 DATSCAN
NDA #022454
Priority 942 diagnostic agent yes
1/21/2017
01/18/2011 NATROBA
NDA #022408
Standard 552 Head lice NO
1/21/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 118
01/21/2011 VIIBRYD
NDA #022567
Standard 2177 psychiatric yes
1/21/2017
02/25/2011 EDARBI NDA
#200796
Standard 4814 CVS yes
1/21/2017
02/28/2011 DALIRESP
NDA #022522
Standard 4438 Respiratory yes
1/21/2017
03/14/2011 GADAVIST
NDA #201277
Standard 4549 Diagnostic no
1/21/2017
04/06/2011 HORIZANT
NDA #022399
Standard 2300 Restless leg syndrome yes Orphan 1/21/2017
04/06/2011 CAPRELSA
NDA #022405
Priority 231 Cancer yes Orphan 1/21/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 119
04/28/2011 ZYTIGA NDA
#202379
Priority 1070 cancer NO
1/21/2017
05/02/2011 TRADJENTA
NDA #201280
Standard 4000 endocrine yes
1/22/2017
05/13/2011 VICTRELIS
NDA #202258
Priority 2095 antiviral NO D/C 1/22/2017
05/20/2011 EDURANT
NDA #202022
Standard 1368 antiviral yes
1/22/2017
05/23/2011 INCIVEK
NDA #201917
Priority 1797 antiviral no
1/22/2017
05/27/2011 DIFICID NDA
#201699
Priority 564 Antibiotic yes
1/22/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 120
06/10/2011 POTIGA NDA
#022345
Standard 1365 CNS yes
1/22/2017
07/01/2011 ARCAPTA
NEOHALER
NDA #022383
Standard 2516 Respiratory No
1/22/2017
07/01/2011 XARELTO
NDA #022406
Standard 4487 CVS yes
1/22/2017
07/20/2011 BRILINTA
NDA #022433
Standard 10000 cvs No
1/22/2017
08/17/2011 ZELBORAF
NDA #202429
Priority 807 cancer yes Orphan 1/22/2017
08/25/2011 FIRAZYR
NDA #022150
Priority 223 hereditary angioedema
(HAE)
yes Orphan 1/22/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 121
08/26/2011 XALKORI
NDA #202570
Priority 255 cancer yes Orphan -
Accel
1/22/2017
10/14/2011 FERRIPROX
NDA #021825
Standard 642 Iron overload yes Orphan -
Accel
1/22/2017
10/21/2011 ONFI NDA
#202067
Standard 633 CNS yes Orphan 1/22/2017
11/16/2011 JAKAFI NDA
#202192
Priority 617 Myelofibrosis yes Orphan 1/22/2017
01/23/2012 PICATO NDA
#202833
Standard 499 keratosis no
1/22/2017
01/27/2012 INLYTA NDA
#202324
Standard 715 cancer no
1/22/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 122
01/30/2012 ERIVEDGE
NDA #203388
Priority 138 cancer yes
1/22/2017
01/31/2012 KALYDECO
NDA #203188
Priority 353 cystic fibrosis yes Orphan 1/22/2017
02/10/2012 ZIOPTAN
NDA #202514
Standard 905 ophthalmic NO
1/29/2017
03/06/2012 SURFAXIN
NDA #021746
Standard 643 Respiratory D/C 1/29/2017
03/14/2012 NATAZIA
NDA #022252
Standard 1867 contraception no
1/29/2017
03/27/2012 OMONTYS
NDA #202799
Standard 1066 anemia due to chronic
kidney disease
yes D/C 1/29/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 123
04/06/2012 AMYVID
NDA #202008
Priority 496 Radiocontrast
diagnostic
yes
1/29/2017
04/27/2012 STENDRA
NDA #202276
Standard 1923 erectile dysfunction No
1/29/2017
05/01/2012 ELELYSO
NDA #022458
Standard 60 Gaucher disease yes Orphan 1/29/2017
06/27/2012 BELVIQ NDA
#022529
Standard 3451 weight management yes
1/29/2017
06/28/2012 MYRBETRIQ
NDA #202611
Standard 2736 overactive bladder. GU yes
1/29/2017
07/16/2012 PREPOPIK
NDA #202535
Standard 1195 GI YES
1/29/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 124
07/20/2012 KYPROLIS
NDA #202714
Standard 526 Cancer yes Orphan -
Accel
1/29/2017
07/23/2012 TUDORZA
PRESSAIR
NDA #202450
Standard 1471 Respiratory no
1/29/2017
08/27/2012 STRIBILD
NDA #203100
Standard 1408 antiviral yes
1/29/2017
08/30/2012 LINZESS
NDA #202811
Standard 5830 GI yes
1/29/2017
08/31/2012 XTANDI
NDA #203415
Priority 800 Cancer yes
1/29/2017
09/04/2012 BOSULIF
NDA #203341
Standard 546 Cancer yes Orphan 1/29/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 125
09/12/2012 AUBAGIO
NDA #202992
Standard 844 Multiple Sclerosis yes
1/29/2017
09/12/2012 CHOLINE C-11
NDA #203155
Priority 176 Diagnostic Cancer NO
1/29/2017
09/27/2012 STIVARGA
NDA #203085
Priority 500 Cancer yes Orphan 1/29/2017
10/22/2012 FYCOMPA
NDA #202834
Standard 1038 CNS yes
1/29/2017
10/26/2012 SYNRIBO
NDA #203585
Standard 163 Cancer yes Orphan -
Accel
1/29/2017
11/06/2012 XELJANZ
NDA #203214
Standard 2685 rheumatoid Arthritis yes
1/29/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 126
11/29/2012 COMETRIQ
NDA #203756
Priority 330 Cancer yes orphan 1/29/2017
12/14/2012 SIGNIFOR
NDA #200677
Standard 162 cushings disease,
endocrine
yes Orphan 1/29/2017
12/14/2012 ICLUSIG
NDA #203469
Priority 449 Cancer yes Orphan -
Accel
1/29/2017
12/21/2012 GATTEX KIT
NDA #203441
Standard 566 GI yes Orphan 1/29/2017
12/21/2012 JUXTAPID
NDA #203858
Standard 29 Lipid lowering CVS yes Orphan 1/29/2017
12/28/2012 ELIQUIS
NDA #202155
Priority 11885 CVS yes
1/29/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 127
12/28/2012 SIRTURO
NDA #204384
Priority 335 Antibiotic yes Orphan -
Accel
1/29/2017
12/31/2012 FULYZAQ
NDA #202292
Priority 696 GI, HIV-antidiarrheal yes
1/29/2017
01/25/2013 NESINA NDA
#022271
Standard 8500 Endocrine, DM yes
1/29/2017
01/29/2013 KYNAMRO
NDA #203568
Standard 261 Lipid lowering CVS yes orphan 1/29/2017
02/08/2013 POMALYST
NDA #204026
Standard 219 cancer yes Orphan -
Accel
1/29/2017
02/26/2013 OSPHENA
NDA #203505
Standard 1892 GU DYSparunia no
1/29/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 128
03/13/2013 LYMPHOSEEK
KIT NDA
#202207
Standard 542 Diagnostic Cancer yes
1/29/2017
03/20/2013 DOTAREM
NDA #204781
Priority 2813 Diagnostic yes
1/29/2017
03/27/2013 TECFIDERA
NDA #204063
Standard 1529 Multiple Sclerosis yes
1/29/2017
03/29/2013 INVOKANA
NDA #204042
Standard 1667 endocrine DM yes
1/29/2017
05/10/2013 BREO ELLIPTA
NDA #204275
Standard 7700 Respiratory no
1/29/2017
05/15/2013 XOFIGO
NDA #203971
Priority 600 cancer yes
1/29/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 129
05/29/2013 TAFINLAR
NDA #202806
Standard 586 cancer yes Orphan 1/29/2017
05/29/2013 MEKINIST
NDA #204114
Standard 329 cancer yes Orphan 2/4/2017
07/12/2013 GILOTRIF
NDA #201292
Priority 3800 cancer yes Orphan 2/4/2017
08/12/2013 TIVICAY
NDA #204790
Priority 1655 antiviral yes
2/4/2017
09/30/2013 TRINTELLIX
NDA #204447
Standard 4746 psychiatric yes
2/4/2017
10/03/2013 DUAVEE
NDA #022247
Standard 6210 Gynecologic no
2/4/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 130
10/08/2013 ADEMPAS
NDA #204819
Priority 490 cvS no Orphan 2/4/2017
10/18/2013 OPSUMIT
NDA #204410
Standard 742 CVS yes Orphan 2/4/2017
10/25/2013 VIZAMYL
NDA #203137
Standard 761 Diagnostic NO
2/4/2017
11/08/2013 APTIOM
NDA #022416
Standard 1195 CNS yes
2/4/2017
11/13/2013 IMBRUVICA
NDA #205552
Priority 111 Cancer yes Orphan -
Accelerated
2/4/2017
11/14/2013 LUZU NDA
#204153
Standard 616 antifungal yes
2/4/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 131
11/22/2013 OLYSIO NDA
#205123
Priority 1178 antiviral yes
2/4/2017
12/06/2013 SOVALDI
NDA #204671
Priority 650 antiviral yes
2/4/2017
12/18/2013 ANORO ELLIPTA
NDA #203975
Standard 8138 Respiratory No
2/4/2017
01/08/2014 FARXIGA
NDA #202293
Standard 2338 diabetes - Endocrine yes
2/4/2017
01/31/2014 HETLIOZ
NDA #205677
Priority 1346 CNS - Sleep Wake
syndrome
no Orphan 2/4/2017
02/18/2014 NORTHERA
NDA #203202
Priority 485 CNS Yes Orphan -
Accelerated
2/4/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 132
03/19/2014 NEURACEQ
NDA #204677
Standard 978 Diagnostic no
2/4/2017
03/19/2014 IMPAVIDO
NDA #204684
Priority 299 Antibiotic yes Orphan 2/4/2017
03/21/2014 OTEZLA
NDA #205437
Standard 990 psoriatic arthritis -
general
yes
2/4/2017
04/29/2014 ZYKADIA
NDA #205755
Priority 255 Cancer yes Orphan -
Accelerated
2/4/2017
05/08/2014 ZONTIVITY
NDA #204886
Standard 13186 CVS NO
2/4/2017
05/23/2014 DALVANCE
NDA #021883
Priority 1778 Antibiotic yes
2/4/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 133
06/06/2014 JUBLIA NDA
#203567
Standard 1227 Antifungal yes
2/4/2017
06/20/2014 SIVEXTRO
NDA #205435
Priority 1050 Antibiotic yes
2/4/2017
07/03/2014 BELEODAQ
NDA #206256
Priority 129 Cancer yes Orphan -
Accelerated
2/4/2017
07/07/2014 KERYDIN
NDA #204427
Standard 791 antifungal yes
2/4/2017
07/23/2014 ZYDELIG
NDA #205858
Standard 364 cancer yes Orphan -
Accelerated
2/4/2017
07/23/2014 ZYDELIG
NDA #206545
Priority 364 Cancer yes Orphan -
Accelerated
2/4/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 134
07/31/2014 STRIVERDI
RESPIMAT
NDA #203108
Standard 3104 Respiratory no
2/4/2017
08/01/2014 JARDIANCE
NDA #204629
Standard 1976 diabetes - Endocrine yes
2/5/2017
08/06/2014 ORBACTIV
NDA #206334
Priority 976 Antibiotic yes
2/5/2017
08/13/2014 BELSOMRA
NDA #204569
Standard 1263 CNS no
2/5/2017
08/19/2014 CERDELGA
NDA #205494
Priority 126 Gaucher disease yes orphan 2/5/2017
09/16/2014 MOVANTIK
NDA #204760
Standard 1497 GI yes
2/5/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 135
09/23/2014 OTEZLA
NDA #206088
Standard 1493 psoriatic arthritis -
general
yes
2/5/2017
10/10/2014 LUMASON
NDA #203684
Standard 6307 radiocontrast agent -
diagnostic
yes
2/5/2017
10/10/2014 AKYNZEO
NDA #205718
Standard 1538 GI, cancer yes
2/5/2017
10/10/2014 HARVONI
NDA #205834
Priority 1080 antiviral yes
2/5/2017
10/15/2014 ESBRIET
NDA #022535
Priority 1400 Respiratory no orphan 2/5/2017
10/15/2014 OFEV NDA
#205832
Priority 1000 Respiratory yes orphan,
Fast Track,
2/5/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 136
Break
through
12/17/2014 XTORO NDA
#206307
Priority 618 Antibiotic no
2/5/2017
12/19/2014 LYNPARZA
NDA #206162
Priority 300 cancer yes Orphan -
Accelerated
2/5/2017
12/19/2014 RAPIVAB
NDA #206426
Standard 1399 antiviral yes
2/5/2017
01/08/2015 SAVAYSA
NDA #206316
Standard 11130 CVS yes
2/5/2017
02/03/2015 IBRANCE
NDA #207103
Priority 755 cancer yes Accelerated
approval
2/5/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 137
02/13/2015 LENVIMA
NDA #206947
Priority 1108 cancer yes Orphan 2/5/2017
02/23/2015 FARYDAK
NDA #205353
Priority 758 Cancer yes Orphan -
Accelerated
2/5/2017
02/25/2015 AVYCAZ
NDA #206494
Priority 169 Antibiotic yes
2/5/2017
03/06/2015 CRESEMBA
NDA #207500
Priority 403 Antifungal yes Orphan 2/5/2017
03/17/2015 CHOLBAM
NDA #205750
Priority 91 Single enzyme
deficiency - Bile acid
yes orphan 2/5/2017
04/15/2015 CORLANOR
NDA #206143
Priority 3260 CVS no
2/5/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 138
04/29/2015 KYBELLA
NDA #206333
Standard 513 GI YES
2/5/2017
05/27/2015 VIBERZI
NDA #206940
Priority 1700 GI Yes
2/5/2017
06/22/2015 KENGREAL
NDA #204958
Standard 13301 CVS no
2/5/2017
07/02/2015 ORKAMBI
NDA #206038
Priority 1108 cystic fibrosis YES orphan 2/5/2017
07/07/2015 ENTRESTO
NDA #207620
Priority 4203 CVS yes
2/5/2017
07/10/2015 REXULTI
NDA #205422
Standard 1054 psychiatric yes
2/5/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 139
07/24/2015 ODOMZO
NDA #205266
Standard 229 cancer yes
2/5/2017
07/24/2015 DAKLINZA
NDA #206843
Priority 1900 antiviral yes
2/5/2017
08/18/2015 ADDYI NDA
#022526
Standard 2997 Gynecologic - women
health
yes
2/5/2017
09/01/2015 VARUBI
NDA #206500
Standard 2800 GI - Cancer yes
2/5/2017
09/04/2015 XURIDEN
NDA #208169
Priority 4 hereditary orotic
aciduria.
yes orphan 2/5/2017
09/17/2015 VRAYLAR
NDA #204370
Standard 1733 psychiatric yes
2/5/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 140
09/22/2015 LONSURF
NDA #207981
Standard 533 cancer yes
2/5/2017
09/25/2015 TRESIBA
NDA #203314
Standard 1102 endocrine - diabetes YES
2/5/2017
10/05/2015 ARISTADA
NDA #207533
Standard 880 psychiatric no
2/5/2017
10/21/2015 VELTASSA
NDA #205739
Standard 666 Hyperkalemia yes
2/5/2017
10/23/2015 YONDELIS
NDA #207953
Priority 755 cancer yes orphan 2/5/2017
11/05/2015 GENVOYA
NDA #207561
Standard 866 antiviral yes
2/5/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 141
11/10/2015 COTELLIC
NDA #206192
Priority 247 cancer yes orphan 2/5/2017
11/13/2015 TAGRISSO
NDA #208065
Priority 411 cancer yes Orphan -
Accelerated
2/5/2017
11/20/2015 NINLARO
NDA #208462
Priority 360 cancer - multiple
Myeloma
no orphan 2/5/2017
12/11/2015 ALECENSA
NDA #208434
Priority 253 Cancer yes Orphan -
Accelerated
2/5/2017
12/15/2015 BRIDION
NDA #022225
Priority 2914 reversal of
neuromuscular
blockade
yes
2/5/2017
12/21/2015 UPTRAVI
NDA #207947
Standard 1156 CVS no orphan 2/5/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 142
12/22/2015 ZURAMPIC
NDA #207988
Standard 1021 gout yes
2/5/2017
02/18/2016 BRIVIACT
NDA #205836
Standard 2437 CNS yes
2/5/2017
03/30/2016 DEFITELIO
NDA #208114
Priority 176 CVS – veno-occlusive
disorder
yes
2/5/2017
04/29/2016 NUPLAZID
NDA #207318
Priority 1200 psychiatric YES
2/5/2017
04/11/2016 VENCLEXTA
NDA #208573
Priority 240 cancer yes Accelerated
approval
2/5/2017
05/27/2016 OCALIVA
NDA #207999
Priority 432 GI yes Accelerated
approval
2/5/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 143
05/27/2016 AXUMIN
NDA #208054
Priority 877 Diagnostic no
2/5/2017
06/01/2016 NETSPOT
NDA #208547
Priority 264 radioactive diagnostic no
2/5/2017
06/28/2016 EPCLUSA
NDA #208341
Priority 1035 antiviral yes
2/5/2017
07/11/2016 XIIDRA NDA
#208073
Priority 1401 ophthalmic no
2/5/2017
07/27/2016 ADLYXIN
NDA #208471
Standard 2896 endocrine - diabetes yes
2/5/2017
09/19/2016 EXONDYS 51
NDA #206488
Priority 107 Duchenne muscular
dystrophy
yes Accelerated
approval
2/5/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 144
12/23/2016 SPINRAZA
NDA #209531
Priority 173 spinal muscular atrophy yes
2/5/2017
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 145
Appendix H
Time to First, Second, Third Safety Labeling Changes for Database of NME-1 Approved from 01/01/2000 – 12/31/2016
Date
approved
Drug name Date of 1st
safety
labeling
change
Type
of
1st
SLC
Date of
2nd safety
labeling
change
Type of 2nd
SLC
Date of 3rd
safety
labeling
change
Type
of
3rd
SLC
Days
to first
SLC
Days
to
second
SLC
Days
to
Third
SLC
01/11/2000 EVOXAC
NDA #020989
12/13/2005 A 12/8/2006 A
2163 2523
01/14/2000 TRILEPTAL
NDA #021014
4/1/2002 A -
W
3/25/2005 A 10/28/2005 A -
P
808 1897 2114
02/02/2000 PROTONIX
NDA #020987
10/28/2002 P 12/30/2003 A, P 1/9/2004 P 999 1427 1437
02/09/2000 LOTRONEX
NDA #021107
2/18/2005 C -
B -
W -
P
3/10/2006 C, and P 4/1/2008 B, A,
W
and
P
1836 2221 2974
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 146
03/27/2000 ZONEGRAN
NDA #020789
10/7/2002 W 4/23/2009 W and P 4/19/2010 W, P 924 3314 3675
04/12/2000 VISUDYNE
NDA #021119
3/25/2005 A 6/28/2012 A, P
1808 4460
04/13/2000 MOBIC NDA
#020938
4/28/2003 P 7/16/2004 P, A 8/11/2005 B, W
and
P, A,
C
1110 1555 1946
04/18/2000 ZYVOX NDA
#021130
2/6/2001 A,
W, P
1/5/2004 P 2/10/2005 P, A 294 1357 1759
04/20/2000 LANTUS
NDA #021081
4/25/2007 P 10/18/2013 W, P 2/25/2015 W, P 2561 4929 5424
04/21/2000 EXELON
NDA #020823
1/5/2001 A,
W
6/27/2006 A - P 10/1/2013 C,
W,
P, A
259 2258 4911
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 147
and
P
05/17/2000 MYLOTARG
NDA #021174
2/23/2001 B,
W,
A
5/25/2001 B, P, W 4/16/2004 A 282 373 1430
05/26/2000 WELCHOL
NDA #021176
10/10/2003 P 7/10/2006 A 9/6/2006 P 1232 2236 2294
06/07/2000 NOVOLOG
NDA #020986
12/4/2002 P 3/19/2004 P 9/13/2005 P 910 1381 1924
06/15/2000 TRELSTAR
NDA #020715
10/20/2005 A 1/14/2011 W and P 5/19/2011 W
and
P
1953 3865 3990
06/30/2000 ARGATROBAN
NDA #020883
9/1/2005 A 5/5/2008 P
1889 2866
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 148
07/14/2000 INNOHEP
NDA #020484
2/5/2002 A,
W
and
P
11/7/2006 P 12/29/2008 W,
P, A
571 2307 3090
07/18/2000 COLAZAL
NDA #020610
6/18/2002 P 12/20/2006 W, P, A 7/9/2008 P, A 700 2346 2913
08/11/2000 CETROTIDE
NDA #021197
4/30/2004 C,
A, P
4/4/2008 P
1358 2793
09/25/2000 TRISENOX
NDA #021248
7/23/2010 A
3588
09/28/2000 MIFEPREX
NDA #020687
12/22/2004 A 7/19/2005 W, B 4/24/2009 W, A 1546 1755 3130
12/15/2000 ANGIOMAX
NDA #020873
5/7/2004 A, P,
W
9/2/2005 A 11/30/2005 A 1239 1722 1811
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 149
12/22/2000 STARLIX
NDA #021204
11/26/2002 A 7/1/2004 P 11/9/2006 A 704 1287 2148
01/26/2001 CANCIDAS
NDA #021227
9/20/2002 P 3/17/2004 A 9/29/2004 A 602 1146 1342
02/28/2001 RAZADYNE
NDA #021169
4/19/2002 W 5/2/2005 P 4/27/2006 A, W 415 1524 1884
02/16/2001 FORADIL
NDA #020831
6/19/2006 B,
W,
P, A
6/2/2010 B, C, W, P,
A
9/27/2012 W
AND
P, A
1949 3393 4241
02/05/2001 GEODON
NDA #020825
2/15/2002 C -
W
8/13/2004 W, P, A 8/17/2005 B, P
and
W
375 1285 1654
03/16/2001 TRAVATAN
NDA #021257
2/13/2003 C
and
P
9/7/2011 A
699 3827
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 150
03/16/2001 LUMIGAN
NDA #021275
8/26/2002 P 6/22/2006 P 3/15/2012 A 528 1924 4017
05/07/2001 AXERT NDA
#021001
6/1/2004 P, A,
W
3/27/2009 W, P, A 4/30/2009 W
and
P
1121 2881 2915
05/10/2001 GLEEVEC
NDA #021335
10/31/2003 A
and
P
6/23/2004 P 5/31/2006 P
and
A
904 1140 1847
07/05/2001 REMODULIN
NDA #021272
11/24/2004 W, P 2/4/2008 W, A 1/8/2010 P, W
and
A
1238 2405 3109
07/31/2001 DEFINITY
NDA #021064
7/8/2002 P 10/10/2007 B, C, A, W,
P
5/12/2008 B,
W,
C, A
342 2262 2477
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 151
08/10/2001 NATRECOR
NDA #020920
4/20/2005 A 11/30/2006 A 6/12/2009 A, P 1349 1938 2863
08/20/2001 ZOMETA
NDA #021223
2/27/2004 A,
W
and
P
3/24/2004 A 1/31/2005 W, P 921 947 1260
08/29/2001 SPECTRACEF
NDA #021222
3/24/2004 A, P 12/20/2005 A 8/6/2012 A, W 938 1574 3995
10/03/2001 NUVARING
NDA #021187
7/29/2005 C,
W, P
10/2/2007 W and P 10/4/2013 W, P 1395 2190 4384
10/26/2001 VIREAD
NDA #021356
12/2/2002 W
and
A
7/1/2004 B, W, P 5/12/2005 A, P 402 979 1294
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 152
11/08/2001 FROVA NDA
#021006
3/3/2009 W
and
A, P
2672
11/16/2001 BEXTRA
NDA #021341
11/1/2002 W -
A -
C
4/23/2004 P 11/24/2004 B, C,
W,
P, A
350 889 1104
11/20/2001 TRACLEER
NDA #021290
10/6/2003 P, A 11/24/2004 C, and P, A 11/29/2005 tBox
w,
W,
P, A
685 1100 1470
11/20/2001 AVODART
NDA #021319
12/23/2005 P 3/31/2008 C, A 6/15/2010 W
and
P, A
1494 2323 3129
11/21/2001 INVANZ
NDA #021337
4/30/2004 A 5/20/2004 A 5/18/2005 A, P 891 911 1274
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 153
12/07/2001 ARIXTRA
NDA #021345
12/4/2002 A
and
P
5/28/2004 C, W, P, A 5/26/2005 C,
W,
P, A
362 903 1266
12/13/2001 ELIDEL NDA
#021302
11/24/2004 P 1/19/2006 B, W 8/10/2007 A 1077 1498 2066
12/21/2001 CLARINEX
NDA #021165
1/29/2004 A 12/14/2006 A and P 4/23/2014 A 769 1819 4506
01/18/2002 ORFADIN
NDA #021232
2/13/2013 A
4044
04/25/2002 BENICAR
NDA #021286
10/25/2002 W
and
P, A
2/12/2003 A and P 11/12/2004 A
and
P
183 293 932
04/25/2002 FASLODEX
NDA #021344
8/2/2005 A 9/9/2010 W and P 7/13/2012 A 1195 3059 3732
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 154
05/24/2002 VFEND NDA
#021266
3/28/2003 A
and
P
4/21/2004 C and P 3/24/2005 P 308 698 1035
05/31/2002 IMAGENT
NDA #021191
07/17/2002 XYREM NDA
#021196
12/17/2012 C 4/11/2014 P
3806 4286
07/24/2002 ZELNORM
NDA #021200
4/15/2004 w
and
P, A
4/21/2004 w and P, A 6/15/2004 P
and
A
631 637 692
08/09/2002 ELOXATIN
NDA #021492
1/9/2004 P
and
A
11/4/2004 A 3/13/2009 A 518 818 2408
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 155
09/20/2002 HEPSERA
NDA #021449
8/19/2004 B,
W,
A,
4/28/2006 A 9/20/2006 P 699 1316 1461
10/25/2002 ZETIA NDA
#021445
7/23/2004 A
and
P
9/22/2004 A 3/2/2005 P
and
A
637 698 859
11/15/2002 ABILIFY
NDA #021436
4/8/2004 W 9/29/2004 A and P 3/1/2005 W 510 684 837
11/22/2002 ALINIA NDA
#021498
6/16/2005 A 7/11/2016 A
937 4980
11/26/2002 STRATTERA
NDA #021411
2/1/2005 W
and
P
5/26/2005 P 11/8/2005 B,
W, P
798 912 1078
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 156
12/20/2002 EXTRANEAL
NDA #021321
12/17/2004 P
and
A
2/23/2007 W and P 4/7/2009 Bs,
W
and
P, A,
C
728 1526 2300
12/26/2002 RELPAX
NDA #021016
5/6/2004 P 7/21/2010 W, A 4/13/2011 A 497 2764 3030
03/13/2003 FUZEON
NDA #021481
10/15/2004 W,
P, A
6/29/2005 P 9/29/2006 P, A 582 839 1296
03/25/2003 SOMAVERT
NDA #021106
8/18/2008 P, A 7/3/2012 P, A 12/10/2013 A 1973 3388 3913
03/26/2003 EMEND NDA
#021549
1/15/2004 A 12/15/2004 P 12/22/2004 P 295 630 637
04/04/2003 FACTIVE
NDA #021158
7/28/2004 P 9/7/2004 W, P 10/26/2006 P 481 522 1301
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 157
05/05/2003 IRESSA NDA
#021399
5/6/2004 P 11/19/2004 P, A
367 564
05/13/2003 VELCADE
NDA #021602
5/25/2004 P, A 3/25/2005 P, A 12/8/2005 P, A 378 682 940
05/16/2003 BONIVA
NDA #021455
3/24/2005 P, A 2/13/2007 P 11/28/2008 P, A,
W
678 1369 2023
06/12/2003 UROXATRAL
NDA #021287
3/17/2006 P, A 11/16/2006 A 3/29/2007 P 1009 1253 1386
06/20/2003 REYATAZ
NDA #021567
3/16/2004 W
and
P
7/6/2004 W and A 10/5/2004 P 270 382 473
07/02/2003 EMTRIVA
NDA #021500
6/13/2005 B,
W
12/2/2005 P 12/22/2006 W,
P, A
712 884 1269
07/25/2003 ALOXI NDA
#021372
8/23/2006 A 2/6/2014 P, W 5/27/2014 P 1125 3849 3959
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 158
07/31/2003 ZAVESCA
NDA #021348
2/29/2008 A W 11/23/2010 P
1674 2672
08/12/2003 CRESTOR
NDA #021366
3/2/2005 A,
W
and
P
7/23/2007 W, P, A 11/8/2007 w, P,
A, C
568 1441 1549
08/19/2003 LEVITRA
NDA #021400
5/13/2005 P 7/8/2005 P, A 4/6/2007 W
and
P
633 689 1326
09/12/2003 CUBICIN
NDA #021572
10/14/2005 A, P 5/25/2006 A, P 10/24/2006 P 763 986 1138
10/02/2003 RADIOGARDASE
(PRUSSIAN
BLUE) NDA
#021626
8/20/2014 W,
P, A
3975
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 159
10/16/2003 NAMENDA
NDA #021487
5/2/2005 P 4/19/2006 A 10/4/2006 P 564 916 1084
10/16/2003 ELESTAT
NDA #021565
12/20/2011 A
2987
11/21/2003 CIALIS NDA
#021368
3/31/2005 P 7/8/2005 P, A 3/7/2006 A 496 595 837
11/25/2003 PLENAXIS
NDA #021320
12/10/2003 ERTACZO
NDA #021385
01/30/2004 SPIRIVA
NDA #021395
12/8/2006 A 6/20/2008 A 3/3/2009 A, W 1043 1603 1859
02/04/2004 ALIMTA
NDA #021462
8/19/2004 A 7/28/2006 W, A 7/28/2006 A 197 905 905
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 160
03/08/2004 SENSIPAR
NDA #021688
10/4/2007 P 2/28/2008 W, A, P 5/2/2008 P 1305 1452 1516
04/01/2004 KETEK NDA
#021144
2/9/2005 P 11/2/2005 P, A 6/29/2006 W,
P, A,
C
314 580 819
04/09/2004 CHIRHOSTIM
NDA #021256
04/16/2004 APIDRA NDA
#021629
4/12/2007 P 10/24/2008 W, P, A,C 9/6/2013 W, P 1091 1652 3430
04/20/2004 APOKYN
NDA #021264
12/31/2008 P 9/2/2010 W, P
1716 2326
05/05/2004 VITRASE
NDA #021640
05/17/2004 TINDAMAX
NDA #021618
5/21/2007 B -
W -
1099
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 161
P -
A -
C
05/19/2004 VIDAZA
NDA #050794
1/26/2007 A 8/20/2008 W, P, A 8/17/2011 A 982 1554 2646
05/25/2004 XIFAXAN
NDA #021361
1/30/2007 A 3/12/2014 W, P
980 3578
05/28/2004 SANCTURA
NDA #021595
12/7/2006 A 6/1/2009 P 1/31/2011 W, P 923 1830 2439
06/10/2004 NUTRESTORE
NDA #021667
07/29/2004 CAMPRAL
NDA #021431
12/13/2010 P
2328
08/03/2004 CYMBALTA
NDA #021427
2/18/2005 Bs,
P, W
6/6/2006 P 9/20/2006 W -
P
199 672 778
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 162
08/11/2004 PENTETATE
CALCIUM
TRISODIUM
NDA #021749
8/4/2005 P
358
08/11/2004 PENTETATE
ZINC
TRISODIUM
NDA #021751
8/4/2005 P
358
09/17/2004 MACUGEN
NDA #021756
3/8/2006 C,
A, P
10/12/2011 P
537 2581
10/26/2004 FOSRENOL
NDA #021468
3/3/2006 P 10/23/2008 P 4/27/2011 W,
P, A,
C
493 1458 2374
10/26/2004 AMPHADASE
NDA #021665
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 163
11/10/2004 LOVAZA
NDA #021654
4/20/2009 A 9/16/2009 P 12/22/2010 A 1622 1771 2233
11/18/2004 TARCEVA
NDA #021743
11/2/2005 W 4/27/2007 P, A 9/12/2008 W,
P, A
349 890 1394
11/19/2004 VESICARE
NDA #021518
7/12/2007 A 2/8/2008 A 11/18/2008 A 965 1176 1460
11/23/2004 MULTIHANCE
NDA #021357
9/4/2007 Bs,
W
10/1/2009 W 12/20/2010 Bs,
W
and
P
1015 1773 2218
12/15/2004 LUNESTA
NDA #021476
1/29/2008 W
and
P
2/3/2014 A 5/15/2014 W, P 1140 3337 3438
12/16/2004 VISIONBLUE
NDA #021670
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 164
12/22/2004 ENABLEX
NDA #021513
4/18/2008 A 12/12/2008 A 10/19/2010 w
and
P, A
1213 1451 2127
12/28/2004 PRIALT NDA
#021060
4/18/2007 A
841
12/28/2004 CLOLAR
NDA #021673
10/17/2008 W,
P, A
1/10/2013 P, A 9/15/2014 W,
P, A
1389 2935 3548
12/29/2004 VENTAVIS
NDA #021779
8/24/2005 W,
P, A
3/4/2008 A 9/22/2008 A, P 238 1161 1363
12/30/2004 LYRICA NDA
#021446
6/21/2007 W,
P, A
4/23/2009 W, P 4/26/2011 A 903 1575 2308
03/16/2005 SYMLIN
NDA #021332
8/4/2008 A 6/27/2014 W, P, A 2/25/2015 W, P 1237 3390 3633
03/16/2005 MYCAMINE
NDA #021506
8/6/2007 P 1/22/2008 C, P, A 6/8/2011 A 873 1042 2275
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 165
03/29/2005 BARACLUDE
NDA #021797
2/23/2007 A 7/24/2007 B, P, W 6/3/2008 A 696 847 1162
04/28/2005 BYETTA
NDA #021773
10/12/2006 P, A 12/22/2006 P, A 1/11/2008 P 532 603 988
06/15/2005 TYGACIL
NDA #021821
7/12/2006 P, A 5/18/2007 W, P 1/29/2009 W,
P, A
392 702 1324
06/16/2005 LEVEMIR
NDA #021536
4/27/2012 W,
P, A
5/18/2012 P, A 3/9/2013 W, P 2507 2528 2823
06/22/2005 APTIVUS
NDA #021814
8/11/2006 B,
W,
A, P
5/14/2007 W 10/4/2007 C,
W,
P, A
415 691 834
07/07/2005 EXJADE
NDA #021882
4/20/2007 W,
A
12/21/2007 W, A 10/2/2008 W,
P, A
652 897 1183
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 166
07/22/2005 ROZEREM
NDA #021782
10/20/2008 C,
A, P,
W
11/9/2010 P
1186 1936
08/19/2005 NEVANAC
NDA #021862
08/30/2005 INCRELEX
NDA #021839
2/16/2011 C,
W,
P, A
6/14/2012 A 6/3/2014 A 1996 2480 3199
10/25/2005 HYDASE
NDA #021716
10/28/2005 ARRANON
NDA #021877
12/15/2009 W,
P, A
2/6/2012 A
1509 2292
12/01/2005 NEXAVAR
NDA #021923
3/5/2007 P, A 11/16/2007 W, P, A 10/26/2010 W,
P, A
459 715 1790
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 167
12/02/2005 HYLENEX
RECOMBINANT
NDA #021859
10/1/2008 P 1/21/2016 P
1034 3702
12/27/2005 REVLIMID
NDA #021880
6/29/2006 B,
W,
P, A
2/23/2009 P 3/12/2012 W, P 184 1154 2267
12/29/2005 VAPRISOL
NDA #021697
10/8/2008 C - P 5/27/2010 C, W and P 2/1/2012 W
and
P
1014 1610 2225
01/26/2006 SUTENT
NDA #021938
2/2/2007 W,
P, A
11/7/2008 A, W and P 7/1/2010 B,
W,
P, A
372 1016 1617
01/27/2006 RANEXA
NDA #021526
12/17/2007 P 11/5/2008 C, W, P, A 9/23/2010 P 689 1013 1700
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 168
01/31/2006 AMITIZA
NDA #021908
4/29/2008 C,
W,
P, A
10/11/2016 A, W and P
819 3906
02/17/2006 ERAXIS NDA
#021632
11/4/2010 A 7/20/2012 W, P
1721 2345
05/02/2006 DACOGEN
NDA #021790
05/10/2006 CHANTIX
NDA #021928
11/20/2007 P, A 1/31/2008 W, P 5/16/2008 W, P 559 631 737
05/16/2006 AZILECT
NDA #021641
12/9/2009 W, P 5/29/2014 W, P
1303 2935
06/23/2006 PREZISTA
NDA #021976
3/7/2008 W,
P, A
6/15/2009 P ( Drug
interactions)
4/26/2010 C, P 623 1088 1403
06/28/2006 SPRYCEL
NDA #021986
11/8/2007 W,
P, A
7/28/2010 A 10/28/2010 W, P 498 1491 1583
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 169
09/15/2006 NOXAFIL
NDA #022003
5/20/2008 C, P 2/19/2009 P 9/8/2010 W,
P, A
613 888 1454
10/06/2006 ZOLINZA
NDA #021991
9/23/2009 W, P
1083
10/16/2006 JANUVIA
NDA #021995
10/12/2007 C, P,
W,
A
7/22/2008 W, P 10/20/2008 A 361 645 735
10/20/2006 OMNARIS
NDA #022004
11/21/2007 P, A
397
10/25/2006 TYZEKA
NDA #022011
1/23/2009 W 3/4/2010 W, P 12/23/2011 C,
W, P
821 1226 1885
10/31/2006 VEREGEN
NDA #021902
12/19/2007 P, A
414
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 170
12/19/2006 INVEGA
NDA #021999
12/21/2007 W
and
P
5/16/2008 A 8/14/2008 B, W 367 514 604
02/23/2007 VYVANSE
NDA #021977
4/23/2008 W,
P, A
5/22/2009 A 4/5/2010 A 425 819 1137
03/05/2007 TEKTURNA
NDA #021985
8/7/2007 B,
W, P
2/15/2008 P 5/19/2008 P 155 347 441
03/13/2007 TYKERB
NDA #022059
8/20/2007 W,
P, A
7/7/2008 B, P, W, A 1/29/2010 C,
W,
P, A
160 482 1053
04/12/2007 ALTABAX
NDA #022055
9/28/2010 W, P 12/21/2012 W, P, A
1265 2080
05/09/2007 NEUPRO
NDA #021829
4/2/2012 W, P 2/26/2015 W, P, A
1790 2850
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 171
05/30/2007 TORISEL
NDA #022088
6/16/2011 W, P 4/7/2014 W, P, A 10/7/2014 A 1478 2504 2687
06/15/2007 LETAIRIS
NDA #022081
2/14/2008 W,
P, A
5/29/2009 W, P 7/1/2009 W, P 244 714 747
08/06/2007 SELZENTRY
NDA #022128
5/27/2010 C,
W, P
10/21/2011 B, W, P 8/10/2012 W, P 1025 1537 1831
08/23/2007 AMMONIA N 13
NDA #022119
08/30/2007 SOMATULINE
DEPOT NDA
#022074
11/27/2013 A 12/16/2014 W, P
2281 2665
10/12/2007 DORIBAX
NDA #022106
4/16/2009 W,
P, A
4/15/2013 A 1/17/2014 W, P 552 2012 2289
10/12/2007 ISENTRESS
NDA #022145
10/24/2008 A 1/13/2009 A 7/8/2009 A 378 459 635
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 172
10/16/2007 IXEMPRA KIT
NDA #022065
10/2/2009 W, P 5/12/2010 A 10/18/2011 P 717 939 1463
10/29/2007 TASIGNA
NDA #022068
8/21/2009 B,
W, P
6/17/2010 P 1/14/2011 W, P 662 962 1173
12/13/2007 KUVAN NDA
#022181
4/23/2014 W, P 6/13/2016 P, A
2323 3105
12/17/2007 BYSTOLIC
NDA #021742
2/19/2010 W, P
795
01/18/2008 INTELENCE
NDA #022187
9/15/2009 W,
P, A
2/23/2010 P 12/17/2010 A 606 767 1064
02/29/2008 PRISTIQ
NDA #021992
1/30/2009 W 8/31/2009 W, P, A 11/9/2009 A 336 549 619
03/20/2008 TREANDA
NDA #022249
4/22/2009 W, P 2/26/2010 W, P 12/21/2010 A 398 708 1006
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 173
04/10/2008 LEXISCAN
NDA #022161
3/17/2009 W,
P, A
12/23/2009 W, P, A 9/23/2011 W,
P, A
341 622 1261
04/24/2008 RELISTOR
NDA #021964
11/4/2009 A 7/23/2010 W, P, A 8/23/2013 W, P 559 820 1947
05/20/2008 ENTEREG
NDA #021775
11/6/2009 P 10/18/2013 B, P, W, A
535 1977
06/23/2008 DUREZOL
NDA #022212
7/29/2016 A
2958
07/03/2008 EOVIST NDA
#022090
12/20/2010 Bs,
P, W
11/16/2011 W, P, A 10/16/2013 C,
W, P
900 1231 1931
08/01/2008 CLEVIPREX
NDA #022156
12/8/2011 A
1224
08/15/2008 XENAZINE
NDA #021894
6/3/2015 A
2483
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 174
09/19/2008 ADREVIEW
NDA #022290
10/08/2008 RAPAFLO
NDA #022206
3/4/2010 W, P 7/12/2013 C, A
512 1738
10/28/2008 VIMPAT
NDA #022253
2/5/2013 A 4/17/2013 A 9/25/2013 W,
P, A
1561 1632 1793
10/31/2008 TOVIAZ NDA
#022030
2/10/2011 C,
W, P
11/1/2011 W, P 12/30/2011 A 832 1096 1155
11/14/2008 BANZEL
NDA #021911
6/25/2015 W,
P, A
2414
11/20/2008 PROMACTA
NDA #022291
2/25/2011 W, P 2/10/2014 B, P, W, A 4/7/2015 A 827 1908 2329
11/20/2008 NUCYNTA
NDA #022304
11/1/2010 A 7/11/2013 C, W, P, A 10/31/2013 A 711 1694 1806
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 175
12/12/2008 LUSEDRA
NDA #022244
12/15/2008 MOZOBIL
NDA #022311
6/4/2013 C,
W,
P, A
12/4/2014 A
1632 2180
12/22/2008 ABLAVAR
NDA #021711
12/20/2010 B,
W,P
8/7/2013 W, P
728 1689
12/24/2008 FIRMAGON
NDA #022201
3/5/2013 W, P 8/16/2013 A 2/26/2015 W -
P
1532 1696 2255
01/14/2009 SAVELLA
NDA #022256
2/1/2010 W 10/30/2012 P 12/6/2012 A 383 1385 1422
02/13/2009 ULORIC NDA
#021856
1/28/2011 C, P,
A
11/1/2012 W
714 1357
03/30/2009 AFINITOR
NDA #022334
7/9/2010 W,
P, A
5/5/2011 W, P, A 2/20/2014 W,
P, A
466 766 1788
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 176
04/07/2009 COARTEM
NDA #022268
8/6/2012 C,
W, P
4/29/2013 W, P 3/19/2015 A 1217 1483 2172
04/09/2009 ULESFIA
NDA #022129
05/06/2009 FANAPT
NDA #022192
12/1/2010 P 1/27/2012 W, P 1/31/2013 W,
P, A
574 996 1366
05/19/2009 SAMSCA
NDA #022275
2/1/2012 P 11/16/2012 W, P, A 4/9/2013 W,
P, A
988 1277 1421
05/28/2009 BESIVANCE
NDA #022308
07/01/2009 MULTAQ
NDA #022425
1/31/2011 P 2/11/2011 W, P, A 3/11/2011 P 579 590 618
07/10/2009 EFFIENT
NDA #022307
9/26/2011 W, P 11/30/2012 W, P 7/12/2016 P, A 808 1239 2559
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 177
07/31/2009 ONGLYZA
NDA #022350
11/15/2011 C,
A, P,
W
12/16/2011 W, P, A 5/24/2013 C, P,
A
837 868 1393
08/03/2009 LIVALO NDA
#022363
2/28/2012 W,
P, A
10/31/2012 W, P, A 10/16/2013 W, P 939 1185 1535
08/13/2009 SAPHRIS
NDA #022117
12/1/2010 P 8/9/2011 C, W, P, A 10/11/2011 A 475 726 789
08/21/2009 SABRIL NDA
#020427
12/11/2012 W, P 10/26/2013 A 4/3/2014 A 1208 1527 1686
08/21/2009 SABRIL NDA
#022006
12/11/2012 W, P 10/26/2013 A 4/3/2014 A 1208 1527 1686
09/08/2009 BEPREVE
NDA #022288
6/28/2012 C, A
1024
09/11/2009 VIBATIV
NDA #022110
12/3/2014 C,
W, P
1909
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 178
09/24/2009 FOLOTYN
NDA #022468
1/7/2011 W, P 5/30/2012 W, P, A 5/13/2016 P 470 979 2423
11/05/2009 ISTODAX
NDA #022393
9/30/2011 W, P 6/13/2013 P 10/15/2014 W,
P, A
694 1316 1805
11/16/2009 QUTENZA
NDA #022395
01/22/2010 AMPYRA
NDA #022250
1/22/2013 W, P 10/13/2016 A
1096 2456
01/25/2010 VICTOZA
NDA #022341
12/22/2010 A 4/6/2012 W, P, A 12/13/2012 A 331 802 1053
02/26/2010 VPRIV NDA
#022575
5/5/2015 W,
P, A
1894
03/18/2010 CARBAGLU
NDA #022562
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 179
03/30/2010 ASCLERA
NDA #021201
05/06/2010 NATAZIA
NDA #022252
2/13/2012 W, P
648
06/17/2010 JEVTANA KIT
NDA #201023
10/4/2012 B 3/14/2014 W, P, A 6/18/2015 C,
W, P
840 1366 1827
07/28/2010 LASTACAFT
NDA #022134
12/4/2014 C,
A, P,
W
9/30/2015 W, P, A
1590 1890
08/13/2010 ELLA NDA
#022474
5/2/2012 P 6/12/2014 W, P 3/10/2015 W, P 628 1399 1670
09/21/2010 GILENYA
NDA #022527
7/20/2011 W, P 5/9/2012 C, W, P, A 4/30/2014 W, P 302 596 1317
10/19/2010 PRADAXA
NDA #022512
3/4/2011 P 11/9/2011 W, P 1/17/2012 W, P 136 386 455
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 180
10/28/2010 LATUDA
NDA #200603
1/11/2017 B,
W,
A, P
2267
10/29/2010 TEFLARO
NDA #200327
8/31/2015 A 5/27/2016 A, W and P
1767 2037
11/10/2010 EGRIFTA
NDA #022505
11/15/2010 HALAVEN
NDA #201532
8/22/2013 A 8/1/2014 A 1/28/2016 W, P 1011 1355 1900
12/09/2010 SUCRAID
NDA #020772
11/20/2008 C
01/14/2011 DATSCAN
NDA #022454
01/18/2011 NATROBA
NDA #022408
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 181
01/21/2011 VIIBRYD
NDA #022567
12/21/2012 C,
W, P
12/17/2013 A 4/7/2014 A,
W, P
700 1061 1172
02/25/2011 EDARBI NDA
#200796
12/14/2011 B,
W, P
10/4/2012 C, P 4/18/2014 A 292 587 1148
02/28/2011 DALIRESP
NDA #022522
8/23/2013 W, P 11/24/2015 A
907 1730
03/14/2011 GADAVIST
NDA #201277
10/21/2013 C,
W, P
952
04/06/2011 HORIZANT
NDA #022399
12/26/2012 W, P 3/27/2013 W, P
630 721
04/06/2011 CAPRELSA
NDA #022405
10/9/2012 A 7/3/2013 A 3/31/2014 P 552 819 1090
04/28/2011 ZYTIGA NDA
#202379
7/3/2012 A 9/17/2012 A 12/10/2012 C,
W, P
432 508 592
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 182
05/02/2011 TRADJENTA
NDA #201280
5/22/2012 A, P 8/13/2012 W, P, A 9/28/2012 A 386 469 515
05/13/2011 VICTRELIS
NDA #202258
4/20/2012 P 7/30/2012 P 11/2/2012 C,
W,
P, A
343 444 539
05/20/2011 EDURANT
NDA #202022
8/10/2012 W, P 12/7/2012 W, P 6/21/2013 P 448 567 763
05/23/2011 INCIVEK
NDA #201917
3/22/2012 W,
P, C
6/22/2012 W, P 12/14/2012 Bs,
W
and
P, A,
C
304 396 571
05/27/2011 DIFICID NDA
#201699
4/4/2013 C,
W, P
678
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 183
06/10/2011 POTIGA NDA
#022345
9/6/2013 B,
W, P
5/26/2015 A, W and P 5/20/2016 Bs,
W
and
P, A,
C
819 1446 1806
07/01/2011 ARCAPTA
NEOHALER
NDA #022383
9/26/2012 C,
W,
P, A
453
07/01/2011 XARELTO
NDA #022406
1/7/2014 W, P 2/13/2014 P 3/6/2014 Bs,
W
and
P
921 958 979
07/20/2011 BRILINTA
NDA #022433
1/24/2013 C, A 3/29/2013 C, P, W. 12/13/2013 A 554 618 877
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 184
08/17/2011 ZELBORAF
NDA #202429
7/3/2013 W,
P, A
2/6/2014 W, P, A 3/19/2014 W, P 686 904 945
08/25/2011 FIRAZYR
NDA #022150
08/26/2011 XALKORI
NDA #202570
2/17/2012 W, P 10/7/2013 W - P 11/20/2013 W, P 175 773 817
10/14/2011 FERRIPROX
NDA #021825
2/24/2015 P
1229
10/21/2011 ONFI NDA
#202067
11/21/2013 W, P 12/9/2014 C, P, A 12/16/2016 B,
W,
P, A
762 1145 1883
11/16/2011 JAKAFI NDA
#202192
11/25/2013 w 7/25/2014 W, P 12/4/2014 W,
P, A
740 982 1114
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 185
01/23/2012 PICATO NDA
#202833
10/6/2015 C,
W,
P, A
9/13/2016 A
1352 1695
01/27/2012 INLYTA NDA
#202324
9/16/2013 A 8/1/2014 W, P
598 917
01/30/2012 ERIVEDGE
NDA #203388
5/21/2015 B,
W,
P, A
11/2/2016 W, P, A
1207 1738
01/31/2012 KALYDECO
NDA #203188
8/28/2012 A 12/29/2014 W, P 3/4/2015 P 210 1063 1128
02/10/2012 ZIOPTAN
NDA #202514
2/22/2013 A 9/4/2015 A
378 1302
03/06/2012 SURFAXIN
NDA #021746
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 186
03/14/2012 NATAZIA
NDA #022252
2/13/2012 W, P
03/27/2012 OMONTYS
NDA #202799
12/4/2012 C,
W, P
252
04/06/2012 AMYVID
NDA #202008
12/12/2013 A
615
04/27/2012 STENDRA
NDA #202276
4/29/2014 w, P 9/16/2015 C
732 1237
05/01/2012 ELELYSO
NDA #022458
8/27/2014 W,
P, A
6/15/2016 A 12/20/2016 A 848 1506 1694
06/27/2012 BELVIQ NDA
#022529
06/28/2012 MYRBETRIQ
NDA #202611
8/10/2015 W,
P, A
11/2/2015 A 8/16/2016 A 1138 1222 1510
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 187
07/16/2012 PREPOPIK
NDA #202535
07/20/2012 KYPROLIS
NDA #202714
3/27/2015 W, P 1/21/2016 W, P 8/4/2016 W,
P, A
980 1280 1476
07/23/2012 TUDORZA
PRESSAIR
NDA #202450
4/3/2015 W, P 3/16/2016 C, W, P, A
984 1332
08/27/2012 STRIBILD
NDA #203100
10/2/2013 W,
P, A
10/23/2013 W, P, A 12/17/2014 W,
P, A
401 422 842
08/30/2012 LINZESS
NDA #202811
7/9/2014 B -
C -
W -
P
8/31/2016 W, P 1/25/2017 Bs,
W
and
P, A,
C
678 1462 1609
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 188
08/31/2012 XTANDI
NDA #203415
8/5/2015 W, P 10/20/2016 W, P, A
1069 1511
09/04/2012 BOSULIF
NDA #203341
9/30/2013 P 11/25/2014 W, P 11/17/2016 A 391 812 1535
09/12/2012 AUBAGIO
NDA #202992
10/17/2014 W, P 6/2/2016 C, W, P, A 11/29/2016 Bs,
W
and
P, C
765 1359 1539
09/12/2012 CHOLINE C-11
NDA #203155
09/27/2012 STIVARGA
NDA #203085
5/29/2013 P 4/13/2015 A 6/7/2016 W, P 244 928 1349
10/22/2012 FYCOMPA
NDA #202834
6/30/2013 W, P 11/3/2016 W, P, A
251 1473
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 189
10/26/2012 SYNRIBO
NDA #203585
11/06/2012 XELJANZ
NDA #203214
3/26/2014 W,
P, A
6/19/2015 W, P 12/22/2015 W,
P, A
505 955 1141
11/29/2012 COMETRIQ
NDA #203756
5/20/2016 W, P
1268
12/14/2012 SIGNIFOR
NDA #200677
12/14/2012 ICLUSIG
NDA #203469
12/20/2013 B,
W, P
12/2/2015 W, P 6/2/2016 W,
P, A
371 1083 1266
12/21/2012 GATTEX KIT
NDA #203441
6/26/2014 A
552
12/21/2012 JUXTAPID
NDA #203858
4/10/2013 W, P 2/18/2014 P 8/8/2014 P 110 424 595
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 190
12/28/2012 ELIQUIS
NDA #202155
1/30/2014 P 6/16/2015 P 9/10/2015 A 398 900 986
12/28/2012 SIRTURO
NDA #204384
5/14/2015 B,
W,
A, P
12/9/2015 A
867 1076
12/31/2012 FULYZAQ
NDA #202292
01/25/2013 NESINA NDA
#022271
8/28/2015 W, P 4/5/2016 W, P 12/12/2016 W,
P, A
945 1166 1417
01/29/2013 KYNAMRO
NDA #203568
2/26/2015 A 5/23/2016 B, P, W, A
758 1210
02/08/2013 POMALYST
NDA #204026
4/23/2015 B,
W,
A, P
6/30/2016 P, A
804 1238
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 191
02/26/2013 OSPHENA
NDA #203505
2/25/2015 C, A
729
03/13/2013 LYMPHOSEEK
KIT NDA
#202207
03/20/2013 DOTAREM
NDA #204781
03/27/2013 TECFIDERA
NDA #204063
12/3/2014 C,
W, P
2/29/2016 W, P 1/19/2017 W,
P, A
616 1069 1394
03/29/2013 INVOKANA
NDA #204042
5/15/2014 P 3/3/2015 A 9/10/2015 W,
P, A
412 704 895
05/10/2013 BREO ELLIPTA
NDA #204275
3/2/2015 W, P 9/15/2015 A 2/16/2016 A 661 858 1012
05/15/2013 XOFIGO
NDA #203971
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 192
05/29/2013 TAFINLAR
NDA #202806
12/26/2013 A
211
05/29/2013 MEKINIST
NDA #204114
07/12/2013 GILOTRIF
NDA #201292
12/28/2015 A 4/15/2016 W, P 10/4/2016 A 899 1008 1180
08/12/2013 TIVICAY
NDA #204790
5/12/2014 P 12/19/2014 A 8/5/2015 A, P 273 494 723
09/30/2013 TRINTELLIX
NDA #204447
7/17/2014 W,
P, A
8/30/2016 A 10/17/2016 A 290 1065 1113
10/03/2013 DUAVEE
NDA #022247
10/08/2013 ADEMPAS
NDA #204819
5/6/2014 P 1/17/2017 C
210 1197
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 193
10/18/2013 OPSUMIT
NDA #204410
4/30/2015 A 2/17/2016 A 6/15/2016 A 559 852 971
10/25/2013 VIZAMYL
NDA #203137
12/4/2014 A
405
11/08/2013 APTIOM
NDA #022416
11/13/2013 IMBRUVICA
NDA #205552
1/29/2015 W, P 5/6/2016 A 6/28/2016 A 442 905 958
11/14/2013 LUZU NDA
#204153
11/22/2013 OLYSIO NDA
#205123
9/5/2014 P 4/10/2015 W, P, A 10/5/2015 P, A 287 504 682
12/06/2013 SOVALDI
NDA #204671
11/14/2014 W, P 3/20/2015 W, P, A 8/19/2015 W, P 343 469 621
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 194
12/18/2013 ANORO ELLIPTA
NDA #203975
2/24/2016 A
798
01/08/2014 FARXIGA
NDA #202293
8/8/2014 P 12/4/2015 W, P 6/14/2016 C,
W,
P, A
212 695 888
01/31/2014 HETLIOZ
NDA #205677
02/18/2014 NORTHERA
NDA #203202
10/3/2016 C -
W -
P -
A
958
03/19/2014 NEURACEQ
NDA #204677
8/25/2016 A
890
03/19/2014 IMPAVIDO
NDA #204684
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 195
03/21/2014 OTEZLA
NDA #205437
04/29/2014 ZYKADIA
NDA #205755
7/22/2015 W,
P, A
449
05/08/2014 ZONTIVITY
NDA #204886
05/23/2014 DALVANCE
NDA #021883
12/18/2015 A
574
06/06/2014 JUBLIA NDA
#203567
06/20/2014 SIVEXTRO
NDA #205435
07/03/2014 BELEODAQ
NDA #206256
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 196
07/07/2014 KERYDIN
NDA #204427
07/23/2014 ZYDELIG
NDA #205858
9/21/2016 B,
W,
P, A
791
07/23/2014 ZYDELIG
NDA #206545
9/21/2016 B,
W,
P, A
791
07/31/2014 STRIVERDI
RESPIMAT
NDA #203108
08/01/2014 JARDIANCE
NDA #204629
12/4/2015 W, P 7/8/2016 W, P 12/2/2016 W,
P, A
490 707 854
08/06/2014 ORBACTIV
NDA #206334
1/20/2016 C,
W, P
10/17/2016 W, P
532 803
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 197
08/13/2014 BELSOMRA
NDA #204569
08/19/2014 CERDELGA
NDA #205494
09/16/2014 MOVANTIK
NDA #204760
8/22/2016 W,
P, A
706
09/23/2014 OTEZLA
NDA #206088
10/10/2014 LUMASON
NDA #203684
12/22/2016 W, P
804
10/10/2014 AKYNZEO
NDA #205718
10/10/2014 HARVONI
NDA #205834
3/20/2015 W,
P, A
11/12/2015 C, W, P, A
161 398
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 198
10/15/2014 ESBRIET
NDA #022535
1/11/2017 W, P
819
10/15/2014 OFEV NDA
#205832
12/17/2014 XTORO NDA
#206307
12/19/2014 LYNPARZA
NDA #206162
10/19/2016 W, P 1/26/2017 W, P, A
670 769
12/19/2014 RAPIVAB
NDA #206426
8/12/2016 C -
W -
P -
A
602
01/08/2015 SAVAYSA
NDA #206316
9/10/2015 A 9/15/2016 W, P
245 616
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 199
02/03/2015 IBRANCE
NDA #207103
02/13/2015 LENVIMA
NDA #206947
4/22/2016 W, P 5/13/2016 W, P
434 455
02/23/2015 FARYDAK
NDA #205353
6/6/2016 W, P
469
02/25/2015 AVYCAZ
NDA #206494
6/22/2016 P, A 1/26/2017 W, P, A
483 701
03/06/2015 CRESEMBA
NDA #207500
03/17/2015 CHOLBAM
NDA #205750
04/15/2015 CORLANOR
NDA #206143
1/10/2017 W,
P, A
636
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 200
04/29/2015 KYBELLA
NDA #206333
05/27/2015 VIBERZI
NDA #206940
06/22/2015 KENGREAL
NDA #204958
07/02/2015 ORKAMBI
NDA #206038
5/18/2016 W, P 9/28/2016 A
321 454
07/07/2015 ENTRESTO
NDA #207620
07/10/2015 REXULTI
NDA #205422
9/23/2016 W, P
441
07/24/2015 ODOMZO
NDA #205266
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 201
07/24/2015 DAKLINZA
NDA #206843
08/18/2015 ADDYI NDA
#022526
09/01/2015 VARUBI
NDA #206500
09/04/2015 XURIDEN
NDA #208169
09/17/2015 VRAYLAR
NDA #204370
09/22/2015 LONSURF
NDA #207981
09/25/2015 TRESIBA
NDA #203314
12/16/2016 A
448
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 202
10/05/2015 ARISTADA
NDA #207533
8/18/2016 W,
P, A
318
10/21/2015 VELTASSA
NDA #205739
10/23/2015 YONDELIS
NDA #207953
7/20/2016 W,
P, A
271
11/05/2015 GENVOYA
NDA #207561
9/7/2016 W,
P, A
9/15/2016 C 12/7/2016 W,
P, A
307 315 398
11/10/2015 COTELLIC
NDA #206192
5/31/2016 W, P
203
11/13/2015 TAGRISSO
NDA #208065
11/20/2015 NINLARO
NDA #208462
11/23/2016 W,
P, A
369
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 203
12/11/2015 ALECENSA
NDA #208434
11/4/2016 W, P
329
12/15/2015 BRIDION
NDA #022225
12/21/2015 UPTRAVI
NDA #207947
12/22/2015 ZURAMPIC
NDA #207988
02/18/2016 BRIVIACT
NDA #205836
03/30/2016 DEFITELIO
NDA #208114
04/29/2016 NUPLAZID
NDA #207318
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 204
04/11/2016 VENCLEXTA
NDA #208573
05/27/2016 OCALIVA
NDA #207999
05/27/2016 AXUMIN
NDA #208054
06/01/2016 NETSPOT
NDA #208547
06/28/2016 EPCLUSA
NDA #208341
07/11/2016 XIIDRA NDA
#208073
07/27/2016 ADLYXIN
NDA #208471
THE EFFECT OF SHORTER REVIEW TIMES ON DRUG SAFETY INFORMATION 205
09/19/2016 EXONDYS 51
NDA #206488
12/23/2016 SPINRAZA
NDA #209531
Key: A: Adverse reactions, W: Warnings, P: precautions, C: Contraindications, B: Boxed warning
The effect of shorter review times on drug safety information
Appendix J
Drugs for Which the Safety Database was Obtained Through Review of
the Medical Review Section on the FDA Website.
1. ELESTAT NDA #021565
2. FASLODEX NDA #021344
3. REMODULIN NDA #021272
4. LUMIGAN NDA #021275
5. COLAZAL NDA #020610
6. NOVOLOG NDA #020986
7. MYLOTARG NDA #021174
8. LANTUS NDA #021081
9. TYGACIL NDA #021821
10. NEVANAC NDA #021862
11. HYDASE NDA #021716
12. DACOGEN NDA #021790
13. VEREGEN NDA #021902
14. TORISEL NDA #022088
15. DUREZOL NDA #022212
16. ULESFIA NDA #022129
17. CARBAGLU NDA #022562
18. SUCRAID NDA #020772
19. ZYTIGA NDA #202379