the effect of shorter review times on drug safety

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


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.


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


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


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).


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.


Research question

Do faster NDA reviews sacrifice products safety information?


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


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


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


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.


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


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).


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).


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


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.


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%


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).


d) Warnings (95% CI -11.4941 to 15.3296, Chi-squared 0.087, DF 1, P = 0.7683).


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).


d) Warnings (95% CI -1.7514 to 28.4280, Chi-squared 3.329, DF 1, P = 0.0681).



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


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


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


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.


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.


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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


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


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


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


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


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


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


Table 1.1.2

z-Test: Two Sample for Means for comparison of the time to safety labeling changes

across standard and priority reviews.


Mean (days) 869.5029586 852.8278689

Known Variance 293576.3705 601404.8875



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


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



t Stat 1.056205048

P(T<=t) one-tail 0.147832675


P(T<=t) two-tail 0.29566535



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


z 1.056205048

P(Z<=z) one-tail 0.145437272


P(Z<=z) two-tail 0.290874545



Table 1.2.3

t-Test: Two-Sample Assuming Unequal Variances for comparison of time to safety


Standard vs accelerated (without similarities) Standard accelerated

Mean (days) 864.7310345 738.3030303

Variance 292955.0174 437488.8428

Observations 145 33



t Stat 1.022858295

P(T<=t) one-tail 0.156115245


P(T<=t) two-tail 0.31223049



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


z 1.022858295

P(Z<=z) one-tail 0.153187425


P(Z<=z) two-tail 0.30637485



Table: 1.3.1


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



t Stat -1.191910791

P(T<=t) one-tail 0.11788578


P(T<=t) two-tail 0.23577156



Table 1.3.2


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


z -1.191910791

P(Z<=z) one-tail 0.116648113


P(Z<=z) two-tail 0.233296227



Table 1.3.3



Standard vs Orphan (similarities removed) Standard Orphan

Mean (days) 864.7310345 1033.186441

Variance 292955.0174 952401.9819

Observations 145 59



t Stat -1.24995311

P(T<=t) one-tail 0.107654521


P(T<=t) two-tail 0.215309041



Table 1.3.4


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


z -1.24995311

P(Z<=z) one-tail 0.105658338


P(Z<=z) two-tail 0.211316677



Table 2.1.1


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



t Stat 1.722909062

P(T<=t) one-tail 0.043249219


P(T<=t) two-tail 0.086498438



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


z 1.722909062

P(Z<=z) one-tail 0.042452486


P(Z<=z) two-tail 0.084904971



Table 2.2.1



Second SLC for standard vs accelerated Standard Accelerated

Mean (days) 1522.057143 1248.09375

Variance 757627.7233 636867.5071

Observations 140 32



t Stat 1.721925713

P(T<=t) one-tail 0.045695434


P(T<=t) two-tail 0.091390869



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


z 1.721925712

P(Z<=z) one-tail 0.042541488


P(Z<=z) two-tail 0.085082976



Table 2.2.3



Second SLC for standard vs accelerated (without

similarities)

Standard Accelerated

Mean (days) 1539.918033 1262.821429

Variance 776854.8858 727108.078

Observations 122 28



t Stat 1.540952815

P(T<=t) one-tail 0.065505891


P(T<=t) two-tail 0.131011783



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)


Mean (days) 1539.918033 1262.821429

Known Variance 776854.8858 727108.078

Observations 122 28


z 1.540952815

P(Z<=z) one-tail 0.061664135


P(Z<=z) two-tail 0.12332827



Table 2.3.1



Second SLC for standard vs orphan Standard Orphan

Mean (days) 1522.057143 1476.534483

Variance 757627.7233 898993.2356

Observations 140 58



t Stat 0.314800153

P(T<=t) one-tail 0.376787957


P(T<=t) two-tail 0.753575915



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


z 0.314800153

P(Z<=z) one-tail 0.376456698


P(Z<=z) two-tail 0.752913395



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



t Stat 0.164149114

P(T<=t) one-tail 0.435082741


P(T<=t) two-tail 0.870165483



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


z 0.164149114

P(Z<=z) one-tail 0.434806879


P(Z<=z) two-tail 0.869613759



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



t Stat 2.199372175

P(T<=t) one-tail 0.014566407


P(T<=t) two-tail 0.029132814



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


z 2.199372175

P(Z<=z) one-tail 0.013925735


P(Z<=z) two-tail 0.027851469



Table 3.2.1


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



t Stat 1.110062108

P(T<=t) one-tail 0.136251248


P(T<=t) two-tail 0.272502497



Table 3.2.2

z-Test: Two sample for means for comparison of the time to the third safety


Third SLC for standard vs

accelerated


Mean (days) 1837.09009 1633.115385

Known Variance 1091882.519 622116.1862

Observations 111 26


z 1.110062108

P(Z<=z) one-tail 0.133486132


P(Z<=z) two-tail 0.266972264



Table 3.2.3


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



t Stat 1.056528769

P(T<=t) one-tail 0.148456268


P(T<=t) two-tail 0.296912536



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


z 1.056528769

P(Z<=z) one-tail 0.145363352


P(Z<=z) two-tail 0.290726704



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



t Stat 1.307147891

P(T<=t) one-tail 0.097175503


P(T<=t) two-tail 0.194351007



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


z 1.307147891

P(Z<=z) one-tail 0.095581244


P(Z<=z) two-tail 0.191162489



Table 3.3.3


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



t Stat 0.912377848

P(T<=t) one-tail 0.182775924


P(T<=t) two-tail 0.365551847



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


z 0.912377848

P(Z<=z) one-tail 0.180784923


P(Z<=z) two-tail 0.361569847



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


Mean (number of patients) 2392.004739 1299.471698

Variance 6267061.224 4201541.263




t Stat 4.611589063

P(T<=t) one-tail 2.76826E-06


P(T<=t) two-tail 5.53652E-06



Table 5.2

z-Test: two sample for means for comparison of size of the safety database

across standard and priority drugs



Known Variance 6267061.224 4201541.263



z 4.611589063

P(Z<=z) one-tail 1.99801E-06


P(Z<=z) two-tail 3.99602E-06



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


Variance 6267061.224 247201.2063

Observations 211 47



t Stat 9.77957351

P(T<=t) one-tail 1.09385E-19


P(T<=t) two-tail 2.1877E-19



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




t Stat 8.8893016

P(T<=t) one-tail 3.04205E-17


P(T<=t) two-tail 6.08411E-17



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


Significance level P = 0.8385


Table 7.1.2

Boxed warnings in the

second SLC

Standard Priority


Sample size 140 97

Difference 3.65%

95% CI -

2.5993 to 11.1349

Chi-squared 1.581



Table 7.1.3

Boxed warnings in the

third SLC

Standard Priority


Sample size 111 75

Difference 8.61%

95% CI -0.5136 to 16.8829

Chi-squared 3.975




Table 7.2.1

contraindications in the

first SLC

Standard Priority


Sample size 169 122

Difference 3.31%

95% CI -5.3073 to 11.3623

Chi-squared 0.667



Table 7.2.2

contraindications in the

second SLC

Standard Priority


Sample size 140 97

Difference 5.64%

95% CI -3.0678 to 13.5837

Chi-squared 1.923




Table 7.2.3

Contraindications in the

third SLC

Standard Priority


Sample size 111 75

Difference 2.84%

95% CI -8.0709 to 12.6442

Chi-squared 0.331



Table 7.3.1

warnings in the first SLC Standard Priority


Sample size 169 122

Difference 3.31%

95% CI -8.7442 to 15.1913

Chi-squared 0.312




Table 7.3.2

warnings in the second SLC Standard Priority


Sample size 140 97

Difference 1.95%

95% CI -11.4941 to 15.3296

Chi-squared 0.087



Table 7.3.3

warnings in the third SLC Standard Priority


Sample size 111 75

Difference 13.66%

95% CI -1.7514 to 28.4280

Chi-squared 3.329

DEGREES OF FREEDOM 1



Table 7.4.1

precautions in the first SLC Standard Priority


Sample size 169 122

Difference 6.64%

95% CI -4.2090 to 16.9815

Chi-squared 1.587



Table 7.4.2

precautions in the second SLC Standard Priority


Sample size 140 97

Difference 3.79%

95% CI -8.3530 to 16.2510

Chi-squared 0.401




Table 7.4.3

precautions in the third SLC Standard Priority


Sample size 111 75

Difference 0.40%

95% CI -13.9014 to 14.1007

Chi-squared 0.003



Table 7.5.1

1st for Adverse reactions Standard Priority


Sample size 169 122

Difference 1.30%

95% CI -10.7299 to 13.2150

Chi-squared 0.048




Table 7.5.2

2nd for Adverse reactions Standard Priority


Sample size 140 97

Difference 0.43%

95% CI -12.7694 to 13.3724

Chi-squared 0.004



Table 7.5.3

adverse reaction in the third

SLC

Standard Priority


Sample size 111 75

Difference 4.94%

95% CI -

9.2563 to 19.4299

Chi-squared 0.502




Appendix F

Summary of Drugs Characteristics in the Database


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


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


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


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


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


12/25/2016


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


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


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


12/26/2016

12/22/2000 STARLIX

NDA #021204


12/26/2016


01/26/2001 CANCIDAS

NDA #021227

Priority 623 Antibiotic yes

12/26/2016

02/28/2001 RAZADYNE

NDA #021169


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


05/07/2001 AXERT NDA

#021001


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


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


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


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


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


04/25/2002 BENICAR

NDA #021286


1/1/2017

04/25/2002 FASLODEX

NDA #021344


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


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


12/20/2002 EXTRANEAL

NDA #021321

Standard 493 GU yes Orphan 1/1/2017

12/26/2002 RELPAX

NDA #021016


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


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


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


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


BLUE) NDA

#021626

cesium/non radioactive

lethium

10/16/2003 NAMENDA

NDA #021487


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


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


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


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



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


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


1/3/2017

12/16/2004 VISIONBLUE

NDA #021670

Priority an aid in ophthalmic

surgery

no

1/3/2017


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


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


1/8/2017

06/16/2005 LEVEMIR

NDA #021536


1/8/2017

06/22/2005 APTIVUS

NDA #021814

Priority 1854 antiviral NO Accelerated

approval

1/8/2017


07/07/2005 EXJADE

NDA #021882

Priority 700 chronic iron overload yes Orphan -

Accelerated

1/8/2017

07/22/2005 ROZEREM

NDA #021782


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


Accelerated

1/8/2017


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


01/27/2006 RANEXA

NDA #021526


1/8/2017

01/31/2006 AMITIZA

NDA #021908


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


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


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


1/8/2017

02/23/2007 VYVANSE

NDA #021977


1/14/2017

03/05/2007 TEKTURNA

NDA #021985


1/14/2017

03/13/2007 TYKERB

NDA #022059

Priority 3500 cancer yes

1/14/2017


04/12/2007 ALTABAX

NDA #022055

Standard 2115 Antibiotic NO

1/14/2017

05/09/2007 NEUPRO

NDA #021829


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


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


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


12/17/2007 BYSTOLIC

NDA #021742

Standard 6545 CVS no

1/14/2017

01/18/2008 INTELENCE

NDA #022187


approval

1/14/2017

02/29/2008 PRISTIQ

NDA #021992


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


05/20/2008 ENTEREG

NDA #021775


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


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


10/08/2008 RAPAFLO

NDA #022206

Standard 897 BPH, GU NO

1/14/2017

10/28/2008 VIMPAT

NDA #022253


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


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


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


03/30/2009 AFINITOR

NDA #022334


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


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


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


1/15/2017

08/21/2009 SABRIL NDA

#020427

Standard 4079 CNS yes Orphan 1/15/2017



#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


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


01/22/2010 AMPYRA

NDA #022250

Priority 400 Multiple Sclerosis No Orphan 1/15/2017

01/25/2010 VICTOZA

NDA #022341


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


06/17/2010 JEVTANA KIT

NDA #201023


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


1/16/2017


10/29/2010 TEFLARO

NDA #200327


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


01/21/2011 VIIBRYD

NDA #022567


1/21/2017

02/25/2011 EDARBI NDA

#200796


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



04/28/2011 ZYTIGA NDA

#202379

Priority 1070 cancer NO

1/21/2017

05/02/2011 TRADJENTA

NDA #201280


1/22/2017

05/13/2011 VICTRELIS

NDA #202258

Priority 2095 antiviral NO D/C 1/22/2017

05/20/2011 EDURANT

NDA #202022


1/22/2017

05/23/2011 INCIVEK

NDA #201917

Priority 1797 antiviral no

1/22/2017

05/27/2011 DIFICID NDA

#201699


1/22/2017


06/10/2011 POTIGA NDA

#022345


1/22/2017

07/01/2011 ARCAPTA

NEOHALER

NDA #022383

Standard 2516 Respiratory No

1/22/2017

07/01/2011 XARELTO

NDA #022406


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)



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


01/30/2012 ERIVEDGE

NDA #203388


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


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


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


1/29/2017

08/30/2012 LINZESS

NDA #202811


1/29/2017

08/31/2012 XTANDI

NDA #203415


1/29/2017

09/04/2012 BOSULIF

NDA #203341

Standard 546 Cancer yes Orphan 1/29/2017


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


10/22/2012 FYCOMPA

NDA #202834


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


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


12/14/2012 ICLUSIG

NDA #203469


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


1/29/2017


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


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


1/29/2017

05/15/2013 XOFIGO

NDA #203971


1/29/2017


05/29/2013 TAFINLAR

NDA #202806


05/29/2013 MEKINIST

NDA #204114


07/12/2013 GILOTRIF

NDA #201292


08/12/2013 TIVICAY

NDA #204790


2/4/2017

09/30/2013 TRINTELLIX

NDA #204447


2/4/2017

10/03/2013 DUAVEE

NDA #022247

Standard 6210 Gynecologic no

2/4/2017


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


2/4/2017

11/13/2013 IMBRUVICA

NDA #205552


Accelerated

2/4/2017

11/14/2013 LUZU NDA

#204153

Standard 616 antifungal yes

2/4/2017


11/22/2013 OLYSIO NDA

#205123


2/4/2017

12/06/2013 SOVALDI

NDA #204671


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


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


Accelerated

2/4/2017

05/08/2014 ZONTIVITY

NDA #204886


2/4/2017

05/23/2014 DALVANCE

NDA #021883


2/4/2017


06/06/2014 JUBLIA NDA

#203567

Standard 1227 Antifungal yes

2/4/2017

06/20/2014 SIVEXTRO

NDA #205435


2/4/2017

07/03/2014 BELEODAQ

NDA #206256


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


Accelerated

2/4/2017


07/31/2014 STRIVERDI

RESPIMAT

NDA #203108


2/4/2017

08/01/2014 JARDIANCE

NDA #204629

Standard 1976 diabetes - Endocrine yes

2/5/2017

08/06/2014 ORBACTIV

NDA #206334


2/5/2017

08/13/2014 BELSOMRA

NDA #204569


2/5/2017

08/19/2014 CERDELGA

NDA #205494

Priority 126 Gaucher disease yes orphan 2/5/2017

09/16/2014 MOVANTIK

NDA #204760


2/5/2017


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


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


Break

through

12/17/2014 XTORO NDA

#206307

Priority 618 Antibiotic no

2/5/2017

12/19/2014 LYNPARZA

NDA #206162


Accelerated

2/5/2017

12/19/2014 RAPIVAB

NDA #206426


2/5/2017

01/08/2015 SAVAYSA

NDA #206316


2/5/2017

02/03/2015 IBRANCE

NDA #207103

Priority 755 cancer yes Accelerated

approval

2/5/2017


02/13/2015 LENVIMA

NDA #206947


02/23/2015 FARYDAK

NDA #205353


Accelerated

2/5/2017

02/25/2015 AVYCAZ

NDA #206494


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


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


2/5/2017

07/10/2015 REXULTI

NDA #205422


2/5/2017


07/24/2015 ODOMZO

NDA #205266

Standard 229 cancer yes

2/5/2017

07/24/2015 DAKLINZA

NDA #206843


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


2/5/2017


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


2/5/2017


11/10/2015 COTELLIC

NDA #206192

Priority 247 cancer yes orphan 2/5/2017

11/13/2015 TAGRISSO

NDA #208065


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


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


12/22/2015 ZURAMPIC

NDA #207988

Standard 1021 gout yes

2/5/2017

02/18/2016 BRIVIACT

NDA #205836


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


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


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


12/23/2016 SPINRAZA

NDA #209531

Priority 173 spinal muscular atrophy yes

2/5/2017


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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



CALCIUM

TRISODIUM

NDA #021749

8/4/2005 P

358


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


#020427

12/11/2012 W, P 10/26/2013 A 4/3/2014 A 1208 1527 1686


#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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


20. TUDORZA PRESSAIR NDA #202450

21. IBRANCE NDA #207103

the effect of shorter review times on drug safety

Documents