A
abbreviated new drug application (ANDA) pathway 7
Abreva
direct-to-OTC 31 innovation for 152
prescription market equity 19 safety and efficacy data for 44
active and implantable medical devices. See also devices
actual use studies (AUS) 9 FDA requirement for 43 Oxytrol for Women 107 Prilosec OTC 70, 74
primary behavioral measures in 43 adapalene gel. See Differin Gel (adapalene)
switch
adjudication process (mitigation) 108 Advil
approved by NDAs 23 brand equity 14 retail value of 20
Advisory Committee (ADCOM) meetings Differin (adapalene) Gel meeting 131, 133 first-in-class Rx-to-OTC switches 31 first-in class switches 77
for intranasal steroid switch 137 for OTC statins 87
for Plan B 52, 55 for Singulair 42
in switch process 35, 46, 91 lovastatin switch 84 Mevacor summary 90 Oxytrol 115–117
Pravachol switch 84 pravastatin hearing 86
Prilosec OTC 63, 67, 68, 71, 75 Questran (cholestyramine) switch 82 switch votes by 47
age-based distinction for marketing product 58 allergy Rx-to-OTC switches
brands launched 17. See also intranasal steroids (INS) switch
sales volume from switch 16, 17
Singulair Allergy enchanced DFL warning 42 switch effects for 13
antismoking products. See nicotine replacement therapy (NRT)
approval pathways for switch
centralized process in EU/RoW 162 decentralized procedure in EU/RoW 162 development of 8
full vs. partial switch 34 monograph process 32 new or supplemental NDA 31 Australia
asthma inhalers in 163
pharmacist-only medications in 163 switch process 163
B
brand equity value
consumer benefits in building 19 Nexium 24HR 19
patent expiration effects on 20 Rx brand trademark in switch 19
Index
C
Center for Drug Evaluation and Research (CDER) review divisions 34 China
combined oral contraceptive (COC) 174 switch process 163
cholesterol management. See lipid management switch
Cialis (tadalafil)
commercial value of switch 18 partnering for switch 27 Claritin
new indication for 23 retail sales of 20
clinical trials 9. See actual use studies (AUS) combination product regulatory pathways. See
also constituent parts consumer behavior studies
actual use studies 9–11 Ome-MG 70 execution of 124–130 for support of switch 8–11 human factors studies 9–11 issues addressed 181
label comprehension studies 8–11 self-selection studies 8–11
Consumer Healthcare Products Association (CHPA)
public health benefits of switch 13–29 survey on role of OTC drugs 1, 4 consumer unmet need
erectile dysfunction treatment 170 Oxytrol 17
Plan B (levonorgestrel) case study 51 Prilosec OTC 65
Questran (cholestyramine) 83
Consumer Use Study of Over-the-Counter Mevacor (CUSTOM) 87
controlled access 51 Controloc 162
Convenient Access Responsible Education (CARE) 59
D
data exclusivity with Rx-to-OTC switch 7 Denmark 165, 166
Differin Gel (adapalene) switch 44, 121
Advisory Committee meeting and preparation 131
consumer behavior studies actual use study 126–127 label comprehension study 125 targeted self-selection study 128 DFL comparison with representative acne
product 124 FDA review 130–131 history of adapalene 122–123 indications for switch 121–123 initial FDA meeting 123 NDAC vote on switch 133 package communication of 21 safety demonstrations for 44 supplemental NDA submission 129 supporting the launch 134
timeline of 123 direct-to-OTC 31
Division of Nonprescription Drugs I (DNPD I) 34
Division of Nonprescription Drugs II (DNPD II) 34
Drug Enforcement Agency (DEA), purchase limits 32
Drug Facts label (DFL) decision-making based on 31
Mevacor OTC “Self-Management System” 88 rule for standardized labeling 2
Durham-Humphrey Amendment 2, 5, 31
E
emergency contraception (EC). See Plan B (levonorgestrel) case study
emergency hormonal contraception (EHC) 172.
See also Plan B (levonorgestrel) case study Plan B introduction 173
reclassification of 172–178 single hormone use for 172 switch dynamics 175
Endocrine and Metabolic Drugs Advisory Committee (EMDAC) 84
enterochromaffin-like cells (ECL) 64 erectile dysfunction (ED) 169
counterfeit product use 170 defined 169
OTC product utilization 169 potential value of switch 18 esomeprazole (Nexium Control) 162
ethinylestradiol/norgestrel (Schering PC4) 172
European Medicines Agency (EMA) approved switches 161
European Union/rest of world (EU)/RoW) switches 161
advanced switch markets 163
EMA centralised switch approvals 161 pharmacist-only medicine requirements 162 prescription exemption mechanism 163 regulatory framework for reclassification 175 study requirements for 162
switch supply model options 163 variations in switch activity 165
F
first-in-class switch
consideration for success of 18 Oxytrol for women 17 Flonase 16, 21
Food and Drug Administration (FDA) guidance for consumer use studies 9 jurisdiction for switches 34–49 OTC labeling requirements 2
full switch. See Rx-to-OTC switch process
G
generally recognized as safe and effective (GRASE) 6, 32
general sales list (GSL) status effect on switch in US 165 in EU/RoW 162
Germany
for asymptomatic and chronic conditions 166 sumatriptan approval 162
switch process 163
ulipristal acetate vs.EHC switch 173
Gyne-Lotrimin, normalization/destigmatization of disease 14
H
H2 receptor antagonists (H2RAs) commercial success of 21
Rx-to-OTC switches of 168–178 Harm Reduction Therapeutics (HRT) 44 Hatch-Waxman era 7
HIV pre-exposure prophylaxis (PrEP) medication 33
HRA Pharma, acutal use study in US 175
I
Imodium
prescription vs. OTC sales 20 India, EHC market in 174 indications for switch
consumer unmet need omeprazole 65 Oxytrol 17 Plan B 51–62
Questran (cholestyramine) 83
innovation in welll-established category 121 public health rationale for INS 142–159 Instructions for Use (IFU) validation 44 intranasal steroids (INS) switch 15, 137. See
also allergy Rx-to-OTC switches commercial strategies 152–159 DFL highlights 149
lifecycle management of prescription products manufacturing/supply chain challenges 139
151–159 market volume of 16 need for 137–145
OTC launch insights 155–159 OTC market for allergy products 143,
140–145
prescription market history 137–145 public health rationale 142–145 regulatory strategies and challenges 145 retail sales of switch products 155 strategic decision-making framework 146 Ireland, switch process 163
J
Japan
for chronic and asymptomatic conditions 167 study requirements in 162
switch process 163
Johnson and Johnson (J&J), OTC development 87
L
label comprehension studies (LCS) 8 Differin (adapalene) Gel 125 fold-out back panel use 92 Oxytrol for Women 102 Prilosec OTC 73
Rapid assessment of adult literacy in medicine (realm) for 53
switch requirements 180 labeling
CARE program for Plan B 59 comprehension studies 8–11
consumer-facing translation for switch 182 optimizes commercial potential 180 sample drug facts label 2
levonorgestrel. See emergency hormonal contraception (EHC)
lipid management switch
5th Panel Self-Selection Labeling Aid 93 Advisory Committee 2000 deliberations/
outcomes 87
category for Rx-to-OTC switch 81–98 commercial value of switch 18
FDA negative guidance on switch category 84 generating stakeholder support 91–98
in self-care environment 82 Mevacor back panel label 90 Mevacor system 89
Pfizer/Lipitor (2015) 94 praachol switch program 86 professional treatment guidelines 82 scientific and medical rational for 81 statins as switch candidates
defining target population 83 safety topics to address 83 statins round three at FDA 91
switch program for Questran (cholestyramine) targeted population CUSTOM study 9182 technology-enabled labeling paradigm 93 Lipitor (atorvastatin) 18
M
masking of disease concerns 75 maximal use (MuST) studies 44
MEDDEV. See guidance documents/guidelines Medical Device Regulation (EU MDR). See EU
Medical Device Regulation (EU MDR) medical devices. See devices
medicinal products. See drugs/medicinal products
Medicines Health and Regulatory products Agency (MHRA)
process for switch 163
UK regulator 162 Merck and Co., Inc.
CUSTOM study 87 Nasonex switch 16
Mevacor/Merck statin switch 84
Advisory Committee summary for (2005) 90 CUSTOM study for OTC development
87–98
SELECT study (2007) 91–98
studies supporting lovastatin switch 84 Mevacor OTC “Self-Management System”
(MOTC-SMS) 88 Mucinex, brand equity of 20
Multicenter Assessment of Transdermal Therapy in Overactive Bladder with Oxybutynin TDS 103
N
Nasonex (mometasone) 16 new drug application (NDA)
efficacy supplement for switch 8 Rx-to-OTC switches with 7 New Zealand
contraceptive access in 174 progressiveness in switch 165 sildenafil switch support in 172 switch process 163
nicotine replacement therapies (NRT) 4, 13 commercial value of 17
Rx-to-OTC switch effects 17
nicotine replacement therapy (NRT) 17 Nonprescription Drugs Advisory Committee
Oxytrol for Women 99, 106
Nonprescription Drugs Advisory Committee (NDAC)
FDA convened meeting of 46 Oxytrol for Women decisions 115 Questran (cholestyramine) 82 switch votes of 47
Nonprescription Drug Safe Use Regulatory Expansion (NSURE) initiative 61, 183 Nonprescription Safe Use Regulatory Expansion
(NSURE) 51 Nycomed 162
O
Office of Nonprescription Drugs (ONPD) review divisions of 34
omeprazole magnesium (Ome-Mg). See Prilosec (omeprazole magnesium) OTC
order of entry theory product success and 16 Orlistat (Alli, GSK in 2009) 162 OTC drug review process
monograph process failures 31 OTC Monograph Process
CARES Act reform of 32
GRAS/E concept in switches 6–11
overactive bladder (OAB) 99. See Oxytrol for Women
over-the-counter (OTC) drugs/medicines accessibility of allergy medicines 183 benefits of
access 3 affordability 4
consumer education 14 cost-effectiveness of 14 empowerment and trust 5 for consumer usage 5 characteristics 33
consumer and healthcare system affordability consumer trust of 184184
creation of new categories 5 defined 1–11
first-in-class switch challenges 77 historical eras of 31
1950s–early 1970s 6–11 1970-1980s 6–11 1984–Today 7 IRI value study on 4
Nonprescription Safe Use Regulatory Expansion 10
safety/efficacy requirements 2 sample drug facts label 2
oxybutynin. See Oxytrol for Women oxybutynin transdermal system 17, 99 Oxytrol for Women
actual use studies
adjudication process (mitigation) 108 combined endpoint analysis 112 control 107–108
description of subjects 109–115 primary endpoint 108
primary endpoint analysis 110–115 recruitment 107–108
recruitment and enrollment 109 secondary endpoint analysis 110–115 secondary endpoints 108
Advisory Committee meeting description of subjects 115–117 commercial failure of 20
CONTROL study 112–115 allergic reactions 114 anticholinergic effects 114 bladder cancer risk factors 114 common adverse events 112–115 conclusions from 115
deaths and discontinuations 112 disorientation and confusion 115 falls and accidents 115
gastric retention and glaucoma risks 114 possible urinary tract infection symptoms risk factors for diabetes 114113
serious adverse events 112 urinary retention 113
Drug Facts Label development 118 benefit-risk assessment 118 early consumer testing 100–101 end of Phase 2 meeting 102 indications for switch 99–101 label comprehension studies
diabetes warnings 104
enhanced pregnancy warning 103 full label comprehension 104 pivotal comprehension study 104 safety and risk communication 101 self-diagnosis/selection 101 pre-IND meeting for 99–101
pre-NDA meeting and filing 115–117 prescription market size 17
self-selection studies
targeted, in pregnant women 106 targeted self-selection (men) 106 stage 2 consumer studies 103
P
Pantazole 162 pantoprazole 162 partial switch
prescription product availability 35
sponsor decision on 8
PDE5 inhibitors. See erectile dysfunction (ED) Peck’s Principles 7
Pepcid 20
Plan B. See also emergency hormonal contraception (EHC)
Plan B (levonorgestrel) case study 51, 172 advance provision studies for 56 Advisory Committee meeting 55 AUS study 54–62
consumer unmet need 51 educational program for 59 empowering of women 14 full access battle for 59
label comprehension results by age 53 label comprehension study 53 other behavioral studies for 55–62 Plan B One-Step approval 60 political influence in approval 58–62 public policy/advocacy 52–62
quest for Plan B One-Step OTC approval 60–62
reasons for non-approval 55–62 regulatory history of 52–62 survey summary for 58 Poland
restriction of EHC in 173 reversal of switch 162 sildenafil switch in 171
Pravachol/BMS (2000) statin switch 84 studies supporting pravastatin switch 86 prescription medicines
allergy brands launched by switch 17 to nonprescription status 1
Prevacid
prescription vs. OTC sales 19 spending to build awareness 20 Prilosec (omeprazole magnesium) OTC
Black Box warning 66 building awareness for 19 case study
actual use trial 74
consumers with infrequent heartburn 74 FDA concerns 72
label comprehension study 73
second Advisory Committee meeting 75 consideration in switch
Black Box warning 65–80 considerations for switch 65
Category C for pregnancy 67 dosage form 66–80
minimum effiectiv edose 67 drug-induced hypergastrinemia 75 FDA concerns
brand name confusion 77 comments 71, 74
first Advisory Committee meeting 71 prevention or treatment of heartburn 76 product sampling during launch 77 time to action concerns 76
yearly courses of therapy 76
frequency of switches in 1998-2000 64 genotoxicity and tumororigenicity concerns 75 H2RAs and omeprazole mechanisms of action heartburn prevention studies 69, 68–80, 70, 7265 heartburn treatment studies 68
history of switch 63
length of treatment concerns 75
proposed indications and development plan 68 state of switch in 2000 63–80
unique mechanism of 64 unmet consumer need 63–80
principal display panel (PDP) for communication proton pump inhibitors (PPIs)21
brands launched by switch 19
prescription vs. nonprescription indications 19 Prilosec OTC case study 63–80
purchase decision 92
R
Rapid Assessment of Adult Literacy in Medicine (REALM)
in self-selection studies 129 label comprehension studies 53 real-world data use 162
rest of world (RoW) switches 161 reverse switches 161
Rhinocort brand awareness in switch 19 Rx-to-OTC switch
criteria for switch 183
Rx-to-OTC switch process 1. See also approval pathways for switch
approval if benefits outweigh risks 47 as lifecycle management strategy 14, 179 assessing category dynamics 17
assessing the value of
ability to execute at retail 24–29 high performing team 25–29 strategy implications for 25
barriers and enablers to switches 16, 165 benefits of 13–29
branded vs. private label sales 18 business models for 26
case history of H2RAs 169 commercial success of 14
comparison of enablers and barriers 167 elapsed approval times 46
emergency hormonal contraception 172–178 enhanced DFL warning 42
entry order vs current sales rank 23 erectile dysfunction case study 169–178 evaluating the value of candidates for 13 FDA guidance for sponsor studies 45–49 FDA input on proposed development 45–49 FDA input on proposed NDA 45–49 FDA jurisdiction for 34–49
first-in-class switch 77
for asymptomatic and chronic conditions 166–178
frequency in 1998-2000 64
full vs. partial switches 8, 34–49, 35–49 innovation in an established category 121 in US 31
issues for successful switch program 181–185 lipid management in the US 81
Lotrimin Ultra Pictogram 38
medicines for chronic and prophylactic use 166 models for self-selection tests 183
naming approaches used in 41
OTC Naloxone DFL created by FDA 40 Oxytrol for Women 99
partnerships for 26
PERT/PERS charts for 182 philosophy of 32–49
potential switch supply models 164
pricing premiums for waves of innovation 22 principles for switch candidates 7
proposed development plan 39–49 retail sales of branded 20
sponsor creates DFL 36 sponsor decision on 8
sponsor files NDA with PDUFA timing 46–49
studies and parameters measured 36
therapeutic categories (2020) 16 therapeutic categories for 6 tools for evaluation of 181
value tree method for benefit assessment 33 Voltaren Arthritis Pain Outer Carton 39 Voltaren Arthritis Pain Pictogram 39 Rx-to-OTC switch value
ability to innovate 23–29
Advil products approved by NDA 23 allergy brands and retail sales 17 allergy treatments 15
branded vs. private label smoking cessation products 18
brands launched via switch 15 building awareness for 19–29 building equity 19
category size 14–29
entry order effects on 22–29 evaluating the candidate 13 factors in commercial success
brand equity 19 ease of use 21
pricing on new products 22 spending to build awareness 20 unmet consumer needs 21 media spends for 20 new innovation pricing 22 NSAs vs. INSs retail sales 18 order of entry effects 23
PPI brands launched as result of switch 19 prescription and consumer health business
models 26
side effects and repeat use 22
therapeutic categories in retail sales 16 volume sources for recent switches 17 Rx-to-OTC swith value
consumer awareness 19
S
Scandinavian Simvastatin Survival Study 83 science of switch 8
SELECT study
purchase decision (PD) 92 self-assessment (SA) decision 92
self-care environment. See also self-management effects of COVID-19 on 10
evolution of 1
lipid management switch 82
self-care pyramid 3
Self-Diagnosis/Self-Selection Study Oxytrol for Women 101
Self-Evaluation of Lovastatin to Enhance Cholesterol Treatment (SELECT) 92 self-management. See also self-care environment
acne 122
decisions for lipid management 92–94 for cholesterol treatment 92
for lipids/cholessterol 81 technology as tool for 183 self-selection studies (SSS) 8
Differin Gel (adapalene) switch 128 Differin Gel OTC package warning 129 for Oxytrol 101
Oxytrol in pregnant women 106 Oxytrol label warning for men 106 Serious Adverse Events (SAEs), Oxytrol for
Women 112
sildenafil. See also erectile dysfunction (ED) barriers to access of 170
centralized switch of 171 in European market 170 overall utilitzation of 169
single shelf keeping unit (SKU) vs. “billboard”
Somac 16223 sumatriptan
EU/Row switch 162 UK switch 165
Sweden, influences on switch 166
T
Tagamet 20, 21
U
Ulipristal acetate 30mg (ellaOne, HRA Pharma) under the counter (UTC) puchases 162162
United Kingdom (UK)
contraceptive advertising in 174 desogestrel (DSG) prescription in 174
emergency hormonal contraceptive licensed in prescription and nonprescription schedules in 172 reclassification for access 163, 165163
Zocor (simvastatin) switch 18
V
Viagra 169. See sildenafil
W
World Health Organization (WHO), criteria for contraceptive access 174
Z
Zantac 20
Zegerid brand equity at switch 19
