Transcript Where are we now? - kitasato

Bridging Update
in KOREA
In-Jin Jang, MD
Seoul National University College of Medicine and Hospital
Bridging Concept and
Regulatory Changes in Korea
Major regulatory changes
since 1999

Adoption of the Bridging Concept
: effective since June 2001

Separation of IND from NDA
: Participation in international study enabled
since December 2002
Bridging Concept

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“Bridging Data” = “Korean Data”
“Bridging Study” = “A trial conducted in Korean”
“Bridging Data” means data on the results of trials conducted in
Koreans living home and abroad, which are excerpted or selected
from the clinical data package or obtained from the bridging study.
“Bridging Study” means a trial conducted in Koreans in Korea for the
purpose of obtaining bridging data in case it is difficult to apply the
foreign clinical data as it is because there is a difference in an ethnic
factor relating to the safety and efficacy of a drug.
New Product Approval
New Product
Candidate
At least ONE Bridging Study
in KOREAN
(Global or Local)
7 waiver
categories
Bridging Exemption
Bridging Waiver Category
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
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


Orphan drugs
Drugs for life-threatening diseases
Diagnostic reagents
No systemic effect
Proven ethnic insensitivity
New drugs being developed inside or outside of Korea
that are intended to conduct clinical trials in Korea
Other drugs given waiver by KFDA
Status of Bridging Waiver
Waiver Category
No ethnic difference
Antibiotic / Antiviral
/ Antithrombotic
(2000- Sep.2003)
Product Name (Company)
Zyvox (Pharmacia)
Tamiflu (Roche)
Arixtra (Sanofi-Synthelabo)
Invanz (MSD)
AIDS, Cancer, or Life-threatening Cancidas (MSD)
disease
Vfend (Pfizer)
Asperogilosis / Cancer / HIV
TS1 (Che-il, Taiho)
Iresa (AstraGeneca)
Crixivan (MSD)
Status of Bridging Waiver(2000-Sep.2003)
-continued
Category
Product Name (Company)
Orphan Drugs
Zometa (Novartis)
Visudyne (Novartis)
Agrylin (Yu-han)
Diagnostic Reagents ,
Radio-phacmaceuticals
Optimac (I-yeon)
Teseos (Sang-jung)
No systemic effect
Dermal cream etc.
Vaniqa (BMS), Olcenon (Yu-han),
Renagel (Che-il), Tazorac (Daewoong), Herepair (Bo-ryung),
Elidel (Novartis), Travatan (Alcon),
Seoptanest (Sin-won)
Bridging Experience
Increased Number of Clinical Trials
KFDA database
Local
Multi
120
100
30
80
60
17
40
18
57
45
20
42
42
42
28
27
`99
`00
`01
3
1
`90
38
31
18
0
67
5
`91
`92
`93
`94
`95
`96
`97
`98
`02
`03.9
Increased Number of Multinational
Clinical Trials (Dec. 2002 ~ Sep. 2003)
KFDA database

Approved drugs for label change;
 29
protocol, 21 drugs
 28 Phase III & 1 Phase II studies

Unapproved new drugs;
 Potential
bridging data generation
 39 protocols, 20 compounds
 22 Phase III, 6 Phase II & 1 Phase I studies
Reduced KFDA Review Time
KFDA database
140
120
100
days
80
60
40
20
1998
1999
2000
2001
2002
2003
year
Recent Bridging Studies
(Sep. 2002 ~ Jul. 2003)
KFDA database
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Nine products (10 protocols) got IND’s for bridging studies
Phase III; 6 protocols
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Phase I; 4 protocols
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Antibiotic, Antiepileptic, Antirheumatic (Biological), Osteoporosis Rx.,
Lipid lowering drug, Anticoagulant
Antihistamine, CV biological drug, Lipid lowering drug, Antibiotic
Seven protocols from domestic sponsors for product
licensing-in from Japan and Italy (1)
Approved products by PK bridging
Company
Product
Active
Ingredient
Indication
Glaxowelcome Avandia
Rosiglitazone
maleate
Oral hypoglycemic
agent (Diabetes )
Glaxowelcome Lotronex
Alosetron HCL
Irritable bowel syndrome
Lilly
Actos
Pioglitazone
Oral hypoglycemic
agent (Diabetes )
Bayer
Levitra
Vardenafil
PDE5 inhibitor
Novartis
Zelmac
Tegaserod
Irritable bowel syndrome
* Ten more drugs are under PK bridging study
- Five in review or reporting process
- Five in study or protocol development process
Bridging Issues in Korea

Acceptability of Asian Data
 Asian; Same ethnicity ?
 Mutual recognition of Asian

data ?
Statistics
 Statistically meaningful sample size ?
 Multinational study; subgroup analysis

Many study design issues
 Similarity ? What
 Titration drug
 Placebo

?
metric?
Need more scientific and flexible design & review
 Bayesian,
Mixed effect modeling, Simulation,
Pharmacogenomics, etc.