Transcript VICH Task Force for Efficacy Studies for Combination Products

VICH
members
JMAFF (chair)
K. Noda
JVPA
E. Oishi
IFAH-EU
M. Bobey
EU
K. Healey
US FDA
C. Groesbeck
AHI
B. McKusick
Observer
South Africa, Nat. Dept. health
V. Naidoo
VOF
members
China PR, IVDC
S. Xu
Argentina, SENASA
L. Sbordi
Taiwan, Council of Agriculture
T-R. Jan
UEMOA
K.Th. Domagni
CAMEVET
L. Sbordi
VICH Task Force for Efficacy
Studies for Combination
Products
Progress Report for the 31th SC /5th VOF meeting
Charges
 To elaborate a discussion paper
describing a more focused scope
for the development of a guideline
for efficacy studies for combination
products
<<< Concept paper from China
 The TF will
 Prioritize the target products >Explore Major combination
 Explore the possibility of
a general policy document >Analyse GLs already in Place
Part 1
Major Combination
How to categorize the products?
Code
Categorization elements
Antiparasitics
Antimicrobials
Anthelmintics
AP-Hl
Antiprotozoals
AP-Pr
Ectoparasiticides
AP-Ec
Endectocides
AP-EnEc
Other Antiparasitics
AP-X
Antibacterials
AM-Bc
Antimycotics
AM-Mc
Antivirals
Intramammary
antibacterials
Other Antimicrobials
AM-Vr
AM-IM-Bc
AM-X
Anti-inflammatories
AI
Antiseptics
AS
Disinfectants
(others, if any)
DI
X
Major combination-products
VICH members
Combination-category
AP-Hl
AP-Pr
AP-Ec
AP-EnEc
AP-Hl
AP-Pr
AP-Hl
AP-Ec
AP-Hl
AP-x
AP-EnEc
AP-x
AM-Bc
AM-Mc
AM-Vr
AM-IM-Bc
AM-Bc
AM-Mc
AM-IM-Bc
AM-Bc
AMAM-Bc
AI
Mc
AM-Bc
AI
AM-Bc
AP-Pr
AM-Bc
Hormones
AI
AS
AS
DI
DI
Vitamins
Vitamins
Minerals
Gastrointestinal
Hormones
Cardiology
Total / legislation
Total / member status
JMAFF
1
1
1
1
JVPA
EU
Observer
IFAH-EU US FDA
1
1
1
AHI
S.Africa
1
1
1
1
1
1
1
1
1
1
1
1
1
1
ChinaPR
1
1
1
1
1
VOF members
Argentina/
Taiwan UEMOA
CAMEVET
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
3
1
1
1
1
1
5
2
1
2
0
1
1
1
1
1
2
2
1
1
1
1
1
1
1
1
1
10
1
4
1
10
1
10
45
Subtotal
6
3
5
6
2
2
2
1
8
0
0
3
0
1
6
5
0
0
5
7
16
4
0
61
Total
27
12
8
3
2
0
1
1
1
1
1
2
2
61
30
25
20
15
10
5
0
Major Combination-products
Specific consideration
 A TF member insisted not to include AM combination as a target
category for the putative product type specific GL.
 The EU (SC) delegate indicated not to support the development of
an AM combination GL.
 Regulators do not wish to encourage new developments of the
AM combination.
 A VICH GL on such combination products could be misunderstood
as encouragement for their development.
Ingredients : Antiparasitics
Combination
category
AP-Hl
AP-Pr
JMAFF+JVPA
AP-EnEc
AP-Hl
AP-Hl
AP-Pr
AP-Ec
AP-Hl
AP-x
APEnEc
AP-x
US FDA+AHI
ChinaPR
Argentina/CAMEVET
Ivermectin+pyrantel,
Praziquantel+pyrantel+febantel Ivermectin+clorsulon,
Praziquantel+pyrantel+febant Pyrantel+febantel,
MilbemycinOxime+praziq
el,
Praziquantel+fenbendazole,
uantel,
Emodepside+praziquantel, Derquantel+abamectin,
Emodepside+praziquantel,
Moxidectin+triclabendazole, Febantel+praziquantel+pyr
Emodepside+praziquantel,
antel
Sulfadimethoxine,
pyrimethamine,
Glycarbylamide, dinitolmide,
Fiproni+amitraz+(s)methoptrene,
Imidacloprid+moxidectin,
AP-Ec
EU+IFAH-EU
Febantel+praziquantel+
pyrantel
Amprolium+ethopabate,
Sulfaquinoxaline,
Indoxacarb+permethrin,
Fipronil+(S)-methoprene,
Fipronil+amitraz+(S)Fipronil+cyphenothrin,
methoprene,
Dinotefuran+permethrin+pyripr
oxyfen,
Metaflumizone+amitraz,
Imidacloprid+flumethrin,
Fipronil+permethrin,
MillbemycinOxime+lufenuron Imidacloprid+moxidectin,
,
Spinosad+milbemycin ,
MilbemycinOxime+spinosad, MilbemycinOxime+Lufenuron,
Ivermectin+pyrantel
Closantel+mebendazole,
Closantel+ivermectin,
Praziquantel+ivermectin,
Eprinomectin+fipronil+praziqua
ntel+(S)-methoprene,
Amprolium+ethopabate
+sulfaquinoxaline,
Imidacloprid+permethrin
+piperonyl butoxide,
Cipermethrin+ethion,
Ivermectin+praziquantel,
Ivermectin+clorsulon,
Imidacloprid+Ivermectin,
MilbemycinOxime+
lufenuron,
MilbemycinOxime+lufenur
on+praziquantel,
Imidacloprid+moxidectin,
Ivermectin+pyrantel
Emodepside+toltrazuril,
Emodepside+praziquantel,Narasin+nicarbazin,
Ivermectin+albendazole,
Fipronil+methoprene+am
itraz,
MilbemycinOxime+lufenur
on+Praziquantel,
MilbemycinOxime+lufenur
on,
Taiwan
Pyrantel+fenbendazole+
praziquantel,
Albendazole+praziquant
el,
Ivermectin+clorsulon,
Ivermectin+nitroxinil,
Ivermectin+abamectin,
Category
Ingredients
Clorsulon + Ivermectin
Derquantel + Abamectin
Emodepside + Praziquantel
AP-Hl
(Anthelmintic)
Fenbendazole + Praziquantel
Febantel + Pyrantel
Febantel + Praziquantel + Pyrantel
Ivermectin + Pyrantel
Milbemycinoxime + Praziquantel
Moxidectin + Triclabendazole
AP-Pr
(AntiProtozoal)
Amprolium + Ethopabate + Sulfaquinoxaline
Dinitolmide + Glycarbylamide
Pyrimethamine + Sulfadimethoxine
Amitraz + Fipronil + (S)-methoprene
Amitraz + Metaflumizone
Cipermethrin + Ethion
Dinotefuran + Permethrin + Pyriproxyfen
AP-Ec
Cyphenothrin + Fipronil
(Ectoparasiticides) Fipronil + (S)-methoprene
Fipronil + Permethrin
Flumethrin + Imidacloprid
Imidacloprid + Moxidectin
Imidacloprid + Permethrin + Piperonyl Butoxide
Indoxacarb + Permethrin
No. of Country/Region
1
1
3
1
1
4
1
1
1
2
1
1
1
1
1
1
1
1
1
1
1
1
1
Category
Ingredients
Closantel + Ivermectin
Closantel + Mebendazole
Clorsulon + Ivermectin
Eprinomectin + Fipronil + Praziquantel + (S)-methoprene
AP-EnEc
(Endectocides)
AP-Hl
AP-Pr
AP-Hl
AP-Ec
AP-Hl
AP-x
AP-EnEc AP-x
Imidacloprid + Ivermectin
Imidacloprid + Moxidectin
Ivermectin + Pyrantel
Ivermectin + Praziquantel
Milbemycin + Spinosad
Millbemycinoxime + Lufenuron
Milbemycinoxime + Lufenuron + Praziquantel
Milbemycinoxime + Spinosad
Emodepside + Toltrazuril
Emodepside + Praziquantel
Fipronil + Methoprene + Amitraz
Ivermectin + Albendazole
Narasin + Nicarbazin
Albendazole + Praziquantel
Fenbendazole + Praziquantel + Pyrantel
Milbemycinoxime + Lufenuron,
Milbemycinoxime + Lufenuron + Praziquantel
Abamectin + Ivermectin
Clorsulon + Ivermectin
Ivermectin + Nitroxinil
No. of Country/Region
1
1
1
1
1
2
2
2
1
3
1
1
1
1
1
1
1
1
1
1
1
1
1
1
Part 2
Guidelines in Place
Guidelines/Guidance in Place
Item
#1
Title
Guidance on pharmaceutical fixed
combination products
Product
Category
General
(EMEA/CVMP/83804/05)
#2
#3
#4
#5
#6
Questions and answers on the
CVMP guideline on fixed
combination products
(EMEA/CVMP/83804/2005)
AP
Type of document
Technical requirement guideline
Additional document to #1
European Legislation
(EU Directive 2001/82/EC ),
(p16)Art 13b
General
Legal basis for #1 an #2
CVM GFI #24 Drug Combinations
for Use in Animals
General
Technical requirement guideline
WAAVP guideline:
Anthelmintic combination products
targeting nematode infections of
ruminants and horses
AP
Australian Pesticide and Veterinary
Medicine Agency: Preamble for
WAAVP guideline: Combination
anthelmintic products for ruminants
and horses
AP
Technical requirement guideline
Governmental statement to adopt WAAVP GL
Technical Requirement GLs in Place
Item
#1
Title
Guidance on
pharmaceutical
fixed combination
products
Category
Scope
General
EU data requirements for efficacy, safety
and residues documentation for veterinary
medicinal products, containing 2 or more
active substances.
General
Information and data to demonstrate that
the combination of drugs provides a
benefit that cannot be obtained by the use
of each of the drugs individually
#4
CVM GFI #24 Drug
Combinations for
Use in Animals
#5
•
•
WAAVP guideline:
Anthelmintic
combination
products targeting
nematode infections
of ruminants and
horses
AP
•
A scientific basis for the approval
Anthelmintic products with two or more
constituents with similar spectra of
activity from different pharmacological
classes
For use in addition to the existing
requirements/GLs for single-API
products.
Structure –General GLsParts
Introductory
part
#1: EMEA/CVMP/83804/05
 Introduction (background)
 Scope
 Legal Basis
Discussion
part
 Justification of the Combination
 Interactions
 Indications
 Potential Advantages
• Improvement of activity
• Broadening of the activity spectrum
• Use of a combination product versus
combined use of single substances
 Risk-Benefit assessment
Dossiers
Requirements
part
 General requirements
 New fixed combination products
 Combination products that meet the
criteria for well established use
 Combination products that meet the
criteria for generic application
 Specific Requirements
 Specific requirements for safety and
residues documentation
 Specific requirements for preclinical
and clinical documentation
(Preclinical data, Dose-finding, Tolerance,
Clinical data, Resistance, Exceptions)
#4: FDA/ CVM GFI #24
 Introductory statement






Non-Interference
Rational
Titration
Ranges
General Efficacy
Combination Claims and
Treatment Comparisons
(very in detail)
Structure –AP GL –
Parts
Introductory part
Discussion part
#5: WAAVP/Australia
 Introduction (general)
 Combining anthelmintics: current situation
 Objectives of the anthelmintic combination guideline
 Rationales for the use of anthelmintic combination products
• Managing existing resistance
• Delaying anthelmintic resistance
• Specific targeting of dose-limiting species
• Maximizing breadth of spectrum
 Concerns about fixed-dose anthelmintic combination products
• Drug–drug interactions
• Common mechanisms of resistance
• Best-practice management of combination anthelmintics
Dossiers
Requirements
part
 Justification for the combination
 Dose determination data on the anthelmintic constituent actives in the
combination
 Target animal safety and pharmacokinetic data showing noninterference and acceptable safety
 Product bioequivalence
 Dose confirmation studies
 Field efficacy studies
Question from a member:
Issues to be elaborated In the
General GLs : Remit of VICH?
Issues
a)
A combination product will be applied, only after
approval of the each constituent as new API.
b)
Drug interaction:
• impact on the metabolism of each API
• potential to aggravate the toxicity to target animal
C) Consumer safety:
• residue depletion/withdrawal period
d) Development of resistance
e) Discussion and
Dossiers requirement
yes
no
Conclusion
 Main target combination Product: Anti-Parasitics
 General combination GL
 EU(#1) and US(#4) GLs are the representative General GLs.
 It would be practical to create an internationally harmonized
new GL by extracting appropriate elements from these GLs.
 The major discussion points: handling of “Safety” elements
and “Dossier Requirement” part exist in #1.
 AP combination GL
 Central proposition: Control of Drug Resistance
 Inclusion of the WAAVP(#5) GL into the VICH framework
would reasonably be explored further in collaboration with
the Anthelmintic GLs TF.
Future work
 Based on the progress and discussion at the 31th
SC/5th VOF, the TF will develop a formal discussion
paper with full data submitted by the TF members
and relevant references.
 To complete a global catalogue of major
combination products, the TF wishes to include inputs
from UEMOA and Australia/New Zealand.
Thank you
感謝