#111 
Effectiveness of Anthelmintics: 
Specific Recommendations for Canines 
VICH GL19 
Guidance for Industry 
Draft Guidance 
This guidance document is being distributed for comment purposes only. 
This version of the guidance replaces the version made available June 2002.  This revision   
clarifies the definition of adequate infection in individual animals, updates considerations for 
field studies, and makes additional clarifying changes. 
Submit comments on this draft guidance by the dated provided in the Federal Register notice 
announcing the availability of the draft guidance.  Submit electronic comments to 
https://www.regulations.gov.  Submit written comments to the Dockets Management Staff 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD  
20852.  All comments should be identified with docket number FDA-2022-D-1494. 
For further information regarding this document, contact Aimee Phillippi-Taylor, Center for 
Veterinary Medicine (HFV-114), Food and Drug Administration, 7500 Standish Place, Rockville 
MD 20855, 240-402-0601, email: aimee.phillippi-taylor@fda.hhs.gov. 
Additional copies of this draft guidance document may be requested from the Policy and 
Regulations Staff (HFV-6), Center for Veterinary Medicine, Food and Drug Administration, 
7500 Standish Place, Rockville MD 20855, and may be viewed on the Internet at 
https://www.fda.gov/animal-veterinary, https://www.fda.gov/regulatory-information/search-fda-
guidance-documents, or http://www.regulations.gov. 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Veterinary Medicine (CVM) 
August 2022  
 
VICH GL19 (ANTHELMINTICS: CANINES) 
May 2022 
Revision at Step 9 
For consultation at Step 4 
 
 
 
E A :  
FFICACY OF  NTHELMINTICS  
S R  
PECIFIC  ECOMMENDATIONS
C  
FOR  ANINES
(R 1) 
EVISION 
 
 
 
 
 
Revision at Step 9 
Recommended for Consultation at Step 4 of the VICH Process 
in May 2022 
by the VICH Steering Committee 
 
 
 
 
 
This Guidance has been developed by the appropriate VICH Expert Working Group will be subject to 
consultation by the parties, in accordance with the VICH Process.  At Step 7 of the Process the final draft 
is recommended for adoption to the regulatory bodies of the European Union, Japan and USA. 
 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
 
Table of Contents 
 
I.  Introduction .......................................................................................................................... 1 
A.  General Elements ........................................................................................................... 2 
1.  The Evaluation of Effectiveness Data .................................................................... 2 
2.  Use of Natural or Induced Infections ..................................................................... 2 
3.  Number of Infective Parasitic Forms Recommended for Induced Infections .... 3 
4.  Recommendations for the Calculation of Effectiveness ....................................... 3 
4.1.  Factors to Support a Claim ............................................................................ 3 
4.2.  Number of Animals (Dose Determination, Dose Confirmation and 
Persistency Studies) ........................................................................................ 4 
4.3.  Adequacy of Infection ..................................................................................... 4 
4.4.  Label Claims .................................................................................................... 4 
5.  Treatment Procedures ................................................................................................ 5 
6.  Animal Selection, Allocation and Handling.............................................................. 6 
B.  Specific Evaluation Studies .............................................................................................. 6 
1.  Dose Determination Studies ....................................................................................... 6 
2.  Dose Confirmation Studies ........................................................................................ 6 
3.  Field Effectiveness Studies ......................................................................................... 6 
4.  Persistent Effectiveness Studies ................................................................................. 6 
 
 
i 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
Effectiveness of Anthelmintics: Specific Recommendations for 
Canines 
 
VICH GL19 
 
Draft Guidance for Industry 
 
This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
Administration (FDA or Agency) on this topic.  It does not establish any rights for any person 
and is not binding on FDA or the public.  You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations.  To discuss an alternative approach, 
contact the FDA staff responsible for this guidance as listed on the title page. 
 
I.  Introduction 
The present guidance for canines was developed by the Working Group established by the 
International Cooperation on Harmonisation of Technical Requirements for Registration of 
Veterinary Medicinal Products (VICH), Anthelmintic Guidances, and subsequently revised in 
2022.  It should be read in conjunction with Guidance for Industry (GFI) #90 (VICH GL7), 
Effectiveness of Anthelmintics: General Recommendations,1 which should be referred to for 
discussion of broad aspects for providing pivotal data to demonstrate product anthelmintic 
effectiveness.  The present document is structured similarly to GFI #90/VICH GL7 with the aim 
of simplicity for readers comparing both documents. 
 
The aim of this canine guidance is: (1) to be more specific for certain specific canine issues not 
discussed in GFI #90/VICH GL7; (2) to highlight differences with GFI #90/VICH GL7 on 
effectiveness data recommendations; and (3) to give explanations for disparities with GFI 
#90/VICH GL7. 
 
It is also important to note that technical procedures to be followed in the studies are not the aim 
of this guidance.  We recommend that sponsors refer to the pertinent procedures described in 
detail in other published documents, e.g., World Association for the Advancement of Veterinary 
Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of anthelmintics for dogs and 
cats. Veterinary Parasitology 52: 179-202, 1994, and updated versions as they are published.  
 
The contents of this document do not have the force and effect of law and are not meant to bind 
the public in any way, unless specifically incorporated into a contract.  This document is 
intended only to provide clarity to the public regarding existing requirements under the law.  
FDAs guidance documents should be viewed only as recommendations, unless specific 
regulatory or statutory requirements are cited.  The use of the word should in Agency guidances 
means that something is suggested or recommended, but not required. 
 
1 https://www.fda.gov/media/70349/download 
 
1 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
 
A.  General Elements 
1.  The Evaluation of Effectiveness Data 
The evaluation of effectiveness data is based on parasite counts (adults, larvae) in dose 
determination and dose confirmation studies.  Egg counts/larval identification should be the 
preferred method to evaluate effectiveness in field studies. 
 
The controlled test is the most widely accepted of the testing procedures for evaluation of 
anthelmintic drug effectiveness.  However, the critical test may be appropriate for some 
intestinal species of parasites, e.g., ascarids. 
 
Adequate parasite infection should be defined in the protocol according to regional prevalence or 
historical data and/or statistical analysis. 
 
2.  Use of Natural or Induced Infections 
Dose determination studies should be conducted using induced infections with either laboratory 
strains or recent field isolates. 
 
Dose confirmation studies should be conducted using naturally- or artificially-infected animals.  
Where possible, at least one study should be conducted in naturally-infected animals.  An 
explanation should be provided if this is not possible, e.g., applicable laws or regulations prohibit 
sourcing of naturally-infected animals.  Two studies should be conducted for each parasite 
claimed on the label.  If both studies are conducted using experimentally-infected animals, then 
parasites should originate from naturally-occurring infections from different geographical 
regions no older than 10 years prior to use for inducing infection.  In addition to two dose 
confirmation studies, effectiveness and safety is generally confirmed by data from field studies.  
Echinococcus spp. and Dirofilaria spp. testing may be conducted using animals harboring 
induced infections due to public health considerations for echinococcosis and the complexity of 
the claims for heartworm.  Due to the zoonotic potential of Echinococcus spp., trials conducted 
using this genus should be carried out under high biosecurity provisions. 
 
For the following helminths, induced infections may also be the only available method to 
determine effectiveness of the product because of difficulties in obtaining a sufficient number of 
infected animals: Filaroides milksi, F. hirthi, Dioctophyma renale, Capillaria aerophila, C. 
plica, Spirocerca lupi, Physaloptera spp., Mesocestoides spp., and Crenosoma vulpis.  For 
claims against larval stages, studies with induced infections should be used. 
 
The history of the parasites used in the induced infection studies should be included in the final 
report. 
 
 
2 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
3. Number of Infective Parasitic Forms Recommended for Induced Infections
The number to be used is approximate and will depend on the isolate.  The final number of 
larvae used in the infection should be included in the final report.  Table 1 shows the range of 
numbers recommended for common helminths. 
Table 1. Range of infective stages recommended to produce 
adequate infections in canines for anthelmintic evaluation 
Parasite Anatomical Location 
Range 
Genus Species 
Small Intestine 
Toxocara canis  100  500 * 
Toxascaris leonina  200  3,000 
Ancylostoma caninum  100  300  
Ancylostoma braziliense  100  300  
Uncinaria stenocephala  1,000  1,500  
Strongyloides stercoralis  1,000  5,000 
Echinococcus granulosus  20,000  40,000 
Taenia spp.  5  15 
Large Intestine 
Trichuris vulpis  100  500 
Heart 
Dirofilaria immitis  30  100 ** 
*In suckling canines or canines less than 5 months of age.
** For adulticidal or microfilaricidal testing, 5 to 15 pairs of 
adult worms can be transplanted. 
4. Recommendations for the Calculation of Effectiveness
4.1. Factors to Support a Claim 
To support a claim the following pivotal data should be included: 
a. Two dose confirmation studies conducted with a minimum of six adequately infected
non-medicated animals (control group) in each study.  The infection of animals in the
study will be deemed adequate based on historical, parasitological, and/or statistical
criteria;
b. The differences in parasite counts between treated and control animals should be
statistically significant (p  0.05);
c. Percent effectiveness should be 90% or higher and calculated and interpreted using
the procedures described in section A.4.2. Calculation and Evaluation of Percent
Effectiveness of GFI #90/VICH GL7.  For some parasites with public health or animal
3  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
welfare/clinical implications, e.g., E. granulosus and D. immitis, respectively, higher 
effectiveness standards (i.e., up to 100%) may be appropriate.  The regulatory 
authority of the region in which the product is intended to be registered should be 
consulted; and 
d.  Effectiveness against helminths should be evaluated by examining for the presence or 
absence of parasitic elements in fecal material or blood.  An Echinococcus spp. claim 
does not need field studies due to public health concerns. 
4.2. Number of Animals (Dose Determination and Dose Confirmation Studies) 
The minimum number of animals used per experimental group is a critical point.  Although the 
number of animals will depend on the possibility to process the data statistically according to the 
adequate statistical analysis, it has been recommended, to achieve harmonization, that the 
inclusion of at least six animals in each experimental group is a minimum. 
 
In cases where there are several studies none of which have six adequately infected animals in 
the control group (for example, important rare parasites), the results obtained could be pooled to 
accumulate 12 animals in the studies and statistical significance could then be calculated.  If the 
differences are significant (p < 0.05), effectiveness may be calculated and if the infection is 
deemed adequate, the claim may be granted.  Sampling techniques and estimation of worm 
burden should be similar among laboratories involved in the studies to allow adequate and 
meaningful extrapolation of the results to the population. 
 
4.3. Adequacy of Infection 
The minimum adequate number of helminths in individual control animals should be defined in 
the protocol.  However, final conclusions regarding adequacy of infection should be made as part 
of the final report based on statistical analysis, historical data, literature review, or expert 
testimony.  Generally, a minimum of 5 nematodes in individual control animals is considered an 
adequate infection.  For Dirofilaria immitis microfilaria (mff) claims, 300 mff/mL (blood) is 
considered an adequate infection.  Recommended counts (in individual control animals) to be 
considered adequate for cestodes include: 
-  Echinococcus spp.  5 scolices 
-  Taenia spp.  2 scolices 
-  Dipylidium caninum  2 scolices  
4.4. Label Claims 
A claim for effectiveness against life stages of each parasite should refer to each stage in the case 
of natural infections, or age in days in the case of induced infection.  Table 2 is provided as a 
guide for the recommended time of treatment of induced infections. 
 
 
 
 
 
4 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
Table 2. Recommended time of treatment after infection. 
Parasite  Adult Stages  Larval Stages 
S. stercoralis  5 to 9 days   
T. vulpis  84 days   
A. caninum  > 21 days  6 to 8 days* (L4) 
A. braziliense  > 21 days  6 to 8 days (L4) 
U. stenocephala  > 21 days  6 to 8 days (L4) 
T. canis  49 days  3 to 5 days (L3/L4); 14 to 21 days (L4/L5) 
T. leonina  70 days  35 days (L4) 
2 days (L3); 20 to 40 days (L4); 70 to 120 
D. immitis  180 days 
days (L5); 220 days (microfilariae) 
E. granulosus  > 28 days   
Taenia spp.  > 35 days   
* For somatic larvae, treat within 2 days prior to parturition. 
With the majority of parasites approximately 7 days is a sufficient time period from the 
termination of treatment until the animals are necropsied.  The following parasites are the 
exception to the above general recommendation: 
-  Physaloptera spp., S. lupi, C. plica, D. renale, E. granulosus, Taenia spp., D. 
caninum, Mesocestoides spp.: 10 to 14 days; 
-  C. vulpis: 14 days; 
-  F. milksi, F. hirthi: 42 days; 
-  F. osleri: one-half of the animals at 14 days and the other half at 28 days; and 
-  D. immitis: varies by trial design. 
For claims against transplacental and/or transmammary transmission of T. canis, somatic larvae 
of naturally- or artificially-infected pregnant bitches should be treated prior to parturition and the 
effectiveness checked by counting the larvae in the bitch milk and/or the adult worms in the 
small intestines of the litter.  
 
5.  Treatment Procedures 
The method of administration (oral, parenteral, topical), formulation, and extent of activity of a 
product will influence the protocol design.  It is advisable to consider the weather and animal 
relationship and bathing with regard to effectiveness of topical formulations. 
 
For oral formulations, palatability studies should be included in the evaluation of the 
effectiveness of the product.  For products administered topically, the impact of weather (e.g., 
rainfall, UV light), bathing, and coat length should be included in the evaluation of the 
effectiveness of the product. 
 
 
5 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
6.  Animal Selection, Allocation and Handling 
Approximately 6-month-old canines are suitable for effectiveness studies; however, there are 
exceptions: 
-  S. stercoralis: less than 6 months; 
-  A.caninum, A. braziliense: 6 to 12 weeks; 
-  T. canis, T. leonina: 2 to 6 weeks; 
-  D. caninum: 3 months or older; 
-  Mesocestoides spp.: 8 weeks or older; and 
-  T. vulpis: dogs older than 6 months can be used. 
Naturally-infected animals should be selected based on egg output or expelled proglottids for 
gastrointestinal parasites, and parasitological and/or immunological methods for D. immitis.  
Randomization to treatment group should be performed using an adequate method that should be 
described in the protocol and final report.  Blocking is only recommended if it is expected to 
reduce residual error in the study.  If blocking is used, blocks should be included as a random 
effect in the statistical model.  Nevertheless, blocking is not always the most appropriate method 
for reducing residual error.  Alternative methods may therefore be considered, e.g., a suitably 
selected covariate.   
 
Animal housing, feeding, and care should follow recommendations for welfare for canines.  
Animals should be acclimatized for at least 7 days to the experimental facilities and personnel.  
Animals should be monitored daily to determine adverse reactions. 
 
B. Specific Evaluation Studies 
1.  Dose Determination Studies 
No species-specific recommendations. 
 
2.  Dose Confirmation Studies 
No species-specific recommendation. 
 
3.  Field Effectiveness Studies 
Field (clinical) studies should not be conducted with canines infected with Echinococcus spp. 
 
4.  Persistent Effectiveness Studies 
Due to the differing biologies for the helminths of canines and the lack of experience with 
persistent effectiveness for these parasites, no recommendations can be provided. 
 
 
6