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Effectiveness of Anthelmintics: 
Specific Recommendations for Porcines 
VICH GL16 
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Draft Guidance 
This guidance document is being distributed for comment purposes only.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Submit comments on this draft guidance by the dated provided in the Federal Register notice 
announcing the availability of the draft guidance.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Additional copies of this draft guidance document may be requested from the Policy and 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 GL16 (ANTHELMINTICS: PORCINES) 
May 2022 
Revision at Step 9 
For consultation at Step 4 
 
 
 
E A :  
FFICACY OF  NTHELMINTICS  
S R  
PECIFIC  ECOMMENDATIONS
P  
FOR  ORCINES
(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Draft  Not for Implementation 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 .... 2 
4.  Recommendations for the Calculation of Effectiveness ....................................... 3 
4.1.  Factors to Support a Claim ............................................................................ 3 
4.2.  Number of Experimental Units (Dose Determination, Dose   
Confirmation, and Persistency Studies) ........................................................ 3 
4.3.  Adequacy of Infection ..................................................................................... 4 
4.4.  Label Claims .................................................................................................... 4 
5.  Treatment Procedures ............................................................................................. 4 
6.  Animal Selection, Allocation, and Handling.......................................................... 5 
B.  Specific Evaluation Studies ........................................................................................... 5 
1.  Dose Determination Studies .................................................................................... 5 
2.  Dose Confirmation Studies ..................................................................................... 5 
3.  Field Effectiveness Studies ...................................................................................... 5 
4.  Persistent Effectiveness Studies .............................................................................. 6 
II.  Glossary ................................................................................................................................ 7 
 
 
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Effectiveness of Anthelmintics: Specific Recommendations for 
Porcines 
 
VICH GL16 
 
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 porcines 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 the porcine guidance is: (1) to be more specific for certain specific porcine 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 (WAAVP) Second Edition of Guidelines for Evaluating the Efficacy of 
Anthelmintics in Swine. Veterinary Parasitology 141: 138-149, 2006, 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 
 
1 https://www.fda.gov/media/70349/download 
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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. 
A.  General Elements 
1.  The Evaluation of Effectiveness Data 
Only controlled tests are recommended both for the dose determination and dose confirmation 
studies.  Critical tests are generally considered not to be very reliable for porcine parasites. 
 
Long-acting or sustained-release products should be subject to the same evaluation procedures as 
other therapeutic anthelmintics.  Adequate parasite infection should be defined in the protocol 
according to regional prevalence or historic and/or statistical data. 
 
2.  Use of Natural or Induced Infections 
Dose determination studies generally should be conducted using induced infections with either 
laboratory strains or recent field isolates. 
 
Dose confirmation studies should be conducted using naturally-infected animals.  Induced 
infections with recent field isolates are also acceptable, as well as natural infections which can 
have superimposed induced infections of certain parasites.  This procedure should allow a wide 
range of parasites to be present. 
 
Persistent effectiveness studies should be conducted using induced infections with recent field 
isolates. 
 
The history of the parasites used in the induced infection studies should be included in the final 
report. 
 
3.  Number of Infective Parasitic Forms Recommended for Induced Infections 
The number that should be used is approximate and should depend on the isolate that is used.  
The final number of larvae or eggs used in the infection should be included in the final report. 
Table 1 shows the range of viable L3 or eggs recommended. 
 
Table 1. Range of viable L3 or eggs recommended to 
produce adequate infections in porcine for anthelmintic 
evaluation 
Parasite Anatomical Location  Range of 
Genus Species  Eggs/Larvae 
Stomach   
Ascarops strongylina  200 
Hyostrongylus rubidus  1,000  4,000 
Physocephalus sexalatus  500 
Intestines   
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Parasite Anatomical Location  Range of 
Genus Species  Eggs/Larvae 
Ascaris suum *  250  2,500 
Oesophagostomum spp.  2,000  15,000 
Strongyloides ransomi  1,500  5,000 
Trichuris suis  1,000  5,000 
Lungs 
Metastrongylus spp.  1,000  2,500 
Kidney 
Stephanurus dentatus  1,000  2,000 
*To maximize the establishment of adult worms a trickle
infection with a low number of eggs is recommended.
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
experimental units (individual animals or pens, see section II. Glossary) in the non-
medicated control group in each study.  The infection of the experimental units 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 experimental units
should be statistically significant (p  0.05); and
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.
4.2. Number of Experimental Units (Dose Determination, Dose Confirmation, and 
Persistency Studies) 
The minimum number of experimental units used per experimental group is a critical point.  
Although the number of experimental units 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 experimental units in each experimental group is 
a minimum. 
In cases where there are several studies, none of which have six adequately infected 
experimental units in the control group (for example, important rare parasites), the results 
obtained could be pooled to accumulate 12 experimental units 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 
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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 will be made as part of 
the final report based on statistical analysis, historical data, literature review, or expert testimony.  
If the experimental unit is a pen, an adequately infected pen should be defined by a minimum 
number of adequately infected animals out of the total number of animals in that pen (i.e., 
percentage of adequately infected animals in the pen).  The range of porcine helminths (adults) 
that has been considered adequate to grant a claim varies according to the species.  Generally, a 
minimum of 100 nematodes in individual control animals is considered an adequate infection.  
Lower individual counts are to be expected with A. suum, A. strongylina, P. sexalatus, S. 
dentatus, Metastrongylus spp., and Fasciola spp.  
 
4.4. Label Claims 
Generally, for adult claims, treatment should not be administered earlier than 35 days for A. 
strongylina, 26 days for H. rubidus, 55 days for P. sexalatus, 49 to 63 days for A. suum, 10 days 
for S. ransomi, 28 to 45 days for O. dentatum and O. quadrispinulatum, 50 days for T. suis, 35 
days for Metastrongylus spp., and 10 months after infection for S. dentatus. 
 
Generally, for L4 claims, treatments should be given 7 to 9 days after infection with exceptions: 
3 to 4 days for S. ransomi, 10 to 14 days for A. suum, and 16 to 20 days for T. suis.  The term 
immature on the labelling is not recommended. 
 
For claims against migrating A. suum L3, treatment should be given between 2 and 6 days post-
infection.  Necropsy may be performed when larvae have accumulated in the small intestine, 
either between 10-14 days post-infection (when parasites have matured to L4), or between 
approximately 23-28 days post-infection (after larvae have matured to the L5/adult stage). 
 
For the majority of adult parasites, approximately 5 to 7 days is a sufficient time period from the 
termination of treatment until the animals are necropsied.  For Stephanurus dentatus, the 
recommended time between termination of treatment and necropsy is 6-8 weeks. 
 
For claims against transmammary transmission of S. ransomi somatic larvae, naturally- or 
artificially-infected pregnant sows should be treated at various times prior to parturition and the 
effectiveness checked by counting the larvae in the sow milk and the adult worms in the small 
intestine of the litter. 
 
5.  Treatment Procedures 
The method of administration (oral, parenteral, etc.), formulation, and extent of activity of a 
product will influence the protocol design.  Slow-release products should be tested over the 
entire proposed effective time unless additional information suggests that this is unnecessary, 
e.g., for systemically-acting compounds blood levels demonstrate steady state at all points of the 
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proposed therapeutic period.  When the drug is to be administered in the water or via a feed, it 
should be done following the labeling recommendations.  Palatability studies may be advisable 
for medicated feed.  Samples of medicated water or medicated feed should be collected to 
confirm drug concentration.  The amount of medicated product consumed by each animal or 
experimental units should be recorded to ensure that the treatment satisfies the label 
recommendations. 
 
6.  Animal Selection, Allocation, and Handling 
Test animals should be clinically healthy and representative of the age, sex, and class for which 
the claim of the test anthelmintic is to be made.  In general, the animals should be 2 to 6 months 
of age.  If animals are housed in pens, the animals should also be randomly assigned to each pen.  
The experimental units (animals or pens) should also be assigned randomly to each treatment 
group.  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.  
 
For induced infections, the use of helminth-naive animals is recommended.  Animals not raised 
in a helminth-free environment should be treated with an approved anthelmintic drug to remove 
pre-existing infections followed by fecal examination to determine that the animals are helminth-
free. 
 
Animal housing, feeding, and care should follow recommendations for welfare, including 
vaccination according to local practices. This information should be provided in the final report. 
A minimum 7-day acclimatization period is recommended. Housing and feed/water supply 
should be adequate according to the geographical location.  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 
Confirmation studies are recommended to support each claim: adult and larvae.  For additional 
descriptions of the procedures refer to GFI #90/VICH GL7. 
 
3.  Field Effectiveness Studies 
The experimental unit may be the individual animal or the pen.  The design of the field studies 
should be representative of current commercial conditions and should be replicated in different 
geographic locations and in production class(es) that represent the conditions of use for the 
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indication being pursued.  The protocol should state the number of experimental units per 
treatment group (sample size), describe allocation (proportion) to treatment groups, and include a 
brief description of how the sample size was determined.  The protocol should also describe 
procedures for random selection of animals (number and percentage) to be sampled and the fecal 
and/or urine sampling method.  Regardless of whether one or multiple parasites are being 
evaluated within a study, an appropriate sample size calculation or justification is necessary prior 
to study conduct.  
 
Effectiveness against adult nematodes can be assessed by the reduction of fecal egg counts or 
urine egg counts.  In some cases, identification of larvae or larvae counts (from fecal culture) can 
be performed to support fecal egg counts.  Fecal egg count, urine egg count, and/or larval 
identification should be performed using samples from the same animal before and after 
treatment in both study groups (control and treated).  Post-treatment counts are generally made 
10-14 days after treatment, but the timing of post-treatment counts will depend on the parasite 
species evaluated.  Effectiveness should be calculated using post-treatment fecal egg or urine egg 
counts from the treated and control groups.  A calculation of effectiveness using pre- and post-
treatment fecal egg or urine egg counts may be appropriate in some situations where significant 
individual animal variability is expected.  The primary basis of the effectiveness determination 
should be defined in the protocol.  
 
The potential for false positive and false negative fecal egg counts for A. suum and T. suis, and 
variability in daily egg output for A. suum, should be considered in the study design and 
interpretation of results. 
 
4.  Persistent Effectiveness Studies 
Two basic study designs have been used to pursue persistent effectiveness claims: one using a 
single challenge, another using multiple daily challenges following treatment.  For consistency of 
interpretation of results, a standardized study design is recommended using multiple daily 
challenges, as this most closely mimics what occurs in nature. 
 
A minimum recommended for a persistent effectiveness claim (for each duration and helminth 
claim) should include two trials (with worm counts) each with a non-treated and one or more 
treated groups. At least six experimental units in the control group should be adequately infected. 
Persistent effectiveness claims should only be granted on a species-by-species basis. 
 
In the protocol using multiple daily challenges different groups of animals should be treated and 
exposed to a daily natural or induced challenge for 7, 14, 21, or more days after the treatment. 
Then at approximately 3 weeks after the last challenge (or earlier) the animals should be 
examined for parasite burden.  The challenge interval and schedule may vary for longer-acting 
products and should take into consideration the pharmacological properties of the product. 
 
Persistent effectiveness claims should be supported by a minimum 90% effectiveness at each 
time point, and calculated and interpreted using the procedures described in sections A.4.1. Data 
Analysis Recommendations and A.4.2. Calculation and Evaluation of Percent Effectiveness of 
GFI #90/VICH GL7.  Persistent effectiveness claims should be granted for the longest period 
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between treatment and the last challenge where effectiveness criteria are met, and all preceding 
time points tested meet the criteria as well. 
 
II. Glossary 
EXPERIMENTAL UNIT: The entity (e.g., individual animal or pen) which can be 
independently and randomly assigned to a treatment, and whose response to the assigned 
treatment can be independently evaluated.  The experimental unit is the basic unit for the 
statistical analysis.  The experimental unit may be the individual pig or the pen, depending on the 
circumstances of the study. 
1)  The pen is the experimental unit in the analysis if all pigs in a pen are provided the 
same treatment through medicated feed or water; or 
2)  The individual pig is the experimental unit in the analysis if the treatment can be 
individually administered, the treatments are randomly assigned to pigs within a pen, 
and the endpoint can be evaluated independently for each pig in a pen. 
 
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