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Guidance for Industry 

Effectiveness of Anthelmintics: 

Specific Recommendations for Porcine 

VICH GL16

FINAL GUIDANCE 

This final guidance is intended to standardize and simplify methods used in the evaluation of new 

anthelmintics submitted for approval to the European Union, Japan, and the United States. 

Comments and suggestions regarding the document should be submitted to Division of Dockets 

Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, 

MD 20852. Submit electronic comments to http://www.regulations.gov. All comments should be 

identified with the Docket No 00D-1532. 

For questions regarding this document, contact Janis Messenheimer, Center for Veterinary Medicine, 

(HFV-135), Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855, 240-276-8348, 

e-mail: janis.messenheimer@fda.hhs.gov. 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Veterinary Medicine 

June 27, 2002 
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VICH GL16 (ANTHELMINTICS: PORCINE) 

June 2002 

For implementation at Step 7 

EFFECTIVENESS OF ANTHELMINTICS: SPECIFIC RECOMMENDATIONS FOR PORCINE

Recommended for Implementation 

on June 2001 

by the VICH Steering Committee 

THIS GUIDANCE HAS BEEN DEVELOPED BY THE APPROPRIATE VICH EXPERT WORKING GROUP AND WAS 

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. 
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EFFECTIVENESS OF ANTHELMINTICS: 

SPECIFIC RECOMMENDATIONS FOR PORCINE

Endorsed by the VICH Steering Committee at Step 7 of the 

VICH process at its meeting from June 2001 

This guidance represents the agency's current thinking and does not create or confer 

any rights for or on any person and does not operate to bind FDA or the public. An 

alternative method may be used as long as it satisfies the requirements of the 

applicable statutes and regulations. 

Introduction 

The present guidance for porcine was developed by the Working Group established by the Veterinary 

International Co-operation on Harmonization (VICH), Anthelmintic Guidances. It should be read in 

conjunction with the VICH Effectiveness of Anthelmintics: General Recommendations (EAGR) 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 the EAGR with 

the aim of simplicity for readers comparing both documents. 

The guidance for porcine is part of this EAGR and the aim is (1) to be more specific for certain issues 

for porcine not discussed in the EAGR; (2) to highlight differences with the EAGR on effectiveness 

data recommendations and (3) to give explanations for disparities with the EAGR. 

It is also important to note that technical procedures to be followed in the studies are not the aim of 

this guidance. We recommend to the sponsors to refer to the pertinent procedures described in detail 

in other published documents e.g., WAAVP Guidelines for Evaluating the Effectiveness of 

Anthelmintics in Swine. Veterinary Parasitology 21 : 69 - 82, 1986. 

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. 

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 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 
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superimposed induced infections of certain parasites. This procedure should allow a wide range of 

parasites. 

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. 

Parasites Range 

Stomach

Ascarops strongylina 200 

Hyostrongylus rubidus 1,000 – 4,000 

Physocephalus sexalatus 500 

Intestines 

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 Criteria to Grant a Claim 

To be granted a claim the following pivotal data should be included: 

a) Two dose confirmation studies conducted with a minimum of six adequately infected nonmedicated animals (control group) and six adequately infected medicated animals (treated group) 

in each study; 

b) The differences in parasite counts between treated and control animals should be statistically 

significant (p<0.05); 

c) Effectiveness should be 90% or higher using transformed (geometric means) data; 

d) The infection of the animals in the study should be deemed adequate based on historical, 

parasitological and/or statistical criteria. 
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4.2 Number of Animals (dose determination, dose confirmation and persistency trials) 

The minimum number of animals used per experimental group is a critical point. Although the number 

of animals will depend on the ability to process the data statistically according to 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 

With respect to the minimum adequate number of helminths, the decision should be made when the 

final report is submitted based on statistical and historical data, literature review, or expert testimony. 

The range of porcine helminths (adults) that has been considered adequate to grant a claim varies 

according to the species. Generally the minimal mean number of nematodes recommended as 

adequate is 100. Lower mean counts are to be expected with A.suum, A. strongylina, P. sexalatus, S. 

dentatus, Metastrongylus spp. and Fasciola spp. 

4.4 Label Claims 

For adult claims as a general rule the treatment should not be administered earlier than 35 days for

A. strongylina, 26 days for H. rubidus, 55 days for P. sexalatus, 65 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 for S. dentatus. 

For L4 claims treatments should be given as general rule 7 to 9 days days after infection with 

exceptions: 3 to 4 days for S. ransomi 11 to 15 days for A. suum, and 16 to 20 days for T. suis. The 

term immature on the labelling is not recommended.

For claims against transmammary transmission of S. ransomi somatic larvae, natural 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 proposed therapeutic 

period. When the drug is to be administered in the water or via a premix, it should be done following 

the labelling recommendations. Palatability studies may be advisable for medicated feed. Samples of 

medicated water or feed should be collected to confirm drug concentration. The amount of medicated 

product consumed by each animal or group of animals 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. 

Animals should be assigned randomly to each treatment. Blocking in replicates by weight, sex, age, 
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and/or exposure to parasites may aid in reducing trial variance. Faecal egg/larval counts are also an 

adequate method to allocate the experimental animals. 

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 preexisting infections followed by faecal 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 

seven-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 EAGR. 

3. Field Effectiveness Studies 

No species specific recommendations. 

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 standardised 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 animals 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 three weeks after the last challenge (or earlier) the animals should be examined for 

parasite burden. 

Persistent effectiveness claims should be supported by a minimum 90% effectiveness based on 

geometric means.