SCIENTIFIC DISCUSSION
Duramune DAPPi
I.
Zoetis UK Limited
INTRODUCTION
Duramune DAPPi is a live vaccine for the protection of dogs from diseases caused by:

canine distemper virus (CDV) – which causes canine distemper, a serious, sometimes
fatal disease that mostly affects young dogs; it causes a wide range of clinical signs
including fever, diarrhoea, dullness, loss of appetite, discharge from the eyes and nose,
hardening of the paw pads and neurological signs such as twitching, unco-ordination
and fits;

canine adenovirus (CAV) – which may cause infectious canine hepatitis (CAV type 1),
another potentially fatal disease; and kennel cough, a less serious, but distressing and
debilitating disease (CAV types1 and 2);

canine parvovirus (CPV) - which can cause a serious and possibly fatal gastro-enteritis
in dogs, with vomiting, diarrhoea, a marked reduction in numbers of white blood cells
and sometimes fever;

canine parainfluenza virus (CPi) – which is another cause of kennel cough.
There is no cure for any of these diseases and vaccination is therefore necessary. A vaccine
that is effective against several diseases is clearly advantageous as it reduces the number of
injections needed to provide adequate protection.
Duramune DAPPi contains antigens from attenuated* forms of the four viruses: CDV (strain
Onderstepoort), CAV type 2 (strain V197), CPV (strain SAH) and CPi (strain FDL).
It is supplied in single dose vials of freeze dried viral fraction, and single dose vials of diluent.
The vaccine is intended for subcutaneous injection in dogs from 6 weeks old onwards. It is
designed to produce active immunisation to prevent mortality and disease caused by CDV
and CPV; to prevent mortality and reduce clinical signs due to CAV-1, to reduce clinical signs
and infection caused by CAV-2, and to reduce clinical signs and shedding caused by
infection with CPi.
The initial vaccination programme consists of 2 doses of vaccine with an interval of 2 - 4
weeks. In puppies first vaccinated between 6 and 8 weeks, the second vaccination should
be given after the puppy has reached 10 weeks old. Booster vaccination is recommended at
intervals of between one and three years.
II.
QUALITY ASPECTS
Product Development and Composition
Duramune DAPPi has been developed as one of a “family” of vaccines which contain
different numbers of antigens to protect dogs from a range of common diseases. Duramune
DAPPi contains antigens from four different viruses, as indicated below. Others members of
the family may contain more or fewer antigens and this ensures that animals can be given
the most appropriate vaccine for the diseases they are likely to be exposed to.
*
An attenuated virus is one that has been treated so that it no longer causes disease (i.e. it is not
virulent), but it can still stimulate immunity.
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SCIENTIFIC DISCUSSION
Duramune DAPPi
Zoetis UK Limited
Duramune DAPPi has two main components:
1.
Freeze dried component:
Active ingredients:
 Canine Distemper virus, strain Onderstepoort
 Canine Adenovirus type 2, strain V197
 Canine Parainfluenza virus, Strain FDL
 Canine Parvovirus, strain SAH
Other ingredients:
 Sucrose
 Gelatin
 Bactopeptone
 Potassium phosphate dibasic
 Potassium phosphate monobasic
 Potassium hydroxide
 Eagle’s Earle’s medium with HEPES
 May contain HCl or NaOH for pH correction.
2.
Sterile Solvent:
Sterilised Water for injections
Active Ingredients
The production and, where appropriate, purification of the antigens has been described by
the applicant. The information provided included a detailed description of the manufacturing
process. Each of the four viruses is grown in separate cell monolayers using standard
techniques for the preparation of the cells and the production of the viruses. When the
viruses have grown to the required extent, as evidenced by changes in the cells, they are
collected and stored frozen ready for later use.
Quality control of these antigens has been described, with testing in accordance with the
relevant guidelines. Data provided show freedom from relevant extraneous agents (i.e.
unwanted viruses, bacteria, etc).
Other Ingredients
Certificates of Analysis were provided where appropriate, and reference made to the
appropriate pharmacopoeia.
Packaging Materials
The freeze-dried component and the diluent are each presented in 3 ml glass vials. The
containers and stoppers are sterile, made of standard materials and comply with the
European Pharmacopoeia where necessary.
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SCIENTIFIC DISCUSSION
Duramune DAPPi
Zoetis UK Limited
Manufacture of the Product
All production steps are performed according to GMP*.
equipment and materials are sterile.
Where applicable, conditions,
The required amounts of the antigens are prepared for production, appropriate quantities
determined, and the blending diluent quantity calculated. The final product is then prepared
under sterile conditions. The product may be produced in different batch sizes depending on
the amount needed at the time.
Final production steps are the filling of 3 ml vials with a target volume of 1.2 ml, freezedrying, and capping, followed by quality control.
Validation data were provided for multiple batches of viruses, as was information to show
that production variables did not adversely affect these viruses. Data were also provided on
the stability of the viral antigen stock. The live virus assay was validated, and showed that a
satisfactory batch could be distinguished from a minimum or sub-potent batch, as well as a
concentrated vaccine, thus satisfying consistency requirements. The assays were
repeatable, accurate, precise and showed a log-linear relationship between the quantity of
virus present and potency. The assays described were therefore considered satisfactory for
potency determination of batches. Validation data were also provided for sterilisation
processes. The validation data were considered satisfactory, and demonstrated efficiency
and consistency of manufacture.
In-process control tests were described in detail, and included tests for sterility, mycoplasma
and viral content and identity, and absence of contaminating viruses.
The components of the product were demonstrated to comply with relevant guidance on
minimising the risk of transmitting animal spongiform encephalopathy agents via veterinary
medicines.
Finished Product Control
Standard tests (visual tests, pH, sterility, extraneous agents, etc) are applied to the finished
product. Each viral component is identified by fluorescent antibody, and quantified, under
virus-specific conditions, to confirm the amount of virus is within the range required.
Batch safety tests are carried out in the target species. The specifications for all tests are
appropriate to control the quality of the product.
Results of the analysis of consecutive production runs of finished vaccine were presented,
and show consistency of production.
Stability
Stability of bulk antigen
Satisfactory stability data for storage of the bulk antigen were provided.
Stability of finished product
*
GMP = Good Manufacturing Practice
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SCIENTIFIC DISCUSSION
Duramune DAPPi
Zoetis UK Limited
Stability data for several batches of the finished product were provided. Based on this
information a shelf life of 24 months was approved for the freeze-dried fraction, and 12
months for the diluent.
Stability of the reconstituted product
The reconstituted product is intended to be used immediately on reconstitution, so
information on the stability of the reconstituted product is not relevant.
CONCLUSIONS ON QUALITY
The analytical part of the dossier included satisfactory descriptions of the production and
quality control procedures, including appropriate diagrams. The method of manufacture was
well described, and the in-process controls detailed in full. Starting materials of animal origin
were shown to be compliant with legislative requirements.
The finished product tests, including the potency test and batch safety test, ensure an
efficacious, safe and consistent product. The stability data provided shows that shelf lives of
24 months for the freeze-dried fraction and 12 months for the diluent are justified when
stored at 2 – 8° C, protected from light.
III.
SAFETY ASPECTS
Introduction
The vaccine is intended for dogs from the age of six weeks, and a primary course consists of
two vaccinations, 2 - 4 weeks apart, the second of which must occur after the pup is 10
weeks old. Booster vaccination is recommended at intervals of between one and three
years. The vaccine is administered subcutaneously in a volume of 1 ml.
Details of the batches of Duramune DAPPi used in the laboratory safety trials were provided.
The antigen component was the same as the antigen component of the final authorised
product. The diluent used in the studies contained three additional inactivated antigens,
rather than just water. This is considered acceptable, as any safety issues would be worse
in the presence of additional antigens. Maximum potency batches of product were used in
the studies so that safety of the product could be demonstrated at high potency.
Details of the batches used in the field safety trials were also provided. The batches were
essentially identical to the final licensed product, although again the more complex diluent
was used. Batches of mid - low potency were used, as is usual for such trials.
No studies were performed to investigate safety of the product for pregnant or lactating
animals and the product is therefore not recommended for use in pregnant and lactating
animals.
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SCIENTIFIC DISCUSSION
Duramune DAPPi
Zoetis UK Limited
Laboratory Tests
Laboratory safety studies were carried out in accordance with GLP*, as is required.
The applicant carried out a combined study into the potential side effects of a single dose, a
single overdose (10 times the normal dose) and a repeated dose of the vaccine (3 doses at
two-week intervals). The animals had no antibodies to the antigens of interest at the
beginning of the study.
Safety was assessed clinically, over an appropriate time course, through observation,
physical examination, and body temperature determinations.
The adverse effects seen following administration of an overdose and repeated single doses
in healthy animals of the minimum age for which the vaccine is recommended were minor,
transient and resolved within an acceptable time frame.
Details are given in the SPC:
Following the first vaccination, up to 80% of puppies develop a small visible swelling (<2 cm)
lasting for generally only two days. Following the second vaccination, occasionally a small
visible swelling (up to 5 cm) may be seen at the injection site, which may last for up to five
days. The swelling may be painful for 1 to 2 days. In most cases these small and transient
injection site reactions resolve with no need for treatment.
Overdose: Some puppies may exhibit a transient lethargy by 4 hours post vaccination but
recover by two days post vaccination. Occasionally a small visible swelling (<2 cm) may be
seen at the injection site, which may last for up to 17 days.
Special Requirements for Live Vaccines
Further compulsory tests were carried out on each of the four viruses in the vaccine, to
determine the potential for spread and dissemination of the vaccine constituents, and any
tendency to revert to virulence*. The studies were designed to demonstrate compliance with
the relevant European Pharmacopoeial monographs.
To investigate the properties of CDV, young dogs which had no antibodies to CDV were
inoculated with a suitable amount of the CDV strain used in Duramune DAPPi. No CDV
could be found in nasal swabs or in samples of various tissues collected from these dogs
although, as expected, the dogs did show an antibody response to the virus. Untreated
dogs that were in contact with the treated ones did not have an antibody response to CDV
and this showed that the virus had not spread to these animals. None of the animals showed
any signs of disease.
Similar studies were done using the CAV-2 strain that is used in Duramune DAPPi, but in this
case, virus was found in nasal swabs and tissue samples from treated dogs. The virus was
extracted from these samples and administered to other young dogs. This process was
repeated five more times and at each stage, animals were checked for signs of disease that
could have been caused by CAV-2 if it had reverted to virulence, for example, raised
temperature, discharge from the eyes or nose, sneezing, coughing or retching. No such
*
*
Good Laboratory Practice
If a virus reverts to virulence, it regains the ability to cause disease.
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SCIENTIFIC DISCUSSION
Duramune DAPPi
Zoetis UK Limited
signs were observed, showing that the virus had not reverted to virulence. All the treated
dogs developed antibodies to CAV-2. Untreated dogs that were in contact with the treated
ones also had an antibody response to CAV-2 and this showed that the virus had spread to
these animals, although none of them had any signs of disease.
In the case of CPV, a similar experiment was also done. In this case, CPV was found in
samples of faeces collected from the treated animals. The virus found in the faeces was
extracted and administered to other young dogs. This process was repeated four times and
at each stage, animals were checked for signs of CPV-related disease, such as a reduction
in the number of white blood cells and effects on the intestine. All dogs developed antibodies
to CPV but there were no signs of disease. Two additional studies were specifically aimed at
investigating possible effects of CPV on the thymus as this gland may be targeted by CPV.
No evidence of damage was found.
To complete the additional information required for live vaccines, CPi was tested in a similar
way, with virus being extracted from nasal swabs from the treated animals. This virus was
then administered to more dogs as in the other studies and the process was repeated five
more times. All the dogs (i.e. treated and untreated ones) developed antibodies to CPi,
showing that the virus had spread. However, there were no signs of disease in any animal,
showing that the virus had not reverted to virulence.
To summarise the results of these studies, none of the viruses showed any reversion to
virulence. Specific adverse biological effects of the viruses present in Duramune DAPPi for
example adverse effects on the nervous system (CDV) and enteritis or thymic atrophy*
(CPV), were not observed in any of the studies.
The studies also demonstrated that
dissemination within the vaccinated animal was negligible and that CDV does not spread to
animals which are in contact with the vaccinated animals. Although the other viruses did
spread to in-contact animals, animals are not at risk of disease from this spread because the
viruses do not revert to virulence. The SPC reflects this situation:
The live vaccine strains may spread to unvaccinated animals, but do not cause disease.
Field studies
Two field studies were conducted using vaccine that had been manufactured and tested in
accordance with the dossier. These studies were appropriately controlled and fully
documented. They investigated both the safety and the efficacy of the vaccine.
Dogs of a variety of breeds, aged 6 - 8 weeks old, were examined before entry into the trial.
They were then randomly assigned to one of two groups. One group received the vaccine
while the other group received either a vaccine that was already approved or a placebo
(sterile saline), depending on the trial. The first dose of vaccine was given at 7 - 8 weeks of
age and a second 4 weeks later.
The safety of the vaccine in these young dogs was determined through observation and the
measurement of body temperatures. No animal showed any fever. Reactions at the
injection site were observed, with a maximum dimension of 5 cm. Pain (lasting less than 24
hours) was detected in ⅓ of the vaccinated animals after the first injection, and in ½ after the
second injection. These results were similar to the results of the laboratory studies.
*
Thymic atrophy means that the size of thymus gland (which is an important part of the immune
system) is reduced.
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SCIENTIFIC DISCUSSION
Duramune DAPPi
Zoetis UK Limited
Environmental Safety
The applicant provided a phase 1 environmental risk assessment in compliance with the
relevant guideline. Ecotoxicity was adequately addressed, and the risk to the environment is
considered negligible. Therefore no further assessment is required.
Warnings and precautions are listed in the SPC, and are adequate to ensure safety to the
environment when the product is used as directed.
Dispose of waste by boiling, incineration or immersion in an appropriate
disinfectant approved for use by the competent authorities.
CONCLUSIONS ON THE SAFETY ASPECTS
The safety part of the dossier fulfils the legislative requirements, and provides adequate
information to assess the safety of the product.
The vaccine often produces local reactions in dogs when used, and these are explained in
the SPC. The safety of the product, including biological properties, excretion, spread and
reversion to virulence has been demonstrated by the laboratory studies carried out. The
vaccine was shown to be safe when used in a variety of dog breeds in a normal “field”
situation.
The vaccine contains no ingredients that represent a significant hazard to people
administering the product.
Since the product is for use in dogs only, there are no concerns regarding consumer safety.*
In summary, this product has been shown to be safe when used according to the directions
for use, and the SPC adequately reflects the likelihood and severity of any reaction that may
be seen.
IV.
EFFICACY ASPECTS
Introduction
The vaccine is intended for dogs from the age of 6 weeks. A primary course consists of two
vaccinations, 2 - 4 weeks apart, with the second being given when the animal is at least 10
weeks old. Booster vaccination is recommended at intervals of between one and three
years. The vaccine is administered subcutaneously in a volume of 1 ml.
Information on the composition of batches used in the laboratory efficacy trials was provided.
In cases where the composition differed from that of the authorised product, data were
provided to show that the studies were relevant to Duramune DAPPi.
*
Consumer safety relates to consumers of food derived from treated animals, and is thus only
applicable to food-producing animals such as cattle, sheep, fish and poultry.
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SCIENTIFIC DISCUSSION
Duramune DAPPi
Zoetis UK Limited
Information on the composition of batches used in the field efficacy trials was also provided.
The batches were essentially identical to the final licensed product. Batches were generally
produced in order to be at minimum or low potency in order to investigate if the product is
efficacious even at low potency levels.
Laboratory trials
Laboratory trials were carried out to show short-term efficacy of two doses, duration of
immunity, efficacy of a single booster, and effect of maternal antibody on efficacy for each of
the viral components. Also, as supporting data, the applicant provided information on the
efficacy of a single dose of CDV and of CAV.
Canine Distemper Virus
Young dogs which had no antibodies to CDV were inoculated with complete vaccine on two
occasions, with an interval of 3 weeks. Three weeks after the second vaccination, the
animals were exposed to virulent CDV. Blood samples from the vaccinated animals showed
a strong antibody response to the first vaccination, and antibodies reached protective levels
two weeks after the second vaccination. Vaccinated animals were generally protected
against fever, and showed virtually no clinical signs following exposure to virulent CDV. The
CDV component of the vaccine was shown to be in compliance with the European
Pharmacopoeia monograph.
In two further studies, animals vaccinated twice at 3-week intervals were exposed to virulent
CDV after one or three years. It was shown that antibody levels remained elevated for at
least a year after the course of vaccination and when the animals were exposed to virulent
CDV, there was a strong “memory response”, with protective levels of antibodies being
attained quickly. Animals exposed to virulent CDV one year after vaccination showed no
signs of disease and animals exposed three years after vaccination showed either minimal or
no signs of disease. These data therefore demonstrated a 3-year duration of immunity.
The company also provided data demonstrating protection from virulent CDV three weeks
after the administration of a single injection of the complex vaccine. These data, combined
with the results of a study in which antibody levels were measured following a single booster
dose given one year after the initial two-dose course of vaccination, indicate that a single
booster dose will be sufficient to provide protection.
Studies were conducted to investigate whether the vaccine was efficacious in dogs with
maternal antibodies to CDV. When two doses of vaccine were given, 2 - 4 weeks apart, to
animals with low or moderate levels of maternal antibodies to CDV, the vaccine did provide
protection against CDV, although the protection was not as effective as when the vaccine
was given to animals with no maternal antibodies. It was therefore concluded that the
presence of maternal antibody could affect the performance of the vaccine. The SPC
contains a warning of the potential for interference from maternal antibody and a statement
on the efficacy of the product in the face of low to moderate levels of maternal antibody.
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SCIENTIFIC DISCUSSION
Duramune DAPPi
Zoetis UK Limited
Canine Adenovirus
Young dogs which did not have antibodies to CAV were inoculated with complete vaccine on
two occasions, with an interval of 3 weeks. Three weeks after the second vaccination, one
group of animals was exposed to virulent CAV-1 by intravenous injection to check for
protection against hepatitis and another group of animals was exposed to virulent CAV-2 via
an aerosol to check for protection against respiratory infection.
Vaccinated animals showed a strong antibody response to the vaccine, with protective levels
occurring two weeks after the second inoculation, and antibody levels remained high until the
animals were exposed to virulent CAV-1 or CAV-2. In addition, the vaccinated animals
exposed to virulent CAV-1 showed virtually no signs of hepatitis.
In animals exposed to CAV-2, virus was detected less frequently in nasal swabs from
vaccinated animals than in nasal swabs from unvaccinated animals. The results also
demonstrated that the clinical signs of CAV-2 respiratory infection were significantly reduced
following vaccination. The CAV component of the vaccine complies with the requirements of
the European Pharmacopoeia monograph.
In two further studies, vaccinated animals were exposed to virulent CAV-1 or CAV-2 one
year after the initial course of vaccination. These studies demonstrated that the protection
against both CAV-1 and CAV-2 which was seen in the earlier studies lasted for at least a
year after the initial course of vaccination. In another study, animals were observed over a
3-year period and protective levels of antibodies to both CAV-1 and CAV-2 were found in
vaccinated animals throughout the study, demonstrating that protection lasts for three years.
This conclusion was supported by data showing that vaccinated animals exposed to virulent
CAV-1 three years after vaccination had only minimal signs of disease.
Additional data showed that protection from CAV-1 occurred three weeks after the
administration of only one vaccination with the complex vaccine, and this indicates that a
single booster dose will be sufficient to provide protection. As in the case of CDV, these data
were supplemented by a study in which antibody levels were measured following a single
booster given one year after the initial course of vaccination.
In experiments to address efficacy in the presence of maternal immunity, when two doses of
vaccine were given, 4 weeks apart, to animals with moderate levels of maternal antibodies to
CAV-1, the vaccine provided some protection against exposure to virulent CAV-1. The
antibody response and degree of protection was less than it was when the vaccine was given
to animals without maternal antibodies. It was therefore concluded that the presence of
maternal antibody could affect the performance of the vaccine. The SPC contains a warning
of the potential for interference from maternal antibody and a statement on the efficacy of the
product in the face of low to moderate levels of maternal antibody.
Canine Parvovirus
Young dogs which had no antibodies to CPV were inoculated with complete vaccine on two
occasions, with an interval of 3 weeks. Three weeks after the second vaccination, the
animals were exposed to virulent strains of CPV. Blood samples from vaccinated animals
showed a strong antibody response to the CPV components of the vaccine from two weeks
after the second vaccination. Vaccinated animals were protected against fever and
leucopenia*, showed virtually no signs of disease and only one excreted virus following
exposure to the virulent virus. The vaccine was shown to protect against virulent CPV.
*
Leucopenia is a reduction in the number of white blood cells.
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SCIENTIFIC DISCUSSION
Duramune DAPPi
Zoetis UK Limited
In another study, animals vaccinated twice at 3-week intervals, were exposed to virulent CPV
after one year. This study demonstrated that immunity continued for at least one year after
the initial vaccination programme. A similar study in which vaccinated animals were exposed
to virulent CPV three years later showed that antibody levels remained high throughout the
study and vaccinated animals had few signs of disease when exposed to virulent CPV.
Further data were submitted that showed that, when given on one occasion, the vaccine
protected animals from oral and intranasal exposure to virulent CPV at 3 weeks after
vaccination. Blood samples from vaccinated animals showed a strong antibody response to
CPV, and antibody levels remained high until the animals were exposed to virulent CPV.
Vaccinated animals were relatively protected against CPV infection. This indicates that the
CPV component of the vaccine is efficacious and indicates that a single booster dose will be
sufficient. Full compliance of CPV with the European Pharmacopoeia monograph was
shown in this study. The company also provided data from a study in which antibody levels
were measured following a single booster one year after the initial course of vaccination, and
these data supported the conclusion that a single booster dose is appropriate.
When two doses of vaccine were given, 2 - 4 weeks apart, to animals with low or moderate
levels of maternal antibodies to CPV, the vaccine could provide protection against CPV. The
protection was not as effective as when the vaccine was given to animals without maternal
antibodies. It was therefore concluded that the presence of maternal antibody could affect
the performance of the vaccine. The SPC contains a warning of the potential for interference
from maternal antibody and a statement on the efficacy of the product in the face of low to
moderate levels of maternal antibody.
Canine Parainfluenza Virus
Young dogs which had no antibodies to CPi were inoculated with complete vaccine on two
occasions, with an interval of 3 weeks. Three weeks later the animals were exposed to a
virulent CPi. Blood samples from vaccinated animals showed little or no antibody response
to the first vaccination, followed by a weak response to the second vaccination; no antibodies
could be detected in the blood of unvaccinated dogs. Although the initial antibody response
was weak, vaccinated animals showed a strong antibody response when exposed to virulent
CPi. Signs of disease were not significantly different between vaccinated and unvaccinated
controls. Excretion of virus occurred more often in unvaccinated animals than in vaccinated
ones. On the basis of this finding, it can be concluded that the vaccine has a beneficial effect
against CPi. The CPi component of the vaccine complies with the requirements of the
European Pharmacopoeia monograph.
Exposure to virulent CPi was also carried out one year after vaccination, on a further group
of animals. Antibody levels had dropped by one year, although a strong “memory” response
was seen at challenge. Initial studies indicated that it was not possible to demonstrate the
efficacy of these antibodies because unvaccinated dogs showed few signs of illness when
exposed to virulent CPi. Recently further data have been provided which demonstrate d that
immunity continued for at least one year after the initial vaccination programme.
As was the case with the other viruses, data were submitted for dogs given the final vaccine
on two occasions 3 weeks apart, followed by a single booster a year later. Antibody
responses obtained at 7 and 14 days after the booster were higher than those after the
second vaccination. The vaccine was therefore shown to be efficacious for a year after a
single booster dose given 12 months after the initial vaccination.
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SCIENTIFIC DISCUSSION
Duramune DAPPi
Zoetis UK Limited
As can be seen from these experiments, infection with CPi is not characterised by a
significant antibody response, so maternal antibody levels are generally low. However, when
two doses of vaccine were given, 4 weeks apart, to animals with low levels of maternal
antibodies to CPi, there was a significantly higher antibody response in the vaccinated
animals after exposure to virulent CPi two weeks after vaccination. It can be concluded that
the vaccine had the desired effect, despite the presence of maternal antibody.
Field Trials
The antibody responses observed in the laboratory studies were confirmed in two field
studies which were controlled and fully documented, one in Germany, and one in the UK,
using young dogs of various breeds. These studies investigated both the safety and efficacy
of the product, and the safety aspects have already been discussed in Part III of this report.
CONCLUSIONS ON CLINICAL ASPECTS
The data provided on efficacy fulfils the legislative requirements, and allows adequate
assessment of the product.
Each of the viral antigens in the product stimulates an immune response in the susceptible
target animal, and this has been shown to provide protection in each case. The protection
afforded by the CDV, CAV and CPV components has been shown to last three years,
whereas the CPi component provides a 1-year, duration of immunity. An annual booster has
been shown to provide protection. In the presence of high levels of maternal antibody, a
beneficial effect is still obtained, although the vaccine is not as efficacious as when used in
animals without maternal antibodies. This situation is adequately reflected by the warning in
the SPC.
V.
OVERALL CONCLUSION ON THE PRODUCT
The data submitted in the dossier demonstrate that when the product is used in accordance
with the Summary of Product Characteristics, the risk benefit profile for the target species is
favourable and the quality and safety of the product for man and the environment is
acceptable.
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