ALL YOU NEED FOR A NEEDLE-FREE INTRADERMAL FUTURE USE THE MENU BUTTONS TO NAVIGATE THROUGH THE DOCUMENT

The perfect match Contents Needle-free / intradermal benefits Why needle-free Needle tip deterioration Needle-free improves welfare Why intradermal? The way it works How vaccine is deposited in the pig Reduction of skin lesions and stress IDAL 3G device Porcilis intradermal portfolio References

Needle-free and intradermal: the perfect match Needle-free and intradermal application of vaccines is the most advanced method for vaccinating pigs today. The ergonomically designed, reliable and easy-to-use IDAL device makes vaccination safe and less stressful for people and pigs, while ensuring efficacy at the same time. Together with the broadest range of specifically formulated intradermal vaccines Porcilis PCV ID, Porcilis M Hyo ID ONCE, Porcilis PRRS, Prime Pac PRRS and Porcilis Begonia IDAL The IDAL Way is an important step forward in controlling major diseases affecting pig operations worldwide.

NEEDLE-FREE BENEFITS USER SAFETY Needle-free vaccination reduces the risk of self-injection. WELFARE Much less pain and stress for the pigs being vaccinated.4 ANIMAL SAFETY No accidental iatrogenic transmission of pathogens from reusing needles (such as PRRS).1 QUALITY Potential tissue damage is reduced and there is no risk of needle pieces remaining in the meat due to broken needles.1 INTRADERMAL BENEFITS QUALITY Less risks for muscle damage. EFFICACY Quick, effective immune response2, 5, 6 (at least as good as with IM vaccination). Antigen-presenting cells in the epidermis induce a broad range of immune responses.5, 6 Pre-existing immunity may be overcome since (maternal) antibodies are not located in the skin. FOOD SAFETY The injected volume is only 10-20% of the total volume of an intramuscular vaccine dose and the distribution of the vaccine is limited to the skin. SAFETY Fewer adverse systemic events.1, 2

Why needle-free vaccination delivers instant benefits Traditional intramuscular vaccination with a needle and syringe has many disadvantages for pigs and administrators. Needle injections result in stress and pain in pigs and increase the risk for transmitting disease. In addition, accidental needle sticks, disposal of used needles and broken needles are a problem for administrator and consumers. Needle-free vaccination is a great alternative for pigs and administrator. Needle-free devices deposit the exact vaccine dose through the skin under high pressure and in a fraction of a second, resulting in less stress on the pigs and easier vaccination routine for the administrator.

Multiple needle injections negatively impact needle quality3 BRAND NEW NEEDLE USED ONCE Needle becomes dull, even after just one injection. Biological matter (Blood cells, bacteria, etc.). USED X12 Tip is forming a barbed hook. Needle becomes more dull. Even more biological matter (Blood cells, bacteria, etc.).

Vaccinating needle-free improves the welfare of both sows and piglets4 SOW STUDY BEHAVIORAL PARAMETERS 100.0% SOW STUDY PANIC RESPONSE TO OBSERVER 24 HOUR POST-VACCINATION PIGLET STUDY BEHAVIORAL RESULTS IN PIGLETS 100.0% 40.0% 90.0% 90.0% 80.0% Standing Moving Suckling Socializing 80.0% 30.0% 70.0% Resting 70.0% 60.0% 60.0% 50.0% 50.0% 20.0% 40.0% 40.0% 30.0% 30.0% 10.0% 20.0% 20.0% 10.0% 10.0% 0.0% 0.0% High pitch vocalizations Retreat attempts IDAL Turning back Change in behaviour IDAL IM IM No needles, and a vaccination volume of only 0.2 ml, mean no pain and less stress for the pigs. Studies show that fear and pain indicators at time of injection are reduced. Fear response to assessor increased in IM group 24 h post-vaccination. General activity decreased in IM sows vs IDAL (p<0,05). No differences in social behavior, exploration, drinking, resting patterns. 0.0% * * * * IDAL group Control group Day before vaccination * * * * * * * * * * IDAL group Control group Day of vaccination * Indicates a significant difference between IDAL group and control group (p<0.05). * * * * IDAL group Control group Day after vaccination

Why intradermal vaccination stimulates an effective immune response Compared to intramuscular (IM) administration, vaccination into the dermis is advantageous because high concentrations of powerful, specialized cells located in the skin respond very quickly and efficiently to vaccine antigens. Intradermal vaccination stimulates an immune response as efficient or better as following IM administration.2, 5, 6

I I II III Vaccine antigens are administered intradermal using the IDAL device. Dendritic cells are activated in order to capture and process the antigens, carrying important information to the nearest skin-draining lymph node.5, 6 III IV II V Once in the lymph node, dendritic cells present antigen materials to naive T lymphocytes and B lymphocytes found within the lymph node. Now activated, these cells stimulate a direct and strong immune response to the antigen so the pig can start building immunity against future infections. Cytotoxic T lymphocytes destroy virus-infected cells and provide cell-mediated immunity. Helper T lymphocytes help transform B lymphocytes into Plasma B lymphocytes, which produce specific antibodies and also provide humoral immunity. IV V Epidermis Skin-draining lymph node Helper T lymphocytes Dermis Activated dendritic cells Cytotoxic T lymphocytes Vein Naive T lymphocytes Plasma B lymphocytes Antigens Naive B lymphocytes Antibodies Dendritic cells

How vaccine is deposited in the pig3 VACCINE PRESENCE IN THE PIG DEPTH LATERAL SPREAD COMMENT IDAL Extends to 12 mm below skin 18-22 mm Cloud and line like appearance indicative of fine and lateral vaccine dispersion IM Starts at 12 mm and extends to 34 mm 38-48 mm Bolus/depot of vaccine in deeper next region surrounding vertebrae INTRAMUSCULAR THE IDAL WAY Study demonstrates that the IDAL device disperses the vaccine in the dermis layers, resulting in greater exposure to the immune system. INTRAMUSCULAR THE IDAL WAY

Reduction of skin lesions and stress4 REDUCTION OF MUSCULAR LESIONS IN SOWS VACCINATED INTRADERMALLY REDUCTION OF STRESS INDICATOR IN SOWS VACCINATED INTRADERMALLY PERCENTAGE REDUCTION OF ANIMALS WITH INFLAMMATION/SKIN DISCOLORATION WHEN VACCINATED INTRADERMALLY 1 40 +28 HOURS +52 HOURS +7 DAYS +28 DAYS IDAL 47%* 53% 5% 0% IM 9% 22% 22% 26%** 0.8 30 µg/ml µg/ml 0.6 20 10 0.4 0.2 Vaccination 0 IDAL. n = 15 IM. n = 13 0 Chromogranin-A CRP * p-value = 0.064 IDAL. n = 23 IM. n = 21 Needle-free vaccination reduces sow s fear and pain reaction to the vaccination procedure compared to vaccination with a needle-syringe. The absence of any skin reaction at the injection site 28 days post-vaccination and lower CRP levels in needle-free sows compared to needle-syringe sows supports that needle-free vaccination may prevent the acute phase response and long term muscular damage associated with an injection. Needle-free vaccination is therefore a promising alternative for improving the welfare of gestating sows. * **

IDAL 3G Designed for safe and efficient vaccination CONVENIENCE Large numbers of pigs can be vaccinated at once reducing labour and increasing efficiency. Easy maintenance and cleaning before/after each session. Long-lasting batteries. Multiple injection site locations. Safety features included. TRACEABILITY Connected by Bluetooth to a supporting smartphone app. Enhances record keeping and traceability. COMPLIANCE Scientifically proven efficacy and safety. Ensures the proper dose every time. Alerts when the vaccine vial is empty.

Porcilis intradermal vaccine portfolio for needle-free administration The first intradermal PCV vaccine for active immunization of pigs as early as 3 weeks of age. Vaccination reduces PCV2 viremia, viral load in lung and lymphoid tissue, and virus shedding. In addiition, loss of daily weight gain and mortality associated with a PCV2 infection are also reduced. Duration of immunity is 23 weeks following vaccination. One-dose vaccine for immunization of piglets as early as 3 weeks of age to reduce lung lesions and decrease in daily weight gain during the finishing period following a Mycoplasma hyopneumoniae infection. Modified live vaccine for the immunization of pigs against PRRSv throughout the production system from as early as 2 weeks of age. Modified live vaccine for immunization of pigs as early as 2 weeks of age against PRRSv-2. Live, attenuated vaccine for the immunization of pigs against Aujeszky s disease virus (Pseudorabies) infections.

References 1 Chase C.C.L., Daniels C.S., Garcia R., Milward F. and Nation T. Needle-free injection technology in swine: Progress toward vaccine efficacy and pork quality. J Swine Health Prod. 2008;16(5):254-261. 2 Summerfield A. The dermis as a prime site of vaccine delivery. International Pig Topics. October 2014. 3 J. Kauffold & H. Sigmarsson, Large Animal Clinic for Theriogenology and Ambulatory Services; E. Ludewig & M. Alef, Clinic for for Small Animals, Faculty of Veterinary Medicine, University of Leipzig, Germany. Images courtesy of University of Veterinary Medicine Giessen, Germany in Cooperation with MSD Animal Health, Germany. 4 Temple D., Mainau E., Amat M. and Manteca X. Animal welfare benefits of the intradermal vaccination in pregnant sows. Porcine Health Management (2017) 3:9. 5 Romani N., Flacher V., Tripp C., Sparber F., Ebner S. and Stoitzner P. Targeting Skin Dendritic Cells to Improve Intradermal Vaccination. Current Topics in Microbiology and Immunology, 2012. 351: 113-138. 6 Teunissen M., Haniffa M. and Collin M. Insight into the immunobiology of human skin and functional specialization of skin dendritic cell subsets to innovate intradermal vaccination design. Current Topics in Microbiology and Immunology, 2012. 351: 25-76.