1. Flavomycin ® “The original”

2. 2 Content

3. 3 Introduction Stability Flavomycin ® compared with generics - Flavomycin 40 and 80 - in feed - in premix Conclusions Flavomycin

4. 4 Introduction Wallhäuser et al in 1965, designated it as moenomycin Popular names: “bambermycin”, “flavophospholipol”, Flavomycin ® Initially recovered from: –Streptomyces bambergiensis –Three other Streptomyces spp. (S. ghanaensis, S. ederensis, and S. geysiriensis) are also identified Flavophospholipol is stable in: –the pH range from 7 to 9 –the presence of a large variety of enzymes (including trypsin, amylase, lysozyme, and lipase) Is a complex of five active, chemically related, compounds (A, A1/2 C1, C2 and C3), all (Huber et al 1965; Lenoir et al 1970) Characterized as very high molecular weight phosphorus containing glycolipids (1582 g/mol) Biologically, flavophospholipol had particular antibiotic activity against Gram positive bacteria: –no evidence of cross resistance to other antibiotics such as penicillin, tetracycline or macrolides (Wasielewski et al 1965)

5. 5 Flavomycin ® Specifications Flavophospholipol content Moisture* (2% average) Heavy Metals oArsenic ≤ 5 ppm oLead ≤ 10 ppm oCadmium ≤ 5 ppm o Mercury ≤ 0.2 ppm * H 2 O content bound inside the Flavomycin molecule determines heat stability. The Flavomycin molecule is compact due to intra-molecular bounds and contains less H 2 O molecules, compared with generics.

6. 6 Moisture and pH

7. 7 Specifications cont’d Product description Visual (aspect, color) Bulk density (loose) Volumetric check Bulk density (compacted) Volumetric check Flow properties Shear cell test Particle size distribution Laser diffraction test

8. 8 Typical distribution of FPL components: A, A1/2, C1, C3, C4

9. 9 Not the right % spread Typical distribution of FPL components: A, A1/2, C1, C3, C4

10. 10 Stability data summary

11. 11 Flavomycin 40 and 80

12. 12 Flavomycin ® stability data Huvepharma (for regulatory purpose) Fl 80 Fl 40

13. 13 vs. Flavomycin® Stability study performed under stress conditions during 20 days at 55°C Flavomycin ® vs. generics Evolution of FPL content in % of the claimed activity

14. 14 Stability Flavomycin ® in normal storing conditions vs. generics

15. 15 IN FEED

16. 16 Stability in different extruded feeds Flavomycin mixed into piglet and broiler feed undergoing extrusion process Flavomycin mixed into piglet and broiler feed undergoing extrusion process temperature and pressure at head of extruder: 145°C, 50 bar temperature and pressure at head of extruder: 145°C, 50 bar duration of passage through extruder: 5 to 10 sec. duration of passage through extruder: 5 to 10 sec. efficiency of extruder: 300 kg of feed/h values given are the average of 4 replicates efficiency of extruder: 300 kg of feed/h values given are the average of 4 replicates Piglet feedBroiler feed Content of active ingredientMg/kg% % Nominal2010020100 Actual before conditioning211051995 after conditioning199518.894 after extrusion, before cooling21.3106.520.3101.5 after extrusion and cooling20.810420.5102.5 Ref.: Trial report no. 1358 of International Institute of Feed Technology, Braunschweig, Germany

17. 17 Stability under Expansion Conditions Ref.: Trial report no. 1457 of “Research Institute for Feed Technology”, IFF, Braunschweig, Germany Broiler Feed Production line consisted of mixer, conditioner, expander, pellet press and cooler; expander yielded 1t / hour two approaches were run: one using commercially practiced conditions the other using maximum conditions technically possible with equipment employed in heat, pressure and energy. Commercial conditions parameters maximum conditions temperature during expansion90 - 112 ° 124 - 135 ° after expansion95 ° 100 ° after pelleting97 ° 100 ° pressure in expander52 bar 70 bar specific energetic input 33.7 kWh/t 40.8 kWh/t results site of measurement inclusion, ppm %inclusion, ppm % after mixing 28.7 100 28.3 100 after conditioning 25.7 89.5 26.0 91.9 after expansion 26.3 91.6 27.0 95.4 after pelleting/cooling 29.3 102.1 28.3 100 Feed contained 5.2 % fat; dosage used for FLAVOMYCIN is not a recommendation, but was used to minimize random variation

18. 18 In Premix

19. 19 Comparison of Flavomycin and Flaveco* under different storage conditions *Flaveco is based on Chinese FPL

20. 20 Storage condition: 25 °C / 50 % h Comparison of Flavomycin and Flaveco under different storage conditions expected level

21. 21 Storage condition: 40 °C / 75 % h Comparison of Flavomycin and Flaveco under different storage conditions expected level

22. 22 Conclusions

23. 23 Conclusion oBetter stability vs. generics of the additive itself, in feed and in premix which is related to: –Compacter molecule, low nr of H 2 O molecules bound –Fermentation technology and knowledge –Fermentation medium composition –Quality of carrier and additives used in its composition oSuperior formulation –Available as dust free powder or as granule –Standardization technology –Spray dry technology oStrict compliance of the specs of the different components –Five different components (e.g. component A between 40 and 80% of the FLP complex) –Percentage of components is calculated in accordance to the detected potency (relative) –Water content, pH oInvestments in technology & Quality –Modern EU fermentation sites with the most important certifications: HACCP,GMP, GMP+, FDA, ISO. Flavomycin, the original

24. 24 Flavomycin ® “ADDING PERFORMANCE TO YOUR BUSINESS”