Transcript Slide 1

Flavomycin® “The original”
Content
2
Content
OH
HO
CH3
O
HO
CH3
CH3
HO
O
O
CH2
CH3
O
O
HO
H3C
O
O
O
O
CH3
OH
O
CH3
P
OH
O
H
O
O
O
CH3
O
NH
NH
HN
CH3
O
O
COOH
Flavomycin
O
O
HO
OH
NH2
CH3
COOH
HO
HO
OH
• Introduction
• Stability Flavomycin® compared with generics
- Flavomycin 40 and 80
- in feed
- in premix
• Conclusions
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Introduction
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•
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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
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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)
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•
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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)
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Flavomycin® Specifications
• Flavophospholipol content
• Moisture* (2% average)
• Heavy Metals
o
o
o
o
Arsenic ≤ 5 ppm
Lead ≤ 10 ppm
Cadmium ≤ 5 ppm
Mercury ≤ 0.2 ppm
* H2O content bound inside the Flavomycin molecule
determines heat stability. The Flavomycin molecule is
compact due to intra-molecular bounds and contains less
H2O molecules, compared with generics.
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Moisture and pH
Loss during drying
9
9%
8
5%
1%
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pH
G
en
er
ic
B
G
en
er
ic
A
en
er
ic
G
Loss of
C
7,5
40
3%
Fl
av
om
yc
in
%
7%
pH
8,5
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Specifications cont’d
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•
•
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Product description
Bulk density (loose)
Bulk density (compacted)
Flow properties
Particle size distribution
Visual (aspect, color)
Volumetric check
Volumetric check
Shear cell test
Laser diffraction test
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Typical distribution of FPL
components: A, A1/2, C1, C3, C4
%
Components distribution %
90
80
70
60
50
40
30
20
10
0
A
A1/2
C1
C3
C4
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Typical distribution of FPL
components: A, A1/2, C1, C3, C4
Not the right % spread
A1/2
C1
C3
3
er
ic
2
G
en
er
ic
1
G
en
G
en
er
ic
9
8
7
6
5
4
3
2
20
18
16
14
12
10
8
6
4
2
0
1
%
Components without A
C4
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Stability data summary
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Flavomycin 40 and 80
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Flavomycin® stability data Huvepharma
(for regulatory purpose)
Stability Flavomycin Huvepharma
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Fl 80
10
%
8
6
4
Fl 40
2
0
0
1
2
3
6
9
months
40°C RH 75% Moisture
40°C RH 75% Activity
25°C RH 60% Moisture
25°C RH 60% Activity
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Stability study performed under stress
conditions during 20 days at 55°C
Flavomycin® vs. generics
Residual
stability
FLP
vs. Flavomycin®
Evolution of FPL
content in
% of the
claimed
activity
100
95
Huvepharma
%
90
Generic 1
85
Generic 2
80
Generic 3
75
70
0
5
10
20
Time lines in days
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Stability Flavomycin® in normal storing
conditions vs. generics
µg/mg
Stability Flavo next to generics
44
42
40
38
36
34
32
30
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Declared
Flavomycin 40
+6md
Generic A
+9 md
Generic B
+12 md
Generic C
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IN FEED
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Stability in different extruded feeds
• Flavomycin mixed into piglet and broiler feed undergoing
extrusion process
• temperature and pressure at head of extruder: 145°C, 50 bar
• 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
Piglet feed
Content of active ingredient
Broiler feed
Mg/kg
%
Mg/kg
%
20
100
20
100
before conditioning
21
105
19
95
after conditioning
19
95
18.8
94
after extrusion, before cooling
21.3
106.5
20.3
101.5
after extrusion and cooling
20.8
104
20.5
102.5
Nominal
Actual
Ref.: Trial report no. 1358 of International Institute of Feed Technology, Braunschweig, Germany
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Broiler Feed
Stability under Expansion
Conditions
• 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
maximum conditions
parameters
temperature
during expansion
after expansion
after pelleting
pressure in expander
specific energetic input
90 - 112 °
95 °
97 °
52 bar
33.7 kWh/t
124 - 135 °
100 °
100 °
70 bar
40.8 kWh/t
results
site of measurement
after mixing
after conditioning
after expansion
after pelleting/cooling
inclusion, ppm %
28.7
100
25.7
89.5
26.3
91.6
29.3
102.1
inclusion, ppm
28.3
26.0
27.0
28.3
%
100
91.9
95.4
100
Feed contained 5.2 % fat; dosage used for FLAVOMYCIN is not a recommendation, but was used to minimize random variation
Ref.: Trial report no. 1457 of “Research Institute for Feed Technology”, IFF, Braunschweig, Germany
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In Premix
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Comparison of Flavomycin and Flaveco*
under different storage conditions
Storage conditions:
25 °C / 50 % h
40 °C / 75 % h
Premix:
Flavomycin
Flaveco
Flavomycin
Flaveco
Batch; Prod. D ate:
U 023; 8/98
098051038; 5/98
U 023; 8/98
098051038; 5/98
Expected content; mg/ kg:
40.000
40.000
40.000
40.000
Initial content 1/ 99:
44.200
33.300
44.200
33.300
After 4 weeks storage:
48.133
34.567
42.250
30.000
After 8 weeks storage:
44.050
31.350
40.050
24.950
After 12 weeks storage:
42.500
31.300
37.700
23.000
After 21 weeks storage:
39.800
29.200
36.600
15.600
*Flaveco is based on Chinese FPL
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Comparison of Flavomycin and Flaveco
under different storage conditions
Storage condition: 25 °C / 50 % h
50.000
Flavomycin
48.133
45.000
40.000
Flaveco
44.200
44.050
42.500
expected level
39.800
35.000
30.000
33.300
34.567
31.350
31.300
29.200
25.000
20.000
start
4 weeks
8 weeks
12 weeks
21 weeks
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Comparison of Flavomycin and Flaveco
under different storage conditions
Storage condition: 40 °C / 75 % h
50.000
Flavomycin
Flaveco
45.000
40.000
44.200
expected level
42.250
35.000
30.000
40.050
37.700
36.600
33.300
30.000
25.000
24.950
20.000
23.000
15.000
15.600
10.000
start
4 weeks
8 weeks
12 weeks
21 weeks
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Conclusions
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Conclusion
Flavomycin, the original
o Better stability vs. generics of the additive itself, in feed and
in premix which is related to:
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–
–
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Compacter molecule, low nr of H2O molecules bound
Fermentation technology and knowledge
Fermentation medium composition
Quality of carrier and additives used in its composition
o Superior formulation
– Available as dust free powder or as granule
– Standardization technology
– Spray dry technology
o Strict 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
o Investments in technology & Quality
– Modern EU fermentation sites with the most important
certifications: HACCP,GMP, GMP+, FDA, ISO.
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Flavomycin®
“ADDING PERFORMANCE TO YOUR BUSINESS”
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