bovine bone sourcing practices and bone gelatin manufacturing processes in the united states j....
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Bovine Bone Sourcing Practices and BoneBovine Bone Sourcing Practices and BoneGelatin Manufacturing ProcessesGelatin Manufacturing Processes
in the United Statesin the United States
J. Michael Dunn, Ph.DVice President, Regulatory Affairs, GELITA North America
Chairman, Regulatory CommitteeGelatin Manufacturers Institute of America (GMIA)
FDA TSE ADVISORY COMMITTEE MEETINGFDA TSE ADVISORY COMMITTEE MEETINGJuly 17, 2003
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US BONE GELATIN MANUFACTURERSUS BONE GELATIN MANUFACTURERS
5%
35%
60%
Photo Pharma Edible
The sourcing practices and processing conditions discussed today will be representative of both US manufacturers
US manufacturers produce primarily limed bone gelatin (Type B) and to some extent acid bone gelatin (Type A)
Eastman Gelatine Corp.Peabody, MA
GELITA USA Inc.Sioux City, IA
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BOVINE BONE SOURCING PRACTICES AND BONE BOVINE BONE SOURCING PRACTICES AND BONE GELATIN MANUFACTURING PROCESSES IN THE USGELATIN MANUFACTURING PROCESSES IN THE US
Overall Objectives Adequately describe the bovine bone sourcing practices
and processing conditions for the manufacturing of bone
gelatin in the US
Confirm that the bone gelatin processing conditions
employed in the US are:
• Virtually the same as those used in the EU
• Meet or exceed all of the minimum processing
requirements as specified in the GME TSE Inactivation
Study Protocol
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BOVINE BONE SOURCING PRACTICESBOVINE BONE SOURCING PRACTICES
Sourcing
Degreased gelatin bone is sourced exclusively from
USDA inspected beef processing facilities in the US
This raw material is derived solely from healthy cattle
that have been deemed fit for human consumption
based upon both ante and postmortem inspections
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BOVINE BONE SOURCING PRACTICESBOVINE BONE SOURCING PRACTICES
SRM’s
All US gelatin bone suppliers have been removing
Specified Risk Materials (SRM’s) with the exception of
vertebrae since as early as 1998
Limited quantities of vertebrae-free gelatin bone have
been available since the Fall of 2002
Currently, there are no FDA or USDA requirements for
the removal of SRM’s in the US
GELATIN MANUFACTURING PROCESS OVERVIEWGELATIN MANUFACTURING PROCESS OVERVIEW
Degreased Gel Bone
HCl Acid Water Labor
Gelatin Process
Dicalcium Phosphate Gelatin
Daily Bone Gelatin Production
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
Acid TreatmentAcid Treatment
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Overall Objectives Hydrolyze collagen
• Hydrolyze sufficient cross-links and peptide bonds within the collagen matrix to render the hydrolyzed collagen (gelatin) highly soluble in water
Purify the gelatin• Employ appropriate processing steps to ensure
its physical, chemical and microbiological purity Concentrate the finished product
• Use additional processes to remove water from the gelatin liquor to produce a dry, stable product
NaOH OptionNaOH Option
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Typical Characteristics
Fat content = 1 to 2.5%
Size range = 1/8 to 5/8”
Mineral/protein ratio = 1.9 - 2.1
Moisture content = 6 to 9%
In contrast, EU gelatin producers have their own degreasing facilities
Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Incoming Gel BoneIncoming Gel BoneAcid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Objectives / Conditions
Produce ossein byremoving the mineral content of the bone
Initiate the hydrolysis of collagen Remove non-collagen impurities
HCL concentration: 4-6% Acidulation time: 5-7 days (counter-current
process) Acidulation temperature: 50° to 65° F Washing: Rinse up to 24 hours to remove
acid salts, fat and other impurities
Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
AcidulationAcidulationAcid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Convert asparagine and glutamine to their respective acids (pI decreases)
Lime slurry concentration: Over saturated Lime slurry pH: Approximately 12.5 Liming time: 25-70 days Liming temperature: 50-70° F Agitation: Daily Lime slurry changes: Weekly
Objectives / Conditions
Continue to hydrolyze collagen Continue to remove non-
collagen impurities
Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Liming / Type BLiming / Type BAcid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Objectives / Conditions
Remove and neutralize excess lime
Remove non-collagen impurities
Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Washing / AcidificationWashing / Acidification
Adjust pH of the ossein slurry
Wash time: 24 to 48 hours Agitation: Vigorous Water temperature: 45° to 70° F Neutralizing acids: Hydrochloric & sulfuric Target pH: 5 to 7
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Objective / Conditions
Condition ossein for extraction at low pH
Traditional• Treatment: Sulfuric acid at pH = 1.0 - 2.0• Treatment time: = 6 hours• Washing: Rinse up to 24 hours to a pH of
2.8 - 3.2 Alkaline pre-treatment option (under review)
• pH is maintained at 13 or greater with NaOH for 3 hours (prior to acid treatment)
Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Acid Treatment / Type AAcid Treatment / Type A
>
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Gelatin ExtractionGelatin Extraction
Objective / Conditions
Solubilize hydrolyzed collagen (gelatin) from the ossein
Water purity: Demineralized Procedure: Series of extractions with
increasing water temperatures Water temperatures: 120° to 200° F Conditioning time: 1 to 6 hours / extraction Number of extractions: 4 to 6
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Initial FiltrationInitial Filtration
Objective / Conditions
Clarify dilute gelatin solution Protect ion exchange system
Vertical leaf pressure filter Pre-coated with diatomaceous earth and
cellulose Gelatin concentration: 4-6%
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Ion ExchangeIon Exchange
Objective / Conditions
Deionize the thin gelatin liquor
Cations removed: Ca+2, Mg+2 and Fe+2
Anions removed: Cl- or S04=
Ash (product): 0.1 to 1%
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Initial ConcentrationInitial Concentration
Objective / Conditions
Concentrate the thin gelatin liquor
Evaporator type: Multiple effect rising film or plate and frame
Concentration target: 15-25% Output temperature: 115° F to 150° F
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Final FiltrationFinal Filtration
Objectives / Conditions
Clarify concentrated gelatin solution
Remove additional coagulated protein and particulate
Plate and flame pressure filters Cellulose / diatomaceous earth filter pads
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
pH AdjustmentpH Adjustment
Objective / Conditions
Fine adjustment of the finished product pH
Final pH targets: 5-7 Caustic adjustment: NaOH
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Final ConcentrationFinal Concentration
Objective / Conditions
Concentrate the thick gelatin liquor
Evaporator type: Thin film / wiped surface or plate and frame multiple effect
Output temperature: 115° to 125° F Concentration target: 25 to 50% (viscosity dependent)
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
SterilizationSterilization
Objective / Conditions
Ensure microbiological purity / product hygiene
Equipment: Direct steam injection / HTST Temperature: 138° to 149° C Time: 8 to 16 seconds
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Chilled ExtrusionChilled Extrusion
Objective / Conditions
Increase the surface area of the gel mass
Glycol - cooled heat exchanger / extruder Temperature: Approx. 70° F Noodle dimensions: 1’ to 2’ long / 1/8” thick
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
DryingDrying
Objective / Conditions
Produce a dry, stable product
Air quality: Heated, dehumidified and filtered Number of zones: 10 to 12 Temperature gradient: 80° to 160° F Time: 1 - 3 hours Moisture content (gelatin): 10 to 12%
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Milling and ScreeningMilling and Screening
Objective / Conditions
Grind gelatin to a uniform size
Equipment: Cage mill Particle size: 8 to 30 mesh
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
BlendingBlending
Blender
Drummingand
weighing
QC/QA Analysis
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
FormulationFormulation
Component Selection
High Capacity Blender
QC/QA Analysis
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option
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Bone /Type BBone /Type B Bone/Type ABone/Type A
AcidulationAcidulation
Lime TreatmentLime Treatment
WashingWashing
AcidificationAcidification
AcidulationAcidulation
WashingWashing
ExtractionExtraction
Initial FiltrationInitial Filtration
Ion ExchangeIon Exchange
Initial ConcentrationInitial Concentration
Final FiltrationFinal Filtration
pH AdjustmentpH Adjustment
Final ConcentrationFinal Concentration
SterilizationSterilization
Chilled ExtrusionChilled Extrusion
DryingDrying
Milling/ScreeningMilling/Screening
BlendingBlending
FormulationFormulation
Final PackagingFinal Packaging
GELATIN MANUFACTURING GELATIN MANUFACTURING PROCESSPROCESS
Final PackagingFinal Packaging
Drums
FIBCs
Small Bags
Acid TreatmentAcid Treatment
NaOH OptionNaOH Option