Bovine Bone Sourcing Practices and Bone Gelatin Manufacturing Processes in the United States

FDA TSE ADVISORY COMMITTEE MEETING

July 17, 2003

J. Michael Dunn, Ph.D

Vice President, Regulatory Affairs, GELITA North America Chairman, Regulatory Committee Gelatin Manufacturers Institute of America (GMIA)

US BONE GELATIN MANUFACTURERS

Eastman Gelatine Corp. Peabody, MA
35%

5%

GELITA USA Inc. Sioux City, IA

60%

Photo

Pharma

Edible

US manufacturers produce primarily limed bone gelatin (Type B) and to some extent acid bone gelatin (Type A)
The sourcing practices and processing conditions discussed today will be representative of both US manufacturers
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BOVINE BONE SOURCING PRACTICES AND BONE GELATIN 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

BOVINE 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

BOVINE BONE SOURCING PRACTICES

SRMs

All US gelatin bone suppliers have been removing Specified Risk Materials (SRMs) 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 SRMs in the US

GELATIN MANUFACTURING PROCESS OVERVIEW

Daily Bone Gelatin Production

Degreased Gel Bone HCl Acid Water Labor

Gelatin Process

Dicalcium Phosphate

Gelatin
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Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Overall Objectives

Extraction Initial Filtration Ion Exchange Initial Concentration

Hydrolyze collagen
Hydrolyze sufficient cross-links and peptide bonds within the collagen matrix to render the hydrolyzed collagen (gelatin) highly soluble in water

Final Filtration
pH Adjustment Final Concentration Sterilization Chilled Extrusion Drying Milling/Screening

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
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Blending
Formulation Final Packaging

Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Incoming Gel Bone

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration

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%

pH Adjustment
Final Concentration Sterilization Chilled Extrusion Drying Milling/Screening Blending Formulation Final Packaging

In contrast, EU gelatin producers have their own degreasing facilities

Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Acidulation
Objectives / Conditions

Extraction Initial Filtration Ion Exchange

Initial Concentration
Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion

Produce ossein by removing 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
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Drying
Milling/Screening Blending Formulation Final Packaging

Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Liming / Type B
Objectives / Conditions

Extraction Initial Filtration Ion Exchange

Initial Concentration
Final Filtration pH Adjustment

Continue to hydrolyze collagen Continue to remove noncollagen impurities Convert asparagine and glutamine to their respective acids (pI decreases)

Final Concentration
Sterilization Chilled Extrusion Drying Milling/Screening Blending Formulation Final Packaging

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
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Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Washing / Acidification
Objectives / Conditions

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration

Remove and neutralize excess lime Remove non-collagen impurities Adjust pH of the ossein slurry

Sterilization
Chilled Extrusion Drying Milling/Screening Blending Formulation Final Packaging

Wash time: 24 to 48 hours Agitation: Vigorous Water temperature: 45 to 70 F Neutralizing acids: Hydrochloric & sulfuric Target pH: 5 to 7
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Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Acid Treatment / Type A
Objective / Conditions

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion

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)

Drying
Milling/Screening Blending Formulation Final Packaging

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Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Gelatin Extraction
Objective / Conditions

Extraction

Initial Filtration
Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion

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
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Drying
Milling/Screening Blending

Formulation
Final Packaging

Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Initial Filtration
Objective / Conditions

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion Drying Milling/Screening Blending Formulation Final Packaging
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Clarify dilute gelatin solution Protect ion exchange system Vertical leaf pressure filter Pre-coated with diatomaceous earth and cellulose Gelatin concentration: 4-6%

Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Ion Exchange
Objective / Conditions

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion Drying Milling/Screening Blending Formulation Final Packaging
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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%

Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Initial Concentration
Objective / Conditions

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion

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

Drying
Milling/Screening Blending Formulation Final Packaging

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Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Final Filtration
Objectives / Conditions

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion Drying Milling/Screening Blending Formulation Final Packaging
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Clarify concentrated gelatin solution Remove additional coagulated protein and particulate Plate and flame pressure filters Cellulose / diatomaceous earth filter pads

Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

pH Adjustment
Objective / Conditions

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion Drying Milling/Screening Blending

Fine adjustment of the finished product pH

Final pH targets: 5-7 Caustic adjustment: NaOH

Formulation
Final Packaging
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Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Final Concentration
Objective / Conditions

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion Drying Milling/Screening Blending Formulation Final Packaging

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)
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Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Sterilization
Objective / Conditions

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion Drying Milling/Screening Blending

Ensure microbiological purity / product hygiene Equipment: Direct steam injection / HTST Temperature: 138 to 149 C Time: 8 to 16 seconds

Formulation
Final Packaging
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Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Chilled Extrusion
Objective / Conditions

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion Drying Milling/Screening Blending

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

Formulation
Final Packaging
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Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Drying
Objective / Conditions

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion Drying Milling/Screening Blending Formulation Final Packaging

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%
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Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Milling and Screening
Objective / Conditions
Grind gelatin to a uniform size Equipment: Cage mill Particle size: 8 to 30 mesh

Extraction Initial Filtration Ion Exchange

Initial Concentration
Final Filtration pH Adjustment Final Concentration Sterilization Chilled Extrusion Drying Milling/Screening Blending Formulation Final Packaging
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Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Blending
Blender Drumming and weighing

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration

Sterilization
Chilled Extrusion Drying Milling/Screening Blending Formulation Final Packaging
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QC/QA Analysis

Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Formulation
Component Selection
High Capacity Blender

Extraction Initial Filtration Ion Exchange

Initial Concentration
Final Filtration pH Adjustment

Final Concentration
Sterilization

Chilled Extrusion
Drying Milling/Screening Blending Formulation Final Packaging
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QC/QA Analysis

Bone /Type B Acidulation Lime Treatment Washing Acidification

Bone/Type A Acidulation NaOH Option Acid Treatment Washing

GELATIN MANUFACTURING PROCESS

Final Packaging
Drums
FIBCs

Extraction Initial Filtration Ion Exchange Initial Concentration Final Filtration pH Adjustment Final Concentration

Sterilization
Chilled Extrusion Drying Milling/Screening Blending Formulation Final Packaging
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Small Bags