Transcript Raw Materials Sourcing and Bone Gelatin Manufacturing Practices in Europe

Raw Materials Sourcing
and
Bone Gelatin Manufacturing Practices in
Europe
Presentation to the FDA TSE Advisory Committee
July 17, 2003 by Reinhard Schrieber
Sourcing of Bovine Bones (1)
GME members have taken voluntary steps to ensure the
safety of raw materials sourced from European countries
• Since long before the emergence of BSE, GME members
have
used only raw materials from healthy slaughtered
animals that are released for human consumption.
• No bones at all sourced from the UK.
• 1997: Removal of heads in Europe.
• 1998: Removal of spinal cord in Europe.
• 1998: Partial replacement of European bones by imports.
• 1999: Removal of vertebrae from animals of every age.
No.2
TSEAC July 17, 2003
Sourcing of Bovine Bones (2)
GME members have taken voluntary steps to ensure the
safety of raw materials sourced from
GBR II countries
• Only use of raw materials from healthy slaughtered
animals, released for human consumption.
•1997: Removal of heads.
•1998: Removal of spinal cord.
•1998: Removal of vertebrae from animals of every
age from India, Pakistan and Nigeria.
No.3
TSEAC July 17, 2003
Sourcing of Bovine Bones (3)
Measures required by European Regulation
• 1996: No bones at all from the UK.
• 1999: Implementation of the Edible Gelatin
Regulation.
• 2000: Removal of heads.
• 2000: Removal of spinal cord.
• 2001: BSE testing of all cattle older than 30
months.
• 2001: Removal of vertebrae from animals older
than 12 months.
No.4
TSEAC July 17, 2003
Risk of
Bone Contamination (1)
• Because of the steps taken by the industry there was
always a very little chance that BSE infectivity could be
present in the raw materials used to produce bovine-origin
gelatin.
• Other more recent controls provide additional safety, for
example:
– Rapid post mortem BSE testing,
– the careful removal of specified risk materials (SRMs)
make it almost impossible for highly infective materials to
enter the supply chain.
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TSEAC July 17, 2003
Risk of
Bone Contamination (2)
• As with any processes and systems, there is a possibility
of error.
• For example
– animals with low infectivity may be undetected,
– surveillance systems might be non-adequate,
– removal of SRMs may not be done perfectly,
– infectivity of bone marrow has not been finally clarified.
• Based on our experience, we believe that those risks
are low.
No.6
TSEAC July 17, 2003
Comparison of actual Raw Material
Risks and the GME Study Design
• To account for the potential risk presented by raw
materials, GME has studied the effectiveness of the
gelatin manufacturing process in eliminating BSE
infectivity by assuming that the raw materials are highly
contaminated.
• The tests have been done with a level of infectivity at
least 10,000 times higher than could theoretically have
been possible in practice.
– The tests have assumed that ALL animals used were
clinically infective.
– The tests have assumed that the bones from all animals
contain the full quantity of infective spinal cord and dorsal
root ganglia.
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TSEAC July 17, 2003
The Production Process of Bone Gelatin
in Europe
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Bone transport, inspection, degreasing, drying and storage
Demineralization
Acid / alkaline pre-treatment
Washing and extraction
Filtration, demineralization and concentration
Sterilization
Drying, testing, storage, blending, testing and shipping
All plants are ISO 9000 certified and have a HACCP
system in place. They have been FDA inspected as well.
All relevant production parameters of the processes have
been validated in our plants against the GME study
conditions by the independent
“SGS European Quality Certification Institute”
No.8
TSEAC July 17, 2003
From Raw Bone to Bone Chips
(Degreasing in Europe)
• The fresh bones are collected from the meat processors.
• The only bones collected are those from healthy
slaughtered animals released for human consumption
following ante and post mortem inspection.
• Before processing, the bones are inspected for foreign
materials (also SRM) on sorting belts.
• The bones are crushed (max. 5/8 inch) and in a continuous
process degreased by hot water (appr. 185 oF for appr. 20
minutes with high agitation).
• The solid bone particles are separated, dried with hot air
(the surface temperature will remain below 150 oF), sieved
to remove fine materials and stored in silos.
No.9
TSEAC July 17, 2003
From Bone Chips to Ossein
(Demineralization)
• The bone chips, produced in Europe or imported, are
treated with diluted hydrochloric acid (min. 4 %) in a
countercurrent system for 4 days minimum.
• The phosphate of the bones dissolves and only the
protein matrix, called ossein, remains.
• The ossein is washed and then ready for further pretreatment with either more acid or alkaline (lime or
caustic).
The procedure is the same as in the US.
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TSEAC July 17, 2003
From Demineralization to Extraction (1)
(Pre-treatment)
Two variations of this process are commonly used
1. The wet ossein is directly treated with sulfuric acid for
another 24 hours and then prepared for low pH acid
extraction.
(This process is applied to 2 - 3% of the production for special
gelatin capsules).
2. The wet ossein is treated for at least 20 days with oversaturated lime solution at appr. pH 12,5.
It is then washed and prepared for extraction at appr.
neutral pH.
(This process is the standard for more than 95% of the gelatin).
These manufacturing conditions are applied in Europe and
the US.
No.11
TSEAC July 17, 2003
From Demineralization to Extraction (2)
(Pre-treatment)
Another process variation under review
and not in common use
• The wet ossein is kept after the addition of 0.3 M
NaOH for a minimum of 2 hours at a pH of 13.0 and
then washed, again treated with sulfuric acid for 24
hours and prepared for low pH acid extraction.
(The interest in and potential applications for this type
of product are under review).
No.12
TSEAC July 17, 2003
From Ossein to Gelatin
(Washing and Extraction)
• After pre-treatment the ossein is washed and the pH
adjusted to the desired extraction value.
• Extraction is done stepwise by using 4 to 6 times new
hot water with increasing temperature starting from
about 125 oF up to 200 oF.
• Each time the length of stay is about 4 hours.
• The different extracts have different physical properties
• The intended use of each extract of one production day
might be different (photo, pharma, food).
• All gelatins comply with the regulatory requirements for
food and pharma.
Same procedures in Europe and the US.
No.13
TSEAC July 17, 2003
The Purification of Gelatin
(Filtration, Demineralization, Concentration)
• The diluted (3 - 5 %) gelatin solution is filtered by
different types of centrifuges, cellulose and/or
diatomaceous earth filters.
• Mineral salts, anion and cation, remaining from the pretreatments of the ossein are removed by ion-exchange
columns.
• Afterwards the gelatin solution is concentrated by
ultrafiltration and/or vacuum evaporation.
Same procedures and equipment as in the US.
No.14
TSEAC July 17, 2003
The Sterilization of Gelatin
(UHT Treatment)
• The concentrated gelatin solution (25 to 45 % gelatin)
is sterilized by direct steam injection.
• The temperature under pressure in the liquid phase is
min. 280 oF for at least 4 seconds.
• After expansion the temperature drops back to about
130oF.
Same procedures and equipment as in the US.
No.15
TSEAC July 17, 2003
Final Procedures
(Drying, Testing, Blending, Testing, Shipping)
• Finally the sterilized gelatin solution is chilled to set and
then dried with purified and conditioned air on belt
dryers.
• Each production batch (single extract) is tested for
physical, chemical and bacteriological properties.
• Different production batches with different properties
are dry blended according to customer specification.
• The final blends are again tested for physical, chemical
and bacteriological compliance with regulatory and
customer requirements.
• After testing, the released gelatin is shipped.
Same procedures and equipment as in the US.
No.16
TSEAC July 17, 2003
Heat and Pressure Process
( a Special Case for Low Gelling Gelatin)
Done by only one company in Europe
• Degreasing like standard gelatin.
• 1. Autoclaving the bone chips
(>=270oF, >3 bar, >=20 minutes).
• Extraction with hot water.
• 2. - 7. Autoclaving at lower temperature and shorter time.
• Collection of different extracts.
• Flocculation, ion-exchange, evaporation.
• Drying, testing, blending, testing, shipping.
No.17
TSEAC July 17, 2003
Conclusions (1)
• This review of the gelatin manufacturing process is
intended to show the commercial minimum
manufacturing conditions reflected by the GME
study.
• The study design has been validated against the
actual process parameters used at GME plants.
• The study demonstrates the ability of the gelatin
manufacturing process to remove and inactivate
infectivity - even under conditions in which the raw
materials contain unrealistically high infectivity levels.
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Conclusions (2)
• The safety of European bovine bone gelatin is
established on two principles:
– The safety of the raw materials (as required by GME
practices and EU law) and,
– the safety of the manufacturing process (as
demonstrated by the GME study).
• The Scientific Steering Committee of the European
Union has concluded, based on these principles, in its
“Opinion on the safety of gelatin” that the
“risk is close to zero”.
No.19
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