Raw Materials Sourcing and Bone Gelatin Manufacturing Practices in Europe

1
Raw Materials Sourcing and Bone Gelatin
Manufacturing Practices in Europe

• Presentation to the FDA TSE Advisory Committee
• July 17, 2003 by Reinhard Schrieber

2
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.

3
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.

4
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.

5
Risk ofBone 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.

6
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
  risksare low.

7
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.

8
The Production Process of Bone Gelatin in Europe

• 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

9
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.

10
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
  pre-treatment with either more acid or alkaline
  (lime or caustic).
• The procedure is the same as in the US.

11
From Demineralization to Extraction (1)
(Pre-treatment)

• Two variations of this process are commonly used
• 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).
• The wet ossein is treated for at least 20 days
  with over-saturated 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.

12
From Demineralization to Extraction (2)
(Pre-treatment)

• Another process variation under reviewand 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).

13
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.

14
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 pre-treatments 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.

15
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.

16
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.

17
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 (gt270oF, gt3
  bar, gt20 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.

18
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.

19
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.