Health Scientific Committees Scientific Steering Committee (former MDSC) Outcome of discussions

Opinion on the Safety of Gelatine adopted at the Scientific Steering Committee at its plenary meeting of 26-27 March 1998 following a public consultation on the preliminary opinion adopted on 19-20 February 1998 ( Version updated on 3.04.98 ) - Background

The mandate of the Scientific Steering Committee was to advise the Commission on the risk exposure of humans and animals to BSE from gelatine and its co-product dicalcium-phosphate. For humans special attention should be focused on the use of gelatine in the food chain, pharmaceuticals and cosmetics including parenteral use.

As stated in the opinion of 9 April 1996 of the Scientific Veterinary Committee, there are three major factors that influence the risk of exposure from animal by-products in relation to BSE:

(1) The titre of infectivity likely to be found in the tissue used in its manufacture.

(2) The effectiveness of the process used for the inactivation (or the elimination) of the agent.

(3) The kind of application (e.g. food, cosmetics and medicinal products).

The Scientific Veterinary Committee stressed also "that the full data on all gelatine manufacturing processes have not been published, hence a full risk analysis cannot be carried out for gelatine." By-products, such as gelatine, aminoacids and dicalciumphosphate were recognised as giving the best possible guarantees of safety if produced in a process which ensures that all material is subjected to degreasing, followed by acid and/or alkaline treatment followed by heating to 120° and these up to 138-140°C for 4 seconds. The product should be labelled to show the process to which it has been subjected. The Scientific Veterinary Committee emphasised also that: " the specified bovine offals from UK cattle (brain, spinal cord, thymus, spleen, intestine and tonsils) as well as vertebral column and any tissues resulting from trimming carried out in accordance with EC and UK legislation on BSE, should not be used for any purpose (food, feed, medical, pharmaceutical or cosmetic use), whatever the process to which they are subjected."

A similar procedure should also be carried out for material originating from other countries with native cases of BSE.

The preceding opinion differs largely from the 1992 and 1994 opinions expressed by the Scientific Veterinary Committee, stating that " whatever the tissue source, there is a negligible risk from trading in gelatine for technical use, for consumption or in cosmetics additional guarantees are therefore not necessary".

In its opinion of 15 April 1996 on products derived from bovine tissues, especially gelatine, tallow and di-calcium-phosphate in relation with Bovine Spongiform Encephalopathy, the Scientific Committee Food concluded : "Based upon current incomplete knowledge regarding BSE and its possible transmission to humans and the uncertainty about the inactivation of the infective agent, the Committee at present is only able to advise that bovine source materials for these products are to be taken only from geographical areas where BSE does not occur in epidemic conditions. The Committee urges that data required for a scientifically based risk assessment be generated by relevant bodies. Further research is needed especially to develop specific, sensitive and rapid methods for detection of the causative agent in biological materials."

At its meeting of 16 April, 1996, the Committee for Proprietary Medicinal Products (CPMP) of the European Agency for the Evaluation of Medicinal Products (EMEA) endorsed the following conclusion on the potential risk of gelatine in relation to Bovine Spongiform Encephalopathy (BSE): "Three cumulative factors contribute to the safety of gelatine used in pharmaceuticals:

- Manufacturers of gelatine used for pharmaceutical use should not use tissues derived from bovine animals, slaughtered in the UK .

- The additive effects of washing, acid decalcification followed by acid and/or prolonged alkaline treatment, filtration and sterilisation are sufficient to eliminate any possible risk.

- Source tissues used in the manufacture of gelatine are classified as having no detectable infectivity.

On the 3rd of April, 1997, the Multidisciplinary Scientific Committee (MDSC) expressed a similar opinion ato that of the Scientific veterinary Committee on 9 April, 1996, stressing especially: "That at the moment no production method can be considered as safe for gelatine and related products if the base material used is potentially infectious." The opinion further states: "The control of the nature, the geographical origin and the quality of the starting material is currently the only means to assure the protection of public health. The control applied to the starting materials must be subjected to intensive monitoring." The MDSC also confirms its view that "the following tissues should not be used as starting materials: skull, vertebral column, brain, spinal cord, eye, tonsil, thymus, intestine and spleen. (SEE Commission decision of 11th June, 1996, 96/362/EC). The Committee urgently recommends to establish an effective system for the monitoring and the surveillance of TSEs (especially BSE and scrapie)."

In its "Note for Guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via medicinal products" (Revised draft 14 - rev.1 of 2nd September 1997), the CPMP concludes that the risk of transmission of infectious agents can be greatly reduced by controlling a number of parameters which include:

- the source of the animals (including on the basis of their age);

- the nature of animal tissue used;

- the production and transformation processes,

The European Commission Decision N° 97/534/EC of 30 July 1997 confirms the conditions for the manufacture of gelatine from bone raw material. In the 15 E.U. member states as well as for third countries exporting to the E.U. (the general rule applies to all: both for human consumption and for pharmaceutical and cosmetic use), the following risk materials should be excluded: skull, brain, eye, spinal cord, tonsils. The decision also excludes the use of the vertebral column of cattle, sheep and goats of over 12 months of age for mechanically recovered meat for human consumption.

So far, bones, a raw material for the production of gelatine, have been considered as a material with no detectable infectivity. Bovine bone marrow, by analogy with bone marrow from sheep with scrapie, was classified as belonging to the category of low potential infectivity materials. In its opinion adopted on 8-9 December 1997, the Scientific Steering Committee states:

(on) dorsal root ganglia. New (unpublished) evidence shows that the dorsal root ganglia - located within the general structure of the vertebral column - should be considered as having an infectivity for BSE equivalent to that of the spinal cord. The dorsal root ganglia proved infective at the same time after infection as the spinal cord, i.e. 32 months. The trigeminal ganglia were also infective, but so far no autonomic nervous system tissue has been found to be infective. The dorsal root ganglia cannot be removed without extreme difficulty. This therefore means that as a precautionary proposal the removal of the whole vertebral column (other than the coccyx) is now appropriate. Care needs to be taken to ensure that the removal of the vertebral column incorporates the lateral aspect of the vertebral bodies. This dissection may sometimes be difficult in practice unless the musculature is selectively removed from the vertebral bones for selling as bone-free meat.

(on) Bone marrow :

1. Early studies with mice intracerebrally injected with bone marrow from cattle with spontaneous clinical BSE has not demonstrated infectivity (SEAC, 1994). However, studies on calves, experimentally infected by feeding 100g of BSE infected brain tissue, have now shown bone marrow infectivity in cattle studied at 38 months after feeding the BSE infected brain. These animals were clinically affected by BSE. (MAFF, unpublished evidence 3.12.1997). This has wide-ranging implications because it implies that long bones as well as vertebral columns must be considered potentially infective. The concerns on contamination and the dorsal ganglia mean that on these grounds alone the vertebral columns of older animals should be included in the category of specified risk material.

2. Several issues now emerge from the new report on bone marrow infectivity. First the apparent infectivity of bone marrow might need to be redefined. Bone marrow (on the basis of scrapie studies) was placed in Category III, i.e. as showing low infectivity. In previous bone marrow studies on clinical cases of BSE infected cattle, no infectivity was detected which might have suggested that the WHO classification was inappropriate in persisting with a Category III, rather than a Category IV, rating, i.e. no demonstrable infectivity. However, new evidence shows 2 of 18 mice developing late clinical disease after having been injected with marrow from cattle of 38 months post infection. Another 3 mice also show immunocytological evidence of the presence of PrP ^Sc, having been injected with the same bone marrow extract. Given the late development of this demonstrable infectivity in cattle bone marrow despite the substantial infective dose (100 g untreated BSE infective brain) it now seems appropriate to maintain the WHO classification for BSE as well as for scrapie. This signifies that BSE is increasingly being revealed as having a tissue based infectivity which seems similar to that of scrapie.

3. This conclusion reinforces the concepts [...] that the different levels of infectivity do reflect a graded phenomenon and that it is unwise to consider the BSE agent as either present or absent in particular tissues.

4. The bone marrow findings also raise the issue of whether bones from older animals, e.g. >30 months, should be removed from the human food chain."

As far as infectivity of bone marrow is concerned, the working group on gelatine of the Scientific Steering Committee noted that the above statements referred to infectivity resulting from a single group of experimentally challenged cattle. However, infectivity of the bone marrow of naturally infected bovines has, to present knowledge, not been detected. According to Hadlow et al. (1982), infectivity has been reported in bone marrow of Suffolk sheep with natural, clinical scrapie but (Hadlow et al., 1980) not in goats with natural scrapie.

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