Call for proposals for developing novel tools/technologies/processes and product optimization/Scale up of “Anti Snake Venom”
Snake bite is a common and frequently devastating environmental and occupational disease, especially in rural areas of tropical developing countries and is responsible for tens of thousands of deaths and disabilities every year. The World Health Organisation has added snakebite to the list of Neglected Tropical Diseases in 2009. India is estimated to have the highest snakebite mortality in the world. World Health Organization (WHO) estimates place the number of bites to be 83,000 per annum with 11,000 deaths. India therefore contributes to a significant proportion of global snake bite deaths. Although the full burden of human suffering attributable to snake bite remains obscure, hundreds of thousands of people are known to be envenomed and tens of thousands are killed or maimed by snakes every year. There are four species groups of snakes i.e. ‘Big Four’ are primarily responsible for the highest death rate from snakebite in any country in the world.
Snake venoms are the most complex of all natural venoms and poisons. Snake venom neurotoxins block/excite peripheral neuromuscular junctions by acting at various sites and bind to their receptors with high aﬃnity, making reversal of paralysis by anti-venom implausible. Anti-venom, prepared by immunizing horses or sheep with venom from snakes is the only medically accepted remedy for systemic snake envenomation. Antivenom is derived by immunizing horses with snake venom in gradually increasing doses until the horse reaches a high titre of immunity to the venom. The horse's hyper-immune serum is then refined into antivenom. All Indian antivenom are polyvalent, that is, they are effective against all the Big Four common venomous snakes of India. However, the high cost of generating antibodies in horses and side effects, such as serum sickness, are bona fide problems.
There are growing indications from clinicians that anti-venom produced from venoms of the ‘big four’, mainly sourced from a particular region, may not effectively neutralize envenomation by the ‘big four’ and related species in other parts of the country.
There are some critical issues with ASV, the production of which started 100 years ago in India. The potency of the presently available ASV is less than what it was prior to 1950’s. The main issues with ASV in actual clinical practice are species specificity, difficulty in availability, affordability and ideal storage conditions. One of the principal drawbacks of the immunotherapy is the issue of specificity. There is a huge species variation with current taxonomy identifying one, four and eight species of Russell’s viper, cobras and kraits, respectively. So the variable composition and antigenic reactivity of the venom restricts the use of a particular ASV to a geographical area with relevant specificity. Venom variation, low potency, bites by other species could be responsible for the reported failure of polyvalent ASV in countering the venom effects in India.
Further there are various logistic, marketing and economic issues with the production and supply of ASV. Production in lyophilized form is costly, and there can be physiochemical changes in the product by lyophilization. The liquid form requires cold chain. The production of monovalent ASV is a costly affair. In India the monovalent ASV is not produced. However, it has been proposed that in developing countries, the production of ASV can be sustained at affordable prices if cost efficient methods of production are kept in mind. There needs to be rapid technical advancement in production.
Identification of the snake is important in planning the treatment. Anti-venom is the only medically accepted remedy for systemic snake envenomation. Conventional clinical practice is to administer polyvalent ASV often causes severe anaphylaxis reaction in the victim, seen in up to 30 of the recipient’s worldwide demanding secondary treatment. Acute pulmonary oedemas, cerebellar ataxia and uveitis an immunological complication are some of the complications following polyvalent serum. Though monovalent ASVs are available, lack of a proper diagnostic system preludes this opportunity. Many attempts have been made worldwide to develop species specific diagnostic kit based on antibodies, but have not found successful mainly because of inter-species cross reactivity to the crude venom as also the lack of sensitivity related to the small quantities in which venom is injected.
Considering to the importance of snake venom, it is necessary to evaluate the toxicity of protein components of snake venom. The Snake venom is extracted (milked) from different types of poisonous snakes. This extracted venom is stored in the form of lyophilised powder until its requirement for commercial production for anti-snake venom or for any research organization who want to carry research on snake venom. Snake venom is a very costly substance, but unfortunately we don’t have any data whether the efficacy of venom is increasing or decreasing with respect to time. Snake venom should be remain active for approximately 5 to 7 years from the date of its extraction from snake. There is an immediate need of a facility to assure the efficacy of the venom going to be used for the production of the ASV, to assure the quality, safety and efficacy of the ASV and to assure that the quality of the ASV meets appropriate standards and is consistent.
PURPOSE OF THE CALL
Considering the above and other issues related to snake bite problem in India, BIRAC invites proposals for developing novel tools/technologies/processes pertaining to snake bite problem and product optimization/Scale-up on “Anti Snake Venom”.
This call is to seek individual applications on either of the following:
- Development of Novel and alternate ways of ASV production.
- Development of new diagnostics kits for the identification of the snake biting species.
- Characterization, evaluation and validation facility for ASV (Under BIPP, Category IV only).
SCOPE OF THE CALL
The scope of the call will focus on cost effective, novel and innovative approaches.
- The focus is on generating ASV with better product profiles and greater cost effectiveness than current products in market.
- This call seeks proposals to accelerate production of ASV with increased potency.
- This call will support the various stages of an ASV development including, proof concept establishment, preclinical development, product manufacturing and human clinical trials. Applicants may also request funds for production of clinical grade (manufactured Good Laboratory Practices (GLP) guidelines) ASV production.
What the Project should encompass:
The following are some of the indicative priority areas for submitting the proposals,
- Production of Cost effective and improved quality of anti-venom.
- New ways of producing ASV like Recombinant antibody based ASV production technologies.
- Recombinant antibody based ASV for highly purified, well characterized, less allergic ASV having minimum variability.
- Technologies for increasing the potency
- Identification of herbal/peptide and small molecules for possible enhancement of available window for management.
- Plant-made recombinant snakebite anti-venom antibody cocktail.
- A pan-Asian anti-venom – with high potency anti-venom designed for several countries across the South Asian region, produce in large volumes and dispense in single dose.
- An immunoassay for specific identification of the biting species/venomous snake bite in India (identification of venom toxins which are highly specific to the biting snake species, purification of these proteins and development of specific antibodies to these proteins.)
- A diagnostic kit that would help differentiate venomous from non-venomous and also dry bites.
- Development of bedside diagnostic kits for detection and quantification of poison for determining dose requirement of ASV.
- Characterization , evaluation and validation facility for ASV
A product which has not been listed will also be considered if there is a proper justification. Applicants are encouraged to submit their proposals in collaboration with academic institute(s).
Proposals not falling within the scope of the call
- R and D projects involving exploratory research and not resulting in any technology/product
- Processes that are only slight improvements over existing approaches