The CPI has implemented a strong technological development program which has been essential to consolidate the production activity, since it has introduced innovations and improvements to the production and quality control processes of the antivenoms. Technological research at the CPI has focused mainly on three areas: improving the productivity, efficacy, and safety of antivenoms.
At the same time, collaborations with the academic sector, the industry and governments offer opportunities for the institute to contribute to the solution of national problems where the technology, trajectory and capacities of the CPI are useful to other fields in health care, aside from ophidism.
The new developments produced to satisfy the current needs of different countries and regions around the world are:
Purification of Human Plasma Proteins for Therapeutic Use: Albumin and Immunoglobulins
Human plasma is the liquid portion of the blood. It has more than one hundred proteins which are present in different concentrations and exhibit different physiological functions. Thus, it represents a source of therapeutic proteins for the treatment of different pathological conditions. Given its therapeutic and economic importance, the production of immunoglobulins, albumin, and coagulation factors is the primary focus of the biotechnology industry dedicated to plasma fractionation around the world.
Purified immunoglobulins are medicinal products used to treat ailments like immunodeficiencies, autoimmune diseases, bone marrow transplant, among others. Albumin is used to treat burns, dehydration, malnutrition, and hepatitis.
The Clodomiro Picado Institute developed and patented a methodology for primary human plasma fractionation through an aqueous two-phase system. Furthermore, the purification line for immunoglobulins and albumin was designed independently. The primary fractionation methodology developed at the CPI is an alternative to the Cohn process used by every company in the global industry of hemoderivative production.
After a preliminary design and development stage, successfully carried out at a laboratory scale, the Institute is now at the second stage of the process, which consists of scaling the immunoglobulin and albumin production lines from plasma volumes of 50L. The objective is to demonstrate the scalability of the processes to obtain products that comply with the international quality requirements specified.
Recently, new medical applications have been discovered for human plasma derivative products, which increased their demand in a way that has not been proportional to the growth of blood donations worldwide. This causes a global shortage of hemoderivatives and a price increase that affects mainly countries with less purchasing power. Thus, the technology developed by the Institute could help satisfy the national needs, and eventually, regional needs.
Antivenom for Sri Lanka
Snakebite envenoming represents an important public health danger in Sri Lanka, a country with one of the highest mortality rates caused by this phenomenon. Every year a minimum of 40,000 people are reported with bites from the following snakes: Daboia russelli, Echis carinatus, Hypnale hypnale, Bungarus caeruleus and Naja naja.
Today the only treatment available for these envenomings is the administration of antivenoms fabricated in India. However, there are several problems related to this phenomenon: the price of these products is high, the original design of the antivenoms contemplates venoms from India, not Sri Lanka where there are different snakes, and lastly, there is a possibility that patients treated with these antivenoms display adverse reactions related to their high content of proteins and bacterial endotoxins.
An international collaboration between the Peradeniya University in Sri Lanka, the CPI in Costa Rica, and the non-governmental organization AVRI (Animal Research International) was born as a reaction to this situation. Their objective was the creation of effective, safe, and efficient antivenom to treat people with bites from venomous snakes in this country. Within the CPI this antivenom was designed by the stables and production sections. The purpose of the collaboration, aside from creating a pilot antivenom, is to transfer the technology that will allow Peradeniya University to establish a local production of the antivenom.
The process so far has characterized the venoms, immunized the horses, and produced a first batch of the pilot scale antivenom, which is being assessed for its stability and preclinical neutralization profile against the aforementioned venoms.
The CPI has initiated the process to purify albumin from the same equine plasma used to produce the antivenom. To accomplish this, the primary plasma purification attained with the plasma protein fractionation method using an aqueous two-phase system was researched and developed on a laboratory scale. This is a method developed at the CPI to obtain the antivenom and albumin simultaneously.
Equine albumin can be used in the treatment of horses with colics, equine infectious anemia, brucellosis, salmonellosis, dehydration, and volume depletion. This is a good option for people who use therapeutic saline or protein solutions from other origins, to treat equines who display said symptoms.
The CPI is currently working on the scaling stage of the albumin production line. This stage is carried out with plasma levels of 50L. The objective is to demonstrate the scalability of the processes to obtain albumin that complies with the international quality requirements specified.
The Technological Development and Serpentarium sections have developed a product that can be administered to cattle to prevent the main systemic effects caused by snake envenomings.
This product is a detoxified fer-de-lance (Bothrops asper) venom that, when administered before snakebites happen in cattle vaccine schemes, has the capacity to modulate the immune response of the vaccinated animals, promoting an immune system boost that will eventually act over the injected venom. The final result is a decrease in the toxic effects of the venom, and more valuable time for people to understand what happened to their animals, and keep them from dying or suffering serious systemic problems.
The toxoid does not prevent snakebites, nor can it be used as an alternative to antivenom. It does decrease the systemic effects produced by fer-de-lance (Bothrops asper) venom in cows, and it helps avoid the quick death of the animals, giving time to use the antivenom when needed.
Even though the performance of the toxoid has not been assessed against other snake species, and its functionality in other animals like horses, sheep, goats, and dogs has not been determined, these possibilities are being studied right now in research projects.