Genetic toxicology has a good scope in drug safety evaluation
Dr Mukul Pore, Director, INTOX – Institute for Toxicological Studies, is the first Indian scientist who has been recognised and certified by European Society of Toxicology. Sachin Jagdale puts across a few key queries to him to know more about genotoxicity
How will you define genotoxicity in the scientific terms?
Genotoxicity is the study of adverse effects of physical, chemical and biological agents on the genetic material of cells (DNA or chromosomes) and the subsequent expression of these changes.
What is its application in the pharmaceutical industry?
The safety evaluation of pharmaceuticals involves evaluation for risk that a drug can pose to animals and man with respect to genetic apparatus, normal physiological function and reproductive performance. Genetic toxicology deals with evaluating the effect of a chemical on the genetic apparatus. This evaluation is carried out in order to predict the possible risk of carcinogenesis. Regulatory authorities all over the world require data on the genotoxic potential of New Chemical Entities (NCEs) as part of the safety evaluation process. Genotoxicity assays have become an integral component of regulatory requirements. Genotoxicity evaluation is necessary as there is high correlation between genotoxicity and carcinogenic potential of any compound.
What are the other fields where genotoxicity studies are crucial?
Our environment is full of chemicals foreign to the human and animal body. Life of modern man has been greatly improved by the development of chemicals in the various fields of life such as pharmaceuticals, agrochemicals, cosmetics, food additives, industrial chemicals, biological etc.
All living forms are exposed to these environmental agents either as a part of their day to day life processes, accidentally, occupationally or due to acquired life styles. The knowledge that many environmental agents are associated with human cancer development and that genetic alterations are the basis for neoplasia underscored the need for testing genotoxic potential of chemicals. Genetic toxicology tests are among the early studies conducted on any chemical to assess the safety profile of a compound.
Don’t you think that genotoxicity is less understood or less used concept India?
Although few private toxicology centres like INTOX, Advinus, Jai Research Foundation have been involved in safety assessment of pharmaceuticals, agrochemical and other chemicals for last two decades, by Government of India undertook the initiative to create such facility very recently. Departnemtn of Science and Technology (DST) and Indian Council for Medical research (ICMR) have recently established a National Centre in Mumbai. One of the major objectives of the Centre is to develop more expertise, manpower and disseminate information regularly on recent developments in the field. But there is need to create trained manpower in this field by offering formal degree courses at University level.
What needs to be done in order to attract more professionals to the field of genotoxicity testing?
The Government, Universities and National Laboratories should take lead and start formal training courses in this extremely relevant area to meet the challenges of the 21st century. While the need for regulatory safety testing is becoming increasingly obvious, the growing demand for adequate, trained personnel is not being met. There is big shortage of trained manpower in this field. The lack of trained personnel in this field is hurting the industry.
Government in collaboration with National Laboratories and GLP certified CROs should start training courses in toxicology.
How credible are the Indian genotoxicity testing organisations in the global arena?
International guidelines of genotoxicity are changing very fast. Good Laboratory Practice is mandatory Standard for Laboratories for global acceptance of the work.
More and more CROs are coming in India and work carried out in their laboratories is of international standard.
You are the first Indian scientist who has been recognised and certified by European Society of Toxicology. What is so challenging in getting such recognition?
The last decade witnessed the Herculean task of innovating new drugs by Indian pharma industry in line with global players. Safety assessment of the drugs in laboratory animals is mandatory.
Such toxicity studies are carried out by laboratory certified for GLP is mandatory and evaluated by scientist of DABT or European Registered Toxicologists (ERT) status is desirable.
While the majority of certified toxicologists reside in the USA, approximately six percent of American Board of Toxicology (ABT) diplomats are found in other countries (Canada, Europe, Japan etc).
There are number of benefits of certification of toxicologist to society and to the individual. The DABT/ERT certification process is recognized worldwide, thus providing consistent international standard of competence and expertise on toxicology issues. Toxicologists certified by US (DABT) and Europe (ERT) can be trusted to be competent globally. Certification enhances credibility in consulting and testimony. DABT/ERT certification is considered as global standard for competence in toxicology.
What do you predict about the future scope of genotoxicity evaluation services in India?
The field of genetic toxicology has had an overall life of about seventy years and has undergone several rebirths during this period. The development of short term assay for genetic toxicology served to identify many mutagens and address the relationship between mutagens and cancer causing agents.
Today, the pharma industry is taking up newer challenges like use of biotechnology derived products and nanotechnology derived products. Apart from new drugs, genotoxicity assessment is also required to be conducted on genetic drugs wherein these are number and/or quantity of impurities in the genetic drugs as compared to the existing drug in market. In such cases, the impurities that show genotoxic potential need to be evaluated individually.
With these challenges, it is important to understand the increasing scope of genetic toxicology in drug safety evaluation. Molecular biologists/ scientists with hands-on experience in genetic toxicology could look at openings in these laboratories.