Day 14 – Q 3. What are the risks associated with the development cycle of a medicine or vaccine? What are the regulatory provisions to ensure drug safety in India? Examine. 

3. What are the risks associated with the development cycle of a medicine or vaccine? What are the regulatory provisions to ensure drug safety in India? Examine. 

किसी दवा या वैक्सीन के विकास चक्र से जुड़े जोखिम क्या हैं? भारत में दवा सुरक्षा सुनिश्चित करने के लिए नियामक प्रावधान क्या हैं? जांच करें।

Demand of the question:

It expects students to write about the risk associated with the development of medicine or vaccine along with regulatory provisions to ensure drug safety in India.

Introduction:

The University of Oxford and AstraZeneca Plc.’s experimental vaccine is the first to enter the final stages of clinical trials to assess how well it works in protecting people from becoming infected by the virus that causes the corona virus disease (Covid-19), which has infected 9.4 million and killed 480,000 globally since late December.

Body:

There were 13 experimental vaccines in clinical trials and another 129 in the preclinical evaluation stage on June 22, according to the World Health Organisation’s draft landscape of Covid-19 vaccines.

Risk associated with development cycle of a medicine or vaccine:

• There are two kinds of risk associated with the development of medicine or vaccine. First is associated with the developer of drug or vaccine whereas second associated with the process of development and use of medicine or vaccine.   
• Risks to developer: Cost of research and development (R&D), biological and technical challenges associated with targeting more complex diseases, competition with better standards of care, larger scale of clinical studies to prove safety and efficacy and last but not least an increasingly stringent regulatory environment.
• There is chance of too many resources of pharmaceutical companies might get wasted in development of one particular drug or vaccine in competition with others.
• Vaccine development, on average, takes 10.71 years from the preclinical phase, and has a success rate of 6%, according to a study in the science journal, PLOS One. Some remain elusive for decades despite massive investments, like for vaccines against HIV, the virus that causes AIDS. 
• There is always chance of retreat of disease even before the development of medicine or vaccine dedicated for that disease which might led to financial disaster.  
• Risks associated with processes and use: Scientists and medical experts are concerned that rushing a vaccine could end up worsening the infection in some patients rather than preventing it.
• Risk of vaccine enhancement, where instead of protecting against infection, the vaccine can actually make the disease worse when a vaccinated person is infected with the virus. The mechanism that causes that risk is not fully understood and is one of the stumbling blocks that has prevented the successful development of many vaccines
• Researchers would take months to test for the possibility of vaccine enhancement in animals. Given the urgency to stem the spread of the new corona virus, some drug makers are moving straight into small-scale human tests, without waiting for the completion of such animal tests.
• There is a risk of immune enhancement: Some vaccinated animals developed more severe disease compared with unvaccinated animals when they were exposed to the virus during previous SARS outbreak trials.
• The best-known example occurred in a U.S. trial in the 1960s of a vaccine created by the NIH and licensed to Pfizer Inc to fight respiratory syncytial virus (RSV), which causes pneumonia in infants. The vast majority of babies who received the vaccine developed more severe disease, and two toddlers died. 
• A more recent example occurred in the Philippines, where some 800,000 children were vaccinated with Sanofi’s dengue vaccine, Dengvaxia. Only afterward did the company learn that it could increase the risk of more severe disease in a small percentage of individuals.
• Study of side effects: It might take long time to gauge side effects among vaccinated set and genetic susceptibility of drug or vaccine. 
• Vaccine derived virus: Example of vaccine derived polio virus, on rare occasions, if a population is seriously under-immunized, an excreted vaccine-virus can continue to circulate for an extended period of time. The longer it is allowed to survive, the more genetic changes it undergoes. In very rare instances, the vaccine-virus can genetically change into a form that can paralyse known as a circulating vaccine-derived poliovirus (cVDPV). 
• Ethical challenge: If we could develop a drug or an antibody that would be able to mitigate the disease, we would still need to think about the ethical concerns of a human challenge. There’s also the question of who volunteers for such a challenge. There’s been a whole history extremely fraught where minorities were used as experimental subjects without their understanding or consent.

Regulatory provisions for drug safety in India:

• Under the Drug and Cosmetics Act, 1940 (latest amendment in 1995) subsequent Drugs and Cosmetic Rules, 1945 the regulation of manufacture, sale and distribution of Drugs is primarily the concern of the State authorities.
• While the Central Authorities are responsible for approval of New Drugs, Clinical Trials in the country, laying down the standards for Drugs, control over the quality of imported Drugs, coordination of the activities of State Drug Control Organisations and providing expert advice with a view of bring about the uniformity in the enforcement of the Drugs and Cosmetics Act.
• Drug Controller General of India is responsible for approval of licenses of specified categories of Drugs such as blood and blood products, I. V. Fluids, Vaccine and Sera.
• Demonstration of safety and efficacy of the drug product for use in humans is essential before the drug product can be approved for import or manufacturing and marketing in the country. 
• After preliminary evaluation of application(if goes well), regulatory evaluation starts with the permission to conduct BE-Bioequivalence and Permission to conduct CT-chemical trial, then SEC-Subject expert committee reviews it and give NOC certificate then again review of BE/CT report. 
• Simultaneously, after review of CMC-Chemistry and manufacturing control data; if satisfactory IPC-Indian Pharmacopeia commission testing NOC to applicant. After completion on both front DCGI can inspect on-site facility.   
• DCGI instituted a system of review by a Subject Expert Committee (SEC) in 2012 to decide whether a new drug should be approved for the Indian market. The SEC was meant to have external experts who were specialists in the field of therapy being considered. After a SEC approval, the DCGI is required to take the final call on whether to approve a drug.
• All clinical trials conducted in India to be prospectively registered, i.e. before the enrolment of the first participant to Clinical Trail Registry of India.
• The Clinical Trials Registry- India hosted at the ICMR’s National Institute of Medical Statistics is a free and online public record system for registration of clinical trials being conducted in India. Initiated as a voluntary measure later trial registration in the CTRI has been made mandatory by the Drugs Controller General India (DCGI).
• An Ethics Committee is a committee comprising of medical, scientific, non-medical and non-scientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of human subjects involved in a clinical trial and it shall be responsible for reviewing and approving the protocol, the suitability of the investigators, facilities, methods and adequacy of information to be used for obtaining and documenting informed consent of the study subjects and adequacy of confidentiality safeguards.

Conclusion:

All the forces of medical and pharmaceutical fraternity are working together against the common enemy- corona virus. Unprecedented collaboration at world level will certainly reduce the time of medicine or vaccine development however utmost care and caution necessary to mitigate humanitarian and financial risks associated with development of medicine and vaccine.