nSMOL - A Novel Approach to Quantification of Therapeutic Monoclonal Antibodies!

Bhavik Narsana
Partner
Lifesciences and Healthcare and the
Corporate M & A and PE Team
Khaitan & Co.

Pavi Jain
Senior Associate
Lifesciences and Healthcare and the
Corporate M & A and PE Team
Khaitan & Co .

Clinical trials are emerging as an important activity in India as it is an essential component of the drug discovery and development program to which India is committed. The only robust way to evaluate a new medicine is by doing properly designed clinical trials. This article depicts clinical research scenario in India and historical perspective on Good Clinical Practices, challenges and future of clinical research in India.

India has a robust platform and an equal potential to contribute meaningfully towards the global clinical research and drug development. India presents an attractive platform with a vast population and patient -pool, minimal research costs and quality skill sets in the form of medical practitioners. However, despite the previously targeted growth projections and expansion reports, growth of Indian clinical research has not materialised due to several challenges. The past two decades have seen the rise and fall of clinical trials in India. The Indian clinical trial market grew by 20.3 percent compound annual growth rate (CAGR) between 2005 and 2010 and decreased by - 14.6 percent CAGR between 2010 and 20131. The slowdown in the clinical trial market was a result of the unprecedented regulatory framework, slow regulatory approval process, unwarranted and negative media coverage along with activist engagement, lack of awareness in the public and recuperative initiatives.

Indian Clinical Trial Framework

The Indian clinical trial set-up is mainly governed by: (a) regulations of Schedule Y along with rules 122A, 122B, 122D, 122DA, 122DAC and 122E of the Drugs and Cosmetics Act, 1940 (D & C Act); (b) the Ethical Guidelines for Biomedical Research on Human Subjects prescribed by the Indian Council of Medical Research; and (c) the Indian Good Clinical Practice(GCP) guidelines. Per law, it is mandatory that all clinical research that falls under the ambit of Schedule Y complies with the necessary requirements, which inter -alia comprises of formats for clinical trial protocols, informed consent forms, responsibilities of the sponsors, investigators and monitors, templates for independent ethics committee (IEC) approval and format for reporting of serious adverse events2. On the other hand, compliance with Indian GCP guidelines are only recommended and does not have a statutory status.

GCP Genesis

GCP is a standard for clinical studies or trials that encompasses the design , conduct, monitoring, termination, audit, analyses, reporting and documentation of the studies. It ensures that the studies are implemented and reported in such a manner that there is public assurance that the data from clinical trials is credible, accurate and that the rights, integrity and confidentiality of the subjects are protected. The guidelines seek to establish two cardinal principles: (i) protection of the rights of human subjects; and (ii) authenticity of biomedical data generated.

The Indian GCP guidelines have been prescribed by the Central Drugs Standard Control Organisation (CDSCO).

The genesis of GCP surfaces from the aftermath of World War II, when the importance of protecting participants in clinical research was recognised and the first code addressing the ethical conduct of biomedical research, the Nuremburg Code, 1947 was released. In fact, the Declaration of Helsinki was developed using principles of the Nuremburg Code and the Declaration of Geneva. GCP is now considered the international ethical and quality "standard for the design, recording, performance, monitoring, auditing, recording, conduct and reporting of clinical trials that involve participation of human subjects.*3 Internationally, the International Conference on Harmonization (ICH) GCP guideline is being revised to keep pace with the scale and complexity of clinical trials. The primary responsibility of maintaining GCP lies on the sponsors, clinical investigators, ethics committees, institutional review boards, contract research organizations, monitors etc.

Regulatory Concerns and Changes

Currently, to conduct a clinical trial in India one needs: (a) permission of the Drugs Controller General, India and permission of the new drug advisory committees consisting of sector experts; (b) approval from ethics committee; and (c) mandatory registration on the ICMR maintained website www.ctri.in .

Following the judgment of the Supreme Court in Swasthya Adhikaar Manch4 and in response to the 59th report of the Parliamentary Standing Committee, the Indian regulators passed several amendments to Schedule Y of the D & C Act, many of which lead to immediate fall out of pharmaceutical industry sponsored clinical trials. While mandatory registration of clinical research organisations5 is a welcome change, the other amendments like structure of the ethics committee, tougher site selection process, audio video recording of informed consent process and the reporting deadlines for serious adverse events were taken as adverse.

Amongst the various steps being taken by the government to give an impetus to the clinical trial industry after the slowdown in 2010-2013, the government has brought a fresh slew of reforms including: (a)CDSCO's recently launched new tool(called SUGAM) for online applications as part of efforts to increase accountability, transparency, and efficiency of processing applications with speed6; (b) taking away the restriction of only 3 trials per principal investigator; and (c) removing the restriction of minimum 50 bedded hospital requirement for conducting clinical trials, which now can instead be decided by the ethics committee.

Some of the issues faced by this industry, which if dealt, with will lead to greater protection and participation under a clinical trial, include providing protection to, and ensuring a fair treatment for, the clinical trial subjects, particularly, the vulnerable class such as illiterate and poor people and fair compensation and insurance structure.

Differences between ICH-GCP and Indian GCP

Indian GCP is largely based on the ICH-GCP, has certain areas stricter than the ICH-GCP and endorses all the internationally endorsed principles. Certain Indian GCP requirements are more progressive and stringent as compared to those formulated at the international level, for example registration of IEC7, clinical trials with the registry and usage of language to encourage participants diverse cultural and economic backgrounds 8.

Conclusion

Good clinical practices are important for quality products, safety of patients and also general good health of the industry. Although, lot needs to be done, with the recent amendments and progressive changes to the conduct of clinical trial process, the government is taking the right steps in promoting and encouraging clinical trials in India. India is primarily known for its generics capability and with the right changes, India has the capability, and can do well, as a drug innovator also.

References

1. Burt T, Sharma P, DhillonS, Manchanda M, Mittal S, Trehan N. Clinical Research Environment in India : Challenges and Proposed Solutions. Journal of clinical research & bioethics. 2014;5(6):1-8. doi:10.4172/2155-9627 .1000201.
2. Gogtay N J, Ravi R, Thatte UM. Regulatory requirements for clinical trials in India: What academicians need to know. Indian J Anaesth 2017;61:192-9.
3. Good Clinical Practice Research Guidelines Reviewed, Emphasis Given to Responsibilities of Investigators: Second Article in a Series. Journal of Oncology Practice. 2008;4(5):233-235. doi:10.1200/JOP.0854601.
4. Swasthya Adhikar Manch And Anr. v Union of India (UOI) and Others (WP(C )No. 33/2012 with WP(C)No. 79/2012)
5. Babu G. Centre releases draft rule for chedule Y-1 mandating registration of CROs? Pharmabiz.com, Mumbai. 2009. Jul 11. Available from: http://pharmabiz.com/NewsDetails.aspx?aid=51414&sid=2.
6. Notice by CDSCO; 05 October 2016(CDSCO/IT/2015-(48)). Available from: http://www.cdsco.nic.in/writereaddata/notice%20-dated05-10-2016.pdf.
7. Pandey A, Aggarwal AR, Maulik M, Gupta J, Juneja A, et al. The upgraded Clinical Trials Registry India: a summary of changes. Indian J Med Ethics. 2011;8:186