Shaping of a Regulatory Framework Specific to the Indian Clinical Market

As India emerges as one of the leaders in the production of generic pharmaceuticals, contributing to approximately 20% of the global market¹, it is necessary to have regulatory authorities approve of more number of drugs or clinical trials to address the burden of diseases prevalent in India.

However, to safeguard public health, it is equally important to ensure that national and international pharmaceutical companies comply with stringent regulatory processes laid down for the approval of drugs.

Changes in the Indian Regulatory Scenario

Revision of Schedule Y of the Drugs and Cosmetics act 1945 in 2005 helped in aligning the Indian regulatory framework with internationally accepted definitions and procedures.

In addition, the Indian Good Clinical Practices (GCP) guidelines that were drafted by the expert committee of the Central Drugs Standard Control Organization (CDSCO) helped in ensuring uniformity in the conduct and quality of clinical research across the country.

With the recent introduction of the New Drugs and Clinical Trial Rules by the Ministry of Health and Family Welfare of India in 2019, the government is focusing on fast-tracking the approval of new drugs with equal weightage given to bio-equivalence or bioavailability studies.2

The government has also ensured further strengthening of the regulatory sector by allocating a higher budget of approximately 65 million US dollars at the central and state level.

This has helped in improving the infrastructure, such as setting up of an E-governance portal (SUGHAM) to bring in transparency, accountability, and ease of business.

A good initiative by the CDSCO was the setting up of a pharmacovigilance program in 2010 to have robust systems in place for adverse event reporting.1

The New Regulatory Rules

Some of the regulatory rules that have become effective following the New Drugs and Clinical Trials Rules 2019 are:

• Timelines have been revised for approval of global clinical trial applications to 90 days and 30 days for domestic trials from the previous duration of 6 months.³
• Phase III clinical trials are not required for any new drugs that have been approved for sale in the United States, Canada, Australia, or the United Kingdom.³
• Post-marketing surveillance studies are to be conducted in India to monitor for idiosyncrasies or unexpected adverse events.³
• Orphan drugs have been exempted from phase III and phase IV clinical trials.³
• Participant has access to free drug post-trial if no suitable alternative is available in the market. However, the Sponsor would not be responsible for any complications that occur post the study duration.⁴
• The approval obtained for a clinical trial is valid for 2 years.⁴
• Compensation for death/injury/disability that is related to the trial will be decided by the Drug Controller General of India (DCGI).⁴

 Conclusion

To head towards India’s goal of becoming a competent clinical trial destination, it is important to not only speed up the approval of drugs or clinical trials but also to keep allegiance to the Ethics committee and to the Indian Council of Medical Research’s (ICMR) National Ethical Guidelines for Biomedical and Health Research involving Human Participants, to prevent exploitation of trial participants.⁵ 

Transparency in the drug approval process, and stringent laws with penalties for unethical conduct of trials can become game changers with respect to maintaining high standards of quality for drugs and reliability of data from clinical trials.

The regulatory environment can also see an improvement in the implementation of regulatory laws by increasing the number of skilled staff such as drug inspectors, regulatory specialists, and so on. Equal emphasis should be laid on standard operating procedures (SOPs) and updating guidance documents to help staff understand the current regulatory environment.

Exchange programs with other countries that have sound regulatory processes can be beneficial for the Indian regulatory personnel to appreciate the importance of a well-defined regulatory framework and how some aspects can be practically implemented in the Indian regulatory environment.⁶

Of utmost priority should be a patient’s safety and rights. Having a representative from patient advocacy groups in important decision-making meetings held by the DCGI allows for a patient-centric approach with respect to the review of policies and laws.⁶

To conclude, high-quality drugs and ethical clinical trials are the joint responsibility of sponsors, clinical investigators, and regulatory bodies. Periodically updating the Indian regulations can address loopholes and instill confidence in international pharmaceutical companies to continue investing in India. This will, in turn, propel India’s economic growth.

Sources

1. Medicines regulation. Regulatory systems in India. WHO Drug Information. 2017;31(3). https://www.who.int/medicines/publications/druginformation/issues/WHO_DI_31-3_RegSystemIndia.pdf?ua=1
2. Ramu B, Kumar M S, and Ramakrishna N. Current Regulatory Scenario for Conducting Clinical Trials in India. Pharmaceutical Regulatory Affairs. Open Access. 2015;4:2. https://www.researchgate.net/publication/281765214_Current_Regulatory_Scenario_for_Conducting_Clinical_Trials_in_India
3. Vaidyanathan G. India’s clinical-trial rules to speed up drug approvals. Nature. April 2019. https://www.nature.com/articles/d41586-019-01054-4. Accessed on June 11, 2019.
4. https://www.turacoz.com/2019/04/15/new-drug-and-clinical-trial-rules-2019-india-what-they-bring-to-the-table/ Accessed on June 11, 2019.
5. Jesani A and Srinivasan S. New Drugs and Clinical Trials Rules, 2019: The market trumps ethics and participant rights. Indian Journal of Medical Ethics. 2019. https://doi.org/10.20529/IJME.2019.020. https://ijme.in/articles/new-drugs-and-clinical-trials-rules-2019-the-market-trumps-ethics-and-participant-rights/?galley=print

Disclaimer:

The information contained in this article is intended solely to provide general guidance on matters of interest for the personal use of the reader, who accepts full responsibility for its use. Accordingly, the information in this article is provided with the understanding that the author(s) and publisher(s) are not herein engaged in rendering professional advice or services.

As such, it should not be used as a substitute for consultation with a competent adviser. Before making any decision or taking any action, the reader should always consult a professional adviser relating to the relevant article posting.

While every attempt has been made to ensure that the information contained in this article has been obtained from reliable sources, Veeda Clinical Research is not responsible for any errors or omissions or for the results obtained from the use of this information.

All information in this article is provided “as is,” with no guarantee of completeness, accuracy, timeliness, or of the results obtained from the use of this information, and without warranty of any kind, express or implied, including, but not limited to warranties of performance, merchantability, and fitness for a particular purpose.

Nothing herein shall, to any extent, substitute for the independent investigations and the sound technical and business judgment of the reader. In no event will Veeda Clinical Research, or its partners, employees, or agents, be liable to the reader or anyone else for any decision made or action taken in reliance in the information on this article or for any consequential, special, or similar damages, even if advised of the possibility of such damages.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, electronic, photocopying, recording, or otherwise, without the prior written permission of the publisher.

For information, contact us at:

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Gujarat India.
Phone: +91-79-3001-3000
Fax: +91-79-3001-3010
Email: info@veedacr.com

Advancement in medical sciences has benefited humanity in many ways. However, in the process of conducting clinical trials, incidences of scientific, moral, and ethical misconduct have been unearthed that have shaken up the scientific community and public. This led to the formation of a formal organization in 1979 by the United States (US) namely the “International Ethical Guidelines for Biomedical Research Involving Human Subjects” to protect and safeguard the interests of trial subjects. Following this, many countries drafted their own guidelines for Good Clinical Practices (GCP). However, with increasing number of clinical trials being conducted at sites in multiple countries, it was necessary to have a uniform guideline for conducting clinical trials. This gave rise to the International Conference on Harmonization (ICH)-GCP guidelines in 1996 with the objective of providing a uniform standard that facilitates the acceptance of clinical trial data by the regulatory authorities of the respective countries. Over the course of time, many countries adapted the ICH-GCP guidelines to frame their own guidelines. India too followed suit with the Indian Council of Medical Research (ICMR) introducing the “Ethical Guidelines for Biomedical Research on Human Subjects” that is continuously revised and amended to ensure that clinical trials are conducted with utmost quality, giving priority to the welfare of the subjects involved.1

India – A global destination

India is emerging to be a favorite destination for clinical trials for many international companies due to several factors:

☉  Conducive Regulatory Environment: Internationally harmonized and favorable regulatory processes such as fast track approval of investigational new drugs making the Indian clinical research environment more amenable to conducting clinical trial. Market trends show a compound annual growth rate (CAGR) of approximately 12% (US dollars 987 million) in the Indian clinical trials industry from US dollars 500 million in 2017.1,2,3,4,5

☉  Trained Manpower: Availability of skilled healthcare professionals who are specialists in different therapy areas, well-versed in the English language and who ensure compliance to ICH-GCP guidelines.1,2,3

☉  Technology Infrastructure: World-class technologies in data management and information technology and related services.1,2,3

☉  Patient Pool: Large population who are treatment naïve and have a diverse genetic and ethnic makeup. With India becoming increasingly urbanized and with greater connectivity between the urban and rural areas, it becomes convenient to recruit patients from different geographical areas. In addition, there is a high incidence and prevalence of acute and chronic diseases due to lifestyle changes leading to diseases such as diabetes, cancer, and so on. Such lifestyle-related disorders open up the possibility of conducting more clinical trials in these disease areas.1,2,3,6

☉  Ease of recruitment: In countries such as the US, approximately 86% of the clinical trials fail to recruit the required number of subjects leading to delay of almost a year. This delay costs the sponsor company several million dollars. Some of the reasons for delayed recruitment are unwillingness of patient to participate, stringent safety requirements, and hefty compensation packages. India provides the possibility of recruitment of patients with relative ease with due to increased trial compliance and transparency especially with the recent release of the New Drugs and Clinical Trial Rules 2019 that consists of updated rules and regulations for fast tracking approval of clinical trials. Among countries with fast growing economies, it has been noted that India has a growth rate in recruitment sites of approximately 22.6% with the highest growth rate seen in China (≈36%).1,2,7,8

☉  Competitive costs – Cost effectiveness is a pushing factor for many trials being shifted to India. The cost to develop a new drug is estimated to be almost 50% less than what would be required in the US or in the European Union. 1,2,3

Future of clinical research in India

Specific guidelines are being worked upon by the Central Drugs Standard Control Organization (CDSCO) for stem cell research, biosimilars, and medical devices to protect patients as well as to encourage clinical research and development in the country. After a lull period in the Indian clinical industry before 2015 due to ethical and quality concerns, open communication between sponsor representatives and the regulatory team of CDSCO has helped in reconsidering India once again as a potential global destination for enrolling a diverse population in clinical trials that adhere strictly to ICH-GCP guidelines.6

Disclaimer:

The information contained on this article is intended solely to provide general guidance on matters of interest for the personal use of the reader, who accepts full responsibility for its use. Accordingly, the information on this article is provided with the understanding that the author(s) and publisher(s) are not herein engaged in rendering professional advice or services. As such, it should not be used as a substitute for consultation with a competent adviser. Before making any decision or taking any action, the reader should always consult a professional adviser relating to the relevant article posting.

While every attempt has been made to ensure that the information contained on this article has been obtained from reliable sources, Veeda Clinical Research is not responsible for any errors or omissions, or for the results obtained from the use of this information. All information on this article is provided “as is”, with no guarantee of completeness, accuracy, timeliness or of the results obtained from the use of this information, and without warranty of any kind, express or implied, including, but not limited to warranties of performance, merchantability and fitness for a particular purpose. Nothing herein shall to any extent substitute for the independent investigations and the sound technical and business judgment of the reader. In no event will Veeda Clinical Research, or its partners, employees or agents, be liable to the reader or anyone else for any decision made or action taken in reliance on the information on this article or for any consequential, special or similar damages, even if advised of the possibility of such damages. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, mechanical, electronic, photocopying, recording or otherwise without the prior written permission of the publisher.

For information, contact us at:

Veeda Clinical Research Private Limited

Vedant Complex, Beside YMCA Club, S. G. Highway,

Vejalpur, Ahmedabad – 380 051,

Gujarat India.

Phone: +91-79-3001-3000

Fax: +91-79-3001-3010

Email: info@veedacr.com

Biosimilar or bio generics are bio therapeutic products with large and complex structures that are similar to their innovator product in all aspects including their safety, efficacy, and quality.

There is a palpable sense of urge among researchers and pharmaceutical industries to develop biosimilar for treatment, with its popularity expected to rise in the forthcoming years especially in developing low-cost biosimilar that are easily accessible and affordable for patients.

Market trends show that North America continues to dominate the global oncology biosimilar market followed by Europe, Asia Pacific, Latin America, Middle East, and Africa. The market is purported to reach approximately USD 45 Billion in the year 2026 from the current market of approximately USD 6 Billion.

Understanding the local and global market demand is necessary for companies, research institutes, and investors to study the changing dynamics in the biosimilar market. Segmentation of biosimilar by product, type of cancer, as well as targeted end-user such as hospital/online/retail pharmacies is particularly useful in empowering industries to make informed business decisions. Product segmentation also helps gauge the project’s feasibility so that the pharmaceutical industry can focus on developing safe and commercially viable products. Comprehensive analyses, robust legal and regulatory frameworks, continuing medical education for health care professionals and increased awareness among the public will undoubtedly increase the uptake of biosimilar and help the biosimilar market move ahead competitively.

Importance of Data Integrity

The scientific community has been a witness to some of the worst tragedies in the history of clinical trials data integrity. From the year 2015 till date, The Journal of the American Medical Association (JAMA) and the JAMA Network journals have published at least 18 notices citing concern over data error and/or falsification of data.

¹ For instance, the trials conducted by a Japanese anesthesiologist and researcher to treat post-operative nausea and vomiting were reviewed by the Japanese Society of Anesthesiologists (JSA) in the year 2012 to find startling revelations.

The data obtained from the trials were either totally fabricated or fraudulent, and approximately 210 papers published by the anesthesiologist had falsified data.

² Lapses in data integrity caused a significant loss of revenue, with the direct costs estimated to be close to 525,000 US dollars while indirect costs amounting to approximately 1.3 million US dollars.³

Such scientific misconduct served as a wake-up call to tighten regulations and laws to monitor drug development and drug use.

Scientists acknowledged the need for data integrity at every stage to safeguard human subjects, starting from pre-clinical development to pharmacovigilance.

What is Data Integrity?

Data integrity is defined as paper-based or electronic data that is complete, accurate, consistent, and reliable through its lifecycle from the time of data creation, archival, scanning, retention, and destruction.

⁴ The updated International Council for Harmonization Guideline for Good Clinical Practice (ICH GCP E6[R2]) reiterates the need for data integrity as well as the importance of monitoring clinical data throughout the study.

The United States Food and Drug Administration (FDA) uses the ALCOA acronym to define expectations with respect to data integrity.⁴

Data Compliance Issues

The FDA issued Good manufacturing practices (GMP) warning letters to various countries outside the United States (US), citing compliance issues over data integrity. Figure 1 shows China to have received the maximum GMP warning letters, followed by India and Europe.⁵

Figure 1 GMP warning letters issues outside US⁵

Data Integrity Checkposts

Data integrity can be monitored by keeping a check on the following areas:⁶

• ►Source Data Verification (SDV)
• ►Data access and control
• ►Training of personnel involved in data collection
  such as investigators, data processors, analysts, site staff, and report writers
• ►Data monitoring: On-site, centralized, and risk-based monitoring
• ►Clinical trial quality assurance units (QAU): Some sponsors set up internal QAUs or external QAUs with a contract research organization (CRO) to ascertain trial compliance with standard operating procedures (SOPs) and FDA regulations. QAUs also eliminates the risk of internal bias. Regulatory laws, however, do not mandate the need of a QAU.⁷
• ►Clinical trial audits

SDV

Strict adherence to good documentation practices (GDP) in clinical trial records is a way to ensure data integrity. GDP should be followed for paper records as well as electronic records and signatures.

Equally important is the need to retain and organize essential documents required before the start of a clinical trial, during the trial, and after the completion or termination of a trial.

The collection of essential documents that is kept at the sponsor site and investigator site is called the clinical trial master file (TMF). TMF plays a major role in facilitating trial conduct and management, thereby allowing for data integrity and GCP compliance at all stages of the clinical trial. The TMF is the document that is reviewed during an audit or inspection.⁸

Many pharmaceutical companies are now moving towards electronic TMF (e-TMF) for easier management of large and complex clinical trials that involve numerous departments or CROs.

Data Access and Control

It is necessary to exercise caution while handling data from clinical trials. Confidentiality of data should be maintained during all the phases of a clinical trial, including interim data results.

⁹ The ability to tamper with data, such as changing, deleting, or falsifying data, should be restricted by clearly demarcating roles. This also prevents potential conflicts of interest between similar roles that may hamper data integrity.⁴

The National Institute of Health (NIH) states that only voting members of the Data and Safety Monitoring Board (DSMB) should be permitted to look at the interim analyses results unless circumstances makes it necessary to share data, such as in the case of serious adverse events.

⁹In addition, the DMC members should not have any conflict of interest that would influence the outcome data. The FDA has also recommended the use of an “independent statistician” model to analyze interim data who is independent of the principal investigator and trial sponsor and reports unbiased results to the DMC.¹⁰

Data Monitoring

It is necessary to set up an independent data monitoring committee (DMC) that prioritizes the safety and interests of enrolled subjects and scrutinizes the authenticity of data as well as the clinical trial conduct.⁹

On-site Monitoring: is carried out to trace any discrepancy between the source data and data entered. It is also particularly useful to see if the site staff is familiar with the study document and if the staff has demonstrated accountability to carry out the trial ethically and responsibly.¹¹

Centralized Risk-Based Approach: ICH GCP E6(R2) emphasizes the need for centralized monitoring to reduce the number of trial visits by the clinical monitor and to allow for remote spotting of reliable and unreliable data by statisticians or other data management staff.^4,11

Risk-based Monitoring: The sponsor company is required to develop a robust risk management plan to prevent or mitigate any risk to human subjects by overseeing trial conduct and monitoring data quality across trial sites.¹¹

Data Integrity Audits¹²

• Specific audits look out for any data or metadata that previously went unnoticed, such as deleted or unchecked, misused, orphaned, or reprocessed data.
• The entire data lifecycle should be subjected to scrutiny by all departments involved in the trial, such as but not limited to data management, safety, quality risk management, and statisticians for compliance issues in areas of data management and data access control.^4,8
• Unnecessary incentivization for speedy results or data from high-risk phase II trials should be closely monitored for unscrupulous activities.
• Weightage should be given to raw data, and not summary reports and results should be backtracked for any compliance issues.

Conclusion

To avoid huge financial repercussions and loss of business, sponsor companies and CROs should lay sufficient emphasis on maintaining data integrity at every step of the clinical study for its completeness, accuracy, and consistency.

Sources

1. Bauchner H, Fontanarosa Phil B, Flanagin A et al. Scientific Misconduct and Medical Journals. 2018;320(19):1985-1987 https://jamanetwork.com/journals/jama/fullarticle/2708590

2. George SL and Buyse M. Data fraud in clinical trials. Clin Investig (Lond). 2015; 5(2): 161–173.

3. Michalek AM, Hutson AD, Wicher CP et al. The Costs and Underappreciated Consequences of Research Misconduct: A Case Study. PLoS Med. 2018;7(8):e1000318. https://doi.org/10.1371/journal.pmed.1000318

4. Rutherford M. ICH E6(R2) and Data Integrity: Four Key Principles. Clinical Researcher. 2018 April;32(4):doi:10.14524/CR-18-4021. https://acrpnet.org/2018/04/17/ich-e6r2-data-integrity-four-key-principles/

5. https://www.pharmaceuticalonline.com/doc/an-analysis-of-fda-fy-drug-gmp-warning-letters-0003 Accessed on April 26, 2019

6. Moody LE and McMillan S. Maintaining data integrity in randomized clinical trials. Nur Res. 2002 Mar-Apr;51(2):129-33. https://www.ncbi.nlm.nih.gov/pubmed/11984384

7. http://firstclinical.com/fda-gcp/?show=MonitoringvAuditing&search=compliance&type=&page=1 Accessed on April 26, 2019

8. https://www.ema.europa.eu/en/documents/scientific-guideline/draft-guideline-good-clinical-practice-compliance-relation-trial-master-file-paper/electronic-content-management-archiving-audit-inspection-clinical-trials_en.pdf Accessed on April 26, 2019

9. Fleming TR, Sharples K, McCall J et al. Maintaining confidentiality of interim data to enhance trial integrity and credibility. Clin Trials. 2008;5(2):157-67. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2703711/

10. Ellenberg SS. Protecting Clinical Trial Participants and Protecting Data Integrity: Are We Meeting the Challenges? PLoS Med. 2012 Jun;9(6):e1001234.

11. https://www.thefdagroup.com/thefdgroup-blog/conducting-data-integrity-audits-a-quick-guide Accessed on April 26, 2019.

Disclaimer:

The information contained on this article is intended solely to provide general guidance on matters of interest for the personal use of the reader, who accepts full responsibility for its use. Accordingly, the information on this article is provided with the understanding that the author(s) and publisher(s) are not herein engaged in rendering professional advice or services. As such, it should not be used as a substitute for consultation with a competent adviser. Before making any decision or taking any action, the reader should always consult a professional adviser relating to the relevant article posting.

While every attempt has been made to ensure that the information contained on this article has been obtained from reliable sources, Veeda Clinical Research is not responsible for any errors or omissions or for the results obtained from the use of this information.

All information in this article is provided “as is,” with no guarantee of completeness, accuracy, timeliness, or of the results obtained from the use of this information, and without warranty of any kind, express or implied, including, but not limited to warranties of performance, merchantability, and fitness for a particular purpose.

Nothing herein shall, to any extent, substitute for the independent investigations and the sound technical and business judgment of the reader. In no event will Veeda Clinical Research, or its partners, employees, or agents, be liable to the reader or anyone else for any decision made or action taken in reliance on the information in this article or for any consequential, special, or similar damages, even if advised of the possibility of such damages.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, electronic, photocopying, recording, or otherwise, without the prior written permission of the publisher.

For information, contact us at:

Veeda Clinical Research Private Limited
Vedant Complex, Beside YMCA Club, S. G. Highway,
Vejalpur, Ahmedabad – 380 051,
Gujarat India.
Phone: +91-79-3001-3000
Fax: +91-79-3001-3010
Email: info@veedacr.com

India is emerging as a country with tremendous potential to contribute to the national and international clinical trial platforms.

The Central Drugs Standard Control Organization (CDSCO) is the national regulatory authority of India managed by the Drug Controller General of India (DCGI).^1,2,3

The DCGI is responsible for the coordination of inspections of the sponsors, manufacturing units, as well as trail sites.³

Early Years in Clinical Development

In 2000, the Indian Council of Medical Research (ICMR) set up ethical guidelines for conducting biomedical research on human subjects.⁴ The year 2005 saw a revision of Schedule Y of the Drug & Cosmetics act, 1945, to align Indian regulatory laws to definitions and procedures that are internationally accepted.

The changes included:

• Defining Phase I to Phase IV of a trial
• Demarcated responsibilities of sponsor(s) and investigator(s)
• Options to record any deviation or changes to the approved study protocol

India also signed the trade-related intellectual property rights (TRIPS) agreement in 2005 in order to open up the prospects for conducting more clinical trials in India.⁵

Apart from harmonizing the regulatory acts to international standards, India quickly became a favorable destination for clinical trials as it offered:⁶

• English-speaking professionals in health care
• Technical expertise
• Growing economy
• World-class technology
• Large, diverse, and treatment-naïve population

Set Back for Clinical Trials

Despite changes in the regulations, many multinational pharmaceutical companies took advantage of the large population that had either inadequate knowledge about clinical trials or were illiterate. In addition, an ill-defined healthcare system added to the challenges of monitoring unethical practices.

This led to conducting clinical trials with little supervision, and no recording of patient informed consent either in written or as audio/visual content.

Patients were administered investigational drugs or devices without disclosing known serious adverse effects, some leading to the death of the subjects. Moreover, no independent enquiry committee was set up to ascertain if the death of the patient was related/not related to the investigational product or device.⁴

The years 2010 to 2013 saw a trying phase in the Indian clinical trial scenario due to the accumulated ill effects of conducting unethical trials.

However, with a better regulatory framework in place, the Clinical Trial Registry of India (CTRI) has recorded a steady rise in the number of trials being conducted, as seen in Figure 1. It was also observed that most of the trials were phase III trials.⁷

Figure 1: Clinical trial trends over the years

Figure 2 presents the state-wise distribution of trials in India between 2007 and 2015. Approximately 3330 trails were registered during this period.

It was observed that the maximum number of trials was conducted in Maharashtra, and the least number of trials was conducted in the Northeastern state. Among the Northeastern states, no trials were conducted in Nagaland.⁷

Figure 2: State-wise distribution of clinical trials in India (2007-2015 data)⁷

Revival of the Clinical and Regulatory Scenario

In 2014, the CDSCO constituted 12 new drug advisory committees (NDAC) and 25 subject expert committees (SECs). These committees have a number of experts from eminent government colleges and institutions to expedite the approval timelines of a clinical trial to 6-7 months.

The three-tier process consists of:⁹

 

However, only the SEC reviews global clinical trial applications, and no further approval is required from the Technical committee or the Apex committee. Investigational new drug (IND) applications are also reviewed independently by the IND committee and do not require the approval of the Apex committee.

A Technical committee comes into the picture only if the SEC has rejected a sponsor’s application and the sponsor feels aggrieved by the decision. In such an event, if the Technical committee disagrees with the decision of the SEC, it has the power to overrule the decision of the SEC.¹⁰

In March 2019, the Ministry of Health and Family Welfare, India, released the New Drugs and Clinical Trial Rules 2019 with the intention to fast-track the approval for clinical trials, new drugs, bio-equivalence (BE), or bio-availability (BA) studies.

These rules have also addressed any ambiguity that existed with respect to the regulation of the Ethics committee (EC).¹¹

Highlights of the New Drugs and Clinical Trial Rules, 201911	Updated rules and regulations11
Approval timeline for clinical trials	90 working days from receipt of an application for drugs discovered outside India and 30 working days for new drugs or IND in India
Manufacturing of new drugs or IND, BE & BA studies or test analysis or examination	Permission is required from the Central Licensing Authority (CLA)
Waiver of local clinical trials	· If CLA has approved the marketing of the new drug in other countries or has granted permission to conduct global clinical trials for the new drug in India · No evidence of a difference in metabolism, safety, or efficacy owing to the difference in the genetic profile of the Indian population
Period of validity of a clinical trial	2 years from the date of issue by CLA
Post-trial access to IND or new drug	In unique circumstances, the drug is to be distributed free of cost to trial subjects per the direction of CLA, but no liability lies with the sponsor for the use of the drug after trial.
Pre-submission and post-submission meetings	To seek guidance with respect to law and procedures that governs the process of manufacturing and licensing or granting permission.
Approval for trials conducted by EC and registration of EC	· Approval to be obtained from the EC of another trial site if a trial site does not have an EC, and the EC should be within 50 km of the trial site.· CLA-approved registration of EC remains valid for five years from the date of issue.
Conditions to be fulfilled for the conduct of a clinical trial	· Submission of status report on a quarterly basis or depending on the duration of the trial to track subject enrolment· Online reporting of the status of the clinical trial every six months via the SUGHAM portal to know if the trial is ongoing or completed or has been terminated.
Fee for procuring a license, certificate of registration, and permission for trial	Different fee structures depending upon the purpose of the trial. Fee ranging from INR 50,000 to 5,00,000.

Bridging the Gap

The challenges of dealing with clinical trials are multi-faceted and involve abiding by the regulatory framework in a responsible and ethical way by stakeholders, government, and judicial system alike.

Patient safety and protection should be of utmost importance laying strict rules for:¹²

• informed consent by audio-visual recording and in a language that the patient is comfortable with
• respect for the patient’s cultural, social, economic, and educational background
• timely reporting of SAEs

New ground rules that can open up the possibility of expanding medical research in India are:¹³

• approval of proposals submitted to the DCGI within 30 days of application, if there is no communication from the DCGI
• fast tracking of domestic approvals
• pre and post-submission meetings with the expert committee to bring in more transparency to the process and to set a well-defined timeline for trial completion
• trial compensation in case the investigational drug led to SAEs/death.

Proficient workforce and state-of-art infrastructure also play an important role in attracting sponsor companies. Research has demonstrated that though Phase III trials are being conducted in a big way in India, Phase I trials seem to be limited to the sponsor country.

This could be attributed to the Sponsor’s apprehension in procuring a qualified workforce and technology. To enable indigenous research to happen in India, it is pivotal to provide appropriate exposure or continuing medical education to personnel and access to up-to-date technology to be recognized as a country competent enough to conduct any phase trials.⁹

Equally important is the need for skilled healthcare workers to be available throughout the country to account for the uneven distribution of clinical trials across states.

Concentrating a trial on a particular state could lead to biased conclusions and oversimplify or exaggerate a disease burden or condition. By providing access to people in all states to join a clinical trial, we not only minimize bias but also include diverse ethnic populations.⁹

The Future

With positive, patient-friendly, fast-track, and transparent regulatory laws, India will continue to grow as an international hub for testing and developing innovative medicines and medical devices.

Sources

1. Evangeline L, Mounica NVN, Reddy VS et al. Regulatory process and ethics for clinical trials in India (CDSCO). The Pharma Innovation Journal. 2017;6(4):165-9. http://www.thepharmajournal.com/archives/2017/vol6issue4/PartC/6-4-4-176.pdf

2. Lahiry S, Sinha R, Choudhary S et al. Paradigm Shift in Clinical Trial Regulations in India. Indian Journal of Rheumatology. 2018;13:51-5.

3. Gogtay NJ, Ravi R, and Thatte UM. Regulatory requirements for clinical trials in India: What academicians need to know. Indian Journal of Anaesthesia. 2017 Mar;61(3):192-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372399/

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