Category: Blog

India is rapidly gaining acceptance globally as the go-to destination for clinical research.

The country offers the advantages of having experienced personnel, good infrastructure such as well-equipped hospitals and laboratories, and a diverse patient pool.

Moreover, the increase in life expectancy rate to 65 years and above gives rise to a host of lifestyle diseases such as diabetes, hypertension, neurodegenerative diseases, and more, paving the way for many multinational pharmaceutical companies to invest in clinical trials in India.

Apart from this, cost-effectiveness is an important factor that drives the outsourcing of clinical trials to India.

The recent amendment made by the Ministry of Health and Family Welfare, Government of India, to the regulatory laws (New Drugs and Clinical Trials Rules, 2019) was with the aim of increasing the percentage of clinical trials conducted in India, which hit an all-time low in the period between 2011 and 2013.

In a bid to streamline approval processes, well-defined timelines have been introduced.

The new rules have shortened the approval timeline for clinical trials of drugs manufactured outside India to 90 days.

For drugs manufactured in India, the clinical approval timeline is 30 days.

Pre-submission and post-submission meetings between the sponsor and the Drugs Controller General of India (DCGI) are attempts to increase transparency in all dealings related to the clinical trial.

In addition, the non-refundability clause of the compensation package was removed as this was seen as a major deterrent for international companies, especially if a death/injury was proved to be unrelated to the trial at later stages.

Apart from clinical trials, there has been a boom in the field of data management and medical writing, with a number of homegrown clinical research organizations (CROs) demonstrating expertise to handle end-to-end services for sponsor companies.

Last but not least, concerted efforts and joint participation of the Indian government and Indian pharmaceutical companies in policy-making decisions and prioritization of patients’ safety and health will build confidence in international companies about India’s capability in contributing to the clinical research industry.

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 market ¹ , necessary to have regulatory authorities approve a larger 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 levels.

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

A notable initiative by the CDSCO was the establishment of a pharmacovigilance program in 2010, aimed at implementing robust systems 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 for the approval of global clinical trial applications have been revised to 90 days, and for domestic trials, to 30 days, 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 exempt from Phase III and Phase IV clinical trials. ³
• Participant has access to a 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. Medicine 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 Lifesciences 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 Lifesciences, 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:

Veeda Clinical Research 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@veedalifesciences.com

Advancement in medical sciences have 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 the 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 the 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,” which is continuously revised and amended to ensure that clinical trials are conducted with utmost quality, giving priority to the welfare of the subjects involved.

India – A Global Destination

India is emerging as 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, make the Indian clinical research environment more amenable to conducting clinical trials. 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.
• Trained Manpower: Availability of skilled healthcare professionals who are specialists in different therapy areas, well-versed in the English language, and who ensure compliance with ICH-GCP guidelines.
• Technology Infrastructure: World-class technologies in data management, information technology, and related services.
• 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.
• 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 a delay of almost a year. This delay costs the sponsor company several million dollars. Some of the reasons for delayed recruitment are unwillingness of patients to participate, stringent safety requirements, and hefty compensation packages. India provides the possibility of the recruitment of patients with relative ease due to increased trial compliance and transparency, especially with the recent release of the New Drugs and Clinical Trial Rules 2019, which 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%).
• Competitive costs – Cost effectiveness is a driving 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.

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.

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 Lifesciences 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 Lifesciences, 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 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@veedalifesciences.com

Biosimilars or biogenerics are biopharmaceutical products with large and complex structures that are similar to their innovator products in all aspects, including safety, efficacy, and quality.

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

Market trends indicate that North America remains the dominant force in the global oncology biosimilar market, followed by Europe, the Asia Pacific, Latin America, the Middle East, and Africa.

The market is expected to reach approximately USD 45 billion by 2026, up 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 biosimilars by product, type of cancer, as well as targeted end-users such as hospitals/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 healthcare professionals, and increased awareness among the public will undoubtedly increase the uptake of biosimilars and help the biosimilar market move forward 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 to 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.

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. ¹

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

Lapses in data integrity resulted in a significant loss of revenue, with direct costs estimated to be nearly $525,000 US dollars, while indirect costs totaled approximately $1.3 million US dollars. ^{2, 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.

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. ⁴

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, citing compliance issues related to data integrity.

Figure 1 shows that China has received the maximum number of GMP warning letters, followed by India and Europe. ⁵

Figure 1: GMP warning letters issued outside the US. ⁵

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 eliminate the risk of internal bias. Regulatory laws, however, do not mandate the need for 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.

The ability to tamper with data, such as changing, deleting, or falsifying data, should be restricted by clearly demarcating roles. ⁹

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 analysis results unless circumstances make it necessary to share data, such as in the case of serious adverse events.

In addition, the DMC members should not have any conflict of interest that would influence the outcome data. ⁹

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 the 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 Audits ¹²

• 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, which should be reviewed for any compliance issues.

Conclusion

To avoid huge financial repercussions and loss of business, sponsor companies and CROs should place 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 the 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 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 Lifesciences 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 Lifesciences, 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 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@veedalifesciences.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, overseen by the Drug Controller General of India (DCGI). ^1,2,3

The DCGI is responsible for coordinating inspections of sponsors, manufacturing units, and trial 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 Drugs and Cosmetics Act, 1945, to align Indian regulatory laws with internationally accepted definitions and procedures.

The changes included:

• Defining Phase I to 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 Aspects of Intellectual Property Rights (TRIPS) agreement in 2005, aiming to open up the prospects for conducting more clinical trials in the country. 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 was illiterate.

Additionally, an ill-defined healthcare system contributed 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 audio/visual form.

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 to the investigational product or device. ⁴

The years 2010 to 2013 witnessed a challenging phase in the Indian clinical trial scenario due to the cumulative adverse 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 (NDACs) and 25 subject expert committees (SECs).

These committees comprise experts from eminent government colleges and institutions, aiming to expedite the approval timelines of clinical trials 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 of fast-tracking the approval for clinical trials, new drugs, bioequivalence (BE), and bioavailability (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 regulations 11
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 an 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 an IND or a 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 the law and procedures that govern the process of manufacturing, licensing, or granting permission.
Approval for trials conducted by the EC and registration of the 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 a 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, completed, or has been terminated.
Fee for procuring a license, certificate of registration, and permission for trial	Different fee structures depending on the purpose of the trial. Fees ranging from INR 50,000 to 5,00,000.

Bridging the Gap

The challenges of dealing with clinical trials are multifaceted and involve adhering to the regulatory framework in a responsible and ethical manner by stakeholders, the government, and the 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.

A proficient workforce and state-of-the-art infrastructure also play an important role in attracting sponsor companies.

Research has demonstrated that, although Phase III trials are being conducted extensively in India, Phase I trials appear 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 in India, it is pivotal to provide personnel with appropriate exposure and continuing medical education, as well as access to up-to-date technology, to be recognized as a country competent enough to conduct all phases of trials. ⁹

Equally important is the need for skilled healthcare workers to be available nationwide to address 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/
4. 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
5. Burt T, Sharma P, Dhillon S et al. Clinical Research Environment in India: Challenges and Proposed Solutions. Journal of Clinical Research Bioethics. 2014;5:6. DOI: 10.4172/2155-9627.1000201
6. Chaturvedi M, Gogtay NJ, Thatte UM. Do clinical trials conducted in India match its healthcare needs? An audit of the Clinical Trials Registry of India. Perspectives in Clinical Research. 2017;8(4):172-5.
7. http://ctri.nic.in/Clinicaltrials/news/CTRI_Newsbulletin_July-Dec_2017.pdf Accessed on April 23, 2019.
8. Bhave A and Menon S. Regulatory environment for clinical research: Recent past and expected future. Perspectives in Clinical Research. 2017;8:11.6.
9. Key Highlights of New Drugs & Clinical Trial Rules, 2019. Accessed on April 23, 2019
10. Dan S, Karmakar S, Ghosh B et al. Digitization of Clinical Trials in India: A New Step by CDSCO towards Ensuring the Data Credibility and Patient Safety. Pharmaceutical Regulatory Affairs: Open Access. 2015;4(3): DOI: 10.4172/2167-7689.1000149.
11. https://www.thehindubusinessline.com/news/new-rules-sweeten-the-deal-for-clinical-trials-by-indian-pharma-cos/article26283499.ece. Accessed on April 23, 2019.

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 regarding 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 Lifesciences is not responsible for any errors or omissions or 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 Lifesciences, 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 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@veedalifesciences.com

Veeda, through its V-Konnect series, interacted with Mr. Jayanta Mandal and discussed “Current Outlook for Contract Research Drug Development Segment.”

About the V- Konnect

V-Konnect interview series is a program to get in touch with specialized industry experts to know their views on current relevant subject matters.

About Mr. Jayanta Mandal

Mr. Jayanta Kumar Mandal, M.Pharm, has 20 years’ experience in Pharma R&D, IPR & business development. Worked in the top 10 companies in India.

Lastly, headed R&D, Patent cell, and Pharmacokinetic cells, and managed product selection, all BE and CT studies for the company for all regulated and semi-regulated markets.

Also actively involved in business development for dossier and toll manufacturing business.

Mr. Mandal has a wide range of experience in developing Immediate Release, Sustained Release, MUPS Oral formulations, Liquid and Lyophilized oncology and general Injectable products, Topical Dosage forms, Ophthalmic Dosage forms, and Liquid Oral Products through NDA, ANDA, DCP, Pellets, MRP, and national procedures.

Mr. Mandal has experience in dealing with US and EU patent attorneys and counsels for patent opinion, document discovery, deposition, etc.

Below are the interview questions:

1. What do you think are the most important reasons for pharmaceutical companies to outsource drug development to CRO’s?

A: All big pharma companies cannot cover all products through their in-house R&D.

There are also failures during drug development, and priority for the company to select the important projects relevant for their intended market.

The companies having in-house development with huge infrastructure in place also demand the use of CRO’s for their efficient and cost-effective delivery.

Upgradation of old MAs, life cycle management, filling in the gap of pipeline for the business of pharma companies, and also looking for a quick solution for CRO’s.

Virtual companies do not have a facility or in-house capability to develop projects, and hence CRO’s fill the gap for all these companies.

2. How do you see Contract Research Industry Growth year on year and CAGR in the next five years?

A: There is pressure working in all segments of the pharmaceutical industry, and CRO’s are not immune to that.

The price and ever-demanding regulatory pressure are increasing the cost of development, and the tough phase is expected to be over sooner.

Industry consolidation through mergers and acquisitions is also creating pressure on CRO’s.

It is difficult to predict the year-over-year (YOY) CAGR growth in terms of percentage, but we expect it to be lower than 15% for the next 2-3 years.

Only the best will grow at more than 20%.

3. Which therapeutic segments do you see have business potential across Indian CRO’s?

A: CRO’s are neutral to therapeutic areas and work on a demand basis.

Only the regulatory limitation, even in R&D for Beta-lactam, cephalosporin, etc., limits the CRO to work in this space if they do not have a separate R&D space for these classes.

However, we see a surge in potential or interest in oncology segments and Injectable dosage form development, as the oral segment is crowded.

4. What strategies should Indian CRO’s adopt to nullify competition from International CRO’s?

A: Speed to develop and to retain the cost advantage will keep Indian CRO’s ahead of others.

We have an advantage in language and requisite skills for pharmaceutical development.

Be it chemistry, clinical, or pharmacetics.

The skill set is prevalent in most parts of India.

The regulatory steps or clearances required for R&D are longer in some parts of the country, which need to be made faster and more efficient.

Another factor which will make Indian CRO’s more competitive is to have an in-house scaling-up facility to local government standards to reduce the timeline for pilot BE studies.

The investment needed to do that is high for most of the CRO, and hence an alternate regulatory framework is required to address this to retain our CRO’s competitiveness.

5. How do you visualize Contract Development of Biosimilars with CRO’s and what are the challenges associated with the same?

A: Research and Development on biosimilars is a cost-intensive process that requires a high initial investment with long-term ROI.

It also requires good knowledge of Biology, besides chemistry and pharmaceutical technology.

More close collaboration with universities for biology/biotech competency needs to be developed as a robust, streamlined process to have Biosimilar research to progress.

We lack this at the present moment, which needs to be addressed.

The area of contract research is the future of CRO, as more and more biologics are coming into the market and more are in the pipeline.

In the next 20 years, more and more gene therapy and targeted therapy will be the norm, and there is a good future for Research companies that have embarked on the Biologics space to get a first mover advantage.

6. Do you feel the Need of more contract research organization in India and why?

A: There are thousands of pharmaceutical companies, diagnostic companies, and biotech companies operating in India and for the Indian market, besides serving regulated, semi-regulated, and ROW markets.

The world is moving more towards harmonization of regulatory requirements for drug, diagnostics, and biologics approval processes, with a few local variations.

Current CRO’s have developed over the last 3 decades mostly to cater to the needs of the regulated market.

The space of CRO’s for regulated markets is likely to shrink due to the proliferation of CRO’s in the last 10 years and the consolidation of end-user companies.

The good news for CRO’s is the implementation and upgradation of cGMP norms in the domestic market, where the approval process will require bioequivalence study submission and more vigilant regulatory agencies through their upgraded infrastructure, manpower to implement the cGMP in the industry.

I feel the Indian market will give more growth in the medium term for CRO’s.

7. Looking at the failures of Clinical Trials and BE studies, what is your view on the scientific expertise and knowledge of a contract research organization that can provide support to the Pharmaceutical companies in these areas?

A: For any pharmaceutical product, be it NDA or ANDA, expertise in both pharmaceutical technology and clinical/pharmacology (kinetics/dynamics) is important.

Both go hand in hand as the expertise of drug product to absorb comes from pharmaceutics, whereas how it is absorbed, distributed, and eliminated, eliciting response, is in the domain of clinical /medical experts.

As the biological variations in drug disposition due to the inherent nature of patients/persons and drugs cannot be predicted accurately or controlled, the combined expertise of CRO’s and pharmaceutics will make a long way to resolve the challenges associated with drug development failure of clinical trials and BE studies.

8. How do you see the growth of early-phase and late-phase clinical development by CRO’s in the upcoming years?

A: I do not see a high growth in early phase or late phase clinical development by CRO’s for classical chemical-based drugs due to the transitional change in therapy towards biologics and future targeted gene-based therapies.

Most of the classical early or late phase development of drugs will be shifted more towards mid-size and Venture capital-funded companies.

Biological clinical development programs will drive growth in this segment over the next two decades.

On a closing note, Mr. Mandal added that “As our industry is linked with human beings very closely for its physical and mental health, the industry will always be regarded with respect.

The pace and technology of growth will need to be matched with other industries dealing with health to be relevant.

Artificial intelligence is likely to change the way the healthcare industry currently works in all aspects.

AI will change the way diagnostics are used, prescriptions are made, and dispensing is done.

So is the drug research and development.

I believe that AI will change the way we use animals or human beings in drug development, and will likely be shifted more towards AI-based technologies”.

Disclaimer:

The opinions expressed in this publication are those of the Interviewee and are not intended to malign any ethic group, club, organization, company, individual, or anything. Examples of analysis performed within this publication are only examples.

They should not be utilized in real-world analytic products as they are based only on the personal views of the Interviewee. They do not purport to reflect the opinions or views of the VEEDA CRO or its management. Veeda CRO does not guarantee the accuracy or reliability of the information provided herein

With patents expiring for many successful biologic drugs, researchers are focusing on developing drugs that are competitively priced and affordable to patients who require critical medications for managing chronic diseases.

A biosimilar medicinal product is a replica of the innovator medicinal product with similar safety and efficacy profiles. ^1,2

Some of the popular biosimilars are monoclonal antibody biosimilars for cancer therapeutics, erythropoietin biosimilars, insulin biosimilars, interferon biosimilars, granulocyte colony-stimulating factor biosimilars, and human growth hormone biosimilars.

Small Molecules Versus Large Molecules

Small molecules are chemically synthesized and are simple, well-defined molecules.

They can be characterized fully and have highly predictable functions.

On the other hand, biologics are large molecules, typically protein-based, synthesized from highly complex biological sources.

As living systems are used in the manufacturing of biologics, the process requires sound technological expertise.

Despite large molecules posing challenges such as extreme sensitivity to processing and handling, as well as immunogenicity, their proven efficacy and precision in targeted therapy are making biologics popular in the treatment of many non-communicable and chronic diseases, including blood disorders, cancer, inflammatory diseases, and diabetes. ⁴

Current Scenario of Biosimilars

Approximately 32 biologics will lose patent rights by 2019, the combined sales of which are estimated to be around $51 billion. ⁶

However, developing biologics is a tedious and complex process, with many products taking approximately 10 to 15 years to reach the market. ⁷

Studies have indicated that the market will continue to grow at a rate exceeding 20% due to an increase in the incidence of chronic conditions, resulting in increased utilization of biologics.

The patent expiration of several best-selling biologicals opens the door for the approval of biosimilar versions of the original products.

These biosimilars are typically 20-30% less expensive than the innovator product.

The European Union (EU) has approved more than 20 biosimilars since it first granted consent to use a biosimilar, somatropin, in 2006. ¹⁰

It is anticipated that the global biosimilars market will surpass $35 billion by 2025, with a compound annual growth rate (CAGR) of 33%.

Challenges in Developing Biosimilars

➔ Difference in Regulatory Approval Processes Between Countries:

In the EU, the interchangeability of biosimilars does not require additional regulatory evaluation if the biosimilars demonstrate similar activity as the original product with no additional risk to the patient.

However, this is not acceptable to the US regulatory body that mandates complex and costly trials to demonstrate the interchangeability of biosimilars.

In addition, the USFDA limits the use of data extrapolation.

The additional regulatory requirement not only increases the timeline for biosimilars development but also increases the cost and impedes the manufacturer’s enthusiasm in pursuing biosimilars in the long run. ^{3, 13, 14}

➔ Development and Timeline Challenges:

It is estimated that the cost of developing biosimilars can range from $100 million to $200 million, with a development time of 5-9 years, excluding the cost of failure. ¹⁵

The Pharmaceutical Research and Manufacturers of America (PhRMA) estimated the cost of developing a biosimilar to be approximately $ 375 million as compared to $1.2 billion to develop a new biologic.

However, the development timelines for biosimilars are relatively shorter than those of biologics.

The Phase I and Phase III stages for biosimilars can be shortened, while the Phase II stage can be skipped due to the established therapeutic efficacy and safety of the biologic.¹⁶

➔ Clinical Challenges:

Immunogenicity is a potential risk with biosimilars.

Hence, stringent risk management plans and post-marketing surveillance of the drug should be implemented to monitor any potential adverse events. ^13,17

Another challenge is patient acceptance of biosimilars, which is often hindered by limited knowledge or awareness about these products.

Concerted efforts must be made to ensure that patients understand the basic principles of biosimilars and their ability to exert therapeutic efficacy at significantly lower costs than their biological counterparts. ¹⁸

➔ Analytical Challenges:

The physicochemical and structural comparability of biosimilars with the original product is difficult due to their inherent heterogeneity.

Analytic techniques such as mass spectroscopy, chromatography, or electrophoresis can be used to address some of the hurdles by: ^13,17,19

• Comparing biosimilars lots against a reference product to assess the pharmacokinetics and pharmacodynamics of the biosimilars.
• Understanding multiple mechanisms of action involved in in vitro characterization
• Choosing a bioassay should be a case-by-case decision depending upon the specificity and sensitivity of the biosimilars.

➔ Commercialization and Marketing Challenges:

Major pharmaceutical companies sometimes block other small players from producing biosimilars by creating restricted distribution agreements, leading to the unavailability of the innovator product sample.

In addition, patents are abused to prolong the monopoly of a brand name, thereby delaying patient access to more affordable and life-saving biosimilars. ¹³

➔ Establishing Concrete Guidelines for Market Approval:

The US FDA and regulatory bodies of other countries have yet to establish streamlined guidelines for the marketing approval of biosimilars. ^3,13,14

The Way Forward

➔ Biosimilars manufacturers can promote optimization by: ⁵

• Building trust and confidence between payers and providers by reimbursing biosimilars and providing cost-saving alternative solutions for long-term treatment.
• Engage with regulatory authorities during the early stages of biosimilar development to capture their interest.

➔ Enabling the extrapolation of data by regulatory authorities in the country is one of the crucial steps that can accelerate the development of biosimilars. This, in turn, helps establish fair market trade. ⁵

➔ Contract research organizations (CROs) can lend expertise to sponsor companies:²⁰

• To develop a holistic, tailor-made, and optimal clinical development plan (CDP) without losing focus on the commercial aspect of the business
• By using therapeutic and regulatory expertise, real-world data, and market access strategies to influence access to biosimilars and to establish competitive pricing.

➔ By forging strategic global alliances and enhancing their expertise in biosimilars development.

Conclusion

Advanced manufacturing processes, limiting patent litigations, and changes in physicians’ and patients’ perceptions towards biosimilars can mitigate the current level of complexity and ambiguity involved in promoting biosimilars.¹⁰

In addition, the overall cost of biosimilars can also be reduced by involving a larger number of players; these measures will allow for safer and wider access to biosimilar products to patients around the globe.

Sources

1. Weise M, Bielsky MC, De Smet K et al. Biosimilars—why terminology matters. Nature Biotechnology. 2011 Aug;29:690-3. https://www.nature.com/articles/nbt.1936
2. https://bioprocessintl.com/manufacturing/biosimilarss/opportunities-challenges-biosimilars-development/ Accessed on March 13, 2019.
3. Rozek RP. Economic Aspects of Small and Large Molecule Pharmaceutical Technologies. Advances in Economics and Business. 2013;1(3): 258-69.
4. CN Chan J and TC Chan A. Biologics and biosimilars: what, why, and how? ESMO Open. BMJ Journals. 2017;2(1):e000180.
5. Oo Charles and Kalbag SS. Leveraging the attributes of biologics and small molecules, and releasing the bottlenecks: a new wave of revolution in drug development. Expert Review of Clinical Pharmacology. 2016 Mar;9(6):747-9.
6. Blackstone EAn and Joseph JR PF. The Economics of Biosimilars. Am Health Drug Benefits. 2013 Sep-Oct; 6(8): 469–478. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031732/
7. Blackstone EA and Joseph JR PF. Biologics and Biosimilars. The possibility of encouraging innovation and competition. The SciTech Lawyer. American Bar Association. 2015;11(3).https://pdfs.semanticscholar.org/bf63/c072c5019dbb294f85c8f865adbcc0bd698a.pdf
8. Bressler B and Dingermann T. Establishing a new marketplace for biologic therapy with biosimilar agents: importance of extrapolation of data. Biosimilars. 2015;5:41-8.
9. http://www.gabionline.net/Biosimilarss/General/US-67-billion-worth-of-biosimilars-patents-expiring-before-2020 Accessed on March 13, 2019.
10. Gupta SK, Chaudhari P, and Nath R. Opportunities and Challenges in Biosimilars Development. Bioproces international. https://bioprocessintl.com/manufacturing/biosimilarss/opportunities-challenges-biosimilars-development/ Accessed on March 13, 2019.
11. https://www.variantmarketresearch.com/report-categories/pharmaceuticals/biosimilarss-market Accessed on March13, 2019.
12. http://www.mabxience.com/products/biosimilars/global-biosimilars-market/ Accessed on March 13, 2019.
13. Breaking through on biosimilars. The Biosimilars Council. http://biosimilarsscouncil.org/wp-content/uploads/2018/05/Breaking-Through-on-Biosimilarss-Biosimilarss-Council-White-Paper.pdf Accessed on March 13, 2019.
14. Misra M. Biosimilars: Current perspectives and future implications. Indian Journal of Pharmacology. 2012 Jan-Feb;44(1):12-4.
15. https://www.pfizerbiosimilarss.com/biosimilarss-development Accessed on March 13, 2019.
16. http://www.pharmtech.com/clinical-and-cost-considerations-developing-biosimilars Accessed on March 13, 2019.
17. Cai XY, Wake A, and Gouty D. Analytical and bioanalytical assay challenges to support comparability studies for biosimilar drug development. Bioanalysis 2013 Feb;5(5). https://www.future-science.com/doi/full/10.4155/bio.13.1
18. http://ascopubs.org/doi/full/10.1200/JOP.2017.025734?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed Accessed on March 13, 2019.
19. https://www.biosimilarsdevelopment.com/doc/analytical-challenges-in-biosimilars-development-0001 Accessed on March 13, 2019.
20. https://www.iqvia.com/-/media/library/white-papers/integrated-approach-to-biosimilars-dev-and-commerc.pdf?la=en. Accessed on March 13, 2019.

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 regarding 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 Lifesciences 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 Lifesciences, 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 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@veedalifesciences.com