V-Konnect – Dr. Ashok Kumar

August 9, 2019

Posted in - Veeda

Veeda through its V-Konnect series interacted with Dr. Ashok Kumar and discussed about “Current Outlook of Indian Pharmaceutical industry”

About the V- Konnect

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

About Dr. Ashok Kumar – President, Centre for Research & development at Ipca Laboratories Limited

Dr. Ashok Kumar carried out his Ph.D. work at CDRI, Lucknow under the supervision of Padmashree Dr.Nitya Nand. This was followed by Post-Doctoral studies with Prof. Sir John Cornforth CBE, FRS a Chemistry Nobel Laureate, at the University of Sussex, England from 1981-1984.

He started his carrier with Alchemie Research Centre at ICI, Bombay in 1985 and served Lupin Laboratories before taking up the job with Ipca Laboratories Mumbai, a leading Pharma Company in the year 2000 and is presently heading the Centre for Research & Development of Ipca in the capacity of President.

He is a co-author in more than three dozen papers published in peer reviewed International Journals, co-inventor in more than 150 patent applications filed, has presented scientific papers and keynotes in many National / International Conferences in addition to delivering invited talks on R&D Management, Idea Management, Innovations, Role of Common Sense and Philosophy in Discovery / Research and many more such topics.

Interview Transcript.

1. What are the immediate key priorities for the Indian pharmaceutical industry?
A1: To remain competitive Indian Pharma’s Key priorities should consider the followings:

GMP Regulatory Issues: Strengthening of the regulatory framework and involvement of the relevant automation to at least avoid, if not completely eliminate human errors. Updating the systems may turn out to be costly, but certainly would help in increasing compliance & qualifying US FDA’s needs and expectations.

API Manufacturing: Technological interventions in manufacturing of APIs supported by PAT is likely to make production easy, environmental friendly and cost effective, however, would require development of expertise & mindset. These changes will obviously make API manufacturing more competitive and will also help in reducing our dependence on China to a great extent.

Innovations in API development using intelligent chemistry approach and manufacturing with the help of emerging technologies leading to cost competitiveness is more easy for Indian Pharma companies because it is going to be a mere extension of what we have been doing since long.

2. Is there any one area where you would anticipate growth? How do you see India developing in that area in the coming years?
A2. Though we are yet to discover the way to do something which qualifies under the head ‘Made in India’, India has done reasonably well in providing quality services. Providing economical services to IT sector and being 3rd largest producer & supplier of finished dosage formulations of generic formulations / drugs, across the globe for quite some time, can definitely be considered good examples where India has fared well.

Following service areas, which warrant more skill than creativity, are likely to see reasonable growth in India:

a. Contract & Custom Research and Development.

The global pharmaceutical Contract & Custom Research and Development/Manufacturing market is poised to post a CAGR of >9% during the next four years i.e. 2019-2023. India is contributing to its growth in a big way via significant technological advances in healthcare infrastructure and scientific innovations in drug development pursuit, owing to which MNC giants are outsourcing the Contract & Custom Research and Development and manufacturing operations to the service providers based at India. Skilled labor at economical price, state of art infrastructure along with relative ease of doing business in India is amongst the very many reasons for the growing popularity of outsourcing these activities.

b. Clinical Research

The latest revision of clinical trial rules by DCGI is indeed a boon for the Clinical Research industry in India. Fast-tracked clearance of proposals coupled with incentive will surely boost Clinical Research sector growth.

c. Medical Tourism

India is fast emerging as the preferred Medical Tourism Destination. While the Global Medical Tourism Market is anticipated to grow at a CAGR of 16.1% during next five years i.e. 2019-2025, the Indian medical tourism industry is way ahead at 18% CAGR YOY and is expected to be worth USD 9 billion by 2020 and USD13.3 billion by 2022. 4.95 lakh foreign tourists visited India for medical purposes in 2017, a significant increase from 2.33 lakh in 2015. Currently, India holds close to 18% of the global medical tourism market share and this is expected to increase to 20% by 2020.

d. Assisted Reproductive Technology (ART) for in-vitro fertilization.

The global ART market size was estimated to be around USD 21 billion in 2017. This has now been anticipated to reach USD 50.71 Billion by 2026. In line with the global growth statistics, ART industry in India is expected to grow by a compounded annual growth rate of 10%. Contributing factors to this growth are the increasing number of infertility cases due to lifestyle diseases, growing mental stress and pollution, fertility threatening treatments such as anti-cancer therapy, social stigma of being childless, lengthy adoption processes and favorable regulatory framework.

3. Does the future of Indian Pharma lies beyond generic if yes where we stand today?
A3: New Drug Discovery:
If Indian Pharma wants to make its future secured and sustainable, it will be possible only if India decides to put sincere efforts in New Drug Discovery.

Few companies have seriously attempted and are continuing investment in NCE / NBE development leading to out-licensing or furthering into clinical studies, but to increase the success rate we have to accept few hard facts:

• Blindly synthesizing & testing molecules in search for new drugs is an outdated model & is very unlikely to give anything worthwhile.

• Drug Discovery is no more about developing me-too kind of products but developing the products addressing the unmet medical need.

• In the era, when drug discovery is directed towards the dev. of personalized treatments, the most important thing is to find a new target based on Omics (Genomics, Proteomics, Metabolomics etc.) by investing in the research in basic Biological Sciences. India is somehow not very active in this area & therefore requires a serious / sincere beginning, if we want to remain relevant throughout.

• The cost of drug discovery and development as we all know, is exorbitant with very poor success rate and therefore many drugs these days are developed in collaboration by a no. of Multi-National Companies to share the risk and development cost. The question always comes to my mind is, why Indian Pharma Companies cannot join hands and feel proud for developing new drugs!

• For Indian companies, the easiest and perhaps most rewarding approach to start with for developing and getting US FDA approvals is by repositioning improving the approved drugs with known toxicity profiles and data, which can reduce the time for development with limited resources through 505(b)(2) pathway. It’s not as inexpensive as ANDA but it gives approval as NDA and can get relevant exclusivity & tag of new drugs.•

The only two things which are critical to travel on this path is to be honest & have long term goals supported by serious assessment of the progress. Instead of results, learning should be the aim of this activity. The philosophy from being ‘fast & first’ to ‘creative & innovative’ will be a game changer.

4. Do you think Quality has been a significant challenge for the Indian drug makers over the last few years? If yes then do you think that may improve soon?
A4: To the best of my understanding it’s not about quality, but rather compliance. The reasons for FDA’s observations and warnings are due to the most prevalent practice followed by most of the people in India, called Juggad – taking short-cuts – in qualifying products without following SOPs.

Since it is more to do with attitudes/mind-sets this problem can partly be addressed by making the doers understand the significance of following systems for securing their jobs. People are likely to be more compliant in future as they are aware of the enmass removal of employees by most of the Pharma Companies and non-availability of (repetitive) jobs in future, if the performance of Pharma Industry does not improve.

5. The industry seems to be moving towards heavy automation and electronic data records. Is that a solution?
A5: AI, automation and digitization is likely to have great impact on the compliance & regulatory controls for two main reasons. First, implementation of these emerging technologies will help keeping a track and controlling the process to reduce or completely eliminate compliance related issues and second, by giving a message of ‘perform or perish’. And since availability of jobs is already on decline it will act as a deterrent for employees to take short-cuts.

6. What kind of strategies must be implemented in order to enhance the acceptability of Indian advantages that steroids bring drugs, drug products and related services across the globe?
A6: Simply by ensuring regulatory compliance and this can be achieved by implementing automation & digitization, wherever possible, and continuously working on job specific skill development program for employees.

A change in Philosophy from being ‘fast’ to ‘flawless’ will possibly help companies in changing attitudes of their work force and the outcome.

7. Where India Pharmaceuticals Industry stands Vis-a-Vis to China?
A7. India v/s China
 ⇒ NDDDR: Though both India & China have not created much visible impact on New Drug Discovery and Development but China is way ahead of India on this front. The reason for this difference is due to China’s thrust and progress in the research, mainly biological sciences, including Genomics and Proteomics, key to find and validate new targets & also developing new drugs which are becoming increasingly personalized with time

⇒ Generics / Branded Generics: The 1970 Patent Act was the turning point but given the availability of science graduates, with chemistry and pharmaceutical sciences background, India could take an early lead in Pharma Research creating base for developing and supplying generic &/or branded yet cheaper generic drugs to the whole world

China on the other hand developed strong hold in chemicals and intermediates, key to APIs and are the world leaders in this segment. More than 70% of APIs / intermediates required to manufacture finished products by Indian Pharma companies are sourced from China. Chinese though little late in developing capabilities to meet regulatory requirement of Western World, however, are now catching up fast & quite a good number of Chinese companies have successfully got approvals of large number of ANDAs from USFDA in recent past. As far as the development of Biosimilars/ ‘Follow-on Biologics’ are concerned both the countries are almost at par, at present.

⇒ Industrial Infrastructure: If we compare India with China, the latter possess far better industrial infrastructure. And ‘Made-in-China 2025’, the mission with which China is building up its Modern Chemical Industry, with reforms ensuring greater Safety & Environment, development of Green Industrial Parks & the Eco-Systems having in built controls on emissions, waste disposal, waste water treatment, it will be one of the best in the world. Unfortunately Indian Govt., has not yet given much serious thought towards strengthening our Pharma Industry, which may lead to serious repercussions.

8. What do you consider are the main issues for the generic, bio similar and value-added medicines industries over the next 2-5 years?
A8: Generics are going to face increased challenges mainly due to the non-availability of Block-Busters to copy in the future and increased market competition leading to further price erosions in India as well as in the US. Indian Pharma regaining the growth obtained in past is highly improbable in (near) future. Decline of Para 4 opportunities in the US market also reduces the opportunity of developing Value Added Products.

In the light of the above mentioned facts, leading Indian Pharma companies have already plunged into either Biosimilars or Complex Generics development or are planning to do so.

Developing Biosimilars, though appear to be generic version of biologics but in true sense are not. It is a different ball game all together, and requires huge investment, longer time from Lab to Market (minimum 8 years) with no guarantee of return on investment in short to mid-term. This is important because many companies are focusing their development efforts on few selected molecules without investigating the kind of market competition they may have to face by the time their molecules reach the market.

As evident from the information available in public domain, many generic companies have either suffered heavy losses in the Biosimilars venture or have shut down their development program midway due to predictable non-viability and same may turn out to be true for more players in future, unless they move with caution and awareness.

Development of ‘Complex Generics’ or ‘Hybrid Medicines’, as defined by EMA (because their authorization depends partly on the results of the tests on the reference medicine and partly on new data from clinical trials), have their own challenges because of the lack of guidelines for regulatory approvals. If developed by hit and trial to replicate the innovator’s product, it will be treated as pure generic, and will lack market exclusivity. And if developed through 505(b)(2), the most ideal approach, the product will qualify as new drug and would need to be marketed through sales / market forces by promotion and most generic companies may not be able to do so. IP related issues due to existing patents from innovator companies and the funding required to develop product through US FDA, may cost somewhere between USD 10-20 million / molecule, and thus needs diligent evaluation before venturing into.

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 anyone 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 personal views of the Interviewee. They do not purport to reflect the opinions or views of the VEEDA Clinical Research or its management. Veeda Clinical Research does not guarantee the accuracy or reliability of the information provided herein.

Approach for Rescue Trials

July 30, 2019

Posted in - Veeda

Conducting a clinical trial is a complex and challenging task and involves robust scientific understanding and logistics planning. Although there are international guidelines for good clinical practices, the standard approach may not work for all clinical trials, especially in the case of trials that use orphan drugs, terminally ill patients, epidemiological trials, and so on.

Factors That Plague Clinical Trials

It has been reported that approximately 50% of phase III clinical trials do not achieve their objective or fail to demonstrate the desired results.

Some of the major issues that pharmaceutical companies face while conducting large-scale trials are:

Meeting regulatory deadlines: Inadequate or poor patient recruitment, poor execution, or complicated study design are some reasons that contribute to the inability of a company to meet timelines. Approximately 80% of trials are behind schedule. Analysis shows patient recruitment to be one of the prime reasons for the study delay.

Data quality: A flawed study design and complacency in following the patient eligibility criteria required for enrolment also affect the data quality and ethics of a trial. In addition, lack of patient informed consent or breach of confidentiality are other serious unethical practices that affect final data quality.

Infrastructure and resources: While accounting for infrastructure and resources, sponsor companies sometimes underestimate the requirement of trained staff at each step of a trial. A sponsor may need to recruit more number of clinical trial associates, study coordinators as well as other trained personnel depending on the number of trial sites and targeted cohort size.

At times, the importance of site inspection is also overlooked. Site inspections help in evaluating the technical capability of the staff and confirm if the site is well equipped to handle additional responsibilities.

Unexpected challenges: Sponsor companies are sometimes caught unaware by challenges that crop up during the execution of a trial. Without a risk management plan (RMP), it is impossible to identify warning signs and can also bring the trial to an abrupt halt.

All the above factors require the sponsor to look for remediation measures, and this is where rescue trials come into the picture.

Rescue Trials

There are different approaches that pharmaceutical companies employ for rescue support. For specific issues, the company may choose to bring on board a third party with expertise in a specific function or completely outsource study management and control to a contract research organization (CRO).

Integrating into an ongoing study requires the onboarding team to have the flexibility as well as the insight to identify problem areas that have led to the failure of the Sponsor’s trial.

Therefore, it is necessary for the CRO to have demonstrated expertise in handling a particular therapeutic area or to have the technical know-how of running rescue studies. This will help in seamless knowledge transition and identification of bottlenecks that have caused the trial to fail.

In case the trial is being transferred from another CRO, there should be a clear communication and handover plan from the outgoing CRO to the onboarding CRO and the Sponsor Company.

This communication should include strategic details such as current study status, vendors involved, database migration, documentation, and quality control, current risk management plan, to name some of them.

Key Takeaway

For a successful rescue study, there should be documented compliance and effective documented communication between the sponsor and CRO.

Corrective action and preventive action (CAPA) at each stage of the trial is necessary, especially in the case of rescue studies, to meet study milestones and to avoid any further delay in trial execution.

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 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.

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V-KONNECT with Dr. Arun Bhatt

July 15, 2019

Posted in - Veeda

Veeda, through its V-Konnect series, interacted with Dr. Arun Bhatt and discussed about “Clinical Trials in India and its regulatory perspective with New CT rules.”

About the V- Konnect

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

About Dr. Arun Bhatt – Consultant – Clinical Research & Development

Dr. Bhatt is currently working as a consultant in pharmaceutical medicine and clinical pharmacology. He is the Editor-in-Chief of the ISCR journal- Perspectives in Clinical Research. Dr. Bhatt has extensive three decades in the Indian pharmaceutical industry in clinical research, drug development, and regulatory affairs.

He was the former President of ISCR, President at Clininvent, CEO of CMI (India experience of), and Medical Director at Novartis. He is been awarded with ISCR Special Award in 2017 for his contribution to Research Fraternity, the Outstanding Service award by Drug Information Association in 2012, Honorary Fellowship by Clinical Research UK in 2009.

He is also a qualified assessor of NABH Accreditation for Clinical Trials sites and have more than 150 publications in national and international journals.

Transcript.

1. What are the challenges you see in the Indian clinical trial sector today? Can you please mention how to overcome these challenges?

Quality of trial conduct
Gaps in Knowledge of Regulations, Ethics, and Science
Challenges can be tackled if all stakeholders participate passionately in the training and development of their teams and strive for quality in the conduct of clinical trials. Some of the actions are discussed below.

2. Despite professional competence and large patient pool availability, India is yet to reach its potential in clinical trials. How this can be improved?

Professional competence is not in clinical research but in clinical diagnosis. We need investigators who are trained and passionate about academic clinical research, and who are willing to get trained in clinical trial regulations, ethics, and science, and who are willing to devote time to conduct good clinical research of internationally accepted standards. This is essential to build quality in clinical trials.
Large patient pool is not organized or classified. The sites should develop a detailed database of patients, including demography, disease, and drug information. This would help in quick screening and fast recruitment of subjects.
Government should create awareness about 1) the need for new drug development and clinical trials and 2) regulatory efforts to ensure the protection of rights, safety, and well-being of patients.
Ethics committees should receive support, guidance, and training from government bodies – ICMR – and hospital administration to ensure that they can fulfill their primary responsibility of protection of rights, safety, and well-being of patients.
Industry sponsors should invest in supporting all the above efforts and encouraging academic investigator-initiated trials.

3. With the recent changes in new CT rules, what can be the benefits and shortcomings for clinical trials conducted in India?

• Benefits

Time-bound approvals for clinical trials in 90 working days
Advantages to Indian R & D discovery for initiation of Phase I in 30 working days
Accelerated approval/trial waivers for serious and rare diseases

• Challenges:

Investigators: Academic trials to comply with ICMR guidelines  Ethics committees (EC):
Dual registration from the DCGI office and Dept of Health Research  Composition: 50% non-affiliated members
Short comings
Independent Non-institutional ECs, which may not be competent in ethical oversight, permitted to oversee clinical trials
Sponsor concerns about delays in approval because of irrelevant queries
Lack of clarity/transparency in the regulatory inspection process
No change/improvement in the SEC review process
Approval requirements for non-interventional Phase IV studies
Some of the criteria for accelerated approval/waivers are unclear and are as per discretion of regulatory authorities

4. What are the industry expectations from Indian regulatory going forward?

Transparency and clarity in accelerated/waiver criteria/pathways
Professional regulatory inspection with graded regulatory actions along the lines of FDA and EMA

5. Where do you see the Indian Clinical trials industry in the next 5 years?

Depends on how the new regulations improve the quality and conduct of Indian trials and how the society and media react to the favorable regulatory environment for new drugs and clinical trials
All stakeholders should learn from past deviations and watchfully conduct clinical trials in compliance with regulations.
Over the next 5 years, all stakeholders should strive for ensuring human protection and data integrity and to establish an image of India as a quality innovation R & D hub.
Focus should be on quality, and Quantity will follow.

6. What are the current issues surrounding clinical trial data integrity, and what can be done to improve it?

Attitudinal shift by sponsors to reject data whose integrity is suspect
Strengthen QA and monitoring process
Reward sponsor team members who discover data integrity issues and whistleblowers
Action – suspension of the contract, blacklisting, regulatory notification, information sharing with industry – against responsible parties – in-house staff, CROs, investigator sites
Training in documentation, monitoring, and QA sponsor and investigator site staff
Training of ECs in oversight and monitoring to detect data integrity issues and to take appropriate actions

7. What measures should the industry take to ensure clinical trials are carried out safely?

Training of in-house staff – monitors, project managers, medical monitors, auditors, and site staff in pharmacovigilance, assessment of causality and clinical trial relationship of SAE, regulatory reporting, and compensation
Train the site personnel thoroughly in protocol procedures, especially selection criteria, follow-ups, and safety assessments
Project team should promptly detect important protocol deviations, which can impact the safety of subjects, and take appropriate actions, e.g., exclude patients, stop recruitment and inform EC, etc.
Medical monitor and project team should verify the assessment of causality and clinical trial relationship of SAE by the investigator considering company safety information and medical condition
Ensure that the investigator complies with regulatory requirements of free medical management

8. How do you position Indian ethics committees with respect to functioning and competence in the current global scenario? What is your view on steps to be taken to further improvise the functions of the ethics committee?

Barring a few empowered ECs in major academic institutions, most ECs lack competence in fulfilling their vital responsibility of ensuring the protection of rights, safety, and wellbeing of clinical trial participants.
Department of Health Research should provide training and conduct ongoing monitor/review of the functioning of ECs.

On a closing remark, Dr. Arun Bhatt mentioned that “As a country, we should remember those who forget history are condemned to repeat it and conduct clinical trials balancing the twin requirements of human protection and data integrity. We should comply with regulations and guidelines both in letter and spirit!”

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 anyone 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.

Inhalation clinical trials – Challenges and ways to overcome.

July 9, 2019

Posted in - Veeda

Many respiratory diseases have been historically treated using inhalation drugs as this route of administration allows for a higher drug concentration to reach the target organ thereby reducing systemic effects. Apart from respiratory disorders, trials are ongoing to determine the efficacy of inhaled insulin in diabetes management.1,2 Although pulmonary delivery of insulin is a valuable option with the advantage of ease of administration compared to injections, further research is ongoing to study its safety through the oral route.1,2

An ideal inhalation device is the one that delivers a reproducible and fixed dose of the drug to the lung, is patient-friendly, and not cumbersome. The commonly prescribed inhalation devices are pressurized metered-dose inhalers (MDIs), nebulizers, and dry-powder inhalers. All inhalation devices undergo stringent invivo and invitro testing to determine the safety and efficacy of the drug through these devices.3 However, inhalation clinical trials bring forth a number of challenges.

Device-drug compatibility

There are hiccups that investigators and sponsors face while conducting inhalation trials such as the need to use cumbersome and costly devices as well as the probability of bronchospasm due to the drug or non-drug component(s). In addition, some inhalation drugs can cause withdrawal symptoms. Other factors that influences the trial results are the difference in drug bioavailability in each patient due to varied breathing patterns or the presence of a comorbidity that affects drug absorption. For instance, epoprostenol has a short half-life of 3 to 5 minutes requiring continuous nebulization for long periods making it difficult to administer or prescribe on a long-term basis.3

Safety issues

A number of inhalation trials were terminated in the initial phases due to issues such as poor drug solubility and bioavailability leading to dangerous levels of undissolved drug in the systemic circulation.4

Patient training and adaptability

For effective therapy, the patient should be able to use the device correctly. Inhalation drugs and devices are viewed as complex by many patients and thus would require practical demonstration as well as repeated follow-up by medical staff to ensure that the patient is using the device as intended for optimal drug delivery. The patient should also be encouraged to use e-technologies that help in self-monitoring to look out for symptoms that may require medical intervention and help raise awareness about the respiratory disease.5 many studies have observed that inappropriate use of inhalers is a cause for improper management of respiratory diseases. A study in a university hospital in Northwest Ethiopia by Mebrahtom M et al demonstrated that approximately 71% of the subjects were handling inhalation devices incorrectly due to lack of awareness about MDIs consequently leading to poor asthma control.6 Another study by Arora P et al reported approximately 95% error in subjects using MDI and approximately 82% error in subjects using dry powder inhalers.7

Regulatory laws in India

There are no specific regulatory guidelines laid down by the legislative body, Central Drugs Standard Control Organization (CDSCO) and Drug Controller General of India (DCGI) for inhaled products. As applicable to all trials in India, inhalation clinical trials should also adhere to Schedule Y and Rule 122A to E of the Drugs and Cosmetics Act, 1945, Good Clinical Practices (GCP), and ethical guidelines for biomedical research on human subjects. The guidelines followed for bioavailability and bioequivalence studies are also applied to inhalation trials. However, bioequivalence studies for inhaled drugs are still in its nascent stages in India. Although pharmacokinetic (PK) bioequivalence studies alone are being accepted worldwide to establish equivalence of inhalation products, India is yet to approve second entry orally inhaled drugs with data from PK bioequivalence studies alone.8

Creating a conducive environment for inhalation clinical trials

To build India’s competence in inhalation trials, the recruited staff should have expertise in handling phase I/bioequivalence studies. The DCGI and CDSCO can also come up with specific study timelines as well as suggest appropriate study designs for inhalation trials in consultation with the technical committee. As the comparison of clinical efficacy endpoints between two orally inhaled products provides shallow dose response curves, equal weightage should be given to invitro bioequivalence assessments.8

Emphasis cannot be laid enough about the need for the investigator to share all medical decisions with the patient to improve patient compliance rates in clinical trials.5 Human factor (HF) studies can be designed to include strategies that mitigate errors caused due to improper device use. HF studies also help in understanding the effect of interaction between the patient and device on the safety and efficacy of the inhalation drug. HF studies are gradually showing their presence globally especially in clinical trials that involve the use of devices.9

With companies increasingly seeking alternative solutions, the route of inhalation delivery will continue to grow. This makes it critical for the scientific community to fill the existing gaps for conducting successful inhalation trials.

Sources

1.Cavaiola TS and Edelman S. Inhaled Insulin: A Breath of Fresh Air? A Review of Inhaled Insulin. Clinical Therapeutics. 2014;36(8):1275-89.

2.Oleck J, Kassam S, and Goldman JD. Commentary: Why Was Inhaled Insulin a Failure in the Market. Diabetes Spectrum. American Diabetes Association. 2016;29(3):180-4. https://doi.org/10.2337/diaspect.29.3.180

3.Holgate ST, Bousquet J, Chung KF et al. Summary of recommendations for the design of clinical trials and the registration of drugs used in the treatment of asthma. Respiratory Medicine, 2004;98(6):479–487.

4.Forbes B, O’Lone R, Allen PP et al. Challenges for inhaled drug discovery and development: Induced alveolar macrophage responses. Advanced Drug Delivery Reviews. 2014;71:15-33.

5.Shakshuki A and Agu RU. Improving the Efficiency of Respiratory Drug Delivery: A Review of Current Treatment Trends and Future Strategies for Asthma and Chronic Obstructive Pulmonary Disease. Pulmonary therapy. 2017;3:267-81.

6.Mebrahtom M, Mesfin N, Gebreyesus H et al. Status of metered dose inhaler technique among patients with asthma and its effect on asthma control in Northwest Ethiopia. BMC research notes. 2019;12:15.

7.Arora P, Kumar L, Vohra V et al. Evaluating the technique of using inhalation device in COPD and bronchial asthma patients. Respiratory Medicine. 2014;108(7):992-8.

8.Lee SL, Saluja B, Garcia-Arieta A et al. Regulatory Considerations for Approval of Generic Inhalation Drug Products in the US, EU, Brazil, China, and India. AAPS Journal. 2015;17(5):1285-1304.

9.Vaidya A. Learnings and Challenges of Conducting Human Factors Studies on Inhaler Devices. Clinical Trials Arena. 2017.https://www.clinicaltrialsarena.com/news/case-study-learnings-and-challenges-of-conducting-human-factor-studies-on-inhaler-devices-5852797-2/ Accessed on June 21st, 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 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.

Ensuring Patient Safety and Scientific Credibility in Clinical Trials.

June 29, 2019

Posted in - Veeda

In the clinical research industry, safety norms and processes should be applied to every aspect, starting from drug development to post-marketing use of approved drugs, keep in mind patient safety and data credibility at every stage of clinical development.

Patient safety requires collaborative effort of the regulatory system, healthcare system, and the sponsor. Equally important is the need for effective communication to patients by the regulatory bodies and health care systems to maintain transparency. Such communication also help in instilling confidence in patients about the scientific credibility of the trial. For instance, the Central Drugs Standard Control Organization (CDSCO), India uses information technology to keep the public aware about ongoing and completed trials. All data starting from filing of application to the trial results are available on the website. Sponsors, clinical research organizations, as well as ethics committees are required to furnish their details on the website. Data safety and monitoring boards (DSMB) are also formed to monitor trials, especially large trials, for safety and reliability of data. DSMBs play a significant role in letting the public know if the investigational drug poses any threat as well as to ensure that the sponsor does not purport the results to be unbelievably beneficial to the targeted patient population.

Emphasis should also be laid on novel and practical-oriented training programs for students in the health care profession to expose them to real-world situations. Students should understand the importance of having risk assessment, risk management, and risk mitigation plans in place to improve patient safety. Periodic assessment and continuing medical education programs for medical professionals are also pivotal in ensuring that they remain competent in their respective fields and prioritize patient safety and moral ethics in their profession.
The successful implementation of patient safety and data integrity is a multidisciplinary approach that requires sincere and diligent effort of each individual and organization involved in the conduct of clinical trials.

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

Current outlook of Clinical Research in India

June 20, 2019

Posted in - Veeda

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 way for many multinational pharmaceutical companies to invest in clinical trials in India. Apart from this, cost effectiveness is an important factor that drives 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 that 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 the least, concerted efforts and joint participation of the Indian government and Indian pharmaceutical companies in policy-making decisions and prioritization of patient’s safety and health will build confidence in international companies about India’s capability in contributing to the clinical research industry.