4th Anniversary of Genelife Clinical Research

Not so long ago, on 26 Feb 2010 we started Genelife Clinical Research, after years of planning and analyzing the cost & expenses. On this day our dreams took-off with a lot of enthusiasm, promise and hope in the back drop of recession and limited resources. We knew that if we will survive that period we would have no limits. During those days we had to survive not only the recession but also against mighty established players. We survived that period and emerged as a winner in our own way. The first year was a very emotional year. We had gone through lots of pain and turbulence before we reached our 1st anniversary. But why I am talking about that now.. because this was an equally challenging year.

This year we will be remembering as the year of “reform and regret”. Across the country the quality of care of patients and clinical research was decreasing considerably. The necessary quality standards were available as standard in some places and were unavailable in others. Our regulation which was developed in a piecemeal fashion over a period of time was not able to manage the things properly and industry was in desperate need for reform- which finally happened this year. However, the planning, developing and implementation of this reform took almost a year, which almost killed the Clinical Research industry of India. Many competitor companies including some giants pull their curtains down; some changed their mode of operations. This changed the entire complexion of Clinical Research market, which to some extent is positive because now only those seriously involved companies are left in this serious business.

Everybody in healthcare industry was affected by this “silent” phase and we were no exception. However, with the confidence in our system and support of clients, friends and well-wishers we came out of this period. This could have been even better if we would have not lost some US FDA projects due to this regulatory complication. I still regret that decision of taking those projects in such an unstable regulatory environment. It was hard for us, but even larger concern and my deep apology to those sponsors whose time, energy and money wasted during this tenure.

Since inception, Genelife Clinical Research has focused on strong customer relationship with a vision "To be the most respected partner in providing product development and clinical research needs." The effort of giving the best is a kind of self-motivating mantra which probably separates us from the rest. And probably this is the only thing which helps us to emerge excellent from any given situation.

Looking back at the development of the entire year; it gives me a sense of achievement. We started the year on high note and anticipated a greater growth; however, with all the hiccups, what we achieved is remarkable growth not only in terms of project but also in terms of reach. We now have a global presence and soon we will be operating globally. We have implemented electronic CRF and looking forward to implement CTMS.

I would like to to attribute this year’s success to my team, which stuck to the basics & kept me away from taking any imprudent decisions. The secret of our success this year is not just doing the right thing but doing the right thing in customer centric way cost effectively. Very basic principle we understood our sponsor’s requirement and planned according to their requirement.

On this auspicious occasion, I sincerely appreciate the faith of clients on our ability. We are looking forward to deliver that trust in best possible way. I am greatful to all those who have directly or indirectly helped us to shape our dream and vision. But my greatest thanks to my colleagues and consultants for their commendable effort and believing the ideology of Genelife Clinical Research. This year belong to them and I feel proud to be a part of this excellent team.

I am looking forward for the same kind of trust, faith and support from everyone in future. I know if we perform this good, we will evolve even better in the coming year.

Thank You.

Kind Regards,

Dhirendra V. Singh

Genelife Clinical Research: Ophthalmology Clinical Trials

Genelife Clinical Research has started 12 Phase III Ophthalmology Clinical Trials for DCGI Submission. These 12 studies cover vide range of indications including dry eye, Ocular pain, Intra Ocular pressure, different types of conjunctivitis, pre & post cataract surgery etc. In these studies we are recruiting all kinds of patients from minor to old age people which will be a challenging task for us. 

We have already finished selecting sties for these studies. All the sites are selected very carefully as per the current DCGI guidelines including audio visual regulation. All these sites are multi-specialty/government hospitals with DCGI approved ethics committees and are distributed in all Geographical regions of India. During site selection we have considered seasonal variation as well as on recruitment prevalence of the particular ophthalmic condition from DSR, historic data and geographical location.

 

For adapting and absorbing the complexities aroused due the introduction of audio visual informed consent we have developed our electronic CRF which will be able to capture that also. This will help us to make a complete document for a patient for regulatory purpose and future regulatory audit purpose. During the site selection procedure we have made special emphasis on the infrastructure of site and computational knowledge of site personal.

Like our past studies we are hoping to complete these study before the time we proposed to our Sponsor. Hope we will achieve our target.
Kind Regards,

Rama Rajesh 

Project Manager 

Genelife Clinical Research

Genelife Clinical Research: III Anniversary

We perform at our intellectual best and by exceptional willingness when we know why and what we're doing; with this motivation Genelife Clinical Research was established (on 26th Feb 2010). Every one related to Genelife either employees, clients, consultants, investigators, vendors or well-wisher they all have played their role most effectively and efficiently in the establishment & development of Genelife Clinical Research. On the third anniversary of Genelife Clinical Research I would like to thank everybody who has worked to achieve our goal “To be the most respected partner in providing product development and clinical research needs.” We can say this, because we have been haired more than once by all our sponsors. 

The development of Genelife Clinical Research has proved that marketing and sales is not the only deciding factor for the development of an organization. Our continuous development is because of our young Operations & Biometrics team, which has shown the urge to reach their full potential in order to make each project successful. They proved that the strongest principle of growth lies in one’s choice. We were privileged to receive this choice from our esteemed clients who trusted in our capabilities and entrusted their important projects. Furthermore, our development is also credited to those clients who have given suggestions for process development in place of project, which was equally valuable. And with them we hope to strengthen our relation further. 

Genelife Clinical Research has seen several notable changes this year like: 

• Web CRF 
• New & bigger office 
• Global presence; we now have major clients in Australia, Europe & North America. And now we have operations in Malaysia, Sri Lanka, Bangladesh, Indonesia and South Africa. 

In 4th year of our business we will focus on accelerating our growth strategy while continuing to build on the strength of our brand—by sharing the knowledge of our services & strength through effective marketing. However, we will not follow the conventional method of marketing also. It will be as unique as our “Disease Surveillance Report”. We are very excited about this and truly believe that this will bring a trend in our fraternity. This will also be our first step towards expansion with stability, better service, and global presence while still offering all advantages of a small size CRO. We are also very excited for our new office in Copenhagen which we will open in May 2013. However, our focus will remain on “Creating Innovation” in our project management implementation. 

Looking back on the trails of time and development I feel proud to be a part of this exciting journey. This keeps me encouraged and intrigues me to reach further out to you, our partner, client and ambassador. 

Thank you everybody. 

Kind Regards,

Dhirendra V. Singh

Biosimilar Regulation in India

A biotherapeutic product which is similar in terms of quality, safety and efficacy to an already licensed reference biotherapeutic product is known as Biosimilar.

This could be the single fastest-growing biologics sector in the next five years – albeit from a small base – spurred by the convergence of major dynamics that will see new biosimilars enter the US market, bring additional molecules to Europe, and open up oncology and autoimmune disease areas to biosimilars for the first time ever. Biosimilars also bring clear potential for payers in the emerging pharmaceutical or “pharmerging” markets, such as Brazil, China and India. India have developed new regulatory guidelines for Biosimilar.

In New guideline DCGI has made mandatory the preclinical evaluation of biosimilar. The non-clinical studies should be comparative in nature and design to detect differences if any, between the similar biologics and innovator recombinant product. These should be conducted with the final formulation of the similar biologics intended for clinical use, unless otherwise justified. The non-clinical study design may vary depending upon the clinical parameters such as therapeutic index, the type and number of indications applied for etc. Assays like receptor binding studies or cell based assays (e.g. cell proliferation assays) should be conducted, when appropriate to establish comparability of biological activity. In cases where invitro assays do not reflect the pharamacodynamics, in-vivo studies should be performed. Comparative repeat dose toxicity with immunogenicity testing is also made compulsory in given route of administration, local tolerance should be evaluated.

According to new guideline, comparative Pharmacokinetic (PK) study on healthy subjects, Pharmacodynamics (PD) studies in most patients or healthy volunteers. If PD marker is available in healthy volunteers, PD in healthy volunteers can be done. Followed by a Phase III, Comparative safety and efficacy in relevant patient population is also mandatory for all biosimilar. However, in certain cases it can be waived. DCGI has also mandated the submission of PSUR 6 monthly for first 2 years and then annually for next 2 years, along with a Post Market study.

Regulatory applications and approvals issued at different stages of biosimilars product development

No.	Stage	Agency involved	Application	Approval
1	Manufacturing permission for test, analysis & examination	DCGI	Not Spesific	Permission (Manufacturing NOC)
2	Manufacturing License for test, analysis & examination	Local FDA	Form 30	Form 29
3	R & D	Institutional Biosafety Committee (IBSC)	Not Spesific	Permission (IBSC minutes)
4	Non-Clinical studies permission	RCGM	Form C3	Form C4
5	Submission of Non-clinical study report	RCGM	Form C5	Form C6
6	Clinical Trials	DCGI	Form 44	Permission (CT NOC)
7	Manufacturing License for CT batches	Local FDA (subject to CT NOC)	Form 30	Form 29
8	Manufacturing & Marketing permission	DCGI	Form 44	1. Form 45/46 (Finished product) 2. Form 46A (Bulk product)
9	Commercial Manufacturing License	Local FDA	Form 27 D	Form 28 D

Kind Regards,

Genelife Clinical Research- Ongoing Medical Device Clinical Trials

Genelife Clinical Research has started its first Medical Device Pilot Clinical Study for US FDA submission. Although we have participated in couple of US FDA studies in past but both were Pharmaceutical Clinical Trials. This is first time we are going to start a Medical Device Clinical Trials for Medical Device, within ENT therapeutic area. 

The study will be performed in a single site in India and we are hoping to recruit all patient volunteers in one month. The site selection procedure was dependent on not only the historic performance, type of Institute and its geographic location, paramedical staff, Investigator’s qualifications but we also considered the importance of patient referral. This we did considering the importance of project as well as the dependence of season on recruitment. 

Like our past studies we are hoping to complete this study before the time we proposed to our Sponsor. Hope we will achieve our target.

Kind Regards,

Advantages of eCase Report Form

No experiment is said to be complete until the results had been published or otherwise reported. It becomes even more important when the research directly involve human. Clinical research not only directly involves human subjects but can also affect human health if the reporting is not performed properly. And for proper reporting, proper data collection is very important.

In 70% clinical trials data collection is done manually through paper CRF in which Investigators manually record data on source documents and copy the same to the CRFs. Clinical monitors from CRO/sponsor verify the data and send the CRFs to CDM team. Paper CRF usually has an audit trail that is visible directly on the CRFs. Changes to individual fields are indicated with a single-line cross out, with the changed data appended along with the signature or initial of the person making the change, a date and perhaps a reason for change. Comments are written in the margin of these CRFs. Data clarification forms are appended to the CRF and contain the questions and responses that generated the change. This time honored format creates a complete case record with audit trail that is familiar to regulatory reviewers and investigators.

Though paper CRF gives an accurate, reliable and complete data, it is a laborious process and takes time for collecting CRF from investigational site, performing data entry and validation, and raising and resolving queries via Data Clarification Form (DCF). This has direct impact on time for drug to come in market. This suggested the idea of real time data management tools. Hence technology and innovation is used to its full extent and Electronic Data Capture (EDC) comes into limelight. The concepts for the design of electronic CRF are same as covered for paper.

EDC technology is expected to improve efficiency and accuracy of data, speed up decision making process and reduce cost. It resulted in a reduction of paper consumption and load on clinical monitors to manage such huge volume of paper. This paradigm has reduced the risk of damage of CRF during transit. It is due to these reasons EDC is preferred to traditional method.

GCP and 21 CFR Part 11 require validation for a software system used for processing clinical data. System validation includes user requirement specifications, functional specification, design specifications, implementation and testing. 21 CFR Part 11 defines the criteria under which electronic records and electronic signatures are considered to be trustworthy, reliable and equivalent to paper records. Part 11 has requirements to implement controls including audits, system validations, audit trails, electronic signature and documentation for software and systems involved in processing electronic data that are a) required to be maintained by FDA rules and b) demonstrate compliance to a predicted rule.

In electronic CRF, investigator enters data and signs electronically for accuracy, reliability and completion of all data points. It assembles data from multiple tables into a single Web page. However, the investigator later can add, modify or delete data in the EDC system in future at any time-point, until the electronic CRF are locked and no more updating is permitted. Investigator at this point should sign for the changes made to electronic CRF data points which were entered or changed. At the end, Investigator has to sign for all data entries, modifications or deletions as he is owner of that clinical data. This is why signing by the investigator is so important in electronic data capture.


Audit trails and comments are not found in the margins of an eCRF- they are viewable through links from the CRF and also are simply user-friendly representations of data tables. Electronic CRF is not just a repository but is designed to allow the backend systems to perform efficiently. The forms have built in edit checks and no longer accept entered data. POPs will appear if there is any error in entry/incorrect value. Query management can be done within minutes as opposite to paper CRF. Queries can be managed through computer user interface rather than paper based clinical trial. We can raise query directly on website and monitor can log on the query message and provide his resolutions there. Since high quality data are available at the time of data entry by the study site, biostatistician can review and analyze very early. As a result almost all statistical programs are completed before the visit of last patient.

Roles of data management staffs that have changed with the arrival of eCRF:

1. Data entry task shifted to site personnel/investigator 
2. Data review/cleaning became a joint venture of site personnel/investigator, clinical monitor and CDM team 
3. Trainer is needed in CDM to impact training functionality of EDC software 
4. Clinical monitors to perform source data verification which is a QC task, 
5. CDM members have to generate extra manual review listings and perform this task manually 
6. Clinical monitors or data management team to address/resolve technical issues faced by site personnel/investigators. 

However few challenges exist and researchers are trying to evaluate if quality of data produced by traditional paper based studies is better or equivalent compared to data generated by EDC. Investigational site personnel find data entry as a tedious task. Multiple EDC software has created confusion to non-CDM members. There is a need to develop effective training for EDC software, which is study specific for a given protocol. Hence investigational sites require technical support and guidance. One of the most common deficiencies cited by the FDA is the lack of documentation since the original observations are entered directly into a computer system; in this case electronic record becomes the source document. Paper is eliminated but EDC uses technologies like internet, software EDC and other additional services such as call center, so it cannot be considered as a cost-effective solution.

There is no doubt that electronic data capture is the future as it increases the speed of data processing and assures high quality data with lower error than paper CRF of Clinical Research. However, deployment of these advances should be implemented carefully as it requires consideration of desired outcome and the needs of people involved in the process.

Representing

Genelife Clinical Research - Clinical Data Management Department

Patient Recruitment and Retention- Genelife Approach

With recent times INDIA is booming as developing place for all the fields along with Clinical Research. Because of the large population and diversity India is one of the hot spot for clinical research at the global frontier. The population across country understanding the real health care need and the importance of drug discovery where the critical link is Clinical Research.

Clinical Development is the key milestone for a drug to get into the market shelf. Clinical Studies got vital role for better understanding of the discovered molecule activity in human and the subjects who are intended consumers of the drug.

For a successful drug launch the Clinical Studies and population participation is a demanding process which should happen for achieving the objectives of the drug utility and to provide best health care to save lives.

The connectivity of process and the prominent points of patient recruitment and retention;

·  Clinical development phase initiation                           

·  Clinical Trials protocols development

·  Therapeutic Indications understanding

·  Patient availability & assessments

·  Patient recruitment and retention strategies

Patients Availability and Assessments – The study design and the indications were the base to engage and assess the patients availability and assessments must be done on the basis of:

o   Ethnicity

o   Demographics

o   Geographic

o   Behavioral

o   Psychographic

o   Incidence and Prevalence

o   Epidemiology

Advertising programs brings attention about the research happening and ignites intentions for connecting population to participate in the research. The healthier and understandable advertising with proper methodologies really brings branding for the drug as well. Across globe the concept of medical research and the potential risks and benefits has to be socially publicized through media by having regulatory intimacy.

The consistent advancements through ethical research for establishing bliss for humanity through medicines and participated population and the benefits received by them by value and appreciation must be taken forward into society and public by media. These kinds of steps will enhance awareness across communities for contributing into research and development.

Patient retention throughout the study is the most important task and it can be achieved by the classic methodologies and the intimacy of Investigator and site team plays vital role to achieve maximum retention rate.

Patient retention is possible with; GENELIFE CLINICAL RESEARCH methodology

·      Simple explanation of the study and the milestones of it

·      Clear and complete understanding about the patient importance and expectation from them

·       Explaining the potential benefits risks and facts about the study and their role with intimacy in terms of health, reimbursements (travel & meal) and making patient comfortable at clinic

·     Whom to contact if patient is having any questions or concerns and being available at any time accessible for patients.

·        Make patient clear about quit procedures and its implications and results.

·        Make them feel appreciated and valued as they were critical contributors for the research

·        Consistent interaction with patients and follow up.

Patient recruitment is possible with; GENELIFE CLINICAL RESEARCH methodology.

Focus groups- the population eligible for study participation. Identifying focus groups and finding the communities through available data resources.

·     Communicating and engaging different critical disease communities across the globe by accessing the GP’s and various organization and independent disease surveys making GENELIFE CLINICAL RESEARCH potential with subject availability.

·      The DSR – Disease Surveillance Reports across different horizons with floating life standards and various conditions based survey is making GENELIFE CLINICAL RESEARCH understand the proximities of disease prevalence.

·     Building extensive relationships with research organizations, institutions, academic labs, hospitals, clinics and medical fraternity with ethical research oriented intention is paving way to access patient pool for desires indications across therapeutic indications.

These steps improving the Clinical research employing potential, to move on with best patient recruitment and retention strategies for accomplishing the study primitives.

GENELIFE CLINICAL RESEARCH employs such methodologies with global outreach to provide compendious clinical development solutions      

Regards,

GENELIFE CLINICAL RESEARCH