The advent of peptides and insulin analogs for the treatment of Diabetes Mellitus has enabled improved management of the disorder. The biosimilars in this domain have been enabling increased accessibility to the treatment, cost reduction and overall patient care to the larger population.
On world Diabetes Day, 14th November, it is important to remind ourselves that there is still a significant gap to be filled in ensuring availability of cost effective biosimilars and making the newer and better treatment modalities become more accessible to the global society.
The main challenge with Diabetes is that it is a chronic metabolic condition that is associated with elevated blood sugar levels and which can, over time, lead to serious cardiovascular, ocular, renal, neuronal, and metabolic complications.
The prevalence of Diabetes Mellitus is increasing globally, affecting millions of people worldwide. The number of people with Diabetes is climbing closer to 500 million, primarily driven by the rise in urbanization and sedentary lifestyle.
The condition can broadly be classified in to two categories, Type-1 DM and Type-2 DM
Type 1 Diabetes: In type 1 diabetes, the body does not produce insulin as the immune system destroy the cells in the pancreas that produce insulin. This type of diabetes is usually seen in young adults or children, although it can occur at any age. It is important for people with type 1 diabetes to take insulin every day.
Type 2 Diabetes: In type 2 diabetes, there is insufficient production of insulin. This is a common type of diabetes and can occur at any stage.
Considering its important in diabetes care, insulin has been in the WHO’s Essential Medicines List (EML) since 1977. However, high price of insulin has affected access to diabetes care for many people across the world. In order to ensure health equity, it was important to identify insulin biosimilars. On 01 October, 2021, long-acting insulin and biosimilars that are necessary for the treatment of type 1 diabetes were added onto WHO's new Essential Medicines List (EML).
Navitas Life Sciences’ Euglycemic clamp studies
Navitas Life Sciences has extensive experience and expertise carrying out state of the art Euglycemic clamp studies, the gold standard for assessing insulin sensitivity in humans. The euglycemic clamp studies measure the glucose-lowering effect of biosimilar insulin compounds using a variable glucose infusion rate (GIR).
We met Dr. Shafiq Shaikh, General Manager - Clinical BA BE Services, Navitas Life Sciences, to understand how we support biosimilars through clinical trials, and also to understand the various scientific techniques and designs applied in such trials.
Tell us a bit about your professional background
I started my career in 2007, after medical college, as a contractual medical officer for one year. Later, I worked as an emergency response center physician for Gujarat Government. In 2009, I joined a Clinical Research Center and a clinical research physician, before becoming a clinical investigator and, subsequently, a principal investigator and manager of all doctors and nurses in the facility. I was the principal investigator for 200 studies, and have extensive experience in not only routine studies, but also for complex studies, transdermal, euglycemic, inhalation studies.
Since joining Navitas Life Sciences in 2017, as Head of Clinical facility for Mangalore and Manipal Unit, I have supported many euglycemic clamp studies .
Dr Shafiq Shaikh,
Clinical BA BE Services
Navitas Life Sciences
Please give us a glimpse of your role at Navitas Life Sciences
During my time at Navitas Life Sciences I have supported many challenging studies including multiple euglycemic clamp studies. I provide feasibility, design inputs, safety & ethical aspects review, and overall clinical studies oversight and team management.
In addition to the above, we as a team ensure regulatory compliant systems and processes deployment, support and fulfill internal/external audits and regulatory inspections, which are typically done prior to the grant of market authorization to the submitted dossiers.
Describe your journey supporting Euglycemic clamp Studies
The need for euglycemic clamp studies started gaining traction as the biosimilar players started to make their mark in the diabetes management domain. We as a team worked around the challenge covering all scientific aspects of conducting studies requiring maintenance of euglycemia, planned required infrastructure and team training and initiated recruitment and screening.
It was initially quite challenging to prepare the participating subjects who are required to hold on the clamp requirement sometimes to an extent of 24 hours. Deployment of required instrumentation as another challenge that was very well supported by the management in terms of procuring YSI analyzers and more controlled and monitored wards specially prepared for the purpose of clamp studies. This was supplemented with a very enthusiastic clinical team who were very eager and quick to understand the requirement and get trained in the necessary techniques. This was a very critical and contributing factor in ensuring subject safety while on euglycemia.
What is the significance of euglycemic clamp studies?
The euglycemic clamp technique is the gold standard for assessing insulin sensitivity in humans. Demonstration of similarity Pharmacokinetic and pharmacodynamic profiles of the biosimilar with that of the reference (comparator) is considered the mainstay of proof of similarity in efficacy and safety of the biosimilar when compared to the reference.
What are the purpose built facilities that are available for Euglycemic clamp studies?
We have well-equipped, state of the art euglycemic clamp study facilities in our Mangalore facility. This includes the YSI 2900 analyzer which is the latest and is considered the gold standard bioanalytical instrument to analyze the blood glucose.
We have an automatic infusion pump that we are using to make adjustments in order to maintain the blood glucose level. In case of medical emergency, we have an advanced ICU center that includes all emergency equipment and emergency medications.
Very few clinical research organizations in India have such facilities. Apart from the equipment, there is a need for expertise. It is not just infrastructure but the expertise that is important
We have a team of investigators for managing euglycemic clamp studies, a team of sub-investigators to manage the YSI 200 analyzer, and nurses who are experienced in managing such studies. The nurses need to collect blood sample every 5 minutes, which makes the total sample collected in 24 hours very significant.
Can you describe an incident when we went the extra mile to support unique client needs for euglycemic clamp studies?
As far as euglycemic clamp studies are concerned, meeting timelines is very important. A multinational pharmaceutical required an euglycemic clamp study to be conducted within a very short time. Apart from the technical complexities, with respect to the timelines, the challenge was to arrange the required number of volunteers who are willing to undergo clamp procedure. Additionally, these kinds of studies require intensive safety monitoring, which by itself is a speed limiter. We, with the help of a very strong recruitment and screening team, could fulfill sample size in a timely manner and the clamps were done batch-wise in line with the protocol requirements. Thanks to the team, who put in extraordinary efforts in realization of the study which required almost 160 clamp sessions.
In order to complete the study within the short timelines provided, we leveraged our vast expertise and facilities to increase our euglycemic clamp study capability from 2 to 4 volunteers at a time. There were 116 clamps conducted on 40 volunteers with each clamp lasting for 24 hours and blood sample collected every 5 to 10 minutes. This helped us complete the study within the stipulated timelines and the sponsor was very happy.
What are some of our validated methods that we have pioneered?
Navitas Life Sciences has a robust library of more than 300 validated methods with required sensitivity and has expertise in handling peptides in both LC-MS/MS and LBA based assay formats. Navitas Life Sciences is a pioneer in establishing methods for insulin and its analogs on LC-MS/MS and ECLIA platforms.
How many patient volunteers do we have for conducting euglycemic clamp studies?
We have 22,000 volunteers who we can include in our studies based on need. In addition, we have a pool of 100 fully compliant volunteers who have completed such studies earlier and who we can enroll quickly for any subsequent studies.
How did you manage euglycemic clamp studies during COVID-19?
COVID-19 pandemic has been a great challenge not only for us but for the entire global community involved in clinical research. The regulatory agencies did acknowledge the impact of this challenge on the clinical research in general and published multiple guidelines to provide support and guidance in carrying out research during challenging times. Those guidelines along with the national guidelines on COVID management and COVID appropriate behavior helped us greatly in building the required business continuity plans and processes such as SOPS and work Instructions, which in turn helped us tide over the challenges posed by the pandemic. We were able to complete one of the clamp studies undertaken during the pandemic in a timely manner.
How do you ensure subject centricity?
We ensure that all the potential and participating subjects are counselled and are fully aware about the complexities involved in the study. Our facilities are well equipped to provide comfort during the conduct of the studies. The safety of the participating subjects is of paramount importance in the clinical studies regardless of any design and complexity. We ensure that utmost care is exercised, required safety measures fully deployed and available for the safety and wellbeing of the participating subjects.
This was further ensured during the pandemic by enforcing mandatory COVID-19 testing, enforcing covid appropriate behaviors, fulfilling isolation/quarantine requirements for suspected or diagnosed case of COVID-19 and associated sanitation considerations.
100% of our Generics Development Team have received their COVID-19 vaccination Protecting our staff and clients, we continue to support your Generic Drug Development Needs
We are very happy to inform you that all our staff have been vaccinated. With regards to the participating subjects, COVID specific history is gathered through specific additional CRF and we do counsel and encourage all potential subjects to get vaccinated in the good of the society in general.
Euglycemic Clamp Study Capabilities
Navitas Life Sciences has the capabilities and resources to enable biosimilars companies to bring effective anti-diabetic therapies to the market quickly and safely.