Introduction of the molecular genetics confirmation, gives the much needed ‘diagnostic edge’ to the current newborn screening test

After the government imposed restrictions on commercial banking of stemcells, LifeCell choose to diversify its business portfolio to diagnostics and tissue therapeutics through the launch of its RightStart division. However, low awareness about newborn genetic screening poses a lot of challenges for players in this arena. Ishaan Khanna, CEO of Diagnostic & BioBank Divisions, LifeCell International speaks on the opportunities and challenges in this field and the steps that need to be taken by the industry and the government to leverage the true potential of newborn genetic screening, with Usha Sharma

Why did the government impose restrictions on commercial banking of stem cells and how badly has it hit the industry?

As per the Indian Council of Medical Research (ICMR), at present there is lesser scientific evidence to substantiate clinical benefits with the use of stem cells derived from cord tissue, placenta, tooth extract, adipose tissue, dental pulp, menstrual blood and olfactory ensheathing cells etc. Yet, procurement and banking of these biological samples is increasingly becoming a commercial activity by few private stem cell banks. Most of these facilities that store umbilical cord tissue do so for a very high fee in lakhs of rupees. Hence, care needs to be taken so that there is no exploitation and commoditisation of the resources. As of now, only umbilical cord blood banking is permitted and licensed by the CDSCO. Accordingly, commercial banking of all other biological materials not permitted until further notification.

ICMR was also concerned that some clinics may be offering stem treatments for medical conditions that cannot actually be treated. The council wants to ensure that doctors do not mislead patients into trying untested therapies. Some doctors are fooling patients by offering stem cell therapy for conditions for which there is no scientific evidence. It may not be right to say that it has hit the industry in any way. Its good that ICMR is working toward regulating this industry and Lifecell is in support of that.

In lieu of the recent guidelines issues, Lifecell has ensured and it complies with all the Indian medical guidelines and recommendation through the following measures:
1. Launch Community banking:
2. Stopped collection and storage of cord tissue which many other companies in India are still doing
3. In order to support need for mesenchymal stem cells for approved therapies. ensure clients get access through an approved source while we work on building our tissue bank for the same

Recently, LifeCell diversified its business portfolio to diagnostics and tissue therapeutic. Can you share the details of this development?

LifeCell Diagnostic, the diagnostic division of LifeCell covers wide range of biochemical and genetic test in Mother and Child portfolio. Started in 2012, Lifecell became the first diagnostic company in India to introduce two tier testing for new born screening backed up by a strong R&D team. LifeCell Diagnostics became the first commercial company in India to offer quantitative fluorescent polymerase chain reaction (QF-PCR) in prenatal settings and in 2018, LifeCell launched the revolutionary pentastic marker and became the first in the world to offer a biochemical marker test with a detection ratio of 98 per cent and FPR of 1.2 per cent. The RightStart programme, a recent initiative by LifeCell Diagnostic, is aimed to provide diagnostic confirmation to new born screening result. The integration of genetic sequencing to new born screening will help in reduction of false positives and also assist in faster initiation of treatment.

How is LifeCell’s ‘RightStart’ newborn screening different from other players’ offerings in the market?

In the current scenario, new born screening involves screening of biochemical analytes which predicts the probability of certain genetic conditions in the baby. This method has many complexities, influencing the result and test interpretations, thereby decreasing the precision and increasing the False Positive rate thereby contributing to parental anxiety.

LifeCell Diagnostics’ Rightstart test integrates biochemical screening with molecular genetic testing. The introduction of the molecular genetics confirmation, gives the much needed ‘diagnostic edge’ to the current newborn screening test. Though the current newborn screening practices are effective, the addition of DNA based genetic test reflex enables a molecular diagnosis and rules out the possibility of false positives. Lifecell has packaged this in a single unit to avoid incremental costs.

To what extent is newborn genetic screening practised in India? Do you think it is going to increase in future?

Newborn screening is the most widely used paediatric initiative worldwide, but sadly in India it is still in a very nascent stage considering high prevalence of many life threatening conditions. Our estimates suggest it is less one percent of the total births. With Government of India launching initiatives to create awareness about the importance of screening through its Rashtriya Bal Suraksha Karyakram and various PPP model the programme should see a wide acceptance in the future. Also at the level of pediatricians and gynaecologists, the awareness and understanding on the need for newborn screening has improved over the last few years. We are seeing more and more hospitals adopting this programme and expect that with a solution like ‘Rightstart’ the uptake should significantly improve.

The company is encouraging community banking, how is it going to play an important role in the future?

Recently, two important professional associations of doctors in India have issued statements against private banking of umbilical cord blood. Both the Indian Academy of Pediatrics (IAP) and the Indian Medical Association (IMA) have argued that the chance of a baby using its own stem cells is “negligible”. Both medical opinions consider allogeneic stem cell transplants to be the only valid use of cord blood, and only consider those diseases treated with transplants from a donor. Hence, both the IAP and IMA recommend that families in India should preserve their baby’s cord blood in public banks rather than in private banks. A public cord blood bank is a common pool of stem cells, where patients in need can readily find matching stem cells for treatment In India.

Challenges faced by Public Cord Blood Banks in India Low Inventory: The total inventory of purely public cord blood units in India is below 6500 CBU. Jeevan, the only public bank that lists Indian cord blood units for transplant, has stopped to accept further cord blood donations due to lack of funds4. Globally there are about 750,000 public CBU spread over 55 major public banks in the world.  But the ability to find a donor that is a close enough match for transplant depends on ethnicity, and calculations show that the chance of an Indian finding a match from these global cord blood banks is less than 10 per cent.

High Cost: Currently the cost to procure a single public cord blood unit in India is INR 15-20 lakhs. The cost to procure a public CBU from abroad varies by bank but is typically INR 30 lakhs. An adult patient may require two CBU for a transplant, doubling the cost. Additional expenses, such as hospital costs, might accrue to INR 15-20 lakhs.

LifeCell’s Community Stem Cell Bank works similar to a public bank: Parents contribute their baby’s cord blood stem cells to a common pool for use by themselves and other members of the community. This increases the chances of finding a suitable matching donor and thereby expands the treatment options for patients. Thus the Community Banking model completely meets the IAP and IMA recommendations. Not only does Community Banking solve the challenges and costs of the public banking model, it is also a more sustainable business model compared to public bank LifeCell’s Community Bank currently has over 25,000 qualified cord blood units. This is over four times the inventory of India’s public banks and meets the required size to provide minimum matches for 96 per cent of Indian patients to learn more about cord blood banking. Basis this we see community banking as possibly a great solution for a country like India.

Why there is less awareness about newborn genetic screenings in India and what steps needs to be taken to increase it?

The level of acceptance in metros and in private hospitals has increased significantly in recent years but in tier II and III cities as well as government hospitals there are many challenges. One of the main reason that can be attributed to the same is the cost involved in treatment and management of the disease. And another factor is the absence of doctor specialised on metabolic disorder who can counsel the patients on the diseases and management of the same. Another important factor that plays a role in the low level of acceptance is the high rate of false positives associated with the test and the subsequent high cost involved in confirmation of the screen positive results.

Steps that can help in the increase in awareness of the programme:
1. Public-Private partnership models in endemic states to promote universal screening for every children born- Setting up labs in the government hospital
2. Set up NBS courses for paediatricians for counselling and disease management
3. Subsidised pricing for cost of treatment and management of disease

Tell us the clinical challenges associated with newborn genetic screenings?

Clincal challenges are mostly around ensuring timely diagnosis, ensuring the right treatment and management to be provided which in many cases is not very straightforward and is expensive.

How genetic testing can improve new born screenings? How can state governments make it part of their programme?

LifeCell Diagnostics’ RightStart test integrates biochemical screening with molecular genetic testing. RightStart enables the physicians to take the appropriate decision on disease management. The introduction of the molecular genetics confirmation, gives the much needed “diagnostic edge” to the current newborn screening test. Though the current newborn screening practices are effective, the addition of DNA based genetic test reflex enables a molecular diagnosis and rules out the possibility of false positives. Integration of genetic testing to new born screening helps in providing definitive diagnostic results and faster initiation of treatment. Steps that can help in the increase in awareness of the programme include public-private partnership models in endemic states to promote universal screening for every children born- by setting up localised labs in the hospital or developing nodal labs in the states.

How newborn genetic screening will empower the healthcare scenario from curative to preventive?

According to IMA 2016 data, one out of 20 newborn children is admitted in hospitals with genetic disorders. An efficient universal screening programme with integration of genetic testing will help in early detection and faster initiation of management and treatment of diseases thereby reducing the cost of the treatment and further reducing the mortality rate. Most of the conditions in NBS are normally fatal and can incur huge cost of treatment and management if not diagnosed at the early stage. A simple example is of Congenital Hypothyroidism which is very common in India. If detected soon after birth, a very simple medication regime and prevent mental deterioration in the child, However if left undiagnosed till later, it can cause irreversible damage to the child’s mental development.

Will new born screening be a part of Ayushman Bharat? And are you initiating dialogues with the state and central governments?

We expect it should, we are in discussion with various state governments and central health authorities to see how best this can get incorporated in the state health programmes.

[email protected]