By: Anu Acharya 
CEO, Mapmygenome India Limited

This article was originally written for ABLE ( Association of Biotech Led Enterprises) and published at http://ableindia.in/news/details/742

Covid is a pandemic like never before in our lifetimes, it needs quick intervention by the government and is also a clarion call for our innovators to create, and the government to certify and build internal capability for the entire chain of testing. By any conservative estimate we need to test 1-2% of the population(15-30 million tests) at a minimum before a vaccine or cure is discovered over the next year.  Even though private companies can step in, we suggest a strategy to acquire individual elements in bulk that are required for testing, assemble and distribute to private and public labs by the government for the next 3-4 months for testing. 

There are two main types of testing used globally for testing Covid.  Given the exponential growth rise in several countries, a wise approach would be two pronged, to make sure we scale testing but also spend less from the government.

Many countries have used rapid diagnostics using IgG and IgM antibodies, as they can be used for wide scale screening, followed by RT PCR test, for confirmation. As of now, ICMR has only allowed RT PCR testing, so let me dwell on that for now. I have the previous experience of developing an indigenous kit for H1N1 which was under Rs 500 and went through ICMR validation. 

Scaling for RT PCR may not be as simple as many people think, especially when supply chains are broken. Let me break down the technical parts and other challenges.

Also Read: Covid- To test or not to test, is that a question?

A Bioinformatics team: 

Designing the primers and probes needed for an RT PCR reaction is not necessary at this stage.  We can use the primers and probes designed by the CDC in the US.  

But we need to keep running analysis on genome sequences of the viral sample being published, especially Indian samples that have been sequenced.  The reason is that the virus mutates and could interfere with the primers and probes. Mapmygenome is constantly monitoring these sequences and has written a scientific abstract on mutations seen so far. Currently, we have only 2  Indian samples out of 1111+ samples submitted to GISAID and hopefully this number will continue to increase over the next few days as more testing is done. We can continue to check if any mutations interfere with the primers and probes.  As long as these mutations are not near the primer and probe regions, we can continue to use the CDC designed ones.

Primers and probes: 

These are the unique part of every RT PCR test, as they look at specific parts of the viral genome and bind to those regions. Designing these is important, if one is not selecting what is already published or manufactured by someone else i.e., using the primers released by the CDC. Currently in the case of Covid, most companies that have approval have probably used the CDC published sequences. Kits approved today may need recertification once we know more about the mutations and population specific challenges. 

Manufacturing Oligos for primers and probes is an important part as very few companies do it in India.  Most of the US and European companies already have FDA and other regulatory approvals for the CDC primers and  probes and these can be used immediately in India. These do not cost more than Rs 30 per test for low volumes under 10,000 so this can come down further at scale.

Mastermix : 

This has all the common components (read “ingredients”) needed in a RT PCR reaction and is the most expensive reagent in the process. There are very few approved by the USFDA and are likely to become a bottleneck as testing across the world continues and no one scales up that operation. Also, every equipment manufacturer tries to sell their own mastermix and generic ones that might or might not work on all machines and may need to be optimised.

Government needs to order this at large scale, so that they can be used by all certified labs in India.  Some of the ‘kit’ manufacturers do not provide the mastermix as a standard component. These can cost Rs 300 per reaction and can further reduce at scale. Rates negotiated by the government for nationwide testing can achieve this.

Isolation kits : 

For a RNA virus like the SAR-Cov2, we need RNA isolation kits. This part is most difficult to handle and care needs to be maintained if the virus is not already attenuated. Also this seems to be a big bottleneck worldwide as very few companies make these kits, Qiagen and Takara being some of them. Government needs to make sure we have enough of these kits procured. These will cost around Rs 200 per reaction or lower at scale.  Government orders will be given preference over individual companies.

Collection swabs and kits: 

This is another area where many countries fell short of testing. These will be a major challenge as we try and scale up without sterile kits and collection reagents and PPEs. These should cost around Rs 200 if safety measures are taken. Others would include PPE that should be around Rs 100. 

Positive samples : 

These are the control samples and are usually with NIV or equivalent body/bodies across the country. 

Also Read: The Pandemic of our times – Conversations concerning Covid 19

What can we do as a country?

Kit vs reagents 

If you look at the cost of getting reagents and assembling a full kit, the cost is way lower than buying a kit from any of the US FDA approved US or EU players.   The reason for the high kit cost is the regulatory cost of getting an FDA approval for a diagnostic kit in the US, which could cost around $15-20 million.  There is also a capacity limitation right now at US and European kit companies as they are working with reduced workforce and are producing the kits for the Western countries.

So it is better to get reagents and assemble a kit along with efforts of other Indian vendors who have got approval.

Large order size

  • There have been some press reports that the US banned exports and we cannot get reagents from there.  This is not entirely true as cargo exports from the US are not stopped. The bottleneck is getting these to India, bypassing the current ban on incoming cargo.  If the government can place large volume orders for a few million reactions ( say 10-30 million), we can get the complete reagent set for under Rs 400, possibly lower. Maybe our brave Air India can get these reagents for India leading to huge cost savings and also filling the need for testing in India.

Assembling kits

  • Private and public DBT labs can get together and get the ‘kits’ assembled (basically pipetting the reagents and putting them in vials) and ship it to public and private labs.  This entire process should not take more than two weeks to set up. It will need the PMO or the highest levels of authority to step in and make sure all bottlenecks are addressed.

Swabs and PPEs

  • We need to also make sure that we have enough swabs and proper procedure for collecting the samples.  PPE for labs handling the samples needs to be established and that is another large bottleneck on the ground.  We need to pull in all available scientific personnel, both retired and not working right now, and get them to run these tests.

Home Sampling

  • If we can address the issue of safe home testing where patients or suspects don’t have to come to a hospital and then get them to a central lab, it would change the dynamics. These can be a very effective way to ensure safety and also a great way to scale. This can be safely done by using reagents that are used globally to attenuate the virus. 

Also Read: 10 Ways to Defend Yourself Against Covid-19

Looking at the future 

Automation 

  • When the number of samples increases, there is a need for sharp automation as we cannot suddenly increase the number of technicians. These can be done at public labs for now, but allow our healthtech companies to automate and get them to market.

Multiple labs 

  • Ideally each city should have multiple centers that can test at once and upload data so that the data is real time

Software

  • Sample tracking with barcoding will be essential for tracking in real time across the country. There would be a need for barcode scanners and printers as well.  For Covid this may be difficult; but for the future, we need to create a simple app that can be used by all labs.

Vendor validation

  • We can continue to get vendors in India who make all the components validated by CDSCO/NIV or ICMR.  

5 things we need to do immediately

  1. Acquire Primers and probes in bulk.  
  2. Acquire RNA isolation and mastermix in bulk
  3. Swab and collection kits: These can be with or without attenuating solution if trained phlebotomists are doing the collection. 
  4. Equipment : We might need to add more machines and calibrate existing ones as we sale up testing
  5. PPEs : Buy in bulk or manufacture at scale

Conclusions

The government should assemble kits at scale to address this immediate problem.  Getting a new kit validated is a very long process in India and is not necessary if the primers and probes are from CDC.  Recently we saw a new body called CDSCO formed that has been making quicker decisions.

If we want to test 50 million RT PCR tests, it would mean we would need 500 labs testing at a scale of  1000 tests a day over 100 days. Antibody testing is much more simpler as existing infrastructure can be used. Who knows if this becomes a requirement for future travel until a vaccine or an effective drug is in the market. I hope that ICMR comes out with a directive on this soon to contain the virus.

This article was originally written for ABLE ( Association of Biotech Led Enterprises) and published at http://ableindia.in/news/details/742

Also Read: The science behind Covid for the avid reader

The Covid Series

  1. The Pandemic of our times
  2. 10 ways to defend yourself from Covid
  3. The Science behind Covid for the Avid Reader
  4. To test or not to test, Is that a question?
  5. How to scale Covid Testing in India
  6. Risk and Immunity Report on Covid by Mapmygenome
  7. The Immune System warriors: GAMED antibodies



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