Constraints, Corona & Covid: Update with Everlywell testing, Chloroquine and Plasma Treatments

Goldratt teaches that to improve a system, we must identify the constraints, and then systematically work to relieve them. There are several constrains in the global pandemic:

  1. Is the information about the Coronavirus accurate?
    • How does it spread? (It does *not* aerosolize.)
    • When do symptoms become evident?
    • How many people who get the disease require medical assistance?
    • How many die?
  2. Can we test and identify people that have the virus?
    • Everlywell, an Austin, TX start up that was on Sharktank, has announced a future personal test kit.
  3. If someone comes down with COVID19, is the right equipment available?
    • PPE for the physicians (facemasks, etc.)
    • Respirators and ventilators for treatment
  4. Are there medicines and therapies that can treat or prevent the spread of the infection?
    • Is there a vaccine?
    • Are there medicines which help those who are infected?

A third medicine has been identified – another anti-malarial drug, Chloroquine. It is sold by Aventis (formerly Rhone Poulenc) under the trade name Nivaquine. A less aggressive version, hydroxychloroquine is also shown to work.

It also appears as if blood transfusions from those who have had the disease may also help immunize and activate the immune systems of others.

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Constraints, Corona, and Covid: Treatments – Remdesivir and Camostat Show Promise

Goldratt teaches that systems should be judged by their output, addressed at the highest level, and constraints should be removed. For a patient that has the disease, some treatment options are emerging.

Remdesivir: Nucleotide analog

Produced by Gilead, this class of drug has existed for some time and has been shown to perform well against RNA virsues.

Camostat: Serine protease inhibitor

A German research team found that a cell line was susceptible to Sars-2, and then showed that Camostat was capable of slowing and perhaps stopping the damage created by the virus.

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Corona Virus, Public Health, Goldratt, Goals and Global Health

As SARS-2 containment and COVID19 treatment increase in importance – many global, regional and national systems are activating, cooperating and working towards solutions. The complexity begs for an application of Goldratt’s principles:

  1. Pick a Goal.
  2. Identify constraints between the current setting and your goal.
  3. Remove the biggest known constraints.
  4. Achieve Goal.

The Life Science’s tradition of “First, do no harm” is a noble and well established goal. Do not diminish the public’s health. The virus does diminish health, so stopping its spread (while doing “no harm”), becomes important, as does treating those who have contracted COVID19.

Developing Data

In The Goal, Alex notably never has to deal with an absence of data or a resistance to data development and usage. Alex also exists in a world where there is a strong sense of community and teamwork.

Neither exist clearly in the global response to the new Coronavirus. In the US now, testing capacity is limited. Globally, nations are releasing ‘test’ data that has come under question and faces skepticism.

Testing for Corona

If testing and data are crucial to developing a response to the disease, then that is the current constraint. Goldratt teaches to remove the constraint; testing must be addressed.

Testing is currently performed with the polymerase chain reaction (“PCR”) a method widely taught in high school and college biology classes that breaks, copies and then measures DNA for comparison. Specifically, a reverse transcriptase PCR is used, and there has even been success in using a chest CT scan as a diagnostic tool.


Testing for Corona is the first step in creating an appropriate response. There is a lack of testing equipment;

  1. Create more testing equipment – reduce the constraint directly.
  2. Identify bypasses to the constraint – such as using Chest CT scans, as has been shown to be predictive of positive diagnosis of Corona.

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Fluid Notes: Solar Power, Ceramic Pressure Exchangers and the Cost of Desalination

A group out of MIT made an announcement that they are able to harness solar power with a low cost – lower cost than a conventional desal plant – that was able to deliver 6 liters per hour per square meter of collector. Published in the Journal of Energy and Environmental Science, the paper outlines a device that functions as a multi-layer still, using several evaporation and condensation steps to produce water that exceeds current drinking water standards.

As users on a Hacker News thread pointed out – this is a very energy intense process that requires 173 kWh of solar energy, compared to the 3.2 kWh often used for all of the processes in a conventional desal plant like San Diego’s Carlsbad site. The MIT group isn’t radically altering how the current municipal distribution network for drinking water would work – it is instead providing a technology that would allow for a more off-the-grid (“OTG”) approach for desalination, in the same way that generators allow electricity in wilderness cabins. Depending on the setup costs, it’s easy to see a set up where intercoastal waterways and other marshy areas could support units like this that generate reliable small volumes of liquid to support a single household that might not otherwise be able to justify the cost of a desal situation.

Desalination Materials: Ceramic Pressure Exchangers

Looking at how an OTG situation could change how certain areas can create clean water at a lower cost calls back to past technologies that allowed the centralized growth of desalination. Desal occurs at high pressures – this is one of the biggest differences between air and water filtration.

Salt ions are tiny, and even with cross-flow or tangential filtration, it takes very fine pores (~2 nm or less) and high pressure to create potable water from a saline source of water. The energy required to create that pressure was costly and couldn’t be easily recaptured.

The invention of a specialized ceramic pressure exchanger by Richard Stover allowed desalination plants to conserve and recycle that energy, dramatically lowering the cost to create drinkable water.

Energy Recovery Inc’s (“ERI”) ceramic pressure exchanger made a major impact on the energy requirements to create drinking water using desalination.
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Fluid Notes: PFAS and the Water Supply

PFAS is the new emerging pollutant of concern. It is the big bad in industrial waste. Nearly every session at NEWEA 2020 addressed the topic, and it was the leading buzzword from the event. The EPA has given PFAS its own page.

PFAS – Per- and Polyfluoroalkyl Substances (PFAS) – gets a lot of attention for several reasons:

  1. It still isn’t clear what a ‘safe’ level is.
  2. Testing for it is difficult.
  3. It’s man made.
  4. It appears to be nearly everywhere.
  5. It appears to be conserved at each step where other materials would be destroyed or reduced.

Dr. Linda Lee of Purdue University appeared on WEFTEC’s “Words on Water” podcast, and her review covered how PFAS is affected by most modern water treatment technologies.

Water Treatment and Filtration Processes and their Impact on PFAS

Advanced Oxygen Processes (AOPs) – have no effect.

Membrane Processes – can obstruct the PFAS, but then serve to concentrate the PFAS in the retentate. The resulting biosolids are then full of PFAS.

Reverse Osmosis – RO, like other membrane processes, can create PFAS-free water for drinking. However, the retentate then has concentrated PFAS.

Carbon Bed – carbon can capture the PFAS, but the PFAS remains caught in the carbon. The carbon can be incinerated, but care must be taken to ensure that the PFAS are destroyed.

RO creates clean drinking water, and it concentrates PFAS
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Fluid Notes: From Sea to Shining Sea – US Water Infrastructure from Boston’s Deer Island to San Diego’s Carlsbad

20,000,000 passengers per year fly over the 12 giant anaerobic digester eggs of Boston’s Deer Island. In April 2020, thousands of the world leaders in filtration will visit San Diego, 30 miles South of the Western Hemisphere’s largest desalination plant which provides water to the hotels and beaches that they’ll visit. Nearly 3,000 miles apart these two plants show the diversity of municipal water needs, the economics of water investment, the role of geography and rain fall, and how technology drives water supply and demand.

Deer Island is designed to process waste water and release it far off shore. The Boston metropolitan area has sufficient water supply – the challenge is handling storm water run off in a way that does not pollute the harbors, bays and surrounding wildlife. To halt 10 billion gallons of annual pollution overflow into the bay, nearly $4 billion has been invested by the Massachussetts Water Resource Authority (“MWRA”) to be able to process up to 470 billion gallons of waste per year. Like a mall parking lot designed for the Christmas season – Deer Island must be able to handle flows on the highest days and anticipated future growth.

Deer Island, MA Water Treatment Facility

Carlsbad provides a very different story – at a cost of nearly $1 billion, the desalination plant is capable of processing up to 18 billion gallons per year. About 80% of that water volume is purchased by San Diego, providing 7% of the city’s water needs. The city pays a premium for the security of water supply – on a per acre foot basis, Carlsbad compares well to its competition, but is not cheap:

  • $2500 – Cost to import water from other areas in CA
  • $2200 – Cost of Carslbad water
  • $2000 – Cost of recycled / re-used water (water re-use is the future)
  • $1200 – Area reservoir water
  • $700 – Upstream access when possible

San Diego chose water security over water cost – a wise decision based on the volatility of water rights and access in the Colorado River basin.

Drivers in Water Investment

These plants represent nearly $5 billion in investment in two very different water situations with very different regional needs.

Boston’s Deer Island: Hygiene, Disease and Growth

Boston’s harbor has been the source of constant investment since settlement. Dams were built causing sewage to foul the bay. Million dollar homes cannot look out on raw sewage and smell of the same. Boston’s investment in Deer Island is a long term commitment to managing the city’s hygiene, controlling for disease outbreak, and is ultimately an investment in the area’s future growth.

San Diego: Water Security

Reisner’s Cadillac Desert – the most well known book on water planning – takes place on the Colorado River, the same river on which provides San Diego with water. The Colorado no longer reaches the sea – with upstream water rights, ranching, and agricultural diversions robbing it of the needed flow. In years with low rainfall, San Diego does not have sufficient water.

Investing in the plant put San Diego at the front of the learning curve about how RO and desal can be implemented in the US, and there are already plans for a sister plant further North in Huntington Beach to service Los Angeles. By investing in this technology, San Diego is in a better situation to negotiate with other sources of water, and to understand how the cost of water can be impacted by technology.

Size, Impact and Investment

Mankind creates about 330 km^3 of wastewater per year, and converts over 50 km^3 of saltwater to fresh water via desalination. [Source: Global Fluid Volumes] This puts the 1.7 km^3 (0.5%) max treatment capability of Deer Island and 0.7 km^3 (1.4%) desalination capacity of Carlsbad in context.

Reversing those numbers, we can start to see the scale of investment required:

  • $4 Bn / 1.7 km^3 (0.5%) * 330 km^3 = $800 billion to treat all global waste.
  • $1 Bn / 0.7 km^3 (1.4%) * 50 km^3 = +$70 billion to recreate current global desalination infrastructure
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Fluid Notes: JP Morgan Healthcare Kicks off the 2020 Fluid News Year

San Francisco’s tourist schedule starts each year with JP Morgan’s Healthcare conference – 2020 is the 38th year and 9,000 visitors listened toover 450 company presentations. The biopharmaceutical industry is driving changes in healthcare, and biopharma is at the top of the fluid industry hierarchy.

Having worked in and sold into the fluid industries since 2008, the following subsegments are useful in breaking down product and customer needs:

  1. Biopharma & Healthcare
  2. Food & Beverage – Including agriculture
  3. Industry – From semiconductors to chemicals
  4. Water Treatment – From re-use to storm water

Biopharma and Healthcare are at the top of the fluid hierarchy because it has the broadest impact based on:

  • Number of professionals
    • 10 million physicians, 20 million nurses, 2 million dentists, 2.5 million pharmacists (estimated by the World Health Organization)
  • Total revenue of the industry
  • Biopharma sets the standards
    • Based on the value of their therapies, the 17 million liters of 2020 biopharma capacity are each worth about $5,000 – nearly $20,000 per gallon.
    • The value and volume and precision expectations of these materials set the standards for yield, quality and compliance when working with fluids.

StatNews is the best source of commercial and product news around JP Morgan and other healthcare industry activity – but for the strategic, production and operational issues confronting the industry, BioPharm International is a trade news organization that has great depth and detail.

Four trends will dominate biopharma over the next decade, and their implementation in biopharma will drive them out into other markets that work with fluids and liquids.


Therapies add years to the patients life. Mistakes with therapies kill patients. The precision, cleanliness, and focus on predictable performance within the complex biological systems of the human body require a rigorous and disciplined approach to quality. To drive quality and patient safety, manufacturers encourage cultures of candor and compliance. The long development cycles of new drugs require focus and candor, otherwise small mistakes can compound and derail multi-billion dollar investments. The focus on quality trickles out to vendors and the rest of the supply chain.

Processing Speed:

The constraint to growth in biopharma has long been product development cycles – patient safety concerns drive regulators to be diligent in their approval process. However, as classes of products become more accepted, the industry is seeing the constraints move towards production. With over 70 monoclonal antibodies approved and that number forecast to triple based on FDA applications, the industry is approaching the speed of production systematically in order to get more products to market.


The US FDA is the most successful regulator of all time, directly overseeing more than 2 trillion in products, representing over 10% of US GDP. The FDA’s regulatory powers are much broader, as the standards that are set spill over into other markets – some estimate up to 1/2 of US GDP – and then set the high bar for standards globally. Vendors and manufacturers who can sell into this market are able to have broad impact because they have the ability to work with the highest standards and the most common set of rules available globally.


Fluid dynamics, statistics, big data, internet of things (“IoT”), industrial IoT (“IIoT”), satellite imaging, machine learning, artificial intelligence (“AI”) – name the computational tool or buzzword, and the margins of the biopharma industry make it possible. By leading with data, sensors and other advanced tools, the industry paves the way for their deployment in other parts of the economy.

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