Drug Shortages - Part II (Quality Program)

Note: This article is the second entry of a series of mind maps listing actions that can be taken in various areas, that if/when taken and implemented collectively can contribute to systematically improving the situation.

Framework Needed:

I - Development/Implementation of New Capacity and Capabilities

II - FDA Quality Program

III - Transparency & End-to-End Visibility

IV - Ongoing Oversight and Reaction

V - Overall Coordination of Efforts

VI - Putting It All Together

Update: Interesting development: Valisure and DoD Signed a Cooperative Research & Development Agreement to Conduct a Pharmaceutical Quality Risk Assessment Pilot Study https://www.prnewswire.com/news-releases/valisure-signs-agreement-with-department-of-defense-to-independently-test--quality-score-drugs-301895301.html

Drug Shortages - Part I (New Capacity and Capability)

Background: Drug shortages are back in the news. This time it is a shortage of some essential cancer-fighting drugs such as cisplatin and carboplatin, see: FDA allows temporary import of unapproved Chinese cancer drug to ease U.S. shortage. Although there are multiple factors that can occur to cause drug shortages (see the list of possible causes I put together in 2002 with contemporaneous examples, republished on my blog in 2011 and on LinkedIn in 2015.), in this case the issue was caused by an Indian manufacturer (Intas) halting production at one manufacturing site following the discovery of quality deficiencies during an FDA inspection. This then snowballed, threatening lives, and leading to the FDA's emergency approval of the import of 'unapproved' versions of the drugs from China. 

According to the New York Times - Drug Shortages Near an All-Time High, Leading to Rationing - "The shortages are so acute that they are commanding the attention of the White House and Congress, which are examining the underlying causes of the faltering generic drug market, which accounts for about 90 percent of domestic prescriptions. The Biden administration has assembled a team to find long-term solutions for shoring up the pharmaceutical supply chain..." Unfortunately, we have heard this many times before. For example in 2018, the FDA (once again) put together a drug shortages task force to produce solutions. I expressed skepticism at the time!

It's long been clear to me that there has been a market failure and that a root cause for many of our drug shortage problems is that the segment of our drugs ("old," long-available, off-patent and generic sterile injectable drugs) that are disproportionately responsible for drug shortages are priced too low. As such, the usual 'article of faith' that is so often served up as a supposed solution to the issue (example from the NYT, 2017) i.e. "Increasing the number of competitors for a given drug in the marketplace will also help prevent and mitigate future shortages" is nonsensical!

The below, from January 2018, is exactly why we just have had the availability issues for cisplatin and carboplatin!

Unfortunately, as I observed, a solution that requires higher prices is not very palatable. The fact is that many (most) people think of drug manufacturers as a monolith, instead of recognizing that there are distinct segments that operate under very divergent conditions. In February 2019 I asked the question: "Drug pricing- is there a topic more fraught with simplism in this day and age?" Unfortunately, the answer was and continues to be "no!"

The bottom line? We will need to eschew simplistic thinking if we are to make any lasting progress in this area. Additionally, looking to the FDA to come up with a solution is flat out wrong. The solution to decreasing the frequency of drug shortages and mitigating their effects is multifactorial and will require a 'Whole of Government' approach that also includes collaboration and partnerships with industry, scientific organizations, public-private partnerships, academic organizations, and non-profits.

Note: This article is the first entry of a series of mind maps listing actions that can be taken in various areas, that if/when taken and implemented collectively can contribute to systematically improving the situation. First up, we need to improve pharmaceutical manufacturing capacity and capability!

Framework Needed:

I - New Capacity & Capability - the development and implementation of needed new capacity (e.g. plant, inventory) and new capabilities (e.g. advanced manufacturing technology) for drug manufacturing:

II - FDA Quality Program

III - Transparency & End-to-End Visibility

IV - Ongoing Oversight and Reaction

V - Overall Coordination of Efforts

VI - Putting It All Together

The Tipping Point?

TSMC & TSMC-AZ in the scales. Image credit: SNi 5/23

Taiwan (Republic of China) and China (People's Republic of China) have been in the news recently as tensions between the two have increased recently. The U.S. ostensibly agreed to a "One China" policy with The Shanghai Communique of 1972.

FOREIGN RELATIONS OF THE UNITED STATES, 1969–1976, VOLUME XVII, CHINA, 1969–1972 203. Joint Statement Following Discussions With Leaders of the People’s Republic of China1 Shanghai, February 27, 1972.

The U.S. has always maintained some level of ambiguity, acknowledging there is only one China while simultaneously expressing opposition to any unilateral changes of the (undefined) status quo. And there are variations on how the U.S. views Taiwan which have varied depending on who is speaking or acting on the subject e.g. see 'The One-China Policy in Transition.'

OK, given this background, let's focus on semiconductors. Here is a backgrounder by McKinsey & Co. One of the most important and valuable companies that designs and manufactures cutting-edge semiconductors is the Taiwan Semiconductor Manufacturing Company Limited (TSMC) with the majority of its facilities located on the island of Taiwan. This items plays an important role in considerations related to Taiwan, China, and any potential military solution initiated by the Chinese leadership. For example, "𝐁𝐫𝐨𝐤𝐞𝐧 𝐧𝐞𝐬𝐭" is the idea that if China invades Taiwan 𝑡ℎ𝑒 𝑈.𝑆. 𝑠ℎ𝑜𝑢𝑙𝑑 𝑑𝑒𝑠𝑡𝑟𝑜𝑦 𝑇𝑆𝑀𝐶 𝑡𝑜 𝑝𝑟𝑒𝑣𝑒𝑛𝑡 𝐶ℎ𝑖𝑛𝑎 𝑓𝑟𝑜𝑚 𝑔𝑎𝑖𝑛𝑖𝑛𝑔 𝑐𝑜𝑛𝑡𝑟𝑜𝑙. This was first mooted in 2021 in a scholarly journal, Parameters (U.S. Army War College); however, this has been picked up and similar thoughts have been expressed by various U.S. officials, politicians, etc.

However, adherents of this supposedly 'deterrent' suggestion appear not to have seriously thought through this scenario! Since China is already cut off from TSMC chips by U.S. sanctions (see here and here), this would only effect China 𝐥𝐨𝐧𝐠-𝐭𝐞𝐫𝐦 while being a huge and immediate blow to the U.S. (and world) economy. As such, this threat may 𝐧𝐨𝐭 be quite the deterrent some think it is! In fact this could, perversely, 𝐛𝐞 𝐚𝐧 𝐢𝐧𝐜𝐞𝐧𝐭𝐢𝐯𝐞 for China to take action sooner!

Meanwhile, there is another 'wild card' at play in this consideration - following pressure by the U.S. government, TSMC is currently building a huge fab/foundry in the U.S. ( in Arizona) which when completed (initial production is forecast to begin in 2024, with a second fab coming online in 2026) would ensure a safe and sufficient supply of chips for the U.S. So, what might be some of the consequences of this new plant (which I will refer to as TSMC-AZ) to the various parties? There are both beneficial and adverse possibilities.

• What effect might this have on the U.S. commitment to and support of Taiwan? With its reliance on Taiwan-based production eliminated, the opportunity cost to the U.S. of a Chinese takeover of Taiwan would be greatly reduced, and it is conceivable that this could lessen the likelihood of the U.S. choosing to take military action in support of Taiwan!

• What effect might this have on the Chinese calculus with respect to their timeline to 'incorporate' Taiwan? This could depend on their forecast of what the U.S. might do. If they come to believe that the U.S. would indeed be more likely to follow through with a 'broken nest' approach once they were insulated by the Arizona-based manufacturing, then China might feel the need to move on Taiwan before TMSC-AZ achieves critical mass. However, if they come to believe that U.S. support for Taiwan would 'soften' after TMSC-AZ comes online and that 'broken nest' would not be implemented, that might cause the Chinese leadership to opt for a longer time frame before taking any action.

With TMSC-AZ coming along, we might know sooner rather than later!

On a side note, simply destroying the main fabs/foundries in Taiwan, while certainly dealing China a major setback, would not necessarily eliminate the associated knowledge, expertise, and know-how. To really cause a decades-long setback it would be necessary to also destroy all the design facilities, online documentation, knowledge repositories, etc., and also the associated human capital. If I were a Taiwan-based semiconductor engineer/expert, I might be more than a little uncomfortable in the near future.

Microsoft Surface Duo II

 

OK, so I have been using (and enjoying) a Microsoft Surface Duo since September 2020, and Microsoft recently came out with an updated version, the Microsoft Surface Duo 2. Reading the reviews it did not seem that there was a compelling reason to 'upgrade,' but eventually this technophile succumbed and ordered one. Initial pictures below (the black one is the Duo 2):

The specifications: comparing the Surface Duo and Surface Duo 2.  That's all for now (which is why this is titled 'first look.')

Previous related entries:

Microsoft Surface Duo - First look

Online Resources:

XDA Microsoft Duo Forums

Windows Central - Microsoft Duo Forums

Microsoft: Different ways to use Surface Duo

Online Reviews:

Microsoft Duo 2 review: Vastly improved and still flawed

Microsoft Duo 2 review: A unique device for your multitasking life

YouTube (video) reviews:

Microsoft Duo 2 Review

Surface Duo 2 Long-Term Review: Revisiting A Different Kind of Foldable

Surface Duo 2 1-Week Later | Productivity At Its finest

Surface Duo vs. Surface Duo 2 after 6 months: Which to buy

Astro Slide 5G - First look

Finally received the Astro Slide 5G Transformer phone I had backed on Indiegogo in March of 2020. 

This is Planet Computer's third offering in the series - starting with the Gemini (reviews here, here, here, here, here, here, and here) , followed by the Cosmo Communicator (review), and now the Astro Slide 5G Transformer (all three shown left to right below):

Here's a shot showing the Astro Slide Transformer with keyboard open, along with some other keyboard PDAs:

Full specifications

Online Resources:

Astro Slide OESF Forums

Planet Computers YouTube Playlist - Astro Slide 5G Transformer

Astro Slide Reviews:

Planet Computers Astro Slide 5G review (Techradar)

Hands-on with the Astro Slide 5G: Slider in your hand, Debian in your pocket

Planet Computers Astro Slide 5G review: A keyboard-equipped 5G phone with retro appeal (ZDNet)

Astro Slide YouTube Reviews:

Unboxing - Planet Computers Astro Slide 5G 

Astro Slide 5G Unboxing (Japanese)

Astro Slide 5G Smartphone - Dual Boot Android and Linux

Most Powerful 5G Smartphone Pocket Computer Hybrid | Astro Slide

Novalis - Nachtraum (Neumond)

Und wieder verging ein tag so als ob heute schon einmal war

Dieselben straßen dieselben gesichter das warten im regen auf die bahn

Heut’ abend fühle ich wie sehr mein alltag geregelt ist
Er macht much so stark und sicher
Trotzdem bin ich unzufrieden – irgendwie

Die nacht nimmt mich und fliegt mit mir fort
Ich schlümpfe durch wolken davon
Die erde wird kleiner sterne kommen mir nah’
Ich rase immer tiefer ins all

Plötzlich sitze ich auf einem stern mir ist alles so unendlich fern
Die erde gleicht einem spielball
Aufgeregt blitzen meine augen hin und her

Da erscheint aus dem nichts eine gestalt und kommt auf mich zu
Streckt mir wortlos ihre hand entgegen
Entsetzt merke ich, der fremde bin ich
Ich reiss’ mich los von meinem traum
Spüre noch diese hand, suche mein zimmer
Die lampe, das bett ,she’ mich noch von mir steh’n

Nachttraum – Verloren im Traum
Nachttraum – Verloren im Trau

Novalis - Neumond - Nachtraum

Random charts - health

 

Source: America's Health Rankings 2021 (110-pg PDF)