investigation of mRNA production facets

Apr. 2, 2021 Pfizer/BioNTech says its Covid-19 vaccine is 100% effective and well tolerated in adolescents (Pfizer) actually making lipids (LNPs) in this site in Kalamazoo, Michigan,” said McDermott. https://www.cnn.com/2021/03/31/health/pfizer-vaccine-manufacturing/index.html …………................… Dec.2, 2020 CNN looks into how China plans to ship Covid-19 vaccines CNN recei\ved exclusive access to infrastructure preparations at Shenzhen Airport in southern China where Alibaba's logistics and shipping unit, Cainiao, has prepared climate-controlled storage chambers and aircraft cabins to distribute Covid-19 vaccines to parts of the Middle East, Africa and Latin America as soon as China's Central Government approves them. https://us.cnn.com/videos/world/2020/12/02/china-coronavirus-vaccine-distribution-aircraft-culver-pkg-intl-vpx.cnn ……………….....................…. Absolutely remarkable': No one who got Moderna's vaccine in trial developed severe COVID-19 Biotech will ask FDA for emergency approval as final results from efficacy trial back up initial claim of vaccine success 30 Nov 2020 By Jon Cohen Science's COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation. Continuing the spate of stunning news about COVID-19 vaccines, the biotech company Moderna announced the final results of the 30,000-person efficacy trial for its candidate in a press release today: Only 11 people who received two doses of the vaccine developed COVID-19 symptoms after being infected with the pandemic coronavirus, versus 185 symptomatic cases in a placebo group. That is an efficacy of 94.1%, the company says, far above what many vaccine scientists were expecting just a few weeks ago. More impressive still, Moderna's candidate had 100% efficacy against severe disease. There were zero such COVID-19 cases among those vaccinated, but 30 in the placebo group, including one death from the disease.Moderna received $1 billion from the U.S. government's Operation Warp Speed to help develop its mRNA vaccine. https://www.science.org/content/article/absolutely-remarkable-no-one-who-got-modernas-vaccine-trial-developed-severe-covid-19 ………………....................... Exploring the Supply Chain of the Pfizer/BioNTech and Moderna COVID-19 vaccines Published - Jan 10 2021 (Updated: Sep 08 2022 ) Sections of this post were co-authored by Cornelia Scheitz. Noah Leidinger created a German translation. Piotr Kwapin created a Polish translation. Last updated on February 7, 2021. Bert Hubert’s excellent and widely shared article about Reverse Engineering the source code of the Pfizer-BioNTech SARS-CoV-2 Vaccine is all it took to turn hundreds of software engineers and other Silicon Valley types into armchair vaccine experts overnight! Jokes aside, the article explains the 4284 base long mRNA inside the Pfizer-BioNTech’s COVID-19 vaccine for those who are more familiar with software than molecular biology. Bert’s article is primarily about the biology of the vaccine, how it relates to the virus and how it works in the human body, but there’s this one sentence about vaccine production: At the very beginning of the vaccine production process, someone uploaded this code to a DNA printer (yes), which then converted the bytes on disk to actual DNA molecules. Next to it is a picture of a CodexDNA BioXP device that is advertised as producing “custom DNA fragments of up to 7,000 base pairs”. Could this be the next distributed manufacturing revolution? This time with DNA printers making COVID-19 vaccines in our garages instead of 3D printers and plastic widgets? I’ll start with the bad news: Nobody will be making an mRNA vaccine in their garage any time soon. The following text is a collection of notes I wrote down while exploring the process for manufacturing and distributing the two new vaccines that have appeared all over the news and in more and more people’s arms over the recent weeks. I started reading about mRNA but quickly found myself on tangents about glass vials and temperature tracking devices. This text was written over a week worth of evenings in early January 2021. It covers the two vaccines authorized for distribution in the United States at the time of writing: One by Pfizer-BioNTech and one by Moderna. Several other mRNA-based COVID-19 vaccines are in various stages of clinical trials and are likely similar to those covered here in some ways and different in others. It is unlikely that I got everything right. Corrections and suggestions are welcome, please email jn@jonasneubert.com. Ingredients List The list of ingredients, or “bill of materials” in engineering parlance, is a good starting point for understanding the supply chain of any product. The ingredient lists for both Pfizer-BioNTech and Moderna’s vaccines are public and have been widely reported. The Pfizer-BioNTech vaccine is also known under its code name “BNT162b2”, its registered trademark “Comirnaty”, and its international non-proprietary name “Tozinameran”. The list of ingredients can be found in information material available on the various country-specific product websites on www.cvdvaccine.com or government websites like that of the UK’s MHRA. There’s also a Wikipedia page. The Moderna vaccine is also known as “mRNA-1273”, but appears to lack a brand name other than “Moderna COVID-19 Vaccine” which is what it says on the product label. The list of ingredients can be found on the EUA factsheet on Moderna’s website, or in these FDA meeting notes. It, too, has a Wikipedia entry. The two vaccines share some ingredients but not all. The following table is my attempt to sort the available information and compare the two. https://blog.jonasneubert.com/2021/01/10/exploring-the-supply-chain-of-the-pfizer-biontech-and-moderna-covid-19-vaccines/ ……………….................. Fast Growing Pharmaceutical Company Bringing Products to Market to Improve Patient Access To Medicine And Innovation Fosun Pharma USA Inc. is a wholly owned subsidiary of Fosun Pharma with a focus on building a fully integrated innovative biopharmaceutical company focused on the US market. With the backing of one of the strongest Pharma players in China, Fosun Pharma USA is actively looking to partner with late development stage companies globally to build or support the US commercialization of product for unmet medical needs. (Fosun at Boston and Princeton) https://fosunpharmausa.com/ ………….............................. Founded 2017 Employees 32 Manufacturer and developer of injectable products and ophthalmic intended to improve patient access to medicine and innovation. The company is focused on the identification, development and marketing of innovative assets and offers diverse pipeline reflects therapeutic areas of interests including immunology, cardiovascular system, infectious diseases, hematology and oncology. Contact Information Website www.fosunpharmausa.com Primary Industry Medical Supplies Other Industries Pharmaceuticals Primary Office 104 Carnegie Center Drive Suite 204 Princeton, NJ 08540 https://pitchbook.com/profiles/company/513064-54#signals ……….............................

-photo: WuXi Biologics CEO WuXu Biologics Global Network Europe North America Asia Dundalk, Ireland 
Supported by the Irish Government and IDA Ireland, construction of the manufacturing facilities began in 2018 with operations commencing in 2021
Located in Dundalk, Co. Louth, mid-way between Dublin and Belfast, this 26-hectare site is less than an hour’s drive from Ireland’s two largest cities
This “Factory of the Future” will create 400 jobs and provide commercial biologics manufacturing services
 
WuXi Vaccines 
The site is adjacent to the WuXi Biologics “Factory of the Future”
Capabilities at the site will include drug substance and drug product manufacture and quality control
QC potency lab received GMP certificate in 2022 from the Ireland Health Products Regulatory Authority
L‌earn m‌ore 

Leverkusen, Germany 
Over 13,000 sq. m. drug product fill & finish facility (DP7)
Liquid and lyophilization annual fill capacity of 10 million doses
Acquired from Bayer in April 2020 and released for GMP manufacturing in the same year
L‌earn m‌ore 

 Wuppertal, Germany 
30,000 sq. m. drug substance manufacturing facility (MFG19)
38 km (30 minutes driving) from the WuXi Biologics drug product fill & finish facility in Leverkusen (DP7) – both sites will support WuXi Biologics’ “Global Dual Source” strategy
Acquired from Bayer in May 2021 https://www.wuxibiologics.com/locations-facilities/ ……..............................… Products Excipients for mRNA Delivery System Categories PEGs Monodispersed PEGs Excipients for mRNA Delivery System GalNAc Conjugates Intermediates of Anti-diabetic Drug Cosmetic Block Copolymer Copolymer new products  
Polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG] [mPEG2000-DMG] Cas:160743-62-4
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1,2-Distearoyl-sn-glycero-3-phosphocholine[DSPC] Cas:816-94-4
Read More  
2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide [mPEG-DTA] [ALC-0159] CAS: 1849616-42-7
Read More  
((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate [DHA] [ALC-0315] CAS: 2036272-55-4
Read More  
Sodium 8-(2-hydroxybenzamido)octanoate [SNAC] CAS:203787-91-1
Read More  
Soybean lecithin Cas:8002-43-5
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Egg yolk lecithin Cas:93685-90-6
Read More  
Octadecanedioic acid Cas:871-70-5
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α,ω-Dicarboxyl poly(ethylene glycol) [HOOC-PEG-COOH] Cas:39927-08-7
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Methoxypoly(ethylene glycol) succinimidyl butanoate [mPEG-SBA]
Read More  
Methoxypoly(ethylene glycol) succinimidyl propionate [mPEG-SPA] Cas:622405-78-1,874208-94-3,1449390-12-8,874208-92-1,756525-90-3,1316189-13-5,174569-25-6,174569-25-6
Read More  
Semaglutide Side Chain [tBuO-Ste-Glu(AEEA-AEEA-OH)-OtBu]
Read More 
The effective components of the mRNA vaccine are all encapsulated in lipid nanoparticles (LNPs), which protect the mRNA from degradation and can also efficiently complete the intracellular delivery of mRNA. Lipid nanoparticles mainly contain four components: ionizable lipids, neutral auxiliary lipids, cholesterol, and PEGylated lipids. PEG can enhance the stability and life of LNPs. SINOPEG has taken the lead in realizing the commercial production of LNP delivery materials in China. Tributylammonium pyrophosphate 
Molecular Weight: 2KDa, 5KDa, 10KDa, 20KDa, 40KDa 
Package Size: 1g/bottle, 10g/bottle, 100g/bottle 
Storage: Store at -20±5℃, keep dry. 
undecyl 6-((7-(((heptadecan-9-yloxy)carbonyl)oxy)heptyl)(2-(2-hydroxyethoxy)ethyl)amino)hexanoate [HUO Analogue-2] HUO Analogue-2 
abbreviation: HUO Analogue-2 
Package Size: 1g/bottle, 10g/bottle, 100g/bottle 
Storage: Store at -20±5℃, keep dry 
research use only https://www.sinopeg.com/excipients-for-mrna-delivery-system_c138 …………................................ Heptadecan-9-yl 8-((2-(2-hydroxyethoxy)ethyl)(6-oxo-6-(undecyloxy)hexyl)amino)octanoate [HUO Analogue-1] HUO Analogue-1
Abbreviation: HUO Analogue-1 
Package Size: 1g/bottle, 10g/bottle, 100g/bottle 
Storage: Store at -20±5℃, keep dry 
research use only  
Methoxypoly(ethylene glycol) ditetradecylcarbonateamide [mPEG-DTA-3] mPEG-DTA-3 


Abbreviation: mPEG-DTA-3 
Package Size: 1g/bottle, 10g/bottle, 100g/bottle 
Storage: Store at -20±5℃, keep dry 
research use only  
Methoxypoly(ethylene glycol) dimethoxytridecylacetamide [mPEG-DTA-2] mPEG-DTA-2 
Abbreviation: mPEG-DTA-2 
Package Size: 1g/bottle, 10g/bottle, 100g/bottle 
Storage: Store at -20±5℃, keep dry 
research use only  
Methoxypoly(ethylene glycol) -N-tetradecyltetradecanamide [mPEG-DTA-1] mPEG-DTA-1 


Abbreviation: mPEG-DTA-1 
Package Size: 1g/bottle, 10g/bottle, 100g/bottle 
Storage: Store at -20±5℃, keep dry 
research use only 
6-((6-((3-heptylundecanoyl)oxy)hexyl)(2-(2-hydroxyethoxy)ethyl)amino)hexyl 3-hexylundecanoate [DHA-6] DHA-6 


Abbreviation: DHA-6 
Package Size: 1g/bottle, 10g/bottle, 100g/bottle 
Storage: Store at -20±5℃, keep dry 
research use only  
((2-(2-hydroxyethoxy)ethyl)azanediyl)bis(hexane-6,1-diyl) bis(2-octyldodecanoate) [DHA-5] DHA-5 
abbreviation: DHA-5 
Package Size: 1g/bottle, 10g/bottle, 100g/bottle 
Storage: Store at -20±5℃, keep dry 
research use only  
di(heptadecan-9-yl) 8,8'-((4-hydroxybutyl)azanediyl)dioctanoate [DHA-2] DHA-2 


Abbreviation: DHA-2 
Package Size: 1g/bottle, 10g/bottle, 100g/bottle 
Storage: Store at -20±5℃, keep dry 
research use only  
hydroxyethoxy)ethyl)azanediyl)bis(hexane-6,1-diyl) bis(2-hexyldecanoate) [DHA-1] DHA-1 
Abbreviation: DHA-1 
Package Size: 1g/bottle, 10g/bottle, 100g/bottle 
Storage: Store at -20±5℃, keep dry 
research use only  
Cholesterol (plant) CAS: 57-88-5 Cholesterol 


Abbreviation: Cholesterol (plant) 
CAS: 57-88-5 
Package Size: 1g/bottle, 10g/bottle, 100g/bottle 
Storage: Store at -20±5℃, keep dry 
research use only 






  
Methoxypoly(ethylene glycol) dimyristoyl glycerol [mPEG-DMG] Cas: 160743-62-4 mPEG-DMG 


Alternate Name: Methoxypoly(ethylene glycol) dimyristoyl glycerol 
Abbreviation: mPEG-DMG 
CAS: 160743-62-4 
Package Size: 1g/bottle、10g/bottle、100g/bottle 
Storage: Store at -20±5℃, keep dry 
research use only …… 5-5-20 Washington, DC Intellectual Property Rights and Commercial Fraud, Covid-19 HSI partners with Pfizer, 3M, Citi, Alibaba, Amazon, Merck to protect consumers against COVID-19-related fraud Industry experts from Pfizer, 3M, Citi, Alibaba, Amazon and Merck have joined forces with Homeland Security Investigations (HSI) National Intellectual Property Rights Coordination Center (IPR Center) criminal investigators in an unprecedented public-private partnership to combat fraud and other illegal activity surrounding COVID-19. “Scammers and other criminals are exploiting this time of anxiety and uncertainty to take advantage of consumers’ fears, and HSI has made it a top priority to investigate anyone attempting to use the COVID-19 pandemic to defraud other people,” said HSI Acting Executive Associate Director Alysa D. Erichs. “A robust partnership with the private sector is an absolute requirement to effectively disrupt and dismantle COVID-19 criminal networks and strengthen global supply-chain security.” Since the start of the pandemic HSI and other law enforcement agencies have seen a significant increase in criminals attempting to capitalize and profit from the fear and anxiety surrounding the virus, including the sale of counterfeit pharmaceuticals and medical equipment and illicit online sales and trade importation violations of products claiming to be treatment options. “Pfizer is committed to delivering for the world breakthroughs that change patients’ lives,” said Albert Bourla, CEO and chairman, Pfizer Inc. “We are dedicated to protecting patients and applaud the National Intellectual Property Rights Center’s efforts to address harmful and misleading offers for counterfeit and substandard medicines or from fraudulent scams that put patient’s and first responders health and safety at risk.” “At 3M we play a unique and critical role in pandemic preparedness and response. As a result we are attacking the pandemic from all angles, which includes mobilizing all our resources and rapidly increasing output of critical supplies to healthcare workers and first responders. These efforts also include combating fraud and protecting the public against those who seek to exploit the pandemic using 3M’s name connected with price gouging and counterfeiting. We are partnering with national and international law enforcement, tech companies and online retailers to prevent fraud before it starts and stop it where it is happening,” said Mike Roman, 3M chairman and chief executive officer. “Citi is committed to playing an important role in protecting our clients and the financial system from illicit activity,” said Michael Corbat, Citi’s CEO. “Unfortunately the need to combat this type of activity only increases in a crisis like this so we are appreciative of this collaborative effort organized by the IPR Center and determined to continue to do our part.” “Consumer health and safety is Alibaba's top priority. We will continue to enforce a zero-tolerance policy against those engaged in illicit activity, especially with respect to products and services related to COVID-19,” said Michael Evans, president of Alibaba Group. “We are proud to be part of this important collaboration and value our long-standing partnership with the Department of Homeland Security.” “Since the beginning of the COVID-19 crisis, Amazon has proactively stopped more than 6.5 million products with inaccurate claims, removed over 1 million offers for suspected price gouging, suspended more than 10,000 selling accounts for suspected price gouging and referred the most egregious offenders to federal and state law enforcement across the country. Amazon welcomes HSI’s partnership in holding counterfeiters and bad actors accountable, and we look forward to building on our long-standing relationship to protect customers and ensure a trusted shopping experience,” said Dharmesh Mehta, Amazon vice president, customer trust and partner support. “Merck is committed to patient safety and protecting the public from the dangers of counterfeit medicines. We appreciate this collaboration and we will continue to partner with law enforcement and health care officials worldwide to combat the dangers posed by criminals trafficking in illicit medicines,” said David Resch, vice president and chief security officer, Merck & Co., Inc. In April, HSI launched Operation Stolen Promise to prevent and investigate illegal criminal activity surrounding the pandemic, strengthen global supply-chain security and protect the American public. Operation Stolen Promise combines HSI’s expertise in global trade, financial fraud, international operations and cyber-crime to investigate financial fraud schemes, the importation of prohibited pharmaceuticals and medical supplies, websites defrauding consumers, and any other illicit criminal activities associated with the virus that compromises legitimate trade or financial systems or endangers the public. HSI, a component of U.S. Immigration and Customs Enforcement, and the largest investigative arm of the Department of Homeland Security, is working closely with private sector and U.S. government partners to facilitate a speedy, whole-of-government response to combat COVID-19-related fraud and illicit criminal activity. As of May 4, HSI special agents have opened over 315 investigations nationwide; seized over $3.2 million dollars in illicit proceeds; made 11 arrests; executed 21 search warrants; analyzed over 19,000 COVID-19 domain names; and worked alongside U.S. Customs and Border Protection to seize 494 shipments of mislabeled, fraudulent, unauthorized or prohibited COVID-19 test kits, treatment kits, homeopathic remedies, purported anti-viral products and personal protective equipment (PPE).  The IPR Center, which stands at the forefront of the United States government’s response to combatting global intellectual property theft and enforcing international trade laws, is working with its 25 federal and industry partners to identify, interdict, and investigate individuals, companies, and criminal organizations illegally importing COVID-19-related products. https://www.ice.gov/news/releases/hsi-partners-pfizer-3m-citi-alibaba-amazon-merck-protect-consumers-against-covid-19 ………………..