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Over 60 of the largest companies in Ireland have publicly committed to set targets based on science by 2024. They are the first signatories of Business in the Community Ireland’s new Low Carbon Pledge. Business in the Community Ireland, the national network for sustainability, created the initial Low Carbon Pledge in 2018 with the aim of being a starting point for their member companies to commit to cutting their carbon footprint, report annually on their progress and develop a credible roadmap towards a net-zero economy. The new Low Carbon Pledge now calls on businesses to set science-based carbon emission reduction targets no later than 2024 (i.e. what science says is necessary to limit global warming to 1.5°C). The 61 signatories are: A&L Goodbody, Abbvie, ABP Foods, Accenture, Actavo, AIB, ALDI, Allianz, An Post, Arup, Aviva, Bank of Ireland, Bidvest Noonan, Boots, Britvic, BT Ireland, Cairn Homes, Cisco, Cook Medical, Dawn Meats, Deloitte, DePuy Synthes, Diageo, Dublin Bus, EirGrid, Enterprise-Rent-a-Car, ESB, Fujitsu, Gas Networks Ireland, Grant Thornton, HEINEKEN Ireland, Hovione Ireland, Irish Rail, Irish Distillers, Irish Water, Janssen, Johnson & Johnson Vision Care, KBC Bank, Keelings, KPMG, Lidl, M&S, Momentum Support, Mercury Engineering, Musgrave, Ornua, Permanent TSB, PM Group, PwC, RTÉ, Sky, Sodexo, SSE, Tesco, Three Ireland, Ulster Bank, Verizon, Veolia, Virgin Media Ireland, Vodafone and William Fry. The 61 signatory companies will commit to: Record their entire carbon footprint, both direct (Scope 1 & 2) and indirect (Scope 3) emissions Reduce emissions that they are directly responsible for (Scope 1 & 2), as well as play their part in reducing emissions across their Supply Chain (Scope 3) Report individually through an annual report or website or other publicly available equivalent source and collectively through an Annual Business in the Community Ireland Low Carbon Report As our understanding improves, signatory companies are asked to commit to regularly Reviewing their carbon reduction targets to align to the latest climate science. Minister for Communications, Climate Action & Environment, Eamon Ryan T.D. welcomed the announcement and commented, “As COP26 approaches, we must accelerate our climate response across our economy and society. I commend Business in the Community Ireland on this collective action especially as it brings together companies from different sectors and at different levels of maturity on their decarbonization journey. A low carbon economy is imperative for our post-pandemic recovery as it will support our long-term competitiveness, job creation and social cohesion.” The key strength of the Pledge lies in the collaborative platform which enables signatory companies to learn from each other’s successes and challenges. By working collectively, the Low Carbon Pledge movement builds capacity, fosters innovation and drives the ambition in delivering the changes needed. Tomás Sercovich, CEO, Business in the Community Ireland (BITCI), said, “With yesterday’s publication of the Climate Action Bill which commits Ireland to be a net-zero carbon State by 2050, the role of business in reaching this target is vital. Investors, regulators, consumers, suppliers and employees expect business to lead the net-zero vision we all aspire. Transparency and accountability are fundamental for the change to happen. The Low Carbon Pledge is a clear demonstration of businesses driving towards decarbonization, creating the business models, innovation and jobs for a low carbon future. As more businesses join this Pledge, we will use our collective voice to drive the new systems thinking we need to overcome this fundamental challenge.”    

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Ireland: Over 60 companies sign up to BITCI’s new Low Carbon Pledge

Mar 29, 2021

    好利安藥廠火警疏散演習 Fire and evacuation simulator at the pharmaceutical factory “Hovione”   Firefighters fought the fire by the storage tank. The Fire Brigade (CB) held on the morning of February 24th this year, a fire and evacuation simulator with dangerous chemical substances in the pharmaceutical factory “Hovione” together with Hovione FarmaCiencia SA, with the intention of intensifying the measures contingency and the coordination and communication mechanism between both parties in case of incidents. The exercise simulated that a worker discovered that the leak occurred at the connection point of the methanol solution storage tank, thus causing a fire. The employee immediately sounded the fire alarm, the pharmaceutical factory's emergency and contingency team immediately proceeded to the internal contingency action, called the CB to ask for assistance and adopted security measures to evacuate the employees to the evacuation and meeting place. During the evacuation period, there was 1 worker who was injured. After becoming aware of the occurrence of a fire at the pharmaceutical factory “Hovione”, the CB immediately dispatched 9 emergency vehicles and 38 firefighters to the site to fight the fire, carry out the evacuation and search according to the defined plan, as well as provide nursing care for the injured and simulate transport to the hospital. The simulation lasted almost 1 hour. CB and the pharmaceutical factory “Hovione” sent around 160 people to participate in the simulation, whose main purpose is to test the responsiveness and the communication mechanism between the relevant parties in case of incidents. The respective process went well, after the simulation, both parties held a review meeting, whose objectives and expected results were achieved. [Translated from the original]       好利安藥廠火警疏散演習 為加強與好利安藥廠在發生事故時的應變措施及協調溝通機制,消防局於本年2月24日上午,與好利安製藥科學股份有限公司在氹仔好利安藥廠聯合舉行化學危險品火警及疏散演習。 演習模擬工作人員發現一個含有甲醇溶液的儲存缸接駁口出現洩漏並發生火警,工作人員隨即按動火警警報,藥廠緊急應變隊伍即時啟動內部應變計劃,同時致電消防局求助,以及採取安全措施疏散員工到逃生集合點,於疏散期間有一名員工不慎受傷。消防局接報好利安藥廠發生火警後,立即派遣9架緊急車輛及38名隊員趕赴現場,按照既定計劃進行滅火及疏散搜救行動,並對傷者進行即時護理及模擬送院,演習過程歷時約1小時。 消防局和好利安藥廠合共派出近160名人員參與是次演習,主要目的是測試發生事故時雙方的應變能力及溝通機制,演習過程順利,事後雙方進行檢討會議,並達到預期目的及效果。     Simulacro de incêndio e evacuação na fábrica farmacêutica “Hovione” Os bombeiros combateram o fogo junto do tanque de armazenamento. O Corpo de Bombeiros (CB) realizou na manhã do dia 24 de Fevereiro do corrente ano, um simulacro de incêndio e evacuação com substâncias químicas perigosas na fábrica farmacêutica “Hovione” em conjunto com a Hovione FarmaCiencia SA, com o intuito de intensificar as medidas de contingência e o mecanismo de coordenação e comunicação entre ambas as partes em caso de incidentes. O exercício simulou que havia trabalhador que descobriu que ocorreu a fuga no ponto de ligação do tanque de armazenamento da solução de metanol, acontecendo assim um incêndio. O empregado tocou imediatamente o alarme de incêndio, a equipa de emergência e contingência da fábrica farmacêutica procedeu logo à acção de contingência interna, ligou ao CB para pedir auxílio e adoptou as medidas de segurança para evacuar os funcionários para o local de evacuação e encontro. Durante o período de evacuação, havia 1 trabalhador que ficou ferido. Depois de ter tido conhecimento da ocorrência de incêndio na fábrica farmacêutica “Hovione”, o CB enviou de imediato 9 veículos de emergência e 38 bombeiros ao local para combater o fogo, executar a acção de evacuação e busca conforme o plano definido, bem como prestar os cuidados de enfermagem junto do ferido e simular o transporte para o hospital. O simulacro durou quase 1 hora. O CB e a fábrica farmacêutica “Hovione” enviaram cerca de 160 pessoas para participar no simulacro, cuja finalidade principal é testar a capacidade de resposta e o mecanismo de comunicação entre as partes pertinentes em caso de incidentes. O respectivo processo correu bem, depois do simulacro, ambas as partes procederam a uma reunião de revisão, cujos objectivos e resultados esperados foram alcançados.   Read the article at News.Gov.MO        

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Fire and evacuation drill at the pharmaceutical plant “Hovione”

Feb 25, 2021

Over the coming months, Hovione will be hiring for positions in quality control, quality analysis, warehouse operations and production operations. Hovione, a contract pharmaceutical manufacturing and particle engineering company, has announced 48 new jobs for its base in Cork. The expansion follows a partnership agreement between Hovione and biopharma company Ligand to ramp up production of Captisol, a product that can improve the solubility and stability of drugs. Captisol is used in the Covid-19 treatment Veklury, which is produced by US pharma company Gilead. New hires will be based at Hovione’s site in Ringaskiddy, Co Cork, which has been in operation for more than 10 years. It was acquired from Pfizer in 2009 and currently employs around 200 people. According to the company’s talent acquisition specialist, Michelle Ahern, the vacancies will span quality control, quality assurance, process engineering, project management, engineering, warehouse operations and production operations. Recruitment for the roles is underway and the team plan to fill them by the end of 2020. Founded in Portugal in 1959 by Diane and Ivan Villax, Hovione helps to bring new and off-patent drugs to market. The pharma manufacturing company has 1,600 staff members around the world, with facilities in the US, Ireland, China, Portugal, India, Japan, Switzerland and Hong Kong. Jean-Luc Herbeaux, COO of Hovione, said that increased demand for Veklury has meant that Hovione will soon be producing in a month the amount of Captisol it normally produces in a year. “This sudden spike in demand has required unique mobilisation efforts across the Hovione network to secure additional raw-material supply, execute major capital-expenditure projects at our sites, maximise operational efficiency, hire additional talent and identify external partners to expand our overall capacity,” he said. Ligand’s president and COO, Matt Foehr, added that Captisol is a “critical component for a number of life-saving medicines”. Hovione Cork’s general manager, Paul Downing, said that the opportunities are for people “who want to join a fast-paced, dynamic, empowering, diverse, inclusive and exciting organisation”. To learn more about working at Hovione, visit the company’s careers portal here.   Read the article at siliconrepublic.com    

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Pharma manufacturer Hovione announces 48 new jobs for Cork

Oct 02, 2020

Continued clinical progress of Captisol-enabled drugs affirms the value of the proprietary technology   SAN DIEGO--(BUSINESS WIRE)--Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) announces that recent new contracting with partners and investments in manufacturing capacity have contributed to its Captisol business operating at the highest levels in the history of the technology and position Captisol for major growth. Significant new clinical and regulatory developments with Evomela and Kyprolis, among other drugs, are reinforcing the role the proprietary technology serves in enabling important medicines. During 2020, Ligand has facilitated the successful installation of equipment to allow production at significantly higher levels to support anticipated demand. In addition to manufacturing at partner Hovione’s facilities in Ireland and Portugal, Ligand has now added final step processing capacity for Captisol in both the United States and England. Ligand also introduces guidance for 2021 Captisol material sales of approximately $200 million. “The global medical need for Captisol-enabled drugs has never been higher,” said John Higgins, Chief Executive Officer of Ligand. “Our recently expanded operating team has successfully positioned our Captisol technology for the substantial growth we now expect in 2021 and beyond. There is significant ongoing investment by our partners for over 30 Captisol-enabled medicines in clinical development. We have entered into more contracts this year than any other year and are proud to be working closely with Gilead under our recently extended 10-year supply contract. We continue to be pleased with the momentum relating to Captisol, as it is a critical component in multiple life-saving medicines.” Recent Captisol technology business highlights include the following: To date in 2020 Ligand has entered into more than 120 Captisol research use agreements and eight clinical and/or commercial license agreements. This is the highest number of use agreements to be signed in a single year since the invention of Captisol. Captisol is utilized in the formulation of Gilead Sciences’ Veklury® (remdesivir), which has received emergency use authorizations or regulatory approvals for the treatment of moderate or severe COVID-19 in over 50 countries and is included in more than 30 ongoing clinical trials. Ligand is supplying Captisol to Gilead and the company’s voluntary licensing partners who are supplying generic remdesivir to 127 low- and middle-income countries. Ligand expects Captisol orders into 2021 and beyond to Gilead and its partners to help countries around the world manage the pandemic. Ligand recently extended its Captisol supply agreement with Gilead until September 2030. The contract defines terms and conditions for forecasting, supply, order commitments and price. Ligand’s manufacturing partner Hovione announced today that to meet Captisol demand associated with Veklury, Hovione will soon be producing more Captisol per month than it usually produces per year. “This spike in demand has required unique mobilization efforts across the Hovione network to secure additional raw material supply, execute major capital expenditure projects at oursites, maximize operational efficiency, hire additional talent and identify external partners to expand our overall capacity. The pharmaceutical supply chain is working together in an unprecedented fashion to treat patients and save lives. Hovione is privileged to be part of this truly global rapid response,” said Jean-Luc Herbeaux, Chief Operating Officer of Hovione. Recent clinical data have been announced including publication of a study from the Medical College of Wisconsin that compared safety parameters for Captisol-enabled Evomela® versus Alkeran® in patients undergoing autologous stem cell transplantation for the treatment of multiple myeloma. The study of 294 patients demonstrated a statistically significant reduction in 30-day re-hospitalization rates for patients treated with Evomela (6.8% for Evomela vs. 17.9% for Alkeran, p=0.04)a with a similar safety profile to Alkeran. Evomela is marketed by Acrotech Biopharma in the U.S. and by CASI Pharmaceuticals in China. Partner Marinus was recently awarded a BARDA contract by the U.S. government to develop Captisol-enabled IV ganaxolone for the treatment of refractory status epilepticus caused by nerve agent exposure. Ligand’s pivotal trial for Captisol-enabled Iohexol (CE-Iohexol) is planned to initiate in December 2020. CE-Iohexol is an iodine-based contrast agent for hospital-based imaging procedures. The market for iodinated contrast agents is substantial with approximately 20 million imaging procedures per year in the U.S., representing an estimated $1.5 billion in sales. The objective of the clinical trial will be to demonstrate a reduction in the incidence of contrast-induced acute kidney injury and an equivalent image quality compared to GE’s Omnipaque®. The trial is expected to enroll approximately 500 patients and results are expected within two years. Ligand’s forecast for 2021 Captisol material sales of approximately $200 million is based on information it has on anticipated demand from its major partners given growth in existing and new markets, clinical requirements for Captisol-enabled development programs and binding orders from certain commercial or pre-commercial partners. The 2021 Captisol outlook compares with the Company’s guidance for 2020 Captisol material sales of approximately $90 million.   About Captisol® Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Captisol was invented and initially developed by scientists in the laboratories of Dr. Valentino Stella, University Distinguished Professor at the University of Kansas’ Higuchi Biosciences Center for specific use in drug development and formulation. This unique technology has enabled several FDA-approved products, including Gilead’s VEKLURY®, Amgen’s KYPROLIS®, Baxter International’s NEXTERONE®, Acrotech Biopharma L.L.C.’s and CASI Pharmaceuticals’ EVOMELA®, Melinta Therapeutics’ BAXDELA™ and Sage Therapeutics’ ZULRESSO™. There are many Captisol-enabled products currently in various stages of development. Ligand maintains a broad global patent portfolio for Captisol with more than 400 issued patents worldwide relating to the technology (including 37 in the U.S.) and with the latest expiration date in 2033. Other patent applications covering methods of making Captisol, if issued, extend to 2040. About Ligand Pharmaceuticals Ligand is a revenue-generating biopharmaceutical company focused on developing or acquiring technologies that help pharmaceutical companies discover and develop medicines. Our business model creates value for stockholders by providing a diversified portfolio of biotech and pharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure. Our goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable, diversified and lower-risk business than a typical biotech company. Our business model is based on doing what we do best: drug discovery, early-stage drug development, product reformulation and partnering. We partner with other pharmaceutical companies to leverage what they do best (late-stage development, regulatory management and commercialization) to ultimately generate our revenue. Ligand’s OmniAb® technology platform is a patent-protected transgenic animal platform used in the discovery of fully human mono- and bispecific therapeutic antibodies. The Captisol platform technology is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. The Vernalis Design Platform (VDP) integrates protein structure determination and engineering, fragment screening and molecular modeling, with medicinal chemistry, to help enable success in novel drug discovery programs against highly challenging targets. Ab Initio™ technology and services for the design and preparation of customized antigens enable the successful discovery of therapeutic antibodies against difficult-to-access cellular targets. Icagen has established deep biological expertise focused on ion channels and transporters and has a strong track record in ion channel drug discovery from screening to lead optimization. Ligand has established multiple alliances, licenses and other business relationships with the world’s leading pharmaceutical companies including Amgen, Merck, Pfizer, Sanofi, Janssen, Takeda, Servier, Gilead Sciences and Baxter International. For more information, please visit www.ligand.com. Follow Ligand on Twitter @Ligand_LGND. Forward-Looking Statements This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. Words such as “plans,” “believes,” “expects,” “anticipates,” and “will,” and similar expressions, are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding: Ligand’s expectation that Captisol demand will increase significantly in 2021 and beyond (particularly for sales to Gilead and to partners in Gilead’s consortium) and Ligand’s ability to supply Captisol to Gilead and other partners, including Ligand’s ability to increase supply capacity; the timing of initiation, enrollment and expected results with respect to the planned clinical trial of CE-Iohexol; and guidance regarding Ligand’s 2020 and 2021 Captisol material sales. Actual events or results may differ from Ligand's expectations due to risks and uncertainties inherent in Ligand’s business, including, without limitation: Ligand may not receive expected revenue from Captisol sales; the COVID-19 pandemic has disrupted Ligand’s and its partners’ business, including delaying manufacturing, preclinical studies and clinical trials and product sales, and impairing global economic activity, all of which could materially and adversely impact Ligand’s results of operations and financial condition; Ligand may not achieve its Captisol material sales guidance for 2020 and/or 2021; remdesivir may be later shown to not be effective or safe for the treatment of COVID-19 and/or the FDA (and/or equivalent agencies in other countries) may revise or revoke its emergency use authorization for remdesivir for the treatment of COVID-19 in patients hospitalized with moderate or severe disease if the FDA (and/or another such agency) determines that authorization no longer meets the statutory criteria for issuance; alternative COVID-19 therapies or vaccines may be approved or the risk of coronavirus infection could significantly diminish, any of which could materially and adversely affect the commercial opportunity for remdesivir; Gilead may terminate the supply agreement without cause upon 30 days’ prior written notice; Ligand may be unable to scale-up the supply of Captisol or at acceptable prices; Ligand is currently dependent on Hovione as a single source sole supplier for certain Captisol manufacturing functions and failures by such supplier may result in delays or inability to meet the Captisol demands of its partners; Amgen, Acrotech Biopharma or other Ligand partners may not execute on their sales and marketing plans for marketed products for which Ligand has an economic interest; Ligand or its Captisol partners may not be able to protect their intellectual property and patents covering certain products and technologies may be challenged or invalidated; Ligand's Captisol partners may terminate agreements or development or commercialization of products; Ligand may not generate expected revenues under its existing license agreements and may experience significant costs as the result of potential delays under its supply agreements; Ligand and its Captisol partners may experience delays in the commencement, enrollment, completion or analysis of clinical testing for product candidates, or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, which could result in increased costs and delays, or limit the ability to obtain regulatory approval; unexpected adverse side effects or inadequate therapeutic efficacy of Ligand's or its Captisol partners’ product(s) could delay or prevent regulatory approval or commercialization; and ongoing or future litigation could expose Ligand to significant liabilities and have a material adverse effect on the company. The failure to meet expectations with respect to any of the foregoing matters may reduce Ligand's stock price. Additional information concerning these and other risk factors affecting Ligand can be found in prior press releases available at www.ligand.com as well as in Ligand's public periodic filings with the Securities and Exchange Commission available at www.sec.gov. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. a Monahan, et al. Biology of Blood and Marrow Transplantation, September 2020 Read the article on Business Wire website  

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Ligand Announces its Captisol Business is Positioned for Major Growth and Forecasts 2021 Captisol Material Sales of $200 Million

Sep 23, 2020

Hovione recently announced the signing of a partnership agreement with Ligand to significantly ramp up the production output of Captisol, a Ligand product, which is a chemically modified cyclodextrin proven to improve the solubility and stability of drugs.  It is used in the formulation of Gilead’s Covid-19 treatment Veklury (remdesivir). Hovione is the sole producer of this key enabling excipient. The Covid-19 pandemic has to date killed 1 million people; studies show that in the next 3 months cumulative deaths may more than double. “To meet Captisol demand associated with Veklury, Hovione will soon be producing per month the quantity it usually produces in 1 year. This sudden spike in demand has required unique mobilization efforts across the Hovione network to secure additional raw material supply, execute major capital expenditure projects at our sites, maximize operational efficiency, hire additional talent, and identify external partners to expand our overall capacity. The pharmaceutical supply chain is working together in an unprecedented fashion to treat patients and save lives.  Hovione is privileged to be part of this truly global response,” said Jean-Luc Herbeaux, Chief Operating Officer. “Ligand values its long-standing partnership with Hovione,” added Matt Foehr, President and Chief Operating Officer of Ligand. “Their excellent customer service, global commitment to quality, and high pharmaceutical standards make them an ideal partner for Captisol, a critical component for a number of life-saving medicines. We commend them for responsibly and efficiently partnering with Ligand to manage the scale up and expansion of their operations to contribute to global health during the pandemic.” Ligand’s Captisol technology is a patent-protected, uniquely modified cyclodextrin, with a chemical structure that was rationally designed to enable the creation of new products by significantly improving solubility, stability, bioavailability, and dosing of active pharmaceutical ingredients (APIs). It uses a green manufacturing process that uses water as process solvent. Gilead Sciences’ Veklury is an investigational nucleotide analog with broad-spectrum antiviral activity both in vitro and in vivo in animal models against multiple emerging viral pathogens. Multiple ongoing international Phase 3 clinical trials are evaluating the safety and efficacy of Veklury for the treatment of SARS-CoV-2 infection, the virus that causes COVID-19, in different patient populations, formulations, and in combination with other therapies. The US FDA expanded the Emergency Use Authorization (EUA) enabling use of the investigational antiviral Veklury to treat all hospitalized patients with COVID-19, in addition to the previous authorization for patients hospitalized with severe COVID-19. Hovione is an international company with over 60 years of experience as a Contract Development and Manufacturing Organization (CDMO) and is currently a fully integrated supplier offering services for drug substance, drug product intermediate, and drug product. With four FDA inspected sites in the US, China, Ireland, and Portugal and development laboratories in Lisbon, Portugal, and New Jersey, US, the company provides branded pharmaceutical customers services for the development and compliant manufacture of innovative drugs, including highly potent compounds. For generic pharmaceutical customers, the company offers niche API products. Hovione also provides proprietary product development and licensing opportunities for drug products. In the inhalation area, Hovione is the only independent company offering a complete range of services.   Read the article on Drug Development & Delivery website    

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Hovione Announces Partnership to Produce Ligand’s Captisol; Used in Gilead’s Covid-19 Treatment

Sep 23, 2020

Hovione has signed a partnership agreement with Ligand to significantly ramp up the production output of Captisol Captisol, a Ligand product, is a chemically modified cyclodextrin proven to improve the solubility and stability of drugs. It is used in the formulation of Gilead’s Covid-19 treatment Veklury (remdesivir). Hovione is the sole producer of this key enabling excipient. The COVID-19 pandemic has, to date, killed one million people; studies show that in the next 3 months cumulative deaths may more than double. “To meet Captisol demand associated with Veklury, Hovione will soon be producing per month the quantity it usually produces in one year. This sudden spike in demand has required unique mobilisation efforts across the Hovione network to secure additional raw material supply, execute major capital expenditure projects at our sites, maximise operational efficiency, hire additional talent and identify external partners to expand our overall capacity." "The pharmaceutical supply chain is working together in an unprecedented fashion to treat patients and save lives. Hovione is privileged to be part of this truly global response,” said Jean-Luc Herbeaux, Chief Operating Officer. “Ligand values its longstanding partnership with Hovione,” said Matt Foehr, President and Chief Operating Officer of Ligand. “Their excellent customer service, global commitment to quality and high pharmaceutical standards make them an ideal partner for Captisol, a critical component for a number of life-saving medicines." "We commend them for responsibly and efficiently partnering with Ligand to manage the scale up and expansion of their operations to contribute to global health during the pandemic.”   Read the article on Manufacturing Chemist website  

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Hovione to support production of antiviral Veklury for COVID-19

Sep 23, 2020

With the help of outsourcing partners, the small biotech firm Nabriva brought lefamulin to patients by itself. Now it needs to make a profit in the tough-to-crack antibiotic business.   In November 2006, Rosemarie Riedl synthesized an antibacterial molecule that she logged into Nabriva Therapeutics' database as BC-3781. It was not just another entry in a compound collection. In 2019, after almost 13 years of development and testing, the US Food and Drug Administration approved that same molecule, lefamulin, for the treatment of community-acquired bacterial pneumonia. Marketed as Xenleta, lefamulin was the first antibiotic with a novel mechanism of action to win FDA approval for pneumonia in nearly two decades. With the help of contract manufacturing firms from across Europe and China, Nabriva took the drug to market without a big pharma partner. Inventing a drug in its own labs and getting it approved solo is something few biotech firms have done. And yet it won't be enough for the small company. Nabriva must now turn a profit on lefamulin, a goal that has eluded many independent antibiotic developers. Judging from Nabriva's stock price, investors have their doubts that the firm will be in the black anytime soon.   DISCOVERY Although Nabriva's corporate offices are in the US, and its global headquarters are in Ireland, its research efforts are based in Vienna, where the culture is decidedly more European than American. Riedl, Nabriva's senior director of medicinal chemistry, has been with the company and its predecessor, Sandoz, since earning her PhD in pharmaceutical chemistry. And she's not the only long-tenured employee. "The core team has been together for a long, long time," says Werner Heilmayer, Nabriva's vice president for intellectual property and chemistry, manufacturing, and controls. Like Riedl, Heilmayer has been there from the start. He joined Sandoz in 1995 after graduate school and went with Nabriva when it became an independent company in 2006. That was the year that Novartis, Sandoz's parent company, decided it was done researching and developing new antibiotics, a field that has long been a money pit for big pharma. With about $50 million in financing from venture capital firms and its own venture arm, Novartis set the antibiotic operation off on its own. As an independent company, Nabriva continued Sandoz's quest for useful derivatives of pleuromutilin, an antibiotic molecule that occurs naturally in an edible mushroom sometimes called Pleurotus mutilus. Pleuromutilin was discovered in the 1950s, and Sandoz launched two semisynthetic derivatives, tiamulin and valnemulin, as veterinary antibiotics in 1979 and 1999, respectively. GlaxoSmithKline (GSK) later succeeded in creating a topical human drug, but systemic human pleuromutilins with a wider potential market eluded drug hunters for decades. One reason for the lack of success was that, for many years, researchers were focused on finding new beta-lactam antibiotics like amoxicillin and cephalosporin, still the most widely used antibiotic class. Drug company interest in pleuromutilins finally perked up around the turn of the century as bacterial resistance to beta lactams increased, according to a review paper that Riedl and a colleague, Susanne Paukner, published in 2017 in Cold Spring Harbor Perspectives in Medicine. According to the paper, pleuromutilins work by binding to the peptidyl transferase center on the bacterial ribosome, interfering with protein production and impeding growth. It's a unique mode of action for an antibiotic, even among those that work by blocking bacterial growth. Both mechanistic studies and in vitro experiments show a low potential for resistance to develop. While pleuromutilin can kill bacteria in the lab, it doesn't have what it takes to make a good drug. Chemists needed to tweak the molecule to improve properties like how long it lingers in the bloodstream. A year after Novartis spun off Nabriva, the FDA approved the first human pleuromutilin derivative, GSK's retapamulin. But the skin infection treatment, created by modifying the hydroxyacetyl side chain of pleuromutilin with a bicyclic N-methylpiperidine group, only works as an ointment; GSK was unable to put it into a pill or IV bag. XENLETA AT A GLANCE Discovered: 2006 Approved: Aug. 19, 2019 Active ingredient: Lefamulin Indication: Community-acquired bacterial pneumonia Mode of action: Binds to the peptidyl transferase center on the bacterial ribosome, interfering with protein production and impeding growth Although Nabriva wasn't first to the market, the company was determined to come up with a systemic drug. When it became independent, the firm didn't have a viable drug candidate of its own. What it did have was a deep knowledge of pleuromutilin chemistry and well-honed skills for making derivatives. The Nabriva researchers drew on those insights when they, like the chemists at GSK, sought to modify the hydroxyacetyl side chain. Their goal was a modification that would give the natural product the elusive balance of antimicrobial activity, solubility, and metabolic stability needed to turn a molecule into a systemic drug. Unlike their counterparts at GSK, Riedl and her colleagues didn't have huge compound libraries and combinatorial chemistry machinery at their disposal. Instead, they relied on old-fashioned medicinal chemistry savvy. "We always did dedicated chemistry and synthetic derivatives, compound by compound," Heilmayer says. In 2006, Riedl tried yet another modification of the side chain: adding an aminohydroxycyclohexyl group. The result was BC-3781, later renamed lefamulin. Riedl's choice of that side chain involved a bit of luck, of course, but mostly it was the culmination of years of carefully directed effort. She describes the moment modestly: "I always had a good feeling about that idea and that it could solve many of the problems we had at the time."   DEVELOPMENT What Riedl actually got was a mixture of diastereomers that had to be separated on a chiral high-performance liquid chromatography column. And even after separation, BC-3781 did not instill a lot of confidence. It was a difficult-to-handle amorphous salt. And the laboratory synthesis required two classical chromatographic purifications. "You cannot have these things on scale," Heilmayer points out. The Vienna team needed to develop a chirally selective synthesis that avoided chromatography, and a crystalline late-stage intermediate that could be isolated and purified. The team also had to come up with an acceptable salt form. "These were some of the problems we had to solve after discovering lefamulin," Heilmayer says. The team solved them, and by 2014, lefamulin had successfully completed Phase I and II clinical trials showing it was safe as well as effective in a small group of bacterial pneumonia patients. Because the Vienna facility didn't operate under the good manufacturing practice standards required by the FDA, Heilmayer had hired the chemistry outsourcing firms Aptuit and Almac to produce the small quantities of active pharmaceutical ingredient (API) needed for those trials. But Phase III clinical trials and, ultimately, commercialization would be a whole new ball game. New people, new outsourcing partners, and new money would be needed. The company hired a drug industry veteran as CEO and established a US subsidiary in Philadelphia where its clinical development team would be based. The following year Nabriva made an initial public offering of stock on the Nasdaq exchange. One of the new executives was Steven Gelone, who is now Nabriva's president and chief operating officer, responsible for business development and technical operations. Gelone was a good fit. Earlier in his career as an infectious disease clinician at GSK, he and his colleagues were stymied by Sandoz's robust intellectual property (IP) around pleuromutilin derivatives. "We kept hitting roadblocks," he recalls. "We just could not solve the problem, in large part because the Sandoz/Novartis team, which ultimately became Nabriva, had an IP portfolio that blocked us from doing some interesting chemistry on one of the key side chains." When Nabriva later offered Gelone a job, he couldn't say no. Working with the Nabriva executives in the US, Heilmayer looked to secure firms that could manufacture the quantities needed under quality systems that would satisfy inspectors with the FDA and the European Medicines Agency. "Our desire was, as best we could as a small biopharma company, to create a gold standard supply chain for this product," Gelone says. The critical synthetic step in lefamulin production is combining pleuromutilin with the aminohydroxycyclohexyl side chain. Heilmayer and his team needed to find large-scale suppliers of pleuromutilin and a chiral building block for the side chain, and a company to join the two pieces into the API. It also needed firms to produce the tablet and intravenous forms of the drug. For pleuromutilin, Nabriva executives thought they had it easy. Sandoz had pioneered the fermentation of pleuromutilin to produce the two animal antibiotics, and the firm was Nabriva's supplier during clinical development of lefamulin. But in 2014, Eli Lilly and Company acquired the Sandoz/Novartis animal health business. Suddenly, Nabriva was told to look elsewhere for pleuromutilin supply. Heilmayer had to scramble to find a new company that could supply pleuromutilin at the required purity and with quality systems that would satisfy regulators. He soon settled on the Chinese firm SEL Biochem Xinjiang. SEL is the world's largest producer of pleuromutilin, using it mainly for its own production of the animal antibiotic tiamulin, according to Grace Xu, a vice president at Zhejiang University Sunny Technology, which owns SEL. For Nabriva, SEL developed a special high-purity version using higher quality standards, Xu says. For the side chain building block, a cyclohexene carboxylic acid, Nabriva first contracted with an Indian pharmaceutical chemical company, which made it for Nabriva's clinical trials. But because the intermediate is a liquid acid, it had to be shipped from India via sea, rather than air, creating an unacceptably weak link in the supply chain, Heilmayer says. So, with approval and commercialization of lefamulin looking more and more likely, Nabriva sought an intermediate supplier closer to home. It ended up choosing the Irish firm Arran Chemical, which Almac acquired in 2015. Arran had the right capabilities and equipment, and Heilmayer was impressed that it was able to quote a price for the intermediate lower than what Nabriva paid the Indian firm. Companies in Ireland have higher labor costs than do those in India, acknowledges Tom Moody, Almac's vice president of technology development and commercialization. To offset them, Arran drew on other strengths. "In Ireland we have to do things efficiently," he says. Almac, which is based over the border in Northern Ireland, acquired Arran during this period, mainly for its biocatalysis and API building block scale-up skills. Almac had worked with the Irish firm for more than a decade and wanted to bring those capabilities in-house, Moody says. The chiral building block contract with Nabriva was an intriguing sweetener, he adds, because Almac had produced the API in the early days of lefamulin development and formulated it into tablets for administering to patients during clinical trials. To put the intermediates together into the final lefamulin molecule, Heilmayer and his team settled on the pharmaceutical services firm Hovione at its site in Cork, Ireland, just a 3 hour drive from the site in Athlone, Ireland, where Arran makes the side chain. In choosing Hovione, Nabriva weighed the usual factors of quality, technical fit, timing, and price. But underlying the individual considerations was the knowledge that, unlike a big drug company, Nabriva couldn't afford to hire a second supplier in case things went wrong. "Whoever we chose," Gelone says, "we had to be highly confident in, because we knew we weren't going to have a second supplier when we launched lefamulin." Hovione, a Portuguese firm, had acquired the Cork facility from Pfizer in 2009. At the time, the plant made only one API-atorvastatin, the active ingredient in Pfizer's cholesterol-lowering drug Lipitor. But by 2014, when Hovione and Nabriva started discussions, Hovione had succeeded in bringing new products to Cork, including several APIs, recalls Paul Downing, general manager of the site. Staffing at the facility had doubled since the acquisition to about 100. By the time Nabriva and Hovione signed a contract in 2016, it was clear that lefamulin, now in Phase III studies, would need to be made on an accelerated schedule. Hovione typically developed synthetic methods for pharmaceutical chemicals at its pilot plant in Portugal and then produced initial quantities there before transferring the process to the commercial-scale reactors in Cork. "The timeline Nabriva required meant we had to skip the middle piece," Downing says. Both parties knew that Hovione's job was more than just connecting two molecules. The cyclohexene carboxylic acid from Arran had to be taken through further chemical steps to form the aminohydroxycyclohexyl side chain that Riedl had conceived in 2006. And the hydroxyacetyl group on pleuromutilin has to be activated through an exchange of sulfur for oxygen to form a sulfanylacetyl linker that couples with the side chain. "It seems simple, but it's actually a very long process that requires care and attention," says Rui Loureiro, Hovione's director of process chemistry development and the lead chemist on the development project. From start to finish, a production campaign takes about two months. One area that called for special attention was phase separation. In lab tests of the reaction in Portugal, process chemists were surprised to find that three phases resulted, rather than the usual two. "We had to understand how you make sure in the plant that you take out the right phase of three phases," Loureiro says. Another challenge was crystallizing and recrystallizing a molecule with multiple chiral centers. "That's how to ensure that you get the right isomers out of your reaction," Loureiro says. The API that Hovione manufactures in Cork is the heart of Xenleta, but for people to take it, the white powder has to be turned into tablet and IV forms. For the tablet, Heilmayer turned to Almac again. Nabriva had first hired Almac in the early 2010s to produce the lefamulin API for Phase I and II clinical trials. At the time, says Tommy Burns, an Almac project services manager, Nabriva took the logical next step in a good relationship and asked Almac's finished drug division to formulate the API into tablets. Some years later, with clinical successes under its belt, Nabriva came back to Almac looking for tablet manufacturing and packaging for Phase III trials and commercial launch. "Nabriva needed a firm that could help overcome some of the development challenges they faced with the tablet," Burns says. To be effective, lefamulin needs to be administered in high doses, and 600 mg is tough to squeeze into even a large tablet. Moreover, because the API is sticky, Almac was not able to create a traditional pill with the necessary on-dose product identifier embossed on the surface. Instead, Burns says, Nabriva and Almac worked together to develop a nonstandard pill for which the name is applied with an inkjet printer. For vials of the drug for intravenous delivery, Nabriva contracted with Patheon's sterile liquid production facility in Monza, Italy. It also tapped Fresenius Kabi's sterile liquid contract manufacturing facility in Halden, Norway, to produce special companion IV bags to which the sterile drug is added. As Gelone explains, Nabriva scientists realized early in the development of lefamulin that its pH in solution is important and should be maintained. They worked with Fresenius on a bespoke IV bag which they created by adding a citrate buffer to the conventional saline bags made in Halden. When a health-care professional pours a vial of Xenleta into the bag, the resulting solution is close to physiologic pH, Gelone says. In the end, producing and distributing Xenleta requires a supply chain that stretches from China to multiple sites in Europe and, ultimately, the US. Nabriva took the risk of assembling it without knowing if regulators would actually clear the drug, but the bet paid off. The FDA approved Xenleta on Aug. 19, 2019. "We had the product in the channel and ready for patients 16 days after approval," Gelone says.   MARKETING Nabriva's manufacturing partners continue to refine their processes. At Hovione, for example, Loureiro is eager to develop continuous solvent extraction to decrease the amount of solvent required to recover the API. By his calculation, lefamulin generates 3% less waste than the typical API, but he says Hovione can cut waste further. "We believe there is space to improve the process." And Burns says Almac is in the process of moving the granulation process for Xenleta tablets from pilot to commercial scale. Once the switch is complete, Almac's capacity to manufacture the pills will be markedly higher. But even as Nabriva's partners streamline production, healthy demand for Xenleta is far from a sure thing. In the past few years several biotech firms have won FDA approval of new antibiotics that are effective against resistant bacteria, only to find physicians and hospitals reluctant to prescribe them. In 2019 alone, three small antibiotic firms-Melinta Therapeutics, Aradigm, and Achaogen-all declared bankruptcy. Public health experts say doctors and hospitals need new medicines to fight antibiotic-resistant infections, yet the companies that invent them too often find few customers. "One of the conundrums that's very unique for anti-infectives is the strong desire to have innovation available but not wanting to use that innovation for fear you're going to ruin it by creating resistance," Gelone says. The health-care community thus thoroughly reviews the differentiating characteristics of a new antibiotic to understand the patients for which it is best suited. "I've run the committees that do it, and the process takes time," he says. Nabriva contends that Xenleta falls in the right place. Pleuromutilin antibiotics, the firm says, have a lower propensity for resistance than most established antibiotics because they bind to bacterial ribosomes in a unique way and via multiple interactions. And lefamulin has the advantage of being approved in both IV and oral forms, meaning it has the potential to be administered first in a hospital and later at home. New antibiotics aren't going to be billion-dollar-a-year drugs, Gelone acknowledges. "There has to be a perceived unmet medical need that the physician community believes this product will address," he says. "That's where lefamulin fits in." Nabriva is finding the process of fitting in to be slow. In April, the company announced that it is laying off its hospital-oriented salesforce of 66 people, more than a third of its overall staff. Nabriva described the decision as part of a new strategy of focusing on community health-care professionals. Restrictions on interacting with hospital personnel during the coronavirus pandemic also played a role in the layoffs. On May 11, Nabriva reported that it had product sales in the first quarter of 2020 of only $156,000. The firm also disclosed that it was in danger of being delisted from the Nasdaq stock market because its shares were trading for less than $1.00. In early 2017 they were changing hands for more than $12.50. Still, Gelone is optimistic. European regulators just handed down a positive opinion, and Nabriva is working with its partner in China, Sinovant, on approval there. He notes that Xenleta could play a role in treating people infected with the novel coronavirus who also have contracted pneumonia. In Vienna, Heilmayer and Riedl remain proud of what Nabriva has accomplished. Heilmayer wonders if a larger company would have stuck with the compound through the tougher moments. "They establish certain thresholds, and if you don't achieve these thresholds, the compound is gone," Heilmayer says of big drug firms. "In the biotech world, if you have a challenge you will always look for ways to overcome it." Today, Heilmayer and Riedl are tackling new challenges. Heilmayer continues to work with Nabriva's outsourcing partners to support and troubleshoot Xenleta manufacturing. In one recent program, they elucidated and synthesized a new impurity encountered during large-scale API manufacturing. As for Riedl, she and her colleagues are working on next-generation pleuromutilin antibiotics as well as other projects that she is keeping close to the vest. "Stay tuned for the next molecules from Nabriva," she says.   Read the article at C&EN  

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One molecule’s journey from discovery to market

Jun 22, 2020

A PHARMACEUTICAL company has donated hand sanitiser to the HSE as well as local organisations to help the fight against Covid-19. Douglas GAA, camogie and ladies football clubs recently received a large donation of hand sanitiser for those that are helping out in their community during the pandemic. Hovione is a contract pharmaceutical manufacturing company which helps bring new and off-patent drugs to market.  Hovione, based in Ringaskiddy, has been manufacturing in Cork for 11 years and has more than  60 years experience in the development and compliant manufacture of Active Pharmaceutical Ingredients and Drug Product Intermediates. Hovione employs more than 200 people in Cork and approximately 1,800 globally including Lisbon and Loures in Portugal; Macau in China and New Jersey in America. Hovione initially began manufacturing hand sanitiser for the protection of team members on site with dispensers placed across the site.  Since then the demand for hand sanitiser grew in our external community. This lead Hovione to appoint a project team to bring the manufacturing of hand sanitiser to distribution, so that it was readily available for donation to help protect various facilities and institutions across Ireland. Key dates: April 11 – first day of Manufacturing - 17 days after the project kicked off. April 20  – First batch of hand sanitiser was collected for use at St Stephen’s Hospital, Glanmire. A spokesperson for the companys said: "A special thanks to the Hovione’s Project team, Site Leadership Team, Manufacturing and Warehouse Teams for all they have done to help with this fight against Covid-19.  "A heartfelt thank you from all at Hovione must be given to the various suppliers who have helped us fight Covid-19 together - SciChem Laboratory Supplies, OCON Chemicals Ltd, Carbon Group, Quitmann O’Neill Packaging Ltd, Schuetz Packaging and South Coast Sales. "To date Hovione have supplied 17,000 litres across Ireland to nursing homes, care facilities, charities and hospitals. Hovione are working closely with An Garda Síochána to safely distribute hand sanitiser to the HSE across Ireland with 11,000 litres of hand sanitiser  collected from site recently. "On an international scale Hovione are distributing hand sanitiser free across all of our sites to support the local communities of each country we manufacture in." Chairman of Douglas GAA Club, Aidan O'Connor thanks Hovione for their generous donation to the various clubs.   Read the article published at EchoLive.ie  

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Hovione helping out HSE and community groups with donations of hand sanitiser

May 11, 2020

  Hovione Technology recently announced its innovative 8Shot Dry Powder Inhaler (DPI) enabling high-dose drug delivery to the lungs has received the Red Dot 2020 Product Design Award in the Healthcare Daily Living AIDS category. The Red Dot Design Award is an internationally recognized quality seal awarded for innovative and high-quality product design. “The Red Dot jury’s experience and expertise evaluating outstanding product design and technical innovation for more than 60 years is unparalleled. This distinction awarded to our 8Shot DPI is a great success for Hovione Technology”, said Peter Villax, Hovione Technology’s CEO. 8Shot is the world’s first 8-puff, disposable DPI enabling drug delivery of new pharmaceutical compounds requiring very high doses delivered to the lungs. It delivers therapeutic doses up to 400 mg formulated as drug alone or engineered particles in multiple, sequential inhalation maneuvers for maximum therapeutic benefit and patient safety. “We are extremely proud and delighted to accept the Red Dot  Product Design Award, together with our design and development partner WeADD,” said Dr João Ventura Fernandes, Hovione Technology’s Director of Technology Development and Licensing. “The 8Shot™ DPI is uniquely positioned to make available off-the-shelf to pharmaceutical companies a patented high payload DPI to deliver inhaled biologics, antibiotics, anti-virals, vaccines, pain or rescue treatments requiring high-dose drug delivery.” Hovione Technology’s TwinMax and 8Shot dry powder inhalers are designed to enable safe and effective delivery of large doses to the lung. Featuring patented inhaler technology, TwinMax and 8Shot are compatible with drug doses up to 100 mg and 400 mg respectively, delivered conveniently to patients from multiple inhalations. Our Large Dose DPIs are suitable for inhaled delivery of biologics, antibiotics, anti-viral, vaccines, pain or rescue treatments.  Hovione Technology offers access to a complete portfolio of innovative, cost-effective dry powder inhalation devices – disposable, capsule-based, blister-based and large dose DPIs. With over 20 years of expertise developing innovative inhaler technology, Hovione Technology’s team has been behind the first market approved disposable dry powder inhaler for influenza treatment in Japan, the TwinCaps DPI. Millions of patients are being treated every year with Hovione Technology’s innovative inhaler technology. For more information, visit www.hovionetechnology.com WeADD is a Portuguese Company specialized in innovation, development, product engineering and intelligent property in small and large appliances, machinery, functional packaging and consumer electronics in sectors such as health, sports, coffee and internet of things. For more information, visit www.weadd.com   Read the article at DDD    

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Hovione’s Inhaler for High-Dose Delivery Earns Product Design Award

Apr 16, 2020

Chemical companies continue to invest in hand sanitiser in response to the Covid-19 pandemic. A large number of them are now producing in significant volumes. Ineos, the largest European producer of the two key raw materials - isopropyl alcohol (IPA) and ethanol – has announced its intention to produce 1 million bottles of hand sanitiser/month from each of three newly built facilities in the UK, Germany and France. As of the end of March, the company has hit its target of building the first plant near Middlesbrough, UK. It will supply hospitals free of charge “during the crisis period” and is in discussions with retailers. Dow announced on 30 March that its sites at Auburn, Michigan; South Charleston, West Virginia; Seneffe, Belgium; and Hortolândia, Brazil “possess the necessary raw material handling, mixing and packaging capabilities and will produce hand sanitiser”. They join the site at Stade, Germany, which is already manufacturing it. Dow, like Ineos, was already producing raw materials, said that it could adapt its capabilities for downstream production with “little to no impact to normal operations”. Auburn can produce 7 tonnes/week and similar volumes are expected at the other sites. Once all are at full production, the company expects to produce 200 tonnes. All of the hand sanitiser that will be produced has been allocated, with the majority for donation to state and regional health systems and government agencies for distribution. It will also be distributed to Dow production sites to help protect frontline employees. The first deliveries are expected to begin in the first week of April. Plant-based ingredients firm Roquette has adapted one of its pilot lines at its site in Lestrem, France, to manufacture about 5,000 litres/week of a hydro-alcoholic disinfectant solution. The first shipments were sent to Lille University Hospital Centre, the French Blood Donors Organisation and to other local health facilities, in coordination with the Hauts-de-France Regional Health Agency and the local authorities. In Germany, Wacker donated 15,000 litres of hand sanitiser for the production of disinfectants to Bavarian hospitals and care facilities at the request of the state Ministry of Economic Affairs. The alcohol needed, 11,000 liters of 2-propanol, was transported from Nünchritz, Saxony, to the Gendorf chemical industry park in Bavaria to be mixed and sent to an official distribution centre. Swiss pharmaceutical CMDO Siegfried is also supplying disinfectant in those regions where it operates production sites, including the Swiss cantons of Aargau and Valais and around Minden in Germany. “The service including delivery is free of charge to the extent possible,” the company said, adding that it will not supply private or commercial organisations. Meanwhile, Croda International said that it has gifted enough glycerine to regular customers to manufacture five million 250 ml bottles of hand sanitiser, assuming 2% glycerine content. It is also donating saponin vaccine adjuvants to projects working on a vaccine. The company plans to review with customers where more glycerine could be gifted. Similarly in the US, Amyris, which is in discussions for the testing of its fermentation-derived squalene as a vaccine adjuvant for a Covid-19 vaccine, has launched its own No Compromise Pipette Baby branded hand sanitiser. The company said that it “will not price its hand sanitiser at a premium, and plans to donate part of the supply to front-line health staffers and medical personnel”. It plans to produce 30,000 units in the first few weeks. Portugal’s Hovione began producing IPA- and ethanol-based hand sanitiser to a WHO formulation at tonne-scale for itself when supplies were short, it has emerged. The company, another major pharmaceutical CDMO, is now supplying the material free to Portuguese hospitals. Volumes were expected to reach 30 tonnes by the end of the month. Earlier in March, Lanxess added a second shift at its site in Sudbury, UK, to boost production of Vikron sanitiser. Earlier, BASF announced plans to produce hand sanitisers at Ludwigshafen and supply them to hospitals in the Rhine-Neckar metropolitan region. The company has now reallocated tonnes of raw materials, especially IPA, for making the sanitisers and secured legal official permission to make them. Similarly, Huntsman and Syngenta began making hydro alcoholic solution to produce hand sanitiser at Monthey, Switzerland, for free-of-charge supply to hospitals and pharmacies in the Canton of Vaud and the General Hospital in Lausanne. Plans were to ramp up production to 3-5 tonnes/week. Arkema has repurpose da production line at its Rhône-Alpes Research Centre in order to make 20 tonnes/week of alcohol-based solution to be distributed free of charge for the mass restocking of public hospitals. The effort is not limited to chemical companies, of course. Flavours and fragrance giant Firmenich has shifted production at La Plaine, Switzerland, to disinfectant solution, while luxury goods maker LVMH and many manufacturers and distillers of spirits on both sides of the Atlantic have also switched production.   Read the article at Specchemonline    

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Covid-19: Hand sanitiser effort continues

Mar 31, 2020

About 6 weeks ago, the pharmaceutical chemical maker Hovione ran out of disinfectant gel at its plant in Macau. “So the guys just used their heads and started manufacturing it themselves,” CEO Guy Villax says. Hovione is one of a number of chemical, distilling, and other companies that are starting or increasing production of hand sanitizers and sanitizer ingredients needed during the coronavirus pandemic. Some are already in the sanitizer business. Others, like Hovione, jumped in during a time of need. Impressed by the initiative in Macau, Villax put staff at the company’s plant in Loures, Portugal, to work making alcohol-based sanitizer at metric-ton scale. Hovione is distributing it to hospitals, other health-care facilities, and municipalities in solution and gel formulations. Hovione has enlisted a dedicated production line in Loures staffed by a team of about 30 workers. The company is using a formula available from the World Health Organization involving mainly ethanol or isopropyl alcohol and glycerin. Production volume was expected to reach 5 metric tons (t) during the week of March 16 and as much as 30 t by the following week. “At the moment we have hospitals asking us for 6 to 10 t, small entities asking for 100 L,” says Filipe Neves, pilot plant operations director, who is overseeing the project for Hovione in Loures. In Germany, the big chemical maker BASF says it is preparing to manufacture hand sanitizer at its headquarters complex in Ludwigshafen, where it makes raw materials for sanitizers. The company plans to distribute the product to area hospitals. UK-based Psychopomp & Circumstance Distillery, which normally distills gins and rums, is using its still to make sanitizing hand gel that it is giving away. Consumers can top up their own refillable bottles at the firm’s still in Bristol and leave a donation for a local children’s hospital. At the moment we have hospitals asking us for 6 to 10 t small entities asking 100 L. Filipe Neves, pilot plant operations director, Hovione The company started out mixing its alcohol with aloe vera gel but has since switched to glycerin. “We are making as much of it as we can without going bankrupt,” Psychopomp cofounder Liam Hirt says. Ireland-based Listoke Distillery has also switched production from gins to alcohol for hand gels, as have Taiwan Tobacco and Liquor and a number of small US distillers. The flavor and fragrance producer Firmenich has shifted production at its La Plaine, Switzerland, facility to disinfectant solution. LVMH, the parent company of luxury goods maker Luis Vuitton, has switched three of its perfume facilities in France to making “substantial quantities” of alcohol-based hand sanitizer. The firm is giving the product to the French health authorities for free. Specialty chemical manufacturers in the business of making sanitizing and disinfecting chemicals are boosting production. Lanxess is significantly increasing output of its Vikron sanitizer in Sudbury, England—introducing a second shift. The company recently donated a metric ton of disinfectant to hospitals in Wuhan, China, the epicenter of the virus outbreak, and to nearby cities. And Gelest has significantly ramped up production of its Biosafe antimicrobial agent at its facility in Morrisville, Pennsylvania. Based on a silane quaternary ammonium salts, Biosafe punctures the cell membranes of microbes, destroying them on contact. Applications include formulations used by food service workers. Biosafe is also the microbe-killing ingredient in a laundry additive called Certainty Smartboost, from the uniform company Careismatic Brands, which is sold primarily to health-care workers in specialty stores near hospitals. Workers use the treatment on their hospital scrubs or uniforms because it provides antimicrobial protection after they are washed. Drums of Biosafe are “flying off the shelves” to formulators of cleaning products, including nonwoven wipes, according to Gelest CEO Ken Gayer. “We’re now also seeing direct orders from hospitals that want cases and cases of this material and are giving it to staff members.” Read the article at C&EN website    

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Stepping up to the hand sanitizer shortage

Mar 19, 2020

Firms signal preparedness, but warn that prolonged plant closures and travel restrictions may cause significant disruptions Major drug companies have issued statements in recent days assuring the public that their inventories are adequate in the face of supply chain threats stemming from China’s coronavirus outbreak. Suppliers of active pharmaceutical ingredients (APIs) are also assuring customers that they are prepared for temporary interruption in the supply of key ingredients from Chinese firms. However, API makers in Europe and the US warn that supply disruptions could result from a protracted delay in restarting production at plants closed in recent weeks by the Chinese government or prolonged transportation restrictions. James Bruno, president of the consulting firm Chemical and Pharmaceutical Solutions, notes that travel restrictions are already interrupting business with Chinese suppliers. “First of all, nobody is going to be able to get to China,” he says, “so all the audits are going to be canceled.” Bruno adds that the travel restrictions will prolong plant closures stemming from Chinese New Year celebrations, which began on Jan. 25 and are scheduled to run to Feb. 8. “These guys have gone home and may not be able to get back to where they were working,” he says. The initial quarantine of Wuhan, the city first impacted by the virus, has broadened to include travel bans in other major cities, Bruno notes. “It’s not just Wuhan. It’s China.” Bruno says he has received calls from clients asking where they might find alternative sources of materials purchased from China. “The good news is that most of the people dealing with China tend to have inventory,” he says. “But if this doesn’t straighten out in the next 3 months, we could have some real problems with supply disruption.”   Guy Villax, CEO of the pharmaceutical chemical maker Hovione, says 50 people did not show up for work on Feb. 4 at the company’s plant in Macao, which employs 200. “Twenty-five of them live across the border in China, and China’s instructions are to stay at home,” he says. “But the issue is not whether the plant is producing; the real question is whether there will be transport to move goods around. Right now the head of the plant doesn’t know if he’ll get supplies from China.”   Asymchem, a pharmaceutical chemical manufacturer in Tianjin, China, approximately 1,160 km from Wuhan, also notified customers of contingencies related to the virus outbreak. The company told customers on Jan. 30 that it had pre-stocked materials to support production for at least a month and that it has not experienced delays on projects. Asymchem reports that 45 employees, about 1% of its workforce, were quarantined by authorities after traveling during the holiday. The firm says it expects its plants to open on Feb. 10. “We will closely monitor the situation as it evolves, and take action proactively for assurance of supply,” Asymchem Senior Vice President Elut Hsu says in the letter. Sources agree that the full impact of prolonged restrictions in China is difficult to gauge. According to a recent report by the US Food and Drug Administration, China is home to approximately 13% of the 1,788 facilities that manufacture APIs for drugs marketed in the US. Given the reassuring reports from drug companies and API producers, there is no reason to fear a significant disruption in the pharmaceutical supply chain, says industry consultant Steven Lynn, a former head of the FDA’s quality compliance office. “Fearmongering is not something we should be doing,” he says. But API suppliers should take advantage of a short-term disruption to review supply chain and logistics vulnerabilities. “Churchill had a good quote,” Lynn says. “‘Never let a good crisis go to waste.’”.   Read the article  

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Coronavirus puts drug chemical industry on alert

Feb 04, 2020

Portugal-based Hovione Technology, a company developing inhalation devices, announced it has entered a collaboration agreement with the Kiel University’s Institute of Pharmacy in Germany. The agreement will see scientists from the institution utilize Hovione’s portfolio of large dose dry-powder inhalers (DPIs) to conduct research on advanced formulation approaches for high-dose inhalation applications. João Ventura Fernandes, Hovione’s director of technology, development and licensing, told us that the collaboration started in July 2019 and will continue during the course of the next three years. Specifically, researchers will use Hovione’s TwinMax and 8Shot inhalation devices, which enable administration of powder doses of up to 400mg to patients lungs through multiple inhalations manoeuvres. The devices are suitable for inhaled delivery of antibiotics, peptides, anti-virals, vaccines, pain or rescue treatments. Using Hovione’s devices, the researchers will work on formulations containing softpellets and nanocrystals for high-dose administration via dry powder inhalation, and with antibiotics including clarithromycin and rifampicin as model drugs. "In high dose drug delivery, the key in inhaled formulation development is to create an active pharmaceutical ingredient (API)-rich formulation, i.e. with as little as possible excipients, to deliver the required therapeutic dose with the smallest amount of material as possible,"​ Regina Scherließ, director of the Institute of Pharmacy, told us. Scherließ added that, in order to achieve this goal, while concurrently maintaining handling and dispersion properties, the Institute develops two advanced formulation approaches: Softpellets, which can be produced from pure API, i.e. 100% API in the formulation, and provide improved powder handling and aerodynamic dispersion properties when compared to the traditional approach of micronizing the material​ Nanoparticles, which may decrease the dose needed due to higher dissolution rate, and can be formulated to API rich microparticles for inhalation by particle engineering technologies, such as spray drying. This combination is called Trojan particle and also provides improved powder handling and dispersion properties.​ Fernandes said that Hovione aims to answer market needs, after the introduction of new drugs requiring delivery of large lung doses, often within the range of 50 to 150mg. Indications of such drugs include cystic fibrosis, pulmonary arterial hypertension, idiopathic pulmonary fibrosis or lung infections. Earlier this year​, Hovione acquired from Med & Tec the rights to the design of Papillon, a reusable, cost-effective, dry powder inhaler suitable for administration of treatments for chronic or acute pulmonary conditions. Find more about Hovione Technology   You might be interested in: DPI's formulation development Inhalation development services    

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Kiel University and Hovione to develop high-dose inhalation formulations

Sep 13, 2019

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