The COVID-19 pandemic has created a rise in demand for contract services.

Meeting Increased Demand During COVID-19

Takeda and Novavax announced on August 7, 2020 that they are partnering on the development, manufacturing, and commercialization of NVX‑CoV2373, Novavax’s COVID‑19 vaccine candidate, in Japan.

Under the terms of the agreement, the companies will collaborate on the manufacturing, clinical development, and regulatory activities in Japan. Novavax will license and transfer manufacturing technologies to Takeda to manufacture the vaccine antigen, while Takeda will handle the regulatory submission to Japan’s Ministry of Health, Labor, and Welfare (MHLW) and will produce and distribute the vaccine in Japan, a Novavax press release said. Over 250 million doses of the vaccine are expected to be manufactured per year through the collaboration.

“Takeda’s leading position in Japan, technical expertise, regulatory know-how, and manufacturing capacity make the company an ideal partner to further expand the global availability of NVX‑CoV2373,” said Stanley C. Erck, president and CEO of Novavax, in the press release. “We look forward to collaborating with Takeda to rapidly develop, produce, and commercialize the vaccine in Japan.”

“Nothing is more important right now than protecting the world against COVID-19. We are excited to collaborate with Novavax to bring their promising vaccine candidate to Japan,” said Rajeev Venkayya, MD, president of the Global Vaccine Business Unit, Takeda, in the press release. “Today’s announcement builds upon our ongoing support of pandemic preparedness and demonstrates Takeda’s commitment to the health and well-being of the Japanese population.”

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The companies will collaborate on the manufacturing, clinical development, and regulatory activities for Novavax’s COVID-19 vaccine in Japan.



Takeda and Novavax Team Up for COVID-19 Vaccine Development in Japan

 in August 2020 to assist sponsors of investigational new drug (IND) applications and biologic license applications for therapeutic proteins (TPs) in determining the need for drug-drug interaction (DDI) studies. The guidance focuses on therapeutic biological products as defined under section 351 of the Public Health Service Act but may also apply to other biologic products regulated by the Center for Biologics Evaluation and Research.

FDA states in the guidance that “when evaluating the potential for a DDI between a TP and small molecules or between TPs, sponsors should consider the mechanisms of a potential DDI, taking into account the pharmacology and clearance of the TP as well as any co-administered medications in the patient population.” The document gives examples of situations where a DDI of a TP may be needed and recommends “a systematic, science-driven approach to evaluate the DDI potential of TPs.”

Drug Interaction Studies—Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions

Clinical Drug Interaction Studies—Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions

The guidance is intended to assist IND sponsors in determining the need for drug-drug interaction studies.

FDA Publishes Guidance on Drug-Drug Interaction Studies for a Therapeutic Protein

The Aug. 11, 2020 announcement by Russian President Vladimir Putin that the country’s health ministry would approve a COVID-19 vaccine without conducting large-scale clinical trials prompted criticism and alarm from researchers and healthcare groups around the world in various media outlets.

Arguing that the vaccine, Gam-COVID-Vac Lyo, developed by Moscow’s Gamaleya Institute was safe, Putin was quoted on Russian State television saying he knew the vaccine worked effectively, forms strong immunity, and passed all needed checks.

Scientists from other countries noted that the effectiveness of the Russian vaccine cannot be known without independent review of scientific papers on clinical trial results.

 dated Aug. 10, 2020, listed the Gamaleya vaccine in Phase I trials. 

 listed a Phase I study with 38 participants; no results were posted.

Leading vaccine candidates from AstraZeneca, Sinovac, Wuhan Institute of Biological Products/Sinopharm, Moderna, and Pfizer/BioNTech are conducting Phase III trials involving tens of thousands of patients. Another dozen vaccine programs are in Phase I/II trials.

Questions about safety and efficacy surround Putin’s announced approval of a COVID-19 vaccine, with no supporting clinical trial results.

Researchers Question Russia’s COVID-19 Vaccine Claim

Grand River Aseptic Manufacturing (GRAM), a parenteral contract development and manufacturing organization (CDMO), announced on August 6, 2020 that it has been chosen by the US Department of Health and Human Services and the US Department of Defense to support the US government’s Operation Warp Speed efforts by offering capacity for manufacturing and distributing COVID-19 vaccines and therapeutics.

Under the terms of the partnership, the government will reserve fill/finish capacity on a commercial filling line for use by federal partners that are developing COVID-19 vaccines or therapeutic treatments, a GRAM press release said. The company plans to use its 60,00-ft2 large-scale fill/finish facility located in Grand Rapids, MI, to aid in the pandemic efforts.

“We are extremely honored to be chosen to serve our country and help respond to the demands and challenges presented by the COVID-19 pandemic,” said Tom Ross, president and CEO of GRAM, in the press release. “As a homegrown company with a strong culture built on teamwork and accountability, our team will confidently deliver the safest and highest-quality solutions that will ultimately be life-saving for the American people.”

The CDMO will offer capacity for manufacturing and distributing COVID-19 vaccines and therapeutics at its Grand Rapids, MI, fill/finish facility. 

Grand River Selected for Operation Warp Speed Efforts

Less than two weeks after the US International Development Finance Corporation (DFC) announced a letter of interest to provide a $765 million loan to Eastman Kodak to fund the launch of Kodak Pharmaceuticals to produce pharmaceutical components, the agency placed the loan on hold.

On Aug. 7, 2020, the DFC issued a statement via its Twitter feed that “Recent allegations of wrongdoing raise serious concerns. We will not proceed any further unless these allegations are cleared.” 

On the same day, Eastman Kodak announced via a press statement that a committee of independent directors of the Board would “oversee an internal review of recent activity by the Company and related parties in connection with the announcement of a potential loan by the US International Development Finance Corporation to support the launch of Kodak Pharmaceuticals." The announcement said the company would not make further public comment during the review.

DFC did not provide details about the allegations. In announcing the letter of intent on July 28, 2020, DFC noted that the letter signing “indicates Kodak’s successful completion of DFC’s initial screening and will be followed by standard due diligence conducted by the agency before financing is formally committed.”

In the July 28 press release, DFC said the loan would be used for startup costs related to expanding and repurposing Kodak’s existing facilities in Rochester, NY and St. Paul, MN. The facilities, which would produce “critical pharmaceutical components”, would use continuous manufacturing and advanced technology capabilities, the announcement noted.

US International Development Finance Corporatio

Citing undisclosed allegations against Kodak, the DFC placed a hold on a potential $765 million loan to launch US-based API manufacturing.

Allegations Put Kodak Pharmaceuticals Loan on Hold

Jill Wechsler is Pharmaceutical Technology's Washington Editor, jillwechsler7@gmail.com.

The White House initiative to encourage production of essential medicines in the United States calls on FDA to set the parameters for and implement main aspects of the program. Under the 

issued by President Trump on August 6, 2020, FDA first will determine which medicines fall under the program’s requirements. In addition, the agency will collect additional information from manufacturers on drug and ingredient origins and accelerate approval of qualifying products and their production facilities.

FDA has 30 days to draw up a list of “essential medicines, medical countermeasures, and their critical inputs” (i.e., APIs and other components) and another 60 days to finalize it. The list will cover therapies and medical products that the US “must have available” at all times, particularly treatments for infectious diseases and to protect against chemical, biological, radiological, and nuclear (CBRN) threats.

To ensure demand for domestically made medicines, federal agencies that purchase drugs, including the Department of Health and Human Services (HHS), the Department of Defense, and the Department of Veterans Affairs, will develop plans in 90 days for steering procurement and contracts to those essential medicines produced at home. Those agencies will have to submit annual reports in 2021 on where they source these critical products. The US Trade Representative, moreover, will exclude those listed products from free trade agreements, while federal agencies will look to revise environmental and other regulations likely to inhibit construction of new pharmaceutical facilities in the US.

There are some notable exceptions to the program. The Buy American requirements won’t apply to medicines not available in sufficient quantities in the US, to US-made products that are 25% more expensive than imports; or in cases of a national emergency. At the same time, the new policies will aim to combat trade in counterfeit goods and protect intellectual property.

FDA also will seek to reduce supply chain vulnerabilities by collecting information on the sources of and shortages in critical drugs and medical devices and their ingredients, plus information on the date of a facility’s most recent inspection and the results of such inspections. To accomplish these goals, the agency will identify where new regulations or guidance are needed to collect production information and will negotiate with other countries to increase foreign inspections—including unannounced site visits—of firms producing essential medicines. And the government will limit imports from manufacturers that refuse or unreasonably delay an inspection.

At the same time, FDA will encourage pharma manufacturers to shift production to the US by offering accelerated approval of essential medicines made in the US, particularly those needed to counter infectious disease and CBRN threat preparedness. The agency will issue guidance on developing advanced manufacturing techniques for domestic production of essential therapies, while also looking to identify and propose changes in laws and regulations found to erect barriers to domestic production efforts.

A main objection to the “Buy American” policy for pharmaceuticals is that domestically produced critical medicines are likely to be more expensive than those made overseas. Generic-drug makers, in particular, acknowledge that APIs and drugs from China and India are cheaper than those made in the US and that government contracts for pharmaceuticals need to assume higher prices for American-made products.

In this light, the initiative to increase purchases from domestic producers runs counter to an earlier White House announcement advancing four drug price control initiatives, including an international reference pricing scheme for drugs and biologics. President Trump issued 

on July 24 that call for certain health centers to pass on price discounts on insulin and epinephrine

 drug imports from Canada and other countries 

, policies announced previously and already undergoing analysis for impact and implementation. Another proposal would reduce rebates paid to 

“middlemen” managing Medicare drug plans,

 which analysts say would raise premiums for beneficiaries

. Trump again floated the idea of setting an international pricing index, or “most favored nation” policy, to link prices paid for Medicare Part B medicines to those paid overseas.

Manufacturers were livid that the White House was proposing such massive changes in operations with the Buy American plan and a foreign pricing index at a time of great industry focus and investment in developing treatments to combat COVID-19. Big Pharma CEOs rejected Trump’s invitation to come to a White House meeting to discuss these proposals, further escalating tensions between biopharma companies and the administration. Trump has more support for his drug pricing proposals from Democrats, but no further action is expected this year.

The White House initiative to encourage production of essential medicines in the United States calls on FDA to set the parameters for and implement main aspects of the program. 

FDA in Hot Seat on Buy American Drug Policy 

In two separate agreements announced on July 31, 2020, Sanofi and GlaxoSmithKline (GSK) will supply a COVID-19 recombinant protein-based vaccine to the US government and the European Union.

The companies have entered into a collaboration with the US government to accelerate the development and manufacturing of the vaccine candidate, which was developed by Sanofi in partnership with GSK. The vaccine candidate is based on the recombinant protein technology used by Sanofi to produce an influenza vaccine and GSK’s established pandemic adjuvant technology.

Under the collaboration, the US Department of Health and Human Services (HHS) and Department of Defense will help fund the development activities and secure scale-up of Sanofi’s and GSK’s manufacturing capabilities in the United States, which is expected to significantly increase capacity. The US government will provide up to $2.1 billion, more than half of which will go to support further development of the vaccine, including clinical trials, with the remainder used for manufacturing scale up and delivery of an initial 100 million doses of the vaccine. Sanofi will receive the majority of the US government funding. The US government has a further option for the supply of an additional 500 million doses longer term, which helps meet Operation Warp Speed’s goals of providing millions of doses of a safe and effective COVID-19 vaccine.

“The global need for a vaccine to help prevent COVID-19 is massive, and no single vaccine or company will be able to meet the global demand alone,” said Thomas Triomphe, executive vice-president and global head of Sanofi Pasteur, in a company press release. “From the beginning of the pandemic, Sanofi has leveraged its deep scientific expertise and resources to help address this crisis, collaborating with the US Department of Health and Human Services to unlock a rapid path toward developing a pandemic vaccine and manufacturing at large scale. With our partner GSK, we expect our Phase [I/II] study for the recombinant adjuvanted approach to start in September.”

“The portfolio of vaccines being assembled for Operation Warp Speed increases the odds that we will have at least one safe, effective vaccine as soon as the end of this year,” said HHS Secretary Alex Azar in the press release. “Today’s investment supports the Sanofi and GSK adjuvanted product all the way through clinical trials and manufacturing, with the potential to bring hundreds of millions of safe and effective doses to the American people.”

Meanwhile in Europe, Sanofi and GSK are in advanced discussions with the European Commission (EC) to supply up to 300 million doses of the COVID-19 vaccine. The doses would be manufactured in European countries including France, Belgium, Germany, and Italy.

“Today’s announcement helps to ensure that millions of Europeans will have access to a potential vaccine protecting against COVID-19, once proven safe and effective. It has been our steadfast commitment to provide a vaccine that is affordable and accessible to everyone, and we are grateful to the European Commission for their ongoing engagement and shared support of this effort,” Triomphe said in a company press release.

"GSK is proud to be working in partnership with Sanofi to make this vaccine available as soon as possible in Europe. Both companies have significant R&D and manufacturing capability in Europe and are already working hard to scale up production across our networks. This announcement from the EC supports our ongoing efforts,” added Roger Connor, president of GSK Vaccines, in the press release.

Sanofi and GlaxoSmithKline have been selected to supply the US government and the European Union with millions of doses of their COVID-19 vaccine candidate.

Sanofi and GSK to Supply COVID-19 Vaccine to US Government and European Union

The Janssen Pharmaceutical Companies of Johnson & Johnson (J&J) have entered into an agreement with the US government for the large-scale domestic manufacture and delivery of 100 million doses of Janssen’s investigational vaccine against SARS-CoV-2, Ad26.COV2.S. The vaccine will be supplied for use in the United States, following approval by FDA or Emergency Use Authorization given by the agency, J&J stated in an Aug. 5, 2020 press release.

The US government is committing over $1 billion for this agreement through the Biomedical Advanced Research and Development Authority (BARDA), part of the US Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response, and in collaboration with the US Department of Defense. J&J will ultimately provide the vaccine at a global not-for-profit basis for emergency pandemic use, and the US government may also purchase an additional 200 million doses under a subsequent agreement.

J&J developed the SARS-CoV-2 vaccine under an ongoing research and development collaboration with BARDA and under the oversight of FDA. Based on positive preclinical data recently published in the peer-reviewed journal 

, the Phase I/IIa first-in-human clinical trial of the vaccine is underway in healthy subjects in the US and Belgium.

The company is evaluating one- and two-dose regimens in its clinical program. J&J aims to supply more than one billion doses globally through the course of 2021, if the vaccine is proven safe and effective.

The company’s SARS-CoV-2 vaccine program uses Janssen’s AdVac technology, which is the same technology used to develop Janssen’s Ebola vaccine (approved by the European Commission) and to construct its human immunodeficiency virus, respiratory syncytial virus, and Zika vaccine candidates. More than 90,000 individuals have been vaccinated to date using the Janssen AdVac-based platform, according to J&J.

“Johnson & Johnson’s global team of experts has worked tirelessly alongside BARDA and scientific partners to pursue a SARS-CoV-2 vaccine that can help to stop the spread of COVID-19. We greatly appreciate the US government’s confidence in, and support for, our R&D platform and efforts and the scalability of our vaccine technology. We are scaling up production in the US and worldwide to deliver a SARS-CoV-2 vaccine for emergency use,” said Paul Stoffels, MD, vice-chairman of the executive committee and chief scientific officer, Johnson & Johnson, in the press release.

The company is working to ensure broad global access to its COVID-19 vaccine candidate, following approval from regulators.

J&J in $1-Billion Agreement with US Government for 100 Million Doses of Investigational COVID-19 Vaccine

The European Commission (EC) has granted conditional marketing authorization for Rozlytrek (entrectinib), Roche’s tumor-agnostic once-daily oral medicine for treating tumors, in two indications, Roche announced in an Aug. 3, 2020 press release. The drug is indicated for adult and pediatric patients 12 years of age and older with solid tumors expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic, or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor nor have had any satisfactory treatment options. The other indication is for treating adults with ROS1-positive, advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.

The approval is based on results from studies that demonstrated Rozlytrek has durable responses across several NTRK gene fusion-positive solid tumors, including sarcoma, non-small cell lung, salivary mammary analogue secretory carcinoma, secretory and non-secretory breast, thyroid, colorectal, neuroendocrine, pancreatic, ovarian, endometrial carcinoma, cholangiocarcinoma, gastrointestinal cancers, and neuroblastoma as well as ROS1-positive NSCLC.

The European Medicines Agency granted the drug Priority Medicines (PRIME) designation. The PRIME designation was for the use of Rozlytrek in the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumors in patients who have either progressed following prior therapies or who have no acceptable standard therapies. NTRK gene fusions have been identified in a range of solid tumor types and were found to be present in up to 90% of some rare cancer types. In other more common tumors, such as lung and colorectal, the NTRK gene fusion was found in less than 1% of those tumors. ROS1 gene fusions, meanwhile, account for 1%–2% of NSCLC, Roche reported in its press release.

“We are excited to announce the approval of Rozlytrek in Europe for two indications, bringing patients with NTRK and ROS1 gene fusions a new effective treatment even when their cancer has spread to the brain,” said Levi Garraway, MD, PhD, Roche’s chief medical officer and head of Global Product Development, in the press release. “This advance represents another important step forward in cancer care by allowing us to treat certain genetic drivers of cancer irrespective of the location of the tumor within the body. Roche is deeply committed to driving personalized healthcare and addressing the high unmet need in patients around the world with rare cancers.”

The drug was granted accelerated approval in the United States by FDA in August 2019, following receipt of breakthrough therapy designation. In the US, the drug is indicated for adult and pediatric patients 12 years of age and older with solid tumors that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic, or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy. It was also approved for treating adults with ROS1-positive, metastatic NSCLC. In June 2019, Japan’s Ministry of Health, Labor and Welfare (MHLW) also approved Rozlytrek for treating adult and pediatric patients with NTRK fusion-positive, advanced recurrent solid tumors, followed by a later approval in February 2020 for treating ROS1-positive NSCLC. Rozlytrek has also received approvals by health authorities in Australia, Canada, Hong Kong, Israel, New Zealand, South Korea, and Taiwan, according to Roche.

Roche has received approval from the European Commission for Rozlytrek (entrectinib), its newest anti-cancer drug, for two indications.

EC Approves Roche’s Newest Anti-Cancer Drug 

Novilytic, a Purdue Research Park, West Lafayette, IN-based biochemistry analytics company, has been awarded a $1.4-million Phase II Small Business Innovation Research (SBIR) contract by the National Institute of General Medical Sciences, one of the National Institutes of Health (NIH).

The contract will allow Novilytic to continue the research, development, and commercialization of its Proteometer, a new instrument technology being created for process chemists and engineers who need to develop better process quality and control, the company announced in a July 16, 2020 press release. The instrument is designed to test antibody purity in-process.

“The Proteometer represents a truly disruptive technology that will allow process research and manufacturing chemists and engineers to monitor and control antibody growth in process,” said Fred Regnier, chief technology officer and co-founder of Novilytic, and the former J.H. Law Distinguished Professor of Chemistry at Purdue, in the press release. “There is no technology available to do this currently. Novilytic is currently focused on the pharmaceutical bioreactor market that produces monoclonal antibodies, one of the most important biopharmaceuticals used to treat many cancers, diseases, and viruses.”

The company, which is also launching a seed round funding opportunity, will be opening new laboratories and hiring additional scientists in the coming months. Through the support of the Purdue Research Foundation and Purdue Foundry, Novilytic will continue to grow in the West Lafayette area.

“We are very grateful to the NIH and its support of our various developments,” said Paul Dreier, CEO of Novilytic, in the press release. “This marks our sixth straight SBIR grant. Initial grants led to the commercialization of patented medical devices. This award signifies our commitment to developing strong technology and patented instruments here in Indiana.”

The award will help a bioanalytics startup commercialize instrument technology for pharmaceutical antibody manufacturers.

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