Early investment in formulation strategies will maximize the chance of success.

The Earlier the Better in Formulation

Advances in simulation and the development of digital twins.

Computational Fluid Dynamics in Upstream Biopharma Manufacturing

Different methods give different answers when calculating limits for impurities.

Detecting and Determining Quantitation Limits for Impurities

Automatic visual inspection machines and AI highlight inspection deficits.

Visual Inspection: Seeing Room for Improvement?

Despite their promise, alternative drug delivery approaches are complex and must be justified.

Taking an Alternative Approach to Drug Delivery

Traditional statistical process control rules can be relaxed or adjusted to allow charting and evaluation of real-life data. 

Practical SPC Rules to Apply on Pharmaceutical Process Data

Novavax COVID-19 Vaccine Receives EUA in Indonesia

FDA Grants EUA for Pfizer-BioNTech COVID-19 Vaccine Use in Children

Hallie Forcinio is packing editor for Pharmaceutical Technology and Pharmaceutical Technology Europe, editorhal@sbcglobal.net.

With the advent of COVID-19 vaccines that require ultra-cold storage, the demand for shippers with this capability has skyrocketed. One example from CSafe Global, a shipper equipped with double-wall vacuum-insulated panels, provides 10 days of protection at -70 °C and is used by BioNTech. The container can maintain the desired temperature indefinitely with the addition of dry ice as needed. Other features include a custom payload box with a built-in handle to simplify packing and unpacking of vial trays (1).

Another ultra-low temperature (ULT) shipper is being used by Pfizer for its COVID-19 vaccines. Designed by Softbox Systems to protect the vaccines through distribution to storage at point-of-use, the reusable shipper can maintain -90 °C to -60 °C for at least 10 days if unopened. High-performance insulation materials and dry ice ensure long-term ULT control. Based on current guidelines, the Softbox ULT Shipper can be opened twice a day for up to three minutes at a time. This allows clinicians at point-of-use sites to access the vaccine vials required for each day’s immunization clinics without exposing the remaining vaccine in the shipper to ambient temperatures (2).

When correctly managed and topped off with dry ice, the ULT Shipper protects vaccines for more than 30 days. Kevin Valentine, CEO of Softbox Systems, explained in a press release that the company worked with Pfizer during 2020 to develop the ULT shipper. In addition to establishing a fleet of reusable temperature-controlled parcel shippers, Softbox Systems set up two service centers to support ULT shipper refurbishment (2).

A dry-ice-free ULT option, the PC-21 shipper from Thermal Custom Packaging, maintains -21 °C. Reusable, nontoxic phase-change materials help maintain the required temperature, eliminate the need for dry ice, ice in general, or gel packs, and can make many trips. Three sizes of insulated reusable totes can transport between 350 and 2100 vaccine doses at a time (3). This same transport system with phase-change materials designed to maintain 0 °C can be used to store the Moderna vaccine for 30 days or the Pfizer vaccine for five days (4).

A recyclable/compostable cooler from Vericool also offers ULT performance. Designed to hold eight to 16 syringe doses, the shipper maintains temperatures of -70 °C (-94 °F) to -20 °C (-4 °F) for up to 96 hours (5).

Monitoring temperatures through the supply chain plays a vital role in ensuring ULT shippers are performing as expected and no temperature abuse has occurred. The iOn Xtreme Temperature Tag, a smart sensor tag from Cal/Amp, monitors temperatures as low as -270 °C and provides end-to-end supply chain visibility of pharmaceuticals, vaccines, biological materials, and liquid nitrogen. When affixed to an asset or container, the tag captures proximity location and ambient temperature readings at a user-defined logging rate, which is configurable from an intuitive user interface. A proprietary Bluetooth Low Energy signal transmits the data to CalAmp SC iOn gateway devices. The captured data is securely communicated to the Cloud in real-time from the warehouse, during transport, and from the final destination, making the information instantly available to confirm that temperature-sensitive products have been handled properly (6).

1. CSafe Global, “CSafe Global Providing Thermal Protection for COVID-19 Vaccine Shipments from BioNTech Facility,” Press Release, May 5, 2021.

2. Softbox Systems, “Softbox Successfully Supports Pfizer in the Global Cold Chain Distribution of COVID-19 Vaccines,” Press Release, March 10, 2021.

3. Thermal Custom Packaging, “As the Deadly COVID-19 Delta Variant Spreads, State Agencies, School Districts, and Major Hospital Groups Turn to Thermal Custom Packaging (TCP) Totes and Chemical Reactions to Maintain Refrigerated and Frozen Temperatures,” Press Release, Aug. 24, 2021.

4. Thermal Custom Packaging, “With Omicron Variant on the Rise, Thermal Custom Packaging (TCP) is Providing Secure Transportation of COVID Vaccine,” Press Release, Jan. 4, 2022.

5. Vericool, “Vericool Launching Vaccine Recyclable and Compostable Shipping Cooler,” Press Release, Nov. 20, 2020.

6. CalAmp, “CalAmp Releases New iOn Xtreme Temperature Tag to Monitor Pharmaceutical and Biological Shipments,” Press Release, Aug. 19, 2021. 

Articles

Protective external packaging ensures COVID-19 vaccines arrive safely. 

Sustainable Shippers for Ultra-Cold Conditions

Jennifer Markarian is manufacturing editor of Pharmaceutical Technology.

The benefits of digital maturity in pharmaceutical manufacturing were made evident by the COVID-19 pandemic during 2020 and 2021, as the sudden need to develop, manufacture, and distribute treatments and vaccines intersected with travel restrictions, social distancing, and supply chain interruptions. Digital technologies that could meet these new challenges and aid manufacturing scale-up and speed to market, such as automated digital data collection and augmented and virtual reality (AR/VR) remote collaboration tools, were already available and had been adopted by some, but the new demand spurred greater adoption. The need to solve manufacturing challenges gave more companies the incentive to initiate or make further progress on their digital transformation journeys.

“These events directly showed the payoff of information technology (IT)/operational technology (OT) integration achieved over the last several years, but also revealed that we have an opportunity to do much more,” says Dan UpDyke, strategic marketing manager at Rockwell Automation. “The ability for the industry to pivot and quickly bring new therapies to market highlighted the need for flexible, saleable, and connected manufacturing systems. We have already seen an increase in integrating data and recipe management through a manufacturing execution system (MES) and flexible distributed control systems (DCS),” says UpDyke. “These are technologies that enable faster time to market by reducing the efforts to shift to new products.”

“As an industry, we’ve seen we need to be more efficient and we need to be able to monitor and manage processes remotely from a centralized location. People are focused on process intensification and how to better digitize and automate their processes,” says Merrilee Whitney, head of the BioContinuum Platform at MilliporeSigma, the US and Canada life science business of Merck KGaA.

The pandemic created a higher awareness of the need for digitalization, adds Dirk Wollaert, Vertical Market Pharma at Siemens headquarters in Belgium. Digital technologies were key to the success of the rapid development and rollout of the COVID-19 vaccines, facilitating cross-company collaborations even across national borders. “Globalization and industry standardization to facilitate smoother transition from one production plant to another became more important,” he explains.

Another change that accelerated in the past two years was a transition to the cloud for software solutions and data storage, adds Pamela Docherty, Life Sciences Industry Manager at Siemens USA. “The ability to push data from the manufacturing floor to the cloud creates a backbone for digitalization,” she says.

In bio/pharmaceutical manufacturing, the application of “Industry 4.0” techologies, such as digitalization, must be aligned with regulatory requirements, including good manufacturing practices (GMPs). The International Society for Pharmaceutical Engineering (ISPE) has trademarked their initiative as Pharma 4.0, also dubbed the “Smart Factory,” and has developed an operating model, which the Pharma 4.0 special interest group notes goes beyond IT to organizational, process, and resource aspects (1).

“There is a cultural aspect to digitalization because it’s a significant investment that results in changes to the operational structure of a facility; it is beneficial when the digitalization comes from the top,” explains Yvonne Duckworth, automation engineer and Industry 4.0 subject matter expert at the CRB Group, a life sciences engineering and construction company. “We are seeing more often that management is driving the adoption of digitalization in new facilities. It is becoming a standard and expected part of facility design.”

In the past five years, pharma manufacturers have been moving toward digital maturity. Assessed using the BioPhorum Group’s Digital Plant Maturity Model (2), some manufacturers are at level 1 (predigital); some are at level 2 (digital silos and islands of automation); many are at level 3 (connected plants) on their way to level 4 (predictive plant with real-time predictive analysis), and others want to adopt some aspects of level 5 (autonomous, adaptive plant), says Duckworth.

Although in past years, digitalization primarily meant moving away from paper-based systems to digital reports that were then printed to electronic or physical paper, a new paradigm enables a jump from Pharma 2.0 paper-based systems to the Pharma 4.0 operator-centric connected plant, said Gilad Langer, industry practice lead at Tulip, which supplies a cloud-based front-line operations platform (3). “This paradigm shift changes the culture and the processes, but doesn’t significantly change the operator’s workflow. Instead, digital apps are built to bring the physical world to the digital world with sensors and cameras, with digital output as the evidence. Data from equipment and human activities are collected via the industrial Internet of things (IIoT),” explained Langer.

To read the full article, which was published in the December issue of Pharmaceutical Technology, go to 

www.PharmTech.com/view/digitalization-moves-forward-in-pharma-equipment-and-processes.

The benefits of digitalization in bio/pharmaceutical manufacturing were highlighted by speed and successful integration during the COVID-19 pandemic.

Pandemic Drives Digital Transformation 

Shanghai Fosun Pharmaceutical (Fosun Pharma), a China-based healthcare group, and Insilico Medicine, a US-based artificial intelligence (AI)-driven drug discovery and development company, announced on Jan. 11, 2022 that they have entered into a collaboration agreement to advance the discovery and development of drugs targeting a number of different targets globally using AI technology.

The partnership includes an AI-driven drug discovery R&D collaboration on four biological targets as well as the co-development of Insilico’s glutaminyl-peptide cyclotransferase-like (QPCTL) program. Under the agreement, Insilico will receive a total upfront payment of $13 million for the four R&D collaboration projects and the co-development of the QPCTL program. Insilico will also receive potential milestone-based payments and share commercialization profits from the QPCTL program. Fosun Pharma will also make an equity investment in Insilico.

Through the collaboration, Insilico will combine its end-to-end AI-driven drug discovery platforms with Fosun Pharma’s clinical development and commercial expertise. Their goal is to discover and develop a portfolio of novel therapeutics. According to the agreement, Insilico will take responsibility for delivering a preclinical candidate for the QPCTL program and advancing it to the investigational new drug (IND) stage (via its R&D team). After that, Fosun Pharma will conduct human clinical studies and co-develop the candidate globally. Fosun Pharma’s R&D team will also nominate four therapeutic targets to be assessed by Insilico’s AI platform and R&D team in parallel programs.

In addition, as part of the collaboration, Fosun Pharma will gain access to Insilico’s PandaOmics and Chemistry42 platforms to advance its own internal AI-powered discovery and development efforts.

“We are pleased to enter into strategic collaboration with Insilico. Fosun Pharma is committed to promoting innovative R&D and is oriented towards fulfilling unmet clinical needs and improving products’ accessibility. We look forward to working with Insilico to leverage the technological and clinical development strengths of both companies, jointly improving the efficiency of innovative drug R&D and benefiting more patients worldwide," said Yifang Wu, chairman and CEO of Fosun Pharma, in a company press release.

“In partnering with Fosun Pharma, a leading pharmaceutical company, we begin a new era of AI-powered end-to-end drug discovery and development as human-machine collaboration becoming the new normal in precision drug discovery and development. We previously demonstrated that AI can be used to discover novel targets and generate novel molecules that can be tested in humans in record time. Now, we are partnering with one of the leading scientific teams in the pharmaceutical industry to take this technology to the next level for the benefit of patients worldwide,” said Alex Zhavoronkov, founder and CEO of Insilico Medicine, in the press release.

Fosun Pharma and Insilico Medicine will collaborate on AI-driven drug discovery and development of product candidates targeting multiple disease targets.

Fosun Pharma and Insilico Medicine Partner on Drug Discovery and Development Using Artificial Intelligence

According to the company, Lumykras (Sotorasib) is the first targeted therapy approved in the European Union for patients with the 

Amgen announced on Jan. 9, 2022, that the European Commission (EC) granted conditional marketing authorization for the company’s first-in-class KRASG12C inhibitor, LUMYKRAS (sotorasib), for the treatment of advanced non-small cell lung cancer (NSCLC) with 

 G12C mutation in patients that have progressed after one prior line of systemic therapy. The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) 

recommended conditional authorization in November 2021

According to an Amgen press release, the conditional authorization was based on results from a Phase II CodeBreaK 100 clinical trial in NSCLC. “LUMYKRAS 960 mg, administered orally once-daily, demonstrated an objective response rate of 37.1% (95% CI: 28.6-46.2) and a median duration of response (DoR) of 11.1 months. The most common adverse reactions were diarrhea (34%), nausea (25%), and fatigue (21%). The most common severe (grade ≥ 3) adverse reactions were increased alanine aminotransferase level (ALT; 5%), increased aspartate aminotransferase (AST; 4%), and diarrhea (4%),” Amgen stated in the press release.

"The approval of LUMYKRAS, the first and only targeted therapy for 

 G12C-mutated NSCLC with proven efficacy, has the potential to transform treatment outcomes for people in the European Union living with this notoriously difficult-to-treat cancer," said David M. Reese, executive vice president of Research and Development at Amgen, in the press release. "Amgen's landmark scientific discovery allowed investigators to advance the first KRASG12C inhibitor into the clinic, and we look forward to bringing this critical innovation to more patients across the globe."

European Commission Approves Lumykras (Sotorasib) to Treat KRAS G12C-Mutated Advanced Non-Small Cell Lung Cancer

The Janssen Pharmaceutical Companies of Johnson & Johnson announced on Dec. 22, 2021, that the United Kingdom’s National Institute for Health and Care Excellence (NICE) has recommended Darzalex (daratumumab) in combination with Velcade (bortezomib), thalidomide and dexamethasone (DVTd), to treat adults with multiple myeloma, when an autologous stem cell transplant (ASCT) is suitable. Eligible patients in England and Wales will be able to access DVTd through the National Health Service (NHS).

According to a press release, NICE’s recommendation was based on “data from the Phase [III] CASSIOPEIA study (Part 1) with a median follow-up of 18.8 months which compared DVTd to standard of care (bortezomib, thalidomide and dexamethasone [VTd] alone) as induction and consolidation therapy in newly diagnosed multiple myeloma patients eligible for ASCT.”

“Multiple myeloma is a relapsing and remitting cancer, and while existing therapies can control it, these patients are in need of effective and well-tolerated treatment options that are given as early as possible in the treatment pathway to elicit a deep response and improve outcomes,” said Karthik Ramasamy, consultant haematologist at Oxford University Hospitals NHS Foundation Trust and lead clinician for Myeloma for the Thames Valley Cancer Network, in the press release. “A front-line treatment option such as daratumumab in combination with VTd will give clinicians an effective regimen to produce deeper and longer remissions for newly diagnosed myeloma patients compared to VTd alone.”

“We are delighted that people with multiple myeloma in England and Wales will now be able to access DVTd on the NHS,” said Amanda Cunnington, director of Health Economics, Market Access, Reimbursement and Health Affairs, Janssen-Cilag Limited, in the release. “[This] decision means access will now be equal across the UK and we’re proud to have worked collaboratively with stakeholders to achieve this outcome. Importantly, our work in multiple myeloma doesn’t stop here, and we remain committed to furthering advances in science and evolving innovation in blood cancers.”

The UK’s National Institute of Health and Care Excellence has recommended the use of Janssen’s Darzalex (daratumumab) in combination with Velcade (bortezomib), thalidomide and dexamethasone (DVTd) to treat adults with multiple myeloma.

NICE Recommends Darzalex in Combination with Velcade to Treat Multiple Myeloma

: The conference will consider key developments in the transdermal drug delivery field, including the innovations in microneedle technology for a COVID-19 vaccine and opportunities for development in cancer vaccine delivery, advances in microarray patches, and microneedle-based diagnostics.

Key regulatory updates including guidance on classification of microneedle devices and considerations for ensuring quality will be presented by regulatory experts for a comprehensive outlook of this exciting and ever-growing field, and the importance of considering human factors in order to enhance the user experience will be presented by industry experts.

http://transdermal-microneedle-delivery.co.uk/pharmatechWL

Events

SMI’s Transdermal and Microneedle Drug Delivery Conference will discuss recent developments in transdermal drug delivery.

SMI’s Transdermal and Microneedle Drug Delivery Conference: January 24-25, 2022

Bristol Myers Squibb announced on Jan. 10, 2022 that it has entered into a research collaboration and license agreement with Century Therapeutics, a US-based biotechnology company, to develop and commercialize up to four induced pluripotent stem cell (iPSC)-derived, engineered natural killer cell (iNK) and/or T cell (iT) programs for hematologic malignancies and solid tumors.

The first two programs include one in acute myeloid leukemia (AML) and another in multiple myeloma. These programs could incorporate either the iNK or a gamma delta iT platform. Under the agreement, Bristol Myers Squibb has the option to add two additional programs, which can be nominated depending on certain conditions being met in the agreement.

Also under the agreement, Century will be responsible for development candidate discovery and preclinical development activities. Afterwards, Bristol Myers Squibb will be responsible for clinical development and commercialization activities subject to Century’s co-promotion rights on certain programs. Century will receive a $100 million upfront payment, and Bristol Myers Squibb will make a $50 million equity investment in Century’s common stock at $23.14 per share. Furthermore, Century will receive reimbursement of certain preclinical development costs for development candidates licensed by Bristol Myers Squibb. Century is also eligible for additional payments for future program initiations and development, regulatory, and commercial milestone payments totaling more than $3 billion across the four potential programs.

In addition, Century will also receive tiered royalties as a percentage of global net sales in the high-single to low-double digits. It may also elect to co-promote the AML program and one of the additional programs in the United States for no exercise fee. This latter would also trigger enhanced US royalties.

As part of this transaction with Bristol Myers Squibb, Century has amended its agreements with FUJIFILM Cellular Dynamics for Japanese development and commercialization rights for the products in these development programs.

“We are pleased to partner with Bristol Myers Squibb, a global leader in oncology and hematology, to further expand our pipeline of iPSC-derived cell therapy products for challenging hematological and solid tumor malignancies,” said Lalo Flores, CEO, Century Therapeutics, in a company press release. “Bristol Myers Squibb is an ideal partner for us because they bring extensive clinical development and scientific expertise in cell therapy that will increase the probability of technical success of these programs. Additionally, this collaboration will enable deployment of our next-generation iPSC platform to develop products targeting malignancies that are difficult for biotech companies to tackle on their own.”

“The collaboration with Century Therapeutics is an important part of our investment strategy in next-generation cell therapies for hematologic and solid tumors,” said Rupert Vessey, executive vice-president and president, Research & Early Development, Bristol Myers Squibb, in the press release. “Century’s iPSC-based gamma delta T and NK cell platforms show promise and are complementary to Bristol Myers Squibb’s existing cell therapy technologies. We look forward to exploring the full potential of the iPSC approach to develop potentially best-in-class allogeneic cell therapies to help patients with hematologic and solid tumor malignancies.”

The collaboration between Bristol Myers Squibb and Century Therapeutics will combine Century’s iPSC-derived allogeneic cell therapy platform with Bristol Myers Squibb’s expertise in cell therapy and oncology drug development.

Bristol Myers Squibb and Century Therapeutics to Collaborate on Developing iPSC-derived Allogeneic Cell Therapies

Fujifilm Diosynth Biotechnologies is expanding its BioProcess Innovation Center in Research Triangle Park (RTP), N.C., the company announced in a Jan. 5, 2022 press release.

The project, which will feature an additional 89,000 ft

 of laboratory space equipped with state-of-the-art analytical instrumentation, high throughput bioprocessing equipment, and automation technologies, is expected to double the company’s capacity to support process characterization programs and complements the enhanced capabilities at its UK facility. This expansion will also allow Fujifilm Diosynth Biotechnologies to further support its partners in guiding clinical process development that can create more robust commercial processes. 

The expanded space is expected to be operational by mid-2024, which is also when approximately 145 new jobs are anticipated to open up, many of those positions being for researchers and scientists.

“ … We are delighted to be adding this additional capacity to support our growing pipeline of customers,” notes Christine Vannais, chief operating officer, Fujifilm Diosynth Biotechnologies, RTP, North Carolina, in a company press release. “The cutting-edge laboratory equipment and automation tools, combined with the deep technical expertise of our scientific community, will allow us to better serve our partners to rapidly generate and assess data to understand complex molecules, along with the processes used in their manufacture.”

Fujifilm Diosynth Biotechnologies' 89,000 square-foot expansion of its BioProcess Innovation Center in Research Triangle Park, N.C., will double its capacity to support process characterization.

Fujifilm Grows Lab Space at North Carolina Facility

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

In a highly unusual decision for a therapy approved by FDA, the Centers for Medicare and Medicaid Services (CMS) 

 of Biogen’s new and controversial Alzheimer’s treatment Aduhelm (aducanumab). The CMS National Coverage Determination (NCD) did this by 

applying its Coverage with Evidence Development (CED) requirement to the drug

, utilizing a process that has been directed primarily in recent years to a limited number of approved medical products, mainly medical devices and diagnostics. If the proposal is finalized, only patients able to enroll in postapproval trials would have access to the drug.

The aim of the NCD process is to gather further evidence to demonstrate the drug’s potential for improving the health of patients suffering mild cognitive impairment due to Alzheimer’s disease. The CMS policy will authorize access to the drug only to those individuals able to enroll in a clinical trial, most taking place at academic research institutes that CMS will identify and list on its website. Under the accelerated approval granted Aduhelm by FDA’s Center for Drug Evaluation and Research (CDER) in June 2021, Biogen is required to conduct at least one Phase IV trial to demonstrate that the drug’s ability to reduce amyloid in the brain has a broader benefit for patients’ cognitive ability, and that the drug’s serious side effects are limited. Biogen objected loudly to the CMS proposal, noting that it may take years to design and launch postapproval studies, and that such trials will enroll only a limited number of patients. CMS also indicates that its CED requirement will apply to additional monoclonal antibodies targeting amyloid beta in Alzheimer’s disease.

Aduhelm came to market last year amidst heightened controversy over its approval despite limited evidence of efficacy. The debate turned to outrage when Biogen set the price for the new treatment at $56,000 a year. At that level, Medicare spending on the drug was projected to far exceed any other drug if even just a small portion of some 6 million US Alzheimer’s patients sought treatment. In December 2021, after a year of dismal uptake of the drug, Biogen cut its launch price in half to $28,200 a year in an effort to boost prescribing—and avoid a negative NCD from CMS. However, even that reduced cost continued to promise hefty outlays for Medicare. Many leading health centers and physicians said they still would not prescribe the drug due to its limited evidence of efficacy, known side effects and continued too-high cost. The Institute for Clinical and Economic Review (ICER) calculated that Aduhelm would be cost-effective if priced at $3000 to $8000 a year.

In making national coverage decisions, CMS is supposed to evaluate whether a medical product or process is “reasonable and necessary” and not bring cost into the equation. But the fact that a very high number of Medicare patients are potential users of the new drug made that difficult.Before Biogen cut its price, CMS had announced a whopping 15% boost in premiums for the Medicare Part B program, which administers injectables such as Aduhelm. CMS had explained that about half of the premium increase was designed to protect the program against high spending on the new Alzheimer’s therapy. Following Biogen’s cost reduction, Health & Human Services (HHS) secretary Xavier Becerra 

said CMS would reassess the scope of the premium hike

, although the uncertain financial health of the Medicare Trust Fund may deter any significant readjustment in rates.

CMS emphasizes that its CED decision arises from extensive review over the past six months of all relevant published evidence and feedback from stakeholders. The agency opted for the CED process to gain further evidence on whether this new therapy provides any improvement or relief from the effects of Alzheimer’s disease. CMS will accept further public comments on this proposal for 30 days and announce a final coverage decision by April 11, 2022. Alzheimer’s disease groups have called loudly for Medicare coverage of Aduhelm as the only available treatment for the widespread debilitating condition.

It will be interesting to see how the CMS proposal affects other biopharma companies that are testing their own Alzheimer’s therapies. Eli Lilly is conducting clinical trials that directly compare its donanemab to Aduhelm, while Eisai and Roche are moving forward with additional treatments. These and other sponsors now will have to calculate the impact of bringing new drugs to market that would be subject to CED requirements.

Meanwhile, the scientific and medical community continues to criticize the Aduhelm approval. The European Medicines Agency (EMA) recently recommended against approving the drug, and objections have been raised in Canada to a pending review. CMS has navigated its process to greatly limit Aduhelm prescribing and its outlays for the drug, but the debate is far from over.

The Centers for Medicare and Medicaid Services took action to limit prescribing and use of Biogen’s new and controversial Alzheimer’s treatment Aduhelm (aducanumab).

Medicare Limits Aduhelm Coverage to Patients in Clinical Trials

Merck KGaA, Darmstadt, Germany, has agreed to acquire Exelead, a biopharmaceutical contract development and manufacturing organization (CDMO), for approximately $780 million in cash, according to a Jan. 6, 2022 press release. Exelead specializes in complex injectable formulations, including lipid nanoparticle (LNP)-based drug delivery technology and fill/finish. Exelead’s headquarters and operations are located in Indianapolis.

“Novel modalities, particularly mRNA, present a highly attractive business opportunity as pharma and biotech pipelines are increasingly building on them beyond COVID-19. The acquisition of Exelead will further enable us to capture the significant potential of the fast-growing market for mRNA therapies by providing leading CDMO services to our customers,” said Belén Garijo, chair of the executive board and CEO of Merck KGaA, in the press release.

“Exelead’s capabilities and expertise will strengthen our CDMO mRNA offering. We are excited to work with Exelead’s experienced team. Together, we will provide our customers a unique and truly integrated offering across the mRNA manufacturing process. This will significantly decrease supply chain complexity and enhance speed-to-market to ultimately accelerate access to life-enhancing therapeutics for patients worldwide,” added Matthias Heinzel, member of the executive board of Merck KGaA and CEO Life Science, in the press release.

Merck intends to continue to invest in mRNA as a modality and will scale up this technology at Exelead’s existing site in Indianapolis, according to the press release. The transaction is expected to close in the first quarter of 2022 and is subject to regulatory clearances as well as the satisfaction of other customary closing conditions.

The agreeement will add to Merck KGaA’s LNP and mRNA capabilities. 