Overcoming Poor Solubility Through Accelerated Dissolution

Drug Solutions Podcast

The nitrosamines contamination in “sartan” drugs emphasized the importance of risk assessment in API ingredients manufacturing.

What Goes Wrong When API Quality is Compromised?

Adapting to the increasing complexity and poor solubility and bioavailability of molecules in the pipeline.

Adapting to Solubility/Bioavailability Challenges

Addressing key challenges in building commercial-scale mRNA production facilities.

Engineering Challenges in Commercial mRNA Vaccine Manufacturing

Successful digital transformation in biopharma requires an integrated approach to the data lifecycle.

An Integrated Approach to the Data Lifecycle

Automation of pharmaceutical packaging saves costs and time, say contract packagers.

Automating Packaging of Bio/Pharmaceuticals

Development and Scalability of ADCs and CGTs

Drug Digest

Moderna announced on August 9, 2022 an amendment to its agreement with the European Commission (EC) to convert contractually agreed doses of Moderna’s COVID-19 vaccine to its Omicron-containing bivalent vaccines for supply in 2022, pending regulatory approval. The EC has also agreed to purchase an additional 15 million doses of the Omicron-containing vaccine booster candidates from Moderna.

Under the agreement, all remaining contractually agreed doses of Moderna’s SPIKEVAX will be converted to Omicron-containing bivalent vaccines, pending approval by the European Medicines Agency (EMA). Contractually scheduled doses in July and August of SPIKEVAX will be deferred to later in 2022.

"The European Commission and Moderna have been steadfast partners in the fight against the COVID-19 pandemic. This agreement highlights the EC's trust in our mRNA platform and next-generation bivalent COVID-19 vaccines," said Stéphane Bancel, CEO of Moderna, in a press release. "Participating member states will now have access to Omicron-containing vaccine booster candidates, and protection against COVID-19, heading into the winter season."

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Moderna and the European Commission have amended their agreement to convert contractually agreed doses of Moderna’s COVID-19 vaccine to the company’s Omicron-containing bivalent vaccines for supply in 2022.

Moderna and European Commission Amend COVID-19 Vaccine Agreement

Roche announced on August 12, 2022 that FDA has approved a supplemental New Drug Application for Xofluza (baloxavir marboxil) for the treatment of acute uncomplicated influenza in otherwise healthy children aged five to less than 12 who have been symptomatic for no more than 48 hours. FDA also approved the treatment for prevention of influenza in children of this age group following contact with someone with influenza.

According to a company press release, baloxavir marboxil is the first single-dose oral influenza medicine approved in the US for children in this age group. Prior to this announcement, the medicine was also approved for use in people aged 12 and older who are otherwise healthy or at high risk of developing influenza-related complications.

“Despite the ongoing COVID-19 pandemic, influenza continues to be a threat to public health, and effective influenza antivirals remain critical to alleviating the burden on healthcare systems,” said Levi Garraway, chief medical officer and head of Global Product Development. Roche, in the press release. “[Baloxavir marboxil] has proven to be an important tool in fighting and preventing influenza in adults as well as adolescents, and we are pleased to now offer households and younger children our single-dose oral treatment.”

Roche announced that FDA has approved Roche’s Xofluza (baloxavir marboxil) to treat influenza in children aged five years and older.

FDA Approves Roche’s Influenza Treatment for Use in Young Children

FDA approved Daiichi Sankyo’s Enhertu (fam-trastuzumab-deruxtecan-nxki), an IV infusion for the treatment of patients with unresectable or metastatic HER2-low breast cancer. Fam-trastuzumab-deruxtecan-nxki is the first therapy that specifically targets the HER2-low breast cancer subtype, a newly defined subset of HER02 negative breast cancer that describes breast cancers that have some HER2 proteins on the cell surface, but not enough to be classified as HER2-positive.

FDA stated in an August 5, 2022 press release that the approval is based on the findings ofDESTINY-Breast04, a randomized, multicenter, open label clinical trial that enrolled 557 adult patients with unresectable or metastatic HER2-low breast cancer. 373 randomly received fam-trastuzumab-deruxtecan-nxki, while 184 received the physician’s choice of chemotherapy — eribulin, capecitabine, gemcitabine, nab paclitaxel, or paclitaxel. The results demonstrated improvement in both progression-free survival and overall survival in patients with unresectable or metastatic HER-2 low breast cancer.

“Today’s approval highlights the FDA’s commitment to be at the forefront of scientific advances, making targeted cancer treatment options available for more patients,” said Richard Pazdur, director of FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in FDA’s Center for Drug Evaluation and Research, in the press release. “Having therapies that are specially tailored to each patient’s cancer subtype is a priority to ensure access to safe and innovative treatments.”

Daiichi Sankyo’s Enhertu (fam-trastuzumab-deruxtecan-nxki) is the first targeted therapy for HER2-low breast cancer.

FDA Approves First Targeted Therapy for HER2-Low Breast Cancer

Merck, known as MSD outside of the United States and Canada, and Cervance, a Boston biotechnology startup, announced that they have entered a strategic research collaboration on August 9, 2022. The deal will see the companies work together to identify novel targets for Alzheimer’s disease via Cerevance’s Nuclear Enriched Transcript Sort sequencing (NETSseq) platform.

NETSseq isolates cell populations from human brain tissue with the aim of exposing biological pathways underlying neurodegenerative and psychiatric diseases that may be difficult to see in animal models or differentiated human stem cells. According to a company press release, Cerevance will receive a $25 million upfront payment from Merck for the rights to use the platform. Cerevance is also eligible to receive development and commercial milestone payments, totaling approximately $1.1 billion, as well as additional royalties on sales of approved products derived from the collaboration.

“The establishment of this collaboration with Merck, which comes on the heels of our positive Phase 2 data for CVN424 in patients with Parkinson’s disease, represents a significant milestone for Cerevance and reinforces the promise of our NETSseq technology platform,” said Mark Carlton, chief scientific officer, Cerevance, in the release. “We believe we are well-positioned to identify novel targets for neurodegenerative diseases and look forward to collaborating with Merck to potentially bring forward transformative therapeutics for patients with Alzheimer’s disease.”

“Progress in our understanding of the biology of neurodegenerative diseases continues to reveal compelling new mechanisms for potential therapeutic intervention,” said Jason M. Uslaner, vice-president and head of neuroscience discovery, Merck Research Laboratories, in the release. “We look forward to advancing the discovery program as well as taking advantage of the NETSseq platform to identify new targets with the team at Cerevance.”

Merck, known as MSD outside of the United States and Canada, will collaborate with Cerevance to identify novel targets for Alzheimer’s disease.

Merck Enters Alzheimer’s Collaboration with Cerevance

B.S Sathya Durga is Director at Acute Market Reports.

India, the home of more than 10,000 pharmaceutical manufacturing sites, is a major player in the global pharmaceutical market. The country manufactures the majority of the world's active ingredients for generic drugs, is the source of more than 90% of the medications used by Americans, and accounts for more than 60% of global vaccine production, according to data from US Pharmacopeia.

Consequently, India has an ambitious vision: to grow its pharma business to a value of $130 billion by 2030. According to a report from 

, the Indian pharmaceutical business was worth $42 billion in 2020 and is set to grow at a compound annual growth rate of 12% from 2020 to 2030. However, while the Indian pharmaceutical industry is the third largest in terms of volume, it ranks at just fourteenth in terms of value.

To enable rapid growth, India must advance its value proposition amidst intense cost pressures and competition. To stimulate the anticipated growth, it is evident that India needs to undergo a significant transition from generic drug producer to a producer of novel molecules and biosimilars through rigorous R&D initiatives.

Modern technologies are critical in facilitating advancement of India’s pharmaceutical manufacturing industry, as they can enable many crucial process improvements:

Virtual product design allows products to be produced, tested, or assessed virtually without physical prototypes, minimizing research time.

Robust tracking systems automatically alter production to reduce logistics failures.

Intelligent sensors and a connected value chain enable data interchange from design to production and supplier/customer integration.

Autonomous robots provide flexible and adaptive production lines for many models and small customized lots, improving performance.

Predictive maintenance links wirelessly to the cloud for big data and analytics, reducing downtime and improving maintenance.

The organizations that are most likely to have a competitive advantage in the Indian pharma manufacturing market are those who continuously adopt new technology, find ways to harness the technology, and promote business integration. Consequently, significant advancement is predicated on modernization of the complete pharmaceutical manufacturing process.

Technology First Approach – The Need of the Hour

Indian pharmaceutical companies are prioritizing technology to maintain and enhance their market position. All new pharma plants must meet standards set by FDA, World Health Organization, and Pharmaceutical Inspection Co-operation Scheme.

Similarly, an increasing number of Indian pharmaceutical companies are deploying cloud computing, as well as technologies like artificial intelligence/machine learning (AI/ML) and robotic process automation (RPA). This allows them to modernize supply chain processes, extract better insights from data, conduct modeling/simulations more quickly, accelerate the drug development process, and save significant time in drug commercialization.

As a result of the COVID-19 pandemic, Indian companies have adapted to the speed of global digital transformation adoption and increased supply chain efficiencies. Information Technology (IT) companies have been offering different subscription models to the pharma industry that best suit their payment structure. For instance, the “pay as you use '' model charges companies based on usage, making it ideal for expenses like utility bills.

Pharma 4.0 allows pharma businesses to leverage the internet of things (IoT), Cognitive Science, AI/ML, blockchain, and RPA in tandem, utilizing the digital cloud as a foundation. This helps pharma companies enhance distribution and supply chain management by accelerating production and reducing errors. Currently, a medium-sized IT company in India enables more than 150 to 200 pharmaceutical companies to modernize the pharma manufacturing process at some level.

Shifting Priorities to Create Smart Factories

The production capabilities of firms need to be increased in order to create more value-based pharma products. Existing operations in India need to be automated and digitized so that the companies can adhere to the appropriate standards and maintain precise control over the product's quality.

The front-end priority has always prevented Indian companies from focusing on shop-floor technologies, but upgrades to these technologies are increasingly becoming more global. The shop floor is undergoing transformation as a result of developments in the IoT, AI/ML algorithms, 3D printing, machine vision, advanced physical robotics, and parametric optimization.

Development of integrated production capabilities would provide Indian businesses, industries, and the country as a whole with a significant and long-lasting competitive advantage. Existing process technologies need to be scaled up for industrial application so that prices can be reduced. For instance, the University of Calicut discovered a promising method of producing penicillin from wasted fruit by using solid state fermentation rather than submerged fermentation technology. If that technologies like this could be enabled on a widespread scale, it could prove critical to widespread process improvements; the pharmaceutical industry in India must evaluate smart factory developments.

The Indian government has been actively partnering with pharma companies and has been allotting considerable funds for the construction of new pharma facilities, pharma research, healthcare schemes, and so on. These initiatives open new doors for the acceptance of technologies to enhance production efficiency like never before.

However, while technologies such as cloud AI are extensively deployed in the U.S. and Europe, in India modernization of pharma manufacturing is still in its infancy. Companies are finding use cases in many commercial operations and manual procedures to eliminate human interaction and improve accuracy.

As the labor costs in India are lower than in other countries, cost sensitivity must be considered a prime factor. Pharma companies are beginning to use AI and ML, but it's still in the proof-of-concept stage. India is only starting to utilize blockchain for transparent data sharing between contractors and suppliers. While skill and labor aren't a significant issue in India, unstable prices and policies impede sector expansion.

With the current pace and ambitions, active government involvement, and strategic collaborations, it is anticipated that in the coming decade India will grow to adopt advanced modernization technologies in the pharma manufacturing segment to be at par with the developed economies.

Guest contributor B.S. Sathya Durga discusses the importance of modernizing India's pharmaceutical manufacturing industry.

Modernization of India’s Pharma Manufacturing Industry: “Leader” or “Laggard”

FDA’s Center for Drug Evaluation and Research (CDER) Small Business and Industry Assistance (SBIA) is hosting a three half-day virtual conference from August 16–18, 2022. The conference is in collaboration with the Promoting the Quality of Medicines Plus (PQM+) program, which is funded by the US Agency for International Development (USAID) and led by the United States Pharmacopeial Convention (USP).

The event is intended to help National Medicines Regulatory Authorities (NMRA) in low-and-middle income countries (LMICs) gain a better understanding of FDA’s role in international regulatory harmonization, USP and USAID’s PQM+ program’s role in supporting the strengthening of regulatory systems in LMICs, and more. Topics being covered include FDA drug approval pathways and FDA review of drug applications (new and generic drugs), specifically new TB medicines, FDA review of stability testing, bioequivalenceand post-marketing changes, nitrosamines impurities, and more.

Keynote speakers include FDA’s Janet Woodcock, MD, Principal Deputy Commissioner - Office of The Commissioner; USP CEO Ronald T. Piervincenzi, PhD; USAID’s Dr. Atul Gawande, Assistant Administrator for Global Health; WHO’s Tereza Kasaeva, MD, PhD, Director Global TB Programme; and Rogerio Gaspar, PhD Director of Regulation and Prequalification .

The event is virtual, and registration is free.

FDA’s CDER SBIA is hosting a three-day virtual conference regarding regulatory best practices for global access to medicines. 

FDA to Host Multi-Day Global Access Virtual Conference

Pfizer and Global Blood Therapeutics (GBT), a biopharmaceutical company specializing in sickle cell disease (SCD) treatment, announced on Aug. 8, 2022 a definitive agreement under which Pfizer will purchase all outstanding shares of GBT at $68.50 (totaling approximately $5.4 billion). This purchase will grant Pfizer the rights to GBT’s existing Oxbryta (voxelotor) treatment, as well as other treatments in development.

Voxelotor is an oral, once-daily therapy for patients with SCD that increases hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, voxelator inhibits sickle hemoglobin polymerization and the resultant sickling and destruction of red blood cells that leads to hemolysis and hemolytic anemia. Generating net sales of approximately $195 million in 2021, the treatment is currently approved in the United States, European Union, United Aram Emirates, Oman, and Great Britain.

GBT’s pipeline includes two key treatments that received orphan drug and rare pediatric disease designations from FDA. According to a company press release, if approved, GBT’s SCD treatments could achieve combined worldwide peak sales of more than $3 billion.

GBT021601 (GBT601), an oral, once-daily, next-generation sickle hemoglobin polymerization inhibitor in the Phase II portion of a Phase II/III clinical study. GBT601 is designed to improve both hemolysis and frequency of vaso-occlusive crisis (VOC).

Inclacumab is a fully human monoclonal antibody that targets P-selectin. It is currently being evaluated in two Phase III clinical trials as a quarterly treatment to reduce the frequency of VOCs, as well as the hospital readmission rates resulting from VOCs.

“Sickle cell disease is the most common inherited blood disorder, and it disproportionately affects people of African descent. We are excited to welcome GBT colleagues into Pfizer and to work together to transform the lives of patients, as we have long sought to address the needs of this underserved community,” said Albert Bourla, chairman and CEO, Pfizer, in the release. “The deep market knowledge and scientific and clinical capabilities we have built over three decades in rare hematology will enable us to accelerate innovation for the sickle cell disease community and bring these treatments to patients as quickly as possible.”

“Today is an exciting milestone that accelerates GBT’s mission to discover, develop and deliver life-changing treatments that provide hope to underserved patient communities,” said Ted W. Love, president and CEO, GBT, in the release. “Pfizer will broaden and amplify our impact for patients and further propel much-needed innovation and resources for the care of people with sickle cell disease and other rare diseases, including populations in limited-resource countries. We look forward to working together with Pfizer to serve our communities and advance our shared goal of improving health equity and expanding access to life-changing treatments to create a healthier future for all.”

Pfizer’s $5.4 billion acquisition of Global Blood Therapeutics is expected to strengthen its sickle cell disease portfolio.

Pfizer to Acquire Global Blood Therapeutics for $5.4 Billion

Sartorius announced that it has agreed to purchase Alubmedix through its French-listed subgroup Sartorius Stedim Biotech for £415 million (US$429 million) on Aug. 8, 2022. Albumedix is a provider of recombinant human albumin, which is used in various applications in the biopharmaceutical industry, such as an animal-free additive to cell culture media and for the stabilization of vaccines and viral therapies. The purchase is expected to close before the end of the third quarter of 2022.

According to a company press release, Albumedix will join Sartorius' Bioprocess Solutions Division. Its existing 72,000-ft2 site in Nottingham, UK, will be established as a center of excellence for innovation and good manufacturing practice-compliant production of raw materials.

“Albumedix will be an important addition to Sartorius’ advanced therapy solutions, particularly regarding our cell culture media business, as it will enable us to strengthen our position as a relevant supplier of innovative chemically defined media and critical ancillary materials,” said René Fáber, member of the executive board for the Bioprocess Solutions Division of Sartorius, in the press release. “This market offers high growth potential due to the increasing regulatory requirements as well as rising demand for the use of recombinant human albumin in near-patient applications. Albumedix will also add important formulation excipients to our vaccine production solutions, allowing us to expand our existing customer relationships and forge new ones.”

“We are delighted to be joining forces with Sartorius and look forward to accelerating our ambitious growth plans in delivering critical solutions to our global customers,” said Jonas S. Møller, CEO of Albumedix, in the release. “We have been highly impressed with Sartorius’ knowledge and capabilities in the bioprocessing markets, and we are excited to join this purposeful journey. We believe Sartorius will bring tremendous value in strengthening our market reach and broadening our innovation capacity, as well as significantly scaling up our existing platform.”

Sartorius’ £415 million (US$429 million) acquisition of Albumedix is intended to bolster its portfolio with recombinant albumin-based solutions.

Sartorius to Acquire Albumedix for £415 Million

Catalent announced on August 9, 2022 that it has reached an agreement to acquire Metrics Contract Services, a full-service specialty contract development and manufacturing organization (CDMO), for $475 million from Mayne Pharma Group Limited.

Catalent will strengthen its capabilities in integrated oral solid formulation development, manufacturing, and packaging, as well as expand its capacity to handle highly potent compounds upon the completion of the acquisition.

The acquisition will also include Metrics’ 333,000-square-foot facility located in Greenville, NC. The facility features comprehensive capabilities to accelerate and de-risk customer programs from early development through commercial launch through a streamlines one-site solution.

“This acquisition will further expand Catalent’s ability to meet our customers’ expectations in fast-growing areas of the business and patient need. The experienced team and consistently improved, state-of-the-art facility in Greenville will provide Catalent’s customers with immediate, fit-for-scale capacity for in-demand highly potent drugs and other oral solid small-to-mid-size batch needs. This capacity is particularly important for customers with R&D pipelines featuring accelerated, orphan, and rare disease programs for oncology and other important therapeutic areas,” said Dr. Aris Gennadios, group president of Catalent’s Pharma & Consumer Health segment, in a press release.

“Over the past several years, Metrics has undergone a period of transformational change to expand its footprint and service offering, becoming a global end-to-end novel oral solid CDMO. Catalent, a global leader in advanced drug development and manufacturing, is well-positioned to continue to invest in and accelerate the growth of Metrics and we believe this transaction will be extremely positive for our Greenville team and customers,” said Scott Richards, CEO of Mayne Pharma.
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Catalent will acquire Metrics Contract Services for $475 million to expand high-potent capabilities and oral development and manufacturing capacity.

Catalent to Acquire Metrics Contract Services for $475 Million

Coherus BioSciences, a biopharmaceutical company, announced that FDA approved Cimerli (ranibizumab-eqrn) as an interchangeable biosimilar for Lucentis (ranibizumab injection) on Aug. 2, 2022. It is the first biosimilar product interchangeable with Lucentis across all five indications.

Ranibizumab-eqrn is an anti-vascular endothelial growth factor (VEGF) therapy biologic, which has been gaining traction in ophthalmology, according to a company press release. It is Coherus' second FDA approved biosimilar, following Udenyca (pegfilgrastim-cbqv), a biosimilar for Neulasta (pegfilgrastim). Coherus plans to release it in early October 2022 in both 0.3 mg and 0.5 mg dosages. Coherus also plans to release an FDA-approved Humira (adalimumab) biosimilar, Yusimry (adalimumab-aqvh), in 2023.

“[Ranibizumab-eqrn] will provide both greater treatment access and choice for patients, payors, and providers in the US retinal disease community,” said Paul Reider, chief commercial officer, Coherus BioSciences, in the press release. “Coherus is the only company in the $7 billion anti-VEGF ophthalmology market with a demonstrated track record of US commercial biosimilar success.”

“The approval of [ranibizumab-eqrn] and its upcoming launch represent a strategic inflection point for Coherus as we transition to a multi-product revenue stream,” said Denny Lanfear, CEO, Coherus BioSciences, in the press release. “[Pegfilgrastim-cbqv], our first product, established our track record of success competing in the US biosimilars market. Our upcoming launch of [ranibizumab-eqrn] and planned launch next year of our third approved product, our [adalimumab] biosimilar, [adalimumab-aqvh], will leverage this experience and knowledge.”

FDA has approved Coherus’ Cimerli (ranibizumab-eqrn) as an interchangeable biosimilar for all five indications of Lucentis.