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Collaboration and new tools aid efforts to implement new processing technologies for small-molecule drug product manufacturing.

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Experts discuss what data to consider when selecting a high-potential drug candidate.

Early Development Medicinal Chemistry

Effective cleaning and disinfection along with contamination controls is imperative when operating and utilizing a cleanroom.

Cleanroom Cleaning: Proper Methodology and Determining Efficacy

Data may be used to improve (or remove) a corrective action/preventive action.

Put a Cap on CAPAs

The booming cell therapy market has created a need for capacity that outsourcing partners are ready to fill.

Scaling Up Capacity for Cell Therapies

Biologic Drug Development and Manufacturing

Foxx Life Sciences, a US-based manufacturer of biotech, pharmaceutical, and diagnostics products, entered into an online distribution agreement with Thomas Scientific in May 2022 to make selling easier for Foxx’s EZBio made-to-order media bottle assemblies (EZBio MTO). The products will be made available for customization and can be ordered through a direct-to-consumer microsite hosted on the Thomas Scientific website.

Foxx launched the EZBio MTO service in February 2021, and the service was previously only available through the Foxx website. The EZBio MTO service allows customers to select individual laboratory media bottle assembly components best suited to their project needs. Components that can be selected include the volume and material of bottle, brand of thermoplastic elastomers tubing, and type of fitting.

Through the agreement with Foxx, Thomas Scientific customers can now gain access to the EZBio service and product portfolio through a unique dedicated microsite. Compared to traditional media bottle assembly ordering, the microsite’s customization provides users with increased flexibility and offers a significant reduction in lead time, according to a May 3, 2022 press release.

EZBio MTO assemblies are available in polyethylene terephthalate glycol-modified and polycarbonate. These assemblies are applicable to bioprocess storage and sterile fluid transfers that typically require regulation. The microsite’s component selectors can be used to select from more than 400 different combinations in seconds, which can cut down the standard eight-to-10-week lead time to four to six weeks in most instances, according to the companies in the press release.

"The Foxx Thomas EZBio MTO program is an SUT [single-use technology] end user game changer,” said Foxx Life Sciences President and CEO Thomas Taylor in the company press release. “A few simple clicks and you have exactly what you are looking for with your tubing, your connectors, etc. Foxx was the first in the world to create this SUT MTO program."

“This partnership with Foxx gives Thomas the ability to offer fast, flexible, single use solutions to all our customers. It significantly broadens our ability to support them in their manufacturing suites,” said Michael Klipstein, Thomas Scientific’s chief commercial officer in the press release.

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Foxx Life Sciences and Thomas Scientific collaborate to simplify online ordering access to Foxx’s media bottle assembly offerings.

Foxx Life Sciences and Thomas Scientific Partner to Simplify Media Bottle Ordering

On May 20, 2022, Sanofi announced that FDA approved Dupixent (dupilumab) 300 mg weekly to treat eosinophilic esophagitis (EoE) in patients aged 12 years and older who weigh at least 40 kg. According to Sanofi in a company press release, this approval makes Dupixent the first and only medicine specifically indicated to treat EoE in the United States.

A regulatory filing for Dupixent to treat EoE in Europe is under review by the European Medicines Agency, and additional submissions to regulatory authorities in other countries are planned by the end of 2022.

EoE is a chronic inflammatory disease driven by type 2 inflammation, which damages the esophagus and prevents it from working properly. For people with EoE, swallowing can be painful, and they are at risk of choking, even from small amounts of food. In cases where EoE causes the esophagus to narrow, forced and potentially painful dilation of the esophagus may be needed. In severe cases, a feeding tube may be the only option. Approximately 160,000 patients in the US suffer from EoE and are currently treated with therapies not specifically approved for the disease. As a result, approximately 48,000 patients continue to experience symptoms despite multiple treatments.

FDA evaluated Dupixent, which was developed by Regeneron Pharmaceuticals in partnership with Sanofi, under priority review and based its approval on data from a Phase III trial with two parts (Part A and Part B) that evaluated the efficacy and safety of Dupixent 300 mg weekly, compared to placebo, in patients aged 12 years and older with EoE and who weighed at least 40 kg. After 24 weeks, patients treated with this dosing schedule experienced 69% and 64% reduction in disease symptoms from baseline in Part A and Part B, respectively. These results compared to 32% and 41% reduction in symptoms in Part A and Part B, respectively. In addition, the safety results were generally consistent with the known safety profile of Dupixent in its approved indications.

Including this newest indication, Dupixent is now approved for atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, and EoE.

“We have waited a long time for an FDA-approved treatment option for eosinophilic esophagitis—an underdiagnosed and misunderstood disease of the esophagus that can make it extremely challenging and uncomfortable to eat and swallow. Before today, there were no approved treatments specifically for eosinophilic esophagitis, resulting in many people needing to maintain a strict diet and live in constant fear of food getting stuck in their throat. We welcome therapeutic options that can provide much-needed relief for these patients,” said Mary Jo Strobel, executive director, American Partnership for Eosinophilic Disorders (APFED), in the Sanofi press release.

“Eating regularly throughout the day is essential, yet significant difficulty swallowing food is a common symptom for people living with eosinophilic esophagitis. This can be incredibly upsetting and often leads to fear of pain or choking with every meal, every day. A large unmet need exists for treatment options that can provide meaningful symptom relief. Our Phase [III] clinical program showed that Dupixent weekly improved the ability to swallow and reduced inflammation in the esophagus, underscoring the role of type 2 inflammation in this complex disease. This is a landmark FDA approval for patients and their caregivers who now have a new option for treating this devastating disease,” said John Reed, MD, PhD, global head of Research and Development, Sanofi, in the press release.

“It is gratifying that Dupixent, a medicine that we invented in our laboratories, is now approved in yet another disease marked by allergic or type 2 inflammation, namely eosinophilic esophagitis. Eosinophilic esophagitis can be debilitating for patients, by inflaming and damaging the esophagus and limiting the ability to eat normally. Dupixent is the first and only medicine specifically indicated to treat eosinophilic esophagitis in the United States, and today’s approval marks the fourth disease for which Dupixent is now indicated, reinforcing the promise of targeting IL [interleukin]-4 and IL-13 to effectively treat diseases with underlying type 2 inflammation,” said George D. Yancopoulos, MD, PhD, president and chief scientific officer, Regeneron, in the press release.

Dupixent (dupilumab), developed by Regeneron Pharmaceuticals in partnership with Sanofi, has received FDA approval for a new indication—treating eosinophilic esophagitis, a chronic inflammatory disease. 

FDA Approves Sanofi’s and Regneron’s Dupixent to Treat Eosinophilic Esophagitis

On May 24, 2022, Lonza and Israel Biotech Fund (IBF), a venture fund investing in Israeli and Israeli-related biotech companies, announced that they have entered into a framework agreement. Under the agreement, Lonza will provide pre-investment due diligence support to IBF and offer IBF's portfolio companies tailored advice as well as flexibility and services for the development and manufacturing of biologics and small molecules. In return, IBF will provide Lonza with access to its portfolio companies and broad network in the Israeli biotech industry.

The two-year agreement aims to broaden the scope of services provided by Lonza to pharmaceutical companies in the Israeli ecosystem. It also gives Lonza an opportunity to support the unique needs of Israeli pharmaceutical companies looking to simplify and de-risk the development of their molecules.

Israel had more than 1750 life science companies active at the end of 2020, many of which were start-ups and small biotech companies. IBF, started in 2015, is dedicated to investing in and developing the biotech industry in Israel and has played a key role in the Israeli Biotech ecosystem. The organization has exposure to and familiarity with the market and key players in the Israeli pharma industry as well as most biotech companies and projects.

As part of the collaboration, Lonza will advise IBF in its due diligence review of candidate biotech targets and provide a tailored offering, advice, and services to IBF's portfolio companies that are targeting innovations in the healthcare sector and that are focused on developing therapeutic assets and disruptive platforms.

"We chose to collaborate with IBF, a leading investment fund in Israel, due to their unique investment strategy, broad network, and approach. We are excited to implement this framework agreement that will provide IBF and their portfolio companies with services and expertise across multiple modalities,” said Pnina Weitz, global head of Venture Capital Business Development and Relationship Management, Lonza, in a company press release. “IBF’s network will allow Lonza to benefit from these connections and offer services and expertise across multiple modalities. Lonza's customized and scalable solutions in the development and manufacture of both biologics and small molecules will allow these companies to leverage our global network and experience and focus on what they do best—developing innovative and transformative treatments."

"Lonza is a leading and reputative global manufacturer, and we are excited to collaborate with them. The unique business model offered by the collaboration agreement will provide Lonza with broad access to the Israeli market and allow our portfolio companies to leverage Lonza's expertise and innovative business models. Such companies will benefit from a streamlined development and manufacturing process, allowing them to focus on research and development and pre-clinical studies," said Ido Zairi, co-founder and managing partner, IBF, in the press release.

Lonza and Israel Biotech Fund form a two-year agreement to support accelerated development and manufacture of biologics and small molecules.

Lonza, IBF Collaborate to Support Development and Manufacturing of Biologics and Small Molecules

AGC Biologics announced in May 2022 that it is adding viral vector suspension technology and capacity for the development and manufacturing of gene therapies at its commercial-grade campus in Longmont, Colo. The new capabilities will start coming online in the third quarter of 2022 and will complement the site’s adherent viral vector and cell therapy offerings.

This expansion will more than double the Longmont site’s viral vector capacity and will help the company meet market demand. The expansion is part of AGC Biologics’ more than $30 million investment in the new Longmont campus. The new viral vector suspension capabilities include a full complement of bioreactor sizes for product development (AMBR, 10 L and 50 L), and a complete range of commercial manufacturing capacities (50 L, 200 L, 500 L, and 2000 L). The expansion will enable the site to provide support for the entire lifecycle of a product, according to a company press release.

AGC Biologics acquired the Longmont campus in August 2021. The company previously acquired a cell and gene therapy site in Milan, Italy, from MolMed in 2020.

“This investment helps AGC Biologics address the needs of gene therapy developers at our new central location in North America,” said Patricio Massera, CEO of AGC Biologics, in the press release. “When you combine these new capabilities and the technical expertise at our Longmont campus, with our Milan facility’s lentiviral vector platform and its extensive gene therapy CDMO [contract development and manufacturing organization] experience, we can now support virtually any viral vector program being developed anywhere in the world.”

“The suspension expansion helps us offer the most impactful, efficient and scalable technologies for bringing viral vector-based gene therapy products to market,” said Tony Fraij, general manager, AGC Biologics Longmont, in the press release. “This latest investment helps us round out the services we offer at this campus. Now, with a full suite of capabilities and the extensive expertise of our scientists, we can support virtually any type of viral vector or cell therapy development and manufacturing project.”

AGC Biologics is investing in viral vector suspension technology at its new Longmont, Colo., facility.

AGC Biologics Adds Viral Vector Suspension Technology at New US Campus

Lubrizol Life Sciences has launched Apisolex, a novel solubility-enhancing excipient for use in parenteral drug products. The technology has the ability to overcome hurdles in solubility that do not have existing solutions.

According to the press release, 60–90% of potential new APIs that are currently in development and 40% of those in reformulation are poorly water soluble. Solubility impacts bioavailability and efficacy, which is especially relevant in the oncology field, as direct injection of drugs into the bloodstream ensures higher bioavailability and lower patient variability compared to oral delivery.

Apisolex technology is able to improve solubility and support high drug loading. It is meant to streamline manufacturing and minimize API loss and is a non-toxic, non-immunogenic alternative to PEG or surfactants.

“Apisolex is the first solubility-enhancing excipient for parenteral use introduced in more than 20 years,” said Rob Lee, president of the CDMO division of LLS Health, in the press release. “With its toxicity profile and simple processing techniques, Apisolex polymer can both improve existing drugs and enable some important new molecules.”

Lubrizol has launched Apisolex technology to improve solubility and simplify the manufacturing of parenteral drug products.

Lubrizol Launches Apisolex Technology 

AbbVie and Cugene, a clinical-stage biotechnology company specializing in autoimmune treatments, announced on May 16, 2022 an exclusive worldwide license option agreement for Cugene’s lead therapeutic candidate, CUG252, on May 16, 2022. CUG252 is a potential best-in-class regulatory T-cells-select-interleukin-2 (Treg-select IL-2) mutein that AbbVie plans to use in the development of treatments for autoimmune and inflammatory diseases.

Under agreement, Cugene will receive an upfront payment of $48.5 million from AbbVie. Conditional payment structures for achieving various development, regulatory commercialization, and sales-based milestones are also included.

According to a company press release, CUG252 is an engineered IL-2 mutein designed to selectively activate and expand immune-suppressive Treg cells while reducing undesired IL-2 receptor-expressing cells. In addition to CUG252, AbbVie also purchased access to other novel IL-2 muteins from Cugene. CUG252 is currently in a Phase I study in healthy volunteers.

"AbbVie is committed to developing novel therapies in immunology where unmet needs remain for patients living with complex autoimmune and inflammatory conditions," said Tom Hudson, senior vice-president, R&D, chief scientific officer, AbbVie, in the press release. "Our partnership with Cugene is the latest in our efforts to develop and advance potential next-generation therapies like CUG252."

"AbbVie is an ideal partner for CUG252, with [its] commitment to R&D, deep therapeutic area expertise, and the global resources needed to maximize CUG252's therapeutic potential for patients suffering from autoimmune diseases,” said Luke Li, CEO, Cugene, in the press release. “Today's agreement highlights Cugene's unique precision engineering platform that has yielded multiple product candidates, including CUG252. We look forward to collaborating with AbbVie to transform clinical outcomes in autoimmune disease."

AbbVie and Cugene have reached an exclusive license option agreement for CUG252, Cugene’s lead therapeutic candidate.

AbbVie and Cugene Form Autoimmune Disease Collaboration

Fluid Air, a division of Spraying Systems, announced that Sferalp, the R&D arm of Micro-Sphere, has selected their PolarDry technology for use in its research laboratory in Monteggio, Switzerland. Sferalp will use the PolarDry technology for powder processing with its commercial food, pharmaceutical, and nutraceutical customers.

“Our Swissmedic-certified laboratory is authorized to perform chemical-physical quality control tests on medicinal products and active substances in accordance with [good manufacturing practices] for medicinal products, and we know that we can count on Fluid Air technology to help achieve superior results for our customers,” said Michele Müller, general manager of Sferalp, in a May 10, 2022 company press release. “Fluid Air is the only provider in the marketplace whose technology can support our lab’s needs and help us meet the highest industry standards for quality and product performance.”

“Fluid Air is pleased to have its PolarDry technology used by an industry influencer [such as] Sferalp [and] is thrilled to have been selected as a key technology contributor to Sferalp[’s] important work,” said Michel Thenin, president, Fluid Air, in the press release.

Sferalp will use Fluid Air’s PolarDry technology for powder processing.

Sferalp to Use Fluid Air Technology for Laboratory Research

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

A new framework for extrapolating clinical trial data from adult studies seeks to facilitate the testing and approval of therapies for children more quickly and at less cost. The process for achieving such gains is presented in a draft guideline recently released by the International Council for Harmonisation (ICH) that maps out common methods and strategies for identifying how development programs for adult drugs can inform pediatric indications. By establishing common regulatory requirements among regions, the initiative aims to speed the approval of and access to new drugs for young patients around the world, while limiting the number of children needed for testing in clinical trials.

proposed pediatric extrapolation guideline

to gain broader review and assessment by regulatory authorities and drug development sponsors around the world . This harmonization process began in 2017 and now appears on track to adopt a final guideline in 2024. An ICH assembly in Korea in November 2022 is slated to discuss this and several other proposed standards moving through the review process, such as quality risk management and analytical validation requirements, and newer projects on structured product quality, stability testing, and model informed drug development. In recent years, ICH has adopted guidelines on estimands and sensitivity analysis in clinical trials and on reproductive toxicology testing to support clinical studies; a newer initiative aims to update the E8 guideline on the conduct and reporting of clinical trials by incorporating quality-by-design principles into clinical research.

ICH also is moving forward with an initial roadmap for developing guidance on model-informed drug development (MIDD), considered a key approach for achieving a more efficient and more predictive clinical research process, with potential for reducing unnecessary patient exposure. The 

MIDD discussion group released a plan on March 31, 2022 

that lays out general principles, anticipated gains, time frames and options. The aim is to develop a general principles guideline in the next three-to-four years and a completed standard in 10 years. That would set the stage for revisions in several basic guidelines, such as on dose response information, population pharmacokinetic-pharmacodynamic studies, and disease progression modeling.

The ICH initiative on pediatric extrapolation was outlined at a 

organized by FDA and Health Canada to update stakeholders on that and several other ICH projects. Lynne Yao, director of FDA’s Division of Pediatric and Maternal Health in the Center for Drug Evaluation and Research (CDER), described ICH efforts since 1994 to establish common global regulatory standards designed to provide children with access to medicines appropriately evaluated in adults and to support the inclusion of pediatric patients in product development programs where appropriate and feasible.

These initiatives for advancing pediatric clinical investigations have expanded since publication in 2000 of the initial ICH E11 guideline on pediatric clinical investigations. An addendum, E11 (R1), appeared in 2017 and recognized the need for more detailed standards on pediatric extrapolation. In response, an expert working group was formed to develop a reflection paper on the need and scope of an ICH E11A guideline on pediatric extrapolation. Initial steps involved aligning terminology and developing a systematic approach for considering study design, statistical methodologies, and modeling and simulation strategies in this area, Yao explained.

Now a draft ICH E11A guideline provides a framework for utilizing pediatric extrapolation methods to meet regulatory standards for approval. It outlines a systematic approach for pediatric extrapolation studies that involves a full assessment and synthesis of existing data; quantitative predictions on the degree of similarity; development of a framework for potential reduction of required evidence; and later revision of uncertainties and assumptions. Pediatric extrapolation plans would consider patient response to treatment and identify gaps in knowledge involving dose selection, types of efficacy studies, and the need for a safety plan. The goal is to achieve more alignment among regulatory authorities on terminology and what study designs, statistical methodologies, and modeling and simulation strategies will advance pediatric extrapolation in drug development.

ICH standards for pediatric extrapolation, moreover, may help address broader concerns about the scope and extent of data extrapolation to support added indications for new drugs in patients not studied in original pivotal trials. While authorities generally agree that such extrapolation is valid and important for extending disease treatment to added patient populations, some experts question whether sponsors over-rely on limited clinical data to support added indications. This issue was highlighted in the recent debate over the extrapolation of limited clinical evidence in approving the Alzheimer’s treatment Aduhelm for patients with mild cognitive impairment. While experts agree that FDA and sponsors should have flexibility to expand an indication of an approved drug based on extrapolation of initial clinical data, pressure has increased for requiring postapproval studies to support such actions and to provide clear evidence of appropriate use.

A new initiative aims to speed the approval of and access to new drugs for young patients around the world, while limiting the number of children needed for testing in clinical trials.

New Guidelines Aim to Advance Pediatric Drug Development

AstraZeneca has revealed in a May 23, 2022 press release, that its recombinant COVID-19 vaccine originally invented by the University of Oxford, Vaxzevria (ChAdOx1-S), has been given the nod by the European Medicines Agency (EMA) as a third dose booster vaccine for use in the European Union (EU).

Through this latest market authorization, healthcare professionals will be able to use the vaccine as a third dose booster in patients who have already been administered a primary vaccine schedule of either Vaxzevria or other EU-approved messenger RNA (mRNA) COVID-19 vaccines. The authorization has been based on EMA’s Committee for Medicinal Products for Human Use (CHMP) recommendation, for which there was a review of data demonstrating an increased immune response with a third dose booster Vaxzevria jab.

“[This] marketing authorization for AstraZeneca’s COVID-19 vaccine as a third dose booster is an important step towards our goal of providing continued protection against COVID-19 for all populations,” said Mene Pangalos, executive vice-president, BioPharmaceuticals R&D, AstraZeneca, in the press release. “Ensuring a longer duration of immune protection is essential to the long-term management of COVID-19 globally, and boosters can address the waning of protection over time that has been seen with all primary vaccine schedules to date.”

AstraZeneca's recombinant COVID-19 vaccine, originally invented by the University of Oxford, has been approved as a third dose booster vaccine in the EU.

Vaxzevria Gains Approval in EU as a Third Dose COVID-19 Booster in Adults

The European Medicines Agency (EMA) has provided its recommendation for Xenpozyme (olipudase alfa) to receive marketing authorization in the European Union (EU) for the treatment of non-central nervous system (CNS) manifestations of Acid Sphingomyelinase Deficiency (ASMD), which is a rare and progressive genetic disease.

According to a May 20, 2022 press release, the therapy is indicated for use in children and adults of all ages who suffer from type A/B or type B ASMD—a genetic disorder that is historically referred to as Niemann-Pick disease types A (NPD A) and B (NPD B). Currently, there are no approved medicines that modify or slow the progression of the disease within the EU, meaning that patients are only able to receive palliative and supportive care to manage the symptoms.

Xenpozyme is an enzyme replacement therapy, available as a powder solution for intravenous administration every two weeks, that works by replacing the deficient or defective enzyme in patients. The replacement enzyme, which is produced by recombinant DNA technology, then lowers the fat accumulation in cells and relieves disease symptoms.

The recommendation for marketing authorization, made by EMA’s Committee for Medicinal Products for Human Use (CHMP), was based on the results from three clinical trials in patients with ASMD, which demonstrated positive outcomes of the therapy with only mild to moderate adverse events experienced. The therapy has been supported through EMA’s Priority Medicines (PRIME) scheme and CHMP reviewed the marketing authorization application under an accelerated assessment procedure.

EMA has recommended the marketing authorization of Xenpozyme (olipudase alfa) in the European Union. 

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