This compilation allows readers to adjust their thinking to appreciate the full impact certain select technologies will make on the industry by 2026.

Six Approaches Making the Most Significant Impact in the Future

The testing of new convecdiff membranes shows this material to be well suited for lab- and commercial-scale bind-and-elute applications.

Purification of Antibodies Using Novel Convecdiff Membranes Part 1

Cautiously setting aside pandemic practices, pharma workers appear ready for flux, change, evolution, and expanding molecular diversity.

Crossing the Same River Multiple Times

Biologic drug development requires relevant bioassays to measure and help predict cellular response.

Complex Analytical Workflows Increasingly Require Robust Bioassays

Affinity chromatography resins must perform well under mild elution conditions yet withstand robust cleaning and sanitization protocols.

Choosing the Right Resins for Viral Vector Affinity Chromatography

Efforts to optimize the ideal blend of technology and best practices that are needed to protect and deliver time- and temperature-sensitive biologic therapies, vaccines, and cell and gene therapies continue to evolve.

Safeguarding Biologics— Blending Engineering Ingenuity and Managerial Excellence

Health crises, political tension, and budget concerns were major challenges.

Pandemic and Politics Shaped Pharma and FDA in 2022

 Washington Editor, jillwechsler7@gmail.com.

A more harmonized formula and schedule for administering COVID-19 vaccines gained strong support from FDA’s expert advisory panel last week, with agreement on the need to reduce confusion over which shot to take and when in order to increase vaccination rates among both adults and children in the United States. The 21 members of FDA’s Vaccine and Related Biological Products Advisory Committee (VRBAC) voted unanimously for a more simplified approach, setting the stage for the agency to authorize a common bivalent shot for all patients that targets both the original COVID-19 strain and the Omicron subvariants. The new program would end use of Pfizer and Moderna monovalent vaccines that only target the original COVID strain.

FDA received less support for setting a schedule for annual vaccination against COVID, as the advisors expressed uncertainty about the effectiveness of the current shots and questioned what time during the year would be best for a national COVID vaccination campaign. Several panel members urged additional research on the effectiveness of the new formulations on frequently changing variants and the possible need for different vaccination schedules for both young children and older adults with health impairments. The experts called on FDA to provide additional data on vaccine effectiveness and timing to better determine whether all patients would need an annual shot.

The strategy to set a common formula for anti-COVID vaccines across the country aims to increase vaccination rates overall. New data from the Centers for Disease Control and Prevention (CDC) indicates that less than half of all older Americans (over age 65) have received the updated booster, and that vaccination rates are a meager 10% for children under age 4. The hope is that a shift away from differing vaccine compositions and varying immunization schedules, along with clearer alignment between US and European vaccination recommendations, will encourage more people to get such protection.

Pfizer, Moderna, and Novavax reported to VERBAC on efforts underway to produce reformulated bivalent vaccines and supported the plan to establish a common formulation for all manufacturers of the adopted shot to simplify vaccination recommendations and reduce patient uncertainty over effectiveness and safety of vaccines from different companies. The manufacturers emphasized the need for specifics from FDA on the process for updating vaccine strains, including the timing, process, and methodology for producing a data package for new licensure. While such filings are expected to include new preclinical and manufacturing data, sponsors opposed requirements for additional clinical trials, indicating that it will be more productive to assess post-authorization real-world data to confirm effectiveness.

FDA officials proposed to meet with the advisory panel in May or June to decide on which COVID strain to target in vaccines for later this year, anticipating a fast reformulation by manufacturers of messenger (mRNA) vaccines. But Novavax officials indicated that it might need to identify the strain earlier, probably in March, to produce a new vaccine by fall with its more traditional vaccine production process. All three shot manufacturers reported that they were already shifting to use prefilled syringes and single-dose vials, which are important for physicians, clinics and pharmacies planning to administer the new vaccines more widely in the wake of reduced federal government involvement in the program.

A related question is whether FDA will ask manufacturers to produce combination influenza/COVID vaccines to further simplify annual vaccination programs. The three firms reported that they are already studying such combination shots, but any shift towards such products will involve much further assessment of the need for and effectiveness of annual COVID vaccines or combination products.

While advisory committee experts and officials from FDA and other health agencies acknowledged the value of utilizing mRNA platforms to produce anti-COVID vaccines so quickly and effectively at the start of the pandemic, some panel members called for further research on how well the new formulations provide long-term protection and avoid safety issues, urging continued examination of whether more traditional vaccine production methods may have broader benefits moving forward. In its presentation, Novavax presented data indicating a “robust breadth of immunity” and strong manufacturing consistency for its more recently approved preventive.

In concluding the meeting, Peter Marks, director of the Center for Biologics Evaluation and Research, reiterated the need for a “data-driven approach” to achieve a vaccine regimen that is as simple as possible. But he also noted the importance of monitoring vaccine safety and assessing product effectiveness in shifting to a next generation of COVID vaccines able to provide “greater depth of protection.”

Articles

FDA plans to authorize a common bivalent shot that targets both the original COVID-19 strain and Omicron subvariants.

FDA Seeks to Simplify COVID-19 Vaccination Program

FDA released the Biosimilar User Fee Amendments (BsUFA) III Regulatory Science Pilot Program: Research Roadmap to provide additional information about the biosimilar regulatory science research pilot program. The agency also opened a public docket to collect feedback, according to a press release.

The BsUFA facilitates the development of safe and effective biosimilars and interchangeable biosimilars for patients by supporting FDA review of biosimilar submissions. FDA will pilot a regulatory science program to facilitate biosimilar and interchangeable biological product development, as outlined in the BsUFA reauthorization commitment letter for fiscal years 2023–2027.

The regulatory research pilot program is targeted at knowledge gaps and direct research to advance biosimilar development. The BsUFA III regulatory research pilot program has two goals, also known as demonstration projects, which are: advancing the development of interchangeable products, and improving the efficiency of biosimilar product development.

In the roadmap, research areas are highlighted where advancement is expected to impact science-based recommendations and regulatory decision making. More specifically, the research aims to:

increase the accuracy and capability of analytical (structural and functional), and chemistry, manufacturing, and controls characterizations

develop alternatives to and/or reducing the size of studies involving human subjects.

The research team, both external and internal to FDA, should use this roadmap to guide research proposals, collaborations, and other efforts as they seek BsUFA III research funding opportunities. Further, the roadmap includes information on research project deliverable dates and methods to consider for research conducted as part of the pilot program.

In all, the objective of the pilot program is to increase the efficiency and predictability of biosimilar development to help reduce the cost and time of development. This helps increase availability and access to much needed biological treatment options for patients.

The BsUFA facilitates the development of safe and effective biosimilars and interchangeable biosimilars for patients by supporting FDA review of biosimilar submissions.

FDA Releases Research Roadmap for Biosimilars Pilot Program

Agilent and Quest Diagnostics entered into an agreement to expand access to the Agilent Resolution ctDx FIRST liquid biopsy next-generation sequencing (NGS) test. The ctDx FIRST is a single-site premarket approved test that is approved by FDA (1) as a companion diagnostic (CDx) to identify advanced non-small lung cancer (NSCLC) patients who may benefit from treatment with adagrasib (brand name Krazati). Adagrasib is a targeted treatment option for adult patients with KRASG12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy.

According to a Jan. 23, 2023 company press release, under the agreement, Quest will offer ctDx FIRST to healthcare providers in the United States seeking a minimally invasive liquid biopsy test option as a CDx for adagrasib. The test can be ordered online through Quest’s online connectivity platform, and healthcare providers may additionally direct patients to provide specimens at one of Quest’s 2100 patient service centers in the US.

“We are looking forward to the Quest Diagnostics alliance facilitating broad access to ctDx FIRST, our liquid biopsy solution,” said Paul Beresford, vice-president and general manager, Companion Diagnostics Division, Agilent, in the release. “This expands the testing options available for NSCLC patients as patients don’t always have tissue available for molecular analysis.”

"The addition of the ctDx FIRST test to our oncology menu underscores our commitment to providing access to precision medicine innovations to improve care for patients with cancer," said Kristie Dolan, vice-president and general manager, Oncology Franchise, Quest Diagnostics, in the release. "It also reflects our ability to optimize our national physician and patient access network to extend access to important medical innovations with the potential to improve patient outcomes."

1. FDA, “FDA Grants Accelerated Approval to Adagrasib for KRAS G12C-Mutated NSCLC,” Press Release, Dec. 12, 2022.

Agilent will work with Quest Diagnostics to distribute the ctDx FIRST test.

Agilent and Quest Diagnostics to Collaborate on Lung Cancer Diagnostic

Illumina, a DNA sequencing and array-based technologies provider, and Nashville Biosciences, a subsidiary of Vanderbilt University Medical Center (VUMC), have teamed up with Amgen to provide whole-genome sequencing of approximately 35,000 DNA samples. The sequencing of this sample cohort, which primarily comprises DNA from African-Americans, is intended to mitigate their underrepresentation in research for clinical applications of genomics. The sequencing will be performed by deCODE genetics, a subsidiary of Amgen.

According to a press release from Jan. 9, 2023, the sequencing of these samples is the first step in Illumina and Nashville Biosciences Alliance for Genomic Discovery (AGD) program. The agreement intends to whole-genome sequence at least 250,000 de-identified human DNA samples from VUMC’s BioBU biobank over the course of two and a half years.

"The initial cohort will be among the largest sequencing efforts involving African Americans to date," said Leeland Ekstrom, CEO, Nashville Biosciences, in the release. "Once complete, this data set will provide a wealth of new information about the human genome and accelerate the study of disease in—and discovery of new therapeutics for—populations less well represented in prior large-scale sequencing efforts. The opportunity to sequence this diverse set of samples will help broaden our understanding for individuals who have been underrepresented in genetic research and continue to experience health disparities."

"deCODE's sophisticated human data capabilities are well positioned to sequence these samples and analyze the resulting data to provide a better scientific understanding of disease through the context of human diversity," said Kári Stefánsson, founder, deCODE genetics, in the release. "Insights from human data, including both genetics and clinical records, can help inform how medicines may affect different patient populations."

deCODE genetics, a subsidiary of Amgen, will whole-genome sequence 35,000 African-American samples provided by Illumina and Nashville Biosciences.

Amgen, Illumina, and Nashville Biosciences Announce Genome Sequencing Agreement

GeoVax announced on Jan. 25, 2023 that the United States Patent and Trademark Office issued a Notice of Allowance for Patent Application No. 17/000,768 titled, “Method for Generating a Zikv Immune Response Utilizing a Recombinant Modified Vaccinia Ankara Vector Encoding the NS1 Protein.”

According to GeoVax, Zika virus (ZIKV) is linked to an increase in microcephaly in infants and neurodegenerative disease, Guillain-Barre syndrome, in adults. The claims to be granted in the patent cover GeoVax’s modified vaccinia Ankara (MVA) vector comprising a nucleic acid sequence encoding a ZZIKV nonstructural (NS1) protein, of which GEO-ZM02 is designed. The company states its MVA platform holds the potential to address the critical unmet need in vaccination of women of childbearing age and newborns against ZIKV.

“Our novel Zika vaccine candidate, GEO-ZM02, is constructed using our modified vaccinia Ankara (MVA) vector platform. Preclinical studies demonstrated a single dose of GEO-ZM02 provided 100% protection against a lethal dose of Zika virus,” stated GeoVax CEO David Dodd, in a company press release. “Addressing many of the world’s most threatening infectious diseases is part of our vision and corporate priorities for MVA’s applications, which also includes an MVA-based next-generation COVID-19 vaccine currently in Phase II clinical trials.”

The United States Patent and Trademark Office issued a Notice of Allowance for Zika vaccine patent to GeoVax.

USPTO Issues Notice of Allowance for Zika Vaccine Patent 

Eli Lilly and Company (Lilly) announced that FDA had rejected its accelerated approval application for donanemab as a treatment for early symptomatic Alzheimer's disease on Jan. 19, 2022. In its response letter, FDA cited concerns surrounding an insufficient quantity of clinical trial data.

According to a company press release, FDA specifically requested that Lilly provide data from at least 100 patients who received a minimum of 12 months of continued treatment on donanemab. Lilly cited the experimental design of the study, which allowed patients to complete their treatment once targeted deposits of amyloid plaque were reduced to predefined endpoints, as causing the insufficient quantity of data. Lilly is currently in the middle of a confirmatory Phase III clinical trial (TRAILBLAZER-ALZ 2), with topline data expected in the second quarter of 2023.

"We anticipate [TRAILBLAZER-ALZ 2] will confirm the benefit and safety profile we observed in the TRAILBLAZER-ALZ Phase II study and believe that patients and physicians will be well served by having the full Phase III data available alongside our Phase II data when they need to make treatment decisions," said Anne White, executive vice-president and president, Lilly Neuroscience, Eli Lilly and Company, in the press release. "We are committed to working with the FDA to ensure the fastest possible path to bring this potential medicine to patients in need."

In a response letter, FDA stated that it could not grant Eli Lilly and Company accelerated approval due to concerns surrounding insufficient quantity of clinical trial data.

FDA Rejects Accelerated Approval for Lilly’s Alzheimer’s Drug

The FDA is issuing a new guidance to support sponsors in the development of drugs for monkeypox (mpox). The guidance is intended to provide nonclinical, virology, and clinical considerations for mpox drug development programs, targeting on recommendations to support initiation of clinical trials.

In the past, FDA has approved drugs for the treatment of smallpox under regulations commonly referred to as the Animal Rule, but this pathway is not applicable to drugs for mpox because the research team can design and implement clinical trials for mpox that are both ethical and feasible.

The FDA’s guidance documents do not establish legally enforceable responsibilities but instead describe the Agency’s current thinking on a topic and should only be viewed as recommendations.

The guidance is intended to provide nonclinical, virology, and clinical considerations for mpox drug development programs, targeting on recommendations to support initiation of clinical trials.



FDA Issues Guidance on Development of Drugs for Monkeypox

AmMax Bio announced on Jan. 19, 2023 that the European Medicines Agency (EMA) has granted AMB-05X Priority Medicines (PRIME) designation for the treatment of tenosynovial giant cell tumor (TGCT).

“The positive proof-of-concept data from our prior 12-week Phase II study of AMB-05X in TGCT provided the basis for our PRIME application,” said Larry Hsu, PhD, chief executive officer of AmMax Bio, in a press release. “We appreciate EMA’s decision to award AMB-05X its PRIME designation, which validates the high potential therapeutic value of the program and the significant unmet medical need for patients impacted by TGCT.”

AmMax Bio presented positive Phase II data for the novel local administration of AMB-05X in patients with TGCT at the Connective Tissue Oncology Society meeting in November 2022. The efficacy data across multiple clinical endpoints and a favorable safety profile support the potential of AMB-05X as a best-in-class therapy for the treatment of TGCT regardless of surgical resectability.

The PRIME designation was launched by EMA to boost support for the development of medicines that target an unmet medical need. EMA will continue to offer early and proactive support to medicine developers to optimize the generation of robust data on a medicine’s benefits and risks through PRIME, according to the company press release.

The efficacy data across multiple clinical endpoints and a favorable safety profile support the potential of AMB-05X as a best-in-class therapy for the treatment of TGCT regardless of surgical resectability.

AMB-05X Receives EMA PRIME Designation for Treatment of Tenosynovial Giant Cell Tumor

Asimov, a synthetic biology company advancing the design and manufacture of therapeutics, announced a strategic partnership with Center for Breakthrough Medicines (CBM), a contract development and manufacturing organization (CDMO) on Jan. 18, 2023.

The partnership led to Asimov licensing its clonal GMP HEK293 suspension cell line to CBM for pre-clinical and clinical production of viral vectors for its clients. According to the press release, HEK293 cell lines are the industry standard for producing therapeutic viral vectors, which are used mainly in gene therapies.

CBM will now be available for clients to get immediate access to a high-performance clonal good manufacturing practice qualified cell line as a measure of its comprehensive capabilities for vector manufacturing designed to deliver high yields and higher throughput without comprising quality.

“Our partnership with CBM is a major step forward in our goal to advance therapeutics manufacturing,” said Alec Nielsen, CEO of Asimov, in a press release. “This validates our efforts in the viral vector space, and supports other research directions in host cell optimization, genetic system engineering, and bioreactor process modeling and development. By licensing our HEK293 viral vector production platform, CBM will be able to provide their clients with immediate access to reduce the cost of manufacturing these complex therapeutics.”

The agreement finds CDM offering its clients access to the platform as a part of its end-to-end comprehensive capabilities for vector manufacturing designed to accelerate development and manufacturing timelines of vector-based advanced therapies.

“We believe this is the initial step of many with Asimov, an industry leader in mammalian synthetic biology and cell line development,” said Avi Nandi, chief technical officer at CBM, in a press release. “We continue to make significant investments into our technology platforms to ensure our clients have access to an end-to-end solution that allows them to develop and manufacture at lower costs. Our goal is for rare disease therapies to be accessible to as many patients around the world as possible and our relationship with Asimov removes a key barrier to therapy developers.”

The partnership led to Asimov licensing its clonal GMP HEK293 suspension cell line to CBM for pre-clinical and clinical production of viral vectors for its clients. 

Asimov and Center for Breakthrough Medicines Collaborate for Viral Vector Production

On Jan. 19, 2023, Advaxis, Inc., a biotechnology company focused on the discovery, development, and commercialization of immunotherapies, completed a previously announced merger with Ayala Pharmaceuticals, Inc., a clinical-stage oncology company that develops and commercializes small molecule therapeutics for patients who have rare tumors and aggressive cancers.

The merged company will operate under the name Ayala Pharmaceuticals and will target the development and commercialization of Ayala’s lead program, AL102, for the treatment of desmoid tumors. AL102 has received Fast Track Designation from FDA and is currently in phase 3 of a trial for patients with desmoid tumors.

The merged company will operate under the name Ayala Pharmaceuticals and will target the development and commercialization of Ayala’s lead program, AL102, for the treatment of desmoid tumors. 

Advaxis, Ayala Pharmaceuticals Complete Merger

Medigene AG, an immuno-oncology company focused on the development of differentiated, T Cell Receptor engineered T cell (TCR-T) therapies, announced on Jan. 18, 2023, that it has received a $3 million payment from partner 2seventy bio as a part of its T cell receptor agreement in cancer immunotherapy, which may lead to further historical payments in the future.

This payment comes after the strategic alliance between 2seventy bio and JW Therapeutics with a focus on the development of 2seventy bio’s MAGE-A4 program, which services a highly potent TCR discovered in collaboration with Medigene’s proprietary end-to-end technology platform.

Recently, 2seventy bio announced the initiation of a strategic partnership with JW Therapeutics aiming at the collaboration being the development of 2seventy bio’s MAGE-A4 cell therapy in mainland China, Hong Kong, and Macao.

“We are delighted that Medigene’s partnership with 2seventy bio has led to the progress of cell therapies in China through 2seventy bio’s strategic alliance with JW Therapeutics,” said Selwyn Ho, PhD, chief executive officer of Medigene, in a press release. “This alliance, and recent milestone payment to Medigene, further validate our end-to-end technology platform and its potential to deliver differentiated, best-in-class TCRs. We look forward to the commencement of the MAGE A-4 TCR program in mainland China, Hong Kong, and Macao, and the benefits this could mean for patients.”

“We are excited about the ability to accelerate the development of the MAGE-A4 program; made possible in part by the important contributions of our collaboration with Medigene,” said Steve Bernstein, chief medical officer of 2seventy bio, in a press release. “This is a powerful program, supported by our collective areas of expertise and designed to create potentially transformative treatments for patients with solid tumors.”

This recent payment does not alter guidance on the cash runway of Medigene, which is based on current planning into Q4 2024.

Medigene Receives Historic $3 Million Payment from 2seventy Bio

Cambrex, a global contract development and manufacturing organization (CDMO) providing drug substance, drug product, and analytical services, announced on Jan. 18 2023 that it has acquired Snapdragon Chemistry, a US-based provider of chemical process development services to a broad range of emerging and established biopharma customers.

“Today, we welcome our new colleagues from Snapdragon to Cambrex,” said Tom Loewald, CEO of Cambrex, in a press release. “With Snapdragon’s depth of scientific expertise in API process development, I’m certain our customers will see the benefits of this combination and be delighted to work with Snapdragon’s team.”

“I am extremely proud of what our team at Snapdragon has built over the years,” said Matt Bio, CEO of Snapdragon, in a press release. “With Cambrex, we have found an ideal home for our customers and employees, and I look forward to continued success as part of Cambrex.”

Snapdragon Chemistry concentrates in API batch and continuous flow process development, utilizing state-of-the-art automation technology and proprietary equipment to solve complex process and analytical development challenges.

Cambrex is aiming to expand its portfolio of specialized solutions for pharmaceutical development and manufacturing, especially with Snapdragon’s expertise in continuous flow manufacturing and complementing recent investments in continuous flow process development capabilities.