Advancing the Science of Pharmaceutical Manufacturing

Drug Solutions Podcast

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

Breaking Through Barriers to Continuous Manufacturing

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

Pfizer and BioNTech announced on May 17, 2022 that FDA has expanded emergency use authorization (EUA) to include a booster dose after completion of the primary series of the companies’ COVID-19 vaccine in children five through 11 years of age. The booster dose should be given at least five months after the second dose of the two-dose primary series. More than 8 million children aged 5–11 years old have completed a primary series of the vaccine in the United States to date.

The EUA is based on data that show children five through 11 years of age had a significant immune response following a booster dose of the vaccine during the time when Omicron was the prevalent variant. More than 4000 children in this age range have participated in the companies’ COVID-19 vaccine clinical trial to date.

The companies have also submitted an application to the European Medicines Agency for a booster dose in this age group and plan to file similarly with other regulatory agencies around the world. The Pfizer-BioNTech COVID-19 vaccine is currently the only COVID-19 vaccine authorized for use in the US for children in this age group. The vaccine is based on BioNTech’s proprietary mRNA technology, and the company is the Marketing Authorization Holder in the US, European Union, the United Kingdom, and Canada. BioNTech and Pfizer jointly hold EUAs or equivalents in the US and other countries.

Articles

Pfizer and BioNTech’s COVID-19 vaccine has been granted EUA for booster doses in children five through 11 years of age.

Pfizer and BioNTech Granted EUA for Booster Dose of COVID-19 Vaccine in Young Children

Pfizer and BioNTech announced on May 13, 2022 that they have reached an agreement with the European Commission (EC) to update their COVID-19 vaccine supply agreement. The update includes rephased planned deliveries to help support the EC and Member States’ immunization programs.

Doses that were scheduled for delivery in June through August 2022 will now be delivered in September through fourth quarter 2022. The delivery schedule change does not affect the companies’ full-year 2022 revenue guidance or the full-year commitment of doses to be delivered to the EC Member States in 2022.

The companies are continuing to evaluate potential variant-based vaccines and expect to share data in the coming months. The Pfizer-BioNTech COVID-19 vaccine is currently authorized under Emergency Use Authorization in individuals five years of age and older.

The companies have reached an agreement with the European Commission to update their COVID-19 vaccine supply agreement.

Pfizer and BioNTech Update COVID-19 Vaccine Supply Agreement with EC

Chris Spivey is the editorial director of 

Quality will forever be a topic of discussion for the pharmaceutical industry, and who better to share their insight than FDA? Director of FDA’s Office of Pharmaceutical Quality, Michael Kopcha,deputy director of science, Sau Lee, anddeputy director of operations, Cindy Buhse, join Chris Spivey, editorial director, for a discussion about:

The framework for regulatory advanced manufacturing evaluation (FRAME)

Quality as a co-dependent variable of economic outcome

Advanced versus traditional manufacturing

Pandemic pressures and improved communication

Keeping up with biotech and emerging therapies

Re-shoring drug manufacturing to the United States

What manufacturers need to understand about advancing pharmaceutical science


Michael Kopcha, PhD, R.Ph., Director of the FDA’s Office of Pharmaceutical Quality (OPQ)

, PhD, R.Ph., is the director of FDA’s Office of Pharmaceutical Quality (OPQ). This office has more than 1,300 staff responsible for assuring the availability of quality medicines for the American public through assessment, inspection, surveillance, research, and policy. OPQ contributes to the assessment of nearly every type of human drug marketing application including new drug applications (NDAs), abbreviated new drug applications (ANDAs), and biologics license applications (BLAs), including 351(k) applications (i.e., biosimilars). OPQ also performs the quality assessment of investigational new drug applications (INDs) and establishes quality standards for over-the-counter drug products and facilities. Dr. Kopcha earned his doctorate and master’s degrees in pharmaceutical science and a bachelor’s degree in pharmacy from Rutgers University. He served as an adjunct assistant professor in the Department of Pharmaceutics at Ernest Mario School of Pharmacy at Rutgers.

Sau Lee, PhD, Deputy Director of Science, Office of Pharmaceutical Quality, CDER at FDA

, PhD, is the deputy super office director of science in the Office of Pharmaceutical Quality. He directs the activities of staff members in OPQ sub-offices responsible for the quality assessment of regulatory submissions (OBP, OLDP, ONDP, and OPMA). He represents OPQ in programs and activities that impact quality assessments by coordinating with OPQ, the Center of Drug Evaluation and Research (CDER), and ORA. He also serves as the point person for the pharmaceutical industry and scientific/academic groups in developing programs to support science- and risk-based application assessment and approval. Prior to joining FDA, Dr. Lee received a bachelor of science degree in chemical engineering from the University of Virginia with a minor in materials science and a PhD in chemical engineering from Princeton University.

Lucinda (Cindy) Buhse, PhD, Deputy Director of Operations, Office of Pharmaceutical Quality, CDER at FDA

is currently the acting senior advisor for scientific operations in the OPQ in the CDER in the FDA. Dr. Buhse joined FDA in 2001 in OPQ’s office of testing and research. She was the director of the office of testing and research from 2013 to 2017 and the director for the office of quality surveillance (OQS) from 2017 to 2019. Before joining FDA, Dr. Buhse worked in management positions in production, validation, and analytical services at Sigma Aldrich Corporation and as a senior research scientist for Rohm and Haas Company. Dr. Buhse received a B.A. in chemistry from Grinnell College and a PhD in physical chemistry from the University of California, Berkeley. OQS assures that quality medicines are available through signal detection, data analysis, review of the state of quality, and proactive stakeholder engagement.

 presents the Drug Solutions podcast, where the editors will chat with industry experts from across the pharmaceutical and biopharmaceutical supply chain. Join us as experts share insights into your biggest questions—from the technologies, to strategies, to regulations related to the development and manufacture of drug products.

Podcasts

In this episode of the Drug Solutions Podcast, Chris Spivey, editorial director, interviews Michael Kopcha, Sau Lee, and Cindy Buhse of FDA about not being afraid to try new approaches and how they invite fresh ideas and abundant communication.

Drug Solutions Podcast: FDA Weighs in on Advancing the Science of Pharmaceutical Manufacturing

Avacta Group, a clinical-stage oncology drug company, announced that it would be relocating its Therapeutics division on May 11, 2022.The division will now be headquartered at Scale Space in Imperial College’s White City Campus, London, United Kingdom. This move follows Avacta’s recent transition of lead candidate AVA600, a tumor-activated form of doxorubicin, into clinical trials in August 2021.

Scale Space is part of the broader White City Innovation District, which is currently home to over 140 companies across a broad range of industries, including pharmaceutical and biotech. According to a company press release, Avacta’s new HQ will be part of a life science cluster at the west London site.

“This move is the result of a clear vision to bring together the research and development teams into one hub to facilitate the translation of our in-house research from bench to bedside,” said Fiona McLaughlin, chief scientific officer of Avacta, in the press release. “We are now at the heart of the innovative White City community in London, readily accessible to our collaborators around the world and poised to take Avacta to the next level in its evolution as a clinical stage biopharmaceutical company.”

Avacta is relocating its therapeutics headquarters to Scale Space in Imperial College’s White City Campus, London, United Kingdom.

Avacta Establishes New Therapeutics Headquarters

Pfizer announced its $11.7 billion acquisition of Biohaven Pharmaceuticals, a clinical-stage biopharmaceutical company, on May 10, 2022. This acquisition will grant Pfizer the rights to rimegepant, a dual-acting migraine therapy approved in the United States for acute treatment and episodic prevention of migraine in adults. It is also approved in the European Union for acute treatment of migraine and prophylaxis of episodic migraine.

According to a company press release, this deal will also grant Pfizer the rights to zavegepant, which is on track for US approval in the second quarter of 2022 as an intranasal spray for the acute treatment of migraine; it is also in development as an oral soft gel for chronic migraine prevention. Additionally, Pfizer will acquire a portfolio of five other preclinical calcitonin gene-related peptide (CGRP) assets.

“Today’s announcement builds on our legacy of delivering breakthroughs for patients living with complex pain disorders and diseases that disproportionately impact women,” said Nick Lagunowich, global president, Pfizer Internal Medicine, in the press release. “[Rimegepant], which is already the [number one] prescribed migraine medicine in its class in the United States, coupled with Biohaven’s CGRP pipeline, offers hope for patients suffering from migraine worldwide.”

“We are excited to announce Pfizer’s proposed acquisition of Biohaven, recognizing the market leadership of [rimegpant], our breakthrough all in one migraine therapy, and the untapped potential of our CGRP franchise,” said Vlad Coric, chairman and CEO, Biohaven, in the press release. “Pfizer’s capabilities will accelerate our mission to deliver our migraine medicines to even more patients, while the new R&D company is well positioned to bring value to patients and shareholders by focusing on our innovative pipeline for neurological and other disorders. We believe this transaction represents significant future value creation for patients and our collective shareholders.”

Pfizer will acquire Biohaven Pharmaceuticals, a clinical-stage biopharmaceutical company specializing in migraine treatments, for $11.7 billion.

Pfizer to Acquire Biohaven Pharmaceuticals for $11.7 Billion

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

From a business perspective, solid-dose manufacturers are outsourcing more production to contract development and manufacturing organization (CDMOs). Industry stakeholders also are coping with dramatic increases in the costs of raw materials and overcoming supply-chain constraints.

Rising costs, tight supplies, and long lead times are not uncommon today for both product ingredients and packaging materials. “The COVID-19 pandemic has wreaked havoc in the manufacturing of solid-dose bulk [drugs],” reports Pat Elvin, president of Reed-Lane, a privately held company specializing in pharmaceutical contract packaging. He explains, “This shortage of supply is due to an inability to obtain all ingredients and the lack of employees to operate these facilities at this time.” Paperboard and paper stock for labeling have been in particularly short supply. “Therefore,” he says, “when we look at the private-label market, we are seeing that companies are holding their supply-chain inventory extremely tight, and packaging operators are seeing more line changeovers to accommodate smaller and shorter packaging runs.” An agile supply-chain approach and production schedule are needed.

PCI Pharma Services is focusing on supply-chain tools to improve its ability to respond to changes in the market. Its goal is to enhance productivity and provide instant feedback to all stakeholders by better resource management and material allocation. The CDMO, which offers packaging and clinical trial services, uses the pci | bridge digital platform to share real-time insights, customizable reports, and digitized workflows to ensure all factors are included in a connected digital supply chain. “We also leverage digital tools within our manufacturing environment to make client supply chains more agile and create supply-chain efficiencies, optimized inventories, and predictive analytics,” says Justin Schroeder, global vice-president, Product Development and Commercialization, PCI Pharma Services.

To meet sustainability, serialization, and supply-chain issues, CDMOs are expanding packaging material options; adding or upgrading equipment, lines, and technologies; and optimizing operations and supply chains. Adare Pharma Solutions, for example, has added capacity and is completing validation of a high-speed blister packaging line with integrated cartoning and palletizing. Expected to be operational this year, the line will handle traditional solid-dose formats as well as orally dissolving tablets. Other improvements at Adare Pharma Solutions include an expanded vault for products restricted by the US Drug Enforcement Administration and the startup of high-speed stick-pack equipment for filling powders and granules. The company also is on schedule to implement full-scale aggregation capability before the end of 2022, well ahead of the November 2023 DSCSA deadline.

On the materials side, innovations include new materials, barrier substrates, and more sustainable substrates. ACG Films and Foils, for example, has developed high-barrier polyvinylidene chloride (PVDC) films, more sustainable alternatives to PVC, and a five-layer cold-form foil.

Another alternative to PVC is the AmSkythermoformblistersystem from Amcor. Based on polyethylene (PE), the printable material contains no vinyl or aluminum foil and is compatible with PE recycling streams. Barrier properties are said to be equivalent to a 120-gram coating of PVDC. Processability is equivalent to existing materials, and structures can be child-resistant (1).

SÜDPACK Medica also has developed a more sustainable blister film that is a coextruded polypropylene (PP) designed to replace PVC/PVDC blister materials. “PP as a raw substance basis naturally provides an outstanding steam barrier,” noted Michael Hermann, head of Research & Development at SÜDPACK Medica, in a press release statement. The coextrusion technology offers the potential for enhanced barrier properties and closed-loop material management (2).

With counterfeiting an ever-present concern, Holographyx is working with Hazen Paper and Uhlmann Packaging to develop, test, and launch its Holo-Blister technology. Recently granted patents in both the US and Europe, the Holo-Blister technology enables conventional heat-seal blister packaging equipment to cost-effectively apply custom holograms to the back of blister packs. Holo-Blister holograms are designed to only be visible behind each pill/capsule cavity on the back of each blister pack, providing instant verification of authenticity, while leaving space around the recess to print dosage and marketing information (3).

1. Amcor, “AmSky Thermoform Blister System,” 

AmSky Thermoform Blister System | Flexible Packaging | Amcor

2. SÜDPACK Medica, “SÜDPACK Medica Presents PP Films,” Press Release, Oct. 28, 2021.

3. Holographyx, “Holo-Blister Is a New Anti-Counterfeiting System for Pharmaceutical Blister Packs that Has Just Been Awarded Patents in Both the US and Europe,” Press Release, Feb. 23, 2022.

Innovations address sustainability, serialization, and supply-chain issues.

Supply-Chain Challenges and Innovations in Pharma Packaging

Andy Dumelow is PharmaCare manager at I Holland.

With millions of tablets coming off production lines daily, it is no surprise that tooling can be affected. Consistent compaction of granules into a quality solid dose form is challenging enough for manufacturers without the added concern of the tooling not being up to the job.

The condition of punches and dies will have a substantial impact on productivity, so it is crucial that all tablet tooling is optimized through simple maintenance procedures to enhance performance and improve longevity.


Don’t Gamble on Tablet Tooling Maintenance

Pharmaceutical Technology’s Trends in Manufacturing 

Pharmaceutical Technology's May 2022 Trends in Manufacturing eBook

Andy Dumelow is head of Technical Sales at I Holland.

When referring to this article, please cite it as A. Dumelow, “Don’t Gamble on Tablet Tooling Maintenance,” 

Pharmaceutical Technology's Trends in Manufacturing eBook 

By following some fundamental steps, manufacturers can optimize their tablet tooling maintenance and resulting productivity.

Don’t Gamble on Tablet Tooling Maintenance

Feliza Mirasol is the science editor for 

The evolution of technologies on the bioprocessing front is enabling an ability to perform continuous processing for biologic production. Although successes have been shown at small scale, challenges arise when translating continuous processes to large-scale good manufacturing practice (GMP) level. With the help of technological advances and innovative thinking, however, the potential to implement GMP-scale continuous bioprocessing is getting closer to reality. This article looks at real-world experiences of some companies that tested out the implementation of continuous manufacturing systems for GMP-scale biologics manufacture. 

Read the article:
Implementing Continuous Bioprocessing: From Theory to Practice

When referring to this article, please cite it as F. Mirasol, “Implementing Continuous Bioprocessing: From Theory to Practice," 

The struggle to implement continuous biomanufacturing at GMP level is slowly advancing.

Implementing Continuous Bioprocessing: From Theory to Practice

On May 10, 2022, Avantor announced that it had entered into an agreement with Cytovance Biologics, a contract development and manufacturing organization specializing in plasmid DNA, to manufacture research- and good manufacturing practice (GMP)-grade plasmids for viral vectors and messenger RNA (mRNA)-based vaccines and therapeutics.

Plasmid DNA is a critical process element in viral vector-based gene therapy and mRNA vaccines and therapeutics. Under the agreement, Avantor will provide access to plasmid DNA and other mission-critical inputs used in research, clinical testing, and manufacturing scale-up and commercialization while Cytovance Biologics will lend its plasmid current good manufacturing practice manufacturing capabilities.

"Demand for therapeutic biologics in the gene therapy space is increasing rapidly and will require increased manufacturing capacity and expertise,” said Ger Brophy, executive vice-president, Biopharma Production, Avantor, in a company press release. “Our collaboration with Cytovance Biologics demonstrates our commitment to cell and gene therapy biomanufacturers and will support our role in unlocking the potential these therapies hold for patients around the globe."

“Production of plasmid DNA extends our microbial capabilities to support the growth of the cell and gene therapy space. We are delighted to be working closely with Avantor to support the biopharmaceutical industry on a global level,” said Naomi Seresinhe, senior vice-president of business operations, Cytovance Biologics in the press release.

Through a collaboration, Avantor and Cytovance Biologics will accelerate plasmid optimization and sourcing services for viral vectors and mRNA-based vaccines and therapeutics.

Avantor and Cytovance Biologics Partner on Plasmid DNA Development

PCI Pharma Services announced an expansion of capabilities and capacities to its manufacturing facility in Bedford on May 10, 2022. The company is investing $100 million into the facility’s aseptic liquid fill-finish and sterile lyophilization technology.

According to a company press release, the planned expansion consists of a 50,000 ft.² facility that will contain an aseptic fill-finish line with a fully isolated containment system. It will also have twin lyophilizers with auto-loading and unloading systems that can complete 400 vials per minute on a sterile fill-finish line.

“We are excited to introduce clients to our newest facility, which is part of our broader strategy to provide integrated end-to-end drug development, manufacturing, and packaging capabilities,” said Salim Haffar, CEO, PCI Pharma Services. “Our investment in these facilities will ensure that PCI continues to leverage new capabilities in complex formulations, aseptic fill-finish, and lyophilization to meet the needs of our global clients, particularly as biologics continue their strong growth trajectory.”

The Bedford facility, which was obtained in the acquisition of Lyophilization Services of New England in Dec. 2021, is dedicated to high-volume lyophilization, liquid filling, and multi-product handling from one format to another. This announcement follows the company’s construction of the New England Clinical Center of Excellence in Bridgewater, Mass., as well as expansions to their sites in Berlin, San Diego, Rockford, Ill., and Melbourne, Australia.

PCI Pharma Services is investing $100 million in manufacturing capabilities and capacity expansion to its Bedford, NH facility.

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Scaling Up Capacity for Cell Therapies

Drug Solutions Podcast