Conventional and robotic automation inside closed systems reduces risk.

Automating Aseptic Manufacturing

Evolving equipment designs meet the needs of continuous processing techniques.

Adopting Continuous Manufacturing for Solid-Dose Drug Products

Stability programs for biologics are far more complex than small-molecule drugs.

Determining Shelf Life: Reading the Stability Testing Data

Reformulation strategies are useful tools for more than just stretching out return on investment.

Considering Bio/Pharma Reformulation Strategies

Almost half of pharmaceutical industry profits continue to come from biopharmaceuticals.

Trends Affecting Biopharmaceutical Manufacturing

AstraZeneca’s AZD7442 Clinical Trial Meets Primary Endpoint

FDA Advisory Council Unanimously Supports Moderna COVID-19 Booster EUA

Pharma strategizes to reduce its environmental footprint while optimizing output.

Greener API Manufacturing

The FDA Vaccines and Related Biologics Products Advisory Committee (VBPAC) unanimously voted on Oct. 15, 2021, to recommend an Emergency Use Authorization (EUA) for a booster dose of the Johnson & Johnson (J&J) COVID-19 vaccine for adults aged 18 or older at least two months following initial vaccination. This decision comes just one day after a 

The vote followed findings from two J&J clinical trials. One was the Phase III ENSEMBLE 2 study which evaluated booster doses of the company’s COVID-19 vaccine administered two months after the single-shot. According to a company press release, these findings suggested increased protection (94%) against moderate-to-severe COVID-19 in the United States.

J&J’s other clinical trial was a Phase I/IIa study evaluating a booster dose given six months after the first shot. According to the press release, this demonstrated a nine-fold increase in antibody levels one week after the booster and a 12-fold increase four weeks after the booster.

In addition to the clinical trials, data from a real-world study that was conducted from March to the end of July, and then extended to the end of August 2021, was also supplied to the council. This study showed stable vaccine effectiveness of 76% for COVID-19 related infections and 81% for COVID-19-related hospitalizations. There was no evidence of reduced effectiveness over the study duration of six months, which included the time period in which the Delta variant became dominant in the US. However, sequencing data was not available for analysis.

“Today’s recommendation is based on the totality of evidence, with clinical and real-world data showing that while a single shot offers strong and long-lasting protection against COVID-19, a booster given after the single-dose primary vaccination increases protection, in particular against symptomatic COVID-19,” said Paul Stoffels, vice-chairman of the Executive Committee and chief scientific officer, Johnson & Johnson, in the press release.

Articles

The council voted 19-0 to recommend that FDA authorize booster doses of the J&J COVID-19 vaccine just one day after granting Moderna a similar recommendation.

FDA Advisory Council Unanimously Supports Johnson & Johnson COVID-19 Booster EUA

INTERPHEX will be held in person at the Javits Center, October 19–21, 2021, and—to continue a long-standing tradition—the editors of 

Pharmaceutical Technology, Pharmaceutical Technology Europe, and BioPharm International

 have organized Keynote Sessions featuring industry experts and moderated by the editors. Unique to this year, however, the sessions will be premiered by video on the show floor. Come to the Innovation Stage to watch the following presentations.

Serialization on a Global Scale: Deep Dive into the US DSCSA and EU FMD

With the deadline for complying with the aggregation requirements of the US Drug Supply Chain Security Act (DSCSA) just two years away and uncertainties about authentication of medicines in a post-Brexit Europe, questions about compliance—and the security of the drug supply—are at the forefront. In this discussion, global supply chain experts examine implications of the DSCSA’s Nov. 27, 2023, aggregation compliance deadline and topical considerations around the European Union’s (EU) Falsified Medicines Directive (FMD). 

As the aggregation compliance for the DSCSA—delayed from 2019—approaches, what do companies across the bio/pharmaceutical supply chain need to tackle now, and what can they expect going forward?

Within Europe, compliance with the delegated EU FMD regulation has been required since 2019. However, implementation of the delegated regulation has not been smooth sailing. In what position has Brexit left stakeholders with regards to medicines authentication? Has it been/might it be necessary to further update manufacturing and packaging lines to accommodate variances in regulations?

Experts from across the global supply chain will provide insight and answers to these questions:

Rebecca Mullis, Engineering Project Manager, Catalent

Staffan Widengren, Director Corporate Projects at Recipharm

David Bond, Senior Manager, Thermo Fisher Scientific’s Pharma Services

Steve Wood, President & CEO, Covectra, Inc.

Géraldine Lissalde-Bonnet, Director Public Policy, GS1 Global Office

Angela Fernandez, Vice President of Community Engagement, GS1 US.

The technical demands of aseptic processing have long challenged pharmaceutical companies and contract manufacturers to produce different volumes of safe, effective, drugs in a cost-effective manner. Drug recalls and regulatory actions have underlined the technical and regulatory hurdles. In this keynote session, experts in aseptic processing will discuss the evolution of their field, including specifics on what might be required to transform existing processing lines to comply with new regulatory requirements, the variety of challenges and new solutions available to deal with small-batch processing, and the application of single-use systems and associated issues, such as shortages and sterilization difficulties. This session will be moderated by Felicity Thomas, European Editor, 

Hear insight from consultants, academic experts, representatives from industry associations, and technical experts from companies supporting aseptic processing:

Presentations held on Tuesday were “Equipment Trends in Advanced Solid-Dosage Drug Manufacturing” and “Advances in Molecule Characterization and Biomanufacturing for Emerging Therapies.” Look for content from these presentations coming soon to the 

The Pharmaceutical Technology and BioPharm International editors host industry experts in serialization and aseptic processing. 

INTERPHEX Keynote Sessions on Wednesday, Oct. 20

Evonik Health Care, an integrated contract development and manufacturing organization (CDMO) that offers excipients, formulation technologies, and clinical and commercial manufacturing, is also offering a new version of its established LIPEX liposome extruder. The next-generation equipment, LIPEX Flow, will be available worldwide beginning in November, the company announced in an Oct. 15, 2021 press release. Evonik also uses the equipment in-house in its CDMO operations, the company says.

LIPEX Flow meets the market need for more efficient, next-generation high pressure extruders to produce drug products requiring conventional liposomal drug delivery, including drugs for oncology, vaccines, and other applications. Lipid-based particles, in particular conventional liposomes, provide a versatile and flexible drug delivery platform for several classes of APIs including small molecules, drug-lipid conjugates, proteins, and peptides, the company stated in the press release.

The company’s LIPEX extruders are used for size reduction of liposomal drug formulations to achieve a specified vesicle size in a reproducible and scalable process. The next-generation extruder’s patent-pending design maximizes the effective filter area, which results in lower extrusion pressures. The new extruder offers higher throughput, faster batch production times, and a broader operating range. It also supports the scale-up of processes from drug discovery through to good manufacturing practice at lab, pilot, intermediate, and commercial-scale volumes.

Evonik’s LIPEX Flow extruder is a new version of its high-pressure equipment for manufacturing liposomal drug products.

Evonik Launches Next-Generation Liposomal Drug Manufacturing Equipment 

Moderna announced on Oct. 14, 2021, that FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) unanimously recommended that FDA grant an Emergency Use Authorization (EUA) for a booster dose of the Moderna COVID-19 vaccine (mRNA-1273). In a 19–0 vote, the VRBPAC recommended a 50 ug booster shot should be made available to three populations:

People aged 18 to 64 who are at high risk for severe COVID-19

People aged 18 to 64 whose exposure to COVID-19 puts them at risk for COVID-19 complications or severe illness.

Additionally, this booster dose is to be administered only after at least six months have passed since their original vaccination series.

A recent Phase II study of mRNA-1273 was conducted wherein 344 interested participants were given a 50-ug booster dose six to eight months following their second dose. According to the study, neutralizing antibody titers, particularly against variants of concern, had waned prior to this study. However, following a booster dose, neutralizing titers were raised significantly to the Phase III benchmark level.

“We thank the committee for their review and for their positive recommendation in support of [EUA]. This positive recommendation is supported by data on the 50-µg booster dose of our COVID-19 vaccine, which shows robust antibody responses against the original virus, but also against the Delta variant,” said Stéphane Bancel, CEO of Moderna, in a company press release. “We remain committed to staying ahead of the virus and following the evolving epidemiology of SARS-CoV-2. We look forward to making our booster available to people in the U[nited] S[tates] to help protect themselves against this ongoing public health emergency.”

This recommendation is non-binding but will be taken into consideration as it concerns an EUA. The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will also meet to discuss a recommendation on a booster shot.

The council voted 19–0 to recommend that FDA authorize booster doses of the Moderna COVID-19 vaccine for certain populations.

Poseida Therapeutics, a clinical-stage biopharmaceutical company specializing in cell and gene therapeutics, announced that it has entered into a research collaboration and exclusive license agreement with Takeda Pharmaceutical Company in an Oct. 12, 2021, press release. In this collaboration, Takeda will utilize Poseida's nanoparticle delivery technology and other proprietary genetic engineering platforms for the research and development of up to eight gene therapies.

This collaboration will focus on developing non-viral 

 gene therapy programs, including Poseida's Hemophilia A program. Poseida will lead research activities up to candidate selection, after which Takeda will assume responsibility for further development and commercialization.

The parties will collaborate to initially develop up to six 

gene therapy programs under the terms of the agreement, utilizing Poseida's technology platforms—including piggyBac, Cas-CLOVER, and biodegradable nanoparticle technology as well as other technologies. In addition, Takeda can add two additional programs to the collaboration and would then provide funding for all collaboration program R&D costs. Poseida will receive an upfront payment of $45 million and preclinical milestones and is eligible to receive future clinical development, regulatory, and commercial milestone payments.

"Our technologies offer highly efficient gene delivery, fully integrated non-viral genome insertion, and ultra-precise site-specific gene editing,” said Eric Ostertag, CEO of Poseida, in a company press release. “Together with Takeda, we look forward to developing potential cures for a number of genetic diseases with high unmet need."

"Poseida's differentiated platform technologies show great promise in developing non-viral 

 gene therapies using their novel genetic engineering and delivery technologies that complement our existing collaborations," said Madhu Natarajan, head of Takeda’s rare diseases drug discovery unit, in the press release.

In this collaboration, Takeda will utilize Poseida's biodegradable DNA and RNA nanoparticle delivery technology and other proprietary genetic engineering platforms for the research and development of gene therapies.

Poseida Therapeutics and Takeda Partner to Develop Non-Viral In-Vivo Gene Therapy Programs

MilliporeSigma, the United States and Canadian life science business of Merck KGaA, Darmstadt, Germany, announced on Oct. 12, 2021, the opening of its second Carlsbad, Calif. facility, which expands its footprint as a contract development and manufacturing organization (CDMO). The $110 million, 140,000-square-footfacility will more than double the life science business sector’s existing capacity to support large-scale commercial and industrial manufacturing for viral gene therapy.

This is MilliporeSigma’s second Carlsbad, Calif. facility, both of which will focus on cell and gene therapy—specifically viral vector-based therapies. There are 30 cleanroom suites between the two facilities that support small- to large-scale clinical and commercial production. In addition, MilliporeSigma is one of the first CDMOs granted FDA and European Medicines Agency approval for viral vector manufacturing, according to the company press release.

“Today, most gene therapies target rare diseases, but there is an urgent need to efficiently manufacture these treatments to reach larger patient populations,” said Matthias Heinzel, CEO, Life Science, Merck, in the press release. “As a leader in viral vector manufacturing, this increase in capacity and scale is the next step in enabling our customers to bring new curative treatments to market.”

MilliporeSigma announced the opening of its second Carlsbad, California-based facility, which doubles production capacity to support commercial and industrial manufacturing of viral vectors. 

MilliporeSigma Completes $110-Million Contract Development Manufacturing Facility for Gene Therapy

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

In the face of a host of contentious and controversial policy decisions, President Biden appears poised to bring in an experienced and well-regarded hand to lead FDA. The agency has lacked a permanent leader for more than eight months, as the White House has been unable to identify a new commissioner acceptable to politicians and interest groups on all sides.

So as the clock has ticked down on the Nov. 15 deadline for Janet Woodcock to vacate her acting commissioner role, potentially forcing Biden to appoint another acting commissioner, word is out that the White House will name cardiologist and research pro Robert Califf to the top job, a position he held for almost a year at the end of the Obama administration.

Califf’s appointment will bring much-needed stability to FDA as it contends with a host of difficult policy decisions involving vaccines, new anti-COVID therapeutics, access to e-cigarettes, accelerated approval programs, and budget priorities. Califf may face opposition in the Senate, as partisan politics has come to the fore on all sides. Although he wins plaudits for his experience in medical research and his familiarity with FDA operations and requirements, some consumer advocates and liberals criticize his close ties to industry and pro-development attitude. He will need support from Republicans, which may be more tenuous in today’s hotly divisive climate on Capitol Hill.

Another factor driving the FDA nomination is the recent announcement of retirement plans by Francis Collins, long-time director of the National Institutes of Health (NIH). Biden will want to name a new leader for NIH before the end of the year, and that provides an opening to bring a woman scientist into the administration’s health and science leadership cadre.

Hopefully, the politicians will recognize the importance of experienced leadership for the nation’s leading health agencies and put aside partisan politics to agree on a new FDA commissioner, and then a new leader at NIH. FDA has been well-served by acting commissioner Woodcock, but her tenuous position has exposed her to criticism and second-guessing on all sides. With a global pandemic still raging, a seasoned hand is needed to stabilize FDA’s exhausted workforce, ensure funding continuity, and steer debate and decisions on many difficult scientific and policy issues.

After months of deliberation, Biden plans to appoint cardiologist Robert Califf as FDA commissioner.

Can Califf Bring Clarity and Enhanced Credibility to FDA?

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

With the pandemic remaining top-of-mind, parenteral products rank as a primary focus at INTERPHEX 2021 (October 19–21, Javits Center, New York, NY). Demonstrations throughout the show floor display fill/finish, labeling, and inspection systems for vials, cartridges, and syringes. Anticounterfeiting and serialization also garner strong interest.

To make the step up from manual filling, TurboFil Packaging Machines has introduced a benchtop syringe filling machine. Offering full control of filling parameters in single or dual operation, the TipFil unit handles up to 12 syringes/min. It can accommodate a variety of syringe sizes and fill liquid or viscous products through the tip. Infeed scenarios include hoppers and reservoirs, and an optional attachment for filling via bottles and vials. Suckback control helps heighten fill accuracy, and all product contact parts are fully disposable, single-use plastic. Filling occurs when a servo motor-driven piston mechanism draws the needle back via the plunger. The distance the plunger is pulled back dictates the amount filled. This design eliminates the need to clean a metering device and ensures precise, repeatable fill (1).

TurboFil also will display its SimpliFil syringe filling and assembly system. Suitable for small to medium batches, the unit accurately fills syringes via ceramic piston, peristaltic pump, or direct draw from a reservoir bag. Walking beam indexing provides intuitive operation and simple, recipe-based changeover. For heightened precision, TurboFil's TipFil technology allows syringes to be filled through the tip, which is a step-saving innovation eliminating the need to insert plungers post-filling. Rated at 36 syringes/min, the SimpliFil system smoothly handles syringes with tips outfitted for press-on caps and luer caps, as well as safety caps for oral syringes. An optional labeler can wrap syringes with pre-printed labels or print and apply labels for medications requiring variable marking. An automatic syringe loading system also is available, as is fill and label verification (1).

Another new filler designed for small batches, the Versynta FFP from Syntegon, features an integrated isolator. Suitable for potent pharmaceuticals, the modular and configurable system with 100% in-process control precisely fills liquid pharmaceuticals into vials, syringes, and cartridges at rates up to 60 containers/min, and it can be converted to different filling systems including single-use. The Pharma Handling Unit, a four-axis robot developed by Syntegon, safely and gently transports containers without glass-to-glass contact (2).

For combined products, Comecer and ATS have partnered to present a Comecer aseptic isolator equipped with SuperTrak Gen3 Pharma linear motion technology to handle ready-to-mix filling and assembly of combined products. The flexible system also can handle dry powders and pills as well as an array of rigid and flexible packaging formats. Linear motion offers faster speeds than walking beam or other transport systems and reduces particle generation due to minimal moving parts (3).

Labeling, printing, and inspection on show at INTERPHEX

Vial labeling is evolving to accommodate the high-speed glass vial lines producing COVID-19 vaccines and other products. The WL-1-RT wraparound labeler from MG America, the US subsidiary of Italy’s MG2, precisely applies labels at speeds of 600 vials/min. A trunnion system provides positive vial control. The machine can be integrated with thermal-transfer and laser coding and is preconfigured for onboard vision inspection with optical character recognition and verification. Non-conforming labels are rejected prior to application (4).

The AV print inspector from Antares Vision Group, a high-resolution vision system, integrates easily on new or existing labeling, printing, or packaging machines and provides 100% inspection for print-on-demand applications. According to the company, the system provides whole-label inspection at speeds up to 80 m/min and supports all major vision system tools for quality control across a wide array of layout features.

To automate parenteral product inspection, Stevanato Group has developed an artificial-intelligence-ready Vision Robot Unit. The autonomous module is capable of automatically inspecting both cosmetic and particle properties without human intervention. The robotic, human-like inspection system combines flexibility with automation efficiency to meet emerging smart factory needs and enhance control process reliability for biotech products such as monoclonal antibodies, vaccines, and lyophilized drugs (5).

For serialization needs, WIPOTEC-OCS plans to demonstrate two checkweigher-compatible traceability modules: the TQS-SP serialization unit and the TQS-CP aggregation unit. The TQS-SP serialization unit applies track-and-trace data to individual cartons and can handle up to 600 cartons/min. A specially designed, double-guided, top-band system ensures stable positioning. The TQS-CP aggregation unit provides semiautomatic aggregation of manually repacked folding cartons to provide a reliable parent-child relationship. ConfigureFast software controls all components including camera, printer, and transport system and expedites setup and changeover (6).

1. TurboFil, “At INTERPHEX NYC, TurboFil to Showcase Module for Simplified, Automated Syringe Filling and Assembly,” Press Release, Oct. 8, 2021.

2. Syntegon, “INTERPHEX 2021: Syntegon to Showcase New Laboratory and Small Batch Solutions for Solid and Liquid Pharmaceuticals,” Press Release, Sept. 23, 2021.

3. Comecer, an ATS company, “Comecer at INTERPHEX 2021 for Pharma Automation,” 

4. MG America, “At INTERPHEX NYC, MG America to Premier Precision Wraparound Labeler for Vials, and Robust 10-Lane Capsule Checkweigher,” Press Release, Oct. 8, 2021.

5. Stevanato Group, “At INTERPHEX NYC, Stevanato Group to Demo Robotic Inspection Unit, Present Modular Assembly Solutions and Recent After-sales Expansion,” Press Release, Sept. 9, 2021.

Back in person at the Javits Center, exhibitors present containers, components, equipment, and services to fill, ship, protect, and optimize the packaging process. 

INTERPHEX Features Pharma Packaging Innovations

Aceto, a provider of specialty materials, announced its acquisition of A&C Bio Buffer, a good manufacturing practices (GMP) manufacturer of custom buffer and chemical blend products used in the manufacturing of biopharmaceutical drug products, in an Oct. 12, 2021, press release. At A&C Bio Buffer’s ISO 9001:2015-certified facility in Limerick, Ireland, the company manufactures more than 50 products, including biological buffers, process solutions, cleaning solutions, and water for injection.

“A&C Bio Buffer is a natural add-on to our acquisition of A&C and aligns with our commitments to the biopharmaceutical space,” said Gilles Cottier, CEO of Aceto, in the press release. “It is a nimble, highly customer-centric organization serving some of the top biopharmaceutical manufacturers in Europe. Its rapid growth reflects a reputation for service and quality, which recently led to its key role in the raw material supply chain for COVID-19 vaccines. A&C Bio Buffer enhances our growing European manufacturing footprint and commercial presence. We believe the shared lineage reflected in A&C Bio Buffer’s skills, culture and customer focus will further support our evolution as a leading supplier of critical raw materials in the life sciences sector.”

Earlier this year, Aceto also acquired A&C, a global manufacturer of GMP specialty excipients and custom process solutions. According to Aceto’s press release, the company will continue to support A&C BioBuffer’s manufacturing facilities and offices in Ireland. However, financial terms were not disclosed.

Aceto will acquire A&C Bio Buffer, including the company’s custom buffer and chemical blend portfolio.

Aceto Acquires A&C Bio Buffer, Expanding GMP Product Lines in Biopharma

PharmaLex Group announced the formal launch on Oct. 12, 2021, of the Biopharma Excellence brand, a major new service line that fuses the scientific, regulatory, and commercialization expertise of PharmaLex, ERA Consulting, and Biopharma Excellence. Christian K. Schneider, the former scientific lead of the Medicines and Healthcare products Regulatory Agency, will head the new unit as chief medical officer.

This new service line combines over 35 years of empirical experience and respected regulator relationships and has a global team of over 70 scientific, regulatory, and commercial professionals that can offer strategic product development and proactive regulatory services that are aimed specifically at developers of advanced therapy medicinal products (ATMPs).

The launch of Biopharma Excellence coincides with the maturation of the biopharma industry, in which the development of ATMPs has accelerated, giving rise to commercial opportunity for innovation in fields such as cell and gene therapies, monoclonal antibodies, vaccines, and biosimilars.

Biopharma Excellence is intended to serve biopharmaceutical companies ranging from small startups to divisions of large, established life sciences organizations. Its multi-disciplinary solutions are geared toward commercial as well as scientific and regulatory success.

“Gene and cell therapies have reached ‘adolescence’ now,” said Schneider, who was previously chair of the European Medicines Agency’s Committee for Advanced Therapies, in a company press release. “Ten years ago, there wasn’t a single treatment authorized, but now we see numerous successes emerging from clinical trials, or treatments already authorized, from CAR [chimeric antigen receptor] T-cell therapy to gene therapies designed to correct rare, hereditary diseases.”

“This, in turn, is opening the door for innovative biopharmaceutical developers. But because their ambitions invariably involve difficult clinical indications, their route to market is far from straightforward—which is where Biopharma Excellence comes in. Our combined breadth of knowledge, and the ability to apply this strategic, multi-disciplinary scientific, regulatory and commercial expertise to biopharma specifically, makes for a very powerful proposition,” Schneider added. “I’d like to see Biopharma Excellence become a clear leader in biotech: in actively enabling the advancement of cutting-edge medicines. We’re very well placed for this, and I hope my 15 years at the front end of Regulatory Science will further help to ensure that our clients strike the right balance between meeting Agency scientific requirements and creating a compelling proposition for investors and payers.”

Pharmalex has launched the Biopharma Excellence brand, a new service line that combines the expertise of PharmaLex, ERA Consulting, and Biopharma Excellence.