Early investment in formulation strategies will maximize the chance of success.

The Earlier the Better in Formulation

Advances in simulation and the development of digital twins.

Computational Fluid Dynamics in Upstream Biopharma Manufacturing

Different methods give different answers when calculating limits for impurities.

Detecting and Determining Quantitation Limits for Impurities

Automatic visual inspection machines and AI highlight inspection deficits.

Visual Inspection: Seeing Room for Improvement?

Despite their promise, alternative drug delivery approaches are complex and must be justified.

Taking an Alternative Approach to Drug Delivery

Traditional statistical process control rules can be relaxed or adjusted to allow charting and evaluation of real-life data. 

Practical SPC Rules to Apply on Pharmaceutical Process Data

Novavax COVID-19 Vaccine Receives EUA in Indonesia

FDA Grants EUA for Pfizer-BioNTech COVID-19 Vaccine Use in Children

A published report details discussions by international regulators on the effectiveness of the COVID-19 vaccines on the omicron variant, regulatory requirements for a variant vaccine, and clinical study design. The International Coalition of Medicines Regulatory Authorities (ICMRA) organized the Jan. 12, 2022 workshop on the global response to the COVID-19 omicron variant, which was co-chaired by the European Medicines Agency (EMA) and FDA.

Workshop participants reviewed data on the impact of the variant and concluded that while the current vaccines offer less protection against infection with the COVID-19 omicron variant and mild disease, they do offer protection against severe disease and hospitalization, especially with a booster dose.

“When looking at possible vaccination approaches against Omicron and other virus variants, the meeting participants agreed that the administration of multiple booster doses at short intervals is not a sustainable approach in the longer term. There is a need to develop a long-term strategy on the types of vaccines needed to manage COVID-19 in the future. This is an ongoing global discussion that sits at the crossroads of science, public policy, and public health and will require coordination among public health decision-makers at all levels,” EMA stated in a press release.

According to EMA, regulators are encouraging developers to look for alternative approaches to monovalent vaccines and explore the possibility of developing bivalent or multivalent variant vaccines. Workshop participants stressing that clinical studies should be performed to support the use of a new vaccine. “These studies should be designed to demonstrate that the immune response, measured as neutralizing antibodies, generated by the updated vaccine is superior to that achieved with current vaccines. The ability of the updated vaccines to cross-neutralize other variants of concern would be an additional feature with respect to the breadth of protection provided by the updated vaccine,” EMA stated in the release.

Articles

A report by international regulators reviews the effectiveness of current COVID-19 vaccines against the omicron variant.

COVID-19 Vaccination Offers Protection from Hospitalization due to Omicron Variant, According to Report

Mylan Pharmaceuticals, a Viatris company, announced on Jan. 18, 2022, that it is voluntarily recalling one batch of non-interchangeable Semglee (insulin glargine injection), 100 units/mL (U-100), 3mL prefilled pens because of a possible missing label in the batch. The recalled batch was manufactured by Biocon Sdn Bhd and distributed by Mylan Specialty L.P. in the United States between May 11, 2021 and Nov. 11, 2021. The recall does not apply to interchangeable biosimilars, Semglee (insulin glargine-yfgn) injection, a branded product, or Insulin Glargine (insulin glargine-yfgn) injection, an unbranded product.

Non-interchangeable Semglee (insulin glargine injection) is a long-acting human insulin analog used to improve glycemic control in patients with type 1 and type 2 diabetes mellitus. According to the company, a missing label could cause a mix-up of products/strengths and lead to administration of the incorrect insulin.

There have been no reports of adverse events related to the recall as of the date of the recall notice. Adverse events may be reported to FDA via the agency’s MedWatch Adverse Event Reporting program.

The company is voluntarily recalling one batch of Semglee prefilled pens because of a potential missing label.

Mylan Recalls Semglee Prefilled Pens

AstraZeneca has announced, in a Jan. 17, 2022 press release, that the Scottish Medicines Consortium (SMC) has accepted Osimertinib (Tagrisso) for use as a monotherapy for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations.

Lung cancer is a significant cause of cancer-related death in Scotland, with NSCLC being recorded as the most common form of the disease. It is estimated, by AstraZeneca, that through the recent acceptance of Tagrisso, approximately 192 patients in Scotland will be eligible for targeted therapy to treat locally advanced or metastatic EGFR mutated NSCLC each year.

“Osimertinib is a third-generation EGFR inhibitor that has demonstrated clear survival benefit in clinical trials when compared to the previous generation of these medicines,” said Brian Clark, consultant clinical oncologist at Beatson West of Scotland Cancer Centre, in the press release. “Getting access to this treatment is an important development for people living with advanced lung cancer in Scotland, as it provides them with a treatment option that has the potential to improve their outcomes and does not compromise quality of life.”

“This decision from the SMC is further welcome news aligned with the Scottish Government’s commitment to cancer as a national clinical priority,” added Tom Keith-Roach, president, AstraZeneca UK, in the press release. “Providing access to cutting-edge treatments like osimertinib is an important part of getting back on track post-COVID.”

“With almost half of all lung cancers in Scotland diagnosed at a late stage, there is a clear unmet need for additional effective treatment options,” said Arun Krishna, head of Oncology, AstraZeneca UK, in the press release. “Osimertinib can significantly increase survival of patients with EGFR mutation-positive NSCLC, with a comparable safety profile to first generation EGFR TKIs [tyrosine kinase inhibitors].”

AstraZeneca's Tagrisso has been accepted for use as a monotherapy for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with activating EGFR mutations in Scotland.

AstraZeneca’s Tagrisso Accepted for Use in Scotland to Treat EGFR Mutated Advanced Lung Cancer

Air France KLM Martinair Cargo (AFKLMP Cargo) and Envirotainer—provider of secure cold-chain solutions for the air transportation of pharmaceuticals—are collaborating on more sustainable air transport of pharmaceuticals, it was revealed in a Jan. 18, 2021 press release.

The companies have been partners for a long time, and each has a strong focus on sustainability. With this announcement, the companies have specified that they will intensify their partnership to strengthen their initiatives for sustainability through collaboration.

AFKLMP Cargo will be implementing in its booking system the new Envirotainer Releye container, which is reported to deliver up to 90% reduction in CO

 emissions compared with other available passive solutions when based on life-cycle analysis. Envirotainer will be investing in Sustainable Aviation Fuel (SAF), which is produced from sustainable feedstock and is claimed to reduce CO

 emissions by up to 85% when compared with conventional jet fuel.

“We are very happy that a close partner of ours since many years keeps delivering top quality service and secures that the pharmaceutical industry, together with us, provides further capacity of latest technology,” said Don Harrison, head of Global Key Accounts, Airlines at Envirotainer, in the press release.

“We really appreciate our long-term partnership with Envirotainer,” added Marcel Kuijn, global head of Pharmaceutical Logistics at AFKLMP Cargo, in the press release. “Sustainability and Pharmaceuticals are among our strategic focus areas. That is why this initiative is of such great importance to us.”

Air France KLM Martinair Cargo and Envirotainer are collaborating on more sustainable air transport of pharmaceuticals

Air France KLM Martinair Cargo and Envirotainer Collaborate on Sustainability

PharmaLex Group has announced on Jan. 18, 2022, that is has merged with MAP Group, an Italian provider of market access services. Through this merger, PharmaLex broadens its market access expertise and extends its reach into the Italian marketplace.

MAP Group was founded in 2010 and comprises three companies—MA Provider, MAPCOM Consulting, and 3P Solution. The group specializes in highly innovative products, such as advanced therapeutic medicinal products (ATMPs) under development for rare diseases and oncology, and is a leading member of the ATMP forum.

“The merger with PharmaLex perfectly complements our service offerings by leveraging our strong local market knowledge and expertise while providing our clients with broader reach across Europe,” said Elena Paola Lanati, MAP Group CEO and founder, in the company press release. “We share common principles and values with PharmaLex, in particular to help our clients navigate an increasingly complex legislative and commercial marketplace. In addition, the merger with PharmaLex provides an opportunity for our talented people to expand their careers in a broader global marketplace.”

“We are delighted to welcome the MAP Group team to the PharmaLex Group, and we are excited about the opportunity that the merger gives us to further expand our offerings in market access, brand communications, and educational services,” added PharmaLex CEO Thomas Dobmeyer, in the press release. “The merger also enables us to extend our footprint in the important Italian marketplace, adding to our strong existing team in Milan, which provides regulatory, safety, and quality services to local clients. PharmaLex first established an office in Italy 2017 and has since built a strong local footprint. Through the merger with the MAP Group, we are further strengthening our team, allowing us to support clients throughout the product lifecycle in order to deliver exceptional, tailor-made results.”

PharmaLex Group has merged with MAP Group, broadening its market access expertise and extending its reach into the Italian marketplace.

PharmaLex Expands Integrated Market Access Expertise through Merger with MAP Group 

Developer of disease modifying therapies, Cyxone, has appointed a European contract development and manufacturing organization (CDMO) to scale-up and produce the active ingredient of its T20K drug candidate.

According to a Jan. 18, 2022 press release, the agreement will initially cover method development and then, at a later stage, will include the supply of material for use in non-clinical and clinical development activities. Additionally, production of the active ingredient will be performed in accordance with good manufacturing practice (GMP), exploring a novel manufacturing method.

T20K is a peptide that has been developed for the treatment of multiple sclerosis. The drug has demonstrated the potential capability of preventing disease progression in a model system at the preclinical stage.

“We are pleased to have established a collaboration with one of Europe’s leading manufacturers of therapeutic peptides,” said Tara Heitner, CEO, Cyxone, in the press release. “T20K GMP manufacturing is an important step before non-clinical safety studies and future clinical studies. A feasibility study will be the first step of this collaboration permitting further optimization of the scale up process. The agreement represents our commitment to the T20K program and indicates that we are on schedule with our non-clinical plans.”

Cyxone has appointed a European CDMO to scale-up and produce the active ingredient of its T20K drug candidate.

Cyxone Engages European CDMO for Scale-Up and Production of T20K

The corporate venture fund of Colorcon, Colorcon Ventures, has announced, in a Jan. 20, 2022 press release, its investment in a provider of intelligent manufacturing execution systems (MES), Apprentice.io (Apprentice).

The end-to-end platform offered by Apprentice helps streamline pharma manufacturing and remote collaboration. A suite of software solutions is offered, including intelligent batch execution, augmented procedures and workflows, predictive resource management, and immersive training. Through artificial intelligence, machine learning, and augmented reality, the platform becomes more intuitive over time.

“Our customers are striving for faster times to market, improved manufacturing consistency, as well as business continuity through times of crisis,” said Ali Rajabi-Siahboomi, vice-president and chief innovation officer at Colorcon, in the press release. “During COVID, demand for Apprentice has accelerated with several leading pharmaceutical manufacturers, as design weaknesses in legacy manufacturing systems were exposed. Based on the positive outcomes seen by industry participants, we anticipate a broader global adoption of Apprentice’s solutions.”

“We are excited to have Colorcon Ventures join us as a strategic investor on our mission to modernize pharmaceutical manufacturing and realize Pharma 4.0, with the objective of getting medicine to patients faster and safer,” added Angelo Stracquatanio, Apprentice’s founder and CEO, in the press release. “Colorcon’s global footprint and pharma relationships will be invaluable as we begin to expand our geographic reach.”

Colorcon Ventures is investing in a provider of intelligent manufacturing execution systems (MES), Apprentice.io.

Colorcon Ventures Invests in Provider of Intelligent MES

Jennifer Markarian is manufacturing editor of Pharmaceutical Technology.

Digitalization is taking hold in many areas of the pharmaceutical industry. 

 spoke with Marcus Michel, CEO of ACG Engineering, about digitalization in pharmaceutical manufacturing equipment and ACG’s own digital transformation journey.

 What trends do you see currently in use of digitalization/Industry 4.0 technologies for the equipment you supply to bio/pharma manufacturers?

 Industry 4.0, or the ‘digital revolution’, is gaining momentum within the pharmaceutical industry. In particular, Big Data, artificial intelligence, cloud computing, continuous connectivity, and advanced analytics through the Industrial Internet of Things (IIoT) are being utilized by pharma and biopharma manufacturers to deal with issues, such as rising complexities, costs, remote connectivity, and regulations. Smart factories managed with data analytics and machine learning will lower pharmaceutical manufacturing costs, improve quality, and reduce capacity constraints. Ongoing advances in predictive analytics are enabling manufacturers to draw on vast pools of data, including information on resource consumption, machine performance, and storage conditions on shop floors to troubleshoot problems, optimize processes, and boost productivity.

With forward-thinking pharmaceutical companies expediting their plans for digital transformation following the COVID-19 pandemic, a few trends indicate the early stages of adoption of Industry 4.0 in the pharmaceutical manufacturing sector. These trends include smart connected machines and factories; the leap from a reactive to a proactive framework using data analytics; augmented and virtual reality (AR/VR) services, including remote machine maintenance, remote factory acceptance testing, and even installation and commissioning; additive manufacturing; process unit design; digital twin systems; and personalized medicine and the correct use of big data.

ACG began its digital transformation journey in 2017 with four broad objectives: 1) to use emerging digital technologies to transform manufacturing operations, 2) to enhance customer experience, 3) to build smart products and services, and 4) to create new business models. Reducing machine breakdowns and enhancing overall equipment effectiveness in capsule manufacturing were the key business drivers. While the current focus is on transforming operations, ACG is expanding into building smart connected products and services, developing customer experiences, and creating digital-led business models.

 What do you see as the biggest obstacles to the implementation of these technologies?

 The major challenges experienced by the pharmaceutical industry during this digital revolution are:

Integrating new information technology (IT) systems and updating existing systems

To completely capitalize on the potential of the IIoT, pharmaceutical manufacturers need to invest in an IIoT infrastructure that has the capacity to handle their high level of requirements. As data and network security are of paramount importance, manufacturers must also be prepared to integrate existing protocols with the latest security solutions. There must be a check on the data that is flowing out of the plants to the Cloud servers. Manufacturing shop floors typically house a wide variety of equipment and associated software, some of which are legacy systems and no longer enjoy vendor warranty. Therefore, IIoT relevant upgrades are crucial. However, these upgrades can be costly. Additionally, the workforce needs to be trained, upskilled, and educated on the importance of these technological advancements, as they are an integral part of this digital transformation.

 What do you see as needs in workforce training or changing the business and work culture to adapt to these new technologies?

 Building, deploying, and adopting Industry 4.0 initiatives requires a wide variety of technology and domain capabilities. Active collaboration with the original equipment manufacturers, continuous improvement cells, and hands-on training sessions will help in developing the required skill sets. Pharmaceutical manufacturers will have to work on developing a few core competencies, as well as flexibility, to be in the driver’s seat for successful adoption and implementation of digitalization and the technologies of the future. These competencies include:

 Industry 4.0 needs existing systems to be updated and, in some cases, entirely new IT infrastructure setups. Legacy systems are workhorses, but not high on data security, cybersecurity, and flexible communication protocols. Companies need tailored risk management systems, in addition to a strategy for cybersecurity across the organization and value chain.

 Digitalization increases the need for companies to develop new skills at an individual associate level, as well as at an organizational level. To shorten the skill development timeline, recruiting a digitally acquainted workforce and virtual training through AR/VR applications are measures being adopted by companies. This is important in terms of improving quality since we are dealing with pharmaceutical products.

 As horizontal integration will create transparency and flexibility across process chains—from procurement to production and maintenance—vertical networking opens doors to collaborate with customers and [original equipment manufacturers] to build new business models for product-based customized solutions and remote aftermarket services. Remote condition monitoring, data analytics, and sharing insights across the value chain will open avenues for different business models.

 Flexibility for adaptation will be different for different segments in an organization. R&D, services, warehousing, and production have great potential to adapt and benefit from this shift to new technologies. However, the business rules and set process standards make it difficult for warehousing, administration, and sales to transform.

 What do you see as the future in adoption of digitalization technologies in bio/pharma manufacturing?

 The Fourth Industrial Revolution is beginning to flourish within the pharmaceutical sector, which was reluctant to change before COVID-19 hit the world. Due to the pandemic, companies have realized the need for digitalization and are now focusing on a complete adoption of digital technologies. What does Industry 4.0 mean for the pharmaceutical industry? It means increased connectivity, higher productivity, simplification, and transparency in compliance, as well as consolidation and analysis of production information to optimally respond to manufacturing issues as they emerge.

Although there are challenges to be addressed, the digital transformation of equipment has begun. 

Digitalization in Pharmaceutical Manufacturing Equipment

Lohxa LLC announced on Jan. 11, 2022, that it is voluntarily recalling one lot of Senna Syrup 8.8 mg/5mL, unit-dose cups due to microbial contamination. Senna Syrup is a natural vegetable laxative and is packaged in 5-mL unit-dose cups. The affected lot is AM1115S with expiration date of 01/2023 and was distributed to a wholesaler, AvKare. The product may then have been distributed by AvKare to clinics, hospitals, and healthcare providers.

According to the company, use of the contaminated product could be life threatening in patients who are elderly, have weakened immune systems, or who are at risk for heart inflammation. The company has not, as of the date of the press release, received any reports of adverse events related to the recall.

The company is voluntarily recalling one lot of Senna Syrup 8.8mg/5mL, unit-dose cups because of microbial contamination. 

Lohxa Recalls Senna Syrup

FDA has published its review of the accomplishments the agency achieved in 2021. 

FDA 2021 Year in Review–Working for You 

details the agency’s response to COVID-19, including vaccine, treatment, and testing authorizations. FDA has also been monitoring variants of the virus and issuing guidance and contingency plans for dealing with the pandemic. The report also discusses the agency’s efforts for addressing the misuse of prescription drugs, the problem of fraudulent medicines, and the advancement of generic drugs and biosimilars, as well as its work in food safety and tobacco products.

“While much of the attention the agency received in 2021 focused on our response to the pandemic, I am pleased to note that, despite a great deal of uncertainty, the agency was able to accomplish a wide range of its priorities that are already protecting the health and well-being of millions of people living in the US,” said Acting Commissioner Janet Woodcock, MD, in the report. “Every year the FDA reviews hundreds of product applications, ultimately determining which drugs, devices, or biological products (e.g., vaccines) will be marketed in the US. The process involved is rigorous, thoughtful and always adheres to standards for safety and effectiveness. We help to ensure that the human and animal food supply is safe, sanitary, and accurately labeled, and that cosmetic products are safe and properly labeled,” said Woodcock.

The agency discusses its response to COVID-19 and other milestones in its year-end review.