Track-and-Trace Progress Benefits Supply-Chain Security Efforts

COVID-19 vaccines, approved under emergency use authorization, were not required to meet serialization requirements, but they have been properly labelled to meet US Food and Drug Administration (FDA) requirements, he says, complete with 2D barcodes with GTIN, lot, and expiry date. The company decided to serialize its Diprovan anesthetic, a workhorse generic product, using radio frequency identification tags containing the four identifiers (2). "If an agent is handling your product on your behalf, they need to leverage GS1 Standards including GTINs for products [and] global location numbers (GLNs) for physical locations, and share data electronically using electronic product code information services (EPCIS) to capture events from manufacturing to serialization [and] capping to shipping.

Prioritizing Cleaning Validation

Among the observations noted were failure to maintain clean and sanitary conditions;lack of written procedures for cleaning and decontamination of the vessels used to transport and store materials at the site;and no formal requirements to clean and sanitize these vessels after each use. [...]documentation must include the names and signatures of staff performing the work, as well as the product batch number, cleaner expiry date, and disinfectants used. Single-use systems and equipment have eliminated some of those problems, but they persist for hybrid plants still using stainless steel equipment. More work is also being done to use analytical methods to reduce the subjectivity of visual inspection, but Forsyth hasn't seen any consistentlyin place from the time of marketing authorization application (MAA) filing.

COVlD-19 vaccine Distribution: Preparing for the Unexpected

In December 2020, two shipments of the vaccine experienced temperature excursions in which product was actually kept at overly cold temperatures (3). Urgent need to protect data One problem that vaccine developers and regulatory agencies need to address is the urgent need to protect data, says Nigel Thorpe, technology director with Secure Age, which specializes in enterprise data encryption using a public key infrastructure platform. For operators on the plant floor, the efforts required are fraught with potential error, especially during shift changes, says Jim Evans, director of Verista, Inc.'s vision, connectivity, and automation division. Raw materials The speed with which vaccines have been developed and are being distributed pose important questions centred around variability. If we're having a raw materials shortage when the vaccines haven't even been scaled up, what will happen when they get full approval?" he asks.

Clinical Flexibility Breaks Through Drug Development Barriers

With J&J's vaccine, cell-line optimization was also crucial, not only for speeding the vaccine's development but for optimizing its manufacturability and stability, as Paul Stoffels, executive vice president and chief scientific officer told attendees at the 2020 Galien Forum (3). [...]more bio/pharma companies have been using data analytics, including artificial intelligence/machine learning (AIML), which can be applied to real-world data from such diverse data sources as electronic health records, lab test results, and insurance claims, to ensure that trial design and patient recruitment reflect actual conditions. Closer collaboration For bio/pharma companies, one fundamental change that is speeding drug development has been increased collaboration and cross-learning through partnerships, says Lance Minor, national co-leader of life sciences practice for the management consultant, BDO USA LLP. The new pilot would cover new, nontraditional methods of data collection or analysis methods;technologies such as tissue chips that serve as micromodels of specific organ systems for safety tests;and use of artificial intelligence and wearable sensors, which could be used during clinical trials.

Beyond Lyophilization

The company's Lyoguard trays are being used in the production of mAbs;diagnostics tests for COVID-19 virus or antibodies;and some of the key raw materials used in messenger RNA (mRNA) vaccines, including synthetic oligonucleotides, adjuvants, and lipid nanoparticles, he says. [...]it's a question of capacity. Another problem is the fact that lyophilization involves very slow cooling, at a rate of one degree Kelvin per second, says Bill Williams, a professor at the University of Texas and inventor of the thin-film freezing process, which he developed years ago at the Dow Chemical Co. TFF Pharma licensed his technology and commercialized it in 2019. Williams and his team, with corporate and US government funding, are now focusing on research designed to optimize use of thin-film freezing to improve the processing and delivery of biologics, including vaccines, along with the cold chain.

Improving Agility Through Scalability

Miniaturized, modular, and continuous manufacturing processes will help speed scale-up, address supply chain complexity, and prevent shortages of important medications, Janet Woodcock, director of the United States Food and Drug Administration's (FDA's) Centre for Drug Evaluation and Research (CDER), noted during a meeting of the US National Academy of Sciences (NAS) in late February 2020. Describing the research at the NAS meeting (2), Rao said his team has conducted a demonstration project involving Neupogen (filgrastim) and is working with GE on development of remote bioreactor sensors to monitor analytes, oxygen, and carbon dioxide in smallscale systems in real time (2). [...]since research results were first published, he notes, robotics have been improved, and now include integrated online measurement systems using infrared (IR), FourierTransform IR, and high-pressure liquid chromatography and mass spectrometry so that key parameters can be measured in real-time, permitting online process monitoring as well as process optimization. Use of Raman and nuclear magnetic resonance (NMR) spectroscopy, refractive index, excipient identification, metabolite monitoring, and cell counts has now become routine, in both process development and manufacturing, says Christy.

Can Pharma Quality Go High Tech?

"There were questions of how to handle tech transfer, factory and site acceptance tests, and regulatory inspections when the world was no longer travelling," he says. Since July, Stracquantanio says, usage of the platform has expanded by a factor of 17, and new site deployments by a factor of ten. The company is now using the remote approach with all major global regulatory agencies. Since Catalent hosts or performs more than 500 audits each year, new technology has allowed Catalent to keep pace, while observing social distancing requirements, Montano adds. Live facility tours are filmed with a 360-degree camera, and 3-D tours with a 3-D mapping camera, says Sandy Immerman, vice president of Information Technology (IT), Pharma Services. [...]this year, Immerman says, Thermo Fisher has hosted multiple regulatory inspections and more than 125 client audits, focusing efforts on current good manufacturing practice (CGMP) activities in work that has involved FDA, the European Medicines Agency, which issued formal guidance on the use of this technology last May (3), the Russian Ministry of Health (MoH), and the Swedish Medical Products Agency.