Research Progress of Raman Spectroscopy and Raman Imaging in Pharmaceutical Analysis.

The analytical investigation of the pharmaceutical process monitors the critical process parameters of the drug, beginning from its development until marketing and post-marketing, and appropriate corrective action can be taken to change the pharmaceutical design at any stage of the process. Advanced analytical methods, such as Raman spectroscopy, are particularly suitable for use in the field of drug analysis, especially for qualitative and quantitative work, due to the advantages of simple sample preparation, fast, non-destructive analysis speed and effective avoidance of moisture interference. Advanced Raman imaging techniques have gradually become a powerful alternative method for monitoring changes in polymorph distribution and active pharmaceutical ingredient distribution in drug processing and pharmacokinetics. Surface-enhanced Raman spectroscopy (SERS) has also solved the inherent insensitivity and fluorescence problems of Raman, which has made good progress in the field of illegal drug analysis. This review summarizes the application of Raman spectroscopy and imaging technology, which are used in the qualitative and quantitative analysis of solid tablets, quality control of the production process, drug crystal analysis, illegal drug analysis, and monitoring of drug dissolution and release in the field of drug analysis in recent years.

Reimagining drug manufacturing paradigm in today's pharmacy landscape.

The coronavirus disease 2019 pandemic has escalated the ongoing problem of critical medication shortages, which has serious implications for the health of our patients. Currently, active pharmaceutical ingredients (APIs) are synthesized in large-scale batch operations and shipped to drug product manufacturers, where they are produced on a large scale at centralized facilities. In the centralized drug manufacturing process, the formulation components, operations, and packaging are structured to favor long-term storage and shipment of resultant medicines to the point of care, making this process vulnerable to supply chain disruptions. We propose a rethinking of the drug manufacturing paradigm with an upgraded pharmaceutical compounding-based manufacturing paradigm. This paradigm will be based on integration of continuous manufacturing of APIs and manufacturing of medicines at the point of care with application of machine learning, artificial intelligence, and 3-dimensional printing. This paradigm will support implementation of precision medicine and customization according to patients' needs. The new model of drug manufacturing will be less dependent on the supply chain while ensuring availability of medicines in a cost-effective manner.

Transformation of Biopharmaceutical Manufacturing Through Single-Use Technologies: Current State, Remaining Challenges, and Future Development.

Single-use technologies have transformed conventional biopharmaceutical manufacturing, and their adoption is increasing rapidly for emerging applications like antibody-drug conjugates and cell and gene therapy products. These disruptive technologies have also had a significant impact during the coronavirus disease 2019 pandemic, helping to advance process development to enable the manufacturing of new monoclonal antibody therapies and vaccines. Single-use systems provide closed plug-and-play solutions and enable process intensification and continuous processing. Several challenges remain, providing opportunities to advance single-use sensors and their integration with single-use systems, to develop novel plastic materials, and to standardize design for interchangeability. Because the industry is changing rapidly, a holistic analysis of the current single-use technologies is required, with a summary of the latest advancements in materials science and the implementation of these technologies in end-to-end bioprocesses.

Aversion liquid-filled drug releasing capsule (3D-RECAL): A novel technology for the development of immediate release abuse deterrent formulations using a fused deposition modelling (FDM) 3D printer.

COVID19 has caused a significant socioeconomic burden worldwide. Opioid crisis was further intensified with the increasing number of opioid overdose/misuse related deaths in last two years. Abusers have adopted newer/efficient methods for manipulating and abusing commercial opioid formulations. Food and Drug Administration (FDA) has been strategizing tirelessly to prevent misuse/abuse of prescription opioids. One of the strategies is to develop an abuse deterrent formulation (ADF). The current study aims to develop a novel 3D printed drug-releasing capsule shell filled with an aversion liquid (3D-RECAL). Primarily, metformin hydrochloride (MT, model drug) loaded printable filaments of polyvinyl alcohol was prepared using hot melt extrusion. Following extrusion, a 3D printed capsule shell was designed and fabricated using a single nozzle fuse deposition modelling 3D printer. An aversion liquid to be filled in 3D-RECAL capsules was prepared by combining sudan black and sodium polyacrylamide starch in oil base. Mechanical analysis of extruded filaments suggested that the filaments with 20%w/w MT had a higher mechanical strength compared to other drug loadings. Instantaneous gelling and large black non-snortable particles were formed during solvent extraction and physical manipulation studies, respectively. Due to the drug being embedded in the capsule shell, MT release was immediately started with >85% of MT release within 45 mins in 0.1 N HCl. Due to the everlasting need for the newer efficient ADF technologies, 3D-RECAL can be a step in the right direction towards saving lives, providing safe and effective measures to deterring abusers.

Evaluation of portable devices for medicine quality screening: Lessons learnt, recommendations for implementation, and future priorities.

Céline Caillet and co-authors discuss a Collection on use of portable devices for the evaluation of medicine quality and legitimacy.

Understanding Quality Paradigm Shifts in the Evolving Pharmaceutical Landscape: Perspectives from the USP Quality Advisory Group.

Recent changes in the pharmaceutical industry have led to significant paradigm shifts in the pharmaceutical quality environment. Globalization of the pharmaceutical industry, increasingly rapid development of novel therapies, and adoption of new manufacturing techniques have presented numerous challenges for the established regulatory framework and quality environment and are impacting the approaches utilized to ensure the quality of pharmaceutical products. Regulators, industry, and standards-setting organizations have begun to recognize the need to rely more on integrated risk-based approaches and to create more nimble and flexible standards to complement these efforts. They also increasingly have recognized that quality needs to be built into systems and processes throughout the lifecycle of the product. Moreover, the recent COVID-19 crisis has emphasized the need to adopt practices that better promote global supply chain resilience. In this paper, the USP Quality Advisory Group explores the various paradigm shifts currently impacting pharmaceutical quality and the approaches that are being taken to adapt to this new environment. Broad adoption of the Analytical Procedure Lifecycle approach, improved data management, and utilization of digital technologies are identified as potential solutions that can help meet the challenges of these quality paradigm shifts. Further discussion and collaboration among stakeholders are needed to pursue these and other solutions that can ensure a continued focus on quality while facilitating pharmaceutical innovation and development.

Continuous manufacture of hydroxychloroquine sulfate drug products via hot melt extrusion technology to meet increased demand during a global pandemic: From bench to pilot scale.

During pandemics and global crises, drug shortages become critical as a result of increased demand, shortages in personnel and lockdown restrictions that disrupt the supply chain. The pharmaceutical industry is therefore moving towards continuous manufacturing instead of conventional batch manufacturing involving numerous steps, that normally occur at different sites. In order to validate the use of large-scale industrial processes, feasibility studies need to be performed using small-scale laboratory equipment. To that end, the scale-up of a continuous process and its effect on the critical quality attributes (CQAs) of the end product were investigated in this work. Hydroxychloroquine Sulphate (HCQS) was used as the model drug, Soluplus® as a model polymeric carrier and both horizontal and vertical twin screw extruders used to undertake this hot melt extrusion (HME) study. Seven formulations were processed using a small-scale horizontal extruder and a pilot-scale vertical extruder at various drug loadings, temperature profiles and screw speeds. When utilising a horizontal extruder, formulations with the highest drug load and processed at the lowest screw speed and temperature had the highest crystallinity with higher drug release rates. Upon scale-up to a vertical extruder, the crystallinity of the HCQS was significantly reduced, with less variation in both crystallinity and release profile across the different extrudates. This study demonstrates improved robustness with the pilot-scale vertical extruder compared to lab-scale horizontal extruder. The reduced variation with the vertical extruder will allow for short increases in production rate, with minimum impact on the CQAs of the final product enabling high-performance continuous manufacturing with minimum waste of raw materials. Finally, this research provides valuable information for the pharmaceutical industry in accessing continuous technologies for the manufacture of pharmaceutical products, allowing for efficient utilisation of resources upon scale-up and mass production during global pandemics and drug shortages.

Manufacturing a chimpanzee adenovirus-vectored SARS-CoV-2 vaccine to meet global needs.

Manufacturing has been the key factor limiting rollout of vaccination during the COVID-19 pandemic, requiring rapid development and large-scale implementation of novel manufacturing technologies. ChAdOx1 nCoV-19 (AZD1222, Vaxzevria) is an efficacious vaccine against SARS-CoV-2, based upon an adenovirus vector. We describe the development of a process for the production of this vaccine and others based upon the same platform, including novel features to facilitate very large-scale production. We discuss the process economics and the "distributed manufacturing" approach we have taken to provide the vaccine at globally-relevant scale and with international security of supply. Together, these approaches have enabled the largest viral vector manufacturing campaign to date, providing a substantial proportion of global COVID-19 vaccine supply at low cost.

Warp-Speed Covid-19 Vaccine Development: Beneficiaries of Maturation in Biopharmaceutical Technologies and Public-Private Partnerships.

It is anticipated that effective vaccines will enable the resumption of social and economic normalcy. Current calls for masking, social distancing and other restrictive measures for the public-good are difficult to enforce and are unstainable. As ~2-4% of the 50 million SARS-CoV2-infected have succumbed to Covid-19, the US department of Health and Human Services has organized a public-private partnership called Operation Warp Speed (OWS) to develop, produce and deliver 300 million doses of safe and effective vaccines with a January 2021 target. While a majority of the 300+ Covid-19 vaccine candidates are in various stages of preclinical and early-stage clinical testing, 6 clinical candidates are supported with over 10 billion USD plus integrated resources under the OWS agenda. This unprecedented approach is investing in the manufacture of product candidates ahead of product approval. It is enabled by new gene and recombinant pharmaceutical platform technologies that are accelerating the clinical study timeline from ~10 to less than 1 year. It is anticipated that one or more of the 6 candidates under the OWS initiative will be safe, effective and provide a sustained immune response to prevent infection and disease progression. This way, social and economic activities could return to normalcy.

Developing Vaccines for SARS-CoV-2 and Future Epidemics and Pandemics: Applying Lessons from Past Outbreaks.

The COVID-19 pandemic is a stark reminder of the heavy toll that emerging infectious diseases (EIDs) with epidemic and pandemic potential can inflict. Vaccine development, scale-up, and commercialization is a long, expensive, and risky enterprise that requires substantial upfront planning and offers no guarantee of success. EIDs are a particularly challenging target for global health preparedness, including for vaccine development. Insufficient attention has been given to challenges, lessons learned, and potential solutions to support and sustain vaccine industry engagement in vaccine development for EIDs. Drawing from lessons from the most recent Ebola epidemic in the Democratic Republic of the Congo, as well as the 2009 H1N1 influenza, 2014-2016 Ebola, and 2015-16 Zika outbreaks preceding it, we offer our perspective on challenges facing EID vaccine development and recommend additional solutions to prioritize in the near term. The 6 recommendations focus on reducing vaccine development timelines and increasing business certainty to reduce risks for companies. The global health security community has an opportunity to build on the current momentum to design a sustainable model for EID vaccines.