A Multi-centre Study to Evaluate the Long-Term Efficacy and Safety of Biosimilar Infliximab (Infimab™) in Ankylosing Spondylitis in Real-world Clinical Settings - A perspective from Eastern India

Introduction: Owing to dearth of data on infliximab biosimilars in Indian patients, a pan-India case database-based study with infliximab biosimilar BOW015 (Infimab™) was carried out to capture its efficacy and safety in real world clinical settings in India. Here, we assessed its efficacy and safety in ankylosing spondylitis (AS) among patients in the East India cohort. Materials and methods: Data were collected from multiple centers across the eastern region of India. Patients diagnosed with AS, within the preceding 4-6 months during the preceding one year were included in the study. Patients who were given BOW015 for other indications, prior innovator infliximab or other biologics were excluded from the study. Primary variable was Ankylosing Spondylitis Disease Activity Scale (ASDAS) response defined as change of > 2 in the ASDAS score from the baseline by 4-6 months of follow up. Results: The cohort consisted of 149 patients, predominantly male (69.8%), with mean (±SD) age of 36.75 (±11.11) years and mean (±SD) body weight of 58.26 (±15.4) kgs. Of the treated patients, 91 (61.1%) patients were administered four doses, 10 (6.7%) patients were administered three doses, 37 (24.8%) patients were administered two doses and 11 (7.4%) patients were administered only a single dose of BOW015. In the final analysis set, 81 patients had data at baseline and 4th visit. Among the 81 patients, 74 (91%) patients achieved major improvement, 5 (6%) patients achieved clinically important improvement and 2 (3%) were non-responders at 4th visit. Secondarily, cross categorization of the cohort into disease activity categories by number of infusions administered from baseline to 4th visit and assessment of trends in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were also carried out and these too confirmed the efficacy of BOW015. Conclusion: Infimab™ (BOW015) showed significant improvement in ASDAS and BASDAI in patients with AS at the end of 4-6 months of follow up with its clinical benefits being apparent as early as first dose of BOW015

3D Printing in Solid Dosage Forms and Organ-on-Chip Applications

3D printing (3DP) can serve not only as an excellent platform for producing solid dosage forms tailored to individualized dosing regimens but can also be used as a tool for creating a suitable 3D model for drug screening, sensing, testing and organ-on-chip applications. Several new technologies have been developed to convert the conventional dosing regimen into personalized medicine for the past decade. With the approval of Spritam, the first pharmaceutical formulation produced by 3DP technology, this technology has caught the attention of pharmaceutical researchers worldwide. Consistent efforts are being made to improvise the process and mitigate other shortcomings such as restricted excipient choice, time constraints, industrial production constraints, and overall cost. The objective of this review is to provide an overview of the 3DP process, its types, types of material used, and the pros and cons of each technique in the application of not only creating solid dosage forms but also producing a 3D model for sensing, testing, and screening of the substances. The application of producing a model for the biosensing and screening of drugs besides the creation of the drug itself, offers a complete loop of application for 3DP in pharmaceutics

Multilayer Soft Photolithography Fabrication of Microfluidic Devices Using a Custom-Built Wafer-Scale PDMS Slab Aligner and Cost-Efficient Equipment

We present a robust, low-cost fabrication method for implementation in multilayer soft photolithography to create a PDMS microfluidic chip with features possessing multiple height levels. This fabrication method requires neither a cleanroom facility nor an expensive UV exposure machine. The central part of the method stays on the alignment of numerous PDMS slabs on a wafer-scale instead of applying an alignment for a photomask positioned right above a prior exposure layer using a sophisticated mask aligner. We used a manual XYZR stage attached to a vacuum tweezer to manipulate the top PDMS slab. The bottom PDMS slab sat on a rotational stage to conveniently align with the top part. The movement of the two slabs was observed by a monocular scope with a coaxial light source. As an illustration of the potential of this system for fast and low-cost multilayer microfluidic device production, we demonstrate the microfabrication of a 3D microfluidic chaotic mixer. A discussion on another alternative method for the fabrication of multiple height levels is also presented, namely the micromilling approach

Multicellular Cell Seeding on a Chip: New Design and Optimization towards Commercialization

This paper shows both experimental and in-depth theoretical studies (including simulations and analytical solutions) on a microfluidic platform to optimize its design and use for 3D multicellular co-culture applications, e.g., creating a tissue-on-chip model for investigating diseases such as pulmonary arterial hypertension (PAH). A tissue microfluidic chip usually has more than two channels to seed cells and supply media. These channels are often separated by barriers made of micro-posts. The optimization for the structures of these micro-posts and their spacing distances is not considered previously, especially for the aspects of rapid and cost-efficient fabrication toward scaling up and commercialization. Our experimental and theoretical (COMSOL simulations and analytical solutions) results showed the followings: (i) The cell seeding was performed successfully for this platform when the pressure drops across the two posts were significantly larger than those across the channel width. The circular posts can be used in the position of hexagonal or other shapes. (ii) In this work, circular posts are fabricated and used for the first time. They offer an excellent barrier effect, i.e., prevent the liquid and gel from migrating from one channel to another. (iii) As for rapid and cost-efficient production, our computer-aided manufacturing (CAM) simulation confirms that circular-post fabrication is much easier and more rapid than hexagonal posts when utilizing micro-machining techniques, e.g., micro-milling for creating the master mold, i.e., the shim for polymer injection molding. The findings open up a possibility for rapid, cost-efficient, large-scale fabrication of the tissue chips using micro-milling instead of expensive clean-room (soft) lithography techniques, hence enhancing the production of biochips via thermoplastic polymer injection molding and realizing commercialization

A Protocol for Fabrication and on-Chip Cell Culture to Recreate PAH-Afflicted Pulmonary Artery on a Microfluidic Device

Pulmonary arterial hypertension (PAH) is a rare pulmonary vascular disease that affects people of all ethnic origins and age groups including newborns. In PAH, pulmonary arteries and arterioles undergo a series of pathological changes including remodeling of the entire pulmonary vasculatures and extracellular matrices, mis-localized growth of pulmonary arterial cells, and development of glomeruloid-like lesions called plexiform lesions. Traditionally, various animal and cellular models have been used to understand PAH pathophysiology, investigate sex-disparity in PAH and monitor therapeutic efficacy of PAH medications. However, traditional models can only partially capture various pathological features of PAH, and they are not adaptable to combinatorial study design for deciphering intricately intertwined complex cellular processes implicated in PAH pathogenesis. While many microfluidic chip-based models are currently available for major diseases, no such disease-on-a-device model is available for PAH, an under investigated disease. In the absence of any chip-based models of PAH, we recently proposed a five-channel polydimethylsiloxane (PDMS)-based microfluidic device that can emulate major pathological features of PAH. However, our proposed model can make a bigger impact on the PAH field only when the larger scientific community engaged in PAH research can fabricate the device and develop the model in their laboratory settings. With this goal in mind, in this study, we have described the detailed methodologies for fabrication and development of the PAH chip model including a thorough explanation of scientific principles for various steps for chip fabrication, a detailed list of reagents, tools and equipment along with their source and catalogue numbers, description of laboratory setup, and cautionary notes. Finally, we explained the methodologies for on-chip cell seeding and application of this model for studying PAH pathophysiology. We believe investigators with little or no training in microfluidic chip fabrication can fabricate this eminently novel PAH-on-a-chip model. As such, this study will have a far-reaching impact on understanding PAH pathophysiology, unravelling the biological mystery associated with sexual dimorphism in PAH, and developing PAH therapy based on patient sex and age