An updated methodology to review developing-country vaccine manufacturer viability

In 1997, Milstien, Batson, and Meaney published “A Systematic Method for Evaluating the Potential Viability of Local Vaccine Producers.” The paper identified characteristics of successful vaccine manufacturers and developed a viability framework to evaluate their performance. This paper revisits the original study after two decades to determine the ability of the framework to predict manufacturer success. By reconstructing much of the original dataset and conducting in-depth interviews, the authors developed informed views on the continued viability of manufacturers in low- and middle-income country markets. Considering the marked changes in the market and technology landscape since 1997, the authors find the viability framework to be predictive and a useful lens through which to evaluate manufacturer success or failure. Of particular interest is how incumbent and potentially new developing-country vaccine manufacturers enter and sustain production in competitive international markets and how they integrate (or fail to integrate) new technology into the production process. Ultimately, most manufacturers will need to meet global quality standards to be viable. As governments and donors consider investments in vaccine producers, the updated viability factors will be a useful tool in evaluating the prospects of manufacturers over the mid to long term. The paper emphasizes that while up-front investments are important, other critical factors—including investments in a national regulatory authority, manufacturer independence, and ability to adapt and adopt new technology—are necessary to ensure viability

Pulmonary Targeting of Levofloxacin Using Microsphere-Based Dry Powder Inhalation

The objective of the current study was to develop poly (lactic-co-glycolic acid) (PLGA) microspheres loaded with the anti-tuberculosis (anti-TB) fluoroquinolone, Levofloxacin (LVX), in the form of dry powder inhalation (DPI). LVX-loaded microspheres were fabricated by solvent evaporation technique. Central Composite Design (CCD) was adopted to optimize the microspheres, with desired particle size, drug loading, and drug entrapment efficiency, for targeting alveolar macrophages via non-invasive pulmonary delivery. Structural characterization studies by differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction analysis revealed the absence of any possible chemical interaction between the drug and the polymer used for the preparation of microspheres. In addition, the optimized drug-loaded microspheres exhibited desired average aerodynamic diameter of 2.13 ± 1.24 μm and fine particle fraction of 75.35 ± 1.42%, indicating good aerosolization properties. In vivo data demonstrated that LVX-loaded microspheres had superior lung accumulation, as evident by a two-fold increase in the area under the curve AUC0–24h, as compared with plain LVX. Furthermore, LVX-loaded microspheres prolonged drug residence time in the lung and maintained a relatively high drug concentration for a longer time, which contributed to a reduced leakage in the systemic circulation. In conclusion, inhalable LVX-loaded microspheres might represent a plausible delivery vehicle for targeting pulmonary tuberculosis via enhancing the therapeutic efficacy of LVX while minimizing its systemic off-target side effects

Pulmonary Targeting of Inhalable Moxifloxacin Microspheres for Effective Management of Tuberculosis

In the present study, the objective was to attain a localized lung delivery of an anti-tubercular fluoroquinolone, moxifloxacin (MXF), targeting the alveolar macrophages through a non-invasive pulmonary route using inhalable microspheres as a dry powder inhaler approach. MXF-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres (MXF-PLGA-MSs) were fabricated by solvent evaporation technique and optimized by using a central composite statistical design. The morphology and particle size, as well as the flowability of the optimized microspheres, were characterized. In addition, the aerosolization performance of the optimized formula was inspected using an Andersen cascade impactor. Furthermore, in vivo fate following intrapulmonary administration of the optimized formula was evaluated. The optimized MXF-PLGA-MSs were spherical in shape with a particle size of 3.16 µm, drug loading of 21.98% and entrapment efficiency of 78.0%. The optimized formula showed a mass median aerodynamic diameter (MMAD) of 2.85 ± 1.04 µm with a favorable fine particle fraction of 72.77 ± 1.73%, suggesting that the powders were suitable for inhalation. Most importantly, in vivo studies revealed that optimized MXF-PLGA-MSs preferentially accumulated in lung tissue as manifested by a two-fold increase in the area under the curve AUC0–24h, compared to plain drug. In addition, optimized MXF-PLGA-MS sustained drug residence in the lung for up to 24 h following inhalation, compared to plain drug. In conclusion, inhalable microspheres of MXF could be a promising therapeutic approach that might aid in the effective eradiation of tuberculosis along with improving patient adherence to the treatment

Mental Health Programme in India: Has the tide really turned?

Mental disorders in India form a major public health concern and the efforts to tackle these dates back to four decades, by way of the National Mental Health Programme (NMHP) and its operational arm, the District Mental Health Programme (DMHP). Although the progress of NMHP (and DMHP) was relatively slower till recently, the last 4-5 years have seen rapid strides with several initiatives, including (i) expansion of DMHPs to 90 per cent of the total districts of the country, (ii) the National Mental Health Policy and (iii) strengthening the Mental Health Legislation by way of providing explicit provisions for rights of persons with mental illnesses. Among others, factors responsible for this accelerated growth include the easily accessible digital technology as well as judicial activism. Federal and State cooperation is another notable feature of this expansion. In this review, the authors summarize the available information on the evolution of implementation and research aspects related to India's NMHP over the years and provide a case for the positive turn of events witnessed in the recent years. However, the authors caution that these are still baby steps and much more remains to be done