Getting Proactive with Pharma Packaging

According to market research, the pharmaceutical packaging sector is expected to grow at a compound annual rate of 7.4% between 2022 and 2031, reaching an estimated USS178.8 billion (€171.8 billion) by the end of the forecast period (1). "Pharmaceutical waste continues to be a huge problem, so to eliminate non-biodegradable and single-use plastics from the supply chain, more research is taking place around bio-based PET [polyethylene terephthalate]. "By designing a product's primary and secondary packaging well from the outset (including investing ample resources into the process), manufacturers can reduce the amount of materials used and wasted, test new eco materials, ensure safety compliance and efficacy, and benefit from cheaper transportation costs," Quelch surmises. [...]pharma companies can benefit from a packaging supplier with a true global footprint," he says.

Securing the Supply Chain

According to market research, the API market is expected to experience a compound annual growth rate of 6.7% in the forecast period of 2020-2027 (1). "The low-cost benefits of manufacturing APIs and drug products within Asia has helped to turbocharge the generic drug industry and expand global access to a range of lower-cost medication options," says Meudt. "The shift has been positive for patients, allowing consumers to benefit from lower cost drugs from US Food and Drug Administration (FDA) and European Union (EU) inspected current good manufacturing practice (cGMP) facilities while still maintaining quality, innovation, and allowing efficient drug development and commercialization routes," he says. "While manufacturing cost will always be important, pharmaceutical companies are increasingly selecting their long-term CMOs based upon other factors including security of quality and supply, regulatory track record, data control, and environmental sustainability.

Leader of the Pack?

AstraZeneca has potentially taken poll position in the race to develop a novel coronavirus vaccine, but will AZD1222 be ready in 2020? "The interim Phase I/II data for our coronavirus vaccine shows that the vaccine did not lead to any unexpected reactions and had a similar safety profile to previous vaccines of this type," said Professor Andrew Pollard, chief investigator of the Oxford Vaccine Trial at Oxford University and co-author of the trial, in a press release (1). [...]AstraZeneca and the European Commission recently concluded an agreement for the supply of up to 400 million doses (3), which adds to a prior arrangement the company had formed with the Inclusive Vaccines Alliance (4).

Vaccine Administration: The Growing Role of Prefilled Syringes

(Note: The MIDAS database reflects vaccine doses that are dispensed with a prescription in retail or hospital settings, so the COVID-19 vaccines and other public-health-administered vaccines are not fully reflected in that data set.) Stamoran adds, "However, across the rest of the world, vial-based vaccines still make up the majority of the volume dispensed." [...]there is plenty of room for growth for this newer administration device. [...]PFS are now widely used for annual flu shots, heparin injections, and a growing list of injectable therapies across multiple disease states. According to a 2021 article authored byGuillaume Lehee, R&D Innovation Leader for BD Medical-Pharmaceutical Systems, the use of PFS to vaccinate 300 million individuals in the United States in the event of a future pandemic could save more than three million hours of healthcare practitioners' time (1). [...]today's PFS are not yet proven to be compatible with ultrafrozen temperatures as the existing glass materials and other components may not stand up to the extremely low required temperatures," explains Stamoran.

Addressing the Key Pitfalls Hindering Technology Transfer Success

The key challenges that are commonly faced by companies undertaking a tech transfer include: * Client expectations and initial project scope definition: the initial assumptions of the drug developer or marketing authorization holder (MHA) based on their initial information relating to the product can be a significant challenge. Typical examples include product stability issues (typically on legacy products) being evidenced due to a change to more compliant analytical methods;change to product brought about by compliance-related requirements on legacy products, such as nitrosamines, and elemental impurities guidelines, etc.;and regulatory requirements being misjudged at the onset of the project, among other factors. * Product knowledge management: particularly when undertaking tech transfers of legacy products or products in the initial discovery phase, there may be a lack of technical knowledge on the product itself to make a comprehensive and robust tech transfer process. All this may contribute to slowing down the transfer of knowledge, with implications for tech transfer timelines. * Standardization at receiving site: another challenge typically faced by receiving sites of CDMOs is a lack of standardization of their internal processes and or documentation brought about by multiple tech transfers with varying types of clients with multiple requirements. The originating site-particularly if it belongs to a small start-up-may not have team members with specialist experience in handling a transfer, so may need additional support in collating the required information to hand over to the receiving site.

The European Union's New Pharmaceutical Strategy for Europe

[...]on 25 Nov. 2020, the European Commission (EC) announced the new Pharmaceutical Strategy for Europe, which is likely to result in significant changes to the European Union (EU) regulatory framework and will have a substantial impact on both the marketing of medicinal products and the strategic business planning of pharmaceutical companies (2). (2021), the priority areas are as follows: * The performance and adequacy of the current legislation * Unmet medical needs-with a definition or set of principles for "unmet medical needs" under discussion * Incentives for innovation, including the area of unmet needs and a reflexion on regulatory data and market exclusivity * Antimicrobial resistance that includes measures to support innovation of antibiotic development * Future-proofing the regulatory framework for novel products * Improved patient access to, and affordability of, medicines in the EU * Competitiveness of the European markets to ensure affordable medicines, including considering measures to support patients' access to affordable medicines * Encouraging the repurposing of off patent medicines * Ensuring security of supply of medicinal products in the EU * Ensuring high-quality manufacture and distribution in the EU including consideration of the need to strengthen or adapt good manufacturing practice (GMP) to reflect new manufacturing methodologies * Environmental challenges (4). Availability, accessibility, and affordability of medicinal products The section on 'Prioritising unmet medical needs' in the strategy reflects the belief within EU Bianca Piachaud-Moustakis is lead writer at PharmaVision, Pharmavision.co.uk. institutions that "current incentive models neither provide an adequate solution for unmet medical needs nor appropriately incentivise investments in innovation" (2).

EUROPE SEEKING CLARITY IN ADVANCED TRIALS

EU officials acknowledge that the trial landscape in response to the pandemic has been fragmented, with a multitude of small, national trials, struggling to generate robust and actionable clinical data, with great duplication of efforts and direct competition for shared resources and participant populations. The European drug industry worked on complex clinical trials in 2020 with researchers in the European Organization for Research into Treatments for Cancer and specialists in the Association of Clinical Research Organizations, as well as with the European Union's Clinical Trial Expert Group, composed of national health ministry officials. [...]the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) is developing guidelines on Adaptive Clinical Trials with a timeline of 2023, and on Good Clinical Practice Renovation to address the increasing diversity of clinical trial designs and data sources.

EDQM Combats COVID-19 and Makes Plans for Future

Developers can take them into account to help build appropriate analytical control strategies for their COVID-19 candidate vaccines and ensure the quality and safety of the final product," says Keitel. For USP, building trust in the effectiveness of COVID19 vaccines and treatments, ensuring global access to these treatments, and combating falsified and substandard medicines are the focus, according to Fouad Atouf, PhD, vice president, USP Global Biologics. [...]for existing and new therapies, USP compendial tests and methods address common issues shared by all drug manufacturers, such as suitability, validation, contamination control, stability testing, and qualification of raw materials," Atouf adds. -

APPLYING PRE-PANDEMIC BENCHMARKS TO ASSESS FUTURE SPEED STRATEGIES

To name but a few: they have rapidly mobilized scientific and operating teams;entered into an unprecedented number and variety of co-development arrangements;scaled-up manufacturing capabilities;and leveraged technology solutions and advanced analytics to access and analyze data from animal and early human studies and from commercially available therapies treating other diseases. Clinical trial durations and scope metrics were obtained from summaries of drug approvals available on the FDA website, from medical reviews, and from the ClinicalTrials.Gov website. [...]Phase III clinical trial durations have increased by more than 6% between the two time periods, from an average of 26.8 months in the 2008-2013 period to an average of 28.5 months per individual trial in the 2014-2018 timeframe. Very high variation was observed around the mean number of participants per clinical trial and this variation has increased over time. Mean clinical duration for non-orphan drug approvals increased substantially (16.2 months) in the 2014-2018 period, whereas mean regulatory review duration for non-orphan drugs decreased by one month.

Inhalation Vaccine Development

Numerous advantages to inhalation vaccines Vaccines delivered via inhalation enable targeting of the respiratory tract mucosa and generation of both humoral and cell-mediated immunity, according to Pierre A. Morgon, executive vice president. [...]inhaled vaccines delivered as liquids using nebulizers can potentially be administered with lower requirement for extensive healthcare infrastructure or as many trained healthcare personnel within an immunization centre (2). Researchers at McMaster University, for instance, have shown inhalation of a tuberculosis vaccine to be more effective than delivery via nasal sprays, because the vaccine penetrates much deeper into the airway (8). Because inhaled vaccines provide local immunity to the respiratory tract, they are seen to be ideal solutions for interrupting the spread of viruses with high transmission rates and the potential to lead to global pandemics (9). Beyond these two approaches, there are inhalation vaccines under development based on attenuated influenza virus, parainfluenza virus (PIV) 5, lentiviruses, Newcastle disease virus (NDV), and vesicular stomatitis virus (VSV);bacterium vectors, nucleic acids (messenger RNA, DNA), and protein subunits (3).

Incentivizing at‐risk production capacity building for COVID‐19 vaccines

Our study analyzes capacity management for promising vaccine candidates before regulatory approval (i.e., at‐risk capacity building) in the presence of production outsourcing and different operational challenges: misaligned interests, possible ex post negotiations, asymmetric information between developers and manufacturers, and government involvement. We develop analytical models to compare two vaccine production modes: (1) the integrated mode (a single company determines the at‐risk capacity and produces in‐house) and (2) the outsourcing mode (a manufacturer determines the at‐risk capacity and a developer determines a funding level to share the capacity‐building cost). Our study reveals that outsourcing can achieve a higher at‐risk capacity only if it can achieve sufficient cost savings compared to the integrated mode. Our research also proves that both vaccine production modes tend to underinvest in the at‐risk capacity. Following this, we suggest measures to improve the at‐risk capacity building in both vaccine production modes. Our signaling game model reveals that a developer with high competence cannot always send credible signals of its true competence level to the manufacturer. Our incomplete contract model verifies that the relative performance of the two vaccine production modes is robust when ex post negotiation occurs under the outsourcing mode;however, the two parties may show incompatible preferences for the ex post negotiation. Our study also analyzes the optimal allocation of government financial support to development funding and capacity funding to incentivize at‐risk capacity building. We present comprehensive guidelines for the different stakeholders to collectively contribute to ramping up the at‐risk capacity of promising vaccines.

Rescuing orphan drugs

Philip Kranz and colleagues argue that drug regulators should not automatically assume orphan drugs are clinically "superior” for patients, in the absence of robust evidence of their clinical benefits (doi:10.1136/bmj-2022-072796).1 The US offers new evidence that not all drugs benefiting from orphan status are actually for rare diseases (doi:10.1136/bmj-2022-073242).2 A study looking at FDA approved cancer treatments over the past 20 years found that most approvals for cancer indications were designated as orphans. "Are we still getting what we thought we were paying for?” asks Joseph Ross (doi:10.1136/bmj.p928).3 Evidence matters and can take many decades of endeavour to gather, as is the case for a new vaccine to prevent respiratory syncytial virus bronchiolitis in infants (doi:10.1136/bmj.p1023).4 The RSV virus kills very young children, mostly in low to middle income countries, and a pandemic related surge in incidence resulted in many hospital admissions. FDA approval, clinical trial evidence, efficacy, epidemiology, and price for non-orphan and ultra-rare, rare, and common orphan cancer drug indications: cross sectional analysis.

COVID-19, vaccines and international knowledge governance on trial

The production, distribution and availability of vaccines to combat the COVID-19 pandemic are all impacted by the international rules of knowledge governance. These rules include patents, trade secrets and health and efficacy regulatory approval processes. This article discusses how these intellectual property related mechanisms all interfered with vaccine availability. It analyses the international rules, related exceptions (including compulsory licensing and national security) and the possible waiver of the relevant rules found in the World Trade Organization TRIPS Agreement. Throughout the first two years of the pandemic, vaccines were not available widely enough. Although most of the developed world had enough vaccine doses by late 2021, that was not the position in much of the developing world, where the problem became the distribution of vaccines. Distribution may have always been difficult, but the failures in timely local supply exacerbated the problem of vaccine inequality between the developed and developing world. The inequality had several likely causes including intellectual property rules. The problem was not neces-sarily the existence of patents (or other rules) but the insufficiency of checks and balances that are necessary to address global public health needs. This resulted in private interests, whose primary goal is not public health, wielding too much power. The article concludes that collectively the effect of the international rules enacted in domestic laws supports a regime that was not fit for purpose to address the COVID-19 pandemic and is not fit to address future pandemics. © 2022 The Author.

25 years of commercializing nanomedicine: from tissue engineering to fighting COVID

Nanomedicine has already revolutionized medicine through the development of materials that can prolong circulation in the body, avoid immune system clearance, penetrate cells and bacteria, invade tumors, promote tissue growth, inhibit infection, and so much more. New fields have emerged such as 4D printing which can enhance the performance of nanomaterials by 3D printing them into desirable shapes, implant them, and control their shape through external stimuli (such as near infrared excitation, temperature control, and others). This presentation will provide an overview of 25 years of commercializing University based research into real products helping human health. It will cover the promises and pitfalls of commercializing University based research and even discuss if this is the right model to advance science and research into the medical industry. It will also highlight new areas emerging for commcerialization such as the use of 4D printing in medicine for straightening the spine for scoliosis patients, closing of sphincters that weaken as one ages (for example, to decrease acid reflux from the stomach to the esophagus), promote intervertebral tissue growth by increasing pressure on such tissue during regeneration, deliver stem cells on the same materials in which they are cultured to enhance stem cell viability, and more. It will cover additional new areas like picomedicine, implantable sensors and more. It will cover in vitro and in vivo assessment of such materials and discuss what is needed to experience full application of nanomedicine throughout all of medicine.

Remote videolink observation of model home sampling and home testing devices to simplify usability studies for point-of-care diagnostics [version 1;peer review: awaiting peer review]

Both home sample collection and home testing using rapid point-of-care diagnostic devices can offer benefits over attending a clinic/hospital to be tested by a healthcare professional. Usability is critical to ensure that in-home sampling or testing by untrained users does not compromise analytical performance. Usability studies can be laborious and rely on participants attending a research location or a researcher visiting homes;neither has been appropriate during COVID-19 outbreak control restrictions. We therefore developed a remote research usability methodology using videolink observation of home users. This avoids infection risks from home visits and ensures the participant follows the test protocol in their home environment. In this feasibility study, volunteers were provided with models of home blood testing and home blood sampling kits including a model lancet, sampling devices for dried blood spot collection, and model lateral flow device. After refining the study protocol through an initial pilot (n = 7), we compared instructions provided either as written instructions (n = 5), vs addition of video instructions (n = 5), vs written and video instructions plus videolink supervision by the researcher (n = 5). All users were observed via video call to define which test elements could be assessed remotely. All 22 participants in the study accessed the video call and configured their videolink allowing the researcher to clearly observe all testing tasks. The video call allowed the researcher to assess distinct errors during use including quantitative (volume of blood) and qualitative (inaccurate interpretation of results) errors many of which could compromise test accuracy. All participants completed the tasks and returned images of their completed tests (22/22) and most returned completed questionnaires (20/22). We suggest this remote observation via videolink methodology is a simple, rapid and powerful methodology to assess and optimise usability of point-of-care testing methods in the home setting.

Health body, not trade lawyers, ‘should decide patents access’

Speed read Least-developed countries push for patent waivers for COVID-19 drugs, diagnostics Health body should replace WTO oversight of medical patents, says justice advocate But vaccine manufacturing requires substantial infrastructure, skills development Trade negotiations are dictating access to COVID-19 vaccines, treatments and diagnostics. In April, the World Health Organization issued a call for expressions of interest in its mRNA technology hub, which aims to expand production capacity in low-and middle-income countries. Quality control The political will needed to ramp up vaccine production in Africa is deepening, according to analysis from consulting firm McKinsey, citing this year’s launch of the African Continental Free Trade Area (AfCFTA) and the nascent African Medicines Agency. According to McKinsey, the market for African vaccines could grow from US$1.3 billion today, to between $2.3 billion and $5.4 billion by 2030.

‘Catastrophic moral failure’ risk over COVID-19 shots – WHO

Speed read One of the poorest countries has administered only 25 doses of the vaccine Equitable vaccine rollout critical amid new virus variants Vaccine makers are ‘prioritising profits’ over fair access As few as 25 doses of the COVID-19 vaccine have been administered in one of the world’s poorest countries, the head of the World Health Organization (WHO) has said, warning of a “catastrophic moral failure”. Since January 1, the world has been recording an average of almost 12,500 daily deaths and 682,000 recorded cases, according to a report published Tuesday by the Independent Panel for Pandemic Preparedness and Response. According to ourworldindata.org, an initiative by the University of Oxford and partners which is collating data on the pandemic, the United Arab Emirates is currently delivering the highest number of vaccines per 100 people at 1.16 doses.

Challenges in addressing inequity in access to COVID-19 diagnostics, therapeutics and vaccines in Africa

Although the global response to COVID-19 has demonstrated that some progress has been made in ensuring timely access to new medical interventions in Africa, much more needs to be done to strengthen the global systems that enable equitable access to health technologies during public health emergencies.

Psychedelic Mystical Experience: A New Agenda for Theology

When the link between psychedelic drugs and mystical states of experience was first discovered in the 1960s, Huston Smith challenged scholars in religion and philosophy to consider the implications. Very few took up his challenge. Beginning in 2006, hundreds of studies have linked psychedelics not just to mystical states of experience but to potential treatments for many mental health disorders. Regulatory approval for therapies is on the horizon, and hundreds of millions of people worldwide could be treated. Research findings challenge the underlying rationale of the War on Drugs, leading to decriminalization of specific psychedelic drugs or to authorization of their use in mental health contexts. Religious institutions are slowly adapting, with some referring to psychedelics as sacraments or as pathways to deeper spirituality. Religious leaders are also beginning to speak out publicly in support of careful use of these drugs, and some are training to become “psychedelic chaplains” to work alongside mental health professionals administering these drugs. Scholars in theology and religion are encouraged to engage these trends, to explore challenging philosophical and theological issues surrounding mystical states of experience in general, and to consider the long-term cultural impact of the most recent psychedelic research.