Maintaining the quality of vaccines through the use of standards: Current challenges and future opportunities.

An international hybrid meeting held 21-22 June 2023 in Ottawa, Canada brought together regulators, scientists, and industry experts to discuss a set of principles and best practices in the development and implementation of standards. Although the use of international standards (ISs) and international units (IUs) has been an essential part of ensuring human and animal vaccine quality in the past decades, the types and uses of standards have expanded with technological advances in manufacture and testing of vaccines. The needs of stakeholders are evolving in response to the ever-increasing complexity, diversity, and number of vaccine products as well as increasing efforts to replace animal-based potency tests with in vitro assays that measure relevant quality attributes. As such, there must be a concomitant evolution in the design and implementation of both international and in-house standards. Concomitantly, greater harmonization of regulatory expectations must be achieved through collaboration with standard-setting organizations, national control laboratories and manufacturers. Stakeholders provided perspectives on challenges and several recommendations emerged as essential to advancing agreed upon objectives.

The role community-based healthcare providers play in managing hard-to-heal wounds.

It is common for community-based healthcare providers (CHPs)-many of whom have not received specialised training in wound care-to deliver initial and ongoing management for various wound types and diverse populations. Wounds in any setting can rapidly transition to a stalled, hard-to-heal wound (HTHW) that is not following a normal healing trajectory. Failure to recognise or address issues that cause delayed healing can lead to increased costs, healthcare utilisation and suffering. To encourage early intervention by CHPs, a panel of wound care experts developed actionable evidence-based recommendations for CHPs delineating characteristics and appropriate care in identifying and treating HTHWs. A HTHW is a wound that fails to progress towards healing with standard therapy in an orderly and timely manner and should be referred to a qualified wound care provider (QWCP) for advanced assessment and diagnosis if not healed or reduced in size by 40%-50% within 4 weeks. HTHWs occur in patients with multiple comorbidities, and display increases in exudate, infection, devitalised tissue, maceration or pain, or no change in wound size. CHPs can play an important initial role by seeing the individual's HTHW risk, addressing local infection and providing an optimal wound environment. An easy-to-follow one-page table was developed for the CHP to systematically identify, evaluate and treat HTHWs, incorporating a basic toolkit with items easily obtainable in common office/clinic practice settings. A flow chart using visual HTHW clinical cues is also presented to address CHPs with different learning styles. These tools encourage delivery of appropriate early interventions that can improve overall healthcare efficiency and cost.

The Temporal Dynamics of Brain-to-Brain Synchrony Between Students and Teachers Predict Learning Outcomes.

Much of human learning happens through interaction with other people, but little is known about how this process is reflected in the brains of students and teachers. Here, we concurrently recorded electroencephalography (EEG) data from nine groups, each of which contained four students and a teacher. All participants were young adults from the northeast United States. Alpha-band (8-12 Hz) brain-to-brain synchrony between students predicted both immediate and delayed posttest performance. Further, brain-to-brain synchrony was higher in specific lecture segments associated with questions that students answered correctly. Brain-to-brain synchrony between students and teachers predicted learning outcomes at an approximately 300-ms lag in the students' brain activity relative to the teacher's brain activity, which is consistent with the time course of spoken-language comprehension. These findings provide key new evidence for the importance of collecting brain data simultaneously from groups of learners in ecologically valid settings.

3Rs implementation in veterinary vaccine batch-release testing: Current state-of-the-art and future opportunities. A webinar and workshop report.

Regulatory authorities require veterinary batch-release testing to confirm vaccine potency and safety, but these tests have traditionally relied on large numbers of laboratory animals. Advances in vaccine research and development offer increasing opportunities to replace in vivo testing, and some stakeholders have made significant progress in incorporating 3Rs elements in quality control strategies. A three-part event series entitled "3Rs Implementation in Veterinary Vaccine Batch-Release Testing: Current state-of-the-art and future opportunities" was jointly organized by the Animal-Free Safety Assessment Collaboration, HealthforAnimals, and the International Alliance of Biological Standardization. Two webinars and a workshop aimed to outline the state-of-the-art non-animal approaches for veterinary batch-release testing. The events included information on the state of the deletion of obsolete safety testing and the current initiatives implemented by European, North American, and Asian-Pacific stakeholders on 3Rs implementation and regulatory acceptance. The events contributed to a better understanding of the barriers to 3Rs implementation. Participants highlighted the need for open communication, continued collaboration between stakeholders, and international harmonization of regulatory requirements to help accelerate acceptance. Despite the challenges, the countries represented at this three-part event have shared their commitments to advancing the acceptance of alternative methods.

Best practice for wound repair and regeneration use of cellular, acellular and matrix-like products (CAMPs).

There are currently over 80 biomaterials derived from autologous, allogeneic, synthetic and xenogeneic sources, or a combination of any or all these types of materials, available for soft-tissue coverage to effect wound closure. Often generically referred to as cellular and/or tissue-based products (CTPs), they are manufactured under various trade names and marketed for a variety of indications.

Accelerating Global Deletion of the Abnormal Toxicity Test for vaccines and biologicals. Planning common next steps. A workshop Report.

This online workshop Accelerating Global Deletion of the Abnormal Toxicity Test for vaccines and biologicals. Planning common next steps was organized on October 14th, 2021, by the Animal Free Safety Assessment Collaboration (AFSA), the Humane Society International (HSI), the European Federation of Pharmaceutical Industries and Associations (EFPIA), in collaboration with the International Alliance of Biological Standardization (IABS). The workshop saw a participation of over a hundred representatives from international organizations, pharmaceutical industries and associations, and regulatory authorities of 28 countries. Participants reported on country- and region-specific regulatory requirements and, where present, on the perspectives on the waiving and elimination of the Abnormal Toxicity Test. With AFSA, HSI, EFPIA and IABS representatives as facilitators, the participants also discussed specific country/global actions to further secure the deletion of ATT from all regulatory requirements worldwide.

Bid from the Association for the Advancement of Wound Care.

The Association for the Advancement of Wound Care sets out its bid for the WUWHS 2026 Congress to be held in Chicago, Illinois, US.

A Novel Point-of-Care Solution to Streamline Local Wound Formulary Development and Promote Cost-effective Wound Care.

OBJECTIVE: To develop and implement a point-of-care digital solution to streamline the creation and maintenance of wound care product formularies and promote cost-effective wound management. METHODS: Researchers used Design Thinking methodology to develop the Formulary Module, a point-of-care digital solution within a clinical and reimbursement decision support web application for wound care and hyperbaric clinicians. The module was implemented in a US hospital-based outpatient wound clinic as follows: A baseline list of products was established, with brands automatically grouped by product category. Brands within each dressing category were compared, and redundancy eliminated. Study authors assessed the financial impact of formulary implementation in the wound clinic by comparing inventory expenditure before and after implementation. RESULTS: Implementation of the digital Formulary Module resulted in a 36% decrease in products (67 to 43 across 22 types), 38.73% decrease in the monthly average dollar spent on chargeable products, 29.56% decrease in the average dollar amount spent on chargeable products per patient visit, and increased staff efficiency. CONCLUSIONS: The Formulary Module has the potential to increase the adoption of cost-effective practices in wound care significantly.

An international consensus on device-related pressure ulcers: SECURE prevention.

Catherine Milne and colleagues present the findings of their review, ccna2@juno.com.

An extracellular matrix graft (Oasis® wound matrix) for treating full-thickness pressure ulcers: A randomized clinical trial.

AIM: The purpose of the study was to evaluate clinical safety and effectiveness of Oasis® Wound Matrix as a treatment for full-thickness pressure ulcers and compare it to Standard Care. METHODS: A total of 130 adults with Stage III or Stage IV pressure ulcers were randomly assigned, received either multiple topical treatments of SIS plus standard care (n = 67), or standard care alone (n = 63), and were subsequently evaluated. Ulcer size was determined at enrollment and weekly throughout treatment. Healing was assessed at each visit for a period of up to 12 weeks, with incidence of complete healing and 90% reduction in ulcer area being the primary outcome measures. RESULTS: The proportion of complete healing in the SIS group was 40% as compared to 29% in the standard of care group (p = 0.111); the percentage of patients having a 90% reduction in ulcer surface area was 55% in the SIS group versus 38% in the standard of care group (p = 0.037). CONCLUSIONS: The results of this study suggest that within the setting of a comprehensive wound care program, weekly treatment of chronic pressure ulcers with SIS wound matrix increases the incidence of 90% reduction in wound size versus standard of care alone.

Consumer engagement critical to success in an Australian research project: reflections from those involved.

This paper describes the people, activities and methods of consumer engagement in a complex research project, and reflects on the influence this had on the research and people involved, and enablers and challenges of engagement. The 2.5-year Integrating and Deriving Evidence Experiences and Preferences (IN-DEEP) study was conducted to develop online consumer summaries of multiple sclerosis (MS) treatment evidence in partnership with a three-member consumer advisory group. Engagement methods included 6-monthly face-to-face meetings and email contact. Advisory group members were active in planning, conduct and dissemination and translational phases of the research. Engaging consumers in this way improved the quality of the research process and outputs by: being more responsive to, and reflective of, the experiences of Australians with MS; expanding the research reach and depth; and improving the researchers' capacity to manage study challenges. Advisory group members found contributing their expertise to MS research satisfying and empowering, whereas researchers gained confidence in the research direction. Managing the unpredictability of MS was a substantive challenge; the key enabler was the 'brokering role' of the researcher based at an MS organisation. Meaningfully engaging consumers with a range of skills, experiences and networks can make important and unforeseen contributions to research success.

Clinical Evaluation of a Skin Protectant for the Management of Incontinence-Associated Dermatitis: An Open-Label, Nonrandomized, Prospective Study.

PURPOSE: The purpose of this study was to evaluate the efficacy of an investigational skin protectant product at managing severe skin breakdown associated with incontinence. DESIGN: Open-label, nonrandomized, prospective study. SUBJECTS AND SETTING: The sample comprised 16 patients; inclusion criteria were: patients older than 18 years, cared for in the intensive care unit of a level I trauma center hospital or in long-term care facilities in the northeast region of the United States, and had incontinence-associated dermatitis (IAD). Twelve of the patients had epidermal skin loss and 4 had severe redness. METHODS: The investigational product is a formulation based on acrylate chemistry. The skin protectant application schedule was twice weekly for up to 3 weeks for a maximum of 6 applications during the study period. The skin was evaluated via a skin assessment instrument specifically designed for use in this study; this instrument has not undergone validation studies. The main outcome measure was changes in the instrument score over time. In addition, complete reepithelialization was recorded when observed, and pain scores (associated with IAD) were noted in participants who were able to report pain. RESULTS: The IAD score improved in 13 of 16 patients, remained unchanged in 1 patient, and deteriorated in 2 patients. The median percent improvement in the skin assessment instrument was 96% (P = .013). Four of the patients with epidermal skin loss had complete reepithelialization of the skin surface with 4 to 6 applications of the skin protectant, and 5 had substantial improvement. The 4 patients with severe red skin returned to healthy normal skin with 2 to 4 skin protectant applications. Substantial pain reduction was reported by all 9 patients who reported pain at enrollment. No adverse events associated with the skin protectant application were reported during data collection. CONCLUSION: Results of this study suggest that an acrylate-based product, evaluated here for the first time in patients, may be effective as a protective barrier in the presence of continued incontinence. Additional research is needed to confirm these findings.

A multi-dose serological assay suitable to quantify the potency of inactivated rabies vaccines for veterinary use.

The mouse vaccination-challenge test, which is the most widely used method for determining the potency of inactivated rabies vaccines, is imprecise, time-consuming, and causes severe distress to the test animals. An alternative single-dose serological method has been implemented in the European Pharmacopoeia Monograph 0451 to replace the mouse challenge test for batch release. This single-dose limit method provides semi-quantitative results, but is not suitable for quantifying potency. We have now extended this serological method to a multi-dose format which allows a quantification of vaccine potency. In studies including all rabies vaccine strains relevant for Europe, we found dose-dependency for all vaccines and standard preparations. We have demonstrated that the multi-dose serological approach provides reliable quantitative potency results and is more precise than the mouse vaccination-challenge test. We have shown that adjuvanted vaccines can be calibrated against non-adjuvanted material, and that reference material can be calibrated against the International Standard. The method is therefore capable of assigning potency with the additional advantage of requiring fewer animals and reducing distress. Once the applicability of the method has been further verified in a collaborative study, it can complement the single-dose assay and eventually eliminate the need for the mouse challenge test.

Evaluation of a cyanoacrylate protectant to manage skin tears in the acute care population.

Skin tears are a common problem that can impact the quality of life due to pain and the potential of becoming complicated wounds if not treated properly. The use of a cyanoacrylate skin protectant to manage skin tears was evaluated in 30 patients in an acute care setting.

Independent control of COVID-19 vaccines by EU Official Control Authority Batch Release: challenges, strengths and successes.

Vaccines have been a key tool in stemming the tide of the COVID-19 pandemic. The rapid development of effective vaccines against COVID-19, together with their regulatory approval and wide scale distribution has been achieved in an impressively short period thanks to the intense efforts of many. In parallel to vaccine development, the EU considered it important to prepare for the independent control of the COVID-19 vaccines, including testing, to help ensure that only vaccines that comply with the approved quality requirements reach the public and to help improve/increase public confidence in the vaccines. The existing EU Official Control Authority Batch Release (OCABR) system, co-ordinated by the European Directorate for the Quality of Medicines and HealthCare (EDQM), was able to effectively respond to the need, through rapid co-ordination, work-sharing, advance planning and early interaction with manufacturers, the Coalition for Epidemic Preparedness Innovation (CEPI) and regulatory authorities. The Official Medicines Control Laboratories (OMCLs) involved in the OCABR activity, using the strength of the established system in the OCABR network and adaptations to the crisis conditions, were ready to release the first COVID-19 vaccine batches, after protocol review and testing, at the time of the conditional marketing authorisation for each of the COVID-19 vaccines, with no delay for batches reaching the public. Thanks to the dedication of resources by the EU and national authorities as well as by the EDQM, this was done without impacting the release of the other vaccines and human blood and plasma derived medicinal products, essential for public health. Transparency and communication of practices were important factors to support reliance on the OCABR outcome in non-EU countries, with the goal to improve access to vaccines in Europe and beyond. An overview of the process, legal background, challenges and successes of OCABR for COVID-19 vaccines as well as a look at the international perspective and lessons learned is provided.

Factors influencing Scottish dairy farmers' antibiotic use.

BACKGROUND: Good stewardship of antibiotics can reduce the development and impact of antimicrobial resistance (AMR); therefore, understanding farmers' antibiotic use is of interest to stakeholders. To date, few qualitative studies have looked at farmers' antibiotic use on dairy farms in the UK. METHODS: Semi-structured interviews were used to explore 15 Scottish dairy farmers' antibiotic use behaviours and the factors influencing their antibiotic use on farms. RESULTS: Using an inductive process, the results from the interviews were analysed, and four key themes were extracted: use of antibiotics, awareness of AMR, determinants of antibiotic use and future aspirations. LIMITATIONS: Some of the farmers interviewed were wary about discussing their antibiotic use, which could mean that some contentious issues were not discussed. The farmers also all belonged to a single milk-buying group, which may limit the generalisability of the findings. CONCLUSIONS: The quantities of antibiotics used were felt to be driven by the disease prevalence on farms, cows being indoors more, increasing herd sizes resulting in increased stocking densities, retention of poorer cows and substandard housing. Farmer knowledge of antibiotics varied, and not all farmers interviewed were aware of AMR. The farm veterinarian, the press and peers were found to be the main sources of antibiotic information.

LidocAine Versus Opioids In MyocarDial infarction: the AVOID-2 randomized controlled trial.

AIMS: Opioid analgesia has been shown to interfere with the bioavailability of oral P2Y12 inhibitors prompting the search for safe and effective non-opioid analgesics to treat ischaemic chest pain. METHODS AND RESULTS: The lidocAine Versus Opioids In MyocarDial infarction trial was a prospective, Phase II, prehospital, open-label, non-inferiority, randomized controlled trial enrolling patients with suspected STEACS with moderate to severe pain [numerical rating scale (NRS) at least 5/10]. Intravenous lidocaine (maximum dose 300 mg) or intravenous fentanyl (up to 50 µg every 5 min) were administered as prehospital analgesia. The co-primary end points were prehospital pain reduction and adverse events requiring intervention. Secondary end points included peak cardiac troponin I, cardiac MRI (cMRI) assessed myocardial infarct size and clinical outcomes to 30 days. A total of 308 patients were enrolled. The median reduction in pain score (NRS) was 4 vs. 3 in the fentanyl and lidocaine arms, respectively, for the primary efficacy end point [estimated median difference -1 (95% confidence interval -1.58, -0.42, P = 0.5 for non-inferiority, P = 0.001 for inferiority of lidocaine)]. Adverse events requiring intervention occurred in 49% vs. 36% of the fentanyl and lidocaine arms which met non-inferiority and superiority favouring lidocaine (P = 0.016 for superiority). No significant differences in myocardial infarct size and clinical outcomes at 30 days were seen. CONCLUSION: IV Lidocaine did not meet the criteria for non-inferiority with lower prehospital pain reduction than fentanyl but was safe and better tolerated as analgesia in ST-elevation myocardial infarction (STEMI). Future trials testing non-opioid analgesics in STEMI and whether opioid avoidance improves clinical outcomes are needed. TRIAL REGISTRATION: CTRN12619001521112p.