RESUMEN
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.
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Control de Calidad , Vacunas , Humanos , Vacunas/normas , Animales , Canadá , Estándares de ReferenciaRESUMEN
INTRODUCTION: There are rational arguments to replace existing in vivo potency and safety assays for batch release testing of vaccines with more advanced non-animal techniques to measure critical quality attributes. However, the introduction of in vitro alternatives to replace in vivo release assays of authorized vaccines is challenging. AREAS COVERED: This report describes the hurdles encountered in substituting in vivo assays and ways to overcome these and provides arguments why more advanced in vitro alternatives are superior, not only as a tool to monitor the quality of vaccines but also from a practical, economical, and ethical point of view. The rational arguments provided for regulatory acceptance can support a strategy to replace/substitute any in vivo batch release test if an appropriate non-animal testing strategy is available. EXPERT OPINION: For several vaccines, in vivo release assays have been replaced leading to an optimized control strategy. For other vaccines, new assays are being developed that can expect to be introduced within 5-10 years. From a scientific, logistical, and animal welfare perspective, it would be beneficial to substitute all existing in vivo batch release assays for vaccines. Given the challenges related to development, validation, and acceptance of new methods, and considering the relatively low prices of some legacy vaccines, this cannot be done without government incentives and supportive regulatory authorities from all regions.
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Vacunas , Vacunas/normas , Alternativas a las Pruebas en AnimalesAsunto(s)
Anticuerpos , Vacunas , Organización Mundial de la Salud , Anticuerpos/análisis , Anticuerpos/inmunología , Estándares de Referencia , Vacunas/inmunología , Vacunas/normas , Organización Mundial de la Salud/organización & administración , Tratamiento de Urgencia , Valores de Referencia , HumanosRESUMEN
Animal testing has long been integral to the development of biologicals, including vaccines. The use of animals can provide important information on potential toxicity, insights into their mechanism of action, pharmacokinetics and dynamics, physiologic distribution, and potency. However, the use of these same methods is often adopted into the post-licensure phase of the product life cycle for the monitoring of product qualities, such as potency or safety, as part of their routine batch release. The UK National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) and the World Health Organization (WHO) are collaborating on a project to review animal-based testing methods described in WHO manuals, guidelines and recommendations for biologicals to identify where updates can lead to a more harmonised adoption of 3Rs principles (i.e. Replacement, Reduction, and Refinement of animal tests) in batch release testing requirements. An international working group consisting of more than 30 representatives from pharmaceutical and biotechnology companies, national control laboratories and regulatory bodies is performing this review. This project aims to address concerns about inconsistencies in the guidance for the scientifically justified use of animal methods required for the post-licensure quality control and batch release testing of biologicals, and the near absence of recommendations for the application of 3Rs principles within the relevant guidelines. Improved adoption of 3Rs principles and non-animal testing strategies will help to reduce the delays and costs associated with product release testing and help support faster access to products by the global communities who need them most urgently.
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Productos Biológicos , Control de Calidad , Vacunas , Alternativas a las Pruebas en Animales , Animales , Productos Biológicos/normas , Vacunas/normas , Organización Mundial de la SaludRESUMEN
Many of the inactivated viral vaccines for human and animal use are manufactured using formaldehyde as an inactivating agent. Apart from formaldehyde, Triton X-100 is also one of the chemicals commonly used in viral vaccine manufacturing. Triton X-100 is typically used to extract the cell-associated viruses and / or components during manufacturing process. The concentration of formaldehyde and Triton X-100 in the final bulks are also reduced during vaccine purification process. Here we report a simple RP-HPLC-UV based method for the quantification of residual Triton X-100 and formaldehyde as process impurities in viral vaccines. This method is also adopted for the residual impurity determination of either formaldehyde or Triton X-100 in other non-viral vaccines, multivalent as well as sub-unit vaccines, such as liquid pentavalent, includes TT, DT, Hepatitis B (rDNA) and Haemophilus type b conjugate vaccine (adsorbed). This method is rapid and can quantify both Triton X-100 and formaldehyde in a single preparation with improved peak asymmetry. This new assay has a linearity range starting from 0.0625 to 1 µg/mL for formaldehyde and 0.625-10 µg/mL for Triton X-100. This method would be very useful for viral vaccine manufacturing and release.
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Cromatografía Líquida de Alta Presión/métodos , Cromatografía de Fase Inversa/métodos , Formaldehído/análisis , Octoxinol/análisis , Vacunas/química , Contaminación de Medicamentos , Límite de Detección , Modelos Lineales , Reproducibilidad de los Resultados , Espectrofotometría Ultravioleta , Vacunas/normasRESUMEN
Adventitious agent detection during the production of vaccines and biotechnology-based medicines is of critical importance to ensure the final product is free from any possible viral contamination. Increasing the speed and accuracy of viral detection is beneficial as a means to accelerate development timelines and to ensure patient safety. Here, several rapid viral metagenomics approaches were tested on simulated next-generation sequencing (NGS) data sets and existing data sets from virus spike-in studies done in CHO-K1 and HeLa cell lines. It was observed that these rapid methods had comparable sensitivity to full-read alignment methods used for NGS viral detection for these data sets, but their specificity could be improved. A method that first filters host reads using KrakenUniq and then selects the virus classification tool based on the number of remaining reads is suggested as the preferred approach among those tested to detect nonlatent and nonendogenous viruses. Such an approach shows reasonable sensitivity and specificity for the data sets examined and requires less time and memory as full-read alignment methods.IMPORTANCE Next-generation sequencing (NGS) has been proposed as a complementary method to detect adventitious viruses in the production of biotherapeutics and vaccines to current in vivo and in vitro methods. Before NGS can be established in industry as a main viral detection technology, further investigation into the various aspects of bioinformatics analyses required to identify and classify viral NGS reads is needed. In this study, the ability of rapid metagenomics tools to detect viruses in biopharmaceutical relevant samples is tested and compared to recommend an efficient approach. The results showed that KrakenUniq can quickly and accurately filter host sequences and classify viral reads and had comparable sensitivity and specificity to slower full read alignment approaches, such as BLASTn, for the data sets examined.
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Contaminación de Medicamentos/prevención & control , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Metagenómica/métodos , Virus/genética , Línea Celular , Biología Computacional/métodos , ADN Viral/genética , Células HeLa , Humanos , ARN Viral/genética , Vacunas/normas , Virus/aislamiento & purificaciónRESUMEN
A medida que los países avanzan hacia la aprobación nacional de las vacunas, ¿cómo tiene lugar este proceso?
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Betacoronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Neumonía Viral/prevención & control , Pandemias/prevención & control , Vacunas/normas , Protocolo de Ensayo Clínico , Sistemas de Salud/normas , Potencia de la VacunaRESUMEN
Biologics are complex pharmaceuticals that include formulated proteins, plasma products, vaccines, cell and gene therapy products, and biological tissues. These products are fragile and typically require cold chain for their delivery and storage. Delivering biologics, while maintaining the cold chain, whether standard (2°C to 8°C) or deepfreeze (as cold as -70°C), requires extensive infrastructure that is expensive to build and maintain. This poses a huge challenge to equitable healthcare delivery, especially during a global pandemic. Even when the infrastructure is in place, breaches of the cold chain are common. Such breaches may damage the product, making therapeutics and vaccines ineffective or even harmful. Rather than strengthening the cold chain through building more infrastructure and imposing more stringent guidelines, we suggest that money and effort are best spent on making the cold chain unnecessary for biologics delivery and storage. To meet this grand challenge in pharmaceutical research, we highlight areas where innovations are needed in the design, formulation and biomanufacturing of biologics, including point-of-care manufacturing and inspection. These technological innovations would rely on fundamental advances in our understanding of biomolecules and cells.
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Productos Biológicos/normas , COVID-19/terapia , Investigación Farmacéutica/normas , Refrigeración/normas , Productos Biológicos/uso terapéutico , COVID-19/epidemiología , Humanos , Investigación Farmacéutica/tendencias , Refrigeración/tendencias , Vacunas/normas , Vacunas/uso terapéuticoRESUMEN
BACKGROUND: Effective management of the vaccine cold chain system at all levels is one of the crucial factors for maintaining vaccine potency. Vaccines require more complex handling and storage requirements due to increased temperature sensitivity and complicated immunization schedules. This urges adequate knowledge, attitude, and practice. This study assessed the knowledge, attitude, and practice of vaccinators and vaccine handlers' in public health facilities. METHODOLOGY: An institutional-based cross-sectional study design was used to assess the knowledge, attitude, and practice of 127 vaccinators and vaccine handlers in public health facilities of Oromia Special Zone, from September 1 to 30, 2019. Data were collected using self-administered questionnaires and a structured observation checklist. Descriptive and inferential statistics were made using the statistical package for social sciences version 20. Variables with a p-value <0.05 were taken as statistically significant. RESULT: The response rate was (96.94%). Sixty-eight (53.5%; 95% CI: 46.5%, 61.4%), 58 (45.7%; 95% CI: 37.8%, 53.5%) and 62 (48.8%: 95% CI; 41.7%, 56.7%) vaccinators and vaccine handlers had satisfactory knowledge, positive attitude and good practice respectively. Receiving training on cold chain management had a statistically significant association with the level of knowledge on cold chain management (AOR = 3.04, 95% CI: 1.04-8.88). CONCLUSIONS: More than half of vaccinators and vaccine handlers had satisfactory knowledge, while below half of vaccinators and vaccine handlers had a positive attitude and good practice. The determinants of knowledge in cold chain management were receiving training on cold chain management. Providing regular technical support and on the job training on vaccine cold chain management will improve the knowledge, attitude, and practice of vaccinators and vaccine handlers.
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Instituciones de Salud/estadística & datos numéricos , Instituciones de Salud/normas , Refrigeración/normas , Vacunación/estadística & datos numéricos , Vacunación/normas , Vacunas/normas , Adulto , Estudios Transversales , Etiopía , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The vaccines industry has not changed appreciably in decades regarding technology, and has struggled to remain viable, with large companies withdrawing from production. Meanwhile, there has been no let-up in outbreaks of viral disease, at a time when the biopharmaceuticals industry is discussing downsizing. The distributed manufacturing model aligns well with this, and the advent of synthetic biology promises much in terms of vaccine design. Biofoundries separate design from manufacturing, a hallmark of modern engineering. Once designed in a biofoundry, digital code can be transferred to a small-scale manufacturing facility close to the point of care, rather than physically transferring cold-chain-dependent vaccine. Thus, biofoundries and distributed manufacturing have the potential to open up a new era of biomanufacturing, one based on digital biology and information systems. This seems a better model for tackling future outbreaks and pandemics.
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Industria Farmacéutica , Biología Sintética , Vacunas , Productos Biológicos/normas , Industria Farmacéutica/tendencias , Pandemias , Biología Sintética/tendencias , Vacunas/normasRESUMEN
Diversos países já aprovaram, em caráter emergencial ou definitivo, o uso de imunizantes para vacinação da população contra o novo coronavirus. Até o dia 05 de janeiro de 2021, ao menos 48 países já começaram a imunizar suas populações. Os últimos a entrarem na lista foram: República de Palau, Islândia, Singapura, Irlanda, Belarus e a Argentina (CNNBRASIL, 2021a). Com a vacinação da população já iniciada em diferentes países, também é relevante o acompanhamento das doses já administradas em razão da população do país e em números absolutos.
Several countries have already approved, on an emergency or definitive basis, the use of immunizations to vaccination of the population against the new coronavirus. As of January 5, 2021, at least 48 countries have begun immunizing their populations. The last to enter the list were: Republic of Palau, Iceland, Singapore, Ireland, Belarus and Argentina (CNNBRASIL, 2021a). With the vaccination of the population already initiated in different countries, it is also relevant the monitoring of doses already administered due to the population of the country and in absolute numbers.
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Humanos , Masculino , Femenino , Embarazo , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Vacunas/análisis , Vacunas/normas , Vacunas/farmacocinética , Infecciones por Coronavirus/prevención & controlRESUMEN
Vaccine-preventable diseases (VPD) are a significant risk to paediatric solid organ transplant (SOT) recipients on lifelong immunosuppressive therapy. Children progressing to end-stage organ dysfunction are unable to mount a robust immune response. Hence, it is important to plan vaccination early in the course of disease, especially if a child is anticipated to be a SOT candidate. Vaccine recommendations need to be individualised in this population based on vaccine history and serology. Catch-up or accelerated schedules may be used to complete vaccinations before transplant. Post-transplant, immunisation is recommenced in consultation with the transplant team taking into context the time since transplant and the intensity of the immunosuppressive regime. Inactivated vaccines are safe post-transplant but postexposure prophylaxis may still be required in children with inadequate immunity to VPD. Specific vaccines may be advised for SOT recipients travelling abroad (in consultation with a travel clinic) or those entering high-risk professions. Additionally, the vaccination status of all household members and close contacts should be reviewed and optimised, offering additional protection to the transplant recipient.
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Inmunización/métodos , Trasplante de Órganos/efectos adversos , Inmunología del Trasplante/inmunología , Enfermedades Prevenibles por Vacunación/inmunología , Vacunas/normas , Adolescente , Niño , Preescolar , Composición Familiar , Humanos , Inmunización/normas , Inmunosupresores/efectos adversos , Trasplante de Órganos/normas , Profilaxis Posexposición/métodos , Receptores de Trasplantes/educación , Viaje , Enfermedades Prevenibles por Vacunación/complicaciones , Enfermedades Prevenibles por Vacunación/epidemiología , Vacunas/uso terapéuticoRESUMEN
As vaccines get approved by national authorities, learn about National and WHO approval processes for vaccines and how safety is ensured during emergency approval of vaccines. Dr Mariângela Simão explains in Science in 5.
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Betacoronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Neumonía Viral/prevención & control , Pandemias/prevención & control , Vacunas/normas , Protocolo de Ensayo Clínico , Sistemas de Salud/normas , Potencia de la VacunaAsunto(s)
Acreditación , Ética Farmacéutica , Homeopatía , Medicina Estatal , Femenino , Humanos , Acreditación/legislación & jurisprudencia , Administración Sublingual , Anticonvulsivantes/efectos adversos , Comunicación , COVID-19/diagnóstico , COVID-19/epidemiología , Tratamiento Farmacológico de COVID-19 , Fentanilo/administración & dosificación , Homeopatía/economía , Homeopatía/ética , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Medicina Estatal/legislación & jurisprudencia , Medicina Estatal/organización & administración , Congéneres de la Testosterona/efectos adversos , Congéneres de la Testosterona/provisión & distribución , Congéneres de la Testosterona/toxicidad , Reino Unido/epidemiología , Vacunas/normas , Vacunas/uso terapéutico , Ácido Valproico/efectos adversosRESUMEN
The counterfeiting of vaccines is an increasing problem globally with the safety of persons vaccinated, the trust in vaccines generally and the associated reputation of vaccine manufacturers and regulatory agencies at risk. This risk is especially critical with the on-going development of COVID-19 vaccines. The ability to track and trace vaccines through the vaccine supply chain down to persons vaccinated has to be enhanced. In this context of traceability, the global immunization community has recently set the barcoding of the primary packaging of vaccines, specifically vaccine vials and pre-filled syringes, as a top priority. Emerging vaccine manufacturers are already engaged in investigating ways to incorporate barcoding in their labelling and packaging using GS1 international standards. A specific pilot taking place in Indonesia by the national vaccine manufacturer, Bio Farma, shows the innovation of barcoding on primary packaging already underway with a relatively modest level of investment and success at this stage. This article highlights the efforts of industry and governments on the value of traceability and introduction to 2D barcodes. Access to financial resources and support from the international immunization community would accelerate such innovations leading to enhanced security of the vaccine supply chain.
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Medicamentos Falsificados , Industria Farmacéutica/normas , Etiquetado de Medicamentos/normas , Procesamiento Automatizado de Datos , Vacunas/normas , Vacunas contra la COVID-19/normas , Industria Farmacéutica/economía , Industria Farmacéutica/métodos , Etiquetado de Medicamentos/métodos , Humanos , Indonesia , Cooperación Internacional , Invenciones , Inversiones en Salud , Innovación Organizacional , Proyectos PilotoRESUMEN
Wildlife vaccination is of urgent interest to reduce disease-induced extinction and zoonotic spillover events. However, several challenges complicate its application to wildlife. For example, vaccines rarely provide perfect immunity. While some protection may seem better than none, imperfect vaccination can present epidemiological, ecological, and evolutionary challenges. While anti-infection and antitransmission vaccines reduce parasite transmission, antidisease vaccines may undermine herd immunity, select for increased virulence, or promote spillover. These imperfections interact with ecological and logistical constraints that are magnified in wildlife, such as poor control and substantial trait variation within and among species. Ultimately, we recommend approaches such as trait-based vaccination, modeling tools, and methods to assess community- and ecosystem-level vaccine safety to address these concerns and bolster wildlife vaccination campaigns.
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Animales Salvajes/parasitología , Evolución Biológica , Enfermedades Parasitarias en Animales/inmunología , Enfermedades Parasitarias en Animales/prevención & control , Vacunación/normas , Vacunas/normas , Animales , Ecosistema , Enfermedades Parasitarias en Animales/epidemiología , Enfermedades Parasitarias en Animales/parasitologíaRESUMEN
In addition to the vaccines due in the first year of life, the US Advisory Committee on Immunization Practices recommends that children continue to receive vaccines regularly against a variety of infectious diseases. Starting at 12 to 15 months of life, these include the two-dose measles-mumps-rubella vaccine series and the two-dose varicella vaccine series. Also in the second year of life, infants should begin the two-dose hepatitis A vaccine series and complete the Haemophilus influenzae type B vaccine series as well as the pneumococcal conjugate vaccine series. Before 19 months of life, infants should receive the third dose of the poliovirus vaccine and the fourth dose of diphtheria-tetanus-acellular pertussis (DTaP) vaccine. The final doses of poliovirus and tetanus-diphtheria-acellular pertussis vaccines are both due at 4 to 6 years of life. Before each influenza season, every child should receive the influenza vaccine. Those less than 9 years of age who previously received less than two doses need two doses a month apart. At 11 to 12 years of life, all should get two doses of the human papillomavirus vaccine, the adolescent/adult version of the tetanus-diphtheria-acellular pertussis vaccine, and begin a two-dose series of meningococcal ACWY vaccine. Each of these vaccines is due when the vaccine works to protect against both an immediate risk as well as to provide long-term protection. Each vaccine-preventable disease varies in terms of the nature of exposure, the form of the morbidity, the risk of mortality, and potential to prevent or ameliorate its harm.
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Vacunas/uso terapéutico , Adolescente , Factores de Edad , Vacuna contra la Varicela/normas , Vacuna contra la Varicela/uso terapéutico , Niño , Preescolar , Vacuna contra Difteria, Tétanos y Tos Ferina/normas , Vacuna contra Difteria, Tétanos y Tos Ferina/uso terapéutico , Femenino , Vacunas contra la Hepatitis A/normas , Vacunas contra la Hepatitis A/uso terapéutico , Humanos , Lactante , Vacunas contra la Influenza/normas , Vacunas contra la Influenza/uso terapéutico , Masculino , Vacuna Antisarampión/normas , Vacuna Antisarampión/uso terapéutico , Vacunas Meningococicas/normas , Vacunas Meningococicas/uso terapéutico , Vacuna contra la Parotiditis/normas , Vacuna contra la Parotiditis/uso terapéutico , Vacunas contra Papillomavirus/normas , Vacunas contra Papillomavirus/uso terapéutico , Vacuna contra la Rubéola/normas , Vacuna contra la Rubéola/uso terapéutico , Factores Sexuales , Vacunas/normasRESUMEN
A vaccine is a biological product which is an important means for human beings to protect themselves. Most of its users are young children with weak immunity. Once a vaccine has a problem, it will pose a serious threat to the lives of many people. At present, the supervision of vaccine production is very simple. The vaccine production record is completely controlled by the enterprises. Enterprises only submit production records to the supervisory agency for review when the vaccine needs to be sold. Production records are easily forged and modified. In order to solve the shortcomings of traditional centralized management. We propose a supervision method for vaccine production based on double-level blockchain. At first, we have designed a double-level blockchain structure. The first level is private data of vaccine prduction enterprise, including production records and corresponding hash. The next level is public data, including production records hash and vaccine information. In this way, we make vaccine enterprise to submit production records in a timely manner without fear of privacy leaks. We avoid enterprise tampering or falsification of production records through the non-tampering features and time stamps of the blockchain. To improve the time efficiency, we propose a consensus mechanism for multi-node cooperate. The primary supervisory node provides sorting services and verifies the correctness of the blockchain replica. The ordinary supervisory node can replace the primary supervisory node when necessary, and help the primary supervisory node recovers data in case of information loss. The review node is responsible for providing complete and correct blockchain copies for other nodes. So we can avoids the problem of waste of time resources in the traditional blockchain system. In addition, in order to avoid the waste of space caused by the redundancy of the blockchain, we propose a vaccine data cutting mechanism. We use the timestamp of the blockchain and the vaccine validity period to determine if the block can be cutted. At the same time, it is also possible to judge whether the block can be cutted based on the information exchange with the vaccination institution. Through these methods, we have realized spatiotemporal efficiency supervision of vaccine production. And for the time being, research work in the field of vaccine production supervision is still very rare. So Our work is ground-breaking.