Application For Approval Research Articles

The Photosensitizer Temoporfin (mTHPC) - Chemical, Pre-clinical and Clinical Developments in the Last Decade.

This review follows the research, development and clinical applications of the photosensitizer 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (mTHPC, temoporfin) in photodynamic (cancer) therapy (PDT) and other medical applications. Temoporfin is the active substance in the medicinal product Foscan® authorized in the EU for the palliative treatment of head and neck cancer. Chemistry, biochemistry and pharmacology, as well as clinical and other applications of temoporfin are addressed, including the extensive work that has been done on formulation development including liposomal formulations. The literature has been covered from 2009 to early 2022, thereby connecting it to the previous extensive review on this photosensitizer published in this journal [Senge, M. O. and J. C. Brandt (2011) Photochem. Photobiol. 87, 1240-1296] which followed its way from initial development to approval and clinical application.

Cost-effectiveness analyses of 15- and 20-valent pneumococcal conjugate vaccines for Japanese elderly

BackgroundDespite the 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccination programme implementation, pneumococcal disease (PD) remains an important cause of morbidity and mortality among the elderly in Japan, particularly since childhood pneumococcal conjugate vaccine (PCV) vaccination programme continues to alter the serotype PD distribution among the elderly. Recently, in the United States, PCV15/PCV20 were recommended for adults aged ≥ 65 years and those aged 19–64 years with certain underlying conditions. In Japan, PCV15 is under the approval application process and PCV20 undergoing clinical trials, which has warranted the need in evaluating their value for money. MethodsWe conducted cost-effectiveness analyses with Markov model and calculated incremental cost-effectiveness ratios of PCV15/PCV20 vaccination programme compared to status quo from payers’ perspective. Transition probabilities and utility weights in estimating quality-adjusted life-year (QALY), and disease treatment costs were either estimated or obtained from literature. To reflect the situation of COVID-19 pandemic, epidemiological data from 2020 and beyond were used. ResultsCompared to the current vaccination programme, PCV20 vaccination programme gained more QALYs with less cost, while PCV15 vaccination programme cost ¥35,020 (US$318, US$1 = ¥110) to gain an additional QALY. Replacing PPSV23 vaccination programme with PCV20 vaccination programme is cost-saving. One-way sensitivity analyses revealed that lower VE limits of PCVs against non-bacteremic pneumonia (NBP) have large impact to change the result from PCV20 vaccination programme dominated PPSV23 vaccination programme to PPSV23 vaccination programme dominated PCV20 vaccination programme. ConclusionIn the COVID-19 era, replacing current PPSV23 with a single-dose PCV15- or PCV20 immunisation programme for 65-year-old adults in Japan is highly cost-effective, while the PCV 20 vaccination programme was observed to be more favourable.

Time to potential for listing of new drugs on public and private formularies in Canada: a cross-sectional study.

Information about the timing involved in various stages of making new drugs available to Canadians is important for understanding how a national pharmacare plan will affect timely access to new drugs. I explored the timing of the various steps between receiving a Notice of Compliance and a decision by the pan-Canadian Pharmaceutical Alliance (pCPA). I gathered data from various databases (Canadian and other) about new drugs approved between 2011 and 2020, including generic names, date of application for approval (New Drug Submission [NDS]), date of Notice of Compliance, date of marketing, dates when a submission was made to the Canadian Agency for Drugs and Technologies in Health (CADTH) and the pCPA, and when these agencies made a decision. Marketing dates were available for 301 of the 337 new drugs approved. The median time from NDS to marketing was less than the time to a positive pCPA decision for all years between 2011 and 2020. There was no significant change in the difference between the 2 periods over time (p = 0.2). Additional therapeutic value did not make a difference in the delay (p = 0.3) and companies did not take full advantage of the opportunity to file early submissions with CADTH. The delay between when drugs could be listed on private compared with public formularies was at least 1 year. If a national pharmacare plan is instituted, one of the priorities should be to concentrate on consolidating and working to shorten the CADTH and pCPA processes.

The Design and Implementation of Geospatial Information Verification Middle Platform for Natural Resources Government Affairs

Geospatial Information Verification Mid-End Platform for Natural Resource Administration is designed in response to issues such as repeated development, low scalability, and inconsistent verification rules in existing approval and supervision application systems. We first discussed the architecture of the middle platform and micro-services and also examined the business requirements. Secondly, we presented the architecture of the spatial information verification platform. Finally, the application method in the construction land approval business is introduced. Practical applications proved that the spatial information verification platform is highly scalable and maintainable, with reusable business components and data services for a variety of government affairs application systems.

Evaluation of off-label anti-vascular endothelial growth factor and steroid implant medication uses in macular edema due to retinal vein occlusion in Turkey.

Retinal vein occlusion (RVO) is one of the most common causes of vision loss. Anti-vascular endothelial growth factor (anti-VEGF) drugs, ranibizumab and aflibercept, and corticosteroid implants are approved treatment options for RVO-related macular edema (ME) in Turkey. To the best of our knowledge, there is no data regarding the off-label use of these drugs for RVO in English literature. We aimed to evaluate the clinical and demographic characteristics of off-label drug use applications in Turkey for RVO. Applications made to the Turkish Medicines and Medical Devices Agency between January 1 and December 31, 2018, for the use of off-label drugs (ranibizumab, aflibercept, dexamethasone implant) for the diagnosis of RVO from hospitals across Turkey were retrospectively analysed. Data of the applications, such as demographic characteristics, previous treatment regimens, reasons for applications, applicant hospitals and their regions, were recorded. There were 291 approved applications for RVO. The mean age of the patients was 64.88 ± 10.78 years, 48.8% were male, and 51.2% were female. Of these applications, 44.7% were for aflibercept, 35.7% for ranibizumab and 19.6% for dexamethasone implant. No application was made for bevacizumab since it could be used without needing for an application. The most common reasons for applications were due to dose limitations, failure to complete loading doses, and glaucoma, respectively. In terms of the distribution of the applicant hospitals, public university hospitals ranked first with 72.5%, training and research hospitals ranked second with 14.7% and foundation university hospitals ranked third with 13.1% rates. The practice of drug use in RVO in Turkey has changed as of the beginning of 2019. Stepwise therapy has been accepted by the drug regulatory agency Turkish Medicines and Medical Devices Agency. Utilization of licensed drugs, aflibercept, ranibizumab and dexamethasone has been allowed only after administration of 3 doses of intravitreal bevacizumab. After 3 doses of bevacizumab, the physician may continue either with bevacizumab again or a dexamethasone implant. If there is a reason such as the presence of glaucoma, the physician may skip dexamethasone and switch to aflibercept and ranibizumab, but in this case, dexamethasone cannot be administered to the patient for life. The evaluation of the off-label treatments of RVO, which is one of the most frequently followed diseases in retina clinics, not only contributes to the literature but also provides information regarding the most frequently applied treatments and the physicians' off-label drug preferences for RVO.

Data collection on co‐formulants used in representative plant protection product formulations in the context of the EFSA peer review process for approval/renewal of approval of active substances

EFSA collected data on co-formulants contained in plant protection product (PPP) formulations for representative uses as part of applications for approval or renewal of active substances, to collate the information available during the peer review process. Information was extracted from pesticide active substances dossiers for which a peer review output was issued between January 2019 and March 2022, in which a total of 182 co-formulants were found. Most of the data submitted on the identity and physicochemical properties of the co-formulants are complete as required by Regulation (EU) 284/2013. The data related to (eco)toxicological properties mainly refers to the safety data sheet of the individual co-formulants and, if available, to registration dossiers under Regulation (EC) 1907/2006 (REACH). Fifty-three % of the identified co-formulants have been registered under REACH and about 80% of the 53% are registered for more than 1000 tonnes a year for which registrants are required to submit the most complete data set under REACH. For the remaining percentage, a more limited range of toxicological information is available: EFSA will investigate whether they are exempted from registration under REACH. Co-formulants contained in plant protection products may also be subject to other European legislation such as the regulations on biocides, food/feed additives, food contact materials, or are included in lists of excipients or cosmetic ingredients. Observations highlighted in the present report can serve Member State risk assessors and risk managers to harmonise the assessment of co-formulants in collaboration with the EU agencies (EFSA, ECHA).

Profiling the process development of Wurster coating for modified release capsule products in approved drug product applications

In this paper, we have studied Wurster Coating operation for the manufacture of modified release (MR) capsule products submitted to FDA as New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs) by using a data-driven approach. We have collected and classified information into Wurster coating associated process variables, quality attributes, and scale up strategies under Quality by Design (QbD) paradigm. We have quantified the importance and risk of the process variables and quality attributes by analyzing reported frequencies and risk factors, respectively. We have also included analysis of quality attributes listed with high risk factors, such as weight gain, particle size, assay, dissolution of coated beads, and water content/ Loss on drying (LOD) and the process variables with higher risk factors, such as product temperature, spray rate, atomization air pressure, Inlet air volume and Inlet air temperature, etc.We believe that the knowledge obtained through profiling Wurster coating operation will help the industry to further improve the quality of drug product applications regarding the development of this unit operation. We hope systematic profiling of pharmaceutical unit operations under QbD paradigm can provide support for FDA’s IT initiatives aiming at improving the efficiency and consistency of FDA’s quality assessment.

Partial advances in the diagnosis and treatment of gastrointestinal cancer.

Partial advances in the diagnosis and treatment of gastrointestinal cancer.

Practice of Human Resource Development Related to Biopharmaceutical Manufacturing and Quality Control and the International Contribution as Centers of Excellence of Asia-Pacific Economic Cooperation-Life Sciences Innovation Forum-Regulatory Harmonization Steering Committee

In recent years, the development of biologics such as therapeutic antibodies has increased. Around 1980, Japan was the world's leading country in terms of research and development on biologics. However, after that, the development of biologics in Japan has become stagnant. Especially, research and development of therapeutic antibodies, which are critical medical products, is compared to that being conducted in Europe and the United States. The products distributed in Japan are developed and manufactured overseas. Furthermore, related emerging technologies are developed overseas. Therefore, to improve this situation, Biologics Center for Research and Training (BCRET) was established in August 2017 in Kobe city to develop human resources for biologics with the cooperation of Japan Pharmaceutical Manufacturers Association, Japan Agency for Medical Research and Development, Kobe University, and related ministries and agencies. BCRET will develop human resources by providing useful information and experience related to the development and manufacture of biologics in the form of classroom lectures and practical training for process and analysis developers and pharmaceutical affairs related to manufacturing, quality control, and approval applications in the biologics field of pharmaceutical companies, along with reviewers and inspectors of Pharmaceuticals and Medical Devices Agency and inspectors from countries belonging to Asia-Pacific Economic Cooperation (APEC). This is the first attempt in the world to develop human resources in a field of chemistry, manufacturing and control and Good Manufacturing Practice of biologics for inspectors in countries belonging to APEC, and it is expected to contribute internationally for human resources for biologics.

Mechanical and microbiological testing concept for activatable anti-infective biopolymer implant coatings.

An anti-infective bilayer implant coating with selectively activatable properties was developed to prevent biofilm formation and to support the treatment of periprosthetic infection as a local adjunct to current treatment concepts. In a first step, Ti6Al4V discs were coated with a permanent layer of Poly(l-lactide) (PLLA) including silver ions. The PLLA could be optionally released by the application of extracorporeal shock waves. In a second step, a resorbable layer of triglyceride (TAG) with incorporated antibiotics was applied. The second layer is designed for resorption within weeks. Prior to approval and clinical application, a comprehensive evaluation process to determine mechanical/physical and microbiological properties is obligate. To date, none of the existing test standards covers both drug-releasing and activatable coatings for orthopedic implants. Therefore, a comprehensive test concept was developed to characterize the new coating in a pilot series. The coatings were homogeneously applied on the Ti6Al4V substrate, resulting in an adhesion strength sufficient for non-articulating surfaces for PLLA. Proof of the extracorporeal shockwave activation of PLLA was demonstrated both mechanically and microbiologically, with a simultaneous increase of biocompatibility compared to standard electroplated silver coating. Wettability was significantly reduced for both layers in comparison to the Ti6Al4V substrate. Thus, potentially inhibiting biofilm formation. Furthermore, the TAG coating promoted cell proliferation and bacterial eradication. In conclusion, the testing concept is applicable for similar biopolymer coating systems. Furthermore, the extracorporeal activation could represent a completely new supportive approach for the treatment of periprosthetic joint infections.

Regional Mobile Telecommunications Access, Competition and Public Benefits

The Australian Competition and Consumer Commission (ACCC) received an application for merger approval from Telstra Corporation Limited and TPG Telecom Limited related to three interrelated agreements that would put in place a Multi-Operator Core Network (MOCN) arrangement. The three agreements include a MOCN Service Agreement, a Spectrum Authorisation Agreement, and a Mobile Site Transition Agreement. This paper considers the proposed arrangements, identifies that the ACCC’s failure to declare domestic mobile roaming in 2018 was, in some large part, responsible for the market environment that fostered the current proposal, and that the proposed arrangements are not a satisfactory mechanism to fundamentally improve the delivery of reasonably priced, open and competitive, reliable, and high-quality mobile telecommunications in regional and remote areas.

설계도서와 집합건물의 구분소유관계의 관련성에 관한 연구

When the building is completed, the developer decides whether the building is a general building or a condominium building. It is called a juristic act for division that the owner expresses his intention to make a general building into a condominium building. The developer, who is the seller of condominium, should clearly determine the unit and the common element, and the limited common element through the juristic act for division. Otherwise, after the sale of the condominium building, disputes arise between the unit owners due to the unclear expression of units and common elements. If the developer's juristic act for division should be the standard for determining the relationship between unit owners, it is embodied through drawings and specification. The juristic act for division is expressed when applying for a construction permission, parceling out units, or applying the approval of use of condominium based on drawings and specification. However, in reality, drawings and specification are not the criteria for clarifying the relationship between unit owners. This is because the scope of the units and common element, and limited common element are not properly displayed in drawings and specification. In addition, the contents of drawings and specification may vary depending on the designer of the building. The developer of the building is often indifferent to the relationship between unit owners included in the drawings and specification. For this reason, when there are disputes of the relationship between unit owners, juristic act for division or drawings and specification are not the criteria for determining the relationship. To solve these problems, the contents of drawings and specification should be prepared for clarification of the relationship between unit owners, and the content of drawings and specification should be reflected in the contract for parceling out units of condominium, in the application for approval of use of building, and in the condominium building registers. Therefore, it is necessary to make the contents of drawings and specification or building registers a standard for dispute resolution when problems arise among unit owners regarding the relationship of condominium, such as the scope of a unit and common elements, or limited common elements.

Davids versus Goliaths: Pharma and academia threats to individual scientists and clinicians

Background We previously described experiences of clinicians who published adverse drug reaction reports. We now report on threats and intimidations leveled against clinicians and scientists who received publicly documented threats after communicating safety, efficacy, or data integrity findings contrary to corporate interests. Methods Data on threats and intimidations were obtained from transcripts of governmental hearings or agencies, university-affiliated reports, media interviews, and investigative journalism articles. Content and timing of threats and intimidation, subsequent harms, numbers of persons seriously injured or who died from individual toxicities, financial payments from sponsors related to safety, efficacy, or data integrity concerns, and civil settlements and criminal findings were evaluated. Findings Twenty-six individuals who communicated safety, efficacy, or data integrity concerns were targets of threats and intimidation from corporate employees (twenty-three individuals) or regulatory personnel (three). Seventeen individuals identified instances where pharmaceutical sponsors submitted fraudulent data in support of regulatory approval of a drug or device. Scientist and clinician communications were followed by drug/device withdrawals (fourteen drugs/devices), black box warnings (six drugs), withdrawal of a sponsor’s application for regulatory approval (one device), and delay of approval of a sponsor’s application for regulatory approval (one drug). Actions mainly occurred after persons communicated with pharmaceutical employees (fourteen). Intimidation efforts by corporate personnel included threats of lawsuits (eighteen individuals), hiring private investigators (nine), and public disparagement at conferences (eleven). Related intimidation efforts carried out by academia or regulatory agency superiors included threats of: loss of positions (six), loss of grant funding (two), delays in decisions regarding tenure (two); or reassignment to a low-level position (one). Academic harms included lost: hospital or university appointments (nine and six, respectively), grant funding (two), chairperson title of an international clinical trial group (one), and journal editorial board position (one). Corporate harms included payment of $1 million to defense attorneys in three cases filed against clinicians. Interpretation Threats and intimidation carried out by corporate employees and/or academic supervisors followed public communication of concerns regarding patient safety, drug efficacy, or data integrity, including instances where sponsors were identified as having submitted fraudulent data to regulatory or government agencies. Consideration should be given to filing criminal charges against pharmaceutical executives who are discovered by scientists or clinicians to have knowingly submitted fraudulent data to regulatory or governmental agencies, rather than causing the scientists and clinicians who submit such reports to risk losing their reputations and occupations.

The Complex Process of Using the Interconnected Knee Arthroplasty Device Clearance Pathway.

Background: The clearance of medical devices by the US Food and Drug Administration (FDA) has remained largely unchanged since 1976, when the Medical Device Amendments Act established a system classifying devices into 3 categories based on safety risk to the consumer. The system allows for the clearance of many orthopedics devices through the 510(k) premarket pathway, which is based on “predicate ancestors,” previously cleared devices that are “substantially equivalent.” Purpose: We sought to trace the predicate ancestors of modern total knee arthroplasty (TKA) devices, specifically those recently cleared for marketing by the 510(k) pathway that claim substantial equivalence to prior devices, despite potential differences in material science and design. In addition, we aimed to document which TKA devices cleared by the 510(k) pathway have substantial equivalence to devices that have since been recalled by the FDA. Methods: To create a comprehensive list of TKA devices, we used FDA Classification Process Codes corresponding to knee arthroplasty to search the FDA’s databases from May 28, 1976, the start of the 510(k) process, to May 1, 2021. Of 1309 resulting devices, 89 were excluded as not related to arthroplasty. For each of the remaining devices, we analyzed the descendant devices that claimed substantial equivalence, either directly or indirectly. We used data of recalled designs to determine both the absolute number of recalled devices and the number of currently cleared devices that presented substantial equivalence claims upon predicates that have since been recalled. Results: Of 1220 knee devices cleared or approved, 6 (0.5%) were approved through the premarket approval application (PMA) process, and 1214 (99.5%) were cleared through the 510(k) pathway. Of the 1214 cleared devices, 217 (17.9%) have been recalled and 204 (16.8%) have ties to at least 1 recalled predicate device linked through generational claims of substantial equivalence. We found 90 devices (7.4%) linked directly to a recalled predicate device. Conclusions: Most knee arthroplasty devices are cleared for marketing through reliance on a complex web of equivalency to previously cleared predicates. We found that many TKA devices thus connected were cleared decades apart, with multiple iterations of design and material modifications. Many currently marketed TKA devices have claimed equivalency to predicates that have been recalled. Our findings suggest the need for novel regulatory strategies that might further patient safety while balancing the unwanted effects of regulatory burden.

Research and publication ethics knowledge and practices in the health and life sciences: Findings from an exploratory survey

We sought to examine the levels of awareness, preferences, experiences, and practices of researchers in the health and life sciences regarding research and publication ethics. A questionnaire was deployed on the Google Forms to a global audience. Reminder emails and WhatsApp messages containing a brief description and a link to the online survey were sent out through the various platforms until no new responses were received after three reminders. Only 36.7% of study participants were aware of the ICMJE authorship criteria. Less than a quarter (22.0%) of the respondents were aware about the existence of an ethics code. Respondents’ experience with their most recent ethics approval application was poor (11.4%), good (36.0%), and excellent (4.2%) respectively. The practice of research teams to include authors with no or limited significant contribution to an article was frequent (44.3%), common (29.5%), systematic (10.6%). Over 41.7% of the respondents had ever conducted a study involving human research subjects without prior ethical approval. Respondents experience with their most recent ethics approval application was poor (11.4%), good (36.0%), and excellent (4.2%) respectively. Major challenges in obtaining ethical approval were: too much bureaucracy (47.3%), ethical approval application cost (5.3%), and unduly long review turnaround in receiving feedback and decisions (3.8%). Most respondents (83.0%) worked in institutions that hosted a research an ethics committee. Less than half (42.4%) of the respondents had been formerly trained in publication ethics. Ethical misconduct such as having no ethical approval prior to conducting a study, gift and ghost authorships were unacceptably high. Formal training in research and publication ethics should be institutionalized in the courses in universities and research institutions. Academic journals and funders have the duty to support researchers to uphold research ethics and research integrity standards. Institutionalization and awareness raising regarding these best practices are highly needed.

Time to access to novel anticancer drugs in Europe, a case study in seven European countries.

1586 Background: After European Medicines Agency Marketing Authorization (EMA-MA) different national reimbursement processes may contribute to unequal access throughout the EU. The aim of this study is to investigate the access time to new anticancer medicines in seven high-income Northern European countries and factors influencing the reimbursement process. Methods: We performed a retrospective database study. New anticancer medicines were included with a positive CHMP advice between January 2016 and January 2020, leading to EMA-MA followed by an application for national reimbursement approval in Germany, UK, France, The Netherlands, Belgium, Norway and Switzerland. The relevant Health Technology Assessment (HTA) - and reimbursement websites for each country were used to identify reimbursement dates. Time to access was defined as the time between EMA-MA and date of inclusion in the relevant reimbursement list. In addition we investigated the differences in national approval process and study-, medication- and patient- related factors which might influence the time to reimbursement. Results: We found that for the thirty-six new anticancer medicines, national reimbursement came on average 289 days after EMA-MA, with a variety of -125 in Switzerland (i.e. non EU-member) to 1415 days. Of these EMA-MA new anticancer medicines 42% were reimbursed in all countries. The average number of cancer medicines reimbursed in the examined countries was 27 (75%), with a range of 24 (67%) in Belgium to 36 (100%) in Germany. The shortest average time from EMA-MA to reimbursement were in Germany, 2.33 days, France and Switzerland following with 207 days and 279 days respectively. The median time to reimbursement was 227 days with a range of 3 days in Germany to 553 days in Belgium. In Germany, where there is no pricing and reimbursement approval required when launching a pharmaceutical, 100% of the cancer medicines are reimbursed within five days. After one year, In the UK 56% of the medicines are reimbursed, followed by 53% in the Netherlands, France and Switzerland. Belgium and Norway have a one year reimbursement rate of 14% and 11% respectively. Access to anticancer medicines is dependent on regulatory procedures, HTA and price regulations. Germany has a fast market access for anticancer medicines with a price regulation one year after launching the medicines. In the other countries, price regulation is part of the launching process. Other factors which might accelerate the time to reimbursement we are examining are high clinical benefit score (ESMO-MCBS), (non-)orphan status of the medicines and submission by big pharmaceuticals. Conclusions: This study shows that after EMA-MA, except for Germany, on average it takes a long time for anticancer medicines to be reimbursed in Northern European countries. There is a considerably variety both within and among countries.

Regulatory Approval With Real-World Data From Regulatory Science Perspective in Japan

Recently, there has been a growing trend in clinical development to utilize real-world data (RWD) to improve the efficiency of drug/medical device development. Especially, the use of RWD to generate real-world evidence (RWE) in regulatory approval is currently undergoing a period of great change with an increasing degree of active discussion. In Japan, RWE has been used in the control arms of clinical trials, observational studies, post-marketing surveillance, and public knowledge-based applications for regulatory approval. However, the exclusive use of RWE applications has still not been applied. In this paper, we summarize the history and the current situation of RWE and focus on the utilization for the purpose of regulatory approval. In addition, we will discuss the issues and perspectives for registry research in the utilization for regulatory approval in Japan.

The Food and Drug Administration Begins Year With Final Rule on Medical Device Premarket Approval Application and Humanitarian Device Exemption Application Approvals

Corresponding author: Jay Geller, JD, MBA, 121000 Wilshire Blvd, Ste 1250, Los Angeles, CA 20025 ([email protected]). The author declares no conflicts of interest.

Canadian Public Health Laboratory Network guidelines for the use of point-of-care tests for Treponema pallidum in Canada.

Over the past few years, the increase in infectious syphilis outbreaks in major urban centres and remote or rural locations in Canada, often affecting hard-to-reach patient populations, has renewed an interest and urgency in studying the use of point-of-care tests (POCTs) that can provide test results at the time and place of primary health care delivery, obviating the repeat visit necessary with traditional syphilis serology or molecular diagnostic tests. In 2015, the Canadian Public Health Laboratory Network released its first laboratory guideline for the use of POCTs in the diagnosis of syphilis in Canada. Although Canada has no licensed POCT, two POCTs (Syphilis Health Check and the DPP® HIV Syphilis System) have received US Food and Drug Administration (FDA) approval under premarket approval applications. Most syphilis POCTs detect antibodies to treponemal antigens, so their results cannot be used to differentiate between active and past infection. The only POCT that detects antibodies to both treponemal and non-treponemal antigens does not yet have Health Canada or FDA approval. In this updated guideline, the current landscape of POCTs for syphilis, with an emphasis on data from low-prevalence countries, is described. Individual operators should consider the questions of where, when, how, and why a POCT is used before its actual implementation. Training in the operation and interpretation, quality control, proficiency program, safety, and careful documentation of the process and results are especially important for the successful implementation of POCTs.

The Procedure for Concluding a Settlement Agreement in Civil Litigation

In article explores the procedure for concluding a settlement agreement in civil proceedings. It is shown that in accordance with the current civil procedure legislation, the issue of approving a settlement agreement is considered at a court hearing with the mandatory participation of all interested parties. The paper critically evaluates the exception to this rule, expressed in the possibility of sending an application for approval of a settlement agreement in the absence of interested parties (Part 3 of Article 153.10 of the Civil Procedure Code of the Russian Federation, Part 3 of Article 141 Arbitration Procedure Code of the Russian Federation). In the course of the conducted research, it was found that in civil and arbitration proceedings, the issue of approving a settlement agreement concluded at the stage of preparing the case for trial is resolved differently. The author makes critical comments on this. It is argued that the approval of the settlement agreement reached at the stage of preparing the case for trial, both in civil and arbitration proceedings, should take place in the preliminary, and not the main court session.