Requirements Of Regulatory Agencies Research Articles

Well-Characterized Polyethyleneimine-/Carboxylated-Polyethylene-Glycol-Functionalized Gold Nanoparticles as Prospective Nanoscale Control Materials for In Vitro Cell Viability Assays: Particle Characterization and Toxicity Tests in Eight Mammalian Cell Lines.

The safety screening of manufactured nanomaterials (MNMs) is essential for their adoption by consumers and the marketplace. Lately, animal-based testing has been replaced by mechanistically informative in vitro assays due to the requirements of regulatory agencies. Cell viability assays are widely employed for manufactured nanomaterial hazard screening as a first-tier approach. Critical parts of such assays are positive and negative controls that serve as measurement benchmarks. We present the cellular viability and corresponding particle characterization obtained with eight different cell lines that were exposed to Au-PEI and Au-PEG-COOH nanoparticles. We showed that polyethyleneimine- and carboxylate-polyethylene-glycol-conjugated gold nanoparticles (AuPEI and Au-PEG-COOH) qualified for positive and negative controls in the in vitro cell viability assays used for MNM toxicological screening.

Assessment of Solid Waste Management Practices Following Private Partnership Operations in Zaria Urban Area of Kaduna, Nigeria

The safe disposal of municipal waste is very important in promoting a healthy environment. High-quality public services and promoting competition in the waste management sector leads to the formation of private sector participation (PSP) to handle solid waste management in Kaduna. A multi-stage sampling technique was adopted which involves dividing the local government into localities. Stage two involves the purposive sampling technique which was adopted in selecting locality with high population and low population density areas, a total of 400 households from both strata were interviewed. Descriptive statistics was used to analyse the information from the questionnaires and results were presented using frequency tables and charts. The findings revealed that quality of service among the PSP operators recorded high success in the high-income areas and much less in the low and medium-income areas. On average, industry productivity was 5.63 tonnes per day per vehicle. 12 out of which in the study area were above this average and in meeting increased productivity, year of experience in operations, number of trips made, number of times trucks were serviced, and adhering to regulatory agency requirements were among the factors influencing company’s productivity in the state. It also shows less effectiveness of the system in waste management in the area. The study, therefore, recommends that regulatory agency should be more aggressive in playing their statutory roles of managing the PSP operators.

The procedure for implementing the compliance system in the bank

In today's conditions of globalization and increased competition in the financial sector, the introduction of a compliance system in the bank is becoming an extremely urgent task. As banking institutions are leading participants in the financial system, their stability is important for the economy of the state. The activities of banking institutions are aimed at preventing financial crimes, such as money laundering and terrorist financing, through compliance, which consists in checking customers, monitoring financial transactions and identifying suspicious transactions, preventing crises and financial failures. With the growing requirements of regulatory authorities, as well as taking into account potential financial risks and threats from unscrupulous customers or criminal groups, banks need to improve their risk management system and ensure compliance of all operations with legislation and standards. This creates the need to develop and implement an effective compliance system that ensures compliance with all legal and ethical norms in the bank's financial activities. In this context, the study and analysis of the process of implementation of the compliance system becomes an important task that requires careful research and determination of the optimal course of action to achieve successful results in ensuring internal control and compliance in the bank. The compliance system, or internal control, is defined as a set of procedures, policies, and standards that are aimed at ensuring the fulfillment of all internal and legal requirements in the bank, as well as at identifying, evaluating, and managing various risks associated with the bank's activities. In this scientific study, we will consider the process of implementing a compliance system in a bank in the context of regulatory requirements and international standards, as well as investigate the practical aspects of its implementation, including the structure of the compliance team, monitoring and reporting tools, as well as the impact of the compliance system on the bank's business strategy and reputation. Our study will emphasize the importance of properly organizing the process of implementing the compliance system to ensure customer trust and maintain the bank's stability in the modern financial environment.

International Society for Cell and Gene Therapy Clinical Translation Committee recommendations on mesenchymal stromal cells in graft-versus-host disease: easy manufacturing is faced with standardizing and commercialization challenges

Mesenchymal stromal cells (MSCs) have been used in multiple clinical trials for steroid-refractory moderate-severe (grade II–IV) acute graft-versus-host disease (aGVHD) across the world over the last two decades. Despite very promising results in a variety of trials, it failed to get widespread approval by regulatory agencies such as the U.S. Food and Drug Administration and the European Medicines Agency. What lessons can we learn from this for future studies on MSCs and other cell therapy products? Broad heterogeneity among published trials using MSCs in aGVHD was likely the core problem. We propose a standardized approach in regards to donor-related factors, MSCs-related characteristics, as well as clinical trial design, to limit heterogeneity in trials for aGVHD and to fulfill the requirements of regulatory agencies. This approach may be expanded beyond MSCs to other Cell and Gene therapy products and trials in other diseases.

Management of Corporate Distressed Debt: From Terminology to Statistics

The aim of the paper is to systematize definitive approaches of “problem (distressed) debt” and related terms in order to create a conceptual apparatus useful from the point of view of management entities, as well as to statistically study the dynamics and sectoral structure of problem debt based on the banking sector performance indicators in Russia and other countries in 2009–2023. As a result of the analysis of international and Russian documents in the field of banking regulation, two types of problem debt typologies have been identified: classifications of credit risk of the supervisory authority and recommendations of internal credit risk. Two approaches to the definition of “problem (distressed) debt” have been identified: a regulatory (accounting) approach based on the requirements of regulatory authorities and reporting standards; an identification approach that includes a list of various signs of problems. As a result of the synthesis of approaches, the article proposes the author’s understanding of the terms “overdue debt (credit)”, “problem (distressed) debt” and “problem asset”, taking into account the subject composition of debt managers, represented not only by banks, but also by trade creditors. As part of the preparation of the statistical review for 15 years, a constant excess of the share of “bad” loans (with no probability of repayment and complete depreciation of debt) over “problematic” ones was revealed, which confirms the low effectiveness of the banks’ preventive work to prevent borrowers from becoming problematic (troubled). The authors analyzed the dynamics of the ratio of non-performing loans (NPL) to the total volume of loans issued in 28 countries of the world, revealed a relatively high proportion of the indicator in Russia in recent years. An assessment of the sectoral debt structure of Russian companies showed the dominant position of the manufacturing industry, whereas in the structure of overdue debts, the main companies are from the real estate, wholesale and retail trade sectors. The work of credit institutions to manage problem debts is an important issue of ensuring the economic security of the state and should include monitoring the condition of borrowers based on a strategic map and a comprehensive analysis model, using the methodology of managing transformational projects for the financial recovery of troubled companies.

Обучение рабочих и специалистов для горнодобывающей отрасли в аспекте безопасности труда

Labor safety in the mining industry is a set of measures aimed at improving the production environment that affects the health and operability of a person at work and the continuous professional development of employees. The objective assessment of safety of all stages of the production process is a crucial aspect of the enterprise’s activities. It is based on compliance with the requirements of regulatory authorities in the field of labor protection and industrial safety, occupational standards as characteristics of labor conditions, qualifications and professional competence of an employee, as well as compliance with the federal state educational standards as a basis of training of a specialist or a worker who are the main participants of the technological process in mining. The formation of professional competencies of each employee that ensure safe operation at the site or enterprise, the in-depth knowledge, development of operational algorithms, and the skill to perform technological operations at the workplace primarily depend on the basic education of employees obtained under the programs of secondary vocational education. The Federal State Educational Standards existing since 2013 became outdated and were gradually updated in 2022–2023. The training terms were normatively determined within the framework of the federal project «Professionalism» which aimed to resume close cooperation between educational organizations and enterprises. Educational organizations were enabled to increase the time to practice. The qualification of graduates under skilled worker training programs has become universal and does not specify the type of activity, whereas a new type of professional activity, namely ensuring the functioning of the occupational health and industrial safety management system at the site (or enterprise), was introduced for midlevel specialists. All this should ensure the future training of new personnel in compliance with the requirements of Federal Law of July 21, 1997 № 116–FZ «On industrial safety of hazardous production facilities» and the Russian Federation Government Decree of August 17, 2016 № 806 «On application of the risk-oriented approach in the organization of certain types of state control (supervision) and introducing amendments to some acts of the Government of the Russian Federation».

Developing machine learning systems worthy of trust for infection science: a requirement for future implementation into clinical practice.

Infection science is a discipline of healthcare which includes clinical microbiology, public health microbiology, mechanisms of microbial disease, and antimicrobial countermeasures. The importance of infection science has become more apparent in recent years during the SARS-CoV-2 (COVID-19) pandemic and subsequent highlighting of critical operational domains within infection science including the hospital, clinical laboratory, and public health environments to prevent, manage, and treat infectious diseases. However, as the global community transitions beyond the pandemic, the importance of infection science remains, with emerging infectious diseases, bloodstream infections, sepsis, and antimicrobial resistance becoming increasingly significant contributions to the burden of global disease. Machine learning (ML) is frequently applied in healthcare and medical domains, with growing interest in the application of ML techniques to problems in infection science. This has the potential to address several key aspects including improving patient outcomes, optimising workflows in the clinical laboratory, and supporting the management of public health. However, despite promising results, the implementation of ML into clinical practice and workflows is limited. Enabling the migration of ML models from the research to real world environment requires the development of trustworthy ML systems that support the requirements of users, stakeholders, and regulatory agencies. This paper will provide readers with a brief introduction to infection science, outline the principles of trustworthy ML systems, provide examples of the application of these principles in infection science, and propose future directions for moving towards the development of trustworthy ML systems in infection science.

Cooperativism as a solution or as an obligation? The formation of cooperatives in small-scale mining in Brazil

The Brazilian state, through the 1988 Federal Constitution, the 1999 Mining Permit Law, and the 2008. Garimpeiro Statute, endorsed the cooperative organizational model as a priority for organizing mineral activity in artisanal and small-scale mining (ASM) in the country. Brazil's policymakers understood that the cooperative model could more efficiently reduce the sector's informality and promote cooperation. Against this backdrop, this paper seeks to problematize whether the formalization of cooperatives alone can solve many of the governance problems associated with ASM, as well as offer useful insights into the mechanisms by which cooperatives are constituted. This discussion brought up the question of how mineral cooperatives in Brazil function and whether the way they are constituted influences their ability to organize work and how they function. In order to empirically analyze this question, the research delimited the cooperatives in the state of Minas Gerais, in the southeastern region of the country, as the universe of analysis. Fourteen mineral cooperatives were identified. Data collection was carried out by means of on-site interviews and analysis of the founding by-laws and minutes of incorporation of these organizations. Interviews were also held with agents of the local government. The results presented point out that the formation of cooperatives in Minas Gerais is more linked to external demand and to pressure from the environment than to the endogenous motivation of a group. The cooperatives that were created by the workers' initiative tend to follow the principles of cooperativism in an endogenous way. On the other hand, the cooperatives that were created due to the requirements of regulatory agencies have great difficulties assimilating the cooperative model. Finally, we conclude that the pressure for the formalization of cooperatives was not accompanied by the structuring of public policies that support social organization and collective action, thus motivating the merely formal emergence of cooperatives.

Risks of clinical trial protocol amendments according to duration of the trial

Background. No clinical trial could be initiated and conducted without appropriate clinical trial protocol. Any change in information relating to patients’ safety and health during the trial must be recorded and approved by a form of amendment to the clinical trial protocol, which is a time-consuming and financially expensive process for the Sponsors of these studies.Goal. To analyze the probability of releasing of clinical trials protocols amendments and to determine the most "pregnable" period for their occurrence in the course of the trials.Materials and Methods. The results of clinical trial protocols analysis are presented, which were approved by Russian Health Authorities between three years from 2017 to 2019 inclusive. In total, 20 protocols and 39 amendments were analyzed. Results. In the first year of the study, 21 amendments were issued, representing slightly more than half (54%) of the total number of amendments. During the second year, 12 amendments were issued, (31%). For the third year of the trial, only 3 amendments (7%) were made and for the fourth — 4, which is 8% of the total.Conclusion. The largest number of protocol amendments came out at first two years of clinical trial. Thus, they are the most "dangerous" years in the life of a clinical study in connection with the examination of developed protocol in real life. These first two years show how carefully the protocol was designed, how it meets the requirements of regulatory authorities, criteria and recommendations of professional associations, how feasible and effective the various criteria and procedures are.

Pediatric multiple sclerosis: The 2022 ECTRIMS lecture

The 2022 ECTRIMS lecture focused on pediatric-onset multiple sclerosis (POMS), in recognition of the pivotal importance of prompt recognition and treatment of children and youth diagnosed with multiple sclerosis (MS), enabled over the past decade by the formal inclusion of pediatric patients in the McDonald diagnostic criteria. Epidemiologic, genetic and immunologic research has supported the concept that MS is a single disease across the age span and that clues to the inciting and early facets of MS pathobiology might be uniquely discerned through study of the youngest MS patients. Pediatric trials of pharmaceutical agents approved in adult-onset MS are emerging, although innovative study designs, alignment of regulatory agency requirements for trial design, family-centric models for study visits and emphasis on long-term safety and tolerability are essential. Evidence of safety and efficacy of key therapies is key if POMS patients are to be availed of the full armamentarium of MS therapeutic options. Finally, the rarity of POMS necessitates an international community effort to advance care and research. Such collaborations have been facilitated through the International Pediatric Multiple Sclerosis Group, Multiple Sclerosis International Federation, and by national multiple sclerosis societies. International efforts and priorities for the next decade will be highlighted.

Unveiling the Insecurity of Operational Cellular Emergency Services (911): Vulnerabilities, Attacks, and Countermeasures

The cellular network offers a ubiquitous emergency call service with its pervasive coverage. In the United States, it can be consumed by dialing 911 for cellular users, and the emergency call is forwarded to the public safety answer point (PSAP), which handles emergency service requests. According to regulatory authority requirements [1,2,3] for cellular emergency services, anonymous user equipment (UE) is allowed to access them without a SIM (Subscriber Identity Module) card, a valid mobile subscription, or a roaming agreement with the visited cellular network. Such support of the cellular emergency services requires different operations from conventional cellular services, thereby increasing the attack surface of the cellular infrastructure.

Countering antibiotic resistance: a new course of action is needed.

Antibiotic resistance does not seem to be stopping despite international policies that have been aiming to combat this phenomenon for more than 10 years. The World health organization (Who) seeing the relentless growth of the issue has reiterated its recommendations that have been implemented at the national level. In fact, in Italy the new National plan against antibiotic-resistance 2022-2025 (Pncar 2022-2025) is in full operation. At Asl Napoli 3 Sud, which boasts a population of more than 1 million people, an analysis was carried out regarding antibiotic consumption in the first six months of 2022. The results showed consumption deviating from the regional and national average, thus suggesting that swift actions are needed to curb overprescription by physicians as much as possible. This work also aims to raise awareness among physicians and health care professionals of compliance with the requirements of regulatory agencies and scientific societies, so that a virtuous path toward a decisive change of pace can be taken.

The “V” model for decision analysis of additive manufacturing implementation

PurposeThis study aims to broaden the understanding of the additive manufacturing (AM) body of knowledge, presenting a model better suited to the current level of technological development that supports the decision to implement AM in industries, based on the experience of companies in the industry of orthopedic medical implants.Design/methodology/approachBased on the design-science research, the model for the decision to adopt the AM was designed and submitted to experts from the industry of orthopedic implants in Brazil for refinement. For the empirical test of the final model, interviews were used in a company that was considering implementing AM and in another that was not, to evaluate the model.FindingsThe model considers seven dimensions for decision analysis of AM implementation: legal constraints, financial, technological, operational, organizational, supply chain and external factors, being subdivided into 42 criteria that play a relevant role in the implementation decision. The analysis factor of each dimension and criteria are also presented.Originality/valueThe model seeks to be as complete as possible and can be used by various industrial productive sectors, incorporating the analysis of the requirements of health regulatory agencies, suitable for the analysis of the decision to implement AM for the manufacturing of medical implants, not found in other models.

The Moderating Effect of Top Management Team’s Power on the Relationship between CPA Independence & Audit Quality

This research integrates the top management teams (TMT)power theory, CPA economic independence theory, and reputation maintenance theory to explore the impact on audit quality. This study used the sample of firms listed on the Taiwan Stock Exchange (TSE) and Taipei Exchange (TPEx) from 2009 to 2016. The empirical results show that as the TMT power of Taiwan companies increases, the audit quality is higher. It is different from the general research that the TMT will conduct earning management based on self-interested behavior. The inference is due to Taiwan's relatively high proportion of family companies. In the face of the trend of social responsibility and the requirements of regulatory agencies, the company’s strategy of maintaining corporate image and successfully operating over to the next generation is presented with high audit quality. In addition, when CPAs face important clients, the CPA’s economy depends on important customers is greater than the effect of reputation maintenance, the audit quality will be reduced. When the TMT power is greater, it will offset the CPA's economic independence effect and enhance the audit quality.

A ddPCR primer: advantages, challenges, and key considerations when adopting Droplet Digital PCR for viral vector manufacture

<div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/Drouin_headshot.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name" style="color: rgb(93, 83, 138);">Lauren M Drouin</h3><h5 class="author-title" style="color: rgb(93, 83, 138);">Associate Director of Analytical Development, LogicBio TherapeuticsAssociate Director of Analytical Development, LogicBio Therapeutics</h5> Lauren M Drouin leads the Analytical Development group at LogicBio Therapeutics, where she supports the development and implementation of analytical methodologies needed to progress LB-001 and other pipeline products from preclinical development into the clinic and beyond. Current research interests include novel AAV capsid characterization and developing a robust understanding of the factors that influence potency of gene therapy products. Previously, Lauren worked at Voyager Therapeutics where she was responsible for analytical method development and overseeing CMC analytics operations for the Parkinson’s Disease clinical program. Lauren received her PhD in Biochemistry and Molecular Biology from the University of Florida where she utilized molecular, biophysical, and structural techniques to characterize the AAV capsid for improved gene delivery. </div></div></div><div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/F Dorange photo copy.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name" style="color: rgb(0, 167, 149);">Fabien Dorange</h3><h5 class="author-title" style="color: rgb(0, 167, 149);">Head of Analytical CMC, Genethon</h5> Fabien Dorange holds a PhD in virology and worked as a postdoctoral researcher in the gene therapy field. Before joining Genethon, Fabien was Head of R&amp;D viral safety in a CRO company (Texcell, France). He joined Genethon in 2016 and currently heads of the CMC Analytical Department. He is responsible for the analytical activities in the characterization and release testing of gene therapy products. </div></div></div><div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/Bsilvey_headshot_2021 copy.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name" style="color: rgb(0, 117, 137);">Bryan Silvey</h3><h5 class="author-title" style="color: rgb(0, 117, 137);">Head of Quality, A2 Biotherapeutics</h5> Bryan Silvey has been in the biopharmaceutical industry for over 25 years in both Quality technical roles and Regulatory Affairs CMC leadership positions having responsibilities for both product and facilities lifecycle management. Global experience in regulatory authority requirements and expectations in the CMC space with biologics has proved a grounding platform of quality principles that he has applied to successful development and commercialization of two (2) CAR T-Cell therapies while at Kite (a Gilead Company). As Head of Quality for A2 Biotherapeutics, an early stage cell therapy discovery and development company, this journey in CMC science continues to push forward in an effort to address unmet cancer patient needs. </div></div></div><div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/Mark Head Shot 2020 copy.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name" style="color: rgb(85, 85, 89);">Mark White</h3><h5 class="author-title" style="color: rgb(85, 85, 89);">Associate Director of Biopharma Product Marketing, Bio-Rad</h5> Mark White is the Associate Director of Biopharma Product Marketing at Bio-Rad. He has played a key role in the development of multiple core technology capabilities and assays alongside a multidisciplinary team of biologists and engineers at Bio-Rad and previously at Berkeley Lights Inc. Mark obtained his PhD in Biomedical Sciences at the University of California, San Francisco. </div></div></div><div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/Pincus copy.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name" style="color: rgb(0, 59, 76);">Steven Pincus</h3><h5 class="author-title" style="color: rgb(0, 59, 76);">Executive Director Analytical Development, Neurogene</h5> Steven Pincus has a PhD in Biochemistry with training in molecular Virology and Immunology. Steven has over 30 years in the biotech industry leading teams in research and development of vaccines, AAV Gene Therapies and monoclonal antibodies in the areas of infectious disease, autoimmune disease and cancer. He has taken projects from discovery through Phase 2 clinical trials. He has developed qualified and validated release assays and assays for measuring clinical and immunological responses. He has led the transfer of assays to partners, developed and managed collaborations with academic and industrial partners, managed CRO’s and developed and managed project budgets and goals. During his career Steven has gained experience in Quality control, analytical development, regulatory affairs and manufacturing development for vaccines and Gene Therapies. He is currently Executive Director Analytical Development at Neurogene. </div></div></div>

Strategies to support the growth and evolution of nursing and midwifery education in Tasmania

There is a prediction of significant nursing workforce shortfalls across Australia. Tasmania, as an island state of Australia, is more sensitive to such a shortage due to the existing challenges associated with pre-service and postgraduate nurse education, training, recruitment and retention. This paper describes strategies adopted by the School of Nursing (SoN), University of Tasmania to ensure the preparation and sustainability of the registered nurse workforce that is pivotal for state-wide healthcare. Due to lower levels of educational attainment amongst Tasmanian school leavers, the SoN has developed alternative pathway programs that offer entry for students who do not meet standardised entry. Staged progression to pedagogically sound online teaching platforms, pre-requisite limitations and uncoupling subject contents are strategies that have been incorporated in new undergraduate curriculum. The SoN’s postgraduate program includes a suite of 24 specialisations including a post-registration midwifery specialisation and students have the flexible option to exit the program at a graduate certificate, graduate diploma or finish at a master’s level. Partnerships with local industry, nursing associations, healthcare consumers, other health disciplines and students ensure that the SoN is responsive to sector needs and regulatory authority requirements to graduate qualified registered nurses serving in highly-demanding healthcare environments.

Valuating the position of the control object based on a universal complex indicator using structured and unstructured data

Valuating the position of a controlled object using indicators which are management and control tools is widely used in many areas of the economy. Usually such indicators are based on internal data, however, as the volume of available open information grows, algorithms for valuation of the position of certain control objects and on open structured data are appearing. The disadvantage of these models is their narrow specialization and binding only to structured, and sometimes strictly official data, which, as a rule, have a rare publication frequency. This does not allow you to track the change in the position of the object at different times. The authors have proposed a concept for constructing a universal complex indicator (UCI) for express valuation of the position of a controlled object in various types of activity: banking, educational, industrial, etc. Another difference in the construction of the UCI is that the concept presented in the article assumes, as a reference point, to take into account the requirements of regulatory authorities, while in most Russian and foreign studies, indicators are built for the needs of investors. It is also proposed to use, along with structured and unstructured data, tracking the dynamics of changes in the position of the control object. To determine the UCI values on the basis of various econometric models and methods, the components that characterize the requirements of the control bodies to the control object are calculated; using them the UCI value is determined from the truth table. The concept proposed was tested to build an express valuation of the financial position of 108 banks for the period from 1 January 2018 to 1 February 2020. In accordance with the requirements of the Central Bank of the Russian Federation, the values of the three UCI components were obtained, and the value was calculated for each bank. The predictive ability of the constructed model, tested on three banks of the test sample, was confirmed by the consistency of the express valuation with their actual position in March 2020.

Development of a rabbit monocyte activation test as an alternative to the rabbit pyrogen test and its application in the analysis of plasma-derived products

The rabbit pyrogen test (RPT) is a safety test conducted as a part of mandatory requirements of regulatory agencies. RPT is currently performed for routine quality control (QC) by manufacturers and for national lot release of biological products, such as plasma-derived products. However, RPT involves the use of many rabbits, counter to the international efforts to minimize the use of animals in research. Furthermore, pyrogen amount cannot be discerned from the test results and the results may be considerably affected by various factors. Therefore, a need exists for substituting RPT with in vitro assays. As a viable alternative to RPT, we here established a rabbit monocyte activation test (RMAT) based on the human MAT in the European Pharmacopoeia. RMAT uses rabbit peripheral blood mononuclear cells as the source of monocytes instead of live animals. The test detected endotoxin, lipoteichoic acid, peptidoglycan, and zymosan with high sensitivity, showing high correlation with the in vivo RPT results. The results of RMAT and RPT testing of non-pyrogenic plasma-derived products were also consistent. Furthermore, RMAT showed satisfactory recovery rates in an interference test with product samples and spiked-in pyrogens. We conclude that RMAT could replace the existing RPT for routine QC.

The facioscapulohumeral muscular dystrophy Rasch-built overall disability scale (FSHD-RODS).

Background and objectivesFacioscapulohumeral muscular dystrophy (FHSD) is a debilitating inherited muscle disease for which various therapeutic strategies are being investigated. Thus far, little attention has been given in FSHD to the development of scientifically sound outcome measures fulfilling regulatory authority requirements. The aim of this study was to design a patient‐reported Rasch‐built interval scale on activity and participation for FSHD.MethodsA pre‐phase FSHD‐Rasch‐built overall disability scale (pre‐FSHD‐RODS; consisting of 159 activity/participation items), based on the World Health Organization international classification of disease‐related functional consequences was completed by 762 FSHD patients (Netherlands: n = 171; UK: n = 287; United States: n = 221; France: n = 52; Australia: n = 32). A proportion of the patient cohort completed it twice (n = 230; interval 2–4 weeks; reliability studies). The pre‐FSHD‐RODS was subjected to Rasch analyses to create a model fulfilling its requirements. Validity studies were performed through correlation with the motor function measure.ResultsThe pre‐FSHD‐RODS did not meet the Rasch model expectations. Based on determinants such as misfit statistics and misfit residuals, differential item functioning, and local dependency, we systematically removed items until a final 38‐inquiry (originating from 32 items; six items split) FSHD‐RODS was constructed achieving Rasch model expectations. Adequate test‐retest reliability and (cross‐cultural and external) validity scores were obtained.ConclusionsThe FSHD‐RODS is a disease‐specific interval measure suitable for detecting activity and participation restrictions in patients with FSHD with good item/person reliability and validity scores. The use of this scale is recommended in the near future, to determine the functional deterioration slope in FSHD per year as a preparation for the upcoming clinical intervention trials in FSHD.

BIOANALYSIS METHOD DEVELOPMENT AND VALIDATION OF SMALL MOLECULES IN PHARMACEUTICAL INDUSTRY: A BIOANALYST REVIEW POINT

The focus of bioanalysis employed for the quantitative determination of an active analyte(s) and their metabolite(s) in the biological matrix such as plasma, serum, blood, cerebrospinal fluid, and tissues. The extraction of analyte and metabolite in the biological fluids is carried out using different separation methods such as protein precipitation, liquid-liquid extraction, and solid phase extraction. Bioanalytical method development and validation in the pharmaceutical industry are to provide an assessment and interpretation of pharmacokinetics, pharmacodynamics, toxicokinetics, bioavailability/bioequivalence, and therapeutic drug monitoring relationships. This review paper aims to provide a simple and accurate scientific background to improve the quality for development and validation of a bioanalytical method for small molecules with industrial technique as per regulatory agency requirements (United States Food and Drug Administration, EMEA, International Council for Harmonisation and ANVISA).