Regulatory Expectations Research Articles

Study of polymer component migrated in medicinal product from transportation packaging component: A systematic assessment beyond regulatory expectations

Light Density Polyethylene (LDPE) bottles with a specific resin were chosen as container closure system (CCS) to fill “Latanoprost ophthalmic solution” (a generic drug product). As an alternative packaging component, additional manufacturer of LDPE bottles with the same characteristics as the previously selected LDPE bottles was chosen. The appropriateness of both packaging components was evaluated using an extractables and leachable (E&L) study and a formal stability programme that monitored quality of latanoprost ophthalmic solution. The results of relevant quality attributes in stability samples of latanoprost ophthalmic solution packed in both LDPE bottles were compared. It noticed that an unknown impurity in latanoprost ophthalmic solution packaged in LDPE bottles manufactured by an additional manufacturer. Further study revealed that this unknown impurity is Epsilon-caprolactam, a leachable of plastic used in the transportation of LDPE bottles. The leachability was validated through an extraction analysis of a plastic bag used for transportation. Thus, in certain cases, when the source of leachable is not identifiable by an E&L examination of primary, secondary, and tertiary packaging components, the assessment could be extended to include packaging components utilized throughout the supply chain.

Strategic decision-making for sustainable production and distribution in automotive industry: a machine learning enabled dynamic multi-objective optimisation

ABSTRACT Over the last decade, numerous researchers have disclosed that major automotive companies do not conform to regulatory or societal expectations regarding their environmental and social performances. This paper explores the dynamic capabilities of production distribution within the sustainability practices of automotive industries. It offers insights to better grasp and articulate the environmental, economic, and social dimensions of sustainable supply chains. The research framework encloses all supply chain phases, from raw material sourcing to retailing finished products. Three conflicting objective functions are identified: social advantages maximisation, cost minimisation, and emission minimisation. Specifically, the study tackles a dynamic multi-objective optimisation model where each automobile type faces a series of dynamic demands. The dynamic nature of the problem poses significant challenges to conventional evolutionary algorithms for detecting the optimal solutions over time. Therefore, we introduce an interconnected prediction-based dynamic non-dominated sorting algorithm (ICP-DNSGA-II). Finally, extensive computational experiments are conducted to assess the effectiveness of this holistic approach. The findings offer valuable insights for automotive industry stakeholders and policymakers, illustrating its potential to enhance operational efficiency and sustainability performance across the supply chain. Most importantly, this paper proposes an automated decision-making approach to generate optimal solutions with dynamic changes in market demands.

Case Studies on Changes and Proposed Process Development Approaches reflecting applicability of PDA Technical Report No. 89 Strategies for Vaccine Development and Lifecycle Management.

Vaccines are complex and a very diverse group of products with relatively long product lifecycles. The manufacturing programs for these vaccines need to be continually updated to comply with evolving regulatory expectations. Members of the Parenteral Drug Association (PDA) Vaccines Interest Group (VIG) authored and published PDA Technical Report No. 89 Strategies for Vaccine Development and Lifecycle Management (TR 89) which seeks to provide context to vaccine developers and manufacturers regarding key aspects of new or legacy vaccines such as control strategy from process development to vaccine lifecycle management, comparability and lifecycle management including technical, validation, quality and regulatory perspectives. To further explain and illustrate the concepts and topics discussed, seven relevant situations were selected as either case studies associated with changes implemented or proposed process development strategies, which are discussed in this article. The situations described are: working cell bank, modification or update of externally supplied product contact components for vaccine manufacturing, raw material change, new product at an existing site, vaccine development acceleration by leveraging existing platforms, selection and implementation of potency method, and modeling for stability forecast prediction. For each situation, the applicable key concepts from TR#89 are discussed as follows: Control Strategy, Prior Knowledge, Relying on PQS, Classification of Parameters, Validation Approach, Use of a Risk-based Approach, Comparability, Use of ICHQ12 and Additional Regulatory Considerations.

Direct observations of practice in social work education: the role of professional autonomy in policy enactment

ABSTRACT Although the assessment of students via direct observation of practice is a regulatory requirement of social work qualifying programmes in England, there is relative freedom in exactly how this policy is enacted. This study takes a constructionist approach to explore what direct observations are perceived to be and whether this influences their enactment. Interview data was collected from five participants who are all practitioners involved with this assessment method. Training materials were also analyzed and themed along with interview data. Interpretation of the data revealed three themes; participants had a clear concept of direct observations, valued them as an assessment method and they are embedded in social work education. Analysis of the findings revealed that the lack of regulatory expectations supports professional autonomy by enabling the translation of the direct observation policy into practice in a way which supports ownership, commitment and creativity. These findings demonstrate that it can be more beneficial to allow professional expertise to guide policy enactment in educational contexts than the top-down managerial approaches that dominate both educational and practice settings.

Enhancing Pharmaceutical Product Quality With a Comprehensive Corrective and Preventive Actions (CAPA) Framework: From Reactive to Proactive.

Corrective and preventive actions (CAPA) are crucial components of quality assurance (QA) within the pharmaceutical industry, essential for maintaining product quality, safety, and regulatory compliance. The review explores the multifaceted role of CAPA in pharmaceutical manufacturing, emphasizing its structured approach to detecting, addressing, and preventing quality issues. CAPA systems are integral to the broader quality management system (QMS), functioning as a dual-loop mechanism that is reactive and proactive approach aligned with continuous improvement principles outlined by the International Organization for Standardization (ISO) 9001:2000. It details the three distinct phases of CAPA: correction or remedial action, corrective action (CA), and preventive action (PA). It highlights the importance of root cause analysis and the necessity for immediate corrections and long-term preventive measures to avoid recurring issues. Regulatory expectations, such as those from the Food and Drug Administration (FDA) under the Code of Federal Regulations (CFR) title 21 part 820 and theInternational Council for Harmonisationof Technical Requirements for Pharmaceuticals for Human Use (ICH) Q10, are discussed, underscoring the need for a comprehensive CAPA plan that integrates data analysis and ongoing process enhancements. Additionally, the paper introduces the 8D methodology as a structured problem-solving approach to complement CAPA efforts. By providing an in-depth examination of CAPA procedures and their implementation, this article aims to contribute to the understanding and effectiveness of quality systems in pharmaceutical manufacturing.

Expanding the use of Moist Heat for Terminal Sterilization.

This publication reviews the background that shaped the execution of moist heat for terminal sterilization across the global healthcare industry. Despite the clear benefits to patient safety afforded by terminal treatments, narrow regulatory expectations and misinterpretation of scientific principles progress towards broader implementation has been minimal. This paper outlines a means to expanded implementation addressing the need for balancing processing delivering sufficient lethality to reliably destroy the pre-sterilization bioburden while preserving the essential quality attributes of the product. This is accomplished by delivering the correct sterilization process with adjustments to the time-temperature conditions.

Deterrents for corporate carbon disclosures: a study on Indian corporations using Grey-DEMATEL approach

PurposeGlobally, the landscape of corporate carbon disclosures (CCD) is continually evolving as societal, environmental and regulatory expectations change over time. The goal of this study is to examine the challenges faced by Indian firms’ corporate carbon reporting (CCR). The literature recognized the hurdles to reaching net zero emissions and decarbonization, which are equally applicable to carbon disclosure (CD).Design/methodology/approachThe scope 3 emission disclosure barriers (S3EDBs) identified from the literature were ranked, and their relationships were discovered using the “Grey-based decision-making trial and evaluation laboratory” (Grey- DEMATEL) technique.FindingsThe key findings are the S3EDBs, the most prominent barriers, their interrelationships and important insights for managers of organizations in prioritizing the action area for scope 3 CD. Eight S3EDBs were categorized in terms of cause and effect, threshold value is calculated as 0.78. “Quality, and reliability of data,” “Government policies and statutory requirement on emission disclosure” and “Traceability and managing supply chain partners” are the most prominent S3EDBs.Practical implicationsThe results will help industry people in countries with emerging economies that have significant scope 3 carbon footprints. The managers can plan to deal with top S3EDBs as a step towards decarbonization and ultimately fighting climate change (CC).Originality/valueThis study is one of the first to rank these barriers to CD so that industry practitioners can prioritize their actions. The core contribution of this research is to detect the most significant S3EDBs and their interdependencies.

Identifying resilience: a system safety review of trauma and orthopaedic theatres

A prospective, qualitative study, of trauma and orthopaedic theatres was undertaken using the CARe QI handbook and the SEIPS framework, with the aim of preventing future Never Events. The study demonstrated a new approach, focussed on understanding ‘work as done’ to identify opportunities to improve system resilience, tested, using the Model for Improvement. Undertaken during the Covid-19 pandemic, it demonstrates that such conditions should not be a deterrent to observational studies, but requiring greater time and resource than a standard investigation, the approach may not align with current organisational or regulatory expectations. At the conclusion of this study, the mean time between Never Events in theatres had increased from 46 to 224 days, an achievement that had not previously been possible using the regulatory required, safety I, investigatory approach. These findings should be used to inform future PSIRF and Never Event Frameworks, to ensure effective systems-based analysis and improvement.

Improving Access to Patient-Focused, Decentralized Clinical Trials Requires Streamlined Regulatory Requirements: An ASCO Research Statement.

Strategies to bring clinical trials closer to patients gained momentum during the COVID-19 pandemic, enabling more participants to receive treatment and/or testing in their local communities. Incorporation of decentralized trial elements presents both opportunities and challenges, spanning regulatory, technical, and operational aspects. This ASCO research statement includes timely consensus-driven recommendations and a call for engagement of all research stakeholders. ASCO held multistakeholder meetings with leaders in oncology research and concluded that research-related regulatory and administrative requirements and burdens present critical barriers to decentralizing trials. One example is sponsor and contract research organization (CRO) use of US Food and Drug Administration (FDA)'s Statement of Investigator (Form 1572), which was found to exceed FDA's stated intent and used in conservative ways disproportionate to potential risks to participants and scientific integrity. As a result, research sites experience an avalanche of downstream administrative and regulatory activities that consume considerable resources. This statement recommends four key solutions to address such barriers and recalibrate regulatory and administrative expectations for decentralizing trials: (1) FDA should engage the research community in a public-private partnership to modernize standards and enable local access to trials; (2) sponsors and CROs should develop standards and protocols that accommodate flexible approaches, enable local participation, provide clarity around roles and requirements, and promote consistency; (3) research centers, networks, and sites should update policies and procedures to implement decentralized trial elements; and (4) research community should develop a streamlined, uniform mechanism to simplify regulatory data collection and documentation and use it consistently across trials. We can and must prioritize a concerted commitment to simplify and streamline regulatory requirements and practices to broaden access to and participation in cancer clinical trials.

Global perspectives for cellular and gene therapy development and regulatory expectations: a conference report from the 2023 NIFDS-PMDA-USP Workshop for Advanced Therapies

Global perspectives for cellular and gene therapy development and regulatory expectations: a conference report from the 2023 NIFDS-PMDA-USP Workshop for Advanced Therapies

Overdosage Section in US and EU Labeling

The Prescribing Information (PI) in the United States (US) and the Summary of Product Characteristics (SmPC) in the European Union (EU) are approved by the US Food & Drug Administration (FDA), and the European Medicines Agency (EMA), respectively. The inclusion of overdosage information in these documents is a regulatory requirement in both regions. This research evaluates the content of the overdosage section of US and EU labeling. The overdosage sections of labels for drugs approved in the US in three time periods were analyzed: 2000–2001, 2010–2011, and 2020–2021. EU labels for these same products were also reviewed if registered through the Centralized Procedure. Data collection and analyses were performed using a predefined questionnaire, focusing on adherence to regulatory requirements and identifying areas where additional regulatory guidance may be beneficial. The findings indicate that the content of the overdosage sections largely comply with the regulatory requirements of their respective regions. Fewer than half of the labels included information on supratherapeutic doses observed from clinical studies, risk factors for overdose or population specific data associated with overdose. Inconsistencies were noted concerning the incorporation of animal data when human data were available, in addition to the referencing of Poison Centers. The overall utility of non-specific treatment recommendations, in addition to gastric lavage is discussed. While the content of the overdosage section generally aligns with regulatory expectations, additional regulatory guidance could enhance consistency in how this section of labeling is presented and clarify expectations to improve its usefulness for health care professionals (HCPs).

Making it work in practice: how heads of quality negotiate the third space

Recent decades have seen increasingly complex external regulation applied to higher education providers. This has accentuated the role of heads of quality, who require considerable specialist knowledge and insight to ensure that organisational practices align with regulatory expectations. However, while the existing literature recognises that heads of quality do not perform a uniform role, it does not typically discuss the key organisational features which explain the differences in the role or necessarily position of heads of quality as third space professionals. Drawing on a comparative case study of three universities, the article extends our understanding by confirming that heads of quality can legitimately be termed third space professionals and by showing that heads of quality must navigate their environment in different ways according to the degree of access to the third space offered by their organisation. A more structurally situated explanation of third space activity is thus required. The article also reflects on the tendency to discuss a particular group of third space professionals and to characterise their experience as though it were broadly common. It argues for a more nuanced explanation, taking account of organisational structure as a further variable which may help to explain the experience of the third space professional.

Standalone Regulatory Agreements for Product-Development Collaborations in the Medical Products Industry

BackgroundMedical-product companies often outsource research and manufacturing needs to contracting or partnering organizations but then must manage a challenging patchwork of regulatory activities. A standalone regulatory agreement could clarify the relationships and responsibilities between companies working jointly on a single regulated product. This study explored the need for and current use of standalone regulatory agreements.MethodsA survey instrument was developed using an implementation framework and disseminated to mid- to senior-level employees and consultants for sponsor and vendor companies in the medical products sector.ResultsOf 294 respondents, about half, primarily from companies with more than 200 employees, were familiar with standalone regulatory agreements, and half of this subgroup had moved forward to implement them. Such agreements were considered beneficial to clarify regulatory roles and responsibilities, standardize regulatory expectations between the companies, and stimulate earlier discussion about joint regulatory strategies. However, the development of regulatory agreements appears challenged by the fact that such agreements are not required by regulatory agencies overseeing medical products and have no standardized templates, agency or industry guidance. Respondents whose organizations do not now use regulatory agreements either had not considered or did not see a need for a standalone agreement.ConclusionsStandalone regulatory agreements are becoming more common but are not yet implemented fully by most companies. Their usefulness and content appeared to depend upon the type of partner, the complexity of the relationship and the availability of internal expertise and support.

International enforcement of cryptocurrency laws: Jurisdictional challenges and collaborative solutions

The rise of cryptocurrencies has presented new challenges for regulators around the world, particularly in terms of enforcement across international borders. This abstract explores the jurisdictional challenges faced by authorities in enforcing cryptocurrency laws and proposes collaborative solutions to address these challenges. Cryptocurrencies operate on a decentralized network, making them difficult to regulate within traditional legal frameworks. Jurisdictional issues arise when a cryptocurrency transaction involves parties in different countries, as it is often unclear which jurisdiction's laws apply. This ambiguity can lead to regulatory gaps and enforcement challenges, allowing illicit activities such as money laundering and terrorism financing to flourish. To address these challenges, collaborative solutions are needed. International cooperation between regulators, law enforcement agencies, and industry stakeholders is essential to ensure effective enforcement of cryptocurrency laws. This cooperation can take various forms, including information sharing, joint investigations, and the development of common regulatory standards. One example of successful collaboration is the Financial Action Task Force (FATF), an intergovernmental organization that sets standards for combating money laundering and terrorism financing. The FATF's guidance on virtual assets and virtual asset service providers has helped to clarify regulatory expectations and promote consistency in enforcement efforts across jurisdictions. Another example is the Joint Chiefs of Global Tax Enforcement (J5), a coalition of tax authorities from five countries that work together to combat international tax evasion. The J5's focus on cryptocurrency-related tax crimes highlights the importance of cross-border cooperation in tackling cryptocurrency-related illicit activities. In conclusion, while jurisdictional challenges remain a significant hurdle in the enforcement of cryptocurrency laws, collaborative solutions offer a path forward. By working together, regulators, law enforcement agencies, and industry stakeholders can address these challenges and ensure that the benefits of cryptocurrencies are realized while mitigating their risks.

Purification of monoclonal antibodies using novel 3D printed ordered stationary phases

3D printing offers the unprecedented ability to fabricate chromatography stationary phases with bespoke 3D morphology as opposed to traditional packed beds of spherical beads. The restricted range of printable materials compatible with chromatography is considered a setback for its industrial implementation. Recently, we proposed a novel ink that exhibits favourable printing performance (printing time ∼100 mL/h, resolution ∼200 µm) and broadens the possibilities for a range of chromatography applications thanks to its customisable surface chemistry. In this work, this ink was used to fabricate 3D printed ordered columns with 300 µm channels for the capture and polishing of therapeutic monoclonal antibodies. The columns were initially assessed for leachables and extractables, revealing no material propensity for leaching. Columns were then functionalised with protein A and SO3 ligands to obtain affinity and strong cation exchangers, respectively. 3D printed protein A columns showed >85 % IgG recovery from harvested cell culture fluid with purities above 98 %. Column reusability was evaluated over 20 cycles showing unaffected performance. Eluate samples were analysed for co-eluted protein A fragments, host cell protein and aggregates. Results demonstrate excellent HCP clearance (logarithmic reduction value of > 2.5) and protein A leakage in the range of commercial affinity resins (<100 ng/mg). SO3 functionalised columns employed for polishing achieved removal of leaked Protein A (down to 10 ng/mg) to meet regulatory expectations of product purity. This work is the first implementation of 3D printed columns for mAb purification and provides strong evidence for their potential in industrial bioseparations.

The Covid-19 Pandemic and The Future of Work.

The "future of work" refers to workplace modifications projected to occur following large scale events impacting workforce health and safety such as pandemics, technological advancements, or economic shifts. This paper examines the influence of the COVID-19 pandemic on the future of work. The electronic databases PubMed, Google Scholar, and Scopus were explored using search terms such as "post-pandemic," "working force," and "future of work" to retrieve papers published between 2000 and 2023. The main characteristics of the future of work modification revealed are blurring of work-home boundaries, increase in telework and the gig economy, demand for artificial intelligence, smart working, quiet hiring, diversity and inclusion, and algocratic governance. Needed skills include virtual collaboration capability, cross-cultural competency, computational thinking, news media literacy, transdisciplinarity, sense making, and focusing on mental health and well-being. Organizations are remodeling workforces to meet employee, employer, regulatory, and market expectations to adapt to future workplace needs.

From Compliance to Commitment: The Evolving Landscape of Sustainable Supply Chains considering BRSR and other Regulatory Frameworks

The global business landscape has witnessed a paradigm shift towards sustainability in recent years, with an increasing focus on responsible business practices. Maximum environmental impact is created at the value chain rather than the final producers. One crucial aspect of this shift is the adoption of sustainable supply chain management by companies worldwide. This abstract explores the role of companies in adapting to regulations such as the business responsibility and sustainability reporting (BRSR) frameworkand other similar initiatives aimed at enhancing environmental, social, and governance (ESG) performance. Sustainable supply chains play a pivotal role in mitigating traditional business operations’ environmental and social impacts. The BRSR framework and other regulatory mechanisms provide a structured approach for companies to disclose their sustainability efforts and demonstrate transparency in their supply chain activities. This study delves into the critical components of these regulations and how companies arenavigating the complexities of compliance. Companies increasingly recognize that integrating sustainability into their supply chains aligns with regulatory expectations and enhances long-term business resilience. This study will examine the role of sustainable supply chains in their procurement, production, and distribution processes to mitigate risks associated with climate change, resource scarcity, and social inequality. The study also explores companies’ challenges in implementing sustainable practices and innovative strategies to overcome these hurdles. In conclusion, this study emphasizes the evolving landscape of sustainable supply chains and the proactive measures companies take to adapt to regulatory frameworks like BRSR. By embracing sustainability as a core business value, companies comply with regulations, foster innovation, improve stakeholder relationships, and contribute to a more resilient and responsible global business ecosystem.

Patient-Centric Approaches to Gastroretentive Floating Tablets: Tailoring for Diverse Clinical Needs

Gastroretentive tablets have emerged as a promising platform for controlled drug delivery, offering the potential for prolonged gastric residence time and enhanced therapeutic outcomes. This comprehensive review explores the paradigm shift towards patient-centric approaches in the development of gastroretentive tablets. The journey begins with an examination of the historical evolution of gastroretentive technologies, tracing advancements in formulation techniques, materials, and technologies that have paved the way for patient-centric designs. The review delves into patient-centric formulation strategies tailored for diverse populations, including pediatrics and geriatrics. It highlights the importance of considering patient-specific needs, preferences, and physiological characteristics in optimizing dosage forms. Regulatory considerations and compliance-enhancing features are scrutinized, providing insights into the delicate balance between personalized medicine and regulatory expectations. Real-world applications are illuminated through case studies, offering success stories across pediatric, geriatric, and personalized medicine contexts. Clinical outcomes, including adherence metrics and patient satisfaction, provide tangible evidence of the impact of patient-centric gastroretentive tablets. Challenges in formulation development and regulatory implementation are critically examined, with a focus on technical hurdles and strategies for navigating evolving regulatory landscapes. The conclusion distills key findings and outlines implications for future research and clinical practice, emphasizing continued innovation, strategic regulatory engagement, and interdisciplinary collaboration. This review serves as a comprehensive resource for researchers, clinicians, and regulatory professionals engaged in advancing patient-centric gastroretentive tablets. It offers a roadmap for the integration of innovative technologies into clinical practice, fostering a patient-centered approach in the evolution of controlled drug delivery systems.

New approach methodologies (NAMs): identifying and overcoming hurdles to accelerated adoption.

New approach methodologies (NAMs) can deliver improved chemical safety assessment through the provision of more protective and/or relevant models that have a reduced reliance on animals. Despite the widely acknowledged benefits offered by NAMs, there continue to be barriers that prevent or limit their application for decision-making in chemical safety assessment. These include barriers related to real and perceived scientific, technical, legislative and economic issues, as well as cultural and societal obstacles that may relate to inertia, familiarity, and comfort with established methods, and perceptions around regulatory expectations and acceptance. This article focuses on chemical safety science, exposure, hazard, and risk assessment, and explores the nature of these barriers and how they can be overcome to drive the wider exploitation and acceptance of NAMs. Short-, mid- and longer-term goals are outlined that embrace the opportunities provided by NAMs to deliver improved protection of human health and environmental security as part of a new paradigm that incorporates exposure science and a culture that promotes the use of protective toxicological risk assessments.

Early technology review: towards an expedited pathway.

Evidence development for medical devices is often focused on satisfying regulatory requirements with the result that health professional and payer expectations may not be met, despite considerable investment in clinical trials. Early engagement with payers and health professionals could allow companies to understand these expectations and reflect them in clinical study design, increasing chances of positive coverage determination and adoption into clinical practice. An example of early engagement through the EXCITE International model using an early technology review (ETR) is described which includes engagement with payers and health professionals to better inform companies to develop data that meet their expectations. ETR is based on an early evidence review, a framework of expectations that guides the process and identified gaps in evidence. The first fourteen ETRs were reviewed for examples of advice to companies that provided additional information from payers and health professionals that was thought likely to impact on downstream outcomes or strategic direction. Given that limitations were imposed by confidentiality, examples were genericized. Advice through early engagement can inform evidence development that coincides with expectations of payers and health professionals through a structured, objective, evidence-based approach. This could reduce the risk of business-related adverse outcomes such as failure to secure a positive coverage determination and/or acceptance by expert health professionals. Early engagement with key stakeholders exemplified by the ETR approach offers an alternative to the current approach of focusing on regulatory expectations. This could reduce the time to reimbursement and clinical adoption and benefit patient outcomes and/or health system efficiencies.