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The concept of extractables and leachable has introduced a new era for identifying potential impurities in drug products. Pharmaceutical packaging materials encompass a variety of polymers due to their appealing properties for storing the drug product. However, numerous chemical species may leach into the drug product from these polymers, posing significant health hazards in the public domain. Identifying such leachable is crucial for assessing safety and addressing toxicological concerns. Acrylic acids are commonly used materials for adhering needles to the barrel in pre-filled syringes. In this study, we identified acrylic acid leachable impurities in ganirelix drug products available in the market using mass spectrometry as an analytical technique. These impurities leached into the drug product during storage conditions. Characterization of the impurities was carried out through data obtained from HRMS and MS/MS analysis, revealing them as polyacrylic acid-ganirelix adduct impurities. This study offers valuable insights into identifying leachable and susceptible sites, providing a foundation for potential modifications in similar classes of drug products, thereby enhancing their safety and efficacy. [ABSTRACT FROM AUTHOR]

Rationale: Disulfide bridges (DSB) play an important role in stabilizing threedimensional structures of biopharmaceuticals, single purified proteins, and various cyclic peptide drugs that contain disulfide in their structures. Incorrect cross-linking known as DSB scrambling results in misfolded structures that can be inactive, immunogenic, and susceptible to aggregation. Very few articles have been published on the experimental annotation of DSBs in proteins and cyclic peptide drugs. Accurate characterization of the disulfide bond is essential for understanding protein confirmation. Methods: Characterizing DSBs using mass spectrometry (MS) involves the chemical and enzymatic digestion of samples to obtain smaller peptide fragments, in both reduced and nonreduced forms. Subsequently, these samples are analyzed using MS to locate the DSB, either through interpretation or by employing various software tools. Results: The main challenge in DSB analysis methods using sample preparation is to obtain a sample solution in which nonnative DSBs are not formed due to high pH, temperature, and presence of free sulfhydryl groups. Formation of nonnative DSBs can lead to erroneous annotation of disulfide bond. Sample preparation techniques, fragmentation methods for DSB analysis, and contemporary approaches for DSB mapping using this fragmentation were discussed. Conclusions: This review presents the latest advancement in MS-based characterization; also a critical perspective is presented for further annotation of DSBs using MS, primarily for single purified proteins or peptides that are densely connected and rich in cysteine. Despite significant breakthroughs resulting from advancements in MS, the analysis of disulfide bonds is not straightforward; it necessitates expertise in sample preparation and interpretation. [ABSTRACT FROM AUTHOR]

Rationale: Enasidenib (EDB) is an orally active selective mutant isocitrate dehydrogenase‐2 enzyme inhibitor approved by the U.S. Food and Drug Administration to treat acute myeloid leukemia. It lacks a reported forced degradation study and a stability‐indicating assay method (SIAM). This study addresses this gap by establishing a degradation profile in accordance with the International Council for Harmonisation Q1A and Q1B (R2) guidelines and developing a validated SIAM for EDB. Methods: EDB was exposed to forced degradation under various conditions (hydrolytic, photolytic, oxidative, and thermal stress). Degradation samples were analyzed using high‐performance liquid chromatography on an Agilent ZORBAX Eclipse Plus C18 column with a mobile phase consisting of 0.1% formic acid in Milli‐Q water and acetonitrile at a flow rate of 1 mL/min and detection at 270 nm. Liquid chromatography‐quadrupole time‐of‐flight‐high‐resolution mass spectrometry (LC/Q‐TOF HRMS) was used for the identification and characterization of degradation products. Nitrosamine risk assessment was conducted using a modified nitrosation assay procedure (NAP) test due to the presence of a secondary amine group in the drug, which is liable to forming nitrosamine drug substance–related impurities (NDSRI). Results: The drug exhibited significant degradation under acidic, basic, photolytic, and oxidative conditions in the solution state. A total of nine degradation products (DP) were formed (DP‐I, DP‐III, and DP‐IV: acidic conditions; DP‐I and DP‐III: basic conditions; DP‐II, DP‐V, DP‐VI, and DP‐VII: oxidative stress; and DP‐VII, DP‐VIII, and DP‐IX: photolytic conditions), which were separated and identified using reversed‐phase high‐performance liquid chromatography and characterized using liquid chromatography–tandem mass spectrometry. The mechanism behind the formation of EDB degradation products has been discussed, and this study was the first to develop a degradation pathway for EDB. In addition, the possibilities of NDSRI formation for EDB were studied using a modified NAP test, which can contribute to the risk assessment of the drug. Conclusions: Forced degradation studies were conducted by establishing a SIAM for EDB. All the degradation products were characterized by mass spectral data obtained using LC/Q‐TOF‐HRMS. [ABSTRACT FROM AUTHOR]

Several regulatory organizations encourage the quantitative analysis of potentially genotoxic impurities in finished pharmaceutical preparation. For the first time, a sensitive, accurate, and reliable reversed phase‐high‐performance liquid chromatography method was developed and validated for two antihypertensive drugs, three genotoxic impurities of Amlodipine namely methyl benzene sulfonate, ethyl benzene sulfonate, and ethyl‐p‐toluene sulfonate, as well as N‐methyl O‐phenylenediamine dihydrochloride as genotoxic impurities of Telmisartan that is marketed in a single pill combination. reversed phase‐high‐performance liquid chromatography method was developed using a C18 column Agilent (Zorbax C18; 250 × 4.6 mm internal diameter, 5 μm) along with 50 mM ammonium acetate (pH 4.5) and ACN as a mobile phase in gradient mode to achieve the retention of all analytes. The new method's sensitivity allowed the quantification of namely methyl benzene sulfonate, ethyl benzene sulfonate, and N‐methyl‐O‐phenylenediamine dihydrochloride at test concentrations as low as 0.025%. Amlodipine and Telmisartan each had a test concertation of 100 and 800 μg/ml, respectively. The developed analytical method was validated for different applications, that is, for assay and related substance methods. The calibration curves for genotoxic impurities were linear in the range of the Limit of quantitation to 1.2% of the test concentration of the respective drugs. Forced degradation investigations were conducted on selected drugs, and targeted analytes were then quantified. The stability of both drugs in acid and basic hydrolysis was improved compared to when they were evaluated separately, although Amlodipine showed an inverted degradation pattern in a more recent investigation when combined with Telmisartan under oxidative degradation conditions. The validated method was successfully applied for the quantification of the genotoxic impurities of Amlodipine and Telmisartan in finished pharmaceutical preparation. [ABSTRACT FROM AUTHOR]

The protection of biological weapons-related intellectual property is discussed, focusing on the creation of Article X under the Biological Weapons Convention (BWC). Topics include suggested changes to international patent laws, and the effects of patent laws on the global society.

Byline: Sachin Chaturvedi The recent expansion of Indian biotechnology industry backed by strong R&D allocations sets the upward movement of the industry on a new growth trajectory intertwined with innovation and entrepreneurship. This is most likely to take off Indian biopharma industry from 'bio-generics' and 'bio-similars' to a higher pedestal where it may develop 'proprietary processes', carving a new niche for the growth of the sector, giving further push to R&D-intensive activities. The issue is how National Innovation System (NIS), which could provide initial manpower and financial support to the sector, responds to the growing specialisation of the Indian biopharma and help evolve new strategies to sustain the growth in the high-end biopharma sector.

Byline: Sachin Chaturvedi The introduction of genetically modified products has raised several issues related to safety, labelling and identifying preservation. These concerns have trade specific implications as well. This paper makes an effort to take stock of broad institutional arrangements which have come up to address some of these concerns viz. a viz. trade obligations. In this context, the role of the Cartagena Protocol on Biosafety (CPB) is also analysed. Some of the provisions of CPB are in direct conflict with the WTO agreement on Sanitary and Phyto-sanitary Measures (SPS). This poses severe policy challenges to countries like India where the pace of agricultural exports has risen very recently.

This article attempts to understand BRICS from the perspective of a multi-polar world order and the role played by India at the BRICS. Specifically, the article looks at the implication that BRICS has for future of multilateralism, promoting new institutional delivery mechanisms, upholding the space for development and equity, and highlights India's contribution to the shaping of the BRICS agenda. The future of BRICS cooperation and scope for deeper collaboration would necessarily evolve out of the priorities of global governance reforms, contribution to global public goods, meaningful economic cooperation, deepening of institution-building efforts and the convergence of the guiding principles. [ABSTRACT FROM AUTHOR]

The article discusses the legal aspects of biobanking and a right to privacy in India, and it mentions the globalization of science and technology, as well as India's regulation and governance of biomedical research. Emerging technologies are addressed, along with ethical conflicts involving research and development (R&D) and clinical trials. Millennium Development Goals (MDGs) are examined, along with the Indian Council for Medical Research and health research, and non-communicable diseases.

Drawing on the lessons from India and China in Bt cotton, this paper argues that emerging linkages between regulation, promoting innovation and access to innovation call for a new approach. Intellectual property rights and regulatory regimes may constrain diffusion and usage of technology. In the new approach, state’s intervention through appropriate policies for promoting innovation is important and Socio-Economic assessment of technologies should also play a role in policy formulation. The emerging concept of Responsible Research and Innovation (RRI) can be useful in framing the new approach. The paper points out that understanding of access to and availability of innovations can be linked with the RRI framework, and a coherent policy framework that promotes both access and responsible innovation can be developed. It also points out that this framework will facilitate development of socially relevant innovations and will also be useful in addressing controversies in development and use of innovations. [ABSTRACT FROM AUTHOR]

This article examines the emerging trends in India's role as a provider of development assistance to the other developing countries of the global South. Though India has diversified the regional focus and has multiplied the quantum of development assistance, there remain several challenges at various levels. The expectations from the development partners have gone up but is India prepared with the institutional frameworks that would be required to administer the desired scale of response? Is there enough preparedness to undertake impact assessment? This article attempts to address some of these issues. [ABSTRACT FROM AUTHOR]

Although Article 26 of the Cartagena Protocol enables countries to take into account socio-economic aspects in decision-making with respect to Living Modified Organisms (LMOs), translating that into practice has not been easy. Countries have followed different approaches; while some countries have chosen to use a comprehensive list of socio-economic impacts they want to assess, some countries have not given to this much importance. This article explains the need for taking socio-economic aspects into account and analyses the practices followed in this. It suggests a model that differentiates technology regulation from decision-making taking into account the socio-economic aspects. This model takes into account the socio-economic aspects in four stages of commercialisation and it is suggested as a suitable model for developing countries. [ABSTRACT FROM AUTHOR]

Though since 1991, India has been actively pursuing liberalization in external sector, including regulatory processes; however, still there are many initiatives which are to be taken to their logical end. The paper has identified some of the trade-related sectors, which require urgent attention of the policy makers. These sectors include government procurement, trade facilitation, and mutual recognition agreements (MRA) for implementation of sanitary and phytosanitary (SPS)-related provisions. Policy reforms in these areas may further help in rationalizing India's continuously expanding frontiers of new free-trade agreements (FTAs) with that of multilateral commitments. It may also provide further fillip to the idea of reducing transaction costs for the external sector. [ABSTRACT FROM AUTHOR]

The article offers information on a survey of entrepreneurial collaborations among health biotechnology firms in developing countries. According to the survey, though there is a high level of collaboration, there is also a lack of emphasis on new or improved health biotechnology products and processes. Countries included in the survey are Brazil, China, Cuba, Egypt, India, and South Africa and the number of firms surveyed is 467 wherein a total of 288 firms completed the survey. Survey authors recommend the integration of more South-South collaboration in their innovation policies and provide support for firms that want to promote innovation in health biotechnology.

A letter to the editor is presented concerning a survey on collaboration between the Southern and Northern hemispheres in the realm of biotechnology.

The article discusses several issues related to the usage of information and communication technology (ICT) in electronically delivered software (EDS) in India. An overview of relevant World Trade Organization (WTO) councils and their mandate on electronic commerce (e-commerce) is offered. A list of the initiatives made to overcome limitations to the participation of developing countries in e-commerce is presented. It talks about the debate on moratorium on electronic transmission. It cites the global trend in information technology (IT) services export and trends in ICT trade in India. It states the implications of the withdrawal of moratorium on software firms in India.

The article discusses the trade and investment relations of India to Africa. It notes that the trade patterns of the two countries have developed in which India's deal with Africa had been doubled from 5.5 to 12.24 billion dollars in 2006-07. It states that India had introduced various initiatives such as the Pan African Network to give tele-medicine and tele-education benefits to Africa. It speculates that India will become a vital export destination for many African countries in the future.

The emergence of the sectoral systems of innovation (SSI) framework for analysing shifts in technological trajectory and economic growth has evoked a great deal of interest. Many researchers working on the National Systems of Innovation (NSI) concept have welcomed the approach and shown interest in the interplay between national and sectoral frameworks and related policy prescriptions. This paper attempts to analyse emerging and missing linkages between SSI and NSI in the biopharmaceutical sector in India. It does so in the light of major expansion in the Indian pharmaceutical industry and the new efforts to incorporate strategies targeting biotechnology innovation. The paper studies the policy regime facilitating this new era and discusses the future growth prospects of the Indian biopharmaceutical industry. [ABSTRACT FROM AUTHOR]

The study of industry associations occupies an uneasy ground in development economics. There is much empirical work that shows that industry associations fulfil important developmental roles in developing countries, often compensating for inadequacies in the business environment. Yet their status as institutions capable of generating growth is compromised because of the rent-seeking behaviour they embody. We study two different technology-based industries, namely software services and biotechnology, both of which formed industry associations to influence government policy and to aid the growth of their member firms, paying attention to their motivations for setting up, detailing the policies they sought to influence and their success as organisations. [ABSTRACT FROM AUTHOR]

China and India have emerged as highly dynamic economies in recent years. In the Asian region, their growth and economic expansion has generated its own complementarities. The article empirically shows that a surge in the exports of these two countries has significantly contributed to their overall economic growth. Towards this end, both the countries have relied on least developed countries (LDCs) and developing countries for their imports and on markets of industrialised economies for exports. The import dependence of India and China is mostly on the industrial intermediate sector, which is critical for their exports. Supply and technology constraints in LDCs and other countries may be addressed explicitly, and relevance of these two countries as suppliers of foreign direct investment (FDI) and technology is examined. India and China have made steady progress in frontier technologies, such as information and communication technology (ICT) and biotechnology, and they may provide easy access to these technologies to LDCs and other countries. [ABSTRACT FROM AUTHOR]

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Linaclotide (LINA) is a first-in-class guanylate cyclase agonist used for treating irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation. Stress degradation studies were performed to examine LINA's intrinsic stability, adhering to International Council for Harmonisation of Technical ICH) guidelines Q1A (R2). The current study endeavours to elucidate the stability behavior of LINA by exposing various stress conditions. A simple LC method was developed for effective separation of all LINA degradation products using a Waters Symmetry C18 column (150 ×4.6 mm, 3.5 µm) as the stationary phase. The generated degradation products were identified and characterized by using high-resolution mass spectrometry (LC-HRMS), MS/MS studies. The mechanistic fragmentation pathway for the seven degradation products was established and the chemical structure for the identified degradation products was elucidated. LINA was susceptible to degrade under acidic, basic, neutral, photolytic, and oxidative conditions. A total of three Pseudo DPs, DP-1, DP-2, and DP-3, were formed under acidic conditions while using methanol as the co-solvent. Additionally, degradation products (DPs) were identified: DP-4 formed under basic stress condition and DP-5 under neutral, thermal, and photolytic conditions. Furthermore, DP-6 and DP-7 were formed under oxidative stress condition. This study established the mechanistic fragmentation pathways and elucidated the chemical structures of the degradation products, offering valuable insights for generics and novel formulation drug development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mass spectrometry (MS) plays a crucial role in metabolomics, especially in the discovery of disease biomarkers. This review outlines strategies for identifying metabolites, emphasizing precise and detailed use of MS techniques. It explores various methods for quantification, discusses challenges encountered, and examines recent breakthroughs in biomarker discovery. In the field of diagnostics, MS has revolutionized approaches by enabling a deeper understanding of tissue-specific metabolic changes associated with disease. The reliability of results is ensured through robust experimental design and stringent system suitability criteria. In the past, data quality, standardization, and reproducibility were often overlooked despite their significant impact on MS-based metabolomics. Progress in this field heavily depends on continuous training and education. The review also highlights the emergence of innovative MS technologies and methodologies. MS has the potential to transform our understanding of metabolic landscapes, which is crucial for disease biomarker discovery. This article serves as an invaluable resource for researchers in metabolomics, presenting fresh perspectives and advancements that propels the field forward., (© 2024 John Wiley & Sons Ltd.)