Product Licence Research Articles

Comparison of immunogenicity and reactogenicity of split versus subunit influenza vaccine in Korean children aged 6–35 months

Studies comparing the immunogenicity and reactogenicity of trivalent inactivated subunit (SU) and split (SPL) vaccines in children in Asia are limited. In 2008, we assessed the safety and immunogenicity of SU and SPL influenza vaccines in Korean children aged 6-35 months. We studied 2 non-randomized cohorts of children who received either SU or SPL vaccine in an open-label non-stratified controlled trial at 6 hospitals in Korea. We measured antibody titers with a hemagglutination-inhibition assay at baseline and 30 days after the first or second flu shot. The primary goal was the determination of vaccine immunogenicity according to the European Union Committee of Human Medicinal Products licensing criteria. Out of a total of 106 participants aged 6-35 months, 47 received the SPL vaccine and 59 the SU vaccine. After vaccination, 41 (87.2%), 40 (85.1%), and 33 (70.2%) of the 47 subjects in the SPL group had titers ≥ 1:40 against H1N1, H3N2, and B, respectively. In the SU group, 42 (71.2%), 34 (57.6%), and 22 (37.3%) of 59 subjects had titers ≥ 1:40 against H1N1, H3N2, and B, respectively. The post-vaccination geometric mean titers of H1N1, H3N2, and B (SPL vs SU) were 119.1, 99.8, and 61.4 vs 75.4, 51.2, and 24.1, respectively. There were no serious vaccine-related adverse events. There were no differences between the SPL and SU vaccines with respect to adverse events. The immunogenicity of the SPL vaccine appears to be better than that of the SU vaccine in children aged 6-35 months in Korea.

Licensing of products is the right way forward for squeezed specials sector

Licensing of products is the right way forward for squeezed specials sector

The HIV epidemic and human rights violations in Brazil

Efforts to mitigate stigma and discrimination have been central to the national response to HIV in Brazil, a country historically recognized as a leader in human rights-based HIV prevention, treatment and care. Brazil is credited with avoiding a potentially generalized HIV epidemic by providing universal access to antiretroviral therapy (ART) and associated HIV care since 1996. The Brazilian AIDS policy, although hailed as a model worldwide, has been more difficult to implement among more vulnerable groups of people living with HIV/AIDS, such as drug users, homeless persons, people who use drugs and sex workers, who are often stigmatized as noncompliant or difficult to retain in care. (Published: 12 November 2013) Citation: Malta M and Beyrer C. Journal of the International AIDS Society 2013, 16 :18817 http://www.jiasociety.org/index.php/jias/article/view/18817 | http://dx.doi.org/10.7448/IAS.16.1.18817

Steganographic information hiding that exploits a novel file system vulnerability

In this paper, we present DupeFile, a simple yet critical security vulnerability in numerous file systems. By exploiting DupeFile, adversary can store two or more files with the same name/path, with different contents, inside the same volume. Consequently, data-exfiltration exploiting DupeFile vulnerability, hereafter called DupeFile Hiding, becomes simple and easy to execute. In DupeFile Hiding, a known good file is chosen, whose name serves as the cover for hiding the malicious file. Hence we classify DupeFile Hiding as a steganography technique. This vulnerability can also be exploited for legitimate applications - hiding product licence, DRM, etc. DupeFile was first uncovered on a FAT12-formatted disk on Win-98 VM. Nonetheless, the vulnerability exists in numerous file systems, including NTFS, HFS+, and HFS+ Journaled. We have developed two tools: DupeFile Detector and DupeFile Extractor for detecting and recovering hidden files respectively. We have also developed DupeFile Creator for hiding files in legitimate applications.

Improving Software Sustainability: Lessons Learned from <italic>Profiles in Science</italic>

The Profiles in Science® digital library features digitized surrogates of historical items selected from the archival collections of the U.S. National Library of Medicine as well as collaborating institutions. In addition, it contains a database of descriptive, technical and administrative metadata. It also contains various software components that allow creation of the metadata, management of the digital items, and access to the items and metadata through the Profiles in Science Web site [1]. The choices made building the digital library were designed to maximize the sustainability and long-term survival of all of the components of the digital library [2]. For example, selecting standard and open digital file formats rather than proprietary formats increases the sustainability of the digital files [3]. Correspondingly, using non-proprietary software may improve the sustainability of the software–either through in-house expertise or through the open source community.Limiting our digital library software exclusively to open source software or to software developed in-house has not been feasible. For example, we have used proprietary operating systems, scanning software, a search engine, and office productivity software. We did this when either lack of essential capabilities or the cost-benefit trade-off favored using proprietary software. We also did so knowing that in the future we would need to replace or upgrade some of our proprietary software, analogous to migrating from an obsolete digital file format to a new format as the technological landscape changes. Since our digital library's start in 1998, all of its software has been upgraded or replaced, but the digitized items have not yet required migration to other formats.Technological changes that compelled us to replace proprietary software included the cost of product licensing, product support, incompatibility with other software, prohibited use due to evolving security policies, and product abandonment. Sometimes these changes happen on short notice, so we continually monitor our library's software for signs of endangerment. We have attempted to replace proprietary software with suitable in-house or open source software. When the replacement involves a standalone piece of software with a nearly equivalent version, such as replacing a commercial HTTP server with an open source HTTP server, the replacement is straightforward. Recently we replaced software that functioned not only as our search engine but also as the backbone of the architecture of our Web site. In this paper, we describe the lessons learned and the pros and cons of replacing this software with open source software.

Vplyv priamych zahraničných investícií na inovačnú činnosť firiem

We analyse regional spill-over effects from FDI on innovation activities of domestic firms in Eastern European and Asian transition and post-transition countries. The analysis is carried out using the World Bank 2009 Enterprise survey. We look also at the impact of FDI on innovation activities of domestic firms at regional level. We find the evidence for a non-linear impact of foreign firms on innovation. An increasing regional foreign presence at first reduces innovation activities and then beyond a certain point increases it. This is consistent with the literature which suggests that either effect may be plausible. Foreign owned firms are more likely to engage in product innovation and license products from other firms. We also find the evidence for the positive statistically significant impact of access to bank credit, infrastructure, size of the firm, being part of a group of firms and competitive pressure on innovation activities of firms.

Production Sharing Agreements and Licences: A Distinction without a Difference?

This article briefly considers possible reasons why some states prefer production sharing agreements (PSAs), some prefer licences and others prefer a combination of the two when developing their oil and gas resources. Outlines key distinctions between the mechanisms and how the choice of approach may be influenced by factors including: (1) whether a state is developed or developing; (2) the duration of the exploration; (3) whether flexibility is required; (4) the investment risk; (5) the degree of regulatory measures involved; and (6) levels of competition

Drug Development

Drug Development

Evolution of the European guidelines for the clinical development of factor VIII products: little progress towards improved patient management

In the process of clinical development and licensing of factor VIII (FVIII) products for treatment of haemophilia A, the safety concerns generated in the 1980s by the risk of pathogen transmission were tremendously reduced by the implementation of an array of methods for inactivation/removal of blood borne pathogens. The current focus on the risk of FVIII inhibitors does not stem from a new awareness, because this multifactorial complication has long been recognized. With this background, I believe that the current European regulatory guidelines for the clinical development and licensing of FVIII products fail to reflect the tremendous progress made in terms of clinical efficacy and safety, because they are witnessing a continuous increase in the demands from health agencies to the point that clinical studies have become more and more difficult to carry out. This article reviews the evolution of the European regulations on new FVIII products, lists a number of regulatory requirements whose scientific and/or clinical rationale is perhaps questionable and recommends keeping such requirements in reasonable limits of feasibility, without jeopardizing current high standards of efficacy and safety.

Validation of a 30-year-old process for the manufacture of l-asparaginase from Erwinia chrysanthemi

A 30-year-old manufacturing process for the biologic product L-asparaginase from the plant pathogen Erwinia chrysanthemi was rigorously qualified and validated, with a high level of agreement between validation data and the 6-year process database. L-Asparaginase exists in its native state as a tetrameric protein and is used as a chemotherapeutic agent in the treatment regimen for Acute Lymphoblastic Leukaemia (ALL). The manufacturing process involves fermentation of the production organism, extraction and purification of the L-asparaginase to make drug substance (DS), and finally formulation and lyophilisation to generate drug product (DP). The extensive manufacturing experience with the product was used to establish ranges for all process parameters and product quality attributes. The product and in-process intermediates were rigorously characterised, and new assays, such as size-exclusion and reversed-phase UPLC, were developed, validated, and used to analyse several pre-validation batches. Finally, three prospective process validation batches were manufactured and product quality data generated using both the existing and the new analytical methods. These data demonstrated the process to be robust, highly reproducible and consistent, and the validation was successful, contributing to the granting of an FDA product license in November, 2011.

P88 Ulipristal acetate (UPA) is affordable as emergency contraception (EC) if used where levonorgestrel (LNG) is unlicensed

Background/AimOur three GUM clinics are increasingly offering an integrated family planning (FP) service. We audited against three Faculty of Sexual and Reproductive Health EC standards. UPA is licensed to be...

Melanoma diagnosed 27 years after a benoxaprofen-induced photosensitivity reaction

The propionic acid derivative Benoxaprofen was introduced for the treatment of rheumatic disorders in 1980. Its product license was then withdrawn 2 years later due to concerns over serious dermatologic, hepatic and renal side effects. Photosensitivity was the most common side effect with reported incidence of up to 50%. We present the first case report of a patient who presented with a melanoma diagnosed 27 years after a benoxaprofen-induced photosensitivity reaction. With an estimated 1.5 million patients previously on benoxaprofen, a large number of patients may potentially face increased risk of developing malignant melanoma. This case report can only suggest an association between solar injury secondary to benoxaprofen-related photosensitivity and subsequent melanoma. However the primary factor that improves survival from melanoma is early diagnosis, and so clinicians treating this group of patients should be aware of this risk. Although benoxaprofen is no longer in clinical use, the long-term sequelae to its photosensitizing effects may still be clinically important. Clinicians treating this group of patients should be vigilant, and consider a low threshold for diagnostic biopsy of suspicious skin lesions.

How Does Obtaining Intellectual Property Rights Impact Technology Commercialization Strategy? Reconciling the Competing Effects on Licensing vs. Financing

The importance of intellectual property (IP) rights for commercializing innovation is well established. Moreover, separate streams of literature have shown a positive relationship between IP rights and both product licensing and third-party (especially VC) financing. However, since raising third-party finance enables an innovating firm to continue commercializing its innovation alone, it is not clear how obtaining IP rights will impact the choice between licensing product rights and continuing to commercialize the product alone. This paper attempts to reconcile these two alternative effects of obtaining IP rights and the implications for commercialization strategy. The paper empirically examines the relationship between the status of the primary patent covering an innovation and whether the innovating firm’s licenses its innovation or raises external finance. The results show that while filing and allowance of the primary significantly increases the likelihood of raising finance at certain stages of the firm/product’s development, and thereby enable the firm to delay licensing, obtaining patent rights has a much larger, positive effect on licensing. While it is not possible to identify the drivers of these different effects from the empirical analysis, the theory suggests that patent filing may act as a signal to financial investors that enable early-stage firms to raise finance, but ultimately they are most valuable as appropriability mechanisms for facilitating financing.

Why should we care about quality of life in persons with haemophilia?

The very high cost of haemophilia care, including the increase in use of factor prophylaxis in both children and adults requires that funders of clotting factor concentrates require objective measures of health, such as joint status and quality of life (QOL). Many clinical trials, especially those for licensing of new products, are including QOL instruments in their protocols to evaluate the patients' perspective of wellbeing before and during therapy. This article gives a perspective on QOL the importance of QOL measurement in the field of haemophilia and its impact on patient outcome.

Specific allergen concentration of WHO and FDA reference preparations measured using a multiple allergen standard

Specific allergen concentration of WHO and FDA reference preparations measured using a multiple allergen standard

Food safety practices and knowledge among Turkish dairy businesses in different capacities

The Turkish dairy industry has recently implemented HACCP-based food safety management systems according to a new Turkish law. Law 5996, instituted in 2010, establishes food-handling standards for the dairy industry and requires on-farm and plant production HACCP-compliance, to guarantee food safety. The implementation of this law and current food safety standards in Turkish dairy plants were assessed in this study. Researchers developed a survey to characterize overall food safety among dairy businesses in Aydın, Turkey. The survey included a questionnaire, interviews with management and audits of dairy businesses that had production licenses from the Ministry of Food, Agriculture and Livestock in 2010. Dairy businesses’ current food safety practices, staff comprehension of basic hygiene and food safety, and plant standards regarding food safety training were all evaluated. Findings were differentiated based on plant size. Our study found that the majority of food safety problems occurred at the time of raw milk being received, despite 71.4% of dairy businesses implementing supplier safety criteria. However, based on field observations, dairy businesses had limited supplier safety criteria, the processing plants had very poor hygiene practices and HACCP compliance was inadequate among plants. Most of the dairy businesses limited food safety training to permanent workers and did not extend this training to management, technical staff or temporary workers. Management identified several impediments to further food safety training but the majority, also, communicated interest in further food safety training. Generally, larger dairy plants had better compliance with current Turkish food safety codes. Our data, along with the literature in this area, suggests that further governmental programming that trains management in food safety is needed. This training should employ alternative educational strategies and specifically target smaller and medium-sized dairy plant managers. Such programming or grants would advance food safety among Turkish dairy businesses.

RETRACTED: Integrated knowledge exploitation: The complementarity of product development and technology licensing

AbstractIn light of increasing licensing, we challenge the common assumption that product development and technology licensing are substitutes. We develop a resource‐based framework, which distinguishes a firm's technological resource base and technology exploitation processes. We further combine survey, patent, and financial data of 228 medium‐sized and large industrial companies to examine the interactions of firms' product development processes and technology licensing processes in order to explain heterogeneity in new product revenues, licensing performance, and firm performance. The results underscore that product development, which indicates innovative capacity, and technology licensing, which indicates desorptive capacity, are complements rather than substitutes in integrated knowledge exploitation in medium‐sized and large firms. This complementarity is particularly pronounced in firms with an emphasis on cross‐licensing and with a strong patent portfolio. Copyright © 2012 John Wiley & Sons, Ltd.

Better medicines for children: challenges and unmet needs

Better medicines for children: challenges and unmet needs This review deals with the use of medicinal products in children. Many medicinal products administered routinely to paediatric patients have been either not licensed for use in children (unlicensed use) or have been prescribed outside the terms of their product license (off-label prescribing). A lot of surveys have been conducted in the context of identifying the extent of off-label used drugs in children documenting high rates (45-60 %) of such use. Recognising and meeting challenges as development of suitable formulations for very young children and realization of clinical trials involving children present important steps in the enhancement of the present situation. To improve the health of children in Europe, the Regulation (EC) No 1901/2006 addressing the pharmaceutical industry, research teams and member states proposing important incentives and obligations was assigned. Paediatric Investigation Plan and Paediatric Use Marketing Authorisation present the key measures of the EU regulation on medicinal products for paediatric patients.

Many New Measures to Build Safer Chemical Enterprises

This paper presents an account of China's chemical safety management. It starts from the chemical safety legislation and aims to provide the reader with information on current safety priorities. It examines the chemical safety license systems and priorities for supervision and management in details. The chemical safety licenses systems such as the safe production license and safe use license of chemicals have played critical roles in promoting the chemical management. The concept of Two Emphases and One Major are introduced with the aims of reducing major chemical accidents. There is also a brief discuss on chemical process safety to achieve the solid safety management in chemical enterprises. Therefore, the much safer chemical enterprises may be achieved through these new measures.

Barriers and benefits of the implementation of food safety management systems among the Turkish dairy industry: A case study

The aim of this research was to determine the barriers and advantages of the Hazards Analysis and Critical Control Points (HACCP) and food safety programs (FSPS) employed by the dairy industry in Aydın, Turkey. By conducting face-to-face interviews and using questionnaires, the structure of Aydın dairy plants’ food safety management systems was characterized. The questionnaires elicited information about the applications of food safety systems, dairy plant managers’ opinions about any inspection systems, and their expectations for government and local legal authorities in food safety systems. Twenty-eight operating dairy plants in Aydın with a production licence from the Ministry of Food, Agriculture and Livestock show activity in the sector for more than 10 years (53.5%) with joint-stock or limited company status (60.7%). These plants produce white cheese, fermented milk products and butter. Implementing a clear and efficient food safety management system can improve legal issues (85.7%) and increase client trust (64.3%). This is positively correlated with the ages of dairy plant managers in the dairy industry in Aydın (p<0.05 and p<0.01). All the same, not understanding the HACCP was specified as one of the main barriers to its utilization. Almost half of managers (46.5%) reported not really knowing what HACCP was, while 35.8% reported that it was too expensive to employ. On the other hand, the main difficulties with prerequisite program (PRP) applications in Aydın dairy plants was determined to be a result of insufficient physical conditions (35.7%) and cost (46.4%).A lack of knowledge relating to and the cost of HACCP and other food safety programs were the main barriers to implementation in the Aydın dairy industry. Providing periodical training and consultation services for FSMS applications in the dairy industry by the government and also providing financial support must be provided.