Current and future trens in the quality control of pharmaceuticals and biopharmaticals : impacts on Cost of Goods Sold (COGS)

[Summary] 2. Roles of quality control in the pharmaceutical and biopharmaceutical industries. - 2.1. Pharmaceutical industry. - 2.2. Biopharmaceutical industry. - 2.3. Policy and regulatory. - 2.3.1. The US Food and Drug Administration (FDA). - 2.3.2. The European Medicine Agency (EMEA). - 2.3.3. The Japanese Ministry of Work, Labor and Welfare (MHLW). - 2.3.4. The Swiss Agency for Therapeutic Products (Swissmedic). - 2.3.5. The International Conference on Harmonization (ICH). - - 3. Types of testing. - 3.1. Microbiological purity tests. - 3.2. Physiochemical tests. - 3.3. Critical to quality steps. - 3.3.1. API starting materials and excipients. - 3.3.2. Intermediates. - 3.3.3. APIs (drug substances) and final drug product. - 3.3.4. Primary and secondary packaging materials fro drug products. - - 4. Manufacturing cost and quality control. - 4.1.1. Pharmaceutical manufacturing cost breakdown. - 4.1.2. Biopharmaceutical manufacturing cost breakdown. - 4.2. Batch failure / rejection / rework / recalls. - - 5. Future trends in the quality control of pharmaceuticals and biopharmaceuticals. - 5.1. Rapid and real time testing. - 5.1.1. Physio-chemicals testing. - 5.1.2. Rapid microbiology methods

On the Definition of Public Goods. Assessing Richard A. Musgrave's contribution

This paper provides an explanation of the emergence of the standard textbook definition of public goods in the middle of the 20th century. It focuses on Richard Musgrave's contribution in defining public goods as non-rival and non-excludable - from 1939 to 1969. Although Samuelson's mathematical definition is generally used in models of public goods, the qualitative understanding of the specificity of pure public goods owes more to Musgrave's emphasis on the impossibility of exclusion. This paper also highlights the importance of the size of the group to which benefits of a public good accrue. This analysis allow for a reassessment of the Summary table of goods which first appeared in Musgrave and Musgrave (1973) textbook.

Services standardization in the United-States and in Europe: an institutional analysis of private authority

This contribution explores the role of international standards in the rules governing the internationalisation of the service economy. It analyses on a cross-institutional basis patterns of authority in the institutional setting of service standards in the European and Amercian context. The entry into force of the World Trade Organisation (WTO) in 1995 gave international standards a major role in harmonising the technical specifications of goods and services traded on the global market Despite the careful wording of the WTO, a whole range of international bodies still have the capacity to define generic as well as detailed technical specifications affecting how swelling offshore services are expected to be traded on worldwide basis. The analysis relies on global political economy approaches to identify constitutive patterns of authority mediating between the political and the economic spheres on a transnational space. It extends to the area of service standards the assumption that the process of globalisation is not opposing states and markets, but a joint expression of both of them including new patterns and agents of structural change through formal and informal power and regulatory practices. The paper argues that service standards reflect the significant development of a form of transnational hybrid authority, that blurs the distinction between private and public actors, whose scope spread all along from physical measures to societal values, and which reinforces the deterritorialisation of regulatory practices in contemporary capitalism. It provides evidence of this argument by analysing the current European strategy regarding service standardization in response to several programming mandate of the European Commission and the American views on the future development of service standards.

Hospital admission rates for alcoholic intoxication after policy changes in the canton of Geneva, Switzerland.

Background: In February, 2005, the canton of Geneva in Switzerland prohibited the off-premise sale of alcoholic beverages between 9pm and 7am, and banned their sale in gas stations and video stores. The aim of this study is to assess the impact of this policy change on hospital admission rates for alcoholic intoxication.Methods: An interrupted time series analysis of this natural experiment was performed with data on hospitalisations for acute alcoholic intoxication during the 2002-2007 period. The canton of Geneva was treated as the experimental group, while all other Swiss cantons were used as the control group.Results: In the experimental site, the policy change was found to have a significant effect on admission rates among adolescents and young adults. Depending on the age group, hospitalisation rates for alcoholic intoxication fell by an estimated 25-40% as the result of restricted alcohol availability.Conclusions: Modest restrictions on opening hours and the density of off-premise outlets were found to be of relevance for public health in the canton of Geneva. In light of this finding, policy makers should consider such action as a promising approach to alcohol prevention. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Modeling the biophysical impacts of global change in mountain biosphere reserves

Mountains and mountain societies provide a wide range of goods and services to humanity, but they are particularly sensitive to the effects of global environmental change. Thus, the definition of appropriate management regimes that maintain the multiple functions of mountain regions in a time of greatly changing climatic, economic, and societal drivers constitutes a significant challenge. Management decisions must be based on a sound understanding of the future dynamics of these systems. The present article reviews the elements required for an integrated effort to project the impacts of global change on mountain regions, and recommends tools that can be used at 3 scientific levels (essential, improved, and optimum). The proposed strategy is evaluated with respect to UNESCO's network of Mountain Biosphere Reserves (MBRs), with the intention of implementing it in other mountain regions as well. First, methods for generating scenarios of key drivers of global change are reviewed, including land use/land cover and climate change. This is followed by a brief review of the models available for projecting the impacts of these scenarios on (1) cryospheric systems, (2) ecosystem structure and diversity, and (3) ecosystem functions such as carbon and water relations. Finally, the cross-cutting role of remote sensing techniques is evaluated with respect to both monitoring and modeling efforts. We conclude that a broad range of techniques is available for both scenario generation and impact assessments, many of which can be implemented without much capacity building across many or even most MBRs. However, to foster implementation of the proposed strategy, further efforts are required to establish partnerships between scientists and resource managers in mountain areas.

Rules of origin : from analysis to reform

General Introduction This thesis can be divided into two main parts :the first one, corresponding to the first three chapters, studies Rules of Origin (RoOs) in Preferential Trade Agreements (PTAs); the second part -the fourth chapter- is concerned with Anti-Dumping (AD) measures. Despite wide-ranging preferential access granted to developing countries by industrial ones under North-South Trade Agreements -whether reciprocal, like the Europe Agreements (EAs) or NAFTA, or not, such as the GSP, AGOA, or EBA-, it has been claimed that the benefits from improved market access keep falling short of the full potential benefits. RoOs are largely regarded as a primary cause of the under-utilization of improved market access of PTAs. RoOs are the rules that determine the eligibility of goods to preferential treatment. Their economic justification is to prevent trade deflection, i.e. to prevent non-preferred exporters from using the tariff preferences. However, they are complex, cost raising and cumbersome, and can be manipulated by organised special interest groups. As a result, RoOs can restrain trade beyond what it is needed to prevent trade deflection and hence restrict market access in a statistically significant and quantitatively large proportion. Part l In order to further our understanding of the effects of RoOs in PTAs, the first chapter, written with Pr. Olivier Cadot, Celine Carrère and Pr. Jaime de Melo, describes and evaluates the RoOs governing EU and US PTAs. It draws on utilization-rate data for Mexican exports to the US in 2001 and on similar data for ACP exports to the EU in 2002. The paper makes two contributions. First, we construct an R-index of restrictiveness of RoOs along the lines first proposed by Estevadeordal (2000) for NAFTA, modifying it and extending it for the EU's single-list (SL). This synthetic R-index is then used to compare Roos under NAFTA and PANEURO. The two main findings of the chapter are as follows. First, it shows, in the case of PANEURO, that the R-index is useful to summarize how countries are differently affected by the same set of RoOs because of their different export baskets to the EU. Second, it is shown that the Rindex is a relatively reliable statistic in the sense that, subject to caveats, after controlling for the extent of tariff preference at the tariff-line level, it accounts for differences in utilization rates at the tariff line level. Finally, together with utilization rates, the index can be used to estimate total compliance costs of RoOs. The second chapter proposes a reform of preferential Roos with the aim of making them more transparent and less discriminatory. Such a reform would make preferential blocs more "cross-compatible" and would therefore facilitate cumulation. It would also contribute to move regionalism toward more openness and hence to make it more compatible with the multilateral trading system. It focuses on NAFTA, one of the most restrictive FTAs (see Estevadeordal and Suominen 2006), and proposes a way forward that is close in spirit to what the EU Commission is considering for the PANEURO system. In a nutshell, the idea is to replace the current array of RoOs by a single instrument- Maximum Foreign Content (MFC). An MFC is a conceptually clear and transparent instrument, like a tariff. Therefore changing all instruments into an MFC would bring improved transparency pretty much like the "tariffication" of NTBs. The methodology for this exercise is as follows: In step 1, I estimate the relationship between utilization rates, tariff preferences and RoOs. In step 2, I retrieve the estimates and invert the relationship to get a simulated MFC that gives, line by line, the same utilization rate as the old array of Roos. In step 3, I calculate the trade-weighted average of the simulated MFC across all lines to get an overall equivalent of the current system and explore the possibility of setting this unique instrument at a uniform rate across lines. This would have two advantages. First, like a uniform tariff, a uniform MFC would make it difficult for lobbies to manipulate the instrument at the margin. This argument is standard in the political-economy literature and has been used time and again in support of reductions in the variance of tariffs (together with standard welfare considerations). Second, uniformity across lines is the only way to eliminate the indirect source of discrimination alluded to earlier. Only if two countries face uniform RoOs and tariff preference will they face uniform incentives irrespective of their initial export structure. The result of this exercise is striking: the average simulated MFC is 25% of good value, a very low (i.e. restrictive) level, confirming Estevadeordal and Suominen's critical assessment of NAFTA's RoOs. Adopting a uniform MFC would imply a relaxation from the benchmark level for sectors like chemicals or textiles & apparel, and a stiffening for wood products, papers and base metals. Overall, however, the changes are not drastic, suggesting perhaps only moderate resistance to change from special interests. The third chapter of the thesis considers whether Europe Agreements of the EU, with the current sets of RoOs, could be the potential model for future EU-centered PTAs. First, I have studied and coded at the six-digit level of the Harmonised System (HS) .both the old RoOs -used before 1997- and the "Single list" Roos -used since 1997. Second, using a Constant Elasticity Transformation function where CEEC exporters smoothly mix sales between the EU and the rest of the world by comparing producer prices on each market, I have estimated the trade effects of the EU RoOs. The estimates suggest that much of the market access conferred by the EAs -outside sensitive sectors- was undone by the cost-raising effects of RoOs. The chapter also contains an analysis of the evolution of the CEECs' trade with the EU from post-communism to accession. Part II The last chapter of the thesis is concerned with anti-dumping, another trade-policy instrument having the effect of reducing market access. In 1995, the Uruguay Round introduced in the Anti-Dumping Agreement (ADA) a mandatory "sunset-review" clause (Article 11.3 ADA) under which anti-dumping measures should be reviewed no later than five years from their imposition and terminated unless there was a serious risk of resumption of injurious dumping. The last chapter, written with Pr. Olivier Cadot and Pr. Jaime de Melo, uses a new database on Anti-Dumping (AD) measures worldwide to assess whether the sunset-review agreement had any effect. The question we address is whether the WTO Agreement succeeded in imposing the discipline of a five-year cycle on AD measures and, ultimately, in curbing their length. Two methods are used; count data analysis and survival analysis. First, using Poisson and Negative Binomial regressions, the count of AD measures' revocations is regressed on (inter alia) the count of "initiations" lagged five years. The analysis yields a coefficient on measures' initiations lagged five years that is larger and more precisely estimated after the agreement than before, suggesting some effect. However the coefficient estimate is nowhere near the value that would give a one-for-one relationship between initiations and revocations after five years. We also find that (i) if the agreement affected EU AD practices, the effect went the wrong way, the five-year cycle being quantitatively weaker after the agreement than before; (ii) the agreement had no visible effect on the United States except for aone-time peak in 2000, suggesting a mopping-up of old cases. Second, the survival analysis of AD measures around the world suggests a shortening of their expected lifetime after the agreement, and this shortening effect (a downward shift in the survival function postagreement) was larger and more significant for measures targeted at WTO members than for those targeted at non-members (for which WTO disciplines do not bind), suggesting that compliance was de jure. A difference-in-differences Cox regression confirms this diagnosis: controlling for the countries imposing the measures, for the investigated countries and for the products' sector, we find a larger increase in the hazard rate of AD measures covered by the Agreement than for other measures.

The environmental roots of non-communicable diseases (NCDs) and the epigenetic impacts of globalization

BACKGROUND: Non-communicable diseases (NCDs) are increasing worldwide. We hypothesize that environmental factors (including social adversity, diet, lack of physical activity and pollution) can become "embedded" in the biology of humans. We also hypothesize that the "embedding" partly occurs because of epigenetic changes, i.e., durable changes in gene expression patterns. Our concern is that once such factors have a foundation in human biology, they can affect human health (including NCDs) over a long period of time and across generations. OBJECTIVES: To analyze how worldwide changes in movements of goods, persons and lifestyles (globalization) may affect the "epigenetic landscape" of populations and through this have an impact on NCDs. We provide examples of such changes and effects by discussing the potential epigenetic impact of socio-economic status, migration, and diet, as well as the impact of environmental factors influencing trends in age at puberty. DISCUSSION: The study of durable changes in epigenetic patterns has the potential to influence policy and practice; for example, by enabling stratification of populations into those who could particularly benefit from early interventions to prevent NCDs, or by demonstrating mechanisms through which environmental factors influence disease risk, thus providing compelling evidence for policy makers, companies and the civil society at large. The current debate on the '25 × 25 strategy', a goal of 25% reduction in relative mortality from NCDs by 2025, makes the proposed approach even more timely. CONCLUSIONS: Epigenetic modifications related to globalization may crucially contribute to explain current and future patterns of NCDs, and thus deserve attention from environmental researchers, public health experts, policy makers, and concerned citizens.

Experts' consensus on use of electronic cigarettes: a Delphi survey from Switzerland.

OBJECTIVES: In some countries, nicotine-containing electronic cigarettes (e-cigarettes) are considered a consumer product without specific regulations. In others (eg, Switzerland), the sale of e-cigarettes containing nicotine is forbidden, despite the eagerness of many smokers to obtain them. As scientific data about efficacy and long-term safety of these products are scarce, tobacco control experts are divided on how to regulate them. In order to gain consensus among experts to provide recommendations to health authorities, we performed a national consensus study. SETTING: We used a Delphi method with electronic questionnaires to bring together the opinion of Swiss experts on e-cigarettes. PARTICIPANTS: 40 Swiss experts from across the country. OUTCOME MEASURES: We measured the degree of consensus between experts on recommendations regarding regulation, sale, use of and general opinion about e-cigarettes containing nicotine. New recommendations and statements were added following the experts' answers and comments. RESULTS: There was consensus that e-cigarettes containing nicotine should be made available, but only under specific conditions. Sale should be restricted to adults, using quality standards, a maximum level of nicotine and with an accompanying list of authorised ingredients. Advertisement should be restricted and use in public places should be forbidden. CONCLUSIONS: These recommendations encompass three principles: (1) the reality principle, as the product is already on the market; (2) the prevention principle, as e-cigarettes provide an alternative to tobacco for actual smokers, and (3) the precautionary principle, to protect minors and non-smokers, since long-term effects are not yet known. Swiss authorities should design specific regulations to sell nicotine-containing e-cigarettes.

Quand les normes font loi : topologie intégrée et processus différenciés de la normalisation internationale

International standardisation refers to voluntary technical specifications pertaining to the production and exchange of goods and services across borders. The paper outlines a theoretical framework which spells out the contention of emerging hybrid forms of non state authority in the global realm. It argues that international standardisation is confronted with a deep rift between promoters of further socialisation of international standards (i.e. a transfer of the universal scope of law into the official framework of standard-setting bodies) and multinational corporations in favour of globalisation of technical standards (i.e. universal recognition of minimal sectorial market-based standards). The problems related to the development of a possible ISO standard of system management in corporate social responsibility provides evidence of the argument.

La perception de la productivité dans l'industrie hôtelière de luxe : le cas de la Suisse romande

La perception de la productivité SUMMARY The main objective of this thesis is the perception of the productivity in the luxury hospitality industry. Despite a lot of efforts which were already made in the field of the production of goods, this concept (productivity) still remains to be defined in the services sector, more still, in that of the luxury hospitality industry. Since the object of this study is the perception of productivity, we decided to analyze the elements considered to be relevant by the top management in this field. Then, it seemed important to evaluate these same elements for the categories of middle-management and by the in-line employees. As perception is not static, it is dependent in an indirect way on its improvement and however also with the means of improvement. The assumption of our work evokes the possible relationship between productivity and its perception (P), (Q) quality and profitability (R). On this basis we built the P-Q-R model: R=F(P,Q) Finally, our research on this model enabled us to establish a mathematical relation between the three predetermined elements: fR=fP+fQ+c That means that the function efficiency of a process of services -(fR) is the sum of its quality function (intrinsic and extrinsic)-(fP) and of its productivity function - fQ (and the constant of regression "c"). To increase the profitability of the most significant manner, it is necessary to increase at the same time the productivity and quality. On the other hand, according to this formula but also according to the perception of the managers, with a constant profitability, either the productivity decreases in favor of the increase in quality, or the reverse. If the dimensions of the model influence positively or negatively the production process of services, then those wí11 influence in same manner our model (P, Q, R). We advance a point of view saying that profitability depends on the labor productivity which follows same dynamics than the perception of the productivity. The identification of the labor productivity as an essential element of successful management of the hotel is fundamental. The question which always remains in suspense is however the relevance of the concept "labor productivity" for the luxury hospitality industry. It was not proven an obvious correlation between this notion and the one of profitability. We still remain at the stage of perception. It results that one interesting way of future research will be the study of this correlation. As in any kind of luxury industry, the real added value does not consist in the volume produced or in the speed with which the product/service is carried out but in the creativity involved in their results. Let us note that the field of luxury is extremely related to the emotions and to the experience provided to the customers. La perception de la productivité... RÉSUME L'objectif principal de cette thèse est la perception de la productivité dans l'hôtellerie de luxe. Malgré tous les efforts qui ont déjà été faits dans le domaine de la production de biens, ce concept (productivité) reste encore à définir dans le secteur des services, plus encore, dans celui de l'hôtellerie de luxe. Étant donné que l'objet de l'étude est la perception de la productivité, nous avons décidé d'analyser les éléments jugés pertinents par les cadres dirigeants dans ce domaine. Puis, il nous a semblé important d'évaluer ces mêmes éléments pour les catégories de cadres moyens et par les employés in-line. Comme la perception n'est pas statique, elle est liée d'une manière indirecte à son amélioration et cependant également aux moyens d'amélioration. L'hypothèse de notre travail évoque la possible relation entre la productivité et sa perception (P), la qualité (Q) et la rentabilité (R). Sur cette base nous avons construit le modèle P-Q-R de départ R=f(P,Q) Finalement, notre recherche sur ce modèle nous a permis d'établir une relation mathématique entre les trois construits prédéterminés: fR=fP+fQ+c Cela signifie que la fonction rentabilité d'un processus de services -(fR) est la somme de sa fonction qualité (intrinsèque et extrinsèque)-fP et de sa fonction productivité -fQ (plus la constante de régression « c ») Pour augmenter la rentabilité de la manière la plus significative, il faut augmenter en même temps la productivité et la qualité. En revanche, selon cette formule mais selon aussi la perception des managers, à une rentabilité constante, soit la productivité diminue en faveur de l'augmentation de la qualité, soit l'inverse. Si les dimensions du modèle influencent positivement ou négativement le processus de production de services, alors celles-ci vont influencer de la même manière les construits de notre modèle (P, Q, R). Nous avançons un point de vue disant que la rentabilité dépend de la productivité du travail qui suit la même dynamique que la perception de la productivité. L'identification de la productivité du travail comme élément essentiel de gestion réussie de l'hôtel s'avère fondamentale. La question qui reste toujours en suspens est pourtant la pertinence de la notion «productivité du travail » pour l'industrie hôtelière de luxe. Il n'a pas été prouvé une corrélation évidente entre cette notion et celle de la profitabilité. Nous restons donc ici encore au stade de perception. Il en résulte que l'une des voies les plus intéressantes de recherche future sera l'étude de cette corrélation. Comme dans toute industrie de luxe, la vraie valeur ajoutée ne consiste pas toujours dans le volume produit, ni dans la vitesse avec laquelle le produit/service est réalisé, mais parfois dans la créativité emmagasinée dans ces résultats. Notons que le domaine de luxe est extrêmement lié aux émotions et à l'expérience fournie aux clients.

Lessons learned from developing a national NCD programme in low- and middle-income countries (Seychelles)

This paper identifies selected issues and lessons learned from the implementation of a national program of prevention and control of non-communicable diseases (NCD) during the past 20 years in the Seychelles, a small island state in the African region. As early as in 1989, population-based surveys demonstrated high levels of several cardiovascular risk factors, which prompted an organized response by the government. The early creation of a NCD unit within the Ministry of Health, coupled with cooperation with international partners, enabled incremental capacity building and coherent development of NCD programs and policy. Information campaigns and screening for hypertension and diabetes in work/public places raised awareness and rallied increasingly broad awareness and support to NCD prevention and control. A variety of interventions were organized for tobacco control and comprehensive tobacco control legislation was enacted in 2009 (including total bans on tobacco advertising and on smoking in all enclosed public and work places). A recent School Nutrition Policy prohibits the sale of soft drinks in schools. At primary health care level, guidelines were developed for the management of hypertension and diabetes (these conditions are managed in all health centers within a national health system); regular interactive education sessions were organized for groups of high risk patients ("heart health club"); and specialized "NCD nurses" were trained. Decreasing prevalence of smoking is evidence of success, but the raising "diabesity epidemic" calls for strengthened health care to high-risk patients and broader multisectoral policy to mould an environment conducive to healthy behaviors. Key components of NCD prevention and control in Seychelles include effective surveillance mechanisms supplemented by focused research; generating broad interest and consensus on the need for prevention and control of NCD; mobilizing leadership and commitment at all levels; involving local and international expertise; building on existing efforts; and seeking integrated, multi-disciplinary and multisectoral approaches.

The immune space: a concept and template for rationalizing vaccine development.

Abstract Empirical testing of candidate vaccines has led to the successful development of a number of lifesaving vaccines. The advent of new tools to manipulate antigens and new methods and vectors for vaccine delivery has led to a veritable explosion of potential vaccine designs. As a result, selection of candidate vaccines suitable for large-scale efficacy testing has become more challenging. This is especially true for diseases such as dengue, HIV, and tuberculosis where there is no validated animal model or correlate of immune protection. Establishing guidelines for the selection of vaccine candidates for advanced testing has become a necessity. A number of factors could be considered in making these decisions, including, for example, safety in animal and human studies, immune profile, protection in animal studies, production processes with product quality and stability, availability of resources, and estimated cost of goods. The "immune space template" proposed here provides a standardized approach by which the quality, level, and durability of immune responses elicited in early human trials by a candidate vaccine can be described. The immune response profile will demonstrate if and how the candidate is unique relative to other candidates, especially those that have preceded it into efficacy testing and, thus, what new information concerning potential immune correlates could be learned from an efficacy trial. A thorough characterization of immune responses should also provide insight into a developer's rationale for the vaccine's proposed mechanism of action. HIV vaccine researchers plan to include this general approach in up-selecting candidates for the next large efficacy trial. This "immune space" approach may also be applicable to other vaccine development endeavors where correlates of vaccine-induced immune protection remain unknown.