Inferring the Effects of Vertical Integration from Entry Games : An Analysis of the Generic Pharmaceutical Industry

This paper introduces a novel method for examining the effects of vertical integration. The basic idea is to estimate the parameters of a vertical entry game. By carefully specifying firms' payoff equations and constructing appropriate tests, it is possible to use estimates on rival profit effects to make inferences about the existence of vertical foreclosure. I estimate the vertical entry model using data from the US generic pharmaceutical industry. The estimates indicate that vertical integration is unlikely to generate anticompetitive foreclosure effects. On the other hand, significant efficiency effects are found to arise from vertical integration. I use the parameter estimates to simulate a policy that bans vertically integrated entry. The simulation results suggest that such a ban is counterproductive; it is likely to reduce entry into smaller markets.

Lääkepatentit - suojauksen merkitys lääkkeen elinkaaren aikana

Lääkemarkkinat ovat rahassa mitattuna erittäin merkittävät markkinat. Siksi suojauksen merkityksen tarkastelu lääkkeen elinkaaren vaiheissa on mielenkiintoista. Kulutushyödyke- ja lääkemarkkinat ovat luonteeltaan erilaiset lääkemarkkinoiden voimakkaan sääntelyn takia. Myös tutkimus- ja tuotekehityskulut lääkevalmisteilla ovat poikkeuksellisen suuria. Lääkekeksintöjä suojataan patenteilla. Lääkevalmisteen suoja-ajan umpeuduttua myyntihinta putoaa yleensä merkittävästi ja hyvin nopeasti. Lääkeyritysten keinoja välttää suoja-ajan päättymisen mukanaan tuomat myyntitulojen alenemiset ovat muun muassa kokonaan uusien innovaatioiden keksiminen, olemassa olevan lääkevalmisteen ominaisuuksien parantaminen sekä oman geneerisen valmisteen tuominen markkinoille. Tutkimuksen päätarkoituksena oli selvittää, kuvata ja analysoida kolmen kansantaloudellisesti hyvin merkittävän lääkeaineen elinkaaren vaiheita Suomessa. Tutkimuksessa tarkasteltiin suojauksen merkitystä lääkkeiden myyntiin ja kulutukseen sekä kilpailevien valmisteiden osuuteen markkinoilla. Tutkitut lääkeaineet olivat simvastatiini, bisoprololi ja sitalopraami. Tutkimuksessa pohdittiin lääkkeiden suojamekanismin merkitystä ja riittävyyttä eri sidosryhmille. Tutkimuksessa selvitettiin myös patentoinnin merkitystä lääkkeiden myynnin kehittymiseen ja kilpailevien lääkevalmisteiden lukumääriin elinkaaren eri vaiheissa. Tutkittujen valmisteiden patenttien umpeutuessa geneerisiä valmisteita tulee markkinoille pian ja lukumääräisesti paljon. Rinnakkaistuontivalmisteet eivät juuri alentaneet alkuperäislääkkeiden hintoja. Geneeriset valmisteet alensivat hintoja selvästi jopa useita kymmeniä prosentteja. Hintojen romahdus oli keskimäärin noin 75 %. Hintakilpailun takia alkuperäislääkkeen elinkaaren loppupuolella tukkumyynnin arvo koko ajan pieneni kulutuksen kasvaessa tasaisesti. Lisääntynyt hintakilpailu on lisännyt viranomaisille jätettävien hintahakemusten määrää oleellisesti. Hintakilpailusta hyötyvät sekä yhteiskunta ja kuluttajat alkuperäisvalmistajien ja apteekkien kustannuksella. Yhden maan myynnillä ei käytännössä ole nykyisillä suojamekanismeilla mahdollisuutta kattaa lääkkeen kehittämiseen käytettyjä kuluja. Tähän vaaditaan kansainvälisiä markkinoita.

Generic-branded drug competition and the price for pharmaceuticals in procurement auctions

This paper studies the effects of generic drug’s entry on bidding behavior of drug suppliers in procurement auctions for pharmaceuticals, and the consequences on procurer’s price paid for drugs. Using an unique data set on procurement auctions for off-patent drugs organized by Brazilian public bodies, we surprisingly find no statistically difference between bids and prices paid for generic and branded drugs. On the other hand, some branded drug suppliers leave auctions in which there exists a supplier of generics, whereas the remaining ones lower their bidding price. These findings explain why we find that the presence of any supplier of generic drugs in a procurement auction reduces the price paid for pharmaceuticals by 7 percent. To overcome potential estimation bias due to generic’s entry endogeneity, we exploit variation in the number of days between drug’s patent expiration date and the tendering session. The two-stage estimations document the same pattern as the generalized least square estimations find. This evidence indicates that generic competition affects branded supplier’s behavior in public procurement auctions differently from other markets.

Graphene Oxide: A Carrier For Pharmaceuticals And A Scaffold For Cell Interactions.

During the last ten years, graphene oxide has been explored in many applications due to its remarkable electroconductivity, thermal properties and mobility of charge carriers, among other properties. As discussed in this review, the literature suggests that a total characterization of graphene oxide must be conducted because oxidation debris (synthesis impurities) present in the graphene oxides could act as a graphene oxide surfactant, stabilizing aqueous dispersions. It is also important to note that the structure models of graphene oxide need to be revisited because of significant implications for its chemical composition and its direct covalent functionalization. Another aspect that is discussed is the need to consider graphene oxide surface chemistry. The hemolysis assay is recommended as a reliable test for the preliminary assessment of graphene oxide toxicity, biocompatibility and cell membrane interaction. More recently, graphene oxide has been extensively explored for drug delivery applications. An important increase in research efforts in this emerging field is clearly represented by the hundreds of related publications per year, including some reviews. Many studies have been performed to explore the graphene oxide properties that enable it to deliver more than one activity simultaneously and to combine multidrug systems with photothermal therapy, indicating that graphene oxide is an attractive tool to overcome hurdles in cancer therapies. Some strategic aspects of the application of these materials in cancer treatment are also discussed. In vitro studies have indicated that graphene oxide can also promote stem cell adhesion, growth and differentiation, and this review discusses the recent and pertinent findings regarding graphene oxide as a valuable nanomaterial for stem cell research in medicine. The protein corona is a key concept in nanomedicine and nanotoxicology because it provides a biomolecular identity for nanomaterials in a biological environment. Understanding protein corona-nanomaterial interactions and their influence on cellular responses is a challenging task at the nanobiointerface. New aspects and developments in this area are discussed.

Development of a Multicommutated Flow System with Chemiluminometric Detection for Quantification of Gentamicin in Pharmaceuticals

A new flow procedure based on multicommutation with chemiluminometric detection was developed to quantify gentamicin sulphate in pharmaceutical formulations. This approach is based on gentamicin's ability to inhibit the chemiluminometric reaction between luminol and hypochlorite in alkaline medium, causing a decrease in the analytical signal. The inhibition of the analytical signal is proportional to the concentration of gentamicin sulphate, within a linear range of 1 to 4 mu g mL(-1) with a coefficient variation <3%. A sample throughput of 55 samples h(-1) was obtained. The developed method is sensitive, simple, with low reagent consumption, reproducible, and inexpensive, and when applied to the analysis of pharmaceutical formulations (eye drops and injections) it gave results with RSD between 1.10 and 4.40%.

POPREP: a generic report for population management

Genetic variation provides a basis upon which populations can be genetically improved. Management of animal genetic resources in order to minimize loss of genetic diversity both within and across breeds has recently received attention at different levels, e. g., breed, national and international levels. A major need for sustainable improvement and conservation programs is accurate estimates of population parameters, such as rate of inbreeding and effective population size. A software system (POPREP) is presented that automatically generates a typeset report. Key parameters for population management, such as age structure, generation interval, variance in family size, rate of inbreeding, and effective population size form the core part of this report. The report includes a default text that describes definition, computation and meaning of the various parameters. The report is summarized in two pdf files, named Population Structure and Pedigree Analysis Reports. In addition, results (e. g., individual inbreeding coefficients, rate of inbreeding and effective population size) are stored in comma-separate-values files that are available for further processing. Pedigree data from eight livestock breeds from different species and countries were used to describe the potential of POPREP and to highlight areas for further research.

ON GENERIC ROTATIONLESS DIFFEOMORPHISMS OF THE ANNULUS

Let f be a C(r)-diffeomorphism of the closed annulus A that preserves the orientation, the boundary components and the Lebesgue measure. Suppose that f has a lift (f) over tilde to the infinite strip (A) over tilde which has zero Lebesgue measure rotation number. If the rotation number of f restricted to both boundary components of (f) over tilde is positive, then for such a generic f (r >= 16), zero is an interior point of its rotation set. This is a partial solution to a conjecture of P. Boyland.

Liquid-liquid microextraction without phase separation in a multicommuted flow system for diltiazem determination in pharmaceuticals

Liquid-liquid microextraction without phase segmentation was implemented in a multicommuted flow system for determination of the anti-hypertensive diltiazem. The procedure was based on ion pair formation between the drug and the dye bromothymol blue at pH 3.5. The detection was performed without phase separation in a glass tube coupled to a fiber-optics spectrophotometer. The total volume of chloroform was reduced to 50 mu L in comparison with 10 mL consumed in batch. A linear response was observed between 9 and 120 mu mol L(-1), with a detection limit of 0.9 mu mol L(-1) (99.7% confidence level). The coefficient of variation (n = 10), sampling rate and extraction efficiency were estimated as 0.6%, 78 determinations per hour and 61%, respectively. About 30 mu g of bromothymol blue was consumed and the waste volume was 380 mu L per determination. The results for pharmaceutical samples agreed with those obtained by the reference procedure at the 95% confidence level. (C) 2011 Elsevier B.V. All rights reserved.

Generic hyperbolicity of stationary solutions for a reaction-diffusion system

In this paper, we study the generic hyperbolicity of equilibria of a reaction-diffusion system with respect to nonlinear terms in the set of C(2)-functions equipped with the Whitney Topology. To accomplish this, we combine Baire`s Lemma and the usual Transversality Theorem. (C) 2010 Elsevier Ltd. All rights reserved.

One-time signature scheme from syndrome decoding over generic error-correcting codes

We describe a one-time signature scheme based on the hardness of the syndrome decoding problem, and prove it secure in the random oracle model. Our proposal can be instantiated on general linear error correcting codes, rather than restricted families like alternant codes for which a decoding trapdoor is known to exist. (C) 2010 Elsevier Inc. All rights reserved,

An Array Recursive Least-Squares Algorithm With Generic Nonfading Regularization Matrix

We present a novel array RLS algorithm with forgetting factor that circumvents the problem of fading regularization, inherent to the standard exponentially-weighted RLS, by allowing for time-varying regularization matrices with generic structure. Simulations in finite precision show the algorithm`s superiority as compared to alternative algorithms in the context of adaptive beamforming.

Generic drugs in Brazil: historical overview and legislation

The Brazilian generic drugs policy was implemented in 1999 with the aim of stimulating competition in the market, improve the quality of drugs and improve the access of the population to drug treatment. The process of implementing this policy allowed the introduction and discussion of concepts that had never before been used in the context of drug registration in Brazil: bioavailability, bioequivalence, pharmaceutical equivalence, generic drugs, biopharmaceutical classification system, biowaiver. The present article provides definitions for these concepts in the context of Brazilian legislation as well as a historical and chronological description of the implementation of the generic drugs policy in Brazil, including a list of current generic drug legislation. This article contributes to the understanding of the Brazilian generic drugs policy and facilitates the search for information concerning the legal requirements for registration of drugs in Brazil.

Determination of Vecuronium Bromide in Pharmaceuticals: Development, Validation and Comparative Study of HPLC and CZE Analytical Methods

Vecuronium bromide is a neuromuscular blocking agent used for anesthesia to induce skeletal muscle relaxation. HPLC and CZE analytical methods were developed and validated for the quantitative determination of vecuronium bromide. The HPLC method was achieved on an amino column (Luna 150 x 4.6 mm, 5 mu m) using UV detection at 205 nm. The mobile phase was composed of acetonitrile:water containing 25.0 mmol L(-1) of sodium phosphate monobasic (50:50 v/v), pH 4.6 and flow rate of 1.0 mL min(-1). The CZE method was achieved on an uncoated fused-silica capillary (40.0 cm total length, 31.5 cm effective length and 50 mu m i.d.) using indirect UV detection at 230 nm. The electrolyte comprised 1.0 mmol L(-1) of quinine sulfate dihydrate at pH 3.3 and 8.0% of acetonitrile. The results were used to compare both techniques. No significant differences were observed (p > 0.05).

Development and Validation of Stability-Indicating HPLC Methods for Quantitative Determination of Pravastatin, Fluvastatin, Atorvastatin, and Rosuvastatin in Pharmaceuticals

High-performance liquid-chromatographic (HPLC) methods were validated for determination of pravastatin sodium (PS), fluvastatin sodium (FVS), atorvastatin calcium (ATC), and rosuvastatin calcium (RC) in pharmaceuticals. Two stability-indicating HPLC methods were developed with a small change (10%) in the composition of the organic modifier in the mobile phase. The HPLC method for each statin was validated using isocratic elution. An RP-18 column was used with mobile phases consisting of methanol-water (60:40, v/v, for PS and RC and 70:30, v/v, for FVS and ATC). The pH of each mobile phase was adjusted to 3.0 with orthophosphoric acid, and the flow rate was 1.0mL/min. Calibration plots showed correlation coefficients (r)0.999, which were calculated by the least square method. The detection limit (DL) and quantitation limit (QL) were 1.22 and 3.08 mu g/mL for PS, 2.02 and 6.12 mu g/mL for FVS, 0.44 and 1.34 mu g/mL for ATC, and 1.55 and 4.70 mu g/mL for RC. Intraday and interday relative standard deviations (RSDs) were 2.0%. The methods were applied successfully for quantitative determination of statins in pharmaceuticals.

Generic delimitation and phylogenetic uncertainty: An example from a group that has undergone an explosive radiation

Phylogenetic trees can provide a stable basis for a higher-level classification of organisms that reflects evolutionary relationships. However, some lineages have a complex evolutionary history that involves explosive radiation or hybridisation. Such histories have become increasingly apparent with the use of DNA sequence data for phylogeny estimation and explain, in part, past difficulties in producing stable morphology-based classifications for some groups. We illustrate this situation by using the example of tribe Mirbelieae (Fabaceae), whose generic classification has been fraught for decades. In particular, we discuss a recent proposal to combine 19 of the 25 Mirbelieae genera into a single genus, Pultenaea sens. lat., and how we might find stable and consistent ways to squeeze something as complex as life into little boxes for our own convenience. © CSIRO.