License Compliance Issues For Biopharmaceuticals: Special Challenges For Negotiations Between Companies And Non-Profit Research Institutions

Biopharmaceuticals are therapeutic products based on biotechnology. They are manufactured by or from living organisms and are the most complex of all commercial medicines to develop, manufacture and qualify for regulatory approval. In recent years biopharmaceuticals have rapidly increased in number and importance with over 400() already marketed in the U.S. and European markets alone. Many companies throughout the world are now ramping up investments in biopharmaceutical R&D and expanding their portfolios through licensing of early-stage biotechnologies from universities and other non-profit research institutions, and there is an increasing number of license agreements for biopharmaceutical product development relative to traditional small molecule drug compounds. This trend will only continue as large numbers of biosimilars and biogenerics enter the market.A primary goal of technology transfer offices associated with publicly-funded, non-profit research institutions is to establish patent protection for inventions deemed to have commercial potential and license them for product development. Such licenses help stimulate economic development and job creation, bring a stream of royalty revenue to the institution and, hopefully, advance the public good or public health by bringing new and useful products to market. In the course of applying for such licenses, a commercial development plan is usually put forth by the license applicant. This plan indicates the path the applicant expects to follow to bring the licensed invention to market. In the case of small molecule drug compounds, there exists a widely-recognized series of clinical development steps, dictated by regulatory requirements, that must be met to bring a new drug to market, such as completion of preclinical toxicology, Phase 1, 2 and 3 testing and product approvals. These steps often become the milestone/benchmark schedule incorporated into license agreements which technology transfer offices use to monitor the licensee's diligence and progress; most exclusive licenses include a commercial development plan, with penalties, financial or even revocation of the license, if the plan is not followed, e.g., the license falls too far behind.This study examines whether developmental milestone schedules based on a small molecule drug development model are useful and realistic in setting expectations for biopharmaceutical product development. We reviewed the monitoring records of all exclusive Public Health Service (PHS) commercial development license agreements for small molecule drugs or therapeutics based on biotechnology (biopharmaceuticals) executed by the National Institutes of Health (NIH) Office of Technology Transfer (OTT) between 2003 and 2009. We found that most biopharmaceutical development license agreements required amending because developmental milestones in the negotiated schedule could not be met by the licensee. This was in stark contrast with license agreements for small molecule chemical compounds which rarely needed changes to their developmental milestone schedules. As commercial development licenses for biopharmaceuticals make up the vast majority of NIH's exclusive license agreements, there is clearly a need to: 1) more closely examine how these benchmark schedules are formed, 2) try to understand the particular risk factors contributing to benchmark schedule non-compliance, and 3) devise alternatives to the current license benchmark schedule structural model. Schedules that properly weigh the most relevant risk factors such as technology classification (e.g., vaccine vs recombinant antibody vs gene therapy), likelihood of unforeseen regulatory issues, and company size/structure may help assure compliance with original license benchmark schedules. This understanding, coupled with a modified approach to the license negotiation process that makes use of a clear and comprehensive term sheet to minimize ambiguities should result in a more realistic benchmark schedule.     

Uniformity as response to soft law: Evidence from compliance and non‐compliance with the Dutch corporate governance code

The objective of the paper is to examine how firms have dealt with the trade‐off between flexibility and uncertainty that is characteristic for the decision‐making of firms in coping with self‐regulatory initiatives in general and the comply‐or‐explain principle in corporate governance in particular. Using unique data for 126 listed Dutch firms, we find that firms respond to this self‐regulatory initiative by largely complying with the code recommendation, possibly out of fear that the firm's reputation may be damaged. Furthermore, we find evidence suggesting that firms confine themselves to adopting a specific set of code recommendations and use similar arguments to explain non‐compliance. Our findings indicate uniformity in adopting the standard of good governance which is not in line with the logic of corporate governance codes and casts doubt on the effectiveness of this form of soft law. Overall, the paper's findings indicate that more restrictive (regulatory) instruments may be necessary to make firms conform to the spirit of codes.     

Validation of Ultrastructural Analysis of Mitochondrial Deposits in Cardiomyocytes as a Method of Detecting Early Acute Myocardial Infarction in Humans*

Abstract: In the present study, ultrastructural analysis of mitochondrial deposits (black dots within mitochondria) as a method for the detection of early acute myocardial infarction (AMI) was evaluated. In 24 patients with AMI and six controls, analysis was performed in the heart of infarcted patients and noninfarcted controls. In the infarction area in lactate dehydrogenase (LDH)‐diagnosed AMI, the percentage of positive mitochondria was significantly higher compared to corresponding heart tissue in control patients and compared to noninfarcted areas within these patients. Also in patients with a clinically diagnosed AMI but no LDH decoloration, a significant higher percentage of positive mitochondria was found in the left ventricle compared to controls and noninfarcted areas. In patients with AMI, an increase in mitochondria with deposits was found in the infarction area compared to controls and noninfarcted tissue within the same patient, suggesting that electron microscopical changes in mitochondria can be used for the diagnosis of AMI less than 3 h old.     

Panel on the Economic and Political Consequences of Chernobyl'

This article summarizes a discussion by a panel of leading experts on Soviet energy analyzing the consequences of the accident at the Chernobyl' nuclear plant in the Ukraine on April 26, 1986.

The near-term economic costs associated with clean-up, relocation, and compensating for losses to electricity supplies are significant but manageable. The longer-term effects will focus on likely modifications in Soviet strategies for the nuclear industry, which may shift emphasis back towards conventional fuels and conservation.

The political consequences were managed fairly well by the leadership. Consistent with Secretary Gorbachev's policy of glasnost' (openness) more information has been available on this event than was the case in previous analogous situations. Journal of Economic Literature, Classification Numbers: 027, 124, 723.     

Definitions and Typologies in Public Administration Research: The Case of Decentralization

The field of public administration knows many concepts. By focusing on one such concept, this research shows how definitions can be deceptive, and how typologies unable to capture all dimensions of a concept can blind policy makers and researchers. We concentrate our attention on decentralization. This has been a core concept in the field of public administration for decades. Definitions and typologies of decentralization have flourished. The present study gives an overview. We categorize definitions and analyse their different emphases. Typologies serve to order and compare items, but have themselves become prone to disorder. We provide a meta-analysis of typologies, exposing the wide variety of policy dimensions. Even after aggregation, typologies ignore—and definitions explicitly exclude—certain aspects of decentralization. One such issue is “silent decentralization.” It is characterized by absence of explicit decentralization reform, and thus distinguishes itself mainly by its potential origins: network changes, initiative shifts, policy emphasis developments, or resource availability alterations. Highlighting this particular aspect might well proof useful for other concepts in the field as well.     

Effects of Delinquency on Alcohol use Among Juveniles in Europe: Results from the ISRD-2 Study

The existence of a correlation between the use of alcohol and juvenile delinquency has long been acknowledged. In order to evaluate the strength and the characteristics of this association in various cultural contexts, we analysed data collected as part of the International Self-Report Delinquency Study- 2 (ISRD-2). The sample consisted of of young people (N?=?57,771) of both sexes, aged between 12 and 16 years, in 25 European countries. After estimating the prevalence of alcohol consumption among young people involved in property offences and violent offences, we assessed the degree to which these types of delinquency were associated with the use of alcohol in the 25 countries. In addition, we attempted to ascertain the influence of belonging to various types of deviant groups on alcohol use. To this end, we used a Mokken Scale Analysis. With this method, we constructed a scale of “gangness” and correlated the scores with alcohol use among juveniles. The results yielded by the present study indicate that alcohol use and delinquency are closely related with one another. In particular, we observed that alcohol consumption seems to be strongly influenced by involvement in delinquent activities. The nature and characteristics of these relationships suggest that the associations between alcohol use and delinquency are reciprocal rather than one-directional. Consequently, alcohol use constitutes a risk factor for criminal behaviour. Likewise, involvement in delinquency increase the risk of alcohol consumption and, especially, of alcohol abuse.     

Physical stature and biological living standards of girls and young women in the Netherlands,born between 1815 and 1865

This is the first study in Dutch anthropometric historiography that describes and analyzes the development of the biological standard of living of girls and young women from the perspective of female adult stature. It is shown that adult stature of women, imprisoned in the second half of the nineteenth century and born between 1815 and 1865, slightly increased, approximately 1cm. From 1850 onwards stature of women born in the cities notably increased. Development of female adult stature was compared to that of male stature; both were quite similar. No circumstantial evidence was found that girls or young women were on a disadvantage with respect to nutrition and (medical) care.     

Sibling incest: A literature review and a clinical study

Abstract

Few previous studies have explored the characteristics and dynamics of adolescent sibling incest. The objectives of this paper were twofold: first, to conduct a literature review that accounts for earlier research in the area, and secondly, to conduct a clinical study to explore differences regarding the characteristics of a group of adolescent sibling incest offenders (n=21) compared to a group of adolescent non-sibling offenders (n=24). Comparisons were made regarding variables such as family dysfunction, the offenders' prior victimization and offending behaviour. The data were derived from intake assessment files and semi-structured interviews with 45 adolescents who had sexually offended. The sibling incest offender group had grown up more often in dysfunctional families. Moreover, the results indicated that the offending behaviour in the sibling incest group was more severe. The study gives some empirical support for the possibility that sibling incest can be one sign, among others, of maltreatment during childhood.