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.     

Chemical enhancement of footwear impressions in blood on fabric – Part 1: Protein stains

A range of protein stains were utilised for the enhancement of footwear impressions on a variety of fabric types of different colours with blood as a contaminant. A semi-automated stamping device was used to deliver test impressions at a set force to minimise the variability between impressions; multiple impressions were produced and enhanced by each reagent to determine the repeatability of the enhancement. Results indicated that while most protein stains used in this study successfully enhanced impressions in blood on light coloured fabrics, background staining caused interference on natural fabrics. Enhancement on dark coloured fabrics was only achieved using fluorescent protein stains, as non-fluorescent protein stains provided poor contrast.A further comparison was performed with commercially available protein staining solutions and solutions prepared within the laboratory from the appropriate chemicals. Both solutions performed equally well, though it is recommended to use freshly prepared solutions whenever possible.     

Investigation of a typology of alcohol‐related violence defined by ultimate goals

Purpose. Alcohol‐related violence is a serious problem and treatments for high‐risk individuals need to be developed. Classification helps to route people into appropriate treatments. Drawing on animal research, we define alcohol‐related violence in relation to ultimate goals. We propose three types of violence: (1) violence in the pursuit of material goals, (2) violence in pursuit of social dominance goals, and (3) violence as defence in response to threat. The aim is to explore factors that we expect to relate to this tripartite typology, with the aim of providing a preliminary validation. Method. Participants were 149 young male prisoners who had committed an offence of violence that was alcohol related. Semi‐structured interviews elicited information about the offence that enabled classification into one of the three types. Differences between groups were examined at the event level – level of violence during the offence and alcohol consumption before the offence – and at group level – trait aggression, trait anxiety, anger control, and alcohol–aggression outcome expectancies. Results. No differences were found in levels of violence or alcohol consumption. Those whose violence was in the pursuit of material goals were high on trait aggression, trait anger, trait anxiety, and anger suppression. Those who used violence in the pursuit of social dominance showed high trait aggression and trait anger. Those whose violence was a defence in response to threat showed lower trait aggression and trait anger. Conclusion. The findings are discussed in relation to differential group profiles and treatment needs.     

Analysis of Pigmented Inkjet Printer Inks and Printed Documents by Laser Desorption/Mass Spectrometry*,†

Abstract: Anyone with a computer, scanner, and color printer has the capability for creating documents such as identification cards, passports, and counterfeit currency. Laser desorption mass spectrometry (LDMS) has been demonstrated as a powerful tool for colorant analysis. Inkjet printers are now moving largely toward the use of pigments as colorants; their insolubility makes analysis by simpler methods such as thin‐layer chromatography no longer an option. Recent developments in pigmented inkjet printer inks, such as gloss optimizers that coat pigment particles, may prohibit colorant analysis by LDMS. We demonstrate here that pigments used in inks from two Epson printers can be detected and analyzed by LDMS. Also, LDMS spectra of various colors created using a 4‐cartridge (cyan/magenta/yellow/black, CMYK) inkset are evaluated, to begin to develop an approach for unraveling LDMS data from real samples, to determine the number of inks used by a printer, and the chemical composition of the colorants.     

Sex offender residence restriction laws: Parental perceptions and public policy

Despite a steady decline in sex crime over the past twenty years, new laws, such as residence restrictions, targeting such crime have proliferated. Some scholars have argued that public concern about sexual offending against young children has served as a catalyst for the emergence of these laws. Few studies, however, have empirically tested this claim. To address this gap and to contribute to scholarship on public opinion about crime and justice, this research tests a central implication flowing from prior work—namely, the notion that people with children will be more likely to endorse increased restrictions on where sex offenders can live. Analyses of public opinion data from a 2006 poll of Florida residents suggest that parents are indeed significantly more likely to support such restrictions. Implications of the study for research and policy are discussed.     

Chemical enhancement of footwear impressions in blood deposited on fabric — Evaluating the use of alginate casting materials followed by chemical enhancement

Most footwear marks made in blood on a surface such as fabric tend to be enhanced in situ rather than physically recovered using a lifting technique prior to enhancement. This work reports on the use of an alginate material to recover the impressed footwear marks made in blood and deposited on a range of fabric types and colours. The lifted marks were then enhanced using acid black 1 and leuco crystal violet with excellent results.This presents a new method for the lifting and recovery of blood impressions in situ from crime scene followed by subsequent mark enhancement of the lifted impression.     

The effect of mark enhancement techniques on the presumptive and confirmatory tests for blood

An investigation into the effects of physical and chemical enhancement on subsequent presumptive and confirmatory tests for human blood is presented. Human blood was deposited onto porous (white 80 gsm paper and brown envelope) and non-porous (tile and linoleum) substrates in a depletion series (30 depletions on non-porous and 20 on porous) and subjected to three ageing periods; 1, 7 and 28?days. A number of enhancement techniques were tested [fluorescence, black magnetic powder (BMP), iron-oxide black powder suspension (PS), cyanoacrylate (CA) fuming, acid violet 17 (AV17), acid yellow 7 (AY7), ninhydrin, DFO and Bluestar Forensic Magnum (BFM) luminol] to evaluate their potential effects on subsequent presumptive and confirmatory tests. AV17 and Bluestar provided the best enhancement and fully enhanced all depletions in the series. The sensitivity of the Kastle-Meyer (KM) (presumptive), Takayama and RSID-Blood tests (confirmatory) was initially investigated to determine the range of detectable depletions. The KM test detected all depletions, whereas the Takayama test detected up to depletion 6 and RSID-Blood detected up to depletion 20 (paper), 10 (envelope), 15 (tile) and 9 (lino). The abilities of these tests to detect blood after enhancement were then observed.A number of techniques resulted in little to no effect on any of the blood tests, whereas adverse effects were observed for others. Ninhydrin and CA fuming caused weak but instantaneous positive KM results whereas methanol-based AV17 and AY7 delayed the reaction by as much as 1?min. The Takayama test was not very sensitive, therefore, its performance was easily affected by enhancement and negative results were often observed. RSID-Blood tests were largely unaffected by chemical enhancement although a drop in positive results was observed for some of the techniques when compared to positive controls.Using a standard procedure for DNA extraction, all the tested blood samples (before and after enhancement) gave a detectable quantity of DNA and were successfully profiled. Out of the 45 samples processed for DNA profiling, 41 gave full profiles, while the remaining showed allele drop out in one or two loci.     

Older Youth in Extended Out-of-home Care

The purpose of this study is to examine the permanency experiences of older youth, age 18–21 in out-of-home placements and placement characteristics that influence age of exit from child welfare. Findings suggest a difference between age groups with more 18-year old youth exiting to emancipation than youth who exit at age 21. A higher number of spells in care and a higher number of placement changes during the last spell were associated with exit to emancipation. Additional study findings suggests that youth who leave care before the age of 21 may be more vulnerable than youth who stay through age 21. Implications for practice are discussed.