Spatially offset Raman spectroscopy (SORS) for the analysis and detection of packaged pharmaceuticals and concealed drugs

Spatially offset Raman spectroscopy (SORS) is a powerful new technique for the non-invasive detection and identification of concealed substances and drugs. Here, we demonstrate the SORS technique in several scenarios that are relevant to customs screening, postal screening, drug detection and forensics applications. The examples include analysis of a multi-layered postal package to identify a concealed substance; identification of an antibiotic capsule inside its plastic blister pack; analysis of an envelope containing a powder; and identification of a drug dissolved in a clear solvent, contained in a non-transparent plastic bottle. As well as providing practical examples of SORS, the results highlight several considerations regarding the use of SORS in the field, including the advantages of different analysis geometries and the ability to tailor instrument parameters and optics to suit different types of packages and samples. We also discuss the features and benefits of SORS in relation to existing Raman techniques, including confocal microscopy, wide area illumination and the conventional backscattered Raman spectroscopy. The results will contribute to the recognition of SORS as a promising method for the rapid, chemically-specific analysis and detection of drugs and pharmaceuticals.

The state of the art defence : defining the Australian experience in the context of pharmaceuticals

One of the defences within Part 3-5 of the Australian Consumer Law is the state of the art, or development risk defence. This defence, although significant, has often been neglected in Australian jurisprudential analysis and has triggered at most generic academic analysis. However, with the rise of pharmaceutical and medical device litigation in Australia, it could become a vital weapon for Australian manufacturers against product liability claims. This paper will firstly review the two ways this defence could operate. It will also discuss the three types of defects which the defence could apply to. This paper aims to determine exactly when and how this defence should apply in Australia, in the context of pharmaceutical product liability claims.

A QUM partnership approach to regulating biosimilars in Australia

Despite the realisation of the potential implications from biosimilars is relatively recent, much has already been written about raising the awareness of differences between biosimilars and originating/ reference listed (innovator) pharmaceuticals. The European Medicines Agency has led the global charge in regulating biosimilars. Regardless of sufficient similarities across international regulations, differences do exist across jurisdictions. The consideration of regulating biosimilars demands a congruent approach across all stages: pre-registration (Australian copyright protection, patent, international obligations), registration (confidential information, international regulators, safety and efficacy), post-registration (Pharmaceutical Benefit Scheme, prescriber and dispenser awareness). Our National Medicines Policy could provide the necessary congruent framework and function for national and international regulation of biosimilars. The Policy concedes that pharmaceuticals will be affected by financial policies and trade considerations, international treaty obligations, industrial policies, education policies and the need for public-private partnerships.

Is Australia ready for biosimilars?

The biosimilars market is potentially the single fastest growing pharmaceutical sector with an estimated worth of US$67bn in global sales by 2020. This market generally refers to larger molecule, biological, protein-based pharmaceuticals which have lost its patent. This has stimulated the emergence of non-conventional pharmaceutical investors such as Fujifilm and Samsung as well as host countries such as Brazil, Mexico, China, India, South Korea, Turkey and Russia, which view biosimilars as a key macroeconomic driver of growth. Internationally, the European Medicines Agency has led the regulation of the quality, safety and efficacy of biosimilars; however, many countries have developed their own biosimilar regulatory frameworks. Despite the similarity of these with European guidelines, differences do exist across jurisdictions and have implications for cross-jurisdictional registration and regulation. The consideration of biosimilar regulation, however, demands attention beyond quality, safety and efficacy. The potential implications of extended patent protection, international trade and globalisation require a congruent policy approach to their regulation. Notwithstanding the fact that Australia is a relatively small pharmaceutical market and that there are only 14 biosimilar products currently approved for use, Australia’s geographical proximity to pharm-emerging countries and its trade relation with the major pharmaceutical markets have positioned Australia in a unique position to influence international development and regulation of biosimilars. Australia’s National Medicines Policy (2000) potentially provides the foundation for a partnership approach to biosimilar regulation, minimise duplication of regulatory efforts while at the same time fostering a viable pharmaceutical industry.

Is Australia positioned to take advantage of biosimilars?

Australia currently has a small generic and biosimilar industry despite having a good track record in biomedical research and a sound reputation in producing high quality but small volume biological pharmaceuticals. In recent times, Australia has made incremental changes to its regulation of biosimilars – in patent registration, in the use of commercial confidential information, and in remuneration. These improvements, together with Australia’s geographical proximity and strong trade relationship with the Asian biocluster have positioned Australia to take advantage of potential public cost savings from the increased use of biosimilars.

Single-walled carbon nanotube-based polymer monoliths for the enantioselective nano-liquid chromatographic separation of racemic pharmaceuticals

Many protocols have been used for extraction of DNA from Thraustochytrids. These generally involve the use of CTAB, phenol/chloroform and ethanol. They also feature mechanical grinding, sonication, N2 freezing or bead beating. However, the resulting chemical and physical damage to extracted DNA reduces its quality. The methods are also unsuitable for large numbers of samples. Commercially-available DNA extraction kits give better quality and yields but are expensive. Therefore, an optimized DNA extraction protocol was developed which is suitable for Thraustochytrids to both minimise expensive and time-consuming steps prior to DNA extraction and also to improve the yield. The most effective method is a combination of single bead in TissueLyser (Qiagen) and Proteinase K. Results were conclusive: both the quality and the yield of extracted DNA were higher than with any other method giving an average yield of 8.5 µg/100 mg biomass.

Does chemometrics enhance the performance of electroanalysis?

This review explores the question whether chemometrics methods enhance the performance of electroanalytical methods. Electroanalysis has long benefited from the well-established techniques such as potentiometric titrations, polarography and voltammetry, and the more novel ones such as electronic tongues and noses, which have enlarged the scope of applications. The electroanalytical methods have been improved with the application of chemometrics for simultaneous quantitative prediction of analytes or qualitative resolution of complex overlapping responses. Typical methods include partial least squares (PLS), artificial neural networks (ANNs), and multiple curve resolution methods (MCR-ALS, N-PLS and PARAFAC). This review aims to provide the practising analyst with a broad guide to electroanalytical applications supported by chemometrics. In this context, after a general consideration of the use of a number of electroanalytical techniques with the aid of chemometrics methods, several overviews follow with each one focusing on an important field of application such as food, pharmaceuticals, pesticides and the environment. The growth of chemometrics in conjunction with electronic tongue and nose sensors is highlighted, and this is followed by an overview of the use of chemometrics for the resolution of complicated profiles for qualitative identification of analytes, especially with the use of the MCR-ALS methodology. Finally, the performance of electroanalytical methods is compared with that of some spectrophotometric procedures on the basis of figures-of-merit. This showed that electroanalytical methods can perform as well as the spectrophotometric ones. PLS-1 appears to be the method of practical choice if the %relative prediction error of not, vert, similar±10% is acceptable.

Multicomponent kinetic spectrophotometric determination of pefloxacin and norfloxacin in pharmaceutical preparations and human plasma samples with the aid of chemometrics

A spectrophotometric method for the simultaneous determination of the important pharmaceuticals, pefloxacin and its structurally similar metabolite, norfloxacin, is described for the first time. The analysis is based on the monitoring of a kinetic spectrophotometric reaction of the two analytes with potassium permanganate as the oxidant. The measurement of the reaction process followed the absorbance decrease of potassium permanganate at 526 nm, and the accompanying increase of the product, potassium manganate, at 608 nm. It was essential to use multivariate calibrations to overcome severe spectral overlaps and similarities in reaction kinetics. Calibration curves for the individual analytes showed linear relationships over the concentration ranges of 1.0–11.5 mg L−1 at 526 and 608 nm for pefloxacin, and 0.15–1.8 mg L−1 at 526 and 608 nm for norfloxacin. Various multivariate calibration models were applied, at the two analytical wavelengths, for the simultaneous prediction of the two analytes including classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), radial basis function-artificial neural network (RBF-ANN) and principal component-radial basis function-artificial neural network (PC-RBF-ANN). PLS and PC-RBF-ANN calibrations with the data collected at 526 nm, were the preferred methods—%RPET not, vert, similar 5, and LODs for pefloxacin and norfloxacin of 0.36 and 0.06 mg L−1, respectively. Then, the proposed method was applied successfully for the simultaneous determination of pefloxacin and norfloxacin present in pharmaceutical and human plasma samples. The results compared well with those from the alternative analysis by HPLC.

Adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines

Adjuvant use of nutritional and herbal medicines has potential to increase the efficacy of synthetic pharmaceuticals, and perhaps also decrease their side-effects by allowing lower doses to be prescribed. We evaluated current evidence for adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines; and explored novel future areas of research. The paper also critiques current evidence for co-administration of St. John’s wort with synthetic antidepressants. We performed a systematic search of MEDLINE, CINAHL, PsycINFO, The Cochrane database, China National Knowledge Infrastructure and the Chinese Science Citation Database. Search results were supplemented by a review of reference lists and a forward search using the Web of Science. Where possible we calculated effect sizes. Encouraging evidence exists for the use of omega-3 fatty acids, SAMe, folic acid and l-tryptophan adjuvantly with antidepressants to enhance response and improve efficacy. Various nutrients also have emerging evidence as effective adjuncts with antipsychotics and mood stabilizers. While some evidence supports nutritional adjuvancy with various psychopharmacotherapies, adjuvant use of herbal therapies has not been sufficiently studied to warrant standard clinical application. This remains a promising area of research via robust, safety-conscious studies.

Ecology and bioprospecting

Bioprospecting is the exploration of biodiversity for new resources of social and commercial value. It is carried out by a wide range of established industries such as pharmaceuticals, manufacturing and agriculture as well as a wide range of comparatively new ones such as aquaculture, bioremediation, biomining, biomimetic engineering and nanotechnology. The benefits of bioprospecting have emerged from such a wide range of organisms and environments worldwide that it is not possible to predict what species or habitats will be critical to society, or industry, in the future. The benefits include an unexpected variety of products that include chemicals, genes, metabolic pathways, structures, materials and behaviours. These may provide physical blueprints or inspiration for new designs. Criticism aimed at bioprospecting has been addressed, in part, by international treaties and legal agreements aimed at stopping biopiracy and many activities are now funded by agencies that require capacity-building and economic benefits in host countries. Thus, much contemporary bioprospecting has multiple goals, including the conservation of biodiversity, the sustainable management of natural resources and economic development. Ecologists are involved in three vital ways: first, applying ecological principles to the discovery of new resources. In this context, natural history becomes a vast economic database. Second, carrying out field studies, most of them demographic, to help regulate the harvest of wild species. Third, emphasizing the profound importance of millions of mostly microscopic species to the global economy.

Built to last versus meant to end : time bounds specification in strategic alliances

This article explores an important temporal aspect of the design of strategic alliances by focusing on the issue of time bounds specification. Time bounds specification refers to a choice on behalf of prospective alliance partners at the time of alliance formation to either pre-specify the duration of an alliance to a specific time window, or to keep the alliance open-ended (Reuer & Ariňo, 2007). For instance, Das (2006) mentions the example of the alliance between Telemundo Network and Mexican Argos Comunicacion (MAC). Announced in October 2000, this alliance entailed a joint production of 1200 hours of comedy, news, drama, reality and novella programs (Das, 2006). Conditioned on the projected date of completing the 1200 hours of programs, Telemundo Network and MAC pre-specified the time bounds of the alliance ex ante. Such time-bound alliances are said to be particularly prevalent in project-based industries, like movie production, construction, telecommunications and pharmaceuticals (Schwab & Miner, 2008). In many other instances, however, firms may choose to keep their alliances open-ended, not specifying a specific time bound at the time of alliance formation. The choice between designing open-ended alliances that are “built to last”, versus time bound alliances that are “meant to end” is important. Seminal works like Axelrod (1984), Heide & Miner (1992), and Parkhe (1993) demonstrated that the choice to place temporal bounds on a collaborative venture has important implications. More specifically, collaborations that have explicit, short term time bounds (i.e. what is termed a shorter “shadow of the future”) are more likely to experience opportunism (Axelrod, 1984), are more likely to focus on the immediate present (Bakker, Boros, Kenis & Oerlemans, 2012), and are less likely to develop trust (Parkhe, 1993) than alliances for which time bounds are kept indeterminate. These factors, in turn, have been shown to have important implications for the performance of alliances (e.g. Kale, Singh & Perlmutter, 2000). Thus, there seems to be a strong incentive for organizations to form open-ended strategic alliances. And yet, Reuer & Ariňo (2007), one of few empirical studies that details the prevalence of time-bound and open-ended strategic alliances, found that about half (47%) of the alliances in their sample were time bound, the other half were open-ended. What conditions, then, determine this choice?

Plant-made vaccines for humans and animals

Summary: The concept of using plants to produce high-value pharmaceuticals such as vaccines is 20 years old this year and is only now on the brink of realisation as an established technology. The original reliance on transgenic plants has largely given way to transient expression; proofs of concept for human and animal vaccines and of efficacy for animal vaccines have been established; several plant-produced vaccines have been through Phase I clinical trials in humans and more are scheduled; regulatory requirements are more clear than ever, and more facilities exist for manufacture of clinic-grade materials. The original concept of cheap edible vaccines has given way to a realisation that formulated products are required, which may well be injectable. The technology has proven its worth as a means of cheap, easily scalable production of materials: it now needs to find its niche in competition with established technologies. The realised achievements in the field as well as promising new developments will be reviewed, such as rapid-response vaccines for emerging viruses with pandemic potential and bioterror agents. © 2010 The Author. Journal compilation © 2010 Blackwell Publishing Ltd.

High level protein expression in plants through the use of a novel autonomously replicating geminivirus shuttle vector

We constructed a novel autonomously replicating gene expression shuttle vector, with the aim of developing a system for transiently expressing proteins at levels useful for commercial production of vaccines and other proteins in plants. The vector, pRIC, is based on the mild strain of the geminivirus Bean yellow dwarf virus (BeYDV-m) and is replicationally released into plant cells from a recombinant Agrobacterium tumefaciens Ti plasmid. pRIC differs from most other geminivirus-based vectors in that the BeYDV replication-associated elements were included in cis rather than from a co-transfected plasmid, while the BeYDV capsid protein (CP) and movement protein (MP) genes were replaced by an antigen encoding transgene expression cassette derived from the non-replicating A. tumefaciens vector, pTRAc. We tested vector efficacy in Nicotiana benthamiana by comparing transient cytoplasmic expression between pRIC and pTRAc constructs encoding either enhanced green fluorescent protein (EGFP) or the subunit vaccine antigens, human papillomavirus subtype 16 (HPV-16) major CP L1 and human immunodeficiency virus subtype C p24 antigen. The pRIC constructs were amplified in planta by up to two orders of magnitude by replication, while 50% more HPV-16 L1 and three- to seven-fold more EGFP and HIV-1 p24 were expressed from pRIC than from pTRAc. Vector replication was shown to be correlated with increased protein expression. We anticipate that this new high-yielding plant expression vector will contribute towards the development of a viable plant production platform for vaccine candidates and other pharmaceuticals. © 2009 Blackwell Publishing Ltd.