Substantial Equivalence Research Articles

Cognitive Performance following Carotid Endarterectomy or Stenting in Asymptomatic Patients with Severe ICA Stenosis

Background. Endarterectomy (CEA) or stenting (CAS) of a stenotic carotid artery is currently undertaken to reduce stroke risk. In addition removal of the arterial narrowing has been hypothesized to improve cerebral hemodynamics and provide benefits in cognitive functions, by supposedly resolving a “hypoperfusion” condition. Methods. In this study we sought to test whether resolution of a carotid stenosis is followed by measurable changes in cognitive functions in 22 subjects with “asymptomatic” stenosis. Results. A main finding of the study was the statistically significant pre-post difference observed in the performance of phonological verbal fluency and Rey's 15-word immediate recall. Remarkably, there was a significant interaction between phonological verbal fluency performance and side of the carotid intervention, as the improvement in the verbal performance, a typical “lateralized” skill, was associated with resolution of the left carotid stenosis. Conclusion. The results reflect a substantial equivalence of the overall performance at the before- and after- CEA or CAS tests. In two domains, however, the postintervention performance resulted improved. The findings support the hypothesis that recanalization of a stenotic carotid could improve brain functions by resolving hypothetical “hypoperfusion” states, associated with the narrowing of the vessels.

Assessment of Genetically Modified Soybean in Relation to Natural Variation in the Soybean Seed Metabolome

Genetically modified (GM) crops currently constitute a significant and growing part of agriculture. An important aspect of GM crop adoption is to demonstrate safety and equivalence with respect to conventional crops. Untargeted metabolomics has the ability to profile diverse classes of metabolites and thus could be an adjunct for GM crop substantial equivalence assessment. To account for environmental effects and introgression of GM traits into diverse genetic backgrounds, we propose that the assessment for GM crop metabolic composition should be understood within the context of the natural variation for the crop. Using a non-targeted metabolomics platform, we profiled 169 metabolites and established their dynamic ranges from the seeds of 49 conventional soybean lines representing the current commercial genetic diversity. We further demonstrated that the metabolome of a GM line had no significant deviation from natural variation within the soybean metabolome, with the exception of changes in the targeted engineered pathway.

Do transgenesis and marker-assisted backcross breeding produce substantially equivalent plants? - A comparative study of transgenic and backcross rice carrying bacterial blight resistant gene Xa21

BackgroundThe potential impact of genetically modified (GM) plants on human health has attracted much attention worldwide, and the issue remains controversial. This is in sharp contrast to the broad acceptance of plants produced by breeding through Marker Assisted Backcrossing (MAB).ResultsFocusing on transcriptome variation and perturbation to signaling pathways, we assessed the molecular and biological aspects of substantial equivalence, a general principle for food safety endorsed by the Food and Agricultural Organization and the World Health Organization, between a transgenic crop and a plant from MAB breeding. We compared a transgenic rice line (DXT) and a MAB rice line (DXB), both of which contain the gene Xa21 providing resistance to bacterial leaf blight. By using Next-Generation sequencing data of DXT, DXB and their parental line (D62B), we compared the transcriptome variation of DXT and DXB. Remarkably, DXT had 43% fewer differentially expressed genes (DEGs) than DXB. The genes exclusively expressed in DXT and in DXB have pathogen and stress defense functions. Functional categories of DEGs in DXT were comparable to that in DXB, and seven of the eleven pathways significantly affected by transgenesis were also perturbed by MAB breeding.ConclusionsThese results indicated that the transgenic rice and rice from MAB breeding are substantial equivalent at the transcriptome level, and paved a way for further study of transgenic rice, e.g., understanding the chemical and nutritional properties of the DEGs identified in the current study.

The Pharmaceutical Year That Was, 2013

Last year ended with Europe wallowing in its Euro-crisis, the United States (US) Congress wrangling over its budget (eventually unresolved, leading to a legislative ‘sequestration’), the promise of a Pharmacovigilance Risk Assessment Committee (PRAC) within the European Medicines Agency (EMA), a European initiative towards publication of clinical trials data, and an unremarkable number of truly new product approvals on both sides of the Atlantic [1]. Much of that carried on this year, while the economic situation continues to stagger and stutter. As mentioned last year, 2013 has seen the PRAC getting into its stride at the EMA [2]. The PRAC advises the Committee for Medicinal Products for Human Use (CHMP), the Co-ordination Group for Mutual Recognition and Decentralised Procedures-Human (CMDh), the EMA secretariat and the European Commission on all aspects of pharmacovigilance and risk management. The PRAC is comprised of: a Chairperson, a member (or alternate) from every member state, six members ex officio and technically qualified from the European Commission (EC), and another two EC members (with alternates) for public calls of interest for healthcare professionals and patients. They all have 3 year terms, renewed easily the first time, and after competition thereafter. The PRAC aims to review all Product Licence Applications (PLAs) from the point of view of proposed pharmacovigilance and risk management activities. These are all Module 1 components of the electronic Clinical Trials Dossier (eCTD), and thus are restricted to the European marketplaces. In addition, the PRAC will be reviewing Periodic Safety Update Reports (PSURs; these now require formal risk-benefit assessments), Post-Assessment Safety Studies (PASS), as well as doing general signal detection and making ‘for cause’ pharmacovigilance inspection decisions. For licensed products, these responsibilities differ little between centralised process and other approvals. Lastly, the PRAC is empowered to take urgent action on its own initiative in cases of serious threats to the public health. Flexing its muscles, in January 2013 PRAC recommended the withdrawal of three products from the entire EU, and most recently (September 2013) is recommending against short-acting beta-agonists in pregnancy [3]. A slang has developed in the United Kingdom: purity, efficacy and safety come first, and then the National Institute for Health and Care Excellence (NICE) has become known as a ‘fourth hurdle’. The PRAC might yet become known as the fifth hurdle. A new distraction this year is that the US Food and Drug Administration (FDA) doesn’t quite know whether it can regulate ‘electronic cigarettes’ [4]. In ordinary parlance, these breath-actuated inhalational devices deliver vaporized nicotine, and are shaped like a cigarette. The amusing angle of this regulatory uncertainty is that the FDA is, however, now attempting to regulate tobacco itself. The Family Smoking Prevention and Tobacco Control Act (2009) gave the FDA the authority to regulate products containing tobacco. A regulatory pathway for tobacco products has been contrived, based upon the notion of ‘‘substantial equivalence’’. On this basis, there have been two new product approvals and at least four rejections [5]. The two approvals so far (‘‘Newport Non-menthol Gold Box 100s’’ and ‘‘Newport Non-menthol Gold Box’’) had A. W. Fox is the Consulting Editor for Pharmaceutical Medicine.

Application of ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) metabolomic fingerprinting to characterise GM and conventional maize varieties

The feasibility of metabolomic fingerprinting approach based on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-QTOFMS) was studied to assess its ability to discriminate between maize varieties, and to show the associations between them on the metabolomic level. The non-targeted metabolomic analysis was applied to assess the variability within two varieties grown under different environmental conditions and to characterise the association within a sample set comprising both conventional and transgenic (MON-ØØ81Ø-6) maize varieties cultivated under the same environmental conditions (locality). Typical metabolomic fingerprints were established for individual plants. The plants representing two varieties formed well separated clusters. Metabolomic fingerprints of the second sample set enabled their unambiguous discrimination. The differences in metabolomic fingerprints between maize varieties were identified and documented by grouping in PCA and/or CA. The results indicate a similar genetic basis of transgenic maize varieties as they descend from a MON 810 event. The results explicitly showed that the variability of the metabolites in MON 810 did not exceed the ranges measured within the conventional varieties, thus supporting the concept of substantial equivalence.  

Effect of calf death loss on cloned cattle herd derived from somatic cell nuclear transfer: Clones with congenital defects would be removed by the death loss

To increase public understanding on cloned cattle derived from somatic cell nuclear transfer (SCNT), the present review describes the effect of calf death loss on an SCNT cattle herd. The incidence of death loss in SCNT cattle surviving more than 200 days reached the same level as that in conventionally bred cattle. This process could be considered as removal of SCNT cattle with congenital defects caused by calf death loss. As a result of comparative studies of SCNT cattle and conventionally bred cattle, the substantial equivalences in animal health status, milk and meat productive performance have been confirmed. Both sexes of SCNT cattle surviving to adulthood were fertile and their reproductive performance, including efficiency of progeny production, was the same as that in conventionally bred cattle. The presence of substantial equivalence between their progeny and conventionally bred cattle also existed. Despite these scientific findings, the commercial use of food products derived from SCNT cattle and their progeny has not been allowed by governments for reasons including the lack of public acceptance of these products and the low efficiency of animal SCNT. To overcome this situation, communication of the low risk of SCNT technology and research to improve SCNT efficiency are required.

The optimisation and application of a metabolite profiling procedure for the metabolic phenotyping of Bacillus species

The rapid advances in sequencing technologies over the last decade have enabled routine sequencing of microbial genomes. Despite notable achievements, metabolomics/metabolite profiling has not progressed with the same rapidity, which in part is due to the intrinsic complex chemical nature of the metabolome. However, well characterised metabolomes are essential if a comprehensive understanding of biological function and biotechnological applications are to be revealed and implemented. In the present study a hyphenated MS metabolite profiling procedure has been developed, predominantly for Bacillus species. The approach has been systematic in its development, delivering optimised procedures for the quenching of bacterial metabolism, extraction of metabolites, the separation and detection of components as well as data analysis, integration and visualisation workflows. Collectively, the procedure has enabled the detection of 27 % of the predicted Bacillus subtilis metabolome in the industrial HU36 strain. The analytical platform developed has been used to assess the chemotype of commercially used probiotic Bacillus strains, including a novel pigmented Bacillus strain HU36 that has potential either as a probiotic or source of antioxidants. The results are discussed in a biochemical context, revealing: (i), specific metabolic networks associated with pigment biosynthesis in HU36 and (ii), biotechnological applications through the demonstration of substantial equivalence.

Tobacco company efforts to influence the Food and Drug Administration-commissioned Institute of Medicine report clearing the smoke: an analysis of documents released through litigation.

Spurred by the creation of potential modified risk tobacco products, the US Food and Drug Administration (FDA) commissioned the Institute of Medicine (IOM) to assess the science base for tobacco "harm reduction," leading to the 2001 IOM report Clearing the Smoke. The objective of this study was to determine how the tobacco industry organized to try to influence the IOM committee that prepared the report. We analyzed previously secret tobacco industry documents in the University of California, San Francisco Legacy Tobacco Documents Library, and IOM public access files. (A limitation of this method includes the fact that the tobacco companies have withheld some possibly relevant documents.) Tobacco companies considered the IOM report to have high-stakes regulatory implications. They developed and implemented strategies with consulting and legal firms to access the IOM proceedings. When the IOM study staff invited the companies to provide information on exposure and disease markers, clinical trial design for safety and efficacy, and implications for initiation and cessation, tobacco company lawyers, consultants, and in-house regulatory staff shaped presentations from company scientists. Although the available evidence does not permit drawing cause-and-effect conclusions, and the IOM may have come to the same conclusions without the influence of the tobacco industry, the companies were pleased with the final report, particularly the recommendations for a tiered claims system (with separate tiers for exposure and risk, which they believed would ease the process of qualifying for a claim) and license to sell products comparable to existing conventional cigarettes ("substantial equivalence") without prior regulatory approval. Some principles from the IOM report, including elements of the substantial equivalence recommendation, appear in the 2009 Family Smoking Prevention and Tobacco Control Act. Tobacco companies strategically interacted with the IOM to win several favored scientific and regulatory recommendations.

Abstract 343: Cardiovascular Device Recalls in 2012

Background: For the fiscal year 2012, the Food and Drug Administration (FDA) classified 1,190 medical device recalls. Of these, 132 (11%) were for cardiovascular (CV) devices. Class I recalls, representing the greatest health risk, result from finding a reasonable probability that device use will cause serious adverse health consequences or death. FDA approves or clears devices for the US market through either the Pre-Market Approval (PMA) pathway or, more commonly, through a substantial equivalence determination known as 510(k) clearance. Methods: Recalled devices were categorized into nine broad CV device groups. Recall data was included on class, marketing path, and the number of distributed devices. Results: PMA devices represented 14% of the CV device recalls and 510(k) devices represented 82%. There were four Class I recalls -- two PMA and two 510(k). Circulatory support and surgical (CS) was the device group with highest number of recalls (43, 33%). Physiologic monitors (PM) had the second highest (28, 21%) and Vascular catheters (VC) the third highest (17, 13%). The remaining recalls (44, 33%) were included in these device groups: Implanted pacemakers, defibrillators and leads (ID), Non-implantable EP devices (EP), External defibrillators (ED), Vascular access (VA), Stents/grafts/valves (SG), and Others (OT). Over 16 million distributed devices were recalled in the year, with the highest average number per recall seen in the CS group and the lowest in the EP group. Class I recalls varied based both on market pathway and the number of distributed devices. Thoratec’s Heartmate II - PMA - 3,852 St Jude Medical’s Riata - PMA -128,000 Draeger’s Infinity System - 510(k) -1 Cardiac Science Powerheart - 510(k) -12,782 Conclusion: Most of the CV recalls in 2012 were 510(k) devices that were in the CS, PM, or VC device group. Failures in medical devices pose risk to the public and FDA strives to mitigate risk to the public health through the promotion of safe and effective devices, and the removal from the US market of those determined to be unsafe or ineffective.

Natural Variation in Grain Composition of Wheat and Related Cereals

The wheat grain comprises three groups of major components, starch, protein, and cell wall polysaccharides (dietary fiber), and a range of minor components that may confer benefits to human health. Detailed analyses of dietary fiber and other bioactive components were carried out under the EU FP6 HEALTHGRAIN program on 150 bread wheat lines grown on a single site, 50 lines of other wheat species and other cereals grown on the same site, and 23-26 bread wheat lines grown in six environments. Principal component analysis allowed the 150 bread wheat lines to be classified on the basis of differences in their contents of bioactive components and wheat species (bread, durum, spelt, emmer, and einkorn wheats) to be clearly separated from related cereals (barley, rye, and oats). Such multivariate analyses could be used to define substantial equivalence when novel (including transgenic) cereals are considered.

Safety assessment of the post-harvest treatment of button mushrooms (Agaricus bisporus) using ultraviolet light

Wild mushrooms are an excellent source of vitamin D. The presence of vitamin D in mushrooms is attributed to sunlight exposure, which catalyzes the conversion of fungal ergosterol to vitamin D2 via a series of photochemical/thermal reactions. Mushroom growers now incorporate UV light treatments during processing to produce mushrooms with levels of vitamin D that compare to those in wild mushrooms. Presented herein is a comprehensive review of information relevant to the safety of introducing vitamin D mushrooms, produced using UV light technologies, to the food supply. Historical reference to the use of UV light for production of vitamin D is discussed, and studies evaluating the nutritional value and safety of vitamin D mushrooms are reviewed. Traditional safety evaluation practices for food additives are not applicable to whole foods; therefore, the application of substantial equivalence and history-of-safe-use is presented. It was demonstrated that vitamin D in mushrooms, produced using UV light technologies, are equivalent to vitamin D in mushrooms exposed to sunlight, and that UV light has a long-history of safe use for production of vitamin D in food. Vitamin D mushrooms produced using UV light technologies were therefore considered safe and suitable for introduction to the marketplace.

Justice Kagan's Presidential Administration and Bioengeneered Foods: Making the Case for Congressional Guidance as a Check to Presidential Policy Setting

Imagine a system of government where the President is accorded a great deal of deference in matters of legislation. A combination of these two elements - “president and legislation” - immediately gives us cause for pause, considering our deliberate tripartite system of checks and balances. Imagine also the advancement of a completely new technology, like cloning. As industry works to perfect the new technology, the question inevitably becomes who is best placed to regulate this industry. As we explore our options, should one of the options be for the Office of the President to set regulations? These are the questions that areas, such as biotechnology, faces or will face. As biotechnology has evolved, the public has become increasingly concerned that processes for approving bio-tech foods are not transparent. The power to approve biotech foods is delegated to administrative agencies, which receive considerable deference from the courts. Added to this judicial deference is the documented involvement of the President's office in setting policy in this area. Justice Kagan labeled Presidential involvement in administrative agencies' decisions as “Presidential Administration.” “Presidential Administration,” according to Justice Kagan, refers to the President directly setting policies by providing directives to administrative agencies. Tracing this practice from President Reagan to President Clinton, Justice Kagan explains that presidents have regularly used the administrative process to set policies as well as take ownership of administrative policies. This Article explores the issues inherent in presidential control of administrative regulatory processes related to genetically modified foods. In that context, especially, congressional silence is unsatisfactory because it unevenly shifts the balance of power to influential interest groups and to the President's office. This awkward balancing has been made all the more evident by Monsanto Co. v. Geertson Seeds Farms, the Supreme Court's first decision regarding genetically altered crops. Monsanto and other cases illustrate the legal and ethical complexities of balancing of the public's interest with that of biotech companies and monitoring federal agencies. Thus far, the balancing of interests has erred in favor of biotech companies. The standards applied by the courts for evaluating biotech foods are insufficient and vague. What is more, the procedures in place for overseeing and regulating biotech products are needlessly complex and inefficient. This Article points out deficiencies in the regulation of bioengineered foods and demonstrates that regulating agencies have sponsored a policy that fails to concentrate on the potential harm to human health; rather, the policy focuses on market aggrandizement. The “substantial equivalence” doctrine applied by regulating agencies when evaluating bioengineered products is under particular scrutiny in this Article. Under the substantial equivalence test, bioengineered products have been assumed to be safe by virtue of the initial presidential command, construing bioengineered foods as equivalent to natural foods. This standard, however, is a false equivalence since bioengineered products contain foreign and unknown agents. Continued practice of this type of Presidential control, without consistent input from experts, could lead to greater harm to the population. Considering the high stakes, a more precautionary standard is warranted.Accordingly, this article is divided into the following parts: Part I discusses the application of the Presidential ad-ministration doctrine to biotechnology; it identifies the flaws with that particular approach and explains why a better approach is needed. Part II outlines the sources of laws and the agencies responsible for regulating genetically altered foods. Part III discusses the Supreme Court's first ruling regarding genetically modified crops in Monsanto Co. v. Geertson Seeds Farms as an example of the conflicts congressional silence creates. Part IV discusses problems with the current judicial standard of review applied to agencies' decisions. Part V explores the detrimental impact of biotechnology on poor farmers, both in the United States and abroad. Part VI proposes better paradigms for dealing with bioengineered foods and calls for specific congressional guidance in that area. Finally, Part VII presents the European approach as a potential model for grassroots lobbying.

Programme Outcomes Assessment Models in Engineering Faculties

Malaysia is currently a member of Washington Accord which recognises substantial equivalence in the accreditation of qualifications for engineering programme among member countries. Under this agreement, assessment of programme outcomes (PO) is now mandatory for all engineering programmes in Malaysia. However, the typical PO assessment model practised by many engineering programmes resulted in vague assessment methods and as a result failed to show concrete continual quality improvement (CQI). The major issues with the model are with regard to the aspect of unclear performance criteria, grades as measurement indicators, lack of evidence, detached used of indirect methods and unclear CQI. A new model which is more holistic and based on looking at each PO as a major thrust with specific performance criteria is proposed. It is expected that the new model will allow one to objectively evaluate whether the students have achieved the criteria, subsequently facilitating CQI implementation within the programme and produced quality engineering graduates.

Effects of Genetics and Environment on the Metabolome of Commercial Maize Hybrids: A Multisite Study

This study was designed to elucidate the biological variation in expression of many metabolites due to environment, genotype, or both, and to investigate the potential utility of metabolomics to supplement compositional analysis for substantial equivalence assessments of genetically modified (GM) crops. A total of 654 grain and 695 forage samples from 50 genetically diverse non-GM DuPont Pioneer maize hybrids grown at six locations in the U.S. and Canada were analyzed by coupled gas chromatography time-of-flight-mass spectrometry (GC/TOF-MS). A total of 156 and 185 metabolites were measured in grain and forage samples, respectively. Univariate and multivariate statistical analyses were employed extensively to compare and correlate the metabolite profiles. We show that the environment had far more impact on the forage metabolome compared to the grain metabolome, and the environment affected up to 50% of the metabolites compared to less than 2% by the genetic background. The findings from this study demonstrate that the combination of GC/TOF-MS metabolomics and comprehensive multivariate statistical analysis is a powerful approach to identify the sources of natural variation contributed by the environment and genotype.

Safety evaluation of some wild plants in the New Nordic Diet

One of the dietary components in the New Nordic Diet, is plants from the wild countryside. However, these may have a high content of bioactive components, some of which could be toxic in larger quantities. The objective of this paper is to outline a strategy for safety evaluation of wild plants not covered in current food compositional databases and to apply the method for selected plants used in the New Nordic Diet recipes.Four examples of typical wild edible plants were evaluated (stinging nettle, sorrel, chickweed and common lambsquarters), and based on substantial equivalence with known food plants the majority of the bioactive components reported were within the range experienced when eating or drinking typical food stuffs. For most compounds the hazards could be evaluated as minor. The only precaution found was for common lambsquarters because of its presumed high level of oxalic acid.It is concluded that a substance-by-substance evaluation of intake by equivalence to common foods is a useful and efficient strategy to evaluate the safety of newly introduced wild edible plants. Further evaluation and better compositional analyses are warranted before a daily consumption of significant amounts of wild edible plants can be generally regarded as safe.

Newly Approved Laser Systems for Onychomycosis

Laser systems are a new treatment area for onychomycosis. As of January 2012, the US Food and Drug Administration (FDA) has approved four laser systems for the "temporary increase of clear nail in onychomycosis." The FDA has approved these devices on the basis of "substantial equivalence" to predicate devices with similar technical specifications and applications. Laser therapy appears to be a promising alternative to traditional pharmacotherapy, but these systems have been tested in only limited clinical trials; therefore, it is not possible to compare their efficacy to the oral and topical drugs currently used in the treatment of onychomycosis.

Assessment of substantial equivalence of phytase from genetically modified potato and recombinant Escherichia coli

Assessment of substantial equivalence of phytase from genetically modified potato and recombinant Escherichia coli

Guidelines for the Use of the WAIS-IV with WAIS-III Cross-Cultural Normative Indications

The aim of this article was to provide practitioner guidelines for the use of the Wechsler Adult Intelligence Scale — 4th Edition (WAIS-IV) within the South African context, given the absence of local norms for this edition of the test. Normative indications for WAIS-III test performance (English administration), in respect of South African black African (predominantly Xhosa) first language samples (age range 19–30), demonstrate that Grade 12 and Graduate Xhosa groups with disadvantaged education were significantly lower than the US standardization by 20 to 30 IQ points. This raises the question as to whether practitioners should use the WAIS-III rather than the more clinically advanced WAIS-IV for such testees given the lack of appropriate norms. In response to this dilemma, a mechanism is presented for converting a WAIS-IV raw score test profile into a WAIS-III test profile such that it may be subjected to analysis in terms of available WAIS-III cross-cultural norms. Following this procedure, WAIS-III subtest scaled scores and index scores were calculated from WAIS-IV data for three young adult Xhosa speaking individuals with disadvantaged education. Descriptive comparisons of the original WAIS-IV scores and the derived WAIS-III scores reveal substantial equivalence across each of the three test profiles. Taking both clinical and statistical data into account, a neuropsychological analysis was elucidated in respect of one of these cases, on the basis of which a contextually coherent interpretation of a WAIS-IV brain injury test protocol using the Shuttleworth-Edwards et al. WAIS-III cross-cultural norms is achieved. While further research is warranted, it appears that for diagnostic purposes practitioners can legitimately proceed to the use of the WAIS-IV in respect of such educationally disadvantaged populations by means of cautious application of these WAIS-III local norms.

Efficacy and safety of the novel electrosurgical vessel sealing and cutting instrument BiCision®

The use of energy-based tissue-sealing and cutting instruments is becoming more and more popular in visceral, urological, and gynecological surgery. For their safe and efficacious use in clinical practice, such instruments have to reliably seal vessels with a minimal sealing failure rate, cause minimal thermal damage to adjacent tissue, and have good cutting qualities. The efficacy and safety of the novel energy-based instrument for dissection, hemostasis and cutting (BiCision(®), ERBE) was compared to a commercially available device (EnSeal(®), Ethicon Endo-Surgery). We investigated vessel-sealing reliability (success rate), sealing quality and sealing time, lateral thermal damage cutting quality, tissue sticking to the instrument, burst pressure and delayed complications in an acute and chronic pig model after splenectomy, small bowel resection, nephrectomy, salpingo-oophorectomy, and sealing of peripheral vessels. For all parameters investigated, BiCision(®) was at least equivalent to EnSeal(®). BiCision(®) was even superior to EnSeal(®) with respect to the burst pressure in arteries (p = 0.044) and veins (p = 0.023) and the cut quality in all locations (arteries, p = 0.0009; veins, p = 0.043). The course of the 7-day chronic study was uneventful except for one animal that developed an intestinal obstruction. None of the animals showed any signs of postoperative bleeding. On second-look laparotomy at day 7, macroscopic inspection of the sealed tissue and vessels did not show any signs of complications or evidence that bleeding had occurred. Histologically, the integrity of vessel wall fusion, thermal alterations, and inflammatory reactions were comparable, confirming substantial equivalence. We demonstrated that the efficacy and quality of vessel sealing with BiCision(®) is at least equivalent to those of EnSeal(®) for vessel diameters up to 7 mm. Since EnSeal(®) has already been shown to be safe in clinical practice, BiCision(®) should be as reliable as EnSeal(®) under clinical conditions.

Unintended polar metabolite profiling of carotenoid-biofortified transgenic rice reveals substantial equivalence to its non-transgenic counterpart

Substantial equivalence is a critical concept for biosafety assessment of genetically modified (GM) crops. To investigate substantial equivalence among carotenoid-biofortified GM rice and five conventional rice cultivars having common white (three) and red (two) grain colors, profiles of 52 polar metabolites were analyzed using gas chromatography time-of-flight mass spectrometry. The results were compared to evaluate the differences among GM and non-GM rice cultivars using principal components analysis. The GM rice is more comparable to its non-transgenic counterpart rice variety according to the closer co-separation than for other cultivars tested. This suggests that profiling of unintended polar metabolites could be a useful tool to reveal substantial equivalence of GM rice.