Basic concepts and issues: a primer on distribution and sales representative agreements in the medical device and durable medical equipment industries

Counsel for a manufacturer of medical devices or durable medical equipment must have working knowledge of various legal disciplines to draft contracts with intermediaries (sales representatives and distributors) for the marketing and sale of the manufacturer's products. If the manufacturer wishes to sell its products abroad, counsel must become familiar with the laws and business practices of the target country, and methods of gaining access to the foreign market. This Article gives readers an overview of the applicable legal principles, under U.S. and foreign laws, in the areas of agency, contracts, healthcare regulation, consumer protection, intellectual property protection, and dealer protection. To aid counsel in drafting intermediary agreements, specific contractual terms and issues are explored in depth, including: appointment clauses, performance provisions, provisions concerning pricing and payment, protective clauses (shielding the manufacturer from liability), term and termination provisions, independent contractor clauses, export control clauses, recordkeeping and audit provisions, choice of law clauses, and dispute resolution clauses.     

A study of the precursors, intermediates and reaction by-products in the synthesis of 3,4-methylenedioxymethylamphetamine and its application to forensic drug analysis

3,4-Methylenedioxymethylamphetamine (MDMA) was prepared by three synthetic routes. Analytical data from thin-layer chromatography, gas chromatography and gas chromatographymass spectrometry of the precursors (safrole and isosafrole), intermediates (isosafrole glycol, piperonylmethylketone, N-formyl-3,4-methylenedioxymethylamphetamine, N-formyl-3,4-methylenedioxyamphetamine and 1-(3,4-methylenedioxyphenyl)-2-bromopropane), reaction by-products and the product MDMA were obtained. Further analyses of MDMA using other techniques including ¹H- and ¹³C-nuclear magnetic resonance spectroscopy, X-ray diffraction, infrared spectroscopy, ultraviolet spectroscopy and high performance liquid chromatography were also carried out. The results were then used as reference data for the identification of MDMA in case samples and also to establish the route of synthesis of illicity prepared MDMA by the study of trace impurities.     

Knowing receipt: continuing trusts and conscionability Byers v Saudi National Bank

In Byers v Saudi National Bank [2022] EWCA Civ 43 the Court of Appeal examined a seemingly straightforward question: where rights are dissipated in breach of trust, is it a necessary condition of the recipient being liable for ‘knowing receipt’ that the dissipation did not extinguish the beneficiary's rights? The answer sheds considerable light on the juridical nature of liability for ‘knowing receipt’. This note argues that the Court of Appeal's analysis correctly supports the theory that so-called ‘recipient’ liability is in fact a species of liability for breach of trust. It also examines the implications of that conclusion for the elements of, and remedies for, ‘knowing receipt’.     

Evaluation of Two New Methods for DNA Extraction of “Legal High” Plant Species

A quick, simple, and high-yield nucleic acid isolation process is crucial for high-quality DNA analysis. The ability of the MicroGEM PDQeX phytoGEM system and Omega Bio-tek E.Z.N.A.® Plant DS Mini kit to extract PCR-ready DNA was evaluated by extracting the forensically relevant “legal high” plant species: Ipomoea purpurea, Artemisia absinthium, Mitragyna speciosa, Datura stramonium, and Papaver somniferum. The plant material was pulverized, processed using the manufacturer’s plant protocol for the PDQeX Nucleic Acid Extraction or the manufacturer’s protocol for the Omega extraction, quantified using the Invitrogen Qubit 2.0 Fluorometer, and analyzed for amplifiability by PCR using a Qiagen Rotor-Gene Q instrument and published assays. The DNA amplicons for the legal high species produced high-resolution melt curves concordant with the melts observed when DNA was isolated using the Qiagen DNeasy Plant Mini Kit in previous studies.     

False Positives Observed on the Seratec® PSA SemiQuant Cassette Test with Condom Lubricants

Abstract: In the course of the validation of a new component of the prostate‐specific antigen (PSA) SemiQuant Cassette Test marketed by Seratec^®, a false‐positive reaction was observed when testing samples collected from the surface of unused, lubricated condoms. A variety of personal lubricants and condoms were tested to determine the frequency of the false positive, as well as its potential source. Samples were extracted in both water and the manufacturer‐provided buffer, and the test was performed according to the manufacturer’s suggested protocol. The false positive was observed intermittently, but occurred consistently with samples containing nonoxynol‐9, a strong detergent utilized as a spermicide. The reaction may be attributable to the combination of latex and nonoxynol‐9. Because of the unreliability of the test to confirm the presence of PSA in samples collected from condoms, the PSA cassette is an unsuitable method for confirming the presence of seminal fluid in condoms.     

Forensic applications of stable isotope analysis: Case studies of the origins of water in mislabeled beer and contaminated diesel fuel

This paper describes the use of oxygen (¹⁸O) isotope analysis of water contained in two different materials — beer and diesel fuel — involved in the resolution of two separate cases. In the first case study, it was possible to demonstrate that a sample of beer labelled as premium brand in fact belonged to a cheap brand. The second case related to the contamination of diesel fuel from a service station. The diesel fuel contained visible amounts of water, which caused vehicles that had been filled up with it to become defective. For insurance purposes, it was necessary to determine the source of water. The δ¹⁸O values for the water of nearly all samples of diesel was close to the δ¹⁸O of local tap water at the filling station.     

Analytical Characterization of Erythritol Tetranitrate,an Improvised Explosive

Erythritol tetranitrate (ETN), an ester of nitric acid and erythritol, is a solid crystalline explosive with high explosive performance. Although it has never been used in any industrial or military application, it has become one of the most prepared and misused improvise explosives. In this study, several analytical techniques were explored to facilitate analysis in forensic laboratories. FTIR and Raman spectrometry measurements expand existing data and bring more detailed assignment of bands through the parallel study of erythritol [¹⁵N₄] tetranitrate. In the case of powder diffraction, recently published data were verified, and ¹H, ¹³C, and ¹⁵N NMR spectra are discussed in detail. The technique of electrospray ionization tandem mass spectrometry was successfully used for the analysis of ETN. Described methods allow fast, versatile, and reliable detection or analysis of samples containing erythritol tetranitrate in forensic laboratories.     

A fatal poisoning involving Bromo-Dragonfly

This paper reports a fatal overdose case involving the potent hallucinogenic drug Bromo-Dragonfly (1-(8-bromobenzo[1,2-b; 4,5-b′]difuran-4-yl)-2-aminopropane). In the present case, an 18-year-old woman was found dead after ingestion of a hallucinogenic liquid. A medico-legal autopsy was performed on the deceased, during which liver, blood, urine and vitreous humour were submitted for toxicological examination. Bromo-Dragonfly was identified in the liver blood using UPLC–TOFMS, and was subsequently quantified in femoral blood (0.0047 mg/kg), urine (0.033 mg/kg) and vitreous humour (0.0005 mg/kg) using LC–MS/MS. Calibration standards were prepared from Bromo-Dragonfly isolated from a bottle found next to the deceased. The structure and purity of the isolated compound were unambiguously determined from analysis of UPLC–TOFMS, GC–MS, HPLC–DAD, ¹H and ¹³C NMR data and by comparison to literature data.The autopsy findings were non-specific for acute poisoning. However, based on the toxicological findings, the cause of death was determined to be a fatal overdose of Bromo-Dragonfly, as no ethanol and no therapeutics or other drugs of abuse besides Bromo-Dragonfly were detected in the liver, blood or urine samples from the deceased. To our knowledge, this is the first report of quantification of Bromo-Dragonfly in a biological specimen from a deceased person. This case caused the drug to be classified as an illegal drug in Denmark on 5th December 2007.     

Radiocarbon dating as tool to assist in triaging cases of unidentified human remains in Victoria,Australia: A case series

In cases where human remains are unidentified because there is no initial identification hypothesis, limited contextual information, and/or poor preservation, radiocarbon (¹⁴C) dating may be a useful tool to further assist with identification. Through measuring the amount of ¹⁴C remaining in organic material, such as bone, teeth, nail, or hair, radiocarbon dating may provide an estimated year of birth and year of death for a deceased person. This information, may assist in, establishing whether a case of unidentified human remains (UHR) is actually of medicolegal significance and therefore, requires forensic investigation and identification. This case series highlights the application of ¹⁴C dating to seven of the 132 UHR cases in Victoria, Australia. Cortical bone was sampled from each case and the level of ¹⁴C was measured to provide an estimated year of death. Four of the seven cases analyzed contained the levels of ¹⁴C consistent with an archeological timeframe, one contained a level of ¹⁴C consistent with a modern (i.e., of medicolegal significance) timeframe, and the results for the remaining two samples were inconclusive. Applying this technique not only reduced the number of UHR cases in Victoria but also has investigative, cultural, and practical implications for medicolegal casework in general.     

Dialogue and the Inquisitorial Tradition: French Defence Lawyers in the Pre-Trial Criminal Process

Recent years have seen an intermittent debate amongst journalists, policy-makers and academics in adversarial jurisdictions about the nature and quality of the inquisitorial tradition in criminal process. Much of the political impact of the debate in Britain has stemmed from the view asserted periodically by certain high profile figures that some form of judicial supervision of police investigation – as practised for example in France – might be introduced in England and Wales.¹ Such views tend to find expression when events call into question not just particular rules but also the underlying structures and assumptions of our adversarial tradition of criminal process. Thus in 1991 the public revelation of serious miscarriages of justice led to the appointment of a Royal Commission on Criminal Justice in which the adversarial character of the pre-trial process seemed to be a key point of interrogation.² The police view, demonstrated in a number of key cases, was that once they were clear that a suspect was guilty they had no responsibility to pursue exculpatory lines of investigation. This, combined with the failure of defence lawyers to play the extensive, autonomous investigative role the adversarial system demanded of them, encouraged some to ask whether there might not be advantages in somehow ensuring that the resources and rights of the state were devoted to pursuing exonerating as well as incriminating evidence. Given the limited empirical evidence then available on the workings of judicial supervision in practice⁴ and the sometimes vehement dispute in France itself about the future of its pre-trial process and especially the juge d'instruction(examining magistrate), the proposals were perhaps not surprisingly rejected.⁵ But since the mid 1990s, British funders have begun to finance a number of empirical studies of French criminal justice.⁶ This paper reports the principal findings of a empirical study primarily funded by Britain's Economic and Social Research Council into the role of defence lawyers in France.⁷ Our focus and primary theme is the developing nature of their dialogue and exchanges with key state actors such as judges, prosecutors and the police on the one hand and with clients on the other. But in so doing we aim to cast light on the broader functioning of the pre-trial process in France.     

论药品的警示缺陷责任

药品生产商对药品的警示缺陷应承担无过错责任。在追究药品生产商的严格责任时 ,应注意考察药品生产商在药品危险警示方面是否尽到了充分的、持续的、及时的注意义务。在药品生产商对药品危险具有充分知识而未尽警示义务的情况下 ,药品生产商应对药品对消费者所带来的损害负赔偿责任。对于处方药 ,药品生产商应对医师尽危险警示义务 ,这归因于医师处于权衡利弊并减少损害风险的位置。当药品生产商的促销行为使得医师作为评估者和决策者的地位减弱或丧失时 ,药品生产商应对消费者直接尽警示义务。药品危险警示义务的主体是生产商。药师不负有一般的药品危险警示义务 ,除非存在足以使人警觉从而引发较大注意义务的额外因素。     

Reluctant Bedfellows: Want of Authority and Knowing Receipt

The case note examines the recent decision of the Hong Kong Court of Final Appeal in Thanakharn Kasikorn Thai Chamkat (Mahachon) v Akai Holdings Ltd, where Lord Neuberger of Abbotsbury adopted the test of irrationality in determining whether a defaulting agent had apparent authority to act on behalf of his principal to confer benefits on a third party. His Lordship further held that a concurrent claim in knowing receipt arose against the third party, and the test of unconscionability is substantially the same as that of irrationality. The present note argues that symmetry of the two tests is not necessary, for knowing receipt and apparent authority deal with issues that are categorically different and serve different purposes. It also examines, in the context of benefits conferred upon an underlying agreement that is void, the oft‐overlooked issue as to what amounts to receipt for the purpose of knowing receipt.     

An Ecological Study of Nonresidential Services for Battered Women Within a Comprehensive Community Protocol for Domestic Violence

This paper is an ecological study of services provided to 392 battered women under a comprehensive domestic violence protocol. It focuses on microsystemic interactions between battered women and battered women's services and legal systems. We examine the relationships between women's receipt of services from a battered women's agency, receipt of protective orders, and completion of prosecution of batterers. We also explore the associations between women's receipt of services and protective orders and their partners' subsequent arrests and police contacts. We use open-ended interviews with battered women and with staff of the battered women's agency to expand and illustrate the quantitative data. The analysis shows that when a woman received battered women's services or had a protective order, a completed court case was more likely and numbers of arrests rose. We found that these associations were strongest when women received both battered women's services and at least one protective order.     

Comparative analysis of 1-phenyl-2-propanone (P2P), an amphetamine-type stimulant precursor, using stable isotope ratio mass spectrometry: Presented in part as a poster at the 2nd meeting of the Joint European Stable Isotope User Meeting (JESIUM), Giens, France, September 2008

The isotope ratios of amphetamine type stimulants (ATS) depend as well on the precursor as the synthetic pathway. For clandestine production of amphetamine and methamphetamine, 1-phenyl-2-propanone (P2P, benzylmethylketone) is a commonly used precursor.Our aim was to determine the variation of the isotope ratios within precursor samples of one manufacturer and to compare seized samples of unknown sources to these values. δ¹³C_V-PDB, δ²H_V-SMOW and δ¹⁸O_V-SMOW isotope ratios were determined using elemental analysis (EA) and gas chromatography (GC) coupled to an isotope ratio mass spectrometer (IRMS). The comparison of all seized samples to the data of the samples of one manufacturer revealed considerable differences. The results show that IRMS provides a high potential in differentiating between precursors from different manufacturers for the clandestine production of ATS and identifying corresponding sources.     

Dissemination of information on unapproved/new uses for marketed drugs, biologics, and devices--FDA. Proposed rule

The Food and Drug Administration (FDA) is proposing to issue new regulations pertaining to the dissemination of information on unapproved uses (also referred to as "new uses" and "off-label uses") for marketed drug, including biologics, and devices. The proposal, which would implement the dissemination provisions of the Food and Drug Administration Modernization Act of 1997 (FDAMA), would describe the content of and establish procedures for a manufacturer's submissions to FDA before it may begin disseminating information on the new use. The proposal also would describe how manufacturers seeking to disseminate new use information must agree to submit a supplement for that use within a specified period of time, unless a supplemental application already has been submitted or FDA has exempted the manufacturer from the requirement to submit a supplement. The proposal also would provide for requests to extend the time period for submitting a supplement for a new use, and it would describe how a manufacturer can seek an exemption from the requirement to submit a supplement. Additionally, the proposal would discuss FDA actions in response to manufacturer's submissions, corrective actions that FDA may take, and recordkeeping and reporting requirements.     

Evaluation and classification of fentanyl-related compounds using EC-SERS and machine learning

Multiple analytical techniques for the screening of fentanyl-related compounds exist. High discriminatory methods such as GC–MS and LC–MS are expensive, time-consuming, and less amenable to onsite analysis. Raman spectroscopy provides a rapid, inexpensive alternative. Raman variants such as electrochemical surface-enhanced Raman scattering (EC-SERS) can provide signal enhancements with 10¹⁰ magnitudes, allowing for the detection of low-concentration analytes, otherwise undetected using conventional Raman. Library search algorithms embedded in instruments utilizing SERS may suffer from accuracy when multicomponent mixtures involving fentanyl derivatives are analyzed. The complexing of machine learning techniques to Raman spectra demonstrates an improvement in the discrimination of drugs even when present in multicomponent mixtures of various ratios. Additionally, these algorithms are capable of identifying spectral features difficult to detect by manual comparisons. Therefore, the goal of this study was to evaluate fentanyl-related compounds and other drugs of abuse using EC-SERS and to process the acquired data using machine learning—convolutional neural networks (CNN). The CNN was created using Keras v 2.4.0 with Tensorflow v 2.9.1 backend. In-house binary mixtures and authentic adjudicated case samples were used to evaluate the created machine-learning models. The overall accuracy of the model was 98.4 ± 0.1% after 10-fold cross-validation. The correct identification for the in-house binary mixtures was 92%, while the authentic case samples were 85%. The high accuracies achieved in this study demonstrate the advantage of using machine learning to process spectral data when screening seized drug materials comprised of multiple components.     

Surgical Sutures as a Means of Identifying Human Remains*

Abstract: The Food and Drug Administration does not require surgical sutures to be tracked by manufacturer, physician, or patient; thereby, surgical sutures have been of little use to forensic practitioners who are tasked with establishing a positive identification with biological evidence. This study demonstrates the investigative process used to pinpoint suture manufacturers by presenting a case where surgical sutures were a distinctive characteristic that aided in the positive identification of skeletal remains. The suture’s manufacturer, construction material and structure, size, and medical use was determined by contacting a local surgical suture and orthopedic implant manufacturer and utilizing publicly available manufacturer websites, which provide catalogs and specific product details. This research was one of many lines of evidence used to establish the positive identification of a 47‐year‐old male.     

Paths to Market for Supply Push Technology Transfer

The Rehabilitation Engineering Research Center on Technology Transfer (T²RERC) advances the methods of technology transfer through research, transforms technologies into products through development, and facilitates the commercialization of new and improved assistive technology devices. This paper reviews the T²RERC's process and the three primary Paths to Market employed by the T²RERC for new products proceeding through its Supply Push program (Lane, 1999) in a case study format.