Regulatory aspects of a nanomaterial for imaging therapeutic cells.

The ability to track therapeutic cells upon administration to the patient is of interest to both regulators and developers of cell therapy. The European Commission Horizon2020 project nTRACK from 2017-2022 aimed to develop a multi-modal nano-imaging agent to track therapeutic cells during development of a cell therapy. As part of this project, we investigated the regulatory pathway involved for such a product if marketed as a stand-alone product. An important regulatory hurdle appeared to be the appropriate regulatory classification of the nTRACK nano-imaging agent, as neither the definition for medicinal product nor the definition for medical device appeared to be a good fit for the purpose of the product and we were confronted with diverging views of competent authorities on the classification. As a consequence, the information requirements to fulfill before conducting a First in Human trial are not evident and can only be decided upon by closely collaborating and communicating with the relevant authorities throughout the development of the product. Moreover, standard test methods for demonstrating the quality and safety of a medicinal product or medical device are not always suitable for nanomaterials such as the nTRACK nano-imaging agent. Regulatory agility is therefore a great need to prevent delay of promising medical innovations, although regulatory guidance on these products will likely improve with more experience. In this article, we outline the lessons learnt related to the regulatory process of the nTRACK nano-imaging agent for tracking therapeutic cells and offer recommendations to both regulators and developers of similar products.

Results of a survey among GP practices on how they manage patient safety aspects related to point-of-care testing in every day practice.

BACKGROUND: Point-of-care (POC) tests are devices or test strips that can be used near or at the site where care is delivered to patients, enabling a relatively fast diagnosis. Although many general practitioners (GPs) in the Netherlands are using POC tests in their practice, little is known on how they manage the corresponding patient safety aspects. METHODS: To obtain information on this aspect, an invitation to participate in a web-based questionnaire was sent to a random sample of 750 GP practices. Of this sample 111 GP practices returned a complete questionnaire. Data was analysed by using descriptive statistics. RESULTS: Results show that there is not always attention for quality control measures such as checking storage conditions, executing calibration, and maintenance. In addition, universal hygienic measures, such as washing hands before taking a blood sample, are not always followed. Refresher courses on the use of POC tests are hardly organized. Only a few of the GPs contact the manufacturer of the device when a device failure occurs. Well-controlled aspects include patient identification and actions taken when ambiguous test results are obtained. CONCLUSIONS: We observed a number of risks for errors with POC tests in GP practices that may be reduced by proper training of personnel, introduction of standard operating procedures and measures for quality control and improved hygiene. To encourage proper use of POCT in general practices, a national POCT guideline, dedicated to primary care and in line with ISO standards, should be introduced.

Clinical data on injectable tissue fillers: a review.

Treatment with injectable tissue fillers for aesthetic purposes is increasingly popular. In parallel with this success, questions related to the safety of these treatments and the products involved are being raised more prominently. To gain insight in the safety aspects of injectable tissue fillers, we performed a literature review to collect studies reporting clinical data of injectable tissue fillers. We found several case reports where serious complications after more than three years are described. However, there are only a limited number of well-defined prospective clinical studies available with follow-up periods longer than three years. Furthermore, causes of complications, that is, treatment or product related, are often not specified in literature. Considering the intended functional period of fillers in combination with the known occurrence of long-term complications, there is a need for well-defined prospective clinical studies. In order to be able to discriminate between product failure (a product safety issue) or application methodology (a physician expertise or training issue), better identification of observed complications and whether they are product or treatment related, is needed. For the safe use of the fillers it is important that treatment with injectable tissue fillers is performed by a trained physician, who knows the product specifications and its applications.

Medical technology at home: safety-related items in technical documentation.

OBJECTIVES: This study aimed to investigate the technical documentation of manufacturers on issues of safe use of their device in a home setting. METHODS: Three categories of equipment were selected: infusion pumps, ventilators, and dialysis systems. Risk analyses, instructions for use, labels, and post market surveillance procedures were requested from manufacturers. Additionally, they were asked to fill out a questionnaire on collection of field experience, on incidents, and training activities. RESULTS: Specific risks of device operation by lay users in a home setting were incompletely addressed in the risk analyses. A substantial number of user manuals were designed for professionals, rather than for patients or lay carers. Risk analyses and user information often showed incomplete coherence. Post market surveillance was mainly based on passive collection of field experiences. CONCLUSIONS: Manufacturers of infusion pumps, ventilators, and dialysis systems pay insufficient attention to the specific risks of use by lay persons in home settings. It is expected that this conclusion is also applicable for other medical equipment for treatment at home. Manufacturers of medical equipment for home use should pay more attention to use errors, lay use and home-specific risks in design, risk analysis, and user information. Field experiences should be collected more actively. Coherence between risk analysis and user information should be improved. Notified bodies should address these aspects in their assessment. User manuals issued by institutions supervising a specific home therapy should be drawn up in consultation with the manufacturer.

A rapid and sensitive assay for detection of replication-competent adenoviruses by a combination of microcarrier cell culture and quantitative PCR.

The development of a rapid and sensitive assay for detection of replication-competent adenoviruses (RCAs) is described. This RCA assay consists of an incubation step of 4 days of adenoviral vectors on A549 cells in a microcarrier cell culture system followed by detection of amplified RCAs by E1-specific quantitative PCR. The detection limit of this assay is 3 RCAs in 1 x 10(10) vector particles per 70 ml of microcarrier cell culture. The main advantage of the combination of cell culture and PCR detection is that replicated virus can be detected long before cytopathic effects become visible and therefore, it is much faster than conventional cell culture-based assays. This assay was validated by spiking replication-incompetent adenoviral vectors with wild-type adenovirus serotype 5 (wt Ad5) as a positive control for RCA. It was found that the replication of wt Ad5 is hampered above a vector particle per cell ratio of 50. However, if microcarrier beads are used, many cells can be grown in a small suspension culture and consequently a large number of vector particles can be tested for contamination with RCA.