Specific Standard Operating Procedures Research Articles

Standard Operating Procedure for the Arrests and Detentions of Individuals with Autism in Four Countries

Autism spectrum disorder (ASD) is categorized under neuro-developmental disorders. Individuals with this disorder experience deficits in social interaction and communication skills as well as repetitive patterns of thoughts and behaviours. The purpose of this study was to comparatively analyze the similarities and differences in Malaysian PDRM Autism SOPs with other countries, namely Malaysia, Hong Kong, the United Kingdom, and four countries in the United States, namely, Wisconsin, New Mexico, Illinois, and Virginia. This research focuses on discussing the important elements emphasized in SOPs and some aspects of similarities and differences between them. The research design is based on document analysis. The data were analyzed descriptively and thematically. Research results that autistic people put them at risk of committing violations of the law without realizing or intending to do so. Since they are also categorized as persons with disabilities, they are thus entitled to legal guarantees appropriate to their status. Therefore, their rights to equality and non-discrimination as persons with disabilities attracted worldwide attention holistically, resulting in specific Standard Operating Procedures (SOPs) in several countries, including Malaysia, namely, the Royal Malaysian Police Autism SOP (PDRM). Likewise, there are several important elements outlined in all SOPs, in aspects of their application, legal references, methods of arrest and detention, and intermediary assistance, and there are some similarities and differences between the SOPs analyzed. The implications of this study show the importance of SOPs for autism arrest and prisoners, to meet their specific legal needs.

Establishment of a Biorepository for Down Syndrome: Experience of the Inter-Institutional Multidisciplinary BioBank - BioBIM.

Down syndrome, or Trisomy 21, is the leading genetic cause of cognitive disability in children and is associated with a high risk of several comorbidities, particularly congenital heart defects, early onset Alzheimer's disease, leukaemia, and autoimmune disorders. This study describes the design, methods, and operational procedures employed to establish a biobank dedicated to Down syndrome that can support research projects investigating the effects of various genetic and environmental factors on this complex disease. Blood was collected from all recruited subjects, processed, aliquoted and immediately frozen at -80 °C in the Interinstitutional Multidisciplinary BioBank (BioBIM) facilities. A small aliquot of the sample was used to perform blood tests for which analysis would not be feasible at a later date, such as blood cell counts. Each biological sample was coded, assigned a Standard PREanalytical Code, and registered in the oloBIOBANK software connected to a medical card containing all the donor's anamnestic data. All samples were stored under continuous real-time temperature recording using a freezer connected to a T-GUARD alarm system. In addition, a radiofrequency identification tracking system strictly monitored each cryopreservation operation performed throughout the sample lifecycle. Biological samples were collected from 454 individuals with Down syndrome from 2007 to 2023. A total of 2233 biological samples were available for research purposes, including whole blood in different anticoagulants, serum, plasma, and frozen peripheral blood mononuclear cells. The quality of the nucleic acids obtained through specific standard operating procedures demonstrated that these samples were appropriate for clinical and basic research. By establishing this biobank, we have gathered a significant number of biological samples and clinical data from individuals with Down syndrome, thereby fostering collaboration between different research groups in an open and transparent manner. Sharing expertise and resources among scientists will ultimately facilitate the transfer of knowledge to clinical practice, leading to the development of more effective therapeutic treatments to improve the outcomes and quality of life of patients with Down syndrome.

Grinding as a slaughter method for farmed black soldier fly (Hermetia illucens) larvae: Empirical recommendations to achieve instantaneous killing.

At least 200 billion black soldier fly (Hermetia illucens) larvae (BSFL) are reared each year as food and feed, and the insect farming industry is projected to grow rapidly. Despite interest by consumers, producers, and legislators, no empirical evidence exists to guide producers in practicing humane - or instantaneous - slaughter for these novel mini-livestock. BSFL may be slaughtered via freezing, boiling, grinding, or other methods; however standard operating procedures (SOPs) and equipment design may affect the likelihood of instantaneous death using these methods. We tested how larval body size and particle size plate hole diameter affect the likelihood of instantaneous death for black soldier fly larvae that are slaughtered using a standard meat grinder. Larval body size did not affect the likelihood of instantaneous death for larvae that are 106-175 mg in mass. However, particle size plate hole diameter had a significant effect on the likelihood of instantaneous death, with only 54% of larvae experiencing an instant death when using the largest particle size plate (12-mm hole diameter) compared to 84% using the smallest particle size plate (2.55 mm). However, a higher percentage of instantaneous death (up to 99%) could be achieved by reducing the proportion of larvae that become stuck in the machine. We conclude by outlining specific recommendations to support producers in achieving a 99% instantaneous death rate through specific SOPs to be used with similarly designed machines. We also develop a protocol for producers that wish to test their own grinding SOPs.

Integrating partner notification and contact tracing services across Europe: findings from the Integrate project

BackgroundPartner notification/contact tracing (PN/CT) is a process whereby people diagnosed with an infectious disease notify their sexual and needle-sharing partners/close contacts and invite them for testing and treatment due to exposure to the disease. PN is a necessary testing and prevention tool supported by the European Centre for Disease Prevention and Control (ECDC) and World Health Organization (WHO). Traditionally, PN efforts have been siloed within disease areas, with separate pathways and systems responsible for specific diseases. The INTEGRATE project sought to improve PN/CT outcomes by sharing knowledge across diseases and countries.MethodsINTEGRATE used two mapping exercises to assess the PN landscape in Europe and identify areas for integration and cross-learnings for Sexually Transmitted Infections (STIs) and Tuberculosis. Mapping exercises were surveys to 29 consortium partners and in-depth qualitative interviews at four selected pilot sites: Ireland, Greece, Romania and Italy.ResultsAreas for the improvement of PN/CT emerged: lack of resources and insufficient staff training, different modes of disease transmission, country-specific laws and regulations, the advent of General Data Protection Regulation (GDPR), differences in healthcare system pathways, historical concerns, and cultural differences. Activities highlighted key areas PN/CT outcomes could be improved, including PN/CT specific trainings for staff, improving knowledge on laws, regulations, guidelines and pathways and creating a country/region specific Standard Operating Procedures (SOPs) for PN/CT, incorporating information on all four disease areas. Findings were analyzed and three key areas were identified and implemented for knowledge transfer namely the creation of an online repository of European country guidelines, the transfer of SOPs and PN training in pilot sites.ConclusionA major finding of the project was challenges associated with incorporating Tuberculosis (TB) contact tracing alongside other infectious diseases. Professionals in the field, emphasized that integrating TB contact tracing with the other disease areas would be challenging and arguably unjustified, due to the different ways of transmission of TB and because well-established historical pathways for TB in public health systems already exist. However, the success of TB services presents an ideal model to draw from when strengthening PN systems for other infectious diseases.

To utilize automation or not to utilize automation, that is the question: An evaluation of how drills and procedures impact optronics mast usage from a sociotechnical systems perspective

The delegation of tasks to a non-human agent in a sociotechnical system can extend human capabilities and performance. Effective performance is, however, reliant on a successful relationship between human operators and automation. Optronics is a partially automated system which has replaced periscope on board some modern submarine platforms, operating modes permit the completion of tasks either manually or utilizing automation. A reluctance to utilize automated functionality within the optronics system has been due to operator familiarity with legacy manual procedures based upon the use of a physical periscope. This highlights the gap that is prevalent between innovation, design, training and governance of automation utilization. The current work examined current (Control group) utilization of optronics technology using an expert population in a high fidelity simulator. Findings were utilized to guide the development of novel optronics specific standard operating procedures (Intervention group). Results indicate that automaton disuse was greatly reduced, which had had a positive overall impact on overall system performance with regard to productivity and accuracy. The current work highlights the importance of incorporating governance of use and training as part of an automation design and implementation program is critical to help ‘maximize what you have’.

Modelling Covid-19 mitigation and control strategies in the presence of migration and vaccination: the case of South Africa

The novel coronavirus disease has ravaged many health systems around the world and has brought many economies to their knees. In the absence of an approved curing medicine or approved vaccine to date, the major control of the surge of infections is through use of Non-Pharmaceutical Interventions (NPIs) and imposing specific standard operating procedures (SOPs) in instances when the disease spread curbs are relaxed. It is thus essential to quantify the extent to which specific NPIs can be useful in containing the pandemic. To achieve this, we constructed a mathematical model that accounts for both person to person transmission as well as transmission through contact from pathogen-contaminated surfaces. The model assumes that there is change of behaviour resulting from the surge of the number of cases, hence a class of susceptible individuals who practise self-protection measures. Basic properties of the model including the conditions for existence and stability of steady states are explored. The model was fitted to new-cases data for South Africa and baseline parameter values were estimated. Sensitivity analysis of the model was performed to determine the most influential parameters on the disease threshold. Our results show that practising of self-protection measures is vital in slowing the spread of the infection. In addition, it is evident from the results that minimizing contact through “physical distancing” as well as with contaminated surfaces can significantly help in containing the infection. The model was extended to account for testing and quarantining of both symptomatic and asymptomatic infected individuals. In addition, migration and potential use of a vaccine were explored. In the case of migration, the scenarios considered included aspects when there are both border control and illegal crossings as well as the case where the government is in full control with proper SOPs. Our results show that, although testing and isolating/quarantining of infected individuals is essential in curbing new infections, it ought to be done in conjunction with implementation of other control measures if the disease is to be curtailed in a shorter period of time. More still, when an effective vaccine is available, even a 98% coverage in one community may not be enough to completely stop new infections in the presence of migration. We therefore recommend that vaccination ought to be done universally if the daily number of new infections is to be reduced to zero.

Serious incidents in testicular torsion management in England, 2007–2019: optimizing individual and training factors are the key to improved outcomes

To establish the healthcare factors that contribute to testicular torsion adverse events (orchidectomies) and 'near misses'. The secondary objective was to identify areas suitable for impactful quality improvement initiatives to be undertaken by National Health Service (NHS) healthcare providers nationally. This was a retrospective record review and analysis, carried out in four phases. We applied the well-validated London Protocol patient safety incident analysis framework to all eligible serious incidents related to testicular torsion submitted by English NHS Trusts over a 12-year period to the Strategic Executive Information System database. Clinical reviewers established the incident population (Phase 1), were trained and piloted the feasibility of using the London Protocol (Phase 2), applied the protocol and themed the identified contributing factors linked to adverse events (orchidectomies) and near-misses (Phase 3), and reviewed the evidence for improvement interventions (Phase 4). Our search returned 992 serious incidents, of which 732 were eligible for study inclusion and analysis. Of those, 137 resulted in orchidectomies, equivalent to one serious incident resulting in orchidectomy per month, and 595 were near misses. Factors contributing to all incidents were: individual staff/training (38%); team (18%); work environment (16%); task and technology (14%); and institutional context (13%). Subgroup analysis of incidents resulting in orchidectomies vs near misses demonstrated a different pattern of factors, with individual staff/training factors significantly more prominent: individual/training (88%); work environment (8%); and task and technology (1%). No evidenced improvement interventions were found in the literature. This is the first study to our knowledge to systematically analyse and classify factors that are associated with loss of a testicle and related near-miss incidents in patients presenting with testicular torsion. In England, a significant number of orchidectomies occur annually as a consequence of healthcare serious incidents. In order to improve outcomes, we propose clinical support to aid the diagnosis of torsion, improved national clinical guidelines, development of specific standard operating procedures and (in the longer term) more exposure of trainees and medical students to urology to improve the testicular salvage rate.

Computer system validation

The purpose of this paper is to present a Quality Management System (QMS) for computer systems validation and to identify and demonstrate the validation process on a practical case of a pharmaceutical company. Based on the European and the US legal requirements, we define QMS for computer system validation elements. Validation process example based on the use of a general V-model provides a thorough understanding of the actual validation implementation in practice. Computer system validation in a concrete organization can be implemented, based on general and specific standard operating procedures which form the QMS. Planning, Specifying, Development/Building, Verification and Report validation activities are presented through process diagrams based on a practical Supervisory Control and Data Acquisition (SCADA) manufacturing computer-aided system validation example. Empirical part employed two research strategies: a single case study and action research. Presented computer system validation QMS and process can provide a guideline for all companies where computer systems are important. Although the presented QMS and process for the computer system validation are related to a specific pharmaceutical company case and its legal requirements, the experience from this highly regulated industry can be appropriately used in other less regulated industries. For verification of the proposed model, they need to be further tested within the pharmaceutical and other less regulated industries.

Quality Management Practices of Gene Banks for Livestock: A Global Review.

The genetic diversity of livestock is decreasing and many countries have created gene banks for ex situ-in vitro conservation of animal genetic resources (AnGR). The collection, processing, and storage of animal germplasm require substantial investment and the material collected (and associated data) is highly valuable. Therefore, quality management systems (QMSs) and practices are important. The objective of this study was to review the quality management procedures of livestock gene banks around the world to identify the general strengths and weaknesses of quality control. A survey was administered by means of an online questionnaire consisting of 54 questions, most of which were yes/no with respect to the presence of a particular aspect of quality management. The survey was distributed through networks of the Food and Agriculture Organization of the United Nations that are associated with AnGR. Ninety responses were received from 62 countries. The gene banks were predominantly public institutions, with the main goal of preventing breed extinction. Approximately 30% of the banks reported having a QMS, 15 of which involved formal certification. Many other banks have plans to implement formal quality management within the next 5 years. Regarding specific aspects of quality management, more emphasis was placed on material entering the banks than on eventual utilization. Among the banks processing and freezing material, 90% followed specific standard operating procedures, but only 24% had policies regarding provision of access to external stakeholders. Increased cooperation among livestock gene banks could improve quality management. Sharing of knowledge could standardize procedures and cooperating peers could evaluate each other's QMSs.

Quality control on radiochemical purity in Technetium-99m radiopharmaceuticals labelling: three years of experience on 2280 procedures.

Objective: the purpose of this study was to offer an example of evaluations of the ISO9001 certified internal quality assurance (QA) system of 99mTc-radiopharmaceutical preparations and quality control in vivo use, using industrial kits and generators in order to identify possible sources of errors in the procedures labeling and quality control procedures. Methods: The study was performed at a single institution over a period of three years (July 1st, 2011 - July 1st, 2014), and included a total of 2280 radiopharmaceutical preparations prepared by four different technologists. All the radiopharmaceutical preparations and quality controls were performed according to each SPC provided by the manufacturer. The radiopharmaceutical preparations were the following (trade names are reported in brackets): 99mTc-albumin colloid [Nanocoll] (n=349), 99mTc-oxidronate [Technescan®hdp] (n=701), 99mTc-exametazime [Ceretec] (n=169), 99mTc-sestamibi [Cardiolite] (n=92), 99mTc-albumin aggregated [Technescan®lyomaa] (n=140), 99mTc-tetrofosmin [Myoview]) (n=567), 99mTc-diethylene triamine pentacetic acid [Technescan®dtpa] (n=254), and 99mTc-dimercapto succinic acid [Renocis®] (n=8). Data were analyzed to determine the number and type of radiopharmaceutical labelling failure and to derive the sources of these failures to define corrective actions and optimize the quality assurance program. Results: A total of 2280 procedures were performed and recorded. Following the quality control procedure six out of the 2280 preparations (0.26%) were non-conforming for clinical use with the RCP limits indicated in the SPC. Five of these were due to gross technical errors in measurements and manual procedures and were immediately repeated, returning within the limits of acceptability. The sixth failure was due to short incubation time, though compliant with the manufacturer’s instructions. Conclusions: We concluded that the quality of the final product depends on a controlled production system based on the implementation of specific standard operating procedures (ISO9001, SOP) for each radiopharmaceutical production, according to strict adherence to the SPC of each radiopharmaceutical. Based on these conclusions, in our opinion every quality control suggesting a possible error in the synthesis procedure recommended in the SPC should be immediately reported to the manufacturer, for a revision of the SPC, as well as to the regulatory agencies for an alert. This strategy may in fact allow the continuous improvement of the labelling procedures and therefore the optimization of the quality control procedures frequency to ensure both patients safety and a more rational management of resources for economic sustainability. (www.actabiomedica.it)

Challenges in simulating the human gut for understanding the role of the microbiota in obesity.

There is an elevated incidence of cases of obesity worldwide. Therefore, the development of strategies to tackle this condition is of vital importance. This review focuses on the necessity of optimising in vitro systems to model human colonic fermentation in obese subjects. This may allow to increase the resolution and the physiological relevance of the information obtained from this type of studies when evaluating the potential role that the human gut microbiota plays in obesity. In light of the parameters that are currently used for the in vitro simulation of the human gut (which are mostly based on information derived from healthy subjects) and the possible difference with an obese condition, we propose to revise and improve specific standard operating procedures.

Experiences and Lessons from a Multicountry NIDIAG Study on Persistent Digestive Disorders in the Tropics.

Experiences and Lessons from a Multicountry NIDIAG Study on Persistent Digestive Disorders in the Tropics.

Abstract 52: Isolation, Characterization and Partial Direct Differentiation of Patient Derived Human Primary Cardiac and Placental Fibroblasts From Surgical Discard Tissue into Induced Mesoderm Progenitor Cell

Background: Human primary cells more closely mimic the physiological state of cells in vivo and generate more relevant data representing living systems. Access to the surgical discard tissue enables the possibility of patient derived, disease specific, cellular bio-bank. In achieving this goal, target cellular lines must be isolated, characterized and fully expanded under specific Standard Operating Procedures(SOP). In this project, we aim in achieving and implementing such goal for Fibroblasts derived from two distinct patient tissues. In parallel, in light of cardiac regenerative therapy, with reference to the published work on Cardiomyocyte Direct Differentiation on mouse fibroblasts into induced cardiomyocyte-like cells (iCMs) by transduction with MicroRNAs (1,133a, 208a and 499) we sought to determine whether primary human cardiac and placental fibroblasts could have the potential in direct differentiation to induced cardiomyocyte-like cells (iCM) through sequential administration of small molecule (ITD-1) in combination with MicroRNAs. Methods and Results: Primary right atrial appendage cardiac and smooth chorion laeve placental fibroblast isolates were generated from surgical discard patient derived tissues subjected for identification of the most efficient isolation method through available enzymatic and mechanical techniques. We have shown through FACS analysis that both groups extracellular marker expression can be limited to CD90+CD31-CD44+FBSP+ which constitutes the majority of cultured primary fibroblasts. Respectively, intercellular expression of DDR2+ VIM+ COL1+CD90+ markers was validated through immunofluorescence microscopy. Transcriptional profiling of Noted lines showed expression of Fibroblast specific genes at higher rate.Furthermore, sorted placental fibroblast isolates were subjected to (ITD-1)treatment and mature MicroRNA mimic cocktail. Transcriptional profiling analysis through RT-PCR concluded down regulation of most distinct fibroblast markers and partial expression of MESP1.

Interdisziplinäre Notaufnahme – Schlüssel zum Erfolg?

In Germany, which is also faced with a scarcity of resources, the concept of central, interdisciplinary emergency rooms ("Zentrale Notfallaufnahme", ZNA) is being developed as an answer to the complex demands of modern emergency medicine with increasing numbers of patients and complexity of the medical conditions. This autonomous institution is the first point of contact for all emergency patients. The central tasks of the ZNA are triage and the interdisciplinary primary treatment of patients. The establishment of the ZNA includes specific facilities (treatment rooms, short stay units, resuscitation rooms, triage and management areas, integration of the premises on site) as well as specific processes (triage systems, specific standard operating procedures) and training for the staff (European Curriculum for Emergency Medicine). It could be shown that by establishing a ZNA along with all its structures the satisfaction of the patients (including shorter waiting times), resource management (intensive care capacity), and patient outcome could be significantly improved.

International Society for the Advancement of Cytometry cell sorter biosafety standards.

Flow cytometric cell sorting of biological specimens has become prevalent in basic and clinical research laboratories. These specimens may contain known or unknown infectious agents, necessitating precautions to protect instrument operators and the environment from biohazards arising from the use of sorters. To this end the International Society of Analytical Cytology (ISAC) was proactive in establishing biosafety guidelines in 1997 (Schmid et al., Cytometry 1997;28:99-117) and subsequently published revised biosafety standards for cell sorting of unfixed samples in 2007 (Schmid et al., Cytometry Part A J Int Soc Anal Cytol 2007;71A:414-437). Since their publication, these documents have become recognized worldwide as the standard of practice and safety precautions for laboratories performing cell sorting experiments. However, the field of cytometry has progressed since 2007, and the document requires an update. The new Standards provides guidance: (1) for laboratory design for cell sorter laboratories; (2) for the creation of laboratory or instrument specific Standard Operating Procedures (SOP); and (3) on procedures for the safe operation of cell sorters, including personal protective equipment (PPE) and validation of aerosol containment.

Animal Welfare Evaluation at a Slaughterhouse for Heavy Pigs Intended for Processing.

The Council Regulation (EC) No. 1099/2009 requires slaughterhouse managers to implement specific standard operating procedures for all pre-slaughter stages considered at risk, aimed at achieving adequate levels of animal welfare. This survey was aimed at testing the applicability to an abattoir for heavy pigs of an assessment system of animal welfare through animal-based measures. In the monitoring of handling operations, the number of animals fallen/slipped and prodded, and that of vocalising pigs were recorded. In the monitoring of the immobilisation stage, carried out on the same pigs, vocalisations were recorded at the entrance to the box and falls/slips occurring inside it. Animal welfare assessment during the stunning-sticking-bleeding steps, was carried out by recording the head-only electrical stunning basic parameters set by legislation, vocalisations resulting from hot wanding, and clinical signs of consciousness, sensibility and certain death. Except for immobilisation, the percentage of occurrence of these events above acceptability limits was detected in all other pre-slaughter steps. The most critical stages were: handling in the unloading area and along the single-file chute, stunning and especially bleeding, where 84.13% of animals showed one or more signs of consciousness and/or sensibility recovery. Wrong placement of electrodes observed in 53.98% of the animals, insufficient voltage and low amperage may explain why a high percentage of pigs recovered consciousness and/or sensibility before death. Some simple restructuring of unloading area, slowdown of slaughter line speed, increase of personnel involved in pre-slaughter management and regular calibration of the electrical stunning device could be effectively corrective measures aimed at raising the animal welfare level at the slaughterhouse under study.

Abstract P4-03-05: Characterization of circulating tumor cells identified by high definition assay in patients with benign and malignant breast disease

Abstract Background: Identification of circulating tumor cells (CTC) has the potential for minimally invasive diagnosis and assessment of therapy response. Current CTC assay techniques rely on immunomagnetic bead isolation for CTC enrichment. However, these methods result in low cell yield, limiting the potential use in early stage where CTCs are thought to be less abundant. The high definition (HD)-CTC assay is a novel non-enrichment assay providing unique opportunities to identify single circulating epithelial cells (CepiCs) in patients before or at diagnosis. This study's goal is to determine feasibility and performance of the HD-CTC method for isolating CepiCs in women presenting for diagnostic breast biopsy. Methods: Women undergoing image-guided biopsy for BIRADS 4 and 5 mammographic abnormalities were selected from April 2012 onward at the Duke Breast Clinic. After obtaining informed consent, sample collection and shipping procedures were performed following specific standard operating procedures. Diagnosis was kept blinded during assay analysis. Quantitative measurements were used at the single-cell level to identify and enumerate CepiCs. We morphologically characterized specific high content screening variables including cytokeratin (CK) intensity and epithelial cell adhesion molecule (EpCAM) staining. Measurements included cellular size, shape, and staining pattern. For each draw, 4 monochrome images per frame from 4 stained slides were used for CK/EpCAM evaluation. Results: To date 34 women have been enrolled. Fourteen samples (41%) were drawn before biopsy and 20 (59%) after. Out of the 20, 2 (10%) were non-evaluable and a total of 18 (90%) have HD-CTC assay derived data available. The average diagnosis age was 54; 70% were Caucasian. Six (33%) out of 18 had benign disease (fibrocystic, fibroadenoma and apocrine), 10 (55%) had invasive (ductal or lobular), and 2 (12%) had atypical ductal hyperplasia and ductal carcinoma in situ. Five (83%) benign cases and 4 (40%) invasive had detectable CepiCs (Fisher exact test = 0.43). We found a borderline significant trend between the number of CepiCs and the nodes involved (P for trend = 0.06). No association found with ER, PR or ERBB2 status. The mean number of CepiCs/mL in invasive cases was 45.25 +/-96.65 (range 0 to 270.6) compared to 17.47 CepiCs/mL +/-27.8 (range 0 to 72.3) in benign. Additionally, all the CK(+) morphologically distinct cells were EpCAM(-). There is no significant difference between benign and malignant cases when analyzing draws after biopsy. Conclusion: HD-CTC technology is feasible for detection of CepiCs in early stage breast cancer, and in some cases, results in retrieval of a large number of them. Additional technology refinements including determination of appropriate thresholds are needed to improve discrimination of cancer patients from non-cancer, and follow up will help determine whether HD-CTC assay derived enumeration and characterization of CepiCs are associated with prognosis. These early results are promising and ongoing studies at Duke with TSRI will further evaluate the role of CepiCs in early stage breast cancer along with the isolation and analysis of DNA from single-CepiCs. New data will be available by time of presentation. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-03-05.

On-site management of investigational products and drug delivery systems in conformity with Good Clinical Practices (GCPs)

Investigators and research teams participating in clinical trials have to deal with complex investigational products, study designs, and research environments. The emergence of new drug delivery systems and investigational products combining more than one drug and the development of biodrugs such as monoclonal antibodies, peptides, siRNA, and gene therapy to treat orphan or common diseases constitute a new challenge for investigators and clinical sites. We describe the requirements and challenges of drug management in conformity with Good Clinical Practices (GCPs) for investigators and sites participating in clinical trials. Review At all sites participating in clinical trials, standard operating procedures (SOPs) covering the critical path of drug and drug delivery systems management are required. All steps should be auditable, including reception, validation, storage, access, preparation, distribution, techniques of administration, use, return, and destruction of research products. Biodrugs require traceability and specific SOPs on the management of potential immune reactions. Investigational products must be stored under standard auditable conditions. The traceability of storage conditions (including temperature) requires these conditions to be monitored on a continuous basis. A dedicated space with restricted access limited to authorized qualified personnel facilitates the monitoring. The development of standardized, auditable settings and the application of dedicated, site-specific SOPs for the management of investigational products and drug delivery systems contribute to guarantee the compliance to GCP requirements.