Compliant Facility Research Articles

Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease

Human embryonic stem cell (hESC)-derived midbrain dopaminergic (mDA) cell transplantation is a promising therapeutic strategy for Parkinson's disease (PD). Here, we present the derivation of high-purity mDA progenitors from clinical-grade hESCs on a large scale under rigorous good manufacturing practice (GMP) conditions. We also assessed the toxicity, biodistribution, and tumorigenicity of these cells in immunodeficient rats in good laboratory practice (GLP)-compliant facilities. Various doses of mDA progenitors were transplanted into hemi-parkinsonian rats, and a significant dose-dependent behavioral improvement was observed with a minimal effective dose range of 5,000-10,000 mDA progenitor cells. These results provided insights into determining a low cell dosage (3.15 million cells) for human clinical trials. Based on these results, approval for a phase 1/2a clinical trial for PD cell therapy was obtained from the Ministry of Food and Drug Safety in Korea, and a clinical trial for treating patients with PD has commenced.

Development, Construction and Certification of a Facility for Exterior Noise Regulatory Compliance Testing

OEMs are required to meet applicable regulations for exterior noise. Acceleration noise (typically called pass-by noise) regulations have an upper limit for noise emission. In addition, vehicles which can operate without a combustion engine must comply with regulations for minimum noise emitted during low speed driving. In order to make regulation-compliant measurements for global destinations, a test track meeting requirements of ISO 10844 may be necessary. However, strictly meeting this requirement doesn't guarantee a usable facility for efficient measurements. This paper describes design goals, challenges and construction of a regulation compliant facility in Arizona. The intent was to build a facility with a long usable life before requiring repaving, sufficient isolation from nearby test roads, 24-hour usability and onsite amenities to accommodate technical staffs and vehicle retrofits. Consideration of needs of all stakeholders was necessary to make a facility not only regulation-compliant but also attractive to internal and external customers.

Multi-faceted metagenomic analysis of spacecraft associated surfaces reveal planetary protection relevant microbial composition.

The National Aeronautics and Space Administration (NASA) has been monitoring the microbial burden of spacecraft since the 1970's Viking missions. Originally culture-based and then focused 16S sequencing techniques were used, but we have now applied whole metagenomic sequencing to a variety of cleanroom samples at the Jet Propulsion Lab (JPL), including the Spacecraft Assembly Facility (SAF) with the goals of taxonomic identification and for functional assignment. Our samples included facility pre-filters, cleanroom vacuum debris, and surface wipes. The taxonomic composition was carried out by three different analysis tools to contrast marker, k-mer, and true alignment approaches. Hierarchical clustering analysis of the data separated vacuum particles from other SAF DNA samples. Vacuum particle samples were the most diverse while DNA samples from the ISO (International Standards Organization) compliant facilities and the SAF were the least diverse; all three were dominated by Proteobacteria. Wipe samples had higher diversity and were predominated by Actinobacteria, including human commensals Cutibacterium acnes and Corynebacterium spp. Taxa identified by the three methods were not identical, supporting the use of multiple methods for metagenome characterization. Likewise, functional annotation was performed using multiple methods. Vacuum particles and SAF samples contained strong signals of the tricarboxylic acid cycle and of amino acid biosynthesis, suggesting that many of the identified microorganisms have the ability to grow in nutrient-limited environments. In total, 18 samples generated high quality metagenome assembled genomes (MAG), which were dominated by Moraxella osloensis or Malassezia restricta. One M. osloensis MAG was assembled into a single circular scaffold and gene annotated. This study includes a rigorous quantitative determination of microbial loads and a qualitative dissection of microbial composition. Assembly of multiple specimens led to greater confidence for the identification of particular species and their predicted functional roles.

Development of a human umbilical cord-derived mesenchymal stromal cell-based advanced therapy medicinal product to treat immune and/or\xa0inflammatory diseases

BackgroundUmbilical cord-derived mesenchymal stromal cells (UC-MSCs) revealed their key role in immune regulation, offering promising therapeutic perspectives for immune and inflammatory diseases. We aimed to develop a production process of an UC-MSC-based product and then to characterize UC-MSC properties and immunomodulatory activities in vitro, related to their clinical use and finally, to transfer this technology to a good manufacturing practice (GMP) compliant facility, to manufacture an advanced therapy medicinal product (ATMP).MethodsFifteen human umbilical cords (UCs) were collected to develop the production process. Three batches of UC-MSCs from a single donor were characterized at basal state and after in vitro pro-inflammatory stimulation by interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα). Proliferation, immunophenotype, activation markers’ expression and the inhibition of T cell proliferation were assessed. Finally, this technology was transferred to a GMP-compliant facility to manufacture an UC-MSC-based ATMP, from a single donor, using the explant method followed by the establishment of master and work cell stocks.ResultsTwelve UCs were processed successfully allowing to isolate UC-MSCs with doubling time and population doubling remaining stable until passage 4. CD90, CD105, CD73, CD44, CD29, CD166 expression was positive; CD14, CD45, CD31, HLA-DR, CD40, CD80 and CD86 expression was negative, while CD146 and HLA-ABC expression was heterogeneous. Cell morphology, proliferation and immunophenotype were not modified by inflammatory treatment. Indoleamine 2,3-dioxygenase (IDO) expression was significantly induced by IFNγ and IFNγ + TNFα versus non-treated cells. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression was induced significantly after priming. T cell proliferation was significantly decreased in the presence of UC-MSCs in a dose-dependent manner. This inhibitory effect was improved by IFNγ or IFNγ + TNFα, at UC-MSCs:PBMC ratio 1:10 and 1:30, whereas only IFNγ allowed to decrease significantly T cell proliferation at ratio 1:100. The manufacturing process of the UC-MSC-based ATMP was qualified and authorized by the French regulatory agency for clinical use (NCT04333368).ConclusionThis work allowed to develop an investigational UC-MSC-based ATMP authorized for clinical use. Our results showed that an inflammatory environment preserves the biological properties of UC-MSCs with an improvement of their immunomodulatory functions.

Environmental injustice in Clean Water Act enforcement: racial and income disparities in inspection time

Decades of research has documented that people of color and low-income experience disproportionate environmental burdens, with recent empirical studies showing these burdens are exacerbated by disparities in government regulatory enforcement. Scholars’ attention to enforcement disparities as a source of environmental injustice highlights that government behavior may contribute to ongoing inequities in environmental outcomes. To date, studies analyzing enforcement disparities have employed statistical models to either estimate the probability that a federal or state agency performs an enforcement action or the total number of such actions over some duration of time. In this study, we adopt an alternative approach that analyzes the duration of time it takes for government officials to inspect a facility to determine if there is a difference based on the demographics of the host community. Specifically, we study administrative data from state implementation of the U.S. Clean Water Act (CWA), which we couple with demographic information around large, regulated facilities to analyze the relationship between response time and community characteristics. Estimating event history models, we find that state regulators’ inspection response time is slower toward noncompliant facilities located in communities that have higher percentages of poor and Hispanic citizens. With respect to Black communities, state regulators’ response time to noncompliant facilities is no different than compliant facilities. Collectively, these results indicate that state regulators are not prioritizing CWA facilities that violate performance requirements when they are in environmental justice communities.

High priority violations and intra-firm pollution substitution

We examine the sign and the magnitude of pollution leakage associated with the High Priority Violations Policy (HPVP) under the Clean Air Act. Using 46,012 facility-year observations for 7947 polluting facilities across all industries in the U.S., we find strong evidence of intra-firm pollution substitution associated with the HPVP. On average, a compliant facility increased its toxic air emissions by about 35–56 percent (3600 to 6000 lbs.) if it had at least one other sister facility, within the same 6-digit NAICS industry code and belonging to the same parent firm, concurrently under violation. The magnitude of such intra-firm pollution substitution was stronger towards compliant facilities with no prior history of high priority violation as well as towards those owned by private parent companies. We also find that substitution of pollution from a sister facility under violation increases the risk of violation among currently compliant facilities.

Preclinical Assessment of Autologous Tolerogenic Dendritic Cells From End-stage Renal Disease Patients.

Kidney transplantation is the therapeutic of choice for patients with kidney failure. While immunosuppressive drugs can control graft rejection, their use is associated with increased infections and cancer, and they do not effectively control chronic graft rejection. Cell therapy is an attractive strategy to minimize the use of pharmacological drugs. We recently developed a protocol to generate human monocyte-derived autologous tolerogenic dendritic cells (ATDCs) from healthy volunteers. Herein, we transferred the ATDC manufacturing protocol to a Good Manufacturing Practice (GMP)-compliant facility. Furthermore, we compared the phenotype and in vitro functions of ATDCs generated from patients with end-stage renal disease to those generated from healthy volunteers. We describe the critical steps for GMP-compliant production of ATDCs and define the quality criteria required to allow release of the cell products. Furthermore, we showed that ATDCs generated from healthy volunteers and patients with kidney failure display the same tolerogenic profile based on their phenotype, resistance to maturation, and ability to modulate T-cell responses. Together, these results allowed us to define the production process and the quality criteria for the release of ATDCs before their administration in patients receiving a kidney transplant.

Tackling the unique challenges of capacity planning for autologous cell therapies

<h3>Background & Aim</h3> Capacity planning has been a long-standing issue in the pharmaceutical industry; setting up Good Manufacturing Practices (GMP) compliant facilities is time-consuming and capital-intensive, but for products to be able to generate maximal economic returns during the market exclusivity period, timely availability of manufacturing capacity is vital. Capacity crunches faced by the monoclonal antibody (mAb) industry in the 1990s were estimated to have caused around $3-$4 billion losses in total revenue due to insufficient product supply. In addition, the uncertainties in clinical trial outcomes, market pressures, and regulations make the multi-objective optimisation of capacity planning and product development decisions critical for the industry. In this work, we present a detailed analysis of the above challenges, and propose to develop a mixed-integer linear programming optimisation model to address the unique challenges of autologous cell therapies. <h3>Methods, Results & Conclusion</h3> Previous studies have considered the optimisation of investment strategies for product development, manufacturing facility investment decisions and global multi-site supply chain optimisation for drugs and multi-site continuous bioprocess optimisation for biologics. As more advanced therapeutic medicinal products (ATMPs) move from bench to clinic, the unique challenges for autologous cell therapies present a new problem in the capacity planning domain. Firstly, the unique requirement for autologous cell therapies to be produced on-demand with cell material originating from patients has proven to be commercially challenging. Secondly, with geographical and supply chain constraints, companies are considering building multiple facilities in different regions or finding alternative arrangements such as licensing and outsourcing. Thirdly, fast-track regulatory frameworks introduced by various regulatory authorities are improving the speed-to-market and have allowed faster commercialisation of ATMPs for life-threatening diseases. The clinical development duration can be reduced from 6-7 years (phase 1, phase 2, phase 3 clinical trial) to 2-3 years (small scale clinical trials with surrogate end-points). Therefore, the commercialisation timeline for process, CMC development, and capacity planning decisions should also be considered earlier. The approach can potentially allow the industry to make better-informed investment decisions and accelerate the commercialisation of these life-saving therapies.

Phase I/II Manufacture of Lentiviral Vectors Under GMP in an Academic Setting.

In clinical gene transfer applications, lentiviral vectors (LV) have rapidly become the primary means to achieve permanent and stable expression of a gene of interest or alteration of gene expression in target cells. This status can be attributed primarily to the ability of the LV to (1) transduce dividing as well as quiescent cells, (2) restrict or expand tropism through envelope pseudo-typing, and (3) regulate gene expression within different cell lineages through internal promoter selection. Recent progress in viral vector design such as the elimination of unnecessary viral elements, split packaging, and self-inactivating vectors has established a significant safety profile for these vectors. The level of GMP compliance required for the manufacture of LV is dependent upon their intended use, stage of drug product development, and country where the vector will be used as the different regulatory authorities who oversee the clinical usage of such products may have different requirements. As such, successful GMP manufacture of LV requires a combination of diverse factors including: regulatory expertise, compliant facilities, validated and calibrated equipments, starting materials of the highest quality, trained production personnel, scientifically robust production processes, and a quality by design approach. More importantly, oversight throughout manufacturing by an independent Quality Assurance Unit who has the authority to reject or approve the materials is required. We describe here the GMP manufacture of LV at our facility using a four plasmid system where 293T cells from an approved Master Cell Bank (MCB) are transiently transfected using polyethylenimine (PEI). Following transfection, the media is changed and Benzonase added to digest residual plasmid DNA. Two harvests of crude supernatant are collected and then clarified by filtration. The clarified supernatant is purified and concentrated by anion exchange chromatography and tangential flow filtration. The final product is then diafiltered directly into the sponsor defined final formulation buffer and aseptically filled.

The quality of breast cancer quality measures.

108 Background: To assess quality in breast cancer care, standardized metrics are needed. Many accepted breast performance metrics are based on evidence-based practice; however, most fail to reflect patient choice in treatment decisions. Given the focus on patient-centered breast care, we sought to determine how compliance with established quality metrics correlates with receipt of breast cancer care impacted by patient preference. Methods: American College of Surgeons (ACS) National Cancer Data Base facilities were designated compliant or non-compliant based on Commission of Cancer (CoC) breast metrics MASTRT, BCSRT and HT*, which all improve survival. Compliant facilities met the expected performance rate (EPR) for all three metrics, while non-compliant facilities failed to meet the EPR for any. Rates of breast conserving surgery (BCS) for early stage cancer, immediate breast reconstruction (IBR), and contralateral prophylactic mastectomy (CPM) are proposed metrics that are impacted by patient preference. For these, quality is defined as high rates of BCS, high rates of IBR, and low rates of CPM. Multivariable logistic regression models were used to estimate the association between facility level rates on these measures and the probability of treatment at a CoC compliant facility. Results: 729 facilities were included in the analysis. Based on the CoC measures, 79 (10.8%) were considered compliant and 650 (89.2%) non-compliant. Rates of BCS and IBR did not differ between compliant and non-compliant facilities; however, women treated at compliant facilities were more likely to undergo CPM (26.3% vs 21.4%; p = 0.02). In a multivariate model treatment at compliant facilities was associated with higher rates of BCS, IBR, and CPM; however, the predictive value of these metrics was minimal (Estimated OR range: 1.01-1.03). Conclusions: Rates of preference driven therapies do not differentiate CoC compliant and non-compliant hospitals. The quality of a hospital’s breast care is likely poorly measured by metrics that are influenced by, but cannot account for patient values. *MASTRT (RT≤1yr of diagnosis in women with ≥4 +lymph nodes); BCSRT (RT ≤1yr of diagnosis for women ≤70 receiving BCS); HT (hormone therapy recommended ≤1yr of diagnosis for HR-positive breast cancer)

Muslim service quality dimensions in the tourism and hospitality industry: construct development and measurement validation

Although Muslims make up one of the largest tourist markets in the world, service quality of tourism and hospitality offerings oriented toward this market has not been clearly defined. By means of a multi-dimensional procedure, the authors have developed a scale for measuring Muslim service quality (MSQ) through 29 items classified into six dimensions: tangibility, reliability, responsiveness, assurance, empathy and Shari'ah compliant facilities. The importance of the proposed constructs was theoretically discussed and justified. Using a sample of 345 Muslim tourists, the constructs are then tested and validated. This study provides new theoretical grounds for studying MSQ. It also supplies tourism and hospitality companies with a number of operative factors that may be essential if they are to remain competitive in the dynamic marketplace. It is probably the first to provide an integrative perspective of MSQ constructs in the tourism and hospitality industry.

Relative costs of anesthesiologist prepared, hospital pharmacy prepared and outsourced anesthesia drugs

BackgroundAnesthesia drugs can be prepared by anesthesia providers, hospital pharmacies or outsourcing facilities. The decision whether to outsource all or some anesthesia drugs is challenging since the costs associated with different anesthesia drug preparation methods remain poorly described. MethodsThe costs associated with preparation of 8 commonly used anesthesia drugs were analyzed using a budget impact analysis for 4 different syringe preparation strategies: (1) all drugs prepared by anesthesiologist, (2) drugs prepared by anesthesiologist and hospital pharmacy, (3) drugs prepared by anesthesiologist and outsourcing facility, and (4) all drugs prepared by outsourcing facility. Main resultsA strategy combining anesthesiologist and hospital pharmacy prepared drugs was associated with the lowest estimated annual cost in the base-case budget impact analysis with an annual cost of $225 592, which was lower than other strategies by a margin of greater than $86 000. ConclusionA combination of anesthesiologist and hospital pharmacy prepared drugs resulted in the lowest annual cost in the budget impact analysis. However, the cost of drugs prepared by an outsourcing facility maybe lower if the capital investment needed for the establishment and maintenance of the US Pharmacopeial Convention Chapter <797> compliant facility is included in the budget impact analysis.

Autologous mesenchymal stromal cell transplantation for spinal cord injury: A Phase I pilot study

Background aimsMesenchymal stromal cell (MSC) transplantation has immerged as promising therapeutic approach to treat spinal cord injury (SCI). In this pilot study, we investigated the safety of intrathecal injection of autologous bone marrow–derived MSCs in nine patients with SCI. MethodsPatients with complete SCI at the thoracic level were divided into two groups: chronic (>6 months, group 1) and sub-acute SCI (<6 months, group 2), according to time elapsed since injury. MSCs were isolated by density gradient separation of autologous bone marrow harvested from the iliac crest. Cells were cultured in a Good Manufacturing Practice–compliant facility to produce clinical scale dose. After quality control testing, MSCs were injected back to patients by intrathecal injection. Safety was defined as absence of adverse event and side effects after 1 month after receiving the injection. ResultsSix patients had chronic SCI with a median duration of 33 months since date of injury (range: 10–55 months), and three patients were in sub-acute phase of disease. Each patient received two or three injections with a median of 1.2 × 106 MSCs/kg body weight. No treatment-related adverse event was observed during median follow-up of 720 days (range: 630–826 days) in group 1 and 366 days (range: 269–367 days) in group 2, respectively. DiscussionThis pilot study demonstrated that autologous MSCs can be safely administered through intrathecal injection in spinal cord injury patients. Further investigation through randomized, placebo-controlled trials is needed.

Code Compliant School Buildings Boost Student Achievement

1. Ronald B. Lumpkin[1][1] 2. Robert T. Goodwin Jr.[1][1] 3. Warren C. Hope[1][1] 4. Ghazwan Lutfi[1][1] 1. 1Florida A&M University, Tallahassee, USA 1. Warren C. Hope, College of Education, Department of Educational Leadership & Counseling, Florida A&M University, Tallahassee, FL 32307, USA. Email: warren.hope{at}famu.edu Much of the focus in the literature in raising student achievement has included parental involvement, principal leadership, quality of instruction, students’ socioeconomic status, curriculum, and use of technology. Limited empirical research relates the condition of the school building as a variable that affects student achievement. Furthermore, there is no research that has examined the impact of building codes on achievement outcomes in the state of Florida. This research determined whether academic achievement of 4th-, 8th-, 9th-, and 10th-grade students as measured by the mathematics and reading subtests of the Florida Comprehensive Achievement Test (FCAT) increased in new school buildings compliant to the 2000 Florida State Requirements for Educational Facilities. A causal-comparative design determined whether the independent variables, old and new school building influenced student achievement as measured by students’ FCAT mathematics and reading subtest scores. The control group was two cohorts of 4th-, 8th-, 9th-, and 10th-grade students who attended school in old buildings. The experimental group was two cohorts of 4th-, 8th-, 9th-, and 10th-grade students who attended school in new buildings. Transition from an old school into a new school was the treatment. Two hypotheses were formulated for testing and the research question for the inquiry was whether the percentage of students passing the FCAT mathematics and reading subtests increases after transitioning from an old school building into a new 2000 UBC (Uniform Building Code) compliant facility. [1]: #aff-1

Accelerated stability and bioassay of a new oral α-ketoglutarate formulation for treating cyanide poisoning

Context: Due to several limitations of existing cyanide antidotes, α-ketoglutarate (α-KG) has been proposed as a promising treatment for cyanide.Objective: This study reports the accelerated stability and bioassay of a new oral α-KG formulation.Materials and methods: Amber-colored PVDF bottles containing 100 ml of 10% α-KG in 70% sorbitol, preservative (sodium methyl paraben and sodium propyl paraben), sweetener (sodium saccharine), flavor (American ice-cream soda and peppermint) and color (tartrazine), at pH 7.0–8.0 were stored in stability chamber (40 ± 2 °C and 75 ± 5% humidity) for 6 months in a GMP compliant facility. Various physical (pH, color, evaporation, extractable volume and clarity), chemical (identification and quantification of active ingredient) and microbiological (total aerobic count) analyses, together with protection studies were carried periodically in mice. Acute toxicity of the formulation and bioavailability of α-KG were assessed in rats at the beginning of the experiment.Results: No physical changes and microbiological growth were observed in the formulation. After 6 months, α-KG content in the formulation diminished by ∼24% but its protective efficacy against cyanide remained at 5.9-fold. Protection was further characterized spectrophotometrically by disappearance of α-KG spectrum in the presence of cyanide, confirming cyanohydrin formation. Oral LD50 of α-KG formulation in rats was >7.0 g/kg body weight, and did not produce any acute toxicity of clinical significance. Also, an appreciable amount of α-KG was measured in blood.Conclusion: As per the guidelines of International Conference on Harmonization, the new α-KG formulation exhibited satisfactory stability, bioefficacy and safety as cyanide antidote.

7.0-T magnetic resonance imaging characterization of acute blood-brain-barrier disruption achieved with intracranial irreversible electroporation.

The blood-brain-barrier (BBB) presents a significant obstacle to the delivery of systemically administered chemotherapeutics for the treatment of brain cancer. Irreversible electroporation (IRE) is an emerging technology that uses pulsed electric fields for the non-thermal ablation of tumors. We hypothesized that there is a minimal electric field at which BBB disruption occurs surrounding an IRE-induced zone of ablation and that this transient response can be measured using gadolinium (Gd) uptake as a surrogate marker for BBB disruption. The study was performed in a Good Laboratory Practices (GLP) compliant facility and had Institutional Animal Care and Use Committee (IACUC) approval. IRE ablations were performed in vivo in normal rat brain (n = 21) with 1-mm electrodes (0.45 mm diameter) separated by an edge-to-edge distance of 4 mm. We used an ECM830 pulse generator to deliver ninety 50-μs pulse treatments (0, 200, 400, 600, 800, and 1000 V/cm) at 1 Hz. The effects of applied electric fields and timing of Gd administration (−5, +5, +15, and +30 min) was assessed by systematically characterizing IRE-induced regions of cell death and BBB disruption with 7.0-T magnetic resonance imaging (MRI) and histopathologic evaluations. Statistical analysis on the effect of applied electric field and Gd timing was conducted via Fit of Least Squares with α = 0.05 and linear regression analysis. The focal nature of IRE treatment was confirmed with 3D MRI reconstructions with linear correlations between volume of ablation and electric field. Our results also demonstrated that IRE is an ablation technique that kills brain tissue in a focal manner depicted by MRI (n = 16) and transiently disrupts the BBB adjacent to the ablated area in a voltage-dependent manner as seen with Evan's Blue (n = 5) and Gd administration.

Novel Hierarchical Test Architecture for SOC Test Methodology Using IEEE Test Standards

Abstract?SOC test methodology in ultra deep submicron (UDSM) technology with reasonable test time and cost has begun to satisfy high quality and reliability of the product. A novel hierarchical test architecture using IEEE standard 1149.1, 1149.7 and 1500 compliant facilities is proposed for the purpose of supporting flexible test environment to ensure SOC test methodology. Each embedded core in a systemon-a-chip (SOC) is controlled by test access ports (TAP) and TAP controller of IEEE standard 1149.1 as well as tested using IEEE standard 1500. An SOC device including TAPed cores is hierarchically organized by IEEE standard 1149.7 in wafer and chip level. As a result, it is possible to select/deselect all cores embedded in an SOC flexibly and reduce test cost dramatically using star scan topology.

Derivation and propagation of human embryonic stem cell lines from frozen embryos in an animal product–free environment

The protocols described here are comprehensive instructions for deriving human embryonic stem (hES) cell lines in xeno-free conditions from cryopreserved embryos. Details are included for propagation, cryopreservation and characterization. Initial derivation is on feeder cells and is followed by adaptation to a feeder-free environment; competent technicians can perform these simplified methods easily. From derivation to cryopreservation of fully characterized initial stocks takes 3-4 months. These protocols served as the basis for standard operating procedures (SOPs), with both operational and technical components, that we set to meet good manufacturing practice (GMP) and UK regulatory body requirements for derivation of clinical-grade cells. As such, these SOPs are currently used in our current GMP compliant facility to derive hES cell lines ab initio, in an animal product-free environment; these lines are suitable for research and potentially for clinical use in cell therapy. So far, we have derived eight clinical-grade lines, which will be freely available to the scientific community after submission/accession to the UK Stem Cell Bank.

Access to emergency and surgical care in sub-Saharan Africa: the infrastructure gap

The effort to increase access to emergency and surgical care in low-income countries has received global attention. While most of the literature on this issue focuses on workforce challenges, it is critical to recognize infrastructure gaps that hinder the ability of health systems to make emergency and surgical care a reality. This study reviews key barriers to the provision of emergency and surgical care in sub-Saharan Africa using aggregate data from the Service Provision Assessments and Demographic and Health Surveys of five countries: Ghana, Kenya, Rwanda, Tanzania and Uganda. For hospitals and health centres, competency was assessed in six areas: basic infrastructure, equipment, medicine storage, infection control, education and quality control. Percentage of compliant facilities in each country was calculated for each of the six areas to facilitate comparison of hospitals and health centres across the five countries. The percentage of hospitals with dependable running water and electricity ranged from 22% to 46%. In countries analysed, only 19-50% of hospitals had the ability to provide 24-hour emergency care. For storage of medication, only 18% to 41% of facilities had unexpired drugs and current inventories. Availability of supplies to control infection and safely dispose of hazardous waste was generally poor (less than 50%) across all facilities. As few as 14% of hospitals (and as high as 76%) among those surveyed had training and supervision in place. No surveyed hospital had enough infrastructure to follow minimum standards and practices that the World Health Organization has deemed essential for the provision of emergency and surgical care. The countries where these hospitals are located may be representative of other low-income countries in sub-Saharan Africa. Thus, the results suggest that increased attention to building up the infrastructure within struggling health systems is necessary for improvements in global access to medical care.

First fully DDA compliant facility in Manchester

First fully DDA compliant facility in Manchester