Coronavirus Disease 2019 and Airborne Transmission: Science Rejected, Lives Lost. Can Society Do Better?

This is an account that should be heard of an important struggle: the struggle of a large group of experts who came together at the beginning of the COVID-19 pandemic to warn the world about the risk of airborne transmission and the consequences of ignoring it. We alerted the World Health Organization about the potential significance of the airborne transmission of SARS-CoV-2 and the urgent need to control it, but our concerns were dismissed. Here we describe how this happened and the consequences. We hope that by reporting this story we can raise awareness of the importance of interdisciplinary collaboration and the need to be open to new evidence, and to prevent it from happening again. Acknowledgement of an issue, and the emergence of new evidence related to it, is the first necessary step towards finding effective mitigation solutions.

What were the historical reasons for the resistance to recognizing airborne transmission during the COVID-19 pandemic?

The question of whether SARS-CoV-2 is mainly transmitted by droplets or aerosols has been highly controversial. We sought to explain this controversy through a historical analysis of transmission research in other diseases. For most of human history, the dominant paradigm was that many diseases were carried by the air, often over long distances and in a phantasmagorical way. This miasmatic paradigm was challenged in the mid to late 19th century with the rise of germ theory, and as diseases such as cholera, puerperal fever, and malaria were found to actually transmit in other ways. Motivated by his views on the importance of contact/droplet infection, and the resistance he encountered from the remaining influence of miasma theory, prominent public health official Charles Chapin in 1910 helped initiate a successful paradigm shift, deeming airborne transmission most unlikely. This new paradigm became dominant. However, the lack of understanding of aerosols led to systematic errors in the interpretation of research evidence on transmission pathways. For the next five decades, airborne transmission was considered of negligible or minor importance for all major respiratory diseases, until a demonstration of airborne transmission of tuberculosis (which had been mistakenly thought to be transmitted by droplets) in 1962. The contact/droplet paradigm remained dominant, and only a few diseases were widely accepted as airborne before COVID-19: those that were clearly transmitted to people not in the same room. The acceleration of interdisciplinary research inspired by the COVID-19 pandemic has shown that airborne transmission is a major mode of transmission for this disease, and is likely to be significant for many respiratory infectious diseases.

Evaluation of aerosol transmission risk during home quarantine under different operating scenarios: A pilot study.

SARS-CoV-2 has been recognized to be airborne transmissible. With the large number of reported positive cases in the community, home quarantine is recommended for the infectors who are not severely ill. However, the risks of household aerosol transmission associated with the quarantine room operating methods are under-explored. We used tracer gas technique to simulate the exhaled virus laden aerosols from a patient under home quarantine situation inside a residential testbed. The Sulphur hexafluoride (SF6) concentration was measured both inside and outside the quarantine room under different operating settings including, air-conditioning and natural ventilation, presence of an exhaust fan, and the air movement generated by ceiling or pedestal fan. We calculated the outside-to-inside SF6 concentration to indicate potential exposure of occupants in the same household. In-room concentration with air-conditioning was 4 times higher than in natural ventilation settings. Exhaust fan operation substantially reduced in-room SF6 concentration and leakage rate in most of the ventilation scenarios, except for natural ventilation setting with ceiling fan. The exception is attributable to the different airflow patterns between ceiling fan (recirculates air vertically) and pedestal fan (moves air horizontally). These airflow variations also led to differences in SF6 concentration at two sampling heights (0.1 m and 1.7 m) and SF6 leakage rates when the quarantine room door was opened momentarily. Use of natural ventilation rather than air-conditioning, and operating exhaust fan when using air-conditioning are recommended to lower exposure risk for home quarantine. A more holistic experiment will be conducted to address the limitations reflected in this study.

Performance characteristics of a fan filter unit (FFU) in mitigating particulate matter levels in a naturally ventilated classroom during haze conditions.

The performance of a low-cost fan filter unit (FFU) in mitigating hazardous particulate matter (PM) levels in a naturally ventilated school classroom is presented. The FFU can be considered as a simplified mechanical ventilation and air-conditioning system without heating and cooling functions. The FFU improves indoor air quality through introduction of cleaned outdoor air to flush out internally generated heat and moisture and reducing infiltration by maintaining indoor pressurization. Indoor particle number concentrations were reduced between 85% and 95%. The particle removal performance (PRFFFU ) of the FFU is determined and incorporated into the augmented façade penetration factor (Paug ). A case-specific recursive dynamic mass balance model is used to characterize the infiltration factor (FINF ), deposition rate (K), and the penetration efficiency (Paug ) from continuously monitored indoor and outdoor mass concentration levels. Computed "Paug " (0.07, 0.09, and 0.13) and "FINF " (0.06, 0.08, and 0.11), respectively, for PM10, PM2.5, and PM1 suggest that exposure to PM was significantly reduced indoors. The effectiveness of the FFU for reduced "FINF " and "Paug " may be attributed to its superior filtration, dilution, and exfiltration mechanisms. In comparison with alternative PM mitigation solutions, the FFU is effective, affordable, and sustainable.

Conduction Mechanisms in Polyvinyl Alcohol: CdS/CdS:Cu Nanoparticle Hybrid Nanocomposites.

The electrical conduction mechanisms were investigated for the CdS and Cu-doped CdS (CdS:Cu) nanoparticles embedded in polyvinyl alcohol (PVA) (PVA/CdS and PVA/CdS:Cu) nanocomposites; synthesized by the chemical Sol Gel method on indium tin-oxide (ITO) substrate. X-ray diffraction pattern results show that the PVA/CdS nanocomposite is hawleyite-sturcture and PVA/CdS:Cu nanocomposites show greenockite-hawelyite mixed structure. The sizes of CdS and CdS:Cu nanoparticles were estimated from transmission electron microscopy (TEM) images and are ≈4 nm and ≈10 nm respectively; which were formed inside the PVA polymer layer. The devices were fabricated with Ag and ITO as electrodes with PVA/CdS and PVA/CdS:Cu nanocomposites as an active layers. The current-voltage (I-V ) relationships measurements shows the nature is extended memrisitve features for both PVA/CdS and PVA/CdS:Cu nanocomposites. The ION/IOFF ratios are enhanced and become more prominent in case of PVA/CdS:Cu nanocomposites device. The resistive switching characteristic show Schottky, Trapped-charge limited current (TCLC) and Space charge limited conduction (SCLC) mechanisms in Ag/PVA/CdS/ITO device; whereas Schottky, Ohmic, TCLC and SCLC were observed in Ag/PVA/CdS:Cu/ITO device.

Self-Perceived Nutritional Competency of Primary Healthcare Physicians in Qassim, Saudi Arabia.

INTRODUCTION: Overnutrition plays a vital role in the development of a spectrum of non-communicable diseases. Diet-related disorders have a huge impact on personal health as well as the country's economy for the management of such disorders. The study aims to assess the primary healthcare physicians' nutrition competency, which will be beneficial for evaluating the current situation and future strategies, training, nutrition care, and disease prevention. METHODOLOGY: Among 147 primary healthcare physicians by simple random sampling from four cities and two rural areas of Qassim, Saudi Arabia, from December 2022 to December 2023 using a validated (NUTCOMP) tool. Data were entered, cleaned, and analyzed with SPSS software version 21.0 (IBM Corp., Armonk, NY). Informed consent was obtained from all study participants. Chi-square and ANOVA tests were applied to draw the significant differences. RESULTS: A total of 147 participants enrolled in this study, and the mean age and standard deviation (SD) of the study population were 34.38 ± 6.57. More than half of the physicians (n = 76, 51.7%) continued education on nutrition. Significant mean differences were observed between some and focused nutrition content received physicians versus no nutrition content received physicians concerning nutrition skill, communication, and nutrition attitude consecutively (P < 0.0001, P < 0.0001, and P < 0.0001). The mean nutrition knowledge, skill, communication, attitude score, and SD of PHCC physicians were 26.91 ± 5.42 (maximum 35), 31.19 ± 6.18 (maximum 40), 36.73 ± 7.48 (maximum 45), and 34.74 ± 6.23 (maximum 40), respectively. CONCLUSIONS: Our study results show primary healthcare physicians perceive themselves to have good nutritional competency.

The Assessment of Geriatric Depression Among Primary Healthcare Physicians in Buraidah City, Saudi Arabia.

BACKGROUND:  The global geriatric population is increasing, leading to a higher prevalence of non-communicable diseases, including depression. This condition often remains underdiagnosed and untreated disease. METHODOLOGY: A cross-sectional study was conducted among 130 primary healthcare physicians (PCPs) in Buraidah to assess their practices in diagnosing geriatric depression from March 2023 to March 2024. After ethical committee approval, data were collected through a self-administered questionnaire, entered, cleaned, and analyzed with Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 21.0, Armonk, NY). Informed consent was obtained and the confidentiality of the participant information was maintained. Statistical tests, including the Chi-square test, were used for inference. RESULTS: Out of 130 PCPs, 85.4% (n=111) were diagnosing depression during their clinical practice. The most common depression scale used in their regular practice was the patient health questionnaire (PHQ)-2 (70%, n=91), followed by the Geriatric Depression Scale (53.8%, n=70). Nearly 26.2% (n=34) of physicians responded that there is no need for routine lab tests for the diagnosis of depression. Concerning the initial plan of depression management, nearly 76.2% (n=99) of physicians preferred non-pharmacological treatment. Regarding barriers to diagnosis of depression in elderly patients, nearly 76.2% (n=99) mentioned the need for more training about geriatric depression, followed by 70% for both short consultation time and the need for Ministry of Health guidelines. There was a statistically significant association observed between <35 years of age group and a preference for a high percentage of pharmacological therapy (P<0.05). CONCLUSIONS: Based on the findings of the study, there was a good number (85.4%) of PCPs diagnosing depression in their clinics, and also three-fourths of the physicians (76.2%) preferred non-pharmacological treatment. Only one-fourth (26.2%) of the PCPs mentioned no lab is required for the diagnosis of depression.

Managing Adult Obese Patients at Primary Health Care Centers in Qassim Province, Saudi Arabia.

Background Overweight and obesity have become a global health problem. This study aims to reduce the same problem, primarily with all levels of physicians and the hidden responsibility of all other allied health care workers and communities, including families and individuals. Objective The objective of this study is to determine the knowledge, attitude, and practice among the physicians toward the management of adult obesity at primary health care centers (PHCCs) of Qassim Province, Saudi Arabia. Methods A cross-sectional study was conducted among the 140 physicians working at the PHCC of Qassim through a self-administered questionnaire. A simple random method was used for the PHCC selection, and all the physicians were included at the PHCC level. Data was collected, cleaned, and analyzed with IBM SPSS Statistics, version 21.0 (IBM Corp., Armonk, NY). Necessary statistical tests were applied. Results The mean age and standard deviation (SD) in the study population were 34.29 ± 9.42, and 55.7% were males. The mean knowledge score and SD of correct answers were 4.61 ± 1.31. About four or more questions were answered correctly out of six knowledge questions (80.7%, n = 113). Out of 13 questions, the mean ± SD of correct practice questions was 9.88 ± 2.02. The mean ± SD of attitude questions was 8.06 ± 1.13. About 33 (23.6%) of the study population received obesity training courses. Conclusions Based on the study results, good knowledge, practice, and attitude were observed among the PHCC physicians of Qassim. However, a smaller number of physicians received obesity training in the study.

Knowledge of Gestational Diabetes Mellitus Among Adult Females in Al Qassim Province, Saudi Arabia: A Cross-Sectional Study.

Background Gestational diabetes mellitus (GDM) is a carbohydrate intolerance of variable severity with onset or first recognition during pregnancy; it does not include diabetics who become pregnant or women who become lactosuric. Knowledge of this problem among the public will promote its prevention, screening, and treatment strategies. This study aims to assess the knowledge of GDM regarding its risk factors, screening, treatment, and complications among women in the Al Qassim Province, Saudi Arabia. Method A cross-sectional study was conducted among 617 females aged 18 years and older through convenience sampling between October 2022 and January 2023. An online questionnaire was distributed using Google Forms (Google LLC, Mountain View, CA, USA) and WhatsApp (Meta, Menlo Park, CA, USA). Data was entered, cleaned, and analyzed using SPSS Statistics version 27 (IBM Corp., Armonk, NY, USA). Informed consent was obtained from every participant, and the participants' information was kept confidential. Results In this study, 52.4% of the women (323/617) had moderate knowledge, and 27.6% (170/617) had excellent knowledge about GDM. Only 13.3% (n = 82) knew the optimum time (24 to 28 weeks of gestational age) for gestational diabetes screening in the absence of risk factors. Moreover, 44.6% (n = 275) knew that insulin is one of the treatments for gestational diabetes, while 45.4% (n = 280) knew that gestational diabetes increases a baby's risk of obesity and type 2 diabetes mellitus (T2DM) later in life. A statistically significant association was found between the development of GDM with multigravida (19.5%), a BMI of >25 (15%), and age 31 to 45 years (17.8%), with corresponding p-values of 0.001, 0.0001, and 0.0001, respectively. Conclusion In this study, almost four-fifths of the study population had moderate to excellent knowledge regarding GDM. However, there is a need to enhance knowledge about optimum screening time and insulin use for gestational diabetes treatment. Therefore, encouraging the existing population to learn more about diabetes education programs and health promotional measures should be undertaken periodically. Further studies are required to support this study's findings.

Optimization of Magnetic Behaviors of Au-NP-Decorated MWCNTs and Reduced Graphene Oxide for Biomedical Applications.

Optimization of electronic/magnetic behaviors of chemically decorated diamagnetic noble-metal gold nanoparticles (Au-NPs ≈5 at. %) on multiwalled carbon nanotubes (MWCNTs) and reduced graphene oxide (r-GO) is studied for future uses of optoelectronic/magnetic and biomedical applications. The changes between Au 4f5/2 and Au 4f7/2 ≈ 3.7 eV in X-ray photoelectron spectroscopy and 1.1 (±0.3) eV shifts in the C K-edge in X-ray absorption near edge structure spectroscopy confirm that the reduced form of Au0 was present in the Au-NP-decorated nanocomposites. The potential difference (ΔV) is built due to charge creations at the interface of r-GO/MWCNTs and Au-NPs and shifts in the Fermi level (ΔE F) due to electronic transfer effects, and as a result, the work functions are reduced from 3.2 eV (MWCNTs) to 3.0 eV (MWCNTs:Au-NPs) and 3.1 (r-GO) to 2.8 eV (r-GO:Au-NPS), respectively. Negligible remanence/coercivity in MWCNTs/r-GO (/Au-NPs) with blocking temperature ≈300 K in MWCNTs:Au-NPs accounted for the existence of diamagnetic Au-NPs in these nanocomposites, which implies a superparamagnetic nature. These results furnish the evidence about the optimization of magnetic behaviors of r-GO/MWCNTs (/Au-NPs) that may possibly be altered as a novel contrast agent for clinical magnetic resonance imaging, drug delivery, and hyperthermia applications.

Possible ferro-electro-magnetic behaviours of graphene-based materials: hydrogenated graphene, MWCNTs and reduced graphene-oxide (GO).

This study investigated the electric polarization and magnetic behaviours of various graphene-based materials, including hydrogenated graphene (H-graphene), multi-wall carbon nanotubes (MWCNTs), and reduced graphene oxide (r-GO). Results showed that MWCNTs exhibit higher magnetization, with a magnetic squareness (M r/M s) of approximately ≈0.5, compared to H-graphene (≈0.25). H-graphene exhibits the highest electric polarization compared to MWCNTs/r-GO, whereas r-GO demonstrates the lowest levels of polarization and magnetization compared to H-graphene/MWCNTs. The valence band maximum (4.08 eV for MWCNTs, 4.26 eV for H-graphene, and 4.78 eV for r-GO) in quasi-localized states at the Fermi level results in defects in the graphene-based lattice, which are associated with dipole moment and lead to alterations in magnetic behaviours. Different density of states (DOS) is attributed from the ultra-violet photoelectron spectra and the small variations in the Fermi edge is observed in H-graphene, MWCNTs, and r-GO are responsible for the observed magnetisation and polarizations. The unique polarization/magnetization behaviours present an opportunity for potential exploitation in storage and information processing technologies in the science and engineering community.

Mandating indoor air quality for public buildings.

If some countries lead by example, standards may increasingly become normalized.

Doctors Perceptions Regarding Electronic Systems at Primary Healthcare Centers in Qassim Region, Saudi Arabia.

BACKGROUND: Close to three-fourths of the population's health problems can be managed by way of providing care and prevention strategies at the primary healthcare center (PHCC) level. Periodical collections of physicians' perceptions about electronic systems at primary healthcare centers are required for quality improvement and also for the benefit of community practice. The objectives of the study are to find the physicians' perceptions, performance, and communication status with electronic systems. METHODOLOGY: A cross-sectional study was conducted among the PHCC physicians during the period from September 2022 to October 2023. Data was collected through semi-structured, self-administered electronic forms distributed to physicians based on the criteria. Data was entered, cleaned, and analyzed with Statistical Package for Social Sciences (SPSS) version 20 software (IBM Corp., Armonk, New York). Necessary statistical tests like proportions and chi-square tests were applied. RESULTS: In the present study, 135 primary healthcare physicians participated. The response rate in the study population was 95%, and the mean age and the standard deviation in the study population were 32.99 ± 8.05. Approximately 91.1% of the physicians expressed that systems are essential in their daily work. Also, a similar percentage (90%) was observed about improving the quality of care. In contrast to this result, 60.8% of the physicians mentioned increased productivity, and decision-making was about 61.5%. CONCLUSIONS: Based on the study findings, physicians gave good perceptions about electronic systems working at PHCC. However, certain domains need to be improved in regard to decision-making and increasing productivity.

A single-blind field intervention study of whether increased bedroom ventilation improves sleep quality.

A four-week-long field intervention experiment was conducted in twenty-nine bedrooms with extract ventilation systems and air inlet vents. During the first week no interventions took place. In the three weeks that followed, each participant slept for one week under a low, moderate, and high ventilation rate condition in a balanced order. These conditions were established by covertly altering the fan speed of the exhaust ventilation system without changing other settings. Participants were not informed when or even whether the changes to bedroom ventilation would be executed. The bedroom environmental quality was monitored continuously and sleep quality was monitored using wrist-worn trackers. Tests of cognitive performance were conducted in the evening and morning. In twelve bedrooms where clear differences between the three ventilation conditions occurred, as indicated by the measured CO2 concentrations, participants had significantly less deep sleep, more light sleep and more awakenings at lower ventilation rate conditions. In twenty-three bedrooms where a clear difference in ventilation rate between the high and low ventilation conditions was observed, as confirmed by the measured CO2 concentrations, the deep sleep was significantly shorter in the low ventilation rate condition. No differences in cognitive performance between conditions were observed. At lower ventilation rate conditions, the concentrations of CO2 increased, as did the relative humidity, while bedroom temperatures remained unchanged. The present results, which were obtained in actual bedrooms, confirm the findings in previous studies of a positive effect of increased ventilation on sleep quality. Further studies with larger populations and better control of bedroom conditions, particularly ventilation, are required.

A review of occupancy-based building energy and IEQ controls and its future post-COVID.

Occupancy schedules and density can have a substantial influence on building plug, lighting, and air conditioning energy usage. In recent years, the study related to occupancy and its impact on building energy consumption has gained momentum and is also promoted by ASHRAE as it has created a multi-disciplinary group to encourage a comprehensive study of occupant behaviour in buildings. Past studies suggest that building systems do not consume the same energy and provide similar Indoor Environmental Quality (IEQ) to their designed specifications due to inaccurate assumptions of occupants and their behaviour. Supplying ASHRAE 62.1 specified minimum required ventilation based on accurate occupancy may lead to significant air-conditioning energy savings. However, the same strategy is not suitable in the current time since minimum required ventilation may not be sufficient to mitigate the SARS-CoV-2 virus spread in confined spaces. High-temperature cooling augmented with elevated air movement across an acceptable range of velocity can maintain the health and comfort of occupants by providing higher ventilation and without an energy penalty. The analysis of the literature highlights strengths, weaknesses, and key observations about the existing occupancy monitoring and occupancy-based building system control methods to help in the direction of future occupancy-based research.

Enhancement of field emission characteristics of carbon nanotubes on oxidation.

Vertically aligned multi-walled carbon nanotubes (CNTs) were grown on p-type silicon wafer using thermal chemical vapor deposition process and subsequently treated with oxygen plasma for oxidation. It was observed that the electron field emission (EFE) characteristics are enhanced. It showed that the turn-on electric field (E(TOE)) of CNTs decreased from 0.67 (untreated) to 0.26 V/microm (oxygen treated). Raman spectra showed that the numbers of defects are increased, which are generated by oxygen-treatment, and absorbed molecules on the CNTs are responsible for the enhancement of EFE. Scanning electron microscopy and Transmission electron microscopy images were used to identify the quality and physical changes of the nanotube morphology and surfaces; revealing the evidence of enhancement in the field emission properties after oxygen-plasma treatment.

Electronic structure, electron field emission and magnetic behaviors of carbon nanotubes fabricated on La0.66Sr0.33MnO3 (LSMO) for spintronics application.

This work elucidates the electronic structure, electron field emission and magnetic anisotropic behaviors of single wall carbon nanotubes (SWCNTs) for the spin-electronics device application grown on the La0.66Sr0.33MnO3 (LSMO)/SrTiO3 (STO) substrate. Micro-Raman spectroscopy, X-ray absorption near-edge structure (XANES) and valence-band photoemission spectroscopy (VBPES) were used for the study of electronics structure. The field emission characteristics were studied from the electron field emission current density (J) versus applied electric field (E(A)) from which the turn-on electric field (E(TOE)) was evaluated. The magnetization behaviors are also presented by the M-H hysteresis loop and were obtained by applying the magnetic field in the parallel and perpendicular direction of the CNTs at 305 K and 5 K temperatures. A magnetic measurement shows that the coercivity of the CNTs/LSMO/STO is higher and has hig anisotropic-nature than the composite LSMO/STO that could be the good material for the future possible spin-electronics device applications.

A survey of bedroom ventilation types and the subjective sleep quality associated with them in Danish housing.

We performed a survey of the types of bedroom ventilation in Danish dwellings (January-February 2020) and the associated subjective sleep quality. Five hundred and seventeen people responded. Their median age was 33 years old and 55.4% of them were males. We used an online questionnaire and collected information on the type of bedroom ventilation, bedroom airing behaviour by the respondents, the bedroom environment, building surroundings and location, and sleep disturbance caused by stuffy air, noise, and the thermal environment. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI); its median among respondents was >5 indicating reduced sleep quality. 35.4% of the bedrooms had mechanical, 24.6% exhaust, and 40.0% natural ventilation. Sleeping in a bedroom with mechanical ventilation tended to reduce sleep disturbance. The absence of mechanical ventilation and the presence of carpet in the bedroom were all associated with stuffy air causing sleep disturbance, which was the second most sleep disturbing factor. PSQI increased significantly with increased sleep disturbance. People who reported that their sleep was disturbed by stuffy air or "too warm" conditions opened windows frequently during the day or night, but no association was found between PSQI and bedroom airing behaviours. Our results are valid for the heating season and the survey would have to be repeated in the non-heating season to permit generalization of the findings. The results present associations and are qualitative, so field measurements are necessary to validate the present observations and provide further explanations.

A Risk-Based Approach to Evaluate and Control Elemental Impurities in Therapeutic Proteins.

Control of elemental impurities in the drug products evolved from the generic visual testing of heavy metals as their sulfides to specific elements of toxicological concern in the final drug products by instrumental analysis. The International Council for Harmonisation (ICH) Q3D (R1) guideline for elemental impurities describes a risk-based approach to identify, assess, and control the potential elemental impurities in drug products within the established permitted daily exposures (PDE). Challenges to this approach include how to assess the risks associated with contributing sources such as utilities, manufacturing equipment, container-closure systems, and excipients. Defining at what stage of development that such assessment should be performed to identify the risk levels can be equally challenging. In this article, we report an approach to control elemental impurities of toxicological concern, compliant to the Q3D (R1) guideline, and a summary of results obtained on multiple protein therapeutic products. This approach follows the elements of Process Validation, i.e., Design, Qualification, and Continuous Verification. The design includes the selection of excipients and their suppliers that meet the Option 1 requirement of Q3D (R1). It also comprises the selection of manufacturing equipment, container-closure systems, and utilities. The qualification includes the testing of the potential sources of elemental impurities, i.e., excipients, utilities, and leachables/extractables from the manufacturing equipment and container-closure systems. The Continuous Verification comes from the testing of representative batches at the initiation of stability studies of clinical or commercial drug product batches and at the end of shelf-life expiry of the drug product, and when changes are made to the manufacturing equipment, sources of excipients and container closure systems, and any formulation changes. Our experience shows that the risk associated with the impurity levels of the ten elements of toxicological concern in the therapeutic protein drug products, parenterally administered, is well below the control threshold (30% PDE) in the drug product recommended by the ICH Guideline. Although our focus is on the injectable therapeutic proteins, this approach can be applied to the products administered via other routes as well.