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Health Hazards in the Pharmaceutical Industry

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Health Hazards in the Pharmaceutical Industry

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Abstract

Extensive research is conducted to evaluate the safety and efficacy of candidate drugs prior to marketing and distribution, but few epidemiological studies have examined the occupational health of production workers who manufacture these drugs. This paper reviewed the occupational health research published during 1973-2014 regarding adverse health outcomes in pharmaceutical manufacturing workers. Most investigations were prompted by suspected disease clusters. Workers generally had a better mortality experience than their referent populations, but they experienced adverse health outcomes including cancer, endocrine dysfunction, cancer, and liver disease. However, most studies lacked detailed occupational exposure data, and they failed to identify the chemicals used in drug manufacture, including the active pharmaceutical ingredients (APIs). Integrated occupational health research is needed to evaluate exposures and long-term health outcomes among these workers. Since manufacturing operations are frequently outsourced to plants in Asia, this research could inform mitigation measures to protect production workers in this global industry.

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... The use of evidence derived from research and that which is observed in practice to influence policy is the latest approach to effectively promote and improve public and occupational health. Exposures to hazardous chemicals in pharmaceuticals have been long recognized to have both positive and negative effects on human health [1,2]. While the potential therapeutic benefits of drugs outweigh the risks of side effects for patients, exposing pharmaceutical industry and health care workers to the same side effects is an unacceptable outcome. ...
... During manufacturing and preparation of pharmaceuticals, workers can be exposed to various chemicals, including the potent active pharmaceutical ingredients (API), chemical intermediates, as well as other chemicals such as solvents, catalysts, acids and bases [2]. To comply with both the drug and WHS regulations, manufacturers must determine chemicals they produce are hazardous. ...
... Occupational exposure to oral contraceptive pills had an adverse health effect on exposed workers resulting in an alteration in liver function and sex hormone levels. Estrogens exposure may increase the risk of Hypoestrogenism in exposed men and women [20] . ...
... [1] well as other chemicals such as solvents, catalysts, acids, and bases. [2] In pharmaceutical industry, many chemicals that are used are nanomaterials as they generate new superior properties and meet current and future demands. Polyacrylate (PA)/ silica nanoparticles are a nanosilica-containing nanocomposite that has broad applications in the pharmaceutical industry. ...
Article
Background: Polyacrylate (PA) powder dust formed in PA manufacturing units is fine sized, i.e., in nanosize. Although several previous studies reported possible significant adverse effects of nanomaterials, studies on the harmful effect of small-sized PA particles on the respiratory health of the workers are scarce. The present study was carried out to assess the effect of PA on respiratory health and lung volumes/rates among the workers of PA manufacturing unit. Materials and methods: The present cross-sectional study included 84 workers of PA manufacturing unit. Using interview technique as a tool for data collection, demographic, occupational, and clinical details of the workers were recorded on the predesigned pro forma. This was followed by detailed clinical examination, spirometry, chest X-ray ( posteroanterior [PA] view), and high-resolution computed tomography (HRCT) examination of each worker. Results: On the basis of clinical examination, chest radiography, and HRCT, 17.9% of the workers were found to have fibrotic and cavitary changes in lung parenchyma. The production department workers had a higher proportion of respiratory morbidities as compared to supervisory or office staff. Age, gender, smoking habit, and duration of exposure were nonsignificant risk factors for respiratory morbidity. The overall mean forced vital capacity, forced expiratory volume in 1st s, Peak Expiratory Flow Rate (PEFR), (Maximal Mid Expiratory Flow Rate) MMEFR0.2-1.2, and MMEFR25%-75% were 3.19 ± 0.77 L, 2.72 ± 0.67 L, 6.82 ± 1.86 L/s, 5.79 ± 2.03 L/s, and 3.16 ± 1.19 L/s, respectively. Females and those having respiratory morbidity had significantly lower values of all spirometric parameters as compared to their counterparts. Conclusions: The workers exposed to engineered fine dust of PA may be at risk of respiratory ill-health.
... Occupational exposure to oral contraceptive pills had an adverse health effect on exposed workers resulting in an alteration in liver function and sex hormone levels. Estrogens exposure may increase the risk of Hypoestrogenism in exposed men and women [20] . ...
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Hazard is a term associated with a substance that is likely to cause an injury in a given environment or situation. Industrial hazards are major occupational health and safety (OHS) issue in Pharmaceutical manufacturing. In recent years chemical safety and the sound management of chemicals have seen great progress at the global level. At the same time, the rapid growth in production and dissemination of both natural and synthetic chemicals has led to concern about their impact on the natural environment, and human health. In this way, the pharmaceutical industry has come to occupy a unique position. Practically no other commercial enterprises present such as a wide variety of potentially toxic exposures or such a rapidly changing advent of new chemical substances. In the pharmaceutical industry, this dynamic situation has been created by the increasing application of organic chemical synthesis as a technique for producing therapeutic substances. This renders the work of the plant physician so instructive. Industrial safety is needed to check all the possible chances of accidents for preventing loss of life and permanent disability of any industrial worker, any damage to machine and material leads to the loss of the whole establishment.
... This study also was incapable to capture model uncertainty owing to the individual difference among the input events in FTA or ETA. There is limited research in the literature related to workers health and safety assessment in pharmaceutical industry [1,5,[45][46][47][48][49] since the quality risk management is commonly studied in this industry. As it is evident in the previous studies in the literature, this paper is the first QRA study performing Fuzzy Bow-Tie for pharmaceutical industry to analyze and visualize risks, causes and consequences of potential risk events and their impacts with possible preventive and protective control measures or barriers in prospective manner. ...
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Risk analysis is a systematic and widespread methodology to analyze and evaluate risks which are exposed in many working areas. One of the Quantitative Risk Analysis (QRA) methods for risk assessment is Bow-Tie analysis which combines features of fault-tree analysis and event-tree analysis to identify the top event; its causes and consequences (outcomes); and possible preventive and protective control measures or barriers. This study proposes an occupational risk assessment approach, which is known as Fuzzy Bow-Tie analysis, for pharmaceutical industry processes and work units. The aim is to evaluate critical risks and risky pharmaceutical work units and take safety precautions against accidents which caused by risky conditions. Thus, this methodology combines the concept of uncertainty which comes from different (Decision Maker) DM’s evaluations and the whole performance of the Bow-Tie analysis for hazard identification and risk assessment. To apply and validate the proposed method, a case study is performed for pharmaceutical industry processes and work units. Based on the computed risk score, which is calculated by multiplying probability ranking and impact ranking of criterion, the risks are prioritized and some measures are suggested for management to prevent accidents occur in the industry.
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Environmental monitoring of anti-neoplastic drug (AND) residues in workplaces is crucial to limit exposure to workers who handle with them. Although wipe sampling is the most appropriate methodology to evaluate the risk, conflicting results are also reported due to the lack of standardized and validated procedures. In this study, procedures for surface contamination of ANDs in workplaces are presented, with a focus on sampling, sample preparation and instrumentation. The analytical method validation parameters are designed to comply with requirements of The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q7 Good Manufacturing Practice (GMP) for active pharmaceutical ingredients. Additionally, the study provides a simple, specific, rapid and multi-component analytical method to evaluate seven ANDs that are Gefitinib, Imatinib, Dasatinib, Axitinib, Erlotinib, Nilotinib and Sorafenib at very low concentration levels, simultaneously. Quantitative, precise and reproducible results obtained from the study show that environmental monitoring procedure and analytical method validation protocol presented in the study can be used to reduce and monitor occupational exposure risk to ANDs in wokplaces.
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Introduction: Exposure to noise is considered as one of the most important health problems in various industries, especially pharmaceutical industry, which can ultimately lead to significant negative effects on labor force and occupational performance. The aim of this study was to investigate the relationship between continuous noise exposure and occupational performance of the workers in the pharmaceutical industry and ampoule production line in Iran. Methods: This cross-sectional study was conducted through a descriptive-analytical method in 2017. The subjects were 100 workers exposed to noise in an ampoule and vial manufacturing factory in Iran. The sound measurement was carried out in accordance with ISO 9612: 2009. The Hersey and Goldsmith questionnaire (ACHIEVE model) was used to investigate the workers’ occupational performance, and the seven dimensions of the questionnaire as well as the final score of occupational performance was determined for each individual. Results: The results showed that there was a low inverse relationship between noise exposure and occupational performance of the total workers in all the halls which was statistically significant (P-value = 0/01, r2 = 0/256). It was also found that there was an inverse relationship between exposure to noise and the seven dimensions, but the relationship was statistically significant only for the dimensions of ability, clarity, and evaluation (P-value
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Artificial neural network (ANN) is a useful technique in decision-making which can replicate the biological thinking pattern of the human decision maker. By providing the learning way of a supervised and unsupervised process, we can train the ANN to give the output as accurate to the human judgment. This technique has been used in solving multiple problems including forecasting and to predict the solution. In this work, ANN has been used for the candidates’ selection in the pharmaceutical company. To mimic the human judgment in the selection process of human resource management by supervised learning. So that we can eliminate the human judgment with ANN.
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Objectives: Pharmaceutical workers involved with the production of antimicrobial drugs are exposed to various antimicrobial chemicals in different steps of manufacturing such as, grinding, sieving, compression, granulation, mixing, filling, etc. These exposures may lead them to the development of multi-drug resistance (MDR) of bacteria. Scientific report on the occupational health hazard of pharmaceutical workers involved with manufacturing of antibiotics is scarce. The present study aimed to compare the degree of bacterial resistance in pharmaceutical workers in Bangladesh to that of non-pharmaceutical people. Methods: Twenty male workers from five local pharmaceutical companies and twenty male non-pharmaceutical subjects were randomly selected. Nasal fluid, mucus/cough and stool specimens were collected from each subject and were cultured separately at 37 °C for 24 hours to obtain bacterial growth. The cultured species were then identified, isolated and subjected to microbial sensitivity test against 18 different antibiotics from eight different groups by disk diffusion method. Staphyllococcus spp., Pseudomonas spp. and Escherichia coli were identified and isolated from the culture of nasal fluids, mucuses and stools, respectively. Results: All the isolated species of bacteria exhibited significant enhancement of the number of multiple-drug resistance to pharmaceutical workers compared to non-pharmaceutical subjects. Workers with longer working history had greater degree of antibiotic resistance and vice-versa. It can be certainly considered that the exposure of antimicrobial agents to the pharmaceutical workers resulted in high incidence of multi-drug resistance. Conclusion: Effective steps should be taken to minimize inherent exposure of antibiotics to pharmaceutical workers during work to prevent antimicrobial drug resistance.
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Full textFull text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (271K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. 323 Selected References These references are in PubMed. This may not be the complete list of references from this article. Hughes S, Calverley PM. Heroin inhalation and asthma. BMJ. 1988 Dec 10;297(6662):1511–1512. [PMC free article] [PubMed]
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Person-years at risk in occupational cohort mortality studies may be defined as "active" (when a person is working) or "inactive" (after a person has left employment at the plant under study). To investigate the effects of employment status (active/inactive) both across studies and within them, we have analyzed ten large cohort studies conducted by the National Institute for Occupational Safety and Health in which no occupational risk had been observed. These ten data sets included 89,376 workers, 1,984,505 person-years, and 18,840 deaths. In these ten studies, the SMR for all causes was positively correlated with the percentage of inactive person-years in the study (r = 0.57, p = 0.08). Considering only inactive person-years, the all-causes SMR was 1.12 (approximately 1.25 before age 65, dropping to 1.00 after age 65). Stratification of inactive person-years by time-since-last-employment showed markedly increased mortality during the first year following employment. The all-causes SMR during active person-years was 0.40 and was fairly constant across age categories. With active and inactive person-years combined, a strong negative trend in SMRs with duration of employment was observed for all causes and for heart disease. These trends were not apparent when person-years were stratified by employment status. These results indicate that investigators should evaluate the effects of employment status when comparing SMRs between multiple cohorts or when interpreting trends in rate ratios within cohorts.
A cross-sectional study of 125 pharmaceutical workers engaged in the manufacture of bulk laxatives based on ispaghula husks (psyllium) and senna pods was conducted. Skin prick tests with extracts of these components revealed that 7.6% were allergic to ispaghula and 15.3% were allergic to senna. Four (3.2%) cases of occupational asthma were identified. The overall prevalence of asthma (6.4%) was less than in a comparable nonexposed Australian population (odds ration, 0.44). Symptoms referrable to the upper airways, eyes, and skin were more prevalent (52.0%) than in the reference population (odds ratio, 1.53). Smokers and nonatopic subjects were more likely to complain of these symptoms if they were sensitized to senna and/or ispaghula than if they were not sensitized (relative risks, 1.9 and 2.6, respectively). Sensitization to ispaghula and/or senna was not a risk factor for asthma. An IgE-mediated allergic mechanism is probably responsible for the allergic symptoms in many of these subjects. Smoking seems to be a cofactor in this process.
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Clenbuterol, a beta antagonist, and ranitidine, a histamine-receptor antagonist, were associated with contact dermatitis in a chemist. The allergen in the former was an intermediate in the synthesis called beta. In the latter, intermediates and the finished base and hydrochloride were responsible.
We assessed the prevalence of occupational asthma and IgE sensitization to psyllium in a pharmaceutical company producing psyllium hydrophilic mucilloid, which is used as a laxative. Workers were intermittently exposed, approximately 5 times/yr, for periods of less than 10 days. Of the 140 employees, 130 (93%) were studied before a processing period via a questionnaire spirometry (n = 125), blood sampling (n = 118), and skin prick tests (n = 120) with 7 common inhaled allergens as well as plantain and psyllium. Thirty-nine workers had a history suggestive of occupational asthma. Twenty-three of 120 (19%) showed a skin wheal diameter greater than or equal to 3 mm to psyllium and 31 of 118 (26%) had increased specific IgE antibodies; 39 (32%) workers had at least 1 of these 2 features. Subjects with a questionnaire suggestive of asthma or occupational asthma were further investigated by serial monitoring of peak expiratory flow rates and PC20 methacholine before and during the psyllium processing period. All workers had spirometry repeated during the processing period. Twenty-one subjects who had a PC20 less than or equal to 16 mg/ml (n = 10) and/or decreased their PC20 by a greater than or equal to 3.2-fold difference (n = 4) and/or changed their FEV1 by greater than or equal to 10% (n = 13) during the processing period were referred for inhalation challenges to psyllium in the laboratory. Five of the 18 workers for whom these tests were feasible gave an immediate bronchoconstrictive reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Hazards associated with work in the pharmaceutical industry are not clearly defined. To investigate this problem during 1973–1981, 672 deaths were identified among present and past employees of a large British pharmaceutical company. Initial comparisons of these deaths with those presenting in the general population suggested that there was an excess for various cancers and pneumonia among company employees of both sexes. Further comparisons were limited to company employees. Specifically, causes of death were analysed according to likely exposure to hazardous substances. The numbers of cases with adequate work histories for these analyses were small. Nonetheless, there was evidence of a possible occupational risk for a range of cancer sites among males. The finding was not statistically significant, but it was consistent with earlier results. Additional studies with a concurrent cohort design are recommended.
Article
This study was designed to investigate whether the mortality of British pharmaceutical industry workers showed any evidence of occupationally related patterns associated with particular sections of the industry with special emphasis on cancers and respiratory diseases. The data were extracted from census schedules by the Office of Population Censuses and Surveys using occupational categories recorded by pharmaceutical workers at the 1961 and 1971 censuses of England and Wales. Subsequent mortality was ascertained through the National Health Service Central Registry. Both cohorts, followed up to the end of 1981, showed a "healthy worker effect," with overall SMRs ranging from 0.77 to 1.04, though comparison with the employed populations of the longitudinal study reduced this effect by 25%. Evidence of inconsistent excess mortality was noted in small numbers for suicide (SMR 0.91 to 2.79) and cancer of the large intestine (SMR 1.09 to 2.38). There was no clear association between the type of industry and the causes of death investigated. Although the census based study has several methodological shortcomings, there was no evidence, on the basis of this study, to suggest any excess mortality risk from employment in the pharmaceutical industry.
Article
A register based study was conducted on the pregnancy outcome of female workers in eight Finnish pharmaceutical factories to determine whether they had a higher risk of spontaneous abortion than the general population or matched controls. Information about all female workers who had been employed in the factories during the years 1973 or 1975 (four factories) to 1980 was obtained from the employers. The workers' pregnancy data were collected from the nation wide hospital discharge register and polyclinic data of hospitals from 1973 to 1981. The total number of 1795 pregnancies included 1179 deliveries, 142 spontaneous abortions, and 474 induced abortions. The spontaneous abortion rate (the number of spontaneous abortions X 100, divided by the number of spontaneous abortions plus the number of births) during employment was 10.9% and before/after employment 10.6%. The rate for all the women in the corresponding central hospital districts was 11.3% [corrected] during the study period. A case-control study was also carried out in which the cases were 44 women who had a spontaneous abortion during employment in the pharmaceutical factory. Three age matched female pharmaceutical factory workers who had given birth to a child were chosen as controls for every case. The information about occupational exposures was collected from questionnaires completed by the occupational physician or nurse at the factory. The response rate was 93%. Exposure to chemicals was more common among the cases than among the controls. For methylene chloride, a solvent commonly used in the pharmaceutical industry, the increase in odds ratio of borderline significance (odds ratio 2.3, p = 0.06). In a logistic regression model (which included oestrogen exposure, solvent exposure frequency of the usage, and heavy lifting) the odds ratio was increased for oestrogens (odds ratio 4.2, p = 0.05) and for continuous heavy lifting (odds ratio 5.7, p = 0.02). The odds ratio for spontaneous abortions was greater among those exposed to four or more solvents (odds ratio 3.5, p=0.05) than among those exposed to one to three solvents (odds ration 0.8, p=0.74).
Article
Three out of four workers from an antibiotic-producing factory developed late asthma and eosinophilia on inhalation challenge testing with ampicillin and related substances. The chemicals to which each worker reacted varied, suggesting differences in the clinically important allergens for each individual. The taking by mouth of ampicillin in one patient, and benzyl penicillin in another in therapeutic doses led to the development of late asthma accompanied by skin and gastro-intestinal disturbances. The inhalation of 200 μg of beclomethasone dipropionate before in one case, and before and 3-hourly after provocation challenge in the other, blocked the late asthmatic reaction. 40 mg sodium cromoglycate similarly given failed to inhibit the reactions. In one patient, 04416–0.24 mg of isoprenaline sulphate inhaled 10 min before or 60 min after inhalation testing prevented the development of late asthma, and when given during the asthmatic reaction led to its rapid reversal.