Approaches for setting occupational exposure limits in the pharmaceutical industry.

The use of pharmaceutical drugs has provided a cure for many diseases. However, unintended exposure to drugs in the manufacturing workplace can cause significant health hazards to workers. It is important to protect the workforce from these deleterious effects by limiting exposure to an acceptable level, the occupational exposure limit (OEL). OEL is defined as airborne concentrations (expressed as a time-weighted average for a conventional 8-h workday and a 40-h work week) of a substance to which nearly all workers may be repeatedly exposed (for a working lifetime) without adverse effects. Determination of OELs has become very challenging over time, requiring an overall assessment of the preclinical and clinical data of the drug being manufactured. Previously, to derive OEL values, toxicologists used animal no-observed-adverse-effect level (NOAEL) data, which have been replaced with the overall assessment of animal and human data, placing a higher emphasis on human health-based data. A major advantage of working with human pharmaceuticals is that sufficient clinical data are available for them in most cases. The present manuscript reviews the latest knowledge regarding the derivation of occupational exposure limits as health-based exposure limits (HBELs) for pharmaceuticals. We have provided examples of OEL calculations for various drugs including levofloxacin (CAS No. 100986-85-4), dienogest (CAS no. 65928-58-7), and acetylsalicylic acid (ASA, CAS no. 50-78-2) using human data. This report will benefit professionals in the OEL domain in understanding this highly important, growing, and challenging field.

Challenges in setting permitted daily exposure limits for pharmaceuticals: A review.

BACKGROUND: When more than one drug is manufactured at a shared facility or equipment in pharmaceutical manufacturing, the potential carry-over of the retained residue of existing drug product on product contact parts of the equipment to the next product can be a source of cross contamination. Permitted daily exposure (PDE) is derived based on the complete nonclinical and clinical data available and is a dose that is unlikely to cause adverse effects if an individual is exposed, by any route, at or below this dose every day over a lifetime. OBJECTIVE: The objective was to present a comprehensive review of available scientific knowledge for derivation of PDE. METHODS: PubMed and ScienceDirect databases were searched using keywords "PDE" and "pharmaceuticals" and all the relevant literature up to March 2021 was reviewed. We have also calculated PDEs for Tobramycin (CAS No. 32986-56-4) and Acetyl Salicylic Acid (ASA, CAS No. 50-78-2). RESULTS: This research will be useful for scientists working in the PDE domain. The given examples emphasize the importance of use of human data in calculating PDE. CONCLUSION: The duty of the risk assessor entrusted with setting PDEs is to derive a data driven, scientifically justified value that is safe for patients, while avoiding unjustified conservativeness that puts unnecessary burden on manufacturing.

HIV prevalence among persons suspected of tuberculosis: policy implications for India.

BACKGROUND: HIV testing of persons referred for tuberculosis diagnosis (TB suspects) is recommended by World Health Organization but is not a policy in India, where HIV prevalence among TB suspects has never been reported. The current Indian policy of offering HIV testing only to TB cases may limit opportunities for early HIV diagnosis and treatment. METHODS: All adult TB suspects examined for diagnostic sputum microscopy in Mandya district (2 million population), in December 2010, were offered voluntary HIV counseling and testing. Participants were assessed for subsequent TB diagnosis. RESULTS: Of 1668 eligible TB suspects, HIV status was ascertained for 1539 (92%). Among these, 108 (7%) were HIV positive. Of the 108, 43 (40%) were newly diagnosed as HIV (ie, not previously known to have HIV infection). To detect a new case of HIV infection, the number needed to screen among TB patients was 13, as compared to an number needed to screen of 37 among "TB suspects not diagnosed as TB". Applied annually in 2010, HIV testing of TB suspects in 2010 could have identified approximately 534 newly diagnosed HIV cases, a 51% increase in district HIV case finding. CONCLUSIONS: Routine HIV testing of TB suspects was feasible and yielded a large number of HIV cases in absolute terms and would increase district HIV case finding by 51%. The number of patients needed to be HIV tested to find a previously undetected HIV case among TB suspects was greater than for TB cases but was potentially acceptable. Given heterogeneity of HIV epidemic in India, broader surveillance is required before national policy decision.