Читать книгу Sustainable Nanotechnology - Группа авторов - Страница 55

For any production unit, the requirement related to in‐house qualification is very important, especially in pharmaceuticals, where every new product needs to be qualified from certain regulatory bodied as well as a good manufacturing practice (GMP) certification for scale‐up and manufacturing process. Apart from these aspects, there is always search for cost‐effective excipients and materials, flexible and uninterrupted production, and process setup. Overall, the industrial production should produce a product of high quality without contamination and free from elemental impurities residual solvent.

Further being expensive, manufacturing may involve accidental exposure that affects the environment and human health. The most common human effect that arises, in this case, are breathing issues and skin rashes. Yet, these issues can be minimized by appropriate awareness for possible hazards, and source of defensive apparel and microfiltered air throughout the production unit are necessary to avoid these consequences. Already discussed in the previous section about the physicochemical properties that make NPs attractive for numerous applications are indeed the properties that are the source of concern as they affect biokinetics and drug activity. The toxic effect flashes are inconsistent as some NPs are comparatively gentle, but others are possibly treacherous. Similarly, the environmental hazards that usually depend on its biodegradability show no surety of safe products and may disperse through the earth or aquatic ecosystems, such as unwanted penetration through cell membranes, the blood–brain barrier, fetuses or infants as the result of breast milk ingestion, placental wall, and causing pregnancy problems, inducing irritation into testicles cells, and being intrusive in sperm production by damaging DNA in germ cells [4]. As the formulation's backbone is similar with respect to size, the material of composition surface charges and more surface area becoming available to react with several such permeations far from target have been reported. Such phenomenon is being risen frequently and need to be taken care of for sustainable large‐scale production. The regulatory bodies need to have separate guidelines for all nanotechnology‐oriented production houses. These manufacturers produce NMs on a large scale. A large number of workers and operators must be involved at different stages of the production who are then prone to skin or tissue penetration; thus for handling, extreme precaution is required.

As one of the characteristics of NMs is their unique size range, they need a number of ultrapurification techniques in mass production. In addition, other ingredients including enzymes, precursors, and catalysts need to be removed if present at the end of the product. In pharmaceuticals, removal of pyrogens and sterilization is also carried out with filtration. Most importantly, the biological activities of such effluents and NMs are unknown and unpredictable. All these effluents also need some techniques to avoid nonbiodegradable NMs being excreted with them, so polluting water, earth, or air can be avoided.

Apart from all the abovementioned manufacturing issues, several conventional issues for industrial sustainability also remain. For example, for 1 g of finally purified and sterilized product, almost 15–20 l of solvent may be used. For large‐scale production, several liters of potable and sterile water are required. The source of water in industries is mostly groundwater. For both potable and sterile water preparation, ultrapurification, reverse osmosis, distillation, and condensation require a cumulative high energy consumption. Several methods of production of NMs require organic solvents as an important part of manufacturing. Removal of them with extra precautions is required to avoid known toxicity related with residual solvents. Filtration of air should also be performed to avoid the interference of particles from outside the reactor with the chemical synthesis. The energy intensity required for a clean room with a class ranging from 1 to 10 is 1.017 kW h cm⁻² year⁻¹ [46].

Taking this into consideration, many organizations have widened the toxicology studies. These studies are not only expensive but also time consuming. One more concern regarding these toxicology studies is about the testing protocol, as no specific guidelines for the toxicology study of NMs are available. These studies are being carried out on cell lines or cell culture models; further assay techniques are then used to detect toxicity on these models. The high reactive nature of NMs due to their unique property also hinders with the assay materials or with detection systems. Such hindrance makes all the results and data questionable as they are inconsistent and conflicting. The regulatory bodies need to intervene with such studies and should coordinate with them globally. Such initiative can record the data of all studies globally so that all arising questions can be answered; most importantly, this will minimize the cost and time for determination of global toxicity record, which is the actual need of the hour.