Manufacturing, pharmaceutical sources

Part 439 pharmaceutical manufacturing point source category... 

Figure 23.1 U.S. shipments of pharmaceuticals. Source Annual Survey oj Manufactures)...

US Environmental protection Agency (1998). Development Document for Pinal Effluent Limitations Guidelines and Standards for the Pharmaceutical Manufacturing Point Source Category, EPA-821-R-98-005. 

Kerker (23), and McGreer (24) of sources found in the normal manufacturing, pharmaceutical, hospital, and home environment have revealed the lack of uniformity in the SPDs of these sources. 

As nutraceuticals are not classified as medicinal products, their manufacture is often not legally regulated. Nutraceuticals are widely available for sale, and the many suppliers may formulate their products differently this leads to variations between products of different manufacturers. Products available for purchase are not necessarily of the same quality as those used in reported clinical trials. For effective and safe use, the products must contain the same active ingredient, at the same concentration, have known bioavailability per delivery system, and state detailed and correct information on packaging or patient leaflet. However, possibly due to purchase from non-pharmaceutical sources such as the Internet, there is often little information on efficacy, drug interactions, effect of long-term use, abrupt discontinuation, or potential adverse effects available to patients. 

For some industries such as pharmaceuticals, electronics, and toiletries, ultra-pure water is always demanded. Pathogens, organic substances, and inorganic substances must be effectively removed to a very low level (e.g., less than 1 ppb TOC in semiconductor fabrication manufacturing). The source water is first filtered by multimedia filters and disinfected by UV light. The water is then treated by membrane units (usually reverse osmosis) and stored. Later on, UV photolysis, ion exchange resin and micro-filters are used alternatively to produce the high pure process water. 

GMPs have spread from being applicable strictly to drug dosage form manufacture, to a world where every dosage form or business sector involved with medicinals or their constituents has a detailed GMP code. These sectors include herbal medicines, active pharmaceutical excipients (inactives), clinical trial manufacture, biotechnology-sourced materials, sunscreen products, and so on. 

Source Scrip Magazine, SCRIP, Annual Review Issues, Reproduced with permission from PJB Publications Ltd, 2002. European Commission 1997 Single Market Review, Impact on Manufacturing, Pharmaceutical Products, Table 4.17, 63. 

CFR439 Pharmaceutical Manufacturing Point Source Categories, Part 439, Title 40-Protection of Environment, Code of Federal Regulations Office of the Federal Register, U.S. National Archives and Records Administration Washington... 

Public drug procurement payments can be made in at least in three ways advance payment, cash on delivery or credit terms. Each of these payment modes affects the manufacturers cash flows, cost of finance and eventually the cost of manufacturing pharmaceuticals. The payment terms can be a source of finance for the firm to use in the production process, or they can cause the producer to seek external expensive finance whilst awaiting payment for goods produced and delivered for periods ranging up to six months. 

Eastman Goal Chemicals. In 1983 Eastman Chemical Co. became the first chemical producer in the United States to return to coal as a raw material for large-scale manufacture of industrial chemicals (35). In that year, Eastman started manufacturing acetic anhydride from coal. Acetic anhydride is a key intermediate for production of coatings, ceUulosic plastics, and cellulose acetate fibers. Acetic anhydride from other sources also is used in the manufacture of pharmaceuticals, starches and sweeteners, and flavors and fragrances. 

As the most reactive and economical source of the acetoacetyl moiety, diketene is used as a valuable synthetic intermediate in the manufacture of acetoacetic acid derivatives and heterocycHc compounds which are used as intermediates in the manufacture of dyestuffs, agrochemicals, pharmaceuticals, and polymers. 

By-Products From Milk. Milk is a source for numerous by-products resulting from the separation or alteration of the components. These components may be used in other so-called nondairy manufactured foods, dietary foods, pharmaceuticals (qv), and as a feedstock for numerous industries, such as casein for glue. 

A considerable quantity of oil can be extracted from waste material from shelling and processing plants, eg, the inedible kernels rejected during shelling and fragments of kernels recovered from shells. About 300 t of pecan oil and 300—600 t of English walnut oil are produced aimuaHy from such sources. The oil is refined and used for edible purposes or for the production of soap the cake is used in animal feeds (see Feeds and feed additives). Fmit-pit oils, which closely resemble and are often substituted for almond oil, are produced on a large scale for cosmetic and pharmaceutical purposes (143). For instance, leaves, bark, and pericarp of walnut may be used to manufacture vitamin C, medicines, dyes and tannin materials (144). 

Menthol Manufacture. Of the menthol isomers, only (-)-menthol [2216-51 -5] and (+)-menthol [15356-70-4] are of commercial importance. The most important natural sources of (—)-menthol are the oUs of Mentha arvensis (75—90%) and Mentha piperita (50—65%). The main suppUers ate Japan, China, BrazU, and Taiwan for the former and the United States, CIS, Bulgaria, and Italy for the latter. (—)-Menthol is known for its refreshing, diffusive odor characteristic of peppermint. It also is known for its strong physiological cooling effect, which is useful in cigarettes, dentifrices, cosmetics, and pharmaceuticals. 

Various processes need waters of a quality better than the public supply, or whatever source is available. Demands vary widely. Pharmaceutical and cosmetics production generally requires good biological quality. So do food and drink manufacture, but brewing and soft drink manufacture often requires a specified mineral content as well. In brewing it is becoming common for water to be largely... 

The first chapter in this section provides a unique account of the ecology, i.e. distribution, survival and life-style, of microorganisms in the factory environment, and should enable process designers, controllers and quality control personnel to comprehend, trace and eradicate the sources of failure due to extraneous microbial contaminants in the finished product. Much of the information given here is applicable to hospital manufacture also, and this is extended in a contribution (Chapter 19) dealing with contamination in hospital pharmaceutical products and in the home. 

Quality control tests or improvement of existing processes. Raw materials from various sources can be used in the manufacture of fine chemicals and pharmaceuticals. The raw materials can contain different impurities at various concentrations. Therefore, before the raw material is purchased and used in a full-scale batch its quality should be tested in a small-scale reactor. Existing full-scale procedures are subject to continuous modifications for troubleshooting and for improving process performance. Laboratory reactors used for tests of these two kinds are usually down-scaled reactors or reactors being a part of the full scale-reactor. 

Tab. 14.1 The role ofGMP (good manufacturing practice) in the production and processing of APIs (active pharmaceutical ingredients) from difference sources. It is not yet clear how biotechnology-derived plants fit into this scheme. Modified from the Good Manufacturing Practice Guide for Active Pharmacuetical Ingreedients, ICH (2000).

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