Residuals from the Manufacturing Process

Certain additives, salts, and bulking agents may be added primarily to improve vaccine stability upon storage (19,20). These excipients such as mannitol, glycine, and trehalose have a direct impact on the stability of the polypeptide or conjugate and are investigated for this purpose. 

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Residual N-bromosuccinimide from the manufacturing process may be identified and/or quantified by making use of its oxidation potential by titration of liberated iodine after addition of potassium iodide in acetic acid (25). 

Process Residuals A source of potential impurities can be process residuals as well as host cells. Process residuals include fermentation media components as well as raw materials used in chromatography (immunoglobulin affinity ligands), etc. According to the ICH Guidelines,2 process-related impurities are impurities that are derived from the manufacturing process. They may be derived from cell substrates, cell culture, or downstream processing. 

Determination of metal residues in drugs remaining from the manufacturing process. Strengths... 

The current BP methods for determination of solvent residues in pharmaceuticals remaining from the manufacturing process rely on direct injection of the sample dissolved in a suitable solvent (often water) and are based on packed column GC. Some examples are given in Table 11.4. 

Another part of the substance is melted in a platinum crucible with nitre and sodium carbonate, the mass obtained being dissolved in water any insoluble residue may contain especially ferric oxide. The solution is acidified with hydrochloric acid, boiled for a long time with alcohol and evaporated almost to dryness, the residue being taken up in water and filtered from any silica which separates the filtrate is tested for the metals, phosphoric acid and boric acid (derivable as an impurity from the manufacturing processes) by the ordinary qualitative methods. 

When using a resin from new it is advisable to pre-condition the material by alternately cycling and rinsing the resin between acid and salt form (Na) for cation exchangers or hydroxide and salt form (Cl) for anion exchangers. This serves to osmotically cycle the resin and flush out residual impurities left over from the manufacturing process. 

Polyester fibers are composed of linear chains of polyethylene terephthalate (PET), which produces benzene, benzoic acid, biphenyl, and vinyl terephthalate on pyrolysis. Acrylic fibers comprise chains made up of acrylonitrile units, usually copolymerized with less than 15% by weight of other monomers, e.g., methyl acrylate, methyl methacrylate, or vinylpyrrolidone. Thermolysis results in the formation of acrylonitrile monomer, dimers, and trimers with a small amount of the copolymer or its pyrolysis product. In this case, the acrylic is Orion 28, which contains methyl vinyl pyridine as comonomer. Residual dimethyl formamide solvent from the manufacturing process is also found in the pyrolysis products. Cotton, which is almost pure cellulose, comprises chains of glucose units. The pyrolysis products of cellulose, identified by GC/MS, include carbonyl compounds, acids, methyl esters, furans, pyrans, anhydrosugars, and hydrocarbons. The major pyrolysis products are levoglucosan (1,6-anhydro-B-D-glucopyranose) and substituted furans. 

MGtalS. A metal that has been exposed to air invariably forms an oxide layer on its surface. This oxide layer may be intrinsically weak or it may adhere poorly to the underlying metal, leading to weak adhesive joints in either case. Furthermore, usually there are organic contaminants present on the surface, ie, residual lubricants from the manufacturing process or substances adsorbed from the atmosphere. In order to prepare a metal surface for bonding, etching... 

The dimensional and mechanical stability of materials is often of critical relevance and may effectively determine their technical applicability. Synthetic polymers are processed at moderate to high temperatures to facilitate transformation into fibers with characteristics that are appropriate for specific applications. Residual frozen-in stress may result from the manufacturing process or from thermomechanical treatments that are applied to fibers as part of the finishing stage of production. 

Simple conventional refining is based essentially on atmospheric distillation. The residue from the distillation constitutes heavy fuel, the quantity and qualities of which are mainly determined by the crude feedstock available without many ways to improve it. Manufacture of products like asphalt and lubricant bases requires supplementary operations, in particular separation operations and is possible only with a relatively narrow selection of crudes (crudes for lube oils, crudes for asphalts). The distillates are not normally directly usable processing must be done to improve them, either mild treatment such as hydrodesulfurization of middle distillates at low pressure, or deep treatment usually with partial conversion such as catalytic reforming. The conventional refinery thereby has rather limited flexibility and makes products the quality of which is closely linked to the nature of the crude oil used. 

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