Control of the Finished Product

In addition to the phaimacopoeial monographs, the guideline on Specifications and control of finished products (Table 2-2) provides details of requirements. Reference should also be made to the ICH draft note for guidance on Specifications [4].The latter details the tests which might be expected for the control of different types of dosage forms. 

Validation of analytical methods used in the finished product specification is required in the same way as for drug substance. Revalidation of these methods may also be necessary if the composition of the product has been changed during development, e.g. to reassess specificity. 

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Control of the finished product—quality specifications including all requirements emd methods of analysis of a batch of the product. 

Quality control of the finished product. The cissay methods, including physical cmd chemical methods, and, where appropriate, biological and microbiological methods. For products analyzed by pharmacopoeial eissay, a photocopy of the method, indicating the name cmd edition of the pharmacopoeia, has to be attached. If the product is manufactured at severed sites, a certificate of the authorities regarding proper GMP at each of the sites, and full details on the sites have to be submitted ... 

Method of manufacture and quality control of the finished product... 

A key attribute of rinse cycle fabric softeners is their viscosity. The control of the finished product viscosity is very delicate, as its value at the end of the formulation depends on several parameters linked to the ingredient composition and the manufacturing procedure. Also, viscosity may vary upon storage. 

For the control of the finished product, a batch of a medicinal product comprises all the units of a pharmaceutical form which are made from the same initial mass of material and have undergone a single series of manufacturing operations or a single sterilisation operation or, in the case of a continuous production process, all the units manufactured in a given period of time . 

A natural or judicial person who acts as an importer has this obligation only as it refers to the quality control of the finished product. 

The manufacture of medicines for homeopathic use us most often concerned with infinitesimal doses of the active principle. This special characteristic usually makes analytical control of the finished product impossible. Consequently, the guarantee of the quality of a homeopathic medicine can be obtained only by the control of the raw materials and above all, by the implementation of good pharmaceutical manufacturing practices. 

The final step in the validation process is the PQ, which is the verification of the suitability of the installation for the intended purpose in the production process. Often quality control of the finished product is involved in carrying out the PQ. An example is the measurement of the homogeneity of a mixture that is produced by a mixing machine. The PQ is performed by the user. When all the above-mentioned steps are completed, the equipment is qualified and can be used in a preparation process. 

The DSC thermograms for brick specimens fired at various temperatures are given in Fig. 27. The heat liberated per unit mass of the specimen (calculated by arbitrarily defining the limits of the peak area) as a function of the firing temperature is indicated in the figure. An inverse proportionality is indicated. The results are dependent on clay composition and other characteristics and will be different for clays of different origin. However, the information can be of value in brick manufacture at an individual plant for quality control of the finished product and for the firing process. 

On the other hand, UV filters, such as p-aminobenzoic acid (PABA) and its derivatives supporting the amine function, could form nitrosamines, which are suspected of having carcinogenic properties (Meyer and Powell, 1991 Chou et al, 1995). Therefore, a rigorous control of the finished product must be carried out. 

A.dditives. Additives control coating behavior during appHcation or they can be used to alter the properties of the finished product. A single chemical additive may be used for several purposes. Some additives are essential to the production of a salable product, and others may be added only to obviate problems of the coating operation. 

A wide variety of particle size measurement methods have evolved to meet the almost endless variabiUty of iadustrial needs. For iastance, distinct technologies are requited if in situ analysis is requited, as opposed to sampling and performing the measurement at a later time and/or in a different location. In certain cases, it is necessary to perform the measurement in real time, such as in an on-line appHcation when size information is used for process control (qv), and in other cases, analysis following the completion of the finished product is satisfactory. Some methods rapidly count and measure particles individually other methods measure numerous particles simultaneously. Some methods have been developed or adapted to measure the size distribution of dry or airborne particles, or particles dispersed inhquids. 

Special additives are often included in a carrier formulation to provide specific properties such as foam control, stabiUty, and fiber lubrication during dyeing. Most important are the solvents used to solubilize the soHd carrier-active chemicals. These often contribute to the general carrier activity of the finished product. For example, chlorinated benzenes and aromatic esters are good solvents for biphenyls and phenylphenols. Flammable compounds (flash point below 60°C) should be avoided. 

For drug substances and drug products, applications for enantiomers and racemates should include a stereochemically specific identity test and/or a stereochemically selective assay. The choice of control tests should be based on the method of manufacture and stability characteristics and, in the case of the finished product, its composition. 

In the final analysis, market price and sales volume are functions of the quality standards offered and the buyer s degree of confidence that the product will conform to the standards. Maintenance of buyer s confidence requires inspection to screen out all nonconforming products, or control over variability of quality during production and distribution to a degree where few, if any, products fail to meet the standards. Screening inspection of the finished product cannot improve quality it merely serves to segregate unacceptable from acceptable product, and results in loss of production capacity and costly waste and salvage. The second consideration provides the only sound basis for quality control in frozen food production and distribution. It operates on the old principle that an ounce of prevention is worth a pound of cure. ... 

Processing is extremely important in regard to tolerance control in certain cases it is the most influential factor. The dimensional accuracy of the finished product relates to the process, the machining accuracy of mold or die, and the process controls, as well as the shrinkage behavior of the plastic. 

In light of the many types of behavior plastics that can manifest and the considerable effect this behavior can have on the performance of the finished product, it behooves designers to become familiar with specific behavior characteristics of each plastic considered for an application. Recognize potential problems. A major cause for problems is not of poor product design but instead that the processes operated outside of their required operating window. This subject will be reviewed latter in this Chapter under PROCESS CONTROL... 

For parenteral use, the antibiotic is packed in sterile vials as a powder (reconstituted before use) or suspension. For oral use it is prepared in any of the standard presentations, such as film-coated tablets. Searching tests are carried out on an appreciable number of random samples of the finished product to ensure that it satisfies the stringent quahty control requirements for potency, purity, freedom horn pyrogens and sterility. 

For nonpharmacopeial materials a full specification should be included in the application. This should include appropriate tests and requirements for physical characteristics, identification, relevant purity tests, and performance-related tests. Characteristics likely to influence bioavailability of the finished product should be controlled. Routine tests and specifications should be described. Methods should be validated. The material should be fully characterized, with full data on the chemistry concerned and including consideration of the safety of the excipient. Any relevant European Directive requirements or other international specifications should be met, but additional requirements might apply depending on the intended use of the product—e.g., for materials to be used in sterile products. 

Soya Proteins. Early attempts to make albumen substitutes from soya protein also ran into problems. A bean flavour tended to appear in the finished product. A solution to these problems has been found. Whipping agents based on enzyme modified soy proteins are now available. The advantage of enzymatic modification is that by appropriate choice of enzymes the protein can be modified in a very controlled way. Chemical treatment would be far less specific. In making these materials the manufacturer has control of the substrate and the enzyme, allowing the final product to be almost made to order. The substrates used are oil-free soy flakes or flour or soy protein concentrate or isolate. The enzymes to use are chosen from a combination of pepsin, papain, ficin, trypsin or bacterial proteases. The substrate will be treated with one or more enzymes under carefully controlled conditions. The finished product is then spray dried. 

Foreign contamination is typically first discovered by quality control checks of the finished product or by the loss of the web for film processes. If a melt filtration system is installed downstream of the extruder, the larger size particles will be collected. After the contaminants are collected they must be analyzed for composition. Some types of contaminants are easily identified using a microscope or hand lens and include paper and cloth fibers, dirt, and metal fragments. Other contaminants such as gels or foreign resins are not as easily identified, and their identification often requires advanced analytical procedures. Many resin manufacturers offer these types of services to their customers. After the contaminant is identified, the source must be determined and then eliminated. Elimination of the source can be simple for common contaminants but can be a challenge for contaminants that exist at a very low level. 

Control analyses rely on the use of appropriate procedures or measurements assuring the identity of the materials involved in each step of the manufacturing process from receipt of raw materials to delivery of the finished products. NIR spectroscopy is an advantageous alternative to wet chemical methods and instrumental techniques such as IR, Raman and nuclear magnetic resonance (NMR) spectroscopies for positive identification. 

There are, of course, special provisions when a Member State can suspend or revoke an authorisation where the product proves to be harmful in the normal conditions of use or where its therapeutic efficacy is found to be lacking or where its qualitative and quantitative composition is not as declared. An authorisation may also be suspended or revoked where the particulars in the dossier are incorrect or have not been amended or when the controls on the finished product have not been carried out. 

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