Manufacturing, pharmaceutical control

Netherlands Pharmaceutical Manufacturers Association National Pharmaceutical Control Bureau (Malaysia) over-the-counter [medicines]... 

Contracting out of activities previously only conducted in-house is already becoming quite common and will probably continue to develop. In the past a so-called full-service pharmaceutical company took direct responsibility for all the activities required for the formulation, manufacture, quality control, and regulatory approval of its drug products. Nowadays the use of specialist contract houses to perform activities such as formulation, analytical methods development, manufacture of clinical trials supplies, supervision of the assembly of an NDA, postmarketing surveillance, and even troubleshooting may be contracted for even by some of the largest companies. 

Detecting known substances, and determining their quantity, is also important. In synthetic research, it is essential to know the relative proportions of various reaction products. In manufacturing, it is important to detect any impurities in the product and to determine whether they are present in a significant amount. Analytical characterization is critical in pharmaceutical products, for instance. Products for practical uses—paint or adhesives, for example—will typically consist of several components. For proper and reliable performance it is important to measure the amounts of each of the components as part of a manufacturing quality control system. Manufacturers also commonly need to analyze the raw materials they receive, measuring the amounts of various substances in them to be sure that the material meets their requirements. Before it can be correctly processed into steel, iron ore must be analyzed to determine how much of other components need to be added to produce a metal alloy of the desired composition and properties. 

The IMPD should summarise the quality, manufacture and control of the IMP including chemical (drug substance), pharmaceutical (drug... 

Peroxidation and free-radical formation should be considered as important aspects of pharmaceutical stability and quality of parenteral nutriton and intravenous drugs. Peroxidation and free-radical formation depend on environmental factors, such as storage conditions and container material, but are also influenced by formulation components or additives such as tocopherols and metabisulfite. Since the generation of these harmful species occurs generally at the time of use, manufacturing quality controls fail in demonstrating their existence. 

U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA) (2004, Dec.), Guidance for industry ANDAs Pharmaceutical solid polymorphism chemistry, manufacturing, and controls information, FDA, Rockville, MD. 

The U.S. FDA states in the Guidance for Nonclinical Studies for Development of Pharmaceutical Excipients (2) that they will continue to consider factors such as use in previously approved products, GRAS-status, or a food additive to evaluate the safety of a new excipient. The FDA states . .. an excipient with documented prior human exposure under circumstances relevant to the proposed use may not require evaluation in a full battery of toxicology studies... FDA also states under some circumstances (e.g., similar route of administration, level of exposure, patient population, and duration of exposure) other factors can adequately qualify an excipient (2). The sponsor of a new excipient should meet with the FDA to provide information regarding the toxicology, chemistry, manufacturing, and controls necessary to evaluate a potential new excipient. 

FDA(2004).Guidancefor Industry ANDAs Pharmaceutical Solid Polymorphism Chemistry, Manufacturing and Controls Information, CDER, Rockville, MD. 

The apparatus used to measure membrane bubble points is shown in its simplest form in Figure 7.7 [4], Bubble point measurements are subjective, and different operators can obtain different results. Nonetheless the test is quick and simple and is widely used as a manufacturing quality control technique. Bubble point measurements are also used to measure the integrity of filters used in critical pharmaceutical or biological operations. 

Complete Chemistry, Manufacturing, and Control (CMC) information provided, including evidence of purity, stability, toxicology testing, and integrity of active pharmaceutical ingredient (API), placebo, and final product. 

The creation of a process to meet FDA requirements is a multidisciplinary activity. Although the Chemical Process Development organization generates the core process, its shaping and implementation to meet the needs of all other parties involved (particularly Regulatory, Manufacturing, Pharmaceutical Sciences, and Quality Assurance) requires an extraordinary level of collaboration. The principal objective is to produce, and to demonstrate that you have indeed produced, a high-quality API in a well-controlled system of operations. 

Pharmaceutical Purity. A safety profile of a generic drug can differ from that of the brand-name product because different impurities may be present in each of the drugs (154). Impurities can arise out of the manufacturing processes and may be responsible for adverse interactions that can occur. For example, serious adverse reactions (Lyell syndrome) were observed upon the use of isoxicam in 1985. These seemed to have resulted from trace elements of a manufacturing by-product that was within the manufacturing quality control specifications. 

CS Kumkumian. Manufacturing and controls guidelines for INDs and NDAs— 1978. Paper presented at the 25th National Meeting of the Academy of Pharmaceutical Sciences, Hollywood, Florida, November 14, 1978. 

When foods have been enriched with vitamins, because of the requirement for the food to contain the stated amount of vitamin after normal storage, manufacturers commonly add more than the stated amount - so-called overage. One of the problems in the debate concerning folate enrichment of flour (Section 10.12) is the relatively small difference between the amount that is considered desirable and the amount that may pose a hazard to vulnerable population groups, and the precision to which manufacturers can control the amount in the final products. In pharmaceutical preparations, considerable latitude is allowed the U.S. Pharmacopeia permits preparations to contain from 90% to 150% of the declared amount of water-soluble vitamins and from 90% to 165% of the fat-soluble vitamins. 

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