Manufacturing quality control

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. 

Any decision to establish automated or robotic systems must carefully consider prerequisites such as the annual numbers of samples to be processed to achieve an acceptable cost-to-benefit ratio. Late phase development stability studies may benefit from fully automated systems based on the enormous numbers of samples to be analyzed for each stability time point. The use of automated systems in manufacturing quality control is now required due to the sheer number of samples to be... 

Control Charts. The control chart approach (Montgomery, 1985), commonly used in manufacturing quality control in another form of screening (for defective product units), offers some desirable characteristics. 

Unattended operation of the laboratory robot extends the working day and permits faster sample turnaround. In a manufacturing/quality control environment, faster release of product for shipment can greatly reduce inventory costs. 

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. 

This book is intended for formulation scientists, analytical scientists and engineers, regulatory and compendia personnel, procurement personnel, preclinical scientists, excipient manufacturers, quality control and assurance personnel, and distributors. 

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. 

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. 

The preceding examples depict the use of Pareto charts in quality and manufacturing. However, these charts are applicable to almost any job or operation. We have seen them used in manufacturing, quality control, inventory control, purchasing and personnel. Think about your personal finances for a minute. More than likely, at least 80% of your income is Utilized for 20%, or less, of your budgeted items. 

Engineering, Marketing, Packaging, Pharmaceutical Manufacturing, Quality Control, and Sales. 

Data on the chemistry and pharmacy of the active ingredients, including their physicochemical structure, method of manufacture, quality control, impurities control, specifications and any other relevant data. 

Change of method of Major manufacture quality (DRA-3) control of finished product New method of manufacture quality control of finished product with the changes highlighted Data to support the new method of manufacture quality control of finished product C4(b)(i)... 

Preservatives are intended to offer further protection against environmental microbial contaminants. However, as they are relatively non-specific in their reactivity (see section 7), it is difficult to calculate with any certainty what proportion of preservative added to all but the simplest medicine will be available for inactivating such contamination. Laboratory tests have been devised to challenge the product with an artificial bioburden. Such tests should form part of formulation development and stability trials to ensure that suitable activity is likely to remain throughout the life of the product. They are not normally used in routine manufacturing quality control. 

The drug development team must ensure that reference standards will be available to support the launch of a newly approved product once FDA approval is obtained. The quality control function is typically separate from the analytical development function in most firms, so a high level of cooperation and communication are critical. As launch approaches, the drug development team must work closely with the commercial manufacturing quality control unit to coordinate the supply of reference standards to the firm s compound distribution system. It is useful to involve marketing forecasts to predict the approximate amounts of reference standards—based on projected batches—that will be necessary to support a worldwide launch. 

Parenteral Drug Association (PDA). 3 Bethesda Metro Center, Suite 1500, Bethesda, MD 20814, U.S.A. Phone +1 301-656-5900, Fax +1 301-986-0296. E-mail info pda.org. URL http //www.pda.org. PDA is a non-profit international association of more than 10,500 scientists involved in the development, manufacture, quality control, and regulation of pharmaceuticals/biopharmaceuticals, and related products. The association also provides educational opportunities for government and university sectors that have a vocational interest in pharmaceutical/biopharmaceutical sciences and technology. The association publishes the PDA Journal of Pharmaceutical Science and Technology. It holds an annual meeting and sponsors several symposia and educational programs. 

Figure 6.1. Schematic showing the various departments in pharmaceutical research discovery research, chemical and pharmaceutical development, drug metabolism and pharmacokinetics (DMPK), and manufacturing quality control. Diagram Courtesy of Waters Corporation.

Formal approval of the plan, indicating the top-level management for each function, is essential to share the responsibility. The VMP shall be supported with approval signatures from multidisciplinary functions, including Engineering, Manufacturing, Quality Control, Quality Assurance, and Validation at a minimum. 

The creation and operation of such a system and the elaboration and application of the measures involved require the participation of the staff responsible for the different department concerned development, manufacturing, quality control, etc. 

Personnel in the manufacturing, quality control, laboratory, warehousing, maintenance and sanitation areas shall be well trained, dependable, conscientious and quality minded. Personnel shall have ... 

Records shall be prepared concurrently with the performance of each step of manufacture, quality control, maintenance, sanitation, etc. 

The term lot number means the numbers, letter or their combination given to a particular lot in order to identify complete history of manufacturing, quality control and distribution. 

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