Glossary

Welding in which the entire operation is performed and controlled completely by hand.

Operations involving receipt of materials, production, packaging, repackaging, labeling, relabelling, quality control, release, storage, and distribution of APIs and related controls.

(ICH Q7) All operations of receipt of materials, production, packaging, repackaging, labeling, relabeling, quality control, release, storage, and distribution of APIs and related controls.

The party responsible for the quality of the drug product.

A person, where required and authorized by a regulatory authority, engaged in manufacturing and/or importantion activities.

A collective term used to describe the functional activities essential for the management and control of production and manufacturing operations in a given organization. (GAMP Americas Forum MES SIG Draft)

All manufacturing and storage steps in the creation of the finished product from the weighing of components through the storing, packaging, and labeling of the finished product, including, but not limited to, the following: Mixing, granulating, milling, molding, formulating, lyophilizing, tableting, encapsulating, coating, sterilizing, and filling.

The basic processes for rDNA fermentation and purification normally include the following steps:1.Inoculum Preparation: The aim is to develop for the production stage fermentation a pure inoculum in sufficient volume and in the fast-growing (logarithmic) phases so that a high population density is obtained. This is accomplished through a seed fermentation train.2.The Medium: This is designed to provide the microorganism with all the nutrients it requires. Provision is usually made to add nutrients during fermentation.3.Oxygen Supply: An adequate supply of oxygen is required. As oxygen is only slightly soluble in water, a number of methods are used to make oxygen more readily available to the microorganisms in the broth, including sparging, mechanical agitators, and dispersion baffles in the fermentor tank.4.Temperature Control: Heat is generated both by the metabolism of nutrients and by the power dissipated in stirring and has to be removed by controlled cooling. Tank jackets or internal coils are used to control temperature.5.Antifoam Agents: Microbiological systems that are vigorously stirred and aerated usually produce foam. Excessive foam cannot be tolerated and so provisions have to be made for adding antifoam agents.6.Harvesting: This is the removal of the cells from the broth. This can be accomplished by cross-flow filtration or centrifugation.7.Cell Lysis: With E. coli fermentations, the product protein is contained within the cell in the form of an inclusion body. High-pressure homogenizers are often used to chop up the E. coli bacteria into fine fragments, liberating the inclusion bodies for further processing.8.Purification: This is the separation of the desired product from the other constituents in the harvested broth. Various processes including refolding, ultrafiltration/diafiltration, centrifugation, and chromatographic columns are employed to purify the product.

(ICH Q5C) Manufacture at the scale typically encountered in a facility intended for product production for marketing.

(ASTM E 2500) Elements of pharmaceutical and biopharmaceutical manufacturing capability, including manufacturing systems, facility equipment, process equipment, supporting utilities, associated process monitoring and control systems, that have the potential to affect product quality and patient safety.

Modified Atmosphere Packaging

1. Verb: To determine the relative positions of loci on a DNA molecule. Linkage mapping is done by estimating the recombination fraction between loci, from the genotypes of offspring of particular matings. The further apart two loci are on a chromosome, the greater will be the frequency of recombination between them up to a maximum of 50%, the situation observed when they are sufficiently far apart on a chromosome that recombinant gametes are as frequent as non-recombinant gametes, or when they are on different chromosomes. Physical mapping is usually performed by the use of in situ hybridization of cloned DNA fragments to metaphase chromosomes.2. Noun: A diagram showing the relative positions of, and distances between, loci.

Mouse Antibody Production

The standard measure of distance between loci, expressed in centiMorgans (cM). Estimated from recombination fraction via a mapping function. For small recombination fractions, map distance equals the percentage of recombination (recombination frequency) between two genes. 1% recombination = 1 cM. Sometimes called a map unit.

A mathematical expression relating observed recombination fraction to map distance expressed in centiMorgans. Two common mapping functions are those developed by Haldane (1919; J. Genet., 8: 299-309) and Kosambi (1944; Ann. Eugen., 12: 172-175). In both functions, the relationship between recombination fraction and map distance is approximately linear for recombination fractions less than 10%; as recombination fraction increases above 10% (up to its maximum of 50%), map distance is increasingly greater than recombination fraction.

A precipitation-hardening treatment applied to a special group of high-nickel iron-base alloys (maraging steels) to precipitate one or more intermetallic compounds in a matrix of essentially carbon-free martensite.

Machine-Readable Cataloguing

An identifiable DNA sequence that facilitates the study of inheritance of a trait or a gene. Such markers are used in mapping the order of genes along chromosomes and in following the inheritance of particular genes: genes closely linked to the marker will generally be inherited with it. Markers must be readily identifiable in the phenotype, for instance by controlling an easily observable feature (such as eye color) or by being readily detectable by molecular means, e.g., microsatellite markers.

The degree to which competition exists in the market for a specific good or service. Higher levels of competitiveness tend to drive higher efficiencies among suppliers.

A statement of generic industry requirements used by the Supplier as an input to their product development life cycle.

An official document issued by the competent drug regulatory authority for the purpose of marketing or free distribution of a product after evaluation for safety, efficacy and quality. It must set out, inter alia (“among other things”), the name of the product, the pharmaceutical dosage form, the quantitative formula (including excipients) per unit dose (using INNs or national generic names where they exist), the shelf-life and storage conditions, and packaging characteristics. It specifies the information on which authorization is based (e.g. "The product(s) must conform with all the details provided in your application and as modified in subsequent correspondence"). It also contains the product information approved for health professionals and the public, the sales category, the name and address of the holder of the authorization, and the period of validity of the authorization. Once a product has been given marketing authorization, it is included on a list of authorized products - the “register” - and is often said to be "registered" or to "have registration". Market authorization may occasionally also be referred to as a license or product license.

(ICH Q1B)The combination of immediate pack and other secondary packaging such as a carton.

The hard constituent produced when steel is cooled from the hardening temperature at a speed greater than its critical cooling rate. Martensite is an acicular phase when seen in the microstructure of steel.

A hard constituent in quenched steel, formed without diffusion and only during rapid cooling below a certain temperature. It is the hardest of the transformation products of austenite.