Glossary

The replacement of a normal gene with a mutated form of the gene by using homologous recombination. Used to study gene function.

A computerized device for synthesizing genes by combing nucleotides (bases) in the proper order.

Determination of the relative positions of genes on a DNA molecule (chromosome or plasmid) and of the distance, in linkage units or physical units, between them.

Landmarks for a target gene, either detectable traits that are inherited along with the gene, or distinctive segments of DNA.

The sum total of genes, with all their variations, possessed by a particular species at a particular time.

Predictions of possible genes made by a computer program based on how well a stretch of DNA sequence matches known gene sequences.

A single-stranded DNA or RNA fragment used in genetic engineering to search for a particular gene or other DNA sequence. The probe has a base sequence complementary to the target sequence and will thus attach to it by base-pairing. By labelling the probe, it can be identified after subsequent separation and purification.

The biochemical material, either RNA or protein, resulting from expression of a gene. The amount of gene product is used to measure how active a gene is; abnormal amounts can be correlated with disease causing alleles.

The determination of the sequence of bases in a DNA strand. The two most widely used methods are the chain-termination method, developed by Sanger in the mid-seventies, and the chemical method developed by Maxam & Gilbert around the same time.

The size of the unspliced transcript, including introns. As gene-prediction programs do not detect untranslated regions, they are not included in this definition.

A stage in the processing of mRNA, occurring only in eukaryote cells, in which intervening sequences (introns) are removed from the primary RNA transcript (hnRNA), and the coding exons are joined together to form the mature mRNA molecule.

The treatment of genetic disease accomplished by altering the genetic structure of either somatic (nonreproductive) or germline (reproductive) cells.

The treatment of inherited diseases by introducing into the cells of affected individuals the wild-type copies of the defective gene causing the disorder. If reproductive cells are modified, the procedure is called germ-line or heritable gene therapy. If cells other than reproductive cells are modified, the procedure is called somatic-cell or non-inheritable gene therapy.

Insertion of unrelated DNA into the cells of an organism. There are many different reasons for gene transfer: for example, attempting to treat disease by supplying patients with therapeutic genes. There are also many possible ways to transfer genes. Most involve the use of a vector, such as a specially modified virus that can take the gene along when it enters the cell.

A more specific version of a general plant layout which includes the system interface points, space requirements, ergonomics, construction issues, manufacturing flow of materials and operators, maintenance requirements, and future expansion or alterations.

Certain FDA statutory provisions designed to control the safety of marketed drugs and devices. The general controls include provisions on adulteration, misbranding, banned devices, good manufacturing practices, notification and record keeping, and other sections of the Medical Device Amendments to the Food, Drug and Cosmetic Act. Federal Food, Drug, & Cosmetic Act, Chapter V, Drugs and Devices.

The relatively uniform reduction of thickness over the surface of a corroding material. It is relatively easy to measure, predict and design against this type of corrosion damage. General corrosion is usually controlled by selecting suitable materials, protective coatings, cathodic protection and corrosion inhibitors. Stainless steels are subject to general corrosion in the presence of many acids and some salt solutions.

A diagram that relates the unit operations of the system to one another. Its development should depend on production requirements, product matrix, and possibilities for future expansion.

(CMC-BWG) An adjustable parameter (variable) of the process that does not have a meaningful effect on product quality or process performance. A key process parameter does not affect critical product quality attributes. Ranges for GPPs are established during process development, and changes to operating ranges will be managed within the quality system.

Designation given to foods, drugs, and other materials that have been used for a considerable period of time and have a history of not causing illness to humans, even though extensive toxicity testing has not been conducted. More recently, certain host organisms for recombinant DNA experimentation have been given this status.

A drug produced and marketed under its chemical or “generic” name (e.g. acetaminophen) as opposed to “Tylenol”, a brand name for the former produced by Johnson & Johnson. A generic drug can be sold only after a proprietary drug goes off patent (i.e. when the patent runs out after 17 years). There are numerous generic drug manufacturers. While generic drugs are cheaper for consumers, they still must meet the standards of GMPs as set out by the FDA.

After a drug goes off-patent, any manufacturer who finds it profitable may produce an equivalent drug and sell it under the drug’s chemical or “generic” name. The original version is then called the brand-name drug, and the new competitive versions generic drugs. The Waxman-Hatch Act made it much easier for generic drugs to compete against their originals.

The term “generic product” has somewhat different meanings in different jurisdictions. The use of this term is therefore avoided as much as possible, and the term “multisource pharmaceutical product” is used instead.Generic products may be marketed either under the approved nonproprietary name or under a brand (proprietary) name. They may be marketed in dosage forms and/or strengths different from those of the innovator products. Where the term “generic product” is used, it means a pharmaceutical product, usually intended to be interchangeable with the innovator product, which is usually manufactured without a license from the innovator company and marketed after expiry of the patent or other exclusivity rights. The term should not be confused with generic names for APIs.

The sequence of nucleotides, coded in triplets (codons) along the mRNA that determines the sequence of amino acids in protein synthesis. The DNA sequence of a gene can be used to predict the mRNA sequence, and the genetic code can in turn be used to predict the amino acid sequence.