Glossary of Terms - R

Radiation Sterilization
Sterilization using gamma radiation emitted from radioactive materials such as cobalt-60, or cesium 137. If proper dosage of nuclear radiation can be documented, sterility testing is not required.

Radio-Immunoassay (RIA)
A highly sensitive method of detecting and measuring the concentration of biological compounds in vivo.

Radioactive Material
A material or combination of materials that spontaneously emits ionizing radiation.

Raw Material
A general term used to denote starting materials, reagents, intermediates, process aids, and solvents intended for use in the production of intermediates or APIs (Active Pharmaceutical Ingredients).

rDNA (Recombinant DNA)
The hybrid DNA produced by joining pieces of DNA from different sources.

Reagent
A substance used (as in detecting or measuring a component, in preparing a product, or in developing photographs) because of its chemical or biological activity.

Reagent Grade Water
Water suitable for use in making up reagents or for use in sensitive analytical procedures. There are several grades of reagent grade water as defined by various professional organizations, such as ASTM, CAP, NCCLS, and ACS:

1. Type I: Used for procedures requiring maximum accuracy and precision, such as atomic spectrometry, flame photometry, enzymology, blood gas, pH and specific ion determinations; reference buffer solutions; and reconstitution of lyophilized materials used as standards. ASTM to produce Type I water specifies distillation pretreatment of feedwater.

2. Type II: Recommended for most analytical or general laboratory testing such as hematological, seralogical, and microbiological procedures as well as chemical methods not specifically stated or proven to require Type I quality. ASTM specifies preparation of Type II by distillation and recommends it whenever freedom from organic impurities is important.

3. Type III: Satisfactory for some general laboratory tests; for most qualitative analyses such as urinalysis, parasitology, and histological procedures; for rinsing of analytical samples; preparation of stock solutions; and for washing or rinsing of glassware (final glassware rinsing should be performed with the water type specified for the procedure performed). Distillation, mixed-bed deionization, and reverse osmosis (with high quality feedwater) can be used to generate Type III.

Recalcification
A technique producing serum from anticoagulated plasma. Citrate and oxalate act as anticoagulants because they are Ca++ (Calcium Ion) chelating agents; Ca++ as calcium chloride is added in excess (1/40 Molar). Ca++ is a coagulation co-factor (catalyst) and promotes clot formation.

Recessive Allele
A gene that is expressed only when its counterpart allele on the matching chromosome is also recessive (not dominant). Autosomal recessive disorders develop in persons who receive two copies of the mutant gene, one from each parent who is a carrier.

Recirculation
Continuous recirculation may be necessary to maintain uniformly high purity in larger water systems. Water is continuously recirculated and reprocessed to prevent stagnation and to rinse out residual impurities in the system. Bacteria flourish in stagnant water, especially if temperature is conducive to growth.

Recombinant
Pertaining to the recombining of generic material from one species into alternate sequences. Plasmids may then be used to incorporate the genetic material into other organisms such as E. coli bacteria.

Recombinant Clone
Clone containing recombinant DNA molecules.

Recombinant DNA Molecules
In the context of the NIH Guidelines, recombinant DNA molecules are those constructed outside living cells by joining natural or synthetic DNA segments to DNA molecules that can replicate in a living cell, or molecules that result from the replication of those described above.

Recombinant DNA (rDNA)
The hybrid DNA produced by joining pieces of DNA from different sources.

Recombinant DNA Techniques
Procedures that transfer genetic material between organisms or species.

Recombinant DNA Technology
Procedure used to join together DNA segments in a cell-free system (an environment outside a cell or organism). Under appropriate conditions, a recombinant DNA molecule can enter a cell and replicate there, either autonomously or after it has become integrated into a cellular chromosome.

Recombination
The process by which progeny derive a combination of genes different from that of either parent. In higher organisms, this can occur by crossing over.

Recovery
Any treatment of materials by a process intended to make them suitable for further use.

Recovery Time
The time after an upset in a room's HVAC environmental parameters for the room to return to "normal" conditions, such as a return to acceptable humidity levels after a room wash down. This occurs within a certain number of air changes after the upset source is removed, minimally six to ten, depending on the severity of the upset, the quality of the air supply, and the degree of mixing of room air.

Reference Standard, Primary
A substance that has been shown by an extensive set of analytical tests, to be authentic material of high purity. This standard may be obtained from a recognized source or may be prepared by independent synthesis or by further purification of existing production material.

Reference Standard, Secondary A substance of established quality and purity, as shown by comparison to a primary reference standard, used as a reference standard for routine laboratory analysis.

Referential Integrity
Relationship between records that ensures data integrity by maintaining unbreakable links between related electronic records. It ensures confidence that a specific record (such as a calculated chromatographic result) is unmodified, unmanipulated, and otherwise uncorrupted after its creation and that still carries the references to the other electronic records that were used to generate it.

Refrigerants
Fluids used for heat transfer in a refrigerating system; the refrigerant absorbs heat and transfers it at a higher temperature and higher pressure, usually with a change of state. Refrigerants can be: 1. Primary refrigerants. Liquids with low boiling points that change from a liquid to a gas after absorbing heat. 2. Secondary refrigerants. Substances that act only as heat carriers, such as brine, air, and water.

Regenerate
Restore ion exchange of resins by reversing the process. An acid rinse is used to restore cation resin capacity and a sodium hydroxide rinse is used to restore anion resin capacity.

Regulatory Affairs
Drug companies must show that their products consistently meet standards set by government agencies. Regulatory affairs departments document those activities, submit proposals, and follow those proposals through completion or approval.

Regulatory Region or Sequence
A DNA base sequence that controls gene expression.

Reject Stream
In reverse osmosis and ultrafiltration, those impurities not able to permeate the membrane are said to be rejected (removed). They are flushed away in the reject (waste) stream.

Relational Database Management System (RDBMS)
A type of database system that stores data in related tables. A relational database is powerful because it does not assume how data are related or how they will be extracted from the database. As a result, the same database can be viewed in many different ways.

Relative Humidity (% RH)
The ratio (measured in percent) of actual water vapor pressure in air to the pressure of saturated water vapor in air at the same temperature and pressure.

Release
The discharge of a microbiological agent or eukaryotic cell from a containment system.

Renaturation
The restoration of biological activity to a denatured protein or nucleic acid. The strands of a DNA duplex, for example, are denatured at high temperatures but can be correctly reformed by a slow cooling.

Representative Sample
A sample that consists of a number of units that are drawn based on rational criteria such as random sampling and intended to assure that the sample accurately portraits the material being sampled.

Reproductive Toxicology
Studies of whether exposure affects male or female fertility.

Reprocessing
A system of reworking batches that do not conform to standards or specifications, including "the steps taken to ensure that the reprocessed batches will conform to all established standards, specifications, and characteristics".

Reprocessing (ICH API definition)
Introducing an intermediate or API, including that which does not conform to standards or specifications, back into the process and repeating a crystallization step or other appropriate chemical or physical manipulation steps (e.g., distillation, filtration, chromatography, milling, etc.) that are part of the established manufacturing process. Continuation of a chemical reaction after an in-process control test shows the reaction to be incomplete is considered to be part of the normal process, and not reprocessing.

Resin
Ion exchange resins are usually bead-like spherical materials with an affinity for particular ions. Cation exchange resins made of styrene and divinylbenzene containing sulfonic acid groups will exchange hydrogen ions for any cations they encounter. Similarly, anion exchange resins made of styrene and divinylbenzene containing quaternary ammonium groups will exchange a hydroxyl ion for any anions.

Resistance (Filter)
The pressure drop across a filter at a stated flow and under given conditions; generally expressed in millimeters water gauge or PSI, or in SI units as N/m² or Pascals.

Resistivity The reciprocal of conductivity (R=1/C). A measure of specific resistance to the flow of electricity. In water, provides an easy mean of continuously measuring the purity of very low Total Dissolved Solids (TDS), or ionic concentration. The fewer the dissolved ions in water, the higher its resistivity. Resistivity is normally expressed in Megohm-cm and is equivalent to one million ohms of resistance measured between two electrodes one centimeter apart. The theoretical maximum ionic purity of water is 18.3 Megohm-cm at 25°C.

Resolution
Degree of molecular detail on a physical map of DNA, ranging from low to high.

Restriction Enzyme, Endonuclease A protein that recognizes specific, short nucleotide sequences and cuts DNA at those sites. Bacteria contain over 400 such enzymes that recognize and cut over 100 different DNA sequences.

Restriction Enzyme Cutting Site
A specific nucleotide sequence of DNA at which a particular restriction enzyme cuts the DNA. Some sites occur frequently in DNA (e.g., every several hundred base pairs), others much less frequently (rarecutter; e.g., every 10,000 base pairs).

Restriction Fragment Length Polymorphism (RFLP)
Variation between individuals in DNA fragments sizes cut by specific restriction enzymes; polymorphic sequences that result in RFLPs are used as markers on both physical maps and genetic linkage maps. RFLPs are usually caused by mutation at a cutting site.

Retest Date
The date when samples of the API (Active Pharmaceutical Ingredient)a material should be re-examined to ensure that material is still suitable for use.

Retinoblastoma
An eye cancer caused by the loss of a pair of tumor-suppressor genes; the inherited form typically appears in childhood, since one gene is missing from the time of birth.

Retrospective Validation
Establishing documented evidence that a system does what it purports to do based on review and analysis of historic information.

Retrovirus
An oncogenic, RNA-containing virus, which replicates through a double-stranded DNA intermediate necessitating the presence of an RNA-dependent DNA polymerase.

Revalidation
Repetition of validation process or a specific portion of it.

Revalidation
Extent of validation necessary to assure that changes made to qualified or validated equipment, utilities, systems and process do not adversely affect the finished product. Implemented changes should be tracked and evaluated through a thorough, dynamic, change control program.

Reverse Osmosis (RO)
The reversal of osmosis to purify water. In osmosis, water diffuses through a semipermeable membrane from a region of higher concentration (such as pure fresh water) into one of lower concentration (such as a solution of water and salt). The flow of water can be reversed with an opposing pressure that exceeds osmotic pressure. With RO, water is forced out of the lower concentrated solution (such as the salt solution), leaving the solute (impurities) behind.

Reverse Osmosis (RO)
RO is one of two acceptable techniques for producing Water For injection (WFI), U.S.P. Procedure involves passing purified water across a semipermeable membrane against an osmotic gradient. R.O. is an excellent pretreatment for deionized water that will be subsequently filtered, because silt and colloids are removed. Usual performance of R.O. is removal of organics, multi-valent ions, and 90% of mono-valent ions.

Reworking
Subjecting an intermediate or API (Active Pharmaceutical Ingredient) that does not conform to standards or specifications, to one or more processing steps that are different from the established manufacturing process so that its quality may be made acceptable (e.g., recrystallizing with a different solvent).

A molecule consisting of a number of ribonucleotides attached together to form a long strand one nucleotide thick. Each nucleotide contains the sugar, ribose, and one of four different bases: cytosine, adenine and guanine (as in DNA) and uracil (as opposed to thymine in DNA). The major portion of cellular RNA occurs as ribosomal RNA (rRNA), to a lesser extent as transfer RNA (tRNA) and less still as messenger RNA (mRNA), all three forms being concerned with transformation of the DNA sequence into the complementary protein sequence. It also occurs in some viruses where it acts as the hereditary material.

Ribonucleotide


Ribosomal RNA (rRNA)
A class of RNA found in the ribosomes of cells.

Ribosomes
Small cellular components composed of specialized ribosomal RNA and protein; site of protein synthesis.

Rickettsias
Gram-negative microorganisms that are often carried by arthropod vectors and may infect humans and other mammals. Generally smaller than other bacteria, they require living cells for growth.

Rinse
The operation that follows regeneration, a flushing out of excess regenerant solution.

Roller Bottles
Small cylindrical bottles often used as bioreactors in the production of products by cell culture. The bottles are kept on a device that rotates them slowly to help assure proper growth. Automated systems may also be used for large arrays of roller bottles introducing sterile media and harvesting finished product automatically.

Rouge
Form of surface corrosion that occurs in some stainless steel piping systems.

Roughness
Consists of the finer irregularities of the surface texture, usually including those irregularities that result from the manufacturing process. These are considered to include traverse feed marks and other irregularities within the limits of the roughness sampling length.