Good Manufacturing Practices Test 1
ISO
International Organization for Standardization= an international, non-governmental, non-profit group of interested volunteer professionals who promulgate standards on a vast array of technical topics
endotoxin
a biological molecule which is shed or excreted by bacteria, which elicits an immune response
alkylating agents
a category of chemical biocides which alkylate various biologically-important molecules
aldehydes
a category of chemical biocides which cross-link various biologically-important molecules
surfactants
a category of chemicals which, above a certain concentration, form micelles capable of sequestering organics, bacteria, particles and thereby serve as cleansing agents
sodium hypochlorite
a chemical biocide commonly found in household bleach whose mode of sterilization is equivalent to hypochlorous acid
hypochlorous acid
a chemical biocide naturally produced by many members of the animal kingdom which is capable of reacting with a wide range of biologically-important molecules
slab-on-grade cleanroom
a cleanroom in which incoming air vents along the sides of the walls
total down flow cleanroom
a cleanroom in which incoming air vents through floor grates down to a subfab directly below the floor
non-traditional compounding pharmacy
a compounding pharmacy which prepares dosage forms other than those of a traditional compounding pharmacy; ingredients may and often do include those not approved for use in the U.S. by the FDA; compounding is rarely if ever in accordance with GMP mandates; compounding is often undertaken in high-volume, and rarely if ever in response to the prescription of a licensed clinical practitioner
traditional compounding pharmacy
a compounding pharmacy which prepares individualized medicines in response to the prescription of a licensed clinical practitioner
tunnel tool
a continuous-flow process tool coupled with a minienvironment
normally-distributed data
a data set which is adequately modeled by a Gaussian curve (aka normal curve)
bioindicator
a device used to confirm the sterilizing performance of a steam sterilizer
ultrafilter
a filter which obstructs the passage of particles greater than about a micron in diameter
defect
a flaw in a part
control chart
a graph of a measured process parameter in which time is on the x-axis, the magnitude of the process parameter is on the y-axis, and both upper and lower control limits are depicted
gamma ray
a high-energy photon= a photon of energy greater than about 1 x 10^8 cm^-1 (reciprocal wave numbers)
steam sterilizer
a machine capable of sterilizing liquids solids, culture media by a series of process steps which minimally include an input of steam into an enclosed and pressurized process chamber at temperatures in excess of 100 degrees Celsius= autoclave= moist-heat sterilizer= pressure vessel
control limits
a maximum or minimum value of a given process parameter within which measured results are expected to fall in the absence of special variablility
process capability
a measure of the ability of a given process to produce product that is within pre-specified spec limits
dosage form
a medicine administered to a patient, a tablet, capsule, suppository, skin patch, inhaler, ointment, syringe-injectable formulation
straining filtration
a method of filtration in which particles within a gas or liquid flow stream are captured by at points of physical constriction within the filter media
diffusion filtration
a method of filtration in which particles within a gas or liquid flow stream are captured by diffusion-driven physical contact and adsorption against the filter media
interception filtration
a method of filtration in which particles within a gas or liquid flow stream are captured by grazing physical contact and adsorption against the filter media
impingement filtration
a method of filtration in which particles within a gas or liquid flow stream are captured by inertial impact and adsorption against the filter media
gamma ray sterilization
a method of physical sterilization by irradiation with gamma rays which results in the destruction or structural alteration of biological molecules, particularly genetic materials and proteins
ozone
a molecule comprised of three atoms of oxygen which acts as a chemical biocide
excipient
a natural or synthetic substance added to an API for the purpose of (i) bulking-up the API ("bulking agent," "filler,", or "diluent"), or (ii) enhancing the final dosage form by facilitating drug absorption, solubility, ease of use
6 sigma
a phrase used to signify a certain acceptable level of process capability, in which 2 defects are expected for every one billion units
3 sigma
a phrase used to signify a certain acceptable level of process capability, in which 26 defects are expected for every 10,000 units
Cpk
a quantitative measure of process capability
RSO
radiation safety officer
21 CFR parts 210 through 226 of the U.S. Code of Federal Regulations
regulations in the CFR which specify Good Manufacturing Practice
21 CFR
regulations of Title 21 of the U.S. Code of Federal Regulations
spec
specification= the specified acceptable value, range of values, max value or min value of a given parameter of a given product or component
483s
summary letters sent by FDA auditors after all on-site inspections
non-ionic surfactants
surfactants which are uncharged
zwitterionic
surfactants which carry both positive and negative charges
ionic surfactants
surfactants which carry positive, negative, and/or both positive and negative charges
out-of-spec
the condition of exceeding spec limits
"Alert" and "Action" levels
the number of bacterial colonies or particles allowed in a given controlled area
aseptic conditions
the physical conditions which result from rigorous adherence to GMP regulations, not necessarily sterile, but clean enough for processing sterile drugs medical devices and containers; emphasis is on preventing objectionable organisms such as molds, yeasts, sporiformers, E. coli, Salmonella
relative frequency
the probability of finding a given value in a data set
environmental monitoring
the process by which samples are collected from multiple sources in the facility to determine the cleanliness of surfaces, air, water personnel, plant systems, and especially equipment that comes into direct contact with product= the systematic sampling of air, water, equipment, (and any potential product contact surfaces) in order to observe and study the environment
pulsing cycle
the process recipe of a steam sterilizer which entails one or more steps involving sub-atmospheric and super-atmospheric pressure changes along the steam curve
vacuum cycle
the process recipe of a steam sterilizer which entails one or more sub-atmospheric evaluations of the chamber
bioburden
the quantity of microbes on an unsterile surface or within an unsterile pharmaceutical
osmosis
the spontaneous movement of liquid from regions of high solute concentration to regions of low solute concentration
decimal reduction time
the time to cross one log cycle in reducing a given bacterial population by steam sterilization; a common metric of the efficacy of a given steam sterilizer or steam sterilization recipe
spec limit
the value of a measured process parameter above or below which a product or component is out-of-spec= those measured product parameters which, when exceeded, result in the production of unsellable or potentially unsellable product
to sterilize
to eliminate all viable microorganisms--bacteria, yeast, molds, prions--on or in a product or surface
API
active pharmaceutical ingredient
vegetative bacterial cells
actively reproducing bacterial cells
population
all possible observations= the entire set of observations which which are obtainable from some phenomenon, often infinite in number
RODAC
an acronym for "replicate organism detection and counting"
minienvironment
an enclosure around a process tool, usually integral with the body of the tool, and usually airtight-sealed
compounding pharmacy
an organization at which ingredients are combined, mixed or altered
out-of-spec part
an unsellable part= a part with a flaw of such magnitude that the part is not within specification; it is "out-of-spec"
adulterated
any drug which was processed in a manner that did not comply with one or more regulations of Title 21 parts 210 through 226 of the U.S. Code of Federal Regulations
pyrogens
any substance which elicits an immune response due to bacteria-derived endotoxins, fragments of dead bacteria, and other bacterial-derived by-products
biocide
anything that reduces or eliminates viable microorganisms on or in a product or surface such as heat, cold, steam, filtration, gamma rays, certain chemicals, certain biologicals; there are three types: physical, chemical, biological
laminar air
flowing air in which flow lines are uniformly straight=unidirectional air
in control
in a state of control= in statistical control= the condition in which the result obtained from measuring a process parameter over time depends solely on natural variability, with no contribution from special variability
steam
invisible water vapor which is 100 deg Celsius at 1 atm
Consent Decrees
letters sent by courts of U.S. federal judicial system which contain legally-binding orders and mandates such as "You will cease operations"; typically sent in response to inadequate responses to Warning Letters
Warning Letters
letters sent by the FDA as a result of repeated uncorrected or egregious violations
viable microorganisms
microorganisms that are able to reproduce
prions
misfolded protein molecules which cause various lethal diseases for which no known cures are currently known
turbulent air
non-unidirectional air
Gaussian curve
normal curve= bell curve= the curve defined by de Moivre's equation
out of control
not in a state of control= the condition in which the result obtained from measuring a process parameter over time depends in part on special variability
FDC guidance
official proclamations of the FDA which have no force of law, but are intended to be helpful in adhering to the CFR
observation
one data point= a measurement
CFR
Code of Federal Regulations= an on-line database of legally-binding documents which specify how U.S. federal agencies interpret acts of Congress
FDC Act
Food, Drug, and Cosmetic Act= an act of Congress originally passed in 1939 which established the general principles of Good Manufacturing Practices, and gave authority to the Food and Drug Administration to enforce the provisions of the act
GMP
Good Manufacturing Practices=guidelines of the U.S. FDA which specify a desired mindset and set of actions and behaviors in the manufacture and distribution of safe and effective health-related products, particularly pharmaceuticals and medical devices
USP
United States Pharmacopeia=(i) a U.S.-based non-profit, non-governmental organization comprised of volunteers who promulgate standards on pharmaceutical-related topics; (ii) the title of the set of standards promulgated by the USP
cleanroom
a room or set of rooms in which air-borne particles are minimized by filtering incoming air, typically accompanied by special gowning protocols of workers within the cleanroom= a airtight-sealed room in which all incoming air is filtered to remove particulate matter
ISO 14644
a set of standards promulgated by the ISO on the classification of air cleanliness, specs for testing and monitoring, test methods, design of facilities, construction of facilities, start-up of facilities and operation of facilities
slab-on-grade-with-raised-floor cleanroom
a slab-on-grade cleanroom in which incoming air vents through the grating of a raised floor
sample
a small but representative collection of observations from a population
downward displacement steam sterilizer
a steam sterilizer in which the insulating effects of air are mitigated by introducing steam at one or more points in the ceiling of the chamber, and thereby forcing less buoyant air to the bottom of the chamber where typically it is evacuated out
RODAC plate
a sterile Petris dish or plate of culture media routinely used for environmental monitoring
lipopolysaccharide
a structural component of the cell wall of bacteria which typically acts as a pyrogen
process capability study
a study whose purpose is to answer the question: "Can the process produce product that meets specs?"
aseptic technique
a technique intended to keep patients or inanimate objects as free from microorganisms as possible
reverse osmosis
a water-purification industrial process by which a flow of solute-laden and/or microorganism-containing solution is pressurized against a semi-permeable membrane, and cause to flow in reverse of the spontaneous, osmotically-driven, direction, thereby tending to produce ultra-pure and/or disinfected water
cGMP
current GMP= the practice of ever-evolving GMP guidelines in light of current knowledge
FFP
finished final product
spore
endospore= a special resting bacterial cell able to withstand conditions that otherwise kill all normal active cells ("vegetative" cells); they are contained within a hard polysaccharide outer pod
to disinfect
to reduce the number of viable microorganisms on or in a product or surface to a level appropriate for subsequent use
to decontaminate
to render a product or surface safe for handling, use, or disposal with respect to any contaminant, not just microbial
to clean
to sanitize= to remove contaminant from a surface or a product
natural variability
variability due to the intrinsic statistical nature of physical phenomena such as chance, randomness, stochastic phenomena
Purified Water
water for the preparation of medicine that are not required to be sterile and apyrogenic
Water for injection
water for the preparation of medicines to be administered parenterally
superheated steam
water vapor at a temperature which is greater than the boiling point for a given pressure
condensate
water vapor at a temperature which is less than the boiling point for a given pressure
Pharmaceutical Water
water which meets the standards of USP 1231
