Definitions of Key Biotech Terms
Below are certain definitions provided by the US Food and Drug Administration
(FDA). The reference document is cited after each definition. Please forward links to other
officially recognized definitions that you think should be on this page to me via:
feedback@keithbower.com.
- Accelerated testing:
Studies designed to increase the rate of
chemical degradation or physical change of a drug substance or drug
product by using exaggerated storage conditions as part of the formal
stability studies. Data from these studies, in addition to long-term
stability studies, can be used to assess longer term chemical effects at
nonaccelerated conditions and to evaluate the effect of short-term
excursions outside the label storage conditions such as might occur
during shipping. Results from accelerated testing studies are not always
predictive of physical changes.
Q1A(R2) Stability Testing of New Drug Substances and Products
- Acceptance criteria:
Numerical limits, ranges, or other suitable
measures for acceptance of the results of analytical procedures which
the drug substance or drug product or materials at other stages of
manufacture should meet.
Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological
Products
- Action limit:
An internal (in-house) value used to assess the
consistency of the process at less critical steps.
Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological
Products
- Biological activity:
The specific ability or capacity of the
product to achieve a defined biological effect. Potency is the
quantitative measure of the biological activity.
Q6B Specifications: Test
Procedures and Acceptance Criteria for Biotechnological/Biological
Products
- Bracketing:
The design of a stability schedule such that only
samples on the extremes of certain design factors (e.g., strength,
package size) are tested at all time points as in a full design. The
design assumes that the stability of any intermediate levels is
represented by the stability of the extremes tested. Where a range of
strengths is to be tested, bracketing is applicable if the strengths are
identical or very closely related in composition (e.g., for a tablet
range made with different compression weights of a similar basic
granulation, or a capsule range made by filling different plug fill
weights of the same basic composition into different size capsule
shells). Bracketing can be applied to different container sizes or
different fills in the same container closure system.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Chemical Development Studies:
Studies conducted to scale-up, optimize, and validate the manufacturing process for a new drug substance.
Q3A Impurities in New Drug Substances
- Chiral:
Not superimposable with its mirror image, as applied to
molecules, conformations, and macroscopic objects, such as crystals. The
term has been extended to samples of substances whose molecules are
chiral, even if the macroscopic assembly of such molecules is racemic.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Climatic zones:
The four zones in the world that are
distinguished by their characteristic, prevalent annual climatic
conditions. This is based on the concept described by W. Grimm (Drugs
Made in Germany, 28:196-202, 1985 and 29:39-47, 1986).
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Combination product:
A drug product that
contains more than one drug substance.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Commitment batches:
Production batches of a drug substance or
drug product for which the stability studies are initiated or completed
postapproval through a commitment made in the registration application.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Comparability Bridging Study:
A study performed to provide
nonclinical or clinical data that allows extrapolation of the existing
data from the drug product produced by the current process to the drug
product from the changed process.
Q5E Comparability of
Biotechnological/Biological Products Subject to Changes in Their
Manufacturing Process
- Comparability Exercise:
The activities, including study
design, conduct of studies, and evaluation of data, that are designed to
investigate whether the products are comparable.
Q5E Comparability of
Biotechnological/Biological Products Subject to Changes in Their
Manufacturing Process
- Comparable:
A conclusion that products have highly similar
quality attributes before and after manufacturing process changes and
that no adverse impact on the safety or efficacy, including
immunogenicity, of the drug product occurred. This conclusion can be
based on an analysis of product quality attributes. In some cases,
nonclinical or clinical data might contribute to the conclusion.
Q5E Comparability of
Biotechnological/Biological Products Subject to Changes in Their
Manufacturing Process
- Container closure system:
The sum of packaging components that
together contain and protect the dosage form. This includes primary
packaging components and secondary packaging components if the latter
are intended to provide additional protection to the drug product. A
packaging system is equivalent to a container closure system.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Contaminants:
Any adventitiously introduced materials (e.g.,
chemical, biochemical, or microbial species) not intended to be part of
the manufacturing process of the drug substance or drug product.
Q6B Specifications: Test
Procedures and Acceptance Criteria for Biotechnological/Biological
Products
- Continuous Process Verification:
An alternative approach to
process validation in which manufacturing process performance is
continuously monitored and evaluated.
Q8 Pharmaceutical Development
- Decision maker(s):
Person(s) with the competence and
authority to make appropriate and timely quality risk management
decisions.
Q9 Quality Risk Management
- Degradation product:
A molecule resulting from a chemical change
in the drug molecule brought about over time and/or by
the action of light, temperature, pH, water, or by reaction with an
excipient and/or the immediate container/closure system. Also called
decomposition product.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Degradation Product:
An impurity resulting from a chemical
change in the drug substance brought about during manufacture and/or
storage of the new drug product by the effect of, for example, light,
temperature, pH, water, or by reaction with an excipient and/or the
immediate container closure system.
Q3B(R2) Impurities in New
Drugs
- Degradation products:
Molecular variants resulting from changes
in the desired product or product-related substances brought about over
time and/or by the action of, e.g., light, temperature, pH, water, or by
reaction with an excipient and/or the immediate container/closure
system. Such changes may occur as a result of manufacture and/or storage
(e.g., deamidation, oxidation, aggregation, proteolysis). Degradation
products may be either product-related substances or product-related
impurities.
Q6B Specifications: Test
Procedures and Acceptance Criteria for Biotechnological/Biological
Products
- Degradation Profile:
A description of the degradation
products observed in the drug substance or drug product.
Q3B(R2) Impurities in New
Drugs
- Delayed release:
Release of a drug (or drugs)
at a time other than immediately following oral administration.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Design Space:
The multidimensional combination and
interaction of input variables (e.g., material attributes) and process
parameters that have been demonstrated to provide assurance of quality.
Working within the design space is not considered as a change. Movement
out of the design space is considered to be a change and would normally
initiate a regulatory postapproval change process. Design space is
proposed by the applicant and is subject to regulatory assessment and
approval.
Q8 Pharmaceutical Development
- Desired Product:
(1) The protein that has the expected
structure, or (2) the protein that is expected from the DNA sequence and
anticipated post-translational modification (including glycoforms), and
from the intended downstream modification to produce an active
biological molecule.
Q6B Specifications: Test
Procedures and Acceptance Criteria for Biotechnological/Biological
Products
- Detectability:
The ability to discover or determine the
existence, presence, or fact of a hazard.
Q9 Quality Risk Management
- Development Studies:
Studies conducted to scale-up,
optimize, and validate the manufacturing process for a drug product.
Q3B(R2) Impurities in New
Drugs
- Dosage form:
A pharmaceutical product type (e.g., tablet,
capsule, solution, cream) that contains a drug substance generally, but
not necessarily, in association with excipients.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Drug product:
(Dosage form; Finished product): A pharmaceutical
product type that contains a drug substance, generally in association
with excipients.
Q6B Specifications: Test
Procedures and Acceptance Criteria for Biotechnological/Biological
Products
- Drug product:
The dosage form in the final immediate packaging
intended for marketing.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Drug substance:
(Bulk material): The material that is
subsequently formulated with excipients to produce the drug product. It
can be composed of the desired product, product-related substances, and
product- and process-related impurities. It may also contain excipients
including other components, such as buffers.
Q6B Specifications: Test
Procedures and Acceptance Criteria for Biotechnological/Biological
Products
- Drug substance:
The unformulated drug substance that may
subsequently be formulated with excipients to produce the dosage form.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Enantiomeric Impurity:
A compound with the same molecular
formula as the drug substance that differs in the spatial arrangement of
atoms within the molecule and is a non-superimposable mirror image.
Q3A Impurities in New Drug
Substances
- Enantiomers:
Compounds with the same molecular formula as the
drug substance, which differ in the spatial arrangement
of atoms within the molecule and are nonsuperimposable mirror images.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Excipient:
An ingredient added intentionally to the drug
substance which should not have pharmacological properties in the
quantity used.
Q6B Specifications: Test
Procedures and Acceptance Criteria for Biotechnological/Biological
Products
- Excipient:
Anything other than the drug substance in the dosage
form.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Expiration date:
The date placed on the container label of a
drug product designating the time prior to which a batch of the product
is expected to remain within the approved shelf life specification, if
stored under defined conditions, and after which it must not be used.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Extended release:
Products that are formulated to make the
drug available over an extended period after
administration.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Extraneous Contaminant:
An impurity arising from any source
extraneous to the manufacturing process.
Q3A Impurities in New Drug
Substances
- Formal Experimental Design:
A structured, organized method
for determining the relationship between factors affecting a process and
the output of that process. Also known as "Design of Experiments."
Q8 Pharmaceutical Development
- Formal stability studies:
Long-term and accelerated (and
intermediate) studies undertaken on primary and/or commitment batches
according to a prescribed stability protocol to establish or confirm the
retest period of a drug substance or the shelf life of a drug product.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Genotoxic carcinogens:
Carcinogens that produce cancer by affecting genes or chromosomes.
Q3C Impurities: Residual
Solvents
- Harm:
Damage to health, including the damage that can occur
from loss of product quality or availability.
Q9 Quality Risk Management
- Hazard:
The potential source of harm (ISO/IEC Guide 51).
Q9 Quality Risk Management
- Herbal Products:
Medicinal products containing, exclusively,
plant material and/or vegetable drug preparations as active ingredients.
In some traditions, materials of inorganic or animal origin can also be
present.
Q3A Impurities in New Drug
Substances
- Highly water soluble drugs:
Drugs with a dose/solubility volume
of less than or equal to 250 mL over a pH range of 1.2 to 6.8. (Example:
Compound A has as its lowest solubility at 370.5 deg.C, milligram
(mg)/milliliter (mL) at pH 6.8, and is available in 100 mg, 200 mg, and
400 mg strengths. This drug would be considered a low
solubility drug, as its dose/solubility volume is
greater than 250 mL (400 mg/1.0 mg/mL = 400 mL)) .
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Identification Threshold:
A limit above (>) which a
degradation product should be identified.
Q3B(R2) Impurities in New
Drugs
- Identification Threshold:
A limit above (>) which an impurity
should be identified.
Q3A Impurities in New Drug
Substances
- Identified Degradation Product:
A degradation product for
which a structural characterization has been achieved.
Q3B(R2) Impurities in New
Drugs
- Identified Impurity:
An impurity for which a structural
characterization has been achieved.
Q3A Impurities in New Drug
Substances
- Identified impurity:
An impurity for which a structural
characterization has been achieved.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Immediate release:
Allows the drug to dissolve
in the gastrointestinal contents, with no intention of delaying or
prolonging the dissolution or absorption of the drug.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Impermeable containers:
Containers that provide a permanent
barrier to the passage of gases or solvents (e.g., sealed aluminum tubes
for semi-solids, sealed glass ampoules for solutions).
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Impurity Profile:
A description of the identified and
unidentified impurities present in a drug product.
Q3B(R2) Impurities in New
Drugs
- Impurity Profile:
A description of the identified and
unidentified impurities present in a new drug substance.
Q3A Impurities in New Drug
Substances
- Impurity:
(1) Any component of the new drug
substance that is not the chemical entity defined as the new
drug substance. (2) Any component of the drug
product that is not the chemical entity defined as the drug
substance or an excipient in the drug product.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Impurity:
Any component of the new drug product that is not
the drug substance or an excipient in the drug product.
Q3B(R2) Impurities in New
Drugs
- Impurity:
Any component of the new drug substance that is not
the chemical entity defined as the new drug substance.
Q3A Impurities in New Drug
Substances
- Impurity:
Any component present in the drug substance or drug
product that is not the desired product, a product-related substance, or
an excipient including buffer components. It may be either process- or
product-related.
Q6B Specifications: Test
Procedures and Acceptance Criteria for Biotechnological/Biological
Products
- In-house primary reference material:
An appropriately
characterized material prepared by the manufacturer from a
representative lot(s) for the purpose of biological assay and
physicochemical testing of subsequent lots, and against which in-house
working reference material is calibrated.
Q6B Specifications: Test
Procedures and Acceptance Criteria for Biotechnological/Biological
Products
- In-house working reference material:
A material prepared
similarly to the primary.
Q6B Specifications: Test
Procedures and Acceptance Criteria for Biotechnological/Biological
Products
- In-process tests:
Tests that may be performed during the
manufacture of either the drug substance or
drug product, rather than as part of the formal battery of
tests that are conducted prior to release.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Intermediate testing:
Studies conducted at 300C/65% RH and
designed to moderately increase the rate of chemical degradation or
physical changes for a drug substance or drug product intended to be
stored long-term at 250C.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Intermediate:
A material produced during steps of the synthesis
of a new drug substance that undergoes further chemical transformation
before it becomes a new drug substance.
Q3A Impurities in New Drug
Substances
- Lifecycle:
A ll phases in the life of a product from the
initial development through marketing until the products
discontinuation.
Q8
Pharmaceutical Development
- Ligand:
An agent with a strong affinity to a metal ion.
Q3A Impurities in New Drug
Substances
- LOEL:
Abbreviation for lowest-observed effect level.
Q3C Impurities: Residual Solvents
- Long-term testing:
Stability studies under the recommended
storage condition for the retest period or shelf life proposed (or
approved) for labeling.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Lowest-observed effect level:
The lowest dose of substance in a
study or group of studies that produces biologically significant
increases in frequency or severity of any effects in the exposed humans
or animals.
Q3C Impurities: Residual
Solvents
- Mass balance:
The process of adding together the assay value and
levels of degradation products to see how closely these add up to 100
percent of the initial value, with due consideration of the margin of
analytical error.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Matrixing:
The design of a stability schedule such that a
selected subset of the total number of possible samples for all factor
combinations is tested at a specified time point. At a subsequent time
point, another subset of samples for all factor combinations is tested.
The design assumes that the stability of each subset of samples tested
represents the stability of all samples at a given time point. The
differences in the samples for the same drug product should be
identified as, for example, covering different batches, different
strengths, different sizes of the same container closure system, and,
possibly in some cases, different container closure systems.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Mean kinetic temperature:
A single derived temperature that, if
maintained over a defined period of time, affords the same thermal
challenge to a drug substance or drug product as would be experienced
over a range of both higher and lower temperatures for an equivalent
defined period. The mean kinetic temperature is higher than the
arithmetic mean temperature and takes into account the Arrhenius
equation. When establishing the mean kinetic temperature for a defined
period, the formula of J. D. Haynes (J. Pharm. Sci., 60:927-929,
1971) can be used.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Modified release:
Dosage forms whose drug
release characteristics of time course and/or location are chosen to
accomplish therapeutic or convenience objectives not offered by
conventional dosage forms, such as a solution or an immediate-release
dosage form. Modified-release solid oral dosage forms include both
delayed- and extended-release drugproducts.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Modifying factor:
A factor determined by professional judgment
of a toxicologist and applied to bioassay data to relate that data
safely to humans.
Q3C Impurities: Residual
Solvents
- Neurotoxicity:
The ability of a substance to cause adverse effects on the nervous system.
Q3C Impurities: Residual
Solvents
- New drug product:
A pharmaceutical product type, e.g., tablet, capsule, solution, cream, etc., that has not
previously been registered in a region or Member State, and that
contains a drug ingredient generally, but not
necessarily, in association with excipients.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- New Drug Substance:
The designated therapeutic moiety that
has not been previously registered in a region or member state (also
referred to as a new molecular entity or new chemical entity). It can be
a complex, simple ester, or salt of a previously approved substance.
Q3B(R2) Impurities in New
Drugs
- New Drug Substance:
The designated therapeutic moiety that has
not been previously registered in a region or member state (also
referred to as a new molecular entity or new chemical entity). It can be
a complex, simple ester, or salt of a previously approved drug
substance.
Q3A Impurities in New Drug
Substances
- New drug substance:
The designated therapeutic moiety that has
not previously been registered in a region or Member State (also
referred to as a new molecular entity or new chemical entity). It may be
a complex, simple ester, or salt of a previously approved drug
substance.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- New molecular entity:
An active pharmaceutical substance not
previously contained in any drug product registered with the national or
regional authority concerned. A new salt, ester, or noncovalent bond
derivative of an approved drug substance is considered a new molecular
entity for the purpose of stability testing under this guidance.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- NOEL:
Abbreviation for no-observed-effect level.
Q3C Impurities: Residual
Solvents
- No-observed-effect level:
The highest dose of substance at which
there are no biologically significant increases in frequency or severity
of any effects in the exposed humans or animals.
Q3C Impurities: Residual
Solvents
- PDE:
Abbreviation for permitted daily exposure.
Q3C Impurities: Residual
Solvents
- Permitted daily exposure:
The maximum acceptable intake per day
of residual solvent in pharmaceutical products.
Q3C Impurities: Residual
Solvents
- Pilot scale batch:
A batch of a drug substance or drug product
manufactured by a procedure fully representative of and simulating that
to be applied to a full production scale batch. For solid oral dosage
forms, a pilot scale is generally, at a minimum, one-tenth that of a
full production scale or 100,000 tablets or capsules, whichever is
larger.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Polymorphic Forms:
Different crystalline forms of the same drug
substance. These can include solvation or hydration products (also known
as pseudo-polymorphs) and amorphous forms.
Q3A Impurities in New Drug
Substances
- Polymorphism:
The occurrence of different crystalline forms of
the same drug substance. This may include solvation or
hydration products (also known as pseudopolymorphs) and amorphous forms.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Potential Impurity:
An impurity that theoretically can arise
during manufacture or storage. It may or may not actually appear in the
new drug substance.
Q3A Impurities in New Drug
Substances
- Primary batch:
A batch of a drug substance or drug product used
in a formal stability study, from which stability data are submitted in
a registration application for the purpose of establishing a retest
period or shelf life, respectively. A primary batch of a drug substance
should be at least a pilot scale batch. For a drug product, two of the
three batches should be at least pilot scale batch, and the third batch
can be smaller if it is representative with regard to the critical
manufacturing steps. However, a primary batch may be a production batch.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Process Analytical Technology (PAT):
A system for designing, analyzing, and controlling manufacturing through timely
measurements (i.e., during processing) of critical quality and
performance attributes of raw and in-process materials and processes
with the goal of ensuring final product quality.
Q8 Pharmaceutical Development
- Process Robustness:
Ability of a process to tolerate
variability of materials and changes of the process and equipment
without negative impact on quality.
Q8 Pharmaceutical Development
- Product lifecycle:
All phases in the life of the product
from the initial development through marketing until the products
discontinuation.
Q9 Quality Risk Management
- Production batch:
A batch of a drug substance or drug product
manufactured at production scale by using production equipment in a
production facility as specified in the application.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Qualification Threshold:
A limit above (>) which a
degradation product should be qualified.
Q3B(R2) Impurities in New
Drugs
- Qualification Threshold:
A limit above (>) which an impurity should be qualified.
Q3A Impurities in New Drug
Substances
- Qualification:
The process of acquiring and evaluating data
that establishes the biological safety of an individual degradation
product or a given degradation profile at the levels specified.
Q3B(R2) Impurities in New
Drugs
- Qualification:
The process of acquiring and evaluating data that
establishes the biological safety of an individual impurity or a given
impurity profile at the level(s) specified.
Q3A Impurities in New Drug
Substances
- Quality Attribute:
A molecular or product characteristic
that is selected for its ability to help indicate the quality of the
product. Collectively, the quality attributes define identity, purity,
potency, and stability of the product, and safety with respect to
adventitious agents. Specifications measure a selected subset of the
quality attributes.
Q5E Comparability of
Biotechnological/Biological Products Subject to Changes in Their
Manufacturing Process
- Quality risk management:
A systematic process for the
assessment, control, communication, and review of risks to the quality
of the drug product across the product lifecycle.
Q9 Quality Risk Management
- Quality system:
The sum of all aspects of a system that
implements quality policy and ensures that quality objectives are met.
Q9 Quality Risk Management
- Quality:
The degree to which a set of inherent properties
of a product, system, or process fulfills requirements (see ICH Q6A
definition specifically for quality of drug substance and drug
products).
Q9 Quality Risk Management
- Quality:
The suitability of either a drug substance or drug
product for its intended use. This term includes such attributes as the
identity, strength, and purity (from ICH Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances ).
Q8 Pharmaceutical Development
- Quality:
The suitability of either a drug
substance or drug product for its intended use. This
term includes such attributes as the identity, strength, and purity.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Racemate:
A composite (solid, liquid, gaseous, or in solution)
of equimolar quantities of two enantiomeric species. It is devoid of
optical activity.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Rapidly dissolving products:
An immediate release solid oral
drug product is considered rapidly dissolving when not
less than 80 percent of the label amount of the drug
substance dissolves within 15 minutes in each of the following media:
(1) pH 1.2, (2) pH 4.0, and (3) pH 6.8.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Reagent:
A substance other than a starting material,
intermediate, or solvent that is used in the manufacture of a new drug
substance.
Q3A Impurities in New Drug
Substances
- Reagent:
A substance, other than a starting material or solvent,
that is used in the manufacture of a new drug
substance.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Reporting Threshold:
A limit above (>) which a degradation
product should be reported.
Q3B(R2) Impurities in New
Drugs
- Reporting Threshold:
A limit above (>) which an impurity should
be reported. Reporting threshold is the same as reporting level in Q2B.
Q3A Impurities in New Drug
Substances
- Requirements:
The explicit or implicit needs or
expectations of the patients or their surrogates (e.g., health care
professionals, regulators, and legislators). In this document,
requirements refers not only to statutory, legislative, or regulatory
requirements, but also to such needs and expectations.
Q9 Quality Risk Management
- Retest date:
The date after which samples of the drug substance
should be examined to ensure that the material is still in compliance
with the specification and thus suitable for use in the manufacture of a
given drug product.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Retest period:
The period of time during which the drug
substance is expected to remain within its specification and, therefore,
can be used in the manufacture of a given drug product, provided that
the drug substance has been stored under the defined conditions. After
this period, a batch of drug substance destined for use in the
manufacture of a drug product should be retested for compliance with the
specification and then used immediately. A batch of drug substance can
be retested multiple times and a different portion of the batch used
after each retest, as long as it continues to comply with the
specification. For most biotechnological/biological substances known to
be labile, it is more appropriate to establish a shelf life than a
retest period. The same may be true for certain antibiotics.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Reversible toxicity:
The occurrence of harmful effects that are
caused by a substance and which disappear after exposure to the
substance ends.
Q3C Impurities: Residual
Solvents
- Risk acceptance:
The decision to accept risk (ISO Guide
73).
Q9 Quality Risk Management
- Risk analysis:
The estimation of the risk associated with
the identified hazards.
Q9 Quality Risk Management
- Risk assessment:
A systematic process of organizing
information to support a risk decision to be made within a risk
management process. It consists of the identification of hazards and the
analysis and evaluation of risks associated with exposure to those
hazards.
Q9 Quality Risk Management
- Risk communication:
The sharing of information about risk
and risk management between the decision maker and other stakeholders.
Q9 Quality Risk Management
- Risk control:
Actions implementing risk management
decisions (ISO Guide 73).
Q9 Quality Risk Management
- Risk evaluation:
The comparison of the estimated risk to
given risk criteria using a quantitative or qualitative scale to
determine the significance of the risk.
Q9 Quality Risk Management
- Risk identification:
The systematic use of information to
identify potential sources of harm (hazards) referring to the risk
question or problem description.
Q9 Quality Risk Management
- Risk management:
The systematic application of quality
management policies, procedures, and practices to the tasks of
assessing, controlling, communicating, and reviewing risk.
Q9 Quality Risk Management
- Risk reduction:
Actions taken to lessen the probability of
occurrence of harm and the severity of that harm.
Q9 Quality Risk Management
- Risk review:
Review or monitoring of output/results of the
risk management process considering (if appropriate) new knowledge and
experience about the risk.
Q9 Quality Risk Management
- Risk:
The combination of the probability of occurrence of
harm and the severity of that harm (ISO/IEC Guide 51).
Q9 Quality Risk Management
- Semipermeable containers:
Containers that allow the passage of
solvent, usually water, while preventing solute loss. The mechanism for
solvent transport occurs by absorption into one container surface,
diffusion through the bulk of the container material, and desorption
from the other surface. Transport is driven by a partial pressure
gradient. Examples of semipermeable containers include plastic bags and
semirigid, low-density polyethylene (LDPE) pouches for large volume
parenterals (LVPs), and LDPE ampoules, bottles, and vials.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Severity:
A measure of the possible consequences of a
hazard.
Q9 Quality Risk Management
- Shelf life (also referred to as expiration dating period):The
time period during which a drug product is expected to remain within the
approved shelf life specification, provided that it is stored under the
conditions defined on the container label.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Solvent:
An inorganic or an organic liquid used as a vehicle for
the preparation of solutions or suspensions in the synthesis of a new
drug substance.
Q3A Impurities in New Drug
Substances
- Solvent:
An inorganic or an organic liquid used as a vehicle for
the preparation of solutions or suspensions in the synthesis of a new
drug substance or the manufacture of a new drug
product.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Specific test:
A test that is considered to be applicable to
particular new drug substances or particular new
drug products, depending on their specific properties
and/or intended use.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Specification, Release:
The combination of physical, chemical,
biological, and microbiological tests and acceptance criteria that
determine the suitability of a drug product at the time of its release.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Specification, Shelf life:
The combination of physical,
chemical, biological, and microbiological tests and acceptance criteria
that determine the suitability of a drug substance throughout its retest
period, or that a drug product should meet throughout its shelf life.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Specification:
A list of tests, references to analytical
procedures, and appropriate acceptance criteria that are numerical
limits, ranges, or other criteria for the tests described. It
establishes the set of criteria to which a drug
substance or drug product should conform to be
considered acceptable for its intended use. "Conformance to
specifications" means that the drug substance and/or
drug product, when tested according to the listed
analytical procedures, will meet the listed acceptance criteria.
Specifications are critical quality standards that are proposed and
justified by the manufacturer and approved by regulatory authorities as
conditions of approval.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Specification:See ICH Q6A and Q6B.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Specified Degradation Product:
A degradation product that
is individually listed and limited with a specific acceptance criterion
in the new drug product specification. A specified degradation product
can be either identified or unidentified.
Q3B(R2) Impurities in New
Drugs
- Specified impurity:
An identified or unidentified impurity that
is selected for inclusion in the new drug substance or
new drug product specification and is individually
listed and limited to ensure the quality of the new drug
substance or new drug product.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Specified Impurity:
An impurity that is individually listed and
limited with a specific acceptance criterion in the new drug substance
specification. A specified impurity can be either identified or
unidentified.
Q3A Impurities in New Drug
Substances
- Stakeholder:
Any individual, group, or organization that
can affect, be affected by, or perceive itself to be affected by a risk.
Decision makers might also be stakeholders. For the purposes of this
guidance, the primary stakeholders are the patient, healthcare
professional, regulatory authority, and industry.
Q9 Quality Risk Management
- Starting Material:
A material used in the synthesis of a new
drug substance that is incorporated as an element into the structure of
an intermediate and/or of the new drug substance. Starting materials are
normally commercially available and of defined chemical and physical
properties and structure.
Q3A Impurities in New Drug
Substances
- Storage condition tolerances:
The acceptable variations in
temperature and relative humidity of storage facilities for formal
stability studies. The equipment should be capable of controlling the
storage condition within the ranges defined in this guidance. The actual
temperature and humidity (when controlled) should be monitored during
stability storage. Short-term spikes due to opening of doors of the
storage facility are accepted as unavoidable. The effect of excursions
due to equipment failure should be addressed and reported if judged to
affect stability results. Excursions that exceed the defined tolerances
for more than 24 hours should be described in the study report and their
effect assessed.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Stress testing (drug product):
Studies undertaken to assess the
effect of severe conditions on the drug product. Such studies include
photostability testing (see ICH Q1B) and specific testing of certain
products (e.g., metered dose inhalers, creams, emulsions, refrigerated
aqueous liquid products).
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Stress testing (drug substance):
Studies undertaken to elucidate
the intrinsic stability of the drug substance. Such testing is part of
the development strategy and is normally carried out under more severe
conditions than those used for accelerated testing.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Strongly suspected human carcinogen:
A substance for which there
is no epidemiological evidence of carcinogenesis but there are positive
genotoxicity data and clear evidence of carcinogenesis in rodents.
Q3C Impurities: Residual
Solvents
- Supporting data:
Data, other than those from formal stability
studies, that support the analytical procedures, the proposed retest
period or shelf life, and the label storage statements. Such data
include (1) stability data on early synthetic route batches of drug
substance, small-scale batches of materials, investigational
formulations not proposed for marketing, related formulations, and
product presented in containers and closures other than those proposed
for marketing; (2) information regarding test results on containers; and
(3) other scientific rationales.
Q1A(R2) Stability Testing of
New Drug Substances and Products
- Teratogenicity:
The occurrence of structural malformations in a
developing fetus when a substance is administered during pregnancy.
Q3C Impurities: Residual
Solvents
- Trend:
A statistical term referring to the direction or
rate of change of a variable(s).
Q9 Quality Risk Management
- Unidentified Degradation Product:
A degradation product for
which a structural characterization has not been achieved and that is
defined solely by qualitative analytical properties (e.g.,
chromatographic retention time).
Q3B(R2) Impurities in New
Drugs
- Unidentified Impurity:
An impurity for which a structural
characterization has not been achieved and that is defined solely by
qualitative analytical properties (e.g., chromatographic retention
time).
Q3A Impurities in New Drug
Substances
- Unidentified impurity:
An impurity that is defined solely by
qualitative analytical properties (e.g., chromatographic retention
time).
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Universal test:
A test that is considered potentially applicable
to all new drug substances, or all new drug
products; e.g., appearance, identification, assay, and impurity tests.
Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances
- Unspecified Impurity:
An impurity that is limited by a general
acceptance criterion, but not individually listed with its own specific
acceptance criterion, in the new drug substance specification.
Q3A Impurities in New Drug Substances
©
Keith M. Bower. All rights reserved.