Copyright© 3-A Sanitary Standards, Inc.

, McLean, VA P3-A 001

General Glossary of Terminology Used In

Pharmaceutical 3-A® Standards
P3-A 001

Formulated by
3-A Sanitary Standards, Inc.
Pharmaceutical 3-A (P3-A) Steering Committee

It is the purpose of the Pharmaceutical 3-A (P3-A) Steering Committee in connection with the development of the
Pharmaceutical 3-A Sanitary/Hygienic Standards Program to allow and encourage full freedom for inventive genius or new
developments. This General Glossary of Terminology Used in Pharmaceutical Standards is developed and promulgated to
support and facilitate the use of other P3-A Standards. Additional or updated terminology may be submitted for the joint
consideration of the P3-A Steering Committee and 3-A Sanitary Standards, Inc. (3-A SSI) at any time. The Pharmaceutical
3-A (P3-A) Sanitary/Hygienic Standards and Pharmaceutical 3-A Accepted Practices provide sanitary/hygienic criteria
applicable to equipment and systems used to produce, process, and package active pharmaceutical ingredient(s). Standard
English is the official language of Pharmaceutical 3-A Sanitary/Hygienic Standards and Pharmaceutical 3-A Accepted
Practices.

A SCOPE NIST: National Institute of Standards and Technology

OOS: Out of Specification
A1 This standard shall provide users of OOT: Out of Tolerance; Out of Trend
Pharmaceutical 3-A (P3-A) Standards and PEEK: Poly Ether Ether Ketone
Accepted Practices with definitions of acronyms PET: Polyethylene Terephthalate
and terms widely used in these documents. PE: Polyethylene
PFA: Perfluoroalkoxy
B ACRONYMS AND DEFINITIONS PP: Polypropylene
B1 Acronyms PREN: Pitting Resistance Equivalency Number
PTFE: Polytetrafluoroethylene
ACI: Alloy Cast Institute PVC: Polyvinyl chloride
AISI: American Iron and Steel Institute PVDF: Polyvinylidene fluoride
ANSI: American National Standards Institute QA: Quality assurance
API: Active Pharmaceutical Ingredient QC: Quality control
ASME: American Society of Mechanical Engineers SAE: Society of Automotive Engineers
ASTM: American Society for Testing and Materials SIP: Steam in Place
AWS: American Welding Society SISPQ: Strength, Identity, Safety, Purity, and Quality
BCC: Body centered cubic SOP: Standard Operating Procedure
BPE Bioprocessing Equipment TPV: Third Party Verification
CFR: Code of Federal Regulations USP: United States Pharmacopoeia
CFU: Colony forming units UNS: Unified Numbering System
cGMP: Current Good Manufacturing Practices
CIP: Clean-In-Place B2 Definitions
COP: Clean out of place Acceptance Criteria: Numerical limits, ranges, or other
EPDM: Ethylene Propylene Diene Monomer suitable measures for acceptance of test results.
FCC: Face centered cubic
FDA: Food and Drug Administration Accessible: Shall mean a location that can be safely
GRAS: Generally Recognized As Safe reached by personnel, but not necessarily from a
HAZ: Heat affected zone permanent work area.
HDPE: High density polyethylene
ICH: International Conference on Harmonization Accessible, Easily or Readily: Shall mean a location
ISO: International Organization for Standardization which can be safely reached by an employee from the
NDA: New Drug Application floor, platform, or other permanent work area.

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Copyright© 3-A Sanitary Standards, Inc., McLean, VA
Active Pharmaceutical Ingredient (API or Drug
Substance): Shall mean any substance or mixture of
substances intended to be used in the manufacture of a
drug (medicinal) product and that, when used in the
production of a drug, becomes the active ingredient of the
drug product. Such substances are intended to furnish
pharmacological activity or other direct effect in the
diagnosis, cure, mitigation, treatment, or prevention of
disease or that affects the structure and function of the
body.
Anomaly (regarding plastics): A localized surface area that
is out of specification to the surrounding area, and is
classified as abnormal.
API Starting Material: A raw material, intermediate, or an
API that is used in the production of an API and that is
incorporated as a significant structural fragment into the
structure of the API. An API starting material can be an
article of commerce, a material purchased from one or
more suppliers under contract or commercial agreement, or
produced in-house. API starting materials are normally of
defined chemical properties and structure.
Batch: A specific quantity of material produced in a
process or series of processes so that it is expected to be
homogeneous within specified limits. In the case of
continuous production, a batch may correspond to a
defined fraction of the production. The batch size can be
defined either by a fixed quantity or by the amount
produced in a fixed time interval.
Batch Number: A unique combination of numbers, letters,
and/or symbols that identifies a batch (or lot) and from
which the production and distribution history can be
determined.
Bioburden: The level and type (e.g., objectionable or not)
of microorganisms that can be present in raw materials,
API starting materials, intermediates or APIs. Bioburden
should not be considered contamination unless the
specified levels have been exceeded or defined
objectionable organisms have been detected.
Bioprocessing: The creation of a product whose initial
source is a living organism, or the act of recovering and
purifying product from biologically derived material.
Bond: The adhesive or cohesive forces holding materials
together. This definition excludes press and shrink fits.
Borescope, Fiber-optic: A device for internal inspection
of difficult access locations such as equipment and pipes;
non-destructive inspection method by which a camera is
placed within a piece of equipment or the bore of a pipe.
Butt joint: A joint between two members aligned
approximately in the same plane and of the same
thickness, normally welded with a groove weld.
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P3-A 001
Calibration: The demonstration that a particular
instrument or device produces results within specified
limits by comparison with results produced by a reference
or traceable standard over an appropriate range of
measurements.
Carbon Steels: Iron-base alloys with three general
categories of carbon content; low, medium or high, with
various amounts of silicon, manganese, copper, sulfur and
phosphorus. Without protective coating carbon steel
readily oxidizes (rusts) in many environments.
Castings: A metal form at or near finished shape obtained
by solidification of a metal in a mold. Cast alloys
comparable to the AISI 300 Series of wrought alloys are
identified by Alloy Cast Institute designations.
CIP: Clean In Place/ Circulation Cleaning (aka
Mechanical Cleaning or Mechanically Cleaned): Soil
removal by impingement, circulation or flow of chemical
detergent or solvent solutions and rinses onto and over the
surfaces to be cleaned. Movement of these solutions is by
mechanical means using equipment or systems specifically
designed for this purpose.
CIP, Solvent: CIP cleaning that primarily utilizes solvent.
Cleanability: The suitability of the materials, design, and
fabrication techniques used so the equipment or system
can be freed of soil.
Coatings: Shall mean the results of a process where a
different material is deposited to create a new surface.
There is appreciable, typically more than 1 µm build-up of
new material. Coating processes include:
1. Chemical conversion
2. Electrodeposition1
3. Spraying (pneumatic, flame, plasma, arc spray)
4. Physical Vapor Deposition
5. Chemical Vapor Deposition
Compression Set: Permanent deformation of elastomers
subject to compression for a period of time, as quantified
by ASTM D-395.
Computer System: A group of hardware components and
associated software designed and assembled to perform a
specific function or group of functions.
1
Federal Specification #QQ-C-320B for Chromium Plating
(Electrodeposited), June 1954 with Amendment 4 on April 10, 1987.
Federal Specification #QQ-N-290A for Nickel Plating (Electrodeposited),
November 12, 1971. Available from the General Services
Administration, Federal Supply Services Bureau, Specification Section,
470 East L’Enfant Plaza, Suite 8100, Washington, DC 20407 (202) 755-
0325.
Copyright© 3-A Sanitary Standards, Inc., McLean, VA
Computerized System: A process or operation integrated
with a computer system.
Contamination: The undesired introduction of impurities
of a chemical or microbiological nature, or of foreign
matter, into or onto a raw material, excipient, intermediate,
or API during production, sampling, packaging, or
repackaging, storage or transport.
Corrosion Resistant Surface: The property of a surface to
retain sufficient suitable surface characteristic(s) for its
predicted service period when exposed to the conditions of
intended use, including expected contact with product,
cleaning, sanitizing, or sterilization compounds. Rate of
material removal or loss of surface material shall be
acceptable for the conditions of intended use.
Corrosion: The chemical or electrochemical reaction
between a material and its environment that produces a
deterioration of the material and its properties.
Cracks: Fracture-type discontinuities characterized by a
sharp tip and high ratio of length and depth to opening
displacement.
Creep: Time-dependent strain of a material subjected to
mechanical stress.
Critical: Describes a process step, process condition, test
requirement, or other relevant parameter or item that must
be controlled within predetermined criteria to ensure that
the API meets its specification.
Cross-Contamination: Contamination of a material or
product with another material or product.
Demarcation: The boundary separating dissimilar areas
revealed by electropolishing.
Deviation: Departure from an approved instruction or
established standard.
Drainable: Fluid can be removed by gravity except for
typical clingage.
Drug (Medicinal) Product: The dosage form in the final
immediate packaging intended for marketing (Reference
ICH Q1A).
Drug Substance: See Active Pharmaceutical Ingredient.
Ductile Cast Iron/ Ductile Iron: A cast iron that has been
treated while molten with an element such as magnesium
or cerium to induce the formation of free graphite as
nodules or spherulites. Ductile iron has mechanical
properties and corrosion resistance comparable to carbon
steel.
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P3-A 001
Durometer Hardness: Measurement of hardness of a
material specimen (typically rubber) as determined by the
resistance to penetration of an indenter in accordance with
ASTM D-2240.
Elastomer: Rubber or rubber like material that can be
stretched to at least two times its original length and after
release of stress will return to its approximate original
dimension and shape. Common characteristics include
elasticity, compressibility, flexibility, toughness, and
relative impermeability to many gases and liquids.
Electropolishing: The electrochemical process which the
article to be polished is treated anodically in a suitable acid
medium to remove material and produce an enhanced
surface finish.
Excipients: The non-active ingredients that are mixed with
pharmacologically active compounds to form medicines,
particularly tablets. Excipients include binders,
disintegrants, diluents, lubricants, glidants, colorings,
sweeteners, preservatives, suspending or dispersing agents,
film formers and coatings, flavorings, printing inks.
Fluoropolymer: Polymer material having a carbon chain
either partially or completely bonded to fluorine atoms.
Flush, Substantially: Mating surfaces or other juxtaposed
surfaces within 1/32 in. (0.794mm).
Galling: A condition whereby excessive friction between
high spots results in localized welding with subsequent
splitting and a further roughening of rubbing surfaces of
one or both of two mating parts.
Gasket: Deformable material sandwiched and compressed
between two mating surfaces for the purpose of creating a
static seal between the two mating surfaces.
Hand Tools: Shall mean implements normally used by
operating and cleaning personnel such as a screwdriver,
wrench or hammer.
Heat-affected Zone (HAZ): The portion of the base metal
whose mechanical properties or microstructure have been
altered by the heat of welding, brazing, soldering, or
thermal cutting.
Impurity Profile: A description of the identified and
unidentified impurities present in an API.
Impurity: Any component present in the intermediate or
API that is not the desired entity.
Inclusions (regarding metals): Particles of foreign material
in a metallic matrix. The particles are usually compounds
(such as oxides, sulfides or silicates), but may be of any
substance that is foreign to (and essentially insoluble in)
the matrix.
Copyright© 3-A Sanitary Standards, Inc., McLean, VA
Inclusions (regarding polymers): Particles of foreign
material in the polymer matrix. The particles are generally
overheated polymer but may be a foreign substance.
Intermediate: A material produced during steps of the
processing of an API that undergoes further molecular
change or purification before it becomes an API.
Intermediates may or may not be isolated. (Note: this
definition only addresses those intermediates produced
after the point that a company has defined as the point at
which the production of the API begins.)
Lot: An ingredient or volume product identified as
sourcing from a common supply source and/or batch
process and exhibiting ingredient or product characteristics
identified as acceptable within quality specifications.
Lot Number: A means of identifying ingredients or
product as having a common source, process conditions
and batch operation.
Manual Cleaned Out of Place (COP) Cleaning: The
manual cleaning of partially or wholly disassembled
equipment. Soil removal is effected with chemical
solutions and rinses with the assistance of one or a
combination of brushes, nonmetallic abrasive scouring
pads and scrapers, high or low pressure hoses and tanks(s)
which may be fitted with recirculation pump(s) and with
all cleaning aids manipulated by hand.
Manufacture: All operations of receipt of materials,
production, packaging, repackaging, labeling, relabeling,
quality control, release, storage, and distribution of APIs
and related controls.
Material: A general term used to denote materials of
construction.
Mechanical Cleaning or Mechanically Cleaned: See CIP
above. Shall mean soil removal by impingement,
circulation or flowing chemical detergent or solvent
solutions and rinses onto and over the surfaces to be
cleaned by mechanical means in equipment or systems
specifically designed for this purpose. This method is also
known as Cleaned In Place (CIP).
Mechanical Force Seal: The seal established between a
flexible rubber, rubber-like, or plastic material when
pressed into a special groove in a metal or glass
component using a combination of compression, pressure,
and the unique geometrical shapes of the joined materials
to create a tight seal at the interface of the materials joined
during conditions of intended use including processing,
cleaning, sanitizing, or sterilization. A mechanical force
seal is not intended for routine disassembly for cleaning.
Misalignment: Axial or angular offset of joint members.
Nickel-Chromium-Molybdenum Alloys (Ni-Cr-Mo): See
stainless steel and nickel alloys.
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P3-A 001
Nickel-copper Alloys: See stainless steel and nickel alloys.
Nonproduct Contact Surface: A surface other than a
product contact surface.
O-ring: Elastomeric ring seal of generally circular cross
section.
Packaging Material: Any material intended to protect an
intermediate or API during storage and transport.
Passivation: A process of chemical treatment of a
stainless steel or nickel alloy metal surface resulting in the
uniform formation of a passive layer. (For stainless steels
see ASTM A967 and ASTM A380.)
Pit: A small surface void.
Pitting Resistance Equivalency Number (PREN): Pitting
Resistance Equivalency Numbers are a theoretical way to
index the resistance of stainless steel metals to pitting and
crevice corrosion where a higher value PREN generally
indicates a higher resistance to corrosion. PREN is
calculated from the metal composition as:
PREN = %Cr + (3.3 X %Mo) + (16 X %N)
Plastic Additive, n: Any material that is added to a plastic
or polymer to enhance or modify the original physical
and/or chemical properties.
Plastic, adj.: The adjective “plastic” indicates that the
noun is made of, consists of or pertains to plastic.
Polymer: A molecule consisting of many smaller groups.
They can be synthesized either through chain reactions or
by templating. Some examples of polymers are plastics,
proteins, DNA and dendrimers.
Procedure: A documented description of the operations to
be performed, the precautions to be taken, and measures to
be applied directly or indirectly related to the manufacture
of an intermediate or API.
Process Aids: Materials, excluding solvents, used as an
aid in the manufacture of an intermediate or API that do
not themselves participate in a chemical or biological
reaction (e.g., filter aid, activated carbon).
Product Contact Surfaces: All surfaces that are exposed to
the product, and surfaces from which materials may drain,
drop, diffuse, or be drawn into the product or into the
container, and surfaces that touch product contact surfaces
of the container.
Direct Product Contact Surface: All surfaces that
touch the product.
Indirect Product Contact Surface: All surfaces that
touch a product contact surface without necessarily
Copyright© 3-A Sanitary Standards, Inc., McLean, VA
touching the product.
Incidental product contact surface: All surfaces of
materials (such as lubricant) with which there may
occasionally occur chance transfer of materials to a
product contact surface.
Product: Shall mean an active pharmaceutical ingredient,
an active pharmaceutical ingredient dissolved in a solvent,
or an intermediate for an active pharmaceutical ingredient
just prior to the final isolation or chemical transformation.
Profilometer: An instrument for the measurement of the
degree of surface roughness expressed in micrometers or
micro-inches. (See ASME B46.1)
Protocol: A written plan stating how a procedure is to be
executed.
Qualification: Action of demonstrating and documenting
that equipment or ancillary systems are properly installed,
work correctly, and actually lead to the expected results.
Qualification is part of validation, but the individual
qualification steps alone do not constitute process
validation.
Quality Assurance (QA): The sum total of the organized
arrangements made with the object of ensuring that all
APIs are of the quality required for their intended use and
that quality systems are maintained.
Quality Control (QC): Checking or testing that
specifications are met.
Quality Unit(s): An organizational unit independent of
production that fulfills both quality assurance and quality
control responsibilities. This can be in the form of separate
QA and QC units or a single individual or group,
depending upon the size and structure of the organization.
Quarantine: The status of materials that are isolated and
physically secured or by other effective means pending a
decision on their subsequent approval or rejection.
Ra: Log of the arithmetic mean from the centerline of the
surface profile. Usually expressed in µin. or µm as related
to roughness. (See ASME B46.1)
Raw Material: A general term used to denote starting
materials, reagents, and solvents intended for use in the
production of intermediates or APIs.
Removable: Shall mean able to be separated from the
equipment, but more than simple hand tools may be
required.
Removable, Readily or Easily: Shall mean quickly
separated from the equipment with the use of simple hand
tools if necessary.
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P3-A 001
Sanitizing or Sanitization: A process applied to a cleaned
surface which is capable of reducing the numbers of the
most resistant human pathogens as specified by Title 21
Code of Federal Regulations 178.1010.
SDR (Standard Dimension Ratio): The ratio of pipe OD to
wall thickness. Both ASTM and ISO utilize this ratio
when calculating their respective ASTM and ISO pressure
ratings.
Simple Hand Tools: Shall mean implements normally
used by operating and cleaning personnel such as a
screwdriver, wrench or hammer.
Small Molecule Drugs: Those drugs with active
ingredients comprised of molecules with molecular weight
of less than 500 Daltons.
Socket Joint/Weld: A joint between two piping or fitting
members where one component slips into a mating
component and then a final fillet weld is applied
externally. This type of weld results in an internal crevice
area in the joint.
Solution Contact Surfaces: Surfaces which are used
exclusively for supply and recirculation of cleaning and/or
sanitizing solutions, except those surfaces used to supply
concentrated cleaning and/or sanitizing materials to the
point of use.
Solvent: An inorganic or organic liquid used as a vehicle
for the preparation of solutions or suspensions in the
manufacture of an intermediate or API or for cleaning
purposes.
Soil: Any residue on a process equipment surface, which
is not intended to come into contact or be incorporated into
a raw material or product being produced, and therefore
must be removed from the surface before the equipment is
used.
Spalling: The cracking and breaking away of the surface
of a material.
Specification: The set of criteria to which a material or
piece of equipment should conform to be considered
acceptable for its intended use.
Stainless Steel and Nickel Alloys:
Austenitic Stainless Steels: A family of iron-base
alloys containing chromium and nickel and having an
austenitic (FCC) structure at room temperature.
Austenitic stainless steels are widely used in the
pharmaceutical industry for their excellent corrosion
resistance. The alloys are typically identified as
American Iron and Steel Institute (AISI) 300 Series
(e.g. 304L) and may contain additions of molybdenum
(e.g. 316L) and/or other elements.
Copyright© 3-A Sanitary Standards, Inc., McLean, VA P3-A 001

Duplex Stainless Steel: A family of stainless steel
alloys with a structure of approximately 50% austenite
and 50% ferrite. Duplex alloys typically have higher
mechanical strength and may have better corrosion
resistance than the 300 Series stainless steels in certain
environments.
Nickel-Chromium-Molybdenum Alloys (Ni-Cr-Mo): A
family of nickel alloys with superior pitting, crevice
and stress corrosion cracking resistance as well as
general corrosion resistance to stainless steels in low
pH, high chloride environments.
Nickel-copper Alloys: Alloys of approximately 2/3
nickel and 1/3 copper. These alloys have excellent
corrosion resistance to seawater and a range of
reducing and alkaline environments.
Thermoset: Long chain polymers that are usually
connected by crosslinks. Once formed, these materials
cannot be reshaped when heated.
Validation Protocol: A written plan stating how validation
will be conducted and defining acceptance criteria. For
example, the protocol for a manufacturing process
identifies processing equipment, critical process
parameters and/or operating ranges, product
characteristics, sampling, test data to be collected, number
of validation runs, and acceptable test results.
Validation: A documented program that provides a high
degree of assurance that a specific process, method, or
system will consistently produce a result meeting
predetermined acceptance criteria.

Superaustenitic Stainless Steel (6% Mo alloys): A

family of iron-base austenitic alloys normally
containing 6 to 7% molybdenum and higher nickel
than the regular 300 Series stainless steels. The
corrosion resistance of these alloys is generally
superior to the 300 Series, especially in environments
containing high amounts of chlorides where pitting,
crevice corrosion, and stress corrosion cracking may
occur.

Sterilization: The act or process, physical or chemical,

which destroys or eliminates all forms of life (e.g.
microorganisms).

Surface Treatments: Shall mean a process whereby

chemical compositions or mechanical properties of the
existing surfaces are altered. There is no appreciable,
typically less than 1 µm, build-up of new material or
removal of existing material. Surface treatments include:

1. Mechanical (shot peening 2 , glass beading,

polishing)
2. Thermal (surface hardening laser, electron beam)
3. Diffusion (carburizing, nitriding)
4. Chemical (etching, oxidation)
5. Ion Implantation
6. Electropolishing

Temperature of Exposure: Temperatures to which a

material is subjected under conditions of intended use.

Thermoplastic: Long chain polymers that are usually not

connected by crosslinks. Once formed, these materials can
be reshaped when heated.

2
MIL-S-13165C (1), November 1991, Military Specification:
Shot Peening of Metal Parts. Available from Standardization, Document
Order Desk (Department of Navy), 700 Robbins Avenue, Building 4,
Section D, Philadelphia, PA 19111-5094 (215) 697-2179.