3-A Sanitary Standards and Accepted Practices
Criteria for cleanability of dairy processing equipment. They have been adopted by many other liquid processing industries outside of dairy. They are written as a co-operative effort between users, equipment manufacturers, sanitarians and regulatory agencies. The “3 Associations” are the International Association of Milk, Food and Environmental Sanitarians; the U.S. Public Health Service; and the Dairy Industry Committee.
Activated Carbon Bed (AC)
A filtration method for the pre-treatment of water to remove residual chlorine and organic material. Water is passed through a deep bed of granular activated carbon (GAC) at low flow rate (see GAC).
A negatively charged ion.
A treatment process for steel for the purpose of reducing hardness, improving machinability, facilitating cold working, or producing a desired mechanical, physical, or other property.
A localized surface area that is out of specifications to the surrounding area, and is classified as abnormal.
A discontinuity consisting of any localized remelted metal, heat-affected metal, or change in the surface profile of any part of a weld or bas metal resulting from an arc.
Free of pathogenic (causing or capable of causing disease) microorganisms.
Operating in a manner that prevents contamination of the process.
American Society of Mechanical Engineers (ASME)
Creates consensus standards for Mechanical Engineering.
(Pronounced O-JAY). A process for analyzing the composition of metal as a function of surface depth. The surface composition is determined as successive layers are removed by vaporizing the metal with an electron beam. Used to determine the level of chromium-oxide on the surface of austenitic stainless steel.
A piece of equipment used for steam sterilizing components “out of place”. In other words, parts must be placed into the autoclave for sterilization. “Autoclaving” can also refer to the process of using an autoclave. NOTE: a component designed for SIP cannot necessarily be autoclaved!
A weld made by fusion of the base material without the addition of filler (see gas tungsten arc welding).
A layer of trace organic material that can adhere to the interior wall of process line components.
Therapeutic or diagnostic products generated and purified from natural sources.
Ethical pharmaceutical drugs derived through bioprocessing.
The creation of a product utilizing a living organism.
Equipment, systems, or facilities used in the creation of products utilizing living organisms.
Bio Processing Equipment (BPE)
ee of ASME, it creates engineering standards the design, specification, manufacture, and documentation for equipment used for BioPharma processes.
A discontinuity in the face of a fitting.
Excessive melt-through or a hole through the root bead.
Excess material protruding from the edge resulting from cutting
A joint between two members lying approximately in the same plane.
A condition of liquid flow where, after vaporization of the liquid, the subsequent collapse of vapor bubbles can produce surface damage.
Documented testimony by qualified authorities that a system qualification, calibration, validation, or revalidation has been performed appropriately and that the results are acceptable.
Colony Forming Unit (CFU)
A measure of bacterial contamination. Samples are incubated in a growth media (see PCA) and the resulting colonies are counted, each colony is assumed to have been derived from one bacterium.
Comite Europeen de Normalisation (CEN Committee for European Standardization)
Comprised of the 13 national standards organizations in Europe, Creates standards that reflect the best practices in each industry. Used to aid in the application of the directives of the European Commission.
Measurement of a substances ability to conduct an electric current. Measured in µ- mhos/cm, or µ-siemens/cm. Used as a measurement for the purity of water.
Current Good Manufacturing Practices (cGMP)
Written and enforced by the FDA. Consists of some specific, but mostly “umbrella” regulations covering personnel, records, and equipment, leaving much to the interpretation of the Inspector and court system. CGMPs are evolutionary, reflecting the least common denominator of practices in the industry at present (hence the term “current”).
The purification of substances based on the chemical, physical, and biological properties of the molecules involved.
Free of dirt, residues, detergents, or any contaminants that may affect or adulterate the product or process.
Clean in Place (CIP)
The process of cleaning process line components without disassembly.
Steam free from boiler additives that may be purified, filtered, or separated. Usually used for incidental heating in pharmaceutical applications.
The appearance of a milky white hue across some portion of a surface resulting from the electropolish process.
Porosity that occurs in clumps or clusters.
Commission of European Communities (EEE/EC)
Legislative and enforcement body of the European Union. Uses CEN standards to assist in the application of its directives.
A condition in which the surface of a welded joint is depressed relative to the surface of the tube or pipe. Concavity is measured as a maximum distance from the outside or inside diameter surface of a welded joint along a line perpendicular to a line joining the weld toes.
A ring of metal placed between the two elements to be welded that provide filler for the weld, when performed with fusion welding equipment. A consumable insert can also be used for the root pass in a multiple pas weld with the addition of filler wire (also called insert ring).
A Condition in which the surface of a welded joint is extended relative to the surface of the tube or pipe. Convexity is measured as a maximum distance from the outside or inside diameter surface of a welded joint along a line perpendicular to a line joining the weld toes.
Fracture-type discontinuities characterized by a sharp tip and high ratio of length and width to opening displacement. A crack may not be detected with a stylus. A linear crack will produce a liquid penetrant indication during liquid penetration inspection, x-ray, or ultrasound.
A depression at the termination of a weld bead.
Cracks that form in the crater, or end, of the weld bead.
A section of pipe in a closed recirculation loop that does not have a continuous flow through it.
Discontinuities that by nature or accumulated effect (for example, total crack length) render a part, standards, or specifications. This term designates rejectability. See also discontinuity.
Separation into constituent layers.
A localized area that is dissimilar to the surrounding areas with a defined boundary after electropolishing.
A large, smooth-bottomed depression whose diameter or width is greater than its depth and which will not produce an indication.
Deionized or Deionization (DI)
The process of removing ionized salts from water by passing it through ion exchange resins (see IX and Resin).
Deionized Water (DIW)
Water that has been deionized (see DI).
Deutsches Institut für Normung (DIN, German Institute for Standardization)
Creates engineering standards for Germany. Contributing body to CEN and ISO. Other countries and companies have adopted DIN standards.
A relative term indicating the condition of being contaminated.
Any change in surface color from that of the base metal. Usually associated with oxidation occurring on the weld and heat-affected zone on the outside diameter and inside diameter of the weld joi
nt as a result of heating the metal during welding. Colores may range from pale bluish-gray to deep blue, and from pale straw color to a black crusty coating.
Interruption of the typical structure of a weldment, such as a lack of homogeneity in the mechanical, metallurgical, or physical characteristics of the material or weldment. A discontinuity is not necessarily a defect.
The process of purifying water (or other liquid) by boiling the liquid and condensing the vapor. Most contaminants do not vaporize at the same temperature, as the water therefore does not carry over to the distillate.
Distilled Water (DW)
Water that has been distilled (see distillation).
That part of an automatic orbital weld sequence during which the welding current is gradually reduced prior to extinguishing of the welding arc. The downslope portion of a welded joint is seen as a tapering of the end of the weld bead with a reduction of penetration from the beginning to the end of the downslope so that the final weld bead is small with minimal penetration.
A concentration of impurity formed in the weld puddle. It floats to the surface when the metal solidifies (also called slag).
A material that can be stretched or compressed repeatedly and, upon immediate release of stress, will return to its approximate original size.
A component of the Gram-negative organism’s wall. A pyrogen of specific concern in injectable solutions (see Gram-negative and Pyrogen). Temperatures that kill the bacteria themselves do not destroy endotoxins. Measured by LAL. Endotoxins levels are specified for WFI (see WFI and LAAL).
Environmental Protection Agency (EPA, USA)
Agency that sets the standards for potable water.
Equipment Operating Procedure (EOP)
European Hygienic Equipment Design Group (EHEDG)
Comprised of representatives from research institutes, equipment manufacturers, the food and bio-Pharma industry and legislative bodies. The objective of the group is to provide standardization organizations (CEN and ISO) with specialist views on hygienic and aseptic design by publishing requirements and test methods.
European Pharmacopoeia (EP)
European counterpart to USP (see USP)
A controlled substance for the diagnosis or treatment of disease.
Weld penetration that exceeds the acceptance limit for inside diameter convexity (see convexity).
Food and Drug Administration (FDA, USA)
Enforcement agency of the U.S. Government for food, drug and cosmetics manufacturing. Author of the U.S. cGMPs. Responsible for new product approvals, plant inspections and product recalls.
The biochemical synthesis of organic compounds by microorganisms or cultivated cells.
A vessel for carrying out fermentation
A weld joint is said to be fully penetrated when the depth of the weld extends from its face into the weld joint so that the joint is fully fused. For a tube-to-tube weld, no unfused portions of the weld joint shall be visible on the inside diameter of a fully penetrated weld.
The melting together of filler metal and base metal, or of base metal only, that results in coalescence.
Fusion welding Welding in which the base material is fused together without the addition of filler material to the weld (see gas tungsten-arc welding).
Gas tungsten Arc welding(GTAW)(a.k.a. TIG)
A welding process where the welding arc is maintained between non- consumable tungsten electrode and the base metal to be welded. The arc is shielded with an inert gas, typically argon.
Good Manufacturing Practices (GMP)
Refers specifically to FDA cGMPs (see cGMP) or to the standards for manufacturing in a particular country and industry (e.g. EU GMP). Generally refers to standards that are written and enforceable.
One of two groups of microorganisms, as determined by their ability to retain a dye after staining and rinsing. Those retaining the dye are Gram-positive, those that do not retain the dye are Gram-negative. The differences are in the cell-wall structure. The majority of water- borne bacteria are Gram-negative.
Granular Activated Carbon (GAC)
Most common type of activated carbon bed filtration media (see AC).
The separation of cells from growth media. This can be accomplished by filtration, precipitation, or centrifugation.
An alphanumeric identification of a stated tonnage of metal obtained from a continuos melting in a furnace.
That portion of the base metal that has not been melted, but whose microstructure or mechanical properties have been altered by the heat of welding or cutting.
Permanent identification used to trace a part back to the mill heat (batch) from which the part was manufactured, each heat number traces back to an MTR (see MTR).
The volume of liquid remaining in a vessel or piping system after it has been allowed to drain.
A pressure test
of piping, pressure vessels, or pressure-containing parts, usually performed by pressurizing the internal volume with water at a pressure determined by the applicable code.
Of or pertaining to equipment and piping systems that by design, materials of construction, and operation provide for the maintenance of cleanliness so that products produced by these systems will not adversely affect human or animal health.
Hygienic clamp joint
A tube outside diameter union consisting of two neutered ferrules having flat faces with a concentric groove and mating gasket that is secured with a clamp. Providing a nonprotruding, recessless product contact surface.
A tube outside diameter union providing a nonprotruding, recessless product contact surface. Icicles Localized regions of excessive penetration, which usually appear as long, narrow portions of weld metal on the weld underbead (see convexity and excessive penetration).
Particles of foreign material in a metallic matrix. The particles are usually compounds such as oxides, sulfides, or silicates, but may be any substances foreign to and essentially insoluble in the matrix.
Incomplete fusion (or lack of fusion)
A weld discontinuity in which fusion did not occur between weld metal and faces or between adjoining weld beads. Also, in welding of tubing, when the weld fully penetrates the wall thickness but misses the joint, leaving some portion of the inner (inside diameter) weld joint with unfused edges.
Incomplete penetration (or lack of penetration)
A groove weld in which the weld metal does not extend completely through the joint thickness.
A condition or an anomaly of a localized area that has not been classified as being accepted or rejected.
In place. In other words, without disassembly (see CIP and SIP).
Outside of the body.
Inside of the body.
Documentation that an equipment/system has been installed properly according to pre- determined codes and standards. This could include preventive maintenance procedures, spare parts lists. SOPs, part numbers, model numbers. Serial numbers, capacities, performance data, material specifications, etc. International Standards Organization (ISO) Creates consensus standards for engineering and quality systems.
A process in which specific ions are removed from a solution in exchange for equivalently changed ions. The exchange process takes place on the surface of small particles called resin (see Resin).
Japanese counterpart of USP (see USP).
The depth that a weld extend from its face into a joint, exclusive of reinforcement.
Lack of fusion after reflow
A discontinuity in welding of tubing where, after a reflow or second weld pass has been made, the original joint has still not been consumed, leaving the weld joint with unfused edges on the inner surface.
Terrace-like fractures in the base metal with a basic orientation parallel to the wrought surface: caused by the high stress in the thickness direction that results from welding.
Clongated defects in a finished metal product, resulting from the rolling of a welded or other part containing a blowhole. Actually, the blowhole is stretched out in the direction of rolling.
Porosity that occurs in a linear pattern. Linear porosity generally occurs in the root pass from inadequate joint penetration.
Liquid penetrant indication
Refer to ASME BPVC, Section V, Article 6, para. T-600, for testing an anomaly or an indication.
Large Volume Parenteral (LVP)
Injectable solutions for humans greater than 100ml for a single dose.
Limulus Amebocyte Lysate(LAL)
A reagent used for the detection of endotoxins. LAL is made from the blood of the horseshoe crab.
Welding with equipment that performs the welding operation under the constant observation and control of a welding operator. The equipment may or may not perform the loading and unloading of the works (see automatic welding).
Welding in which the entire welding operation is performed and controlled by hand.
A commercial designation for a given chemistry range.
Maximum working pressure
The pressure at which the system is capable of operating for a sustained period of time.
Maximum working temperature
The temperature at which the system must operate for a sustained period of time. The maximum working temperature should relate to the maximum working pressure and the fluids involved.
Multiple Effect (Distillation)
An energy economizing distillation process (see Distillation) where the steam generated in one stage is used to heat the liquid in the next stage, up to 10 or more stages or “effects”.
Of or pertaining to a weld bead that deviates from side to side across the weld joint rather than tracking the joint precisely.
Micron or micrometer (µm)
One-millionth of a meter.
Axial offset of the joint
Two or more straight sections of tube matched and joined in a plane biseeting the angle of junction so as to produce a change of direction.
A surface void anomaly caused by material removal or compression from the surface, whose bottom surface is usually irregular.
Nominal outside diameter
A numerical identification of outside diameter to which tolerances apply.
Nominal wall thickness
A numerical identification of wall thickness to which tolerances apply.
Nonuniform mechanical polishing marks
A localized surface polishing pattern that is dissimilar to the surrounding area.
A measurement of face-to-face squareness.
A measurement of the offset between port centerlines or two planes.
Operating Procedure (OP)
Operational Qualification (OQ)
Demonstration and documentation of the equipment/system’s functionality. Used to prove the operational limits of the equipment/system, often run on a product substitute to prove functionality prior to running on product-for-sale. Other items tested could include failure mode, alarm features and cleanability. Typically executed by the commissioning team.
An appearance of a pebbly surface.
An automated TIG (see TIG or GTAW) welding process that is designed to produce repeatable fusion welds for tubular components. A system consists of a programmable power supply and weld head. The power supply controls the weld parameters of current and electrode speed. The weld head holds the two parts, gas-purges the weld, and moves the electrode using an electrode motor.
The protrusion of weld metal beyond the weld toes or weld root. Also, in an orbital weld, that amount by which the end of the weld bead overlaps the beginning of the weld bead (not including the downslope) on a single-pass weld.
The body upon which final possession or use rests.
The formation of an oxide layer on a metal surface. When oxidation occurs as a result of welding, it is visible as discoloration. The discoloration or heat tint produced by oxidation has been associated with the onset of corrosion in stainless steel piping systems.
An area usually located in the heat-affected zone of the weldment where an oxidation reaction has taken place.
Ozonation or Ozonated Water
The use of ozone (O3) to disinfect water. Ozone is added to water and then neutralized using ultra-violet (UV) light (see UV).
The process of rinsing stainless steel with acid (typically nitric) to form a corrosion resistant chromium-oxide layer on the surface.
A passive oxidized film that form naturally on the stainless steel surface when exposed to air or similar oxidizing environment protecting the underlying base metal from corrosion.
Plate Count Agar (PCA)
The most common growth media for measuring bacteria levels (see CFU).
Parenteral Drug Association (PDA)
Association for manufacturers of injectable drug products. Publishes technical reports and other publications of interest to the industry.
Pipe size is determined by diameter and schedule. For bioprocessing equipment, pipe does not include tube.
A small surface void resulting from a localized loss of base metal by corrosion or etching, or by the removal of surface inclusions during electropolishing or passivation. A pit may or may not produce an indication during liquid penetrant inspection.
To cause to be set at a particular angle or slope. Degree of slope or elevation.
Cavity-type discontinuities formed by gas entrapment during solidification.
Point of Use (POU)
A valved branch in a recirculating utility system (typically a water system).
Process Qualification/Process Validation (PQ/PV)
The demonstration and documentation that the various units and procedures of a process operate as they should. This logically establishes that the product is of the quality the system has purported to yield. Performed after the IQ/OQ has been executed and approved. Typically the acceptance criteria are the same, as the product run is considered product-for- sale. Executed by the manufacturing personnel of the operating company according to the SOP.
Pressure at which a system is designed to operate, allowing for applicable safety factors.
Product contact surface
A surface that contacts raw materials, process materials, and/or product.
A mechanical grinding procedure where a coarse grit material is used first and the successive operations use finer and finer grit until the desired surface roughness is achieved.
Gram-negative bacteria of particular concern in water systems. Pseudomonads Diminuta is used to challenge the efficacy of filtration systems.
Steam that is produced by a steam generator which, when condensed, meets requirements for Water-for-injection (WFI).
Any substance capable of producing a fever in humans. Most commonly organic substances shed by bacteria. Pyrogens are not necessarily destroyed by conditions that kill bacteria (see Endotoxin).
Purified Water (PW)
Ingredient water (not for injection) or rinse water for pharmaceutical products conforming to USPXXIII (EP and JP) guidelines. Obtained by distillation, reverse osmosis, ion exchange or any other suitable process (see USP, EP, JP, Distillation, RO and IX).
Roughness Average (Ra, Ra or RA)
A measure of surface roughness, specifically the average deviation from the mean. Units are length, either µm or µ-inch.
A second weld pass made to correct a lack of fusion or missed joint.
Specifically manufactured polymer beads used in ion exchange processes. Resins are ion specifics and are categorized as either Anion Resins or Cation Resins (see IX, Anion and Cation).
Reverse Osmosis (RO)
The separation of contaminants from water by flowing the feed water stream under pressure across a semi-permeable membrane.
An oxide film on the surface of stainless steel process line components, typically red or black in color. All current theories for the causes of rouging are still Inconclusive.
A weld used to obtain fluid tightness as opposed to mechanical strength.
The elimination of all fluid from the system due to the force of gravity alone.
Semi-automatic arc welding
Arc welding with equipment that controls only the filler metal feed. The advance of the welding is manually controlled.
The life expectancy or number of cycles for which the unit will maintain its performance.
The size of surface deficits is classified in two groups: macro, referring to indications that can be seen in adequate lighting without magnification, and micro, referring to indications that can be seen only with the aid of magnification.
A concentration of nonmetallic impurities (often oxides or nitrides) that forms in the weld pool and solidifies on the underbead or weld top surface. Sometimes referred to as dross.
An incline or deviation from the horizontal. A tube or pipe installed in the horizontal plane is said to slope if one end is positioned higher than the other.
A device used to agitate, oxygenate, or aerate a liquid by means of compressed air or gas.
The metal particles expelled during welding that do not form part of a weld.
A tube end cut perpendicular to the tangent plane.
A type of indication created during the reaction of electrochemical etching process on the foreign or refractory material (dross) on the welds or base metal.
Steam in place (SIP)
The use of steam to sanitize or sterilize a piece of equipment without the use of an autoclave.
Free from living organisms.
The absence of all life forms.
Particles of foreign material in a metallic matrix. The particles are usually compounds such as oxides, sulfides, or silicates, but may be a substance foreign to and essentially insoluble in the matrix.
A foreign substance that adheres to a surface by chemical reaction adhesion, adsorption, or ionic bonding (for example, corrosion, rouging and staining).
Total volume of liquid in the system, including equipment, piping, valving and instrumentation.
Small Volume Parenteral (SVP)
Injectable solutions for humans less than 100ml for a single dose.
Standard Operating Procedure(SOP)
(a.k.a. EOP, OP) A controlled document that outlines the procedure for operating equipment/system. An operator’s adherence to a written SOP is an integral part of the validation process. It is the connecting link between the initial validation process and the daily manufacturing operation.
Steam In Place (SIP)
Sanitization of process line components by the use of steam without disassembly.
Total Dissolved Solids (TDS)
Total amount of material remaining in the water after filtering the suspended material and then evaporating the solution to a dry state (see TSS).
A panel to which process and/or utilities are piped that mechanically precludes erroncous cross connections.
Total Suspended Solids (TSS)
Total amount of solid particles in a solution that are held in suspension (non-dissolved).
Tube is sized by its nominal outside diameter. For bioprocessing equipment, tube does not include pipe.
Tungsten particles transferred into the weld deposit by occasional touching of the tungsten electrode used in the gas tungsten-arc process to the work or to the molten weld metal. These inclusions are often considered defects that must be removed and the weld repaired prior to final acceptance. Tungsten inclusions may be invisible to the unaided eye, but are readily identified in a radiograph.
Leakage level above w
hich the system performance is considered unacceptable by the system user and applicable regulating body.
A groove melted into the base metal adjacent to the weld toe or weld root and left unfilled by weld metal.
A depression on the weld face or root surface extending below the adjacent surface of the base metal (see concavity).
Ultra Filter or Ultra Filtration(UF)
Filters (typically hollow fiber) formed from polymer membranes. UFs have the ability to retain larger molecules while permitting the passage of smaller ones. Often used for the separation of proteins.
Ultraviolet Light or Ultraviolet Radiation (UV)
Radiation in the ultraviolet portion of the spectrum (200 to 400nm) is used to destroy microorganisms. Also used to neutralize ozone.
Uniformly scattered porosity
Porosity that is distributed in a weldment in a uniform pattern.
United States Pharmacopoeia or United States Pharmacopoeia Convention (USP or USPC)
A private, non-profit organization that sets standards for drugs, drug ingredients, medical devices and diagnostics. The Food, Drug and Cosmetics Act recognizes the USP and the National Formulary (both written by the USPC) and obligates the FDA to enforce its established standards. The USP contains the standards for WFI and Purified Water.
Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specification and quality attributes. i.e., does it do what it is supposed to do? And if so, how long will it do it?
Vapor compression (VC ,Distillation)
A method of distillation where the water vapor is compressed, thus raising its temperature, then used as the heating medium for the incoming liquid water. Used as a method for conserving energy.
Undulations or rippling of the surfaces.
Weld joint design
The shape, dimensions, and configuration of the weld joint.
One who operate machine or automatic welding equipment.
Water for Injection (WFI)
Water for use as a solvent for the preparation of parental products conforming to USPXXIII (EP and JP) guidelines. Obtained most commonly by distillation, although other processes are allowed depending on the particular pharmacopoeia (see USP, EP, JP and Distillation).