gmp comparison

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PHARMACEUTICAL cGMP

(21 CFR Part 210 & 211)

Food cGMP (21 CFR Part 110) Advanced Notice of ProposedRulemaking (ANPR) (FR: 2-6-97)

Proposed cGMP for DietaryIngredients and Dietary

Supplements (FR: 3-13-03)

PART 111--CURRENT GOODMANUFACTURING PRACTICEIN MANUFACTURING,PACKING, OR HOLDINGDIETARY INGREDIENTS ANDDIETARY SUPPLEMENTS

Subpart A--General Provisions

111.1 Who is subject to theseregulations? You are subject tothe regulations in this part if youmanufacture, package, or hold adietary ingredient or dietarysupplement.

111.2 What are theseregulations intended toaccomplish? The regulations in this part establishthe minimum current goodmanufacturing practices that youmust use to the extent that youmanufacture, package, or hold adietary ingredient or dietarysupplement.

210.3 Definitions.

(a) The definitions and interpretationscontained in section 201 of the act shall beapplicable to such terms when used in thispart and in parts 211 through 226 of thischapter.

(b) The following definitions of terms applyto this part and to parts 211 through 226 ofthis chapter.

110.3 Definitions

The definitions and interpretations ofterms in section 201 of the FederalFood, Drug, and Cosmetic Act (theact) are applicable to such termswhen used in this part. The followingdefinitions shall also apply:

Definitions

The definitions and interpretations ofterms in section 201 of the FederalFood, Drug, and Cosmetic Act (theact) are applicable to such terms whenused in this part. The followingdefinitions shall also apply:

111.3 What definitions apply tothis Part? The definitions and interpretations ofterms in section 201 of the FederalFood, Drug, and Cosmetic Act (theact) apply to such terms when usedin these regulations. For thepurpose of these regulations, thefollowing definitions also apply:

(20) Acceptance criteria means theproduct specifications andacceptance/rejection criteria, such asacceptable quality level and unacceptablequality level, with an associated samplingplan, that are necessary for making adecision to accept or reject a lot or batch(or any other convenient subgroups ofmanufactured units).

(a) Acid foods or acidified foodsmeans foods that have anequilibrium pH of 4.6 or below.

(1) Act means the Federal Food, Drug, andCosmetic Act, as amended (21 U.S.C. 301et seq.).(7) Active ingredient means anycomponent that is intended to furnishpharmacological activity or other directeffect in the diagnosis, cure, mitigation,treatment, or prevention of disease, or toaffect the structure or any function of thebody of man or other animals. The termincludes those components that mayundergo chemical change in themanufacture of the drug product and bepresent in the drug product in a modifiedform intended to furnish the specifiedactivity or effect.

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(18) Actual yield means the quantity that isactually produced at any appropriate phaseof manufacture, processing, or packing of aparticular drug product.

Actual yield means the quantity thatis actually produced at anyappropriate step of manufacture orpackaging of a particular dietaryingredient or dietary supplement.

(b) Adequate means that which isneeded to accomplish the intendedpurpose in keeping with good publichealth practice.

(a) "Adequate" means that which isneeded to accomplish the intendedpurpose in keeping with good publichealth practice.

(2) Batch means a specific quantity of adrug or other material that is intended tohave uniform character and quality, withinspecified limits, and is produced accordingto a single manufacturing order during thesame cycle of manufacture.

(b) "Batch or Lot" means a specificquantity of a finished product or othermaterial that is intended to haveuniform character and quality, withinspecified limits, and is producedaccording to a single manufacturingorder during the same cycle ofmanufacture.

Batch means a specific quantity of a

dietary ingredient or dietarysupplement that is intended to meetspecifications for identity, purity,quality, strength, and composition,and is produced during a specifiedtime period according to a singlemanufacturing record during thesame cycle of manufacture.

(11) Lot number, control number, or batchnumber means any distinctive combinationof letters, numbers, or symbols, or anycombination of them, from which thecomplete history of the manufacture,processing, packing, holding, anddistribution of a batch or lot of drug productor other material can be determined.

(j) "Lot number" means anydistinctive combination of letters,numbers, or symbols, or anycombination of them from which thecomplete history of the manufacture,processing, packing, holding, anddistribution of a batch or lot of afinished dietary ingredient, dietarysupplement or other material can bedetermined.

Batch number, lot number, or

control number means anydistinctive group of letters,numbers, or symbols, or anycombination of them, from whichthe complete history of themanufacturing, packaging, orholding of a batch or lot of dietaryingredients or dietary supplementscan be determined.

(c) Batter means a semifluidsubstance, usually composed offlour and other ingredients, intowhich principal components of foodare dipped or with which they arecoated, or which may be useddirectly to form bakery foods.

(d) Blanching, except for tree nutsand peanuts, means a prepackagingheat treatment of foodstuffs for asufficient time and at a sufficienttemperature to partially orcompletely inactivate the naturallyoccurring enzymes and to effectother physical or bio-chemicalchanges in the food.

(c) "Blanching" means aprepackaging heat treatment of adietary product for a sufficient timeand at a sufficient temperature topartially or completely inactivate thenaturally occurring enzymes and toeffect other physical or bio-chemicalchanges in the product.

(3) Component means any ingredientintended for use in the manufacture of adrug product, including those that may notappear in such drug product.

(q) "Raw material" means anyingredient intended for use in themanufacture of a dietary ingredient ordietary supplement, including thosethat may not appear in such finishedproduct.

Component means any substance

intended for use in the manufactureof a dietary ingredient or dietarysupplement including those thatmay not appear in the finisheddietary ingredient or dietarysupplement. Component includesingredients and dietary ingredientsas, described in section 20l(ff) of theact.

(d) "Composition" means, asappropriate: (1) the identity of a dietaryingredient or dietary supplement, and (2) the concentration of a dietaryingredient (e.g., weight or other unit ofuse/weight or volume), or the potencyor activity of one or more dietaryingredients, as indicated byappropriate procedures.

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Consumer complaint meanscommunication that contains anyallegation, written or oral,expressing dissatisfaction with thequality of a dietary ingredient or adietary supplement related to goodmanufacturing practices. Examplesof product quality related to goodmanufacturing practices are: Foulodor, off taste, super-potent,subpotent, wrong ingredient, drugcontaminant, other contaminant(e.g., bacteria, pesticide, mycotoxin,glass, lead), disintegration time,color variation, mycotoxin, glass,lead), disintegration time, colorvariation, tablet size or sizevariation, under-filled container,foreign material in a dietarysupplement container, improperpackaging, or mislabeling. For thepurposes of the regulations in thispart, a consumer complaint aboutproduct quality may or may notinclude concerns about a possiblehazard to health. However, aconsumer complaint does notinclude an adverse event, illness, orinjury related to the safety of aparticular dietary ingredientindependent of whether the productis produced under goodmanufacturing practices.

(e) Critical control point means apoint in a food process where thereis a high probability that impropercontrol may cause, allow, orcontribute to a hazard or to filth in thefinal food or decomposition of thefinal food.

(e) "Dietary ingredient" means aningredient intended for use or used ina dietary supplement that is: (1) a vitamin, (2) a mineral, (3) an herb or other botanical, (4) an amino acid, (5) a dietary substance for use byman to supplement the diet byincreasing the total dietary intake, or (6) a concentrate, metabolite,constituent, extract, or combination ofany of the foregoing ingredients.

(f) "Dietary product" means either adietary ingredient or dietarysupplement as defined in this part.

(g) "Dietary supplement" meansdietary supplement as defined insection 201 (ff) of the act.

(4) Drug product means a finished dosageform, for example, tablet, capsule, solution,etc., that contains an active drug ingredientgenerally, but not necessarily, inassociation with inactive ingredients. Theterm also includes a finished dosage formthat does not contain an active ingredientbut is intended to be used as a placebo.

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(5) Fiber means any particulatecontaminant with a length at least threetimes greater than its width.

(f) Food means food as defined insection 201(f) of the act and includesraw materials and ingredients.

(g) Food-contact surfaces arethose surfaces that contact humanfood and those surfaces from whichdrainage onto the food or ontosurfaces that contact the foodordinarily occurs during the normalcourse of operations. "Food-contactsurfaces" includes utensils and food-contact surfaces of equipment.

Contact surface means any surfacethat contacts a component, dietaryingredient, dietary supplement, andthose surfaces from which drainageonto the component, dietaryingredient, dietary supplement, oronto surfaces that contact thecomponent, dietary ingredient, ordietary supplement ordinarilyoccurs during the normal course ofoperations. Examples of contactsurfaces include, but are not limitedto, containers, utensils, tables,contact surfaces of equipment, andpackaging.

(22) Gang-printed labeling means labelingderived from a sheet of material on whichmore than one item of labeling is printed.

(8) Inactive ingredient means anycomponent other than an active ingredient.

Ingredient means any substance

that is used in the manufacture of adietary ingredient or dietarysupplement that is intended to bepresent in the finished dietaryingredient ordietary supplement. An ingredientincludes, but is not necessarilylimited to, a dietary ingredient asdescribed in section 201(ff) of theact.

(9) In-process material means anymaterial fabricated, compounded, blended,or derived by chemical reaction that isproduced for, and used in, the preparationof the drug product.

(h) "In-process material" means anymaterial fabricated, compounded,blended, ground, extracted, sifted,sterilized, derived by chemicalreaction or processed in any otherway that is produced for, and used in,the preparation of a dietary product.

Inprocess material means anymaterial that is fabricated,compounded, blended, ground,extracted; sifted, sterilized, derivedby chemical reaction, or processedin any other way for use in themanufacture of a dietary ingredientor dietary supplement.

(10) Lot means a batch, or a specificidentified portion of a batch, having uniformcharacter and quality within specifiedlimits; or, in the case of a drug productproduced by continuous process, it is aspecific identified amount produced in aunit of time or quantity in a manner thatassures its having uniform character andquality within specified limits.

(h) Lot means the food producedduring a period of time indicated by aspecific code.

(i) "Lot" means "batch" as defined inthis part.

Lot means a batch, or a specific

identified portion of a batch intendedto have uniform identity, purity,quality, strength, and composition;or, in the case of a dietary ingredientor dietary supplement produced bycontinuous process, a specificidentified amount produced in aspecified unit of time or quantity in amanner that is intended to haveuniform identity, purity, quality,strength, and composition.

(12) Manufacture, processing, packing, orholding of a drug product includespackaging and labeling operations, testing,and quality control of drug products.

(k) "Manufacture" or "manufacturing"includes all operations associatedwith the production of dietaryproducts, including packaging andlabeling operations, testing, andquality control of a dietary ingredientor dietary supplement.

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(13) The term medicated feed means anyType B or Type C medicated feed asdefined in 558.3 of this chapter. The feedcontains one or more drugs as defined insection 201(g) of the act. The manufactureof medicated feeds is subject to therequirements of part 225 of this chapter.(14) The term medicated premix means aType A medicated article as defined in558.3 of this chapter. The article containsone or more drugs as defined in section201(g) of the act. The manufacture ofmedicated premixes is subject to therequirements of part 226 of this chapter.

(i) Microorganisms means yeasts,molds, bacteria, and viruses andincludes, but is not limited to,species having public healthsignificance. The term "undesirablemicroorganisms" includes thosemicroorganisms that are of publichealth significance, that subject foodto decomposition, that indicate thatfood is contaminated with filth, orthat otherwise may cause food to beadulterated within the meaning of theact. Occasionally in theseregulations, FDA used the adjective"microbial" instead of using anadjectival phrase containing theword microorganism.

(l) "Microorganisms" means yeasts,molds, bacteria, and viruses andincludes, but is not limited to, specieshaving public health significance. Theterm "undesirable microorganisms"includes those microorganisms thatare of public health significance, thatsubject a dietary product todecomposition, that indicate that adietary ingredient or dietarysupplement is contaminated with filth,or that otherwise may cause a dietaryproduct to be adulterated within themeaning of the act. Occasionally inthese regulations, the adjective"microbial" is used instead of anadjectival phrase containing the wordmicroorganism.

Microorganisms means yeasts,molds, bacteria, viruses, and othersimilar microscopic organismshaving public health or sanitaryconcern. This definition includes,but is not limited to, species that:

(1) Have public health significance;

(2) Could cause a component,dietary ingredient, or dietarysupplement to decompose;

(3) Indicate that the component,dietary ingredient, or dietarysupplement is contaminated withfilth; or

(4) Otherwise may cause thecomponent, dietary ingredient, ordietary supplement to beadulterated.

(p) Shall is used to state mandatoryrequirements.

(u) "Shall" is used to state mandatoryrequirements.

Must is used to state mandatoryrequirements.

(6) Non-fiber-releasing filter means anyfilter, which after any appropriatepretreatment such as washing or flushing,will not release fibers into the componentor drug product that is being filtered. Allfilters composed of asbestos are deemedto be fiber-releasing filters.

(19) Percentage of theoretical yield meansthe ratio of the actual yield (at anyappropriate phase of manufacture,processing, or packing of a particular drugproduct) to the theoretical yield (at thesame phase), stated as a percentage.

(j) Pest refers to any objectionableanimals or insects including, but notlimited to, bird, rodents, flies, andlarvae.

(m) "Pest" refers to any objectionableanimals or insects including, but notlimited to, bird, rodents, flies, andlarvae.

Pest means any objectionableinsects or other animals including,but not limited to, birds, rodents,flies, mites, and larvae.

(k) Plant means the building orfacility or parts thereof, used for or inconnection with the manufacturing,packaging, labeling, or holding ofhuman food.

(n) "Plant" means the building orfacility or parts thereof, used for or inconnection with the manufacturing,packaging, labeling, or holding of adietary product.

Physical plant means all or parts ofa building or facility used for or inconnection with manufacturing,packaging, or holding a dietaryingredient or dietary supplement.

(l) Quality control operation meansa planned and systematic procedurefor taking all actions necessary toprevent food from being adulteratedwithin the meaning of the act.

(o) "Quality control operation" meansa planned and systematic procedurefor taking all actions necessary toprevent a dietary product from beingadulterated within the meaning of theact.

Quality control means a planned

and systematic operation orprocedure for preventing a dietaryingredient or dietary supplementfrom being adulterated.

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(15) Quality control unit means any personor organizational element designated bythe firm to be responsible for the dutiesrelating to quality control.

(p) "Quality control unit" means anyperson or organizational elementdesignated by the firm to beresponsible for the duties relating toquality control operations.

Quality control unit means anyperson or group that you designateto be responsible for quality controloperations.

(21) Representative sample means asample that consists of a number of unitsthat are drawn based on rational criteriasuch as random sampling and intended toassure that the sample accurately portraysthe material being sampled.

(r) "Representative sample" means asample that consists of a number ofunits that are drawn based on rationalcriteria, such as random sampling,and is intended to assure that thesample accurately portrays thematerial being sampled.

Representative sample means a

sample that consists of a number ofunits that are drawn based onrational criteria, such as randomsampling, and intended to ensurethat the sample accurately portraysthe material being sampled.

(m) Rework means clean,unadulterated food that has beenremoved from processing forreasons other than insanitaryconditions or that has beensuccessfully reconditioned byreprocessing and that is suitable foruse as food.

(s) "Rework" means clean,unadulterated material that has beenremoved from processing for reasonsother than insanitary conditions or thathas been successfully reconditionedby reprocessing and that is suitablefor use in the manufacture of a dietaryproduct.

Reprocessing means using, in the

manufacture of a dietary ingredientor a dietary supplement, clean,unadulterated components, dietaryingredients, or dietary supplementsthat have been previously removedfrom manufacturing for reasonsother than insanitary conditions andthat have been made suitable foruse in the manufacture of a diet anyingredient or dietary supplement.

(n) Safe moisture level is a level ofmoisture low enough to prevent thegrowth of undesirablemicroorganisms in the finishedproduct under the intendedconditions of manufacturing, storage,and distribution. The maximum safemoisture level for a food is based onits water activity (aw). An aw will beconsidered safe for food if adequatedata are available that demonstratethat the food at or below the given awwill not support growth ofundesirable microorganisms.

(o) Sanitize means to adequatelytreat food-contact surfaces by aprocess that is effective indestroying vegetative cells ofmicroorganisms of public healthsignificance, and in substantiallyreducing numbers of otherundesirable microorganisms, butwithout adversely affecting theproduct or its safety for theconsumer.

(t) "Sanitize" means to adequatelytreat equipment, containers orutensils by a process that is effectivein destroying vegetative cells ofmicroorganisms of public healthsignificance, and in substantiallyreducing numbers of otherundesirable microorganisms, butwithout adversely affecting theproduct or its safety for the consumer.

Sanitize means to adequately treatequipment, containers, utensils, orany other dietary product contactsurface by applying cumulative heator chemicals on cleaned foodcontact surfaces that whenevaluated for efficacy, yield areduction of 5 logs, which is equal to99.999 percent reduction, of representative diseasemicroorganisms of public healthsignificance and substantiallyreduce the numbers of otherundesirable microorganisms, butwithout adversely affecting theproduct or its safety for theconsumer.

(q) Should is used to staterecommended or advisoryprocedures or identifyrecommended equipment.

(v) "Should" is used to staterecommended or advisoryprocedures or identify recommendedequipment.

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(16) Strength means:

(i) The concentration of the drug substance(for example, weight/weight,weight/volume, or unit dose/volume basis),and/or

(ii) The potency, that is, the therapeuticactivity of the drug product as indicated byappropriate laboratory tests or byadequately developed and controlledclinical data (expressed, for example, interms of units by reference to a standard).(17) Theoretical yield means the quantitythat would be produced at any appropriatephase of manufacture, processing, orpacking of a particular drug product, basedupon the quantity of components to beused, in the absence of any loss or error inactual production.

Theoretical yield means the quantity

that would be produced at anyappropriate step of manufacture orpackaging of a particular dietaryingredient or dietary supplement,based upon the quantity ofcomponents or packaging to beused; in the absence of any loss orerror in actual production.

(r) Water activity (aw) is ameasure of the free moisture in afood and is the quotient of the watervapor pressure of the substancedivided by the vapor pressure ofpure water at the same temperature.

(w) "Water activity (aw)" is ameasure of the free moisture in adietary ingredient or dietarysupplement and is the quotient of thewater vapor pressure of thesubstance divided by the vaporpressure of pure water at the sametemperature.

Water activity (a w ) is a measure of

the free moisture in a component,dietary ingredient, or dietarysupplement and is the quotient of thewater vapor pressure of thesubstance divided by the vaporpressure of pure water at the sametemperature.

We means the United States Food

and Drug Administration (FDA).

You means a person whomanufactures, packages, or holdsdietary ingredients or dietarysupplements.

111.5 Do other statutoryprovisions and regulationsapply?

In addition to the regulations in thispart, you must comply with otherapplicable statutory provisions andregulations under the act related tothe manufacturing, packaging, orholding of dietary ingredients ordietary supplements.

110.19 Exclusions

(a) The following operations are notsubject to this part: Establishmentsengaged solely in the harvesting,storage, or distribution of one ormore "raw agriculturalcommodities," as defined in section201(r) of the act, which areordinarily cleaned, prepared, treated,or otherwise processed before beingmarketed to the consuming public. (b) FDA, however, will issuespecial regulations if it is necessaryto cover these excluded operations.

Exclusions

The following operations are notsubject to this part: Establishmentsengaged solely in the harvesting,storage, or distribution of one or more"raw agricultural commodities," asdefined in section 201(r) of the act,which are ordinarily cleaned,prepared, treated, or otherwiseprocessed before being marketed tothe consuming public.

111.6 Exclusions. Theregulations in this part do not applyto a person engaged solely inactivities related to the harvesting,storage, or distribution of rawagricultural commodities that willbe incorporated into a dietaryingredient or dietary supplement byother persons.

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211.28 Personnel responsibilities.

(d) Any person shown at any time (eitherby medical examination or supervisoryobservation) to have an apparent illness oropen lesions that may adversely affect thesafety or quality of drug products shall beexcluded from direct contact withcomponents, drug product containers,closures, in-process materials, and drugproducts until the condition is corrected ordetermined by competent medicalpersonnel not to jeopardize the safety orquality of drug products. All personnel shallbe instructed to report to supervisorypersonnel any health conditions that mayhave an adverse effect on drug products.

110.10 Personnel

The plant management shall take allreasonable measures andprecautions to ensure the following:

(a) Disease control. Any personwho, by medical examination orsupervisory observation, is shown tohave, or appears to have, an illness,open lesion, including boils, sores,or infected wounds, or any otherabnormal source of microbialcontamination by which there is areasonable possibility of food, food-contact surfaces, or food-packagingmaterials becoming contaminated,shall be excluded from anyoperations which may be expectedto result in such contamination untilthe condition is corrected. Personnel shall be instructed toreport such health conditions to theirsupervisors.

Personnel The plant management shall take allreasonable measures andprecautions to assure the following:

(a) Disease control. Any personwho, by medical examination orsupervisory observation, is shown tohave, or appears to have, an illness,open lesion, including boils, sores, orinfected wounds, or any otherabnormal source of microbialcontamination by which there is areasonable possibility of an in-process or finished dietary productbecoming adulterated, or processingequipment, utensils or packagingmaterials becoming contaminated,shall be excluded from any operationswhich may be expected to result insuch adulteration or contaminationuntil the condition is corrected. Personnel shall be instructed to reportsuch health conditions to theirsupervisors.

Subpart B--Personnel

111.10 What microbialcontamination and hygienerequirements apply?

(a) Microbial contamination. You

must take measures to excludefrom any operations any personwho might be a source of microbialcontamination of any materialincluding components, dietaryingredients, dietary supplements,and contact surfaces used in themanufacture, packaging, or holdingof a dietary ingredient or a dietarysupplement. Such measuresinclude, but are not limited to, thefollowing:

(1) Excluding any person who, bymedical examination or supervisoryobservation, is shown to have, orappears to have an illness, openlesion, or any other abnormalsource of microbial contamination,which may be expected to result inmicrobial contamination ofcomponents, dietary ingredients,dietary supplements, or contact,surfaces, from working in anyoperations until the condition iscorrected; and

(2) Instructing your employees tonotify their supervisor(s) if theyhave or if there is a reasonablepossibility that they have a healthcondition, described in paragraph(a) (1) of this section that couldcontaminate any components,dietary ingredients, dietarysupplements, or any contactsurface.

(b) Cleanliness. All personsworking in direct contact with food,food-contact surfaces, and food-packaging materials shall conformto hygienic practices while on duty tothe extent necessary to protectagainst contamination of food. Themethods for maintaining cleanlinessinclude, but are not limited to:

(b) Cleanliness. All persons workingin direct contact with raw materials,in-process or finished dietaryproducts, processing equipment,utensils or packaging materials shallconform to hygienic practices whileon duty to the extent necessary toprotect against adulteration orcontamination of such materials. Themethods for maintaining cleanlinessinclude, but are not limited to:

(b) Hygienic Practices. If you work

in operations during whichadulteration of the component,dietary ingredients, dietarysupplement, or contact surface mayoccur, you must use hygienicpractices to the extent necessary toprotect against contamination ofcomponents, dietary ingredients,dietary supplements, or contactsurfaces. The hygienic practicesinclude, but are not limited to:

(a) Personnel engaged in the manufacture,processing, packing, or holding of a drugproduct shall wear clean clothingappropriate for the duties they perform

(1) Wearing outer garmentssuitable to the operation in a mannerthat protects against thecontamination of food, food-contact,surfaces or food-packagingmaterials.

(1) Wearing outer garmentssuitable to the operation in a mannerthat protects against the adulterationof in-process or finished dietaryproducts, or contamination ofprocessing equipment, utensils orpackaging materials.

(1) Wearing outer garments in amanner that protects against thecontamination of components,dietary ingredients, dietarysupplements, or any contactsurface;

(b) Personnel shall practice goodsanitation and health habits.

(2) Maintaining adequate personalcleanliness

(2) Maintaining adequate personalcleanliness.

(2) Maintaining adequate personal,cleanliness;

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(3) Washing hands thoroughly (andsanitizing if necessary to protectagainst contamination withundesirable microorganisms) in anadequate hand-washing facilitybefore starting work, after eachabsence from the work station, andat any other time when the handsmay have become soiled orcontaminated.

(3) Washing hands thoroughly (andsanitizing if necessary to protectagainst contamination withundesirable microorganisms) in anadequate hand-washing facility beforestarting work, after each absencefrom the work station, and at anyother time when the hands may havebecome soiled or contaminated.

(3) Washing hands thoroughly (and,sanitizing if necessary to protectagainst contamination withmicroorganisms) in an adequatehand-washing facility:

(i) Before starting work; and

(ii) At any time when the hands mayhave become soiled orcontaminated;

(4) Removing all unsecuredjewelry and other objects that mightfall into food, equipment, orcontainers, and removing handjewelry that cannot be adequatelysanitized during periods in whichfood is manipulated by hand. If suchhand jewelry cannot be removed, itmay be covered by material whichcan be maintained in an intact, clean,and sanitary condition and whicheffectively protects against thecontamination by these objects of thefood, food-contact surfaces, or food-packaging materials.

(4) Removing all unsecuredjewelry and other objects that mightfall into raw materials, in-process orfinished dietary product, equipment,or containers, and removing handjewelry that cannot be adequatelysanitized during periods in which in-process or finished product ismanipulated by hand. If such handjewelry cannot be removed, it may becovered by material which can bemaintained in an intact, clean, andsanitary condition and whicheffectively protects against theadulteration of dietary products orcontamination of processingequipment, utensils or packagingmaterials.

(4) Removing all unsecured jewelryand other objects that might fall intocomponents, dietary ingredients,dietary supplements, equipment, orpackaging, and removing handjewelry that cannot be adequatelysanitized during periods in whichcomponents, dietary ingredients, ordietary supplements aremanipulated by hand. If handjewelry cannot be removed, it mustbe covered by material that ismaintained in an intact, clean, andsanitary condition and thateffectively protects againstcontamination of components,dietary ingredients, dietarysupplements, or contact surfaces;

(5) Maintaining gloves, if they areused in food handling, in an intact,clean, and sanitary condition. Thegloves should be of an impermeablematerial.

(5) Maintaining gloves, if they areused in in-process or finished producthandling, in an intact, clean, andsanitary condition. The gloves shouldbe of a material that adequatelyprotects the product fromcontamination.

(5) Maintaining gloves used inhandling components, dietaryingredients, or dietary supplementsin an intact, clean, and sanitarycondition. The gloves must be of animpermeable material;

(a)Protective apparel, such as head,face, hand, and arm coverings, shall beworn as necessary to protect drugproducts from contamination.

(6) Wearing, where appropriate, inan effective manner, hair nets,headbands, caps, beard covers, orother effective hair restraints.

(6) Wearing, where appropriate, inan effective manner, hair nets, caps,beard covers, or other effective hairrestraints.

(6) Wearing, where appropriate, inan effective manner, hairnets, caps,beard covers, or other effective hairrestraints;

(7) Storing clothing or otherpersonal belongings in areas otherthan where food is exposed or whereequipment or utensils are washed.

(7) Storing clothing or otherpersonal belongings in areas otherthan where in-process or finishedproduct is exposed or whereprocessing equipment or utensils arewashed.

(7) Not storing clothing or otherpersonal belongings in areas wherecomponents, dietary ingredients, ordietary supplements or any contactsurfaces are exposed or wherecontact surfaces are washed;

(8) Confining the following to areasother than where food may beexposed or where equipment orutensils are washed: eating food,chewing gum, drinking beverages,or using tobacco.

(8) Confining the following to areasother than where in-process orfinished product may be stored orexposed, or where processingequipment or utensils are washed: eating food, chewing gum, drinkingbeverages, or using tobacco.

(8) Not eating food, chewing gum,drinking beverages and usingtobacco products in areas, wherecomponents, dietary ingredients,dietary supplements, or any contactsurfaces are exposed, or wherecontact surfaces are washed; and

(9) Taking any other necessaryprecautions to protect againstcontamination of food, food-contact,surfaces, or food-packagingmaterials with micro-organisms orforeign substances including, but notlimited to, perspiration, hair,cosmetics, tobacco, chemicals, andmedicines applied to the skin.

(9) Taking any other necessaryprecautions to protect againstadulteration of raw materials, in-process or finished product, orcontamination of processingequipment, utensils or packagingmaterials with micro-organisms orforeign substances including, but notlimited to, perspiration, hair,cosmetics, tobacco, chemicals, andmedicines applied to the skin.

(9) Taking any other precautionsnecessary to protect against thecontamination of components,dietary ingredients, dietarysupplements, or contact surfaceswith microorganisms, filth, or anyother extraneous materials,including, but not limited to,perspiration, hair, cosmetics,tobacco, chemicals, and medicinesapplied to the skin.

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(c) Only personnel authorized bysupervisory personnel shall enter thoseareas of the buildings and facilitiesdesignated as limited-access areas.

211.25 Personnel qualifications.

(a) Each person engaged in themanufacture, processing, packing, orholding of a drug product shall haveeducation, training, and experience, or anycombination thereof, to enable that personto perform the assigned functions. Trainingshall be in the particular operations that theemployee performs and in current goodmanufacturing practice (including thecurrent good manufacturing practiceregulations in this chapter and writtenprocedures required by these regulations)as they relate to the employee's functions.Training in current good manufacturingpractice shall be conducted by qualifiedindividuals on a continuing basis and withsufficient frequency to assure thatemployees remain familiar with CGMPrequirements applicable to them.

(c) Education and training. Personnel responsible for identifyingsanitation failures or foodcontamination should have abackground of education orexperience, or a combinationthereof, to provide a level ofcompetency necessary forproduction of clean and safe food. Food handlers and supervisorsshould receive appropriate trainingin proper food handling techniquesand food-protection principles andshould be informed of the danger ofpoor personal hygiene and insanitarypractices.

(c) Education and training. Eachperson engaged in the manufacture ofa dietary product should have theproper education, training, andexperience (or any combinationthereof) needed to perform theassigned functions. Training shouldbe in the particular operation(s) thatthe employee performs as they relateto the employee's functions. Appropriate documentation of trainingshall be retained by the manufacturer.

111.12 What personnelqualification requirementsapply?

(a) You must have qualifiedemployees to manufacture,package, or hold dietary ingredientsor dietary supplements; and

(b) Each person engaged inmanufacturing, packaging, orholding must have the training andexperience to perform the person'sduties.

(b) Each person responsible forsupervising the manufacture, processing,packing, or holding of a drug product shallhave the education, training, andexperience, or any combination thereof, toperform assigned functions in such amanner as to provide assurance that thedrug product has the safety, identity,strength, quality, and purity that it purportsor is represented to possess.

(d) Supervision. Responsibility forassuring compliance by allpersonnel with all requirements ofthis part shall be clearly assigned tocompetent supervisory personnel.

d) Supervision. Responsibility forassuring compliance by all personnelwith all requirements of this part shallbe clearly assigned to qualifiedpersonnel with proper education,training and experience (or anycombination thereof).

111.13 What supervisorrequirements apply?

(a) You must assign qualifiedpersonnel to supervise themanufacturing, packaging, orholding of dietary ingredients anddietary supplements.

(b) You and the supervisors you usemust be qualified by training andexperience to supervise.

(c) There shall be an adequate number ofqualified personnel to perform andsupervise the manufacture, processing,packing, or holding of each drug product.

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211.34 Consultants.

Consultants advising on the manufacture,processing, packing, or holding of drugproducts shall have sufficient education,training, and experience, or anycombination thereof, to advise on thesubject for which they are retained.Records shall be maintained stating thename, address, and qualifications of anyconsultants and the type of service theyprovide.

211.56 Sanitation.

(a) Any building used in the manufacture,processing, packing, or holding of a drugproduct shall be maintained in a clean andsanitary condition. Any such building shallbe free of infestation by rodents, birds,insects, and other vermin (other thanlaboratory animals). Trash and organicwaste matter shall be held and disposed ofin a timely and sanitary manner.

211.58 Maintenance.

Any building used in the manufacture,processing, packing, or holding of a drugproduct shall be maintained in a good stateof repair.

110.35 Sanitary operations.

(a) General maintenance. Buildings,fixtures, and other physical facilitiesof the plant shall be maintained in asanitary condition and shall be keptin repair sufficient to prevent foodfrom becoming adulterated withinthe meaning of the act....

Sanitation of Buildings andFacilities

(a) General maintenance. Buildings,fixtures, and other physical facilitiesof the plant shall be maintained in asanitary condition and shall be kept inrepair sufficient to prevent rawmaterials, in-process or finisheddietary products from becomingadulterated within the meaning of theact.

Subpart C--Physical Plant

111.15 What sanitationrequirements apply to yourphysical plant?

(a) Physical plant facilities.

(1) You must maintain yourphysical plant in a clean andsanitary condition; and

(2) You must keep your physicalplant in repair sufficient to preventcomponents, dietary ingredients,dietary supplements or contactsurfaces from becomingcontaminated.

211.56 Sanitation.

(b) There shall be written proceduresassigning responsibility for sanitation anddescribing in sufficient detail the cleaningschedules, methods, equipment, andmaterials to be used in cleaning thebuildings and facilities; such writtenprocedures shall be followed.

(b) Substances used in cleaning andsanitizing; storage of toxic materials.

(1) Cleaning compounds andsanitizing agents used in cleaningand sanitizing procedures shall befree from undesirablemicroorganisms and shall be safeand adequate under the conditions ofuse.

(b) Cleaning and sanitizingmaterials.

(1) Cleaning compounds andsanitizing agents used in cleaning andsanitizing procedures shall be freefrom undesirable microorganismsand shall be safe and adequate underthe conditions of use.

(b) Cleaning compounds. sanitizingagents. and pesticides.

(1) You must use cleaningcompounds and sanitizing agentsthat are free from microorganismsof public health significance andsafe and adequate under theconditions of use.

Compliance with this requirementmay be verified by any effectivemeans including purchase of thesesubstances under a supplier'sguarantee or certification, orexamination of these substances forcontamination.

Compliance with this requirementmay be verified by any effectivemeans including purchase of thesesubstances under a supplier'sguarantee or certification, orexamination of these substances forcontamination.

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Only the following toxic materialsmay be used or stored in a plantwhere food is processed or exposed:

(i) Those required to maintainclean and sanitary conditions;(ii) Those necessary for use inlaboratory testing procedures;(iii) Those necessary for plant andequipment maintenance andoperation; and(iv) Those necessary for use in theplant's operations.

Only the following toxic materialsmay be used or stored in a plantwhere product is processed orexposed:

(i) Those required to maintainclean and sanitary conditions;(ii) Those necessary for use inlaboratory testing procedures;(iii) Those necessary for plant andequipment maintenance andoperation; and(iv) Those necessary for use in theplant's operations.

(2) You must not use or hold toxicmaterials in a physical plant inwhich contact surfaces,components, dietary ingredients, ordietary supplements aremanufactured or exposed, unlessthose materials are necessary:(i) To maintain clean and sanitaryconditions;

(ii) For use in, laboratory testingprocedures;

(iii) For maintaining or operating thephysical plant or equipment; or

(iv) For use in the plant'soperations.

211.56 Sanitation.

(c) There shall be written procedures foruse of suitable rodenticides, insecticides,fungicides, fumigating agents, and cleaningand sanitizing agents. Such writtenprocedures shall be designed to preventthe contamination of equipment,components, drug product containers,closures, packaging, labeling materials, ordrug products and shall be followed.

(2) Toxic cleaning compounds,sanitizing agents, and pesticidechemicals shall be identified, held,and stored in a manner that protectsagainst contamination of food, food-contact surfaces, or food-packagingmaterials.

(2) Toxic cleaning compounds,sanitizing agents, and pesticidechemicals shall be identified, used,held, and stored in a manner thatprotects against adulteration of rawmaterials, in-process or finishedproduct, or contamination ofprocessing equipment or packagingmaterials.

(3) You must identify and hold toxiccleaning compounds, sanitizingagents, pesticides, and pesticidechemicals in a manner that protectsagainst contamination ofcomponents, dietary ingredients,dietary supplements, or contactsurfaces.

Rodenticides, insecticides, and fungicidesshall not be used unless registered andused in accordance with the FederalInsecticide, Fungicide, and Rodenticide Act(7 U.S.C. 135).

All relevant regulations promulgatedby other Federal, State, and localgovernment agencies for theapplication, use or holding of theseproducts should be followed.

All relevant regulations promulgatedby other Federal, State, and localgovernment agencies for theapplication, use or holding of theseproducts should be followed. Rodenticides, insecticides, andfungicides should be registered andused in accordance with the FederalInsecticide, Fungicide, andRodenticide Act.

(d) Sanitation procedures shall apply towork performed by contractors ortemporary employees as well as workperformed by full-time employees duringthe ordinary course of operations.

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(c) Pest control. No pests shall beallowed in any area of a food plant. Guard or guide dogs may be allowedin some areas of a plant if thepresence of the dogs is unlikely toresult in contamination of food, food-contact surfaces, or food-packagingmaterials. Effective measures shallbe taken to exclude pests from theprocessing areas and to protectagainst the contamination of food onthe premises by pests. The use ofinsecticides or rodenticides ispermitted only under precautionsand restrictions that will protectagainst the contamination of food,food-contact surfaces, and food-packaging materials.

(c) Pest control. No pests shall beallowed in any area of a dietaryproduct manufacturing plant. Effective measures shall be taken toexclude pests from the processingareas and to protect against theadulteration of product on thepremises by pests. The use ofinsecticides or rodenticides ispermitted only under precautions andrestrictions that will protect againstthe adulteration of raw materials, in-process or finished product, orcontamination of processingequipment, utensils or packagingmaterials.

(c) Pest control.

(1) You must not allow animals orpests in any area of your physicalplant. Guard or guide dogs areallowed in some areas of yourphysical plant if the presence of thedogs will not result in contaminationof components, dietary ingredients,dietary supplements, or contactsurfaces;

(2) You must take effectivemeasures to exclude pests from thephysical plant and to protect againstcontamination of components,dietary ingredients, dietarysupplements, and contact surfaceson the premises by pests; and

(3) You must not use insecticides,fumigants, fungicides orrodenticides, unless you takeprecautions to protect against thecontamination of components,dietary ingredients, dietarysupplements, or contact surfaces.

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211.48 Plumbing.

(a) Potable water shall be supplied undercontinuous positive pressure in a plumbingsystem free of defects that could contributecontamination to any drug product. Potablewater shall meet the standards prescribedin the Environmental Protection Agency'sPrimary Drinking Water Regulations setforth in 40 CFR part 141. Water notmeeting such standards shall not bepermitted in the potable water system.

110.37 Sanitary facilities andcontrols.

Each plant shall be equipped withadequate sanitary facilities andaccommodations including, but notlimited to:

(a) Water supply. The water supplyshall be sufficient for the operationsintended and shall be derived froman adequate source. Any water thatcontacts food or food-contactsurfaces shall be safe and ofadequate sanitary quality. Runningwater at a suitable temperature, andunder pressure as needed, shall beprovided in all areas where requiredfor the processing of food, for thecleaning of equipment, utensils, andfood-packaging materials, or foremployee sanitary facilities.

(d) Water supply. Potable water at asuitable temperature, and underpressure as needed, shall be providedin all areas where required for theprocessing of dietary products, for thecleaning of processing equipment,utensils, and packaging materials, orfor employee sanitary facilities. Anywater that contacts in-process orfinished dietary products, utensils orprocessing equipment shall meet thestandards prescribed in theEnvironmental Protection Agency'sPrimary Drinking Water Regulations(40 CFR Part 141).

(d) Water supply.

(1) You must provide water that issafe and of adequate sanitaryquality, at suitable temperatures,and under pressure as needed, in allareas where water is necessary for:

(i) Manufacturing dietaryingredients or dietary supplements;

(ii) Making ice that comes incontact with components, dietaryingredients, dietary supplements orcontact surfaces;

(iii) Cleaning any surface; and

(iv) Employee bathrooms and hand-washing facilities.

(2) Water that contactscomponents, dietary ingredients,dietary supplements, or any contactsurface must at a minimum complywith the National Primary DrinkingWater regulations prescribed by theEnvironmental Protection Agencyunder 40 CFR part 141 and anystate and local governmentrequirements;

(3) You must have documentationor otherwise be able to show thatwater that contacts components,dietary ingredients, dietarysupplements, or any contact surfacemeets the requirements inparagraph (d) (2) of this section.

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(b) Drains shall be of adequate size and,where connected directly to a sewer, shallbe provided with an air break or othermechanical device to prevent back-siphonage.

(b) Plumbing. Plumbing shall be ofadequate size and design andadequately installed and maintainedto:

(1) Carry sufficient quantities ofwater to required locationsthroughout the plant.

(2) Properly convey sewage andliquid disposable waste from theplant.

(3) Avoid constituting a source ofcontamination to food, watersupplies, equipment, or utensils orcreating an unsanitary condition.

(4) Provide adequate floor drainagein all areas where floors are subjectto flooding-type cleaning or wherenormal operations release ordischarge water or other liquidwaste on the floor.

(5) Provide that there is notbackflow from, or cross-connectionbetween, piping systems thatdischarge waste water or sewageand piping systems that carry waterfor food or food manufacturing.

(e) Plumbing. Plumbing shall be ofadequate size and design andadequately installed and maintainedto:

(1) Carry sufficient quantities ofwater to required locations throughoutthe plant.

(2) Properly convey sewage andliquid disposable waste from theplant.

(3) Avoid constituting a source ofadulteration to product, orcontamination of water supplies,processing equipment, or utensils orcreating an unsanitary condition.

(4) Provide adequate floor drainageor other appropriate means of waterremoval in all areas where floors aresubject to flooding-type cleaning orwhere normal operations release ordischarge water or other liquid wasteon the floor.

(5) Provide that there is notbackflow from, or cross-connectionbetween, piping systems thatdischarge waste water or sewage andpiping systems that carry water usedfor the manufacture of dietaryproducts.

(e) Plumbing. The plumbing in yourphysical plant must be of anadequate size and design and beadequately installed and maintainedto:

(1) Carry sufficient amounts ofwater to required locationsthroughout the physical plant;

(2) Properly convey sewage andliquid disposable waste from yourphysical plant;

(3) Avoid being a source ofcontamination to components,dietary ingredients, dietarysupplements, water supplies, or anycontact surface, or creating anunsanitary condition;

(4) Provide adequate floor drainagein all areas where floors are subjectto flooding-type cleaning or wherenormal operations release ordischarge water or other liquidwaste on the floor; and

(5) Not allow backflow from, orcross connection between, pipingsystems that discharge waste wateror sewage and piping systems thatcarry water used for manufacturingdietary ingredients or dietarysupplements, for cleaning contactsurfaces, or for use in bathrooms orhand-washing facilities.

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211.50 Sewage and refuse.

Sewage, trash, and other refuse in andfrom the building and immediate premisesshall be disposed of in a safe and sanitarymanner.

(c) Sewage disposal. Sewagedisposal shall be made into anadequate sewerage system ordisposed of through other adequatemeans.

(f) Sewage disposal. Sewagedisposal shall be made into anadequate sewerage system ordisposed of through other adequatemeans.

(f) Sewage disposal. You mustdispose of sewage into an adequatesewage system or through otheradequate means.

211.52 Washing and toilet facilities.

Adequate washing facilities shall beprovided, including hot and cold water,soap or detergent, air driers or single-service towels, and clean toilet facilitieseasily accessible to working areas.

(d) Toilet facilities. Each plantshall provide its employees withadequate, readily accessible toiletfacilities. Compliance with thisrequirement may be accomplishedby:

(1) Maintaining the facilities in asanitary condition.

(2) Keeping the facilities in goodrepair at all times.

(3) Providing self-closing doors.

(4) Providing doors that do not openinto areas where food is exposed toairborne contamination, exceptwhere alternate means have beentaken to protect against suchcontamination (such as double doorsor positive air-flow systems).

(g) Toilet facilities. Each plant shallprovide its employees with adequate,readily accessible toilet facilities. Compliance with this requirementmay be accomplished by:

(1) Maintaining the facilities in asanitary condition.

(2) Keeping the facilities in goodrepair at all times.

(3) Providing self-closing doors.

(4) Providing doors that do not openinto areas where dietary product isexposed to airborne contamination,except where alternate means havebeen taken to protect against suchcontamination (such as double doorsor positive air-flow systems).

(g) Bathrooms. You must provideyour employees with adequate,readily accessible bathrooms. Thebathrooms must be kept clean andmust not become a potential sourceofcontamination to components,dietary ingredients, dietarysupplements, or contact surfaces.You must:

(1) Keep the bathrooms in goodrepair at all times;

(2) Provide self-closing doors; and

(3) Provide doors that do not openinto areas where components,dietary ingredients, dietarysupplements, or contact surfacesare exposed to airbornecontamination except wherealternate means have been taken toprotect against contamination (suchas double doors or positive airflowsystems).

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(e) Hand-washing facilities. Hand-washing facilities shall be adequateand convenient and be furnished withrunning water at a suitabletemperature. Compliance with thisrequirement may be accomplishedby providing:

(1) Hand-washing and, whereappropriate, hand-sanitizing facilitiesat each location in the plant wheregood sanitary practices requireemployees to wash and/or sanitizetheir hands.

(2) Effective hand-cleaning andsanitizing preparations.

(3) Sanitary towel service or suitable drying devices.

(4) Devices or fixtures, such aswater control valves, so designedand constructed to protect againstrecontamination of clean, sanitizedhands.

(5) Readily understandable signsdirecting employees handlingunprotected food, unprotected food-packaging materials, food-contactsurfaces to wash and, whereappropriate, sanitize their handsbefore they start work, after eachabsence from post of duty, and whentheir hands may have become soiledor contaminated. These signs maybe posted in the processing room(s)and in all other areas whereemployees may handle such food,materials, or surfaces.

(6) Refuse receptacles that areconstructed and maintained in amanner that protects againstcontamination of food.

(h) Hand-washing facilities. Hand-washing facilities shall be adequateand convenient and be furnished withrunning water at a suitabletemperature. Compliance with thisrequirement may be accomplished byproviding:

(1) Hand-washing and, whereappropriate, hand-sanitizing facilitiesat each location in the plant wheregood sanitary practices requireemployees to wash and/or sanitizetheir hands.

(2) Effective hand-cleaning andsanitizing preparations.

(3) Air driers, sanitary towelservice or suitable drying devices.

(4) Devices or fixtures, such aswater control valves, so designed andconstructed to protect againstrecontamination of clean, sanitizedhands.

(5) Readily understandable signsdirecting employees handlingunprotected product, packagingmaterials, utensils or processingequipment to wash and, whereappropriate, sanitize their handsbefore they start work, after eachabsence from post of duty, and whentheir hands may have become soiledor contaminated. These signs maybe posted in the processing room(s)and in all other areas whereemployees may handle suchproducts, materials, utensils orequipment.

(6) Refuse receptacles that areconstructed and maintained in amanner that protects againstadulteration of dietary products.

(h) Hand-washing facilities. Youmust provide hand-washingfacilities that are adequate,convenient, and furnish runningwater at a suitable temperature. Youmust do this by providing:

(1) Hand-washing and, whereappropriate, hand-sanitizingfacilities at each location in yourphysical plant where good hygienicpractices require employees towash or to sanitize or both washand sanitize their hands;

(2) Effective hand-cleaning andsanitizing preparations;

(3) Air driers, sanitary towelservice, such as disposable papertowels, or other suitable dryingdevices;

(4) Devices or fixtures, such aswater control valves, designed andconstructed to protect againstrecontamination of clean, sanitizedhands;

(5) Signs that are easy tounderstand and are postedthroughout the physical plant thatdirect employees handlingcomponents, dietary ingredients,dietary supplements, or contactsurfaces to wash and, whereappropriate, to sanitize their handsbefore they start work, after eachabsence from their duty station, andwhen their hands may have becomesoiled or contaminated; and

(6) Trash bins that are constructedand maintained in a manner toprotect against recontamination ofhands and contamination ofcomponents, dietary ingredients;dietary supplements, or any contactsurface.

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(f) Rubbish and offal disposal.Rubbish and any offal shall be soconveyed, stored, and disposed of asto minimize the development ofodor, minimize the potential for thewaste becoming an attractant andharborage or breeding place forpests, and protect againstcontamination of food, food-contactsurfaces, water supplies, and groundsurfaces.

(i) Rubbish disposal. Rubbish shallbe so conveyed, stored, and disposedof as to minimize the development ofodor, minimize the potential for thewaste becoming an attractant andharborage or breeding place for pests,and protect against adulteration of rawmaterials, in-process or finisheddietary products, or contamination ofutensils, processing equipment, watersupplies, and ground surfaces.

(i) Trash disposal. You mustconvey, store, and dispose of trashto:

(1) Minimize the development ofodor;

(2) Minimize the potential for thetrash to attract, harbor, or become abreeding place for pests;

(3) Protect against contamination ofcomponents, dietary ingredients,dietary supplements, any contactsurface, water supplies, andgrounds surrounding your physicalplant; and

(4) Control hazardous waste toprevent contamination ofcomponents, dietary ingredients,dietary supplements, and contactsurfaces.

110.80 Processes and controls.

...Overall sanitation of the plant shallbe under the supervision of one ormore competent individualsassigned responsibility for thisfunction...

(j) Supervision. Overall sanitation ofthe plant shall be under thesupervision of one or moreindividuals qualified by education,experience and training (or anycombination thereof) assignedresponsibility for assuring thatsanitation procedures areaccomplished.

(j) Sanitation supervisors. You must

assign one or more employees tosupervise overall sanitation. Thesesupervisors must be qualified bytraining and experience to developand supervise sanitationprocedures.

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Subpart B--Buildings andFacilities

110.20 Plant and grounds.

(a) Grounds. The grounds about afood plant under the control of theoperator shall be kept in a conditionthat will protect against thecontamination of food. The methodsfor adequate maintenance of groundsinclude, but are not limited to: (1) Properly storing equipment,removing litter and waste, andcutting weeds or grass within theimmediate vicinity of the plantbuildings or structures that mayconstitute an attractant, breedingplace, or harborage for pests. (2) Maintaining roads, yards, andparking lots so that they do notconstitute a source of contaminationin areas where food is exposed. (3) Adequately draining areas thatmay contribute contamination to foodby seepage, foot-borne filth, orproviding a breeding place for pests. (4) Operating systems for wastetreatment and disposal in anadequate manner so that they do notconstitute a source of contaminationin areas where food is exposed. Ifthe plant grounds are bordered bygrounds not under the operator'scontrol and not maintained in themanner described in paragraph(a)(1) through (3) of this section,care shall be exercised in the plantby inspection, extermination, orother means to exclude pests, dirt,and filth that may be a source of foodcontamination.

Plant and Grounds

(a) Grounds. The grounds about adietary product manufacturing plantunder the control of the operator shallbe kept in a condition that will protectagainst the adulteration of dietaryproducts. The methods for adequatemaintenance of grounds include, butare not limited to: (1) Properly storing equipment,removing litter and waste, and cuttingweeds or grass within the immediatevicinity of the plant buildings orstructures that may constitute anattractant, breeding place, orharborage for pests. (2) Maintaining roads, yards, andparking lots so that they do notconstitute a source of adulteration inareas where product is exposed. (3) Adequately draining areas thatmay contribute to product adulterationby seepage, foot-borne filth, orproviding a breeding place for pests. (4) Operating systems for wastetreatment and disposal in an adequatemanner so that they do not constitutea source of adulteration in areaswhere product is exposed. If the plantgrounds are bordered by grounds notunder the operator's control and notmaintained in the manner describedin paragraph (a)(1) through (3) of thissection, care shall be exercised in theplant by inspection, extermination, orother means to exclude pests, dirt,and filth that may be a source ofproduct adulteration.

211.42 Design and constructionfeatures.

(a) Any building or buildings used in themanufacture, processing, packing, orholding of a drug product shall be ofsuitable size, construction and location tofacilitate cleaning, maintenance, andproper operations.

(b) Plant construction and design.

Plant buildings and structures shallbe suitable in size, construction, anddesign to facilitate maintenance andsanitary operations for food-manufacturing purposes. The plantand facilities shall:

(b) Plant construction and design. Plant buildings and structures shall besuitable in size, construction, anddesign to facilitate maintenance,cleaning and sanitary operations fordietary product manufacturingpurposes and to prevent mixupsbetween different raw materials andproducts. The plant and facilitiesshall:

111.20 What design andconstruction requirements applyto your physical plant?

Any physical plant you use in themanufacture, packaging, or holdingof dietary ingredients or dietarysupplements must:

(a) Be suitable in size, construction,and design to facilitate maintenance,cleaning, and sanitizing operations;

(b) Any such building shall have adequatespace for the orderly placement ofequipment and materials to preventmixups between different components,drug product containers, closures, labeling,in-process materials, or drug products,and to prevent contamination. The flow ofcomponents, drug product containers,closures, labeling, in-process materials,and drug products through the building orbuildings shall be designed to preventcontamination.

(1) Provide sufficient space forsuch placement of equipment andstorage of materials as is necessaryfor the maintenance of sanitaryoperations and the production of safefood.

(1) Provide sufficient space forsuch placement of equipment andstorage of materials as is necessaryfor the prevention of mixups,maintenance of sanitary operationsand the production of safe dietaryproducts.

(b) Have adequate space for theorderly placement of equipment andholding materials as is necessaryfor maintenance, cleaning, andsanitizing operations and to preventcontamination and mixups ofcomponents, dietary ingredients,and dietary supplements duringmanufacturing, packaging, orholding;

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(c) Operations shall be performed withinspecifically defined areas of adequate size.There shall be separate or defined areas orsuch other control systems for the firm'soperations as are necessary to preventcontamination or mixups during the courseof the following procedures:

(1) Receipt, identification, storage, andwithholding from use of components, drugproduct containers, closures, and labeling,pending the appropriate sampling, testing,or examination by the quality control unitbefore release for manufacturing orpackaging;

(2) Holding rejected components, drugproduct containers, closures, and labelingbefore disposition;

(3) Storage of released components, drugproduct containers, closures, and labeling;

(4) Storage of in-process materials;

(5) Manufacturing and processingoperations;

(6) Packaging and labeling operations;

(7) Quarantine storage before release ofdrug products;

(8) Storage of drug products after release;

(9) Control and laboratory operations;

(10) Aseptic processing, which includes asappropriate:

(i) Floors, walls, and ceilings ofsmooth, hard surfaces that are easilycleanable;(ii) Temperature and humiditycontrols;(iii) An air supply filtered through high-efficiency particulate air filters underpositive pressure, regardless ofwhether flow is laminar ornonlaminar;(iv) A system for monitoringenvironmental conditions;(v) A system for cleaning anddisinfecting the room and equipment toproduce aseptic conditions;(vi) A system for maintaining anyequipment used to control the asepticconditions.

(2) Permit the taking of properprecautions to reduce the potentialfor contamination of food, food-contact surfaces, or food-packagingmaterials with microorganisms,chemicals, filth, or other extraneousmaterial. ...The potential forcontamination may be reduced byadequate food safety controls andoperating practices or effectivedesign, including the separation ofoperations in which contamination islikely to occur, by one or more of thefollowing means: location, time,partition, air flow, enclosed systems,or other effective means.

(2) Permit the taking of properprecautions to reduce the potential formixups or adulteration of in-processor finished dietary product, orcontamination of processingequipment, utensils or packagingmaterials with microorganisms,chemicals, filth, or other extraneousmaterial. The potential for mixupsand product adulteration may bereduced by adequate product safetycontrols and operating practices oreffective design, including theseparation of operations in whichcontamination is likely to occur, byone or more of the following means: location, time, partition, air flow,enclosed systems, or other effectivemeans.

(c) Permit the use of properprecautions to reduce the potentialfor mixups or contamination ofcomponents, dietary ingredients,dietary supplements, or contactsurfaces, with microorganisms,chemicals, filth, or other-extraneousmaterial. Your physical plant musthave and you must use separate ordefined areas of adequate size orother control systems, such ascomputerized inventory controls orautomated systems of separation, toprevent contamination and mixupsof components, dietary ingredients,and dietary supplements during thefollowing operations:

(1) Receiving, identifying, holding,and withholding from use,components, dietary ingredients,dietary supplements, packaging,and labels that will be used in orduring the manufacturing,packaging, or holding of dietaryingredients and dietarysupplements;

(2) Separating, as necessary,components, dietary ingredients,dietary supplements, packaging,and labels, that are to be used fromcomponents, dietary ingredients,dietary supplements, packaging, orlabels that are awaiting materialreview and disposition decision,reprocessing, or are awaitingdisposal after rejection;

(3) Separating the manufacturing,packaging, and holding of differentproduct types including, but notlimited to, different types of dietaryingredients, dietary supplementsand other foods, cosmetics, andpharmaceutical products;

(4) Performing laboratory analysesand holding laboratory supplies andsamples;

(5) Cleaning and sanitizing contactsurfaces;

(6) Packaging and label operations;and

(7) Holding dietary ingredients ordietary supplements.

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(c) (10) Aseptic processing, whichincludes as appropriate:

(i) Floors, walls, and ceilings of smooth,hard surfaces that are easily cleanable;

(4) Be constructed in such a mannerthat floors, walls, and ceilings maybe adequately cleaned and keptclean and kept in good repair; thatdrip or condensate from fixtures,ducts and pipes does notcontaminate food, food-contactsurfaces, or food-packagingmaterials;

(4) Be constructed in such amanner that floors, walls, and ceilingsmay be adequately cleaned and keptclean and kept in good repair; that dripor condensate from fixtures, ductsand pipes does not adulterate rawmaterials, in-process or finisheddietary products, or contaminateproduct containers, utensils orpackaging materials;

(d) Be designed and constructed ina manner that preventscontamination of components,dietary ingredients, dietarysupplements, or contact surfaces. The design and construction mustinclude, but not be limited to:

(1) Floors, Walls, and ceilings thatare of smooth and hard surfacesthat can be adequately cleaned andkept clean and in good repair;

(2) Fixtures, ducts, and pipes thatdo not contaminate components,dietary ingredients, dietarysupplements, or contact surfaces bydripping or condensate;

(d) Operations relating to the manufacture,processing, and packing of penicillin shallbe performed in facilities separate fromthose used for other drug products forhuman use.

211.46 Ventilation, air filtration, airheating and cooling.

(a) Adequate ventilation shall be provided.

(b) Equipment for adequate control over airpressure, micro-organisms, dust,humidity, and temperature shall beprovided when appropriate for themanufacture, processing, packing, orholding of a drug product.

(c) Air filtration systems, includingprefilters and particulate matter air filters,shall be used when appropriate on airsupplies to production areas. If air isrecirculated to production areas, measuresshall be taken to control recirculation ofdust from production. In areas where aircontamination occurs during production,there shall be adequate exhaust systemsor other systems adequate to controlcontaminants.

(d) Air-handling systems for themanufacture, processing, and packing ofpenicillin shall be completely separatefrom those for other drug products forhuman use.

(6) Provide adequate ventilation orcontrol equipment to minimize odorsand vapors (including steam andnoxious fumes) in areas where theymay contaminate food; and locateand operate fans and other air-blowing equipment in a manner thatminimizes the potential forcontaminating food, food-packagingmaterials, and food-contactsurfaces.

(6) Provide adequate ventilation orcontrol equipment to maintainadequate control overmicroorganisms, dust, humidity, andtemperature, when appropriate, forthe manufacture of dietary products;to minimize odors and vapors(including steam and noxious fumes)in areas where they may adulteratedietary products; and locate andoperate fans and other air-blowingequipment in a manner thatminimizes the potential foradulterating raw materials, in-process or finished dietary products,or contaminating processingequipment, utensils or packagingmaterials.

(3) Adequate ventilation orenvironmental control equipmentsuch as air flow systems, includingfilters, fans, and other air-blowingequipment, that minimize odors andvapors (including steam andnoxious fumes) in areas where theymay contaminate components,dietary ingredients, dietarysupplements, or contact surfaces;

(4) Fans and other air-blowingequipment located and operated in amanner that minimizes the potentialfor microorganisms and particulatematter to contaminate components,dietary ingredients, dietarysupplements, or contact surfaces;

(5) Equipment that controlstemperature and humidity; and

(4)and that aisles or workingspaces are provided betweenequipment and walls and areadequately unobstructed and ofadequate width to permit employeesto perform their duties and to protectagainst contaminating food or food-contact surfaces with clothing orpersonal contact.

(4)and that aisles or workingspaces are provided betweenequipment and walls and areadequately unobstructed and ofadequate width to permit employeesto perform their duties and to protectagainst adulterating in-process orfinished product, or contaminatingprocessing equipment with clothing orpersonal contact.

(6) Aisles or working spacesbetween equipment and walls thatare adequately unobstructed and ofadequate width to permit all personsto perform their duties and to protectagainst contamination ofcomponents, dietary ingredients,dietary supplements, or contactsurfaces with clothing or personalcontact.

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211.44 Lighting.

Adequate lighting shall be provided in allareas.

(5) Provide adequate lighting inhand-washing areas, dressing andlocker rooms, and toilet rooms andin all areas where food is examined,processed, or stored and whereequipment or utensils are cleaned;and

(5) Provide adequate lighting inhand-washing areas, dressing andlocker rooms, and toilet rooms and inall areas where product is examined,processed, or stored and whereequipment or utensils are cleaned;and

(e) Provide adequate light in:

(1) All areas where components,dietary ingredients, or dietarysupplements are examined,processed, or held;

(2) All areas where contactsurfaces are cleaned; and

(3) Hand-washing areas, dressingand locker rooms, and bathrooms.

(5)provide safety-type light bulbs,fixtures, sky-lights, or other glasssuspended over exposed food in anystep of preparation or otherwiseprotect against food contamination incase of glass breakage.

(5)provide safety-type light bulbs,fixtures, sky-lights, or other glasssuspended over exposed product inany step of preparation or otherwiseprotect against product adulteration incase of glass breakage.

(f) Use safety-type light bulbs,fixtures, skylights, or other glassthat is suspended over exposedcomponents, dietary ingredients, ordietary supplements in any step ofpreparation, unless otherwiseconstructed in a manner that willprotect against contamination ofcomponents, dietary ingredients, ordietary supplements in case ofglass breakage.

(3) Permit the taking of properprecautions to protect food in outdoorbulk fermentation vessels by anyeffective means, including:

(i) Using protectivecoverings.

(ii) Controlling areas overand around the vesselsto eliminate harboragesfor pests.

(iii) Checking on a regularbasis for pests and pestinfestation.

(iv) Skimming thefermentation vessels, asnecessary.

(3) Permit the taking of properprecautions to protect dietaryingredients or dietary supplements inoutdoor bulk fermentation vessels byany effective means, including:

(i) Using protectivecoverings.

(ii) Controlling areas overand around the vesselsto eliminateharborages for pests.

(iii) Checking on a regularbasis for pests andpest infestation.

(iv) Skimming thefermentation vessels,as necessary.

(g) Provide protection by anyeffective means againstcontamination of components,dietary ingredients, and dietarysupplements in bulk fermentationvessels, including consideration of:

(1) Use of protective coverings;

(2) Placement in areas where youcan eliminate harborages for pestsover and around the vessels;

(3) Placement in areas where youcan check regularly for pests, pestinfestation, filth or any otherextraneous materials; and

(4) Use of skimming equipment.

(7) Provide, where necessary,adequate screening or otherprotection against pests.

(7) Provide, where necessary,adequate screening or otherprotection against pests.

(h) Use adequate screening or otherprotection against pests, wherenecessary.

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211.63 Equipment design, size, andlocation.

Equipment used in the manufacture,processing, packing, or holding of a drugproduct shall be of appropriate design,adequate size, and suitably located tofacilitate operations for its intended use andfor its cleaning and maintenance.

Subpart CEquipment

110.40 Equipment and utensils.

(a) All plant equipment and utensilsshall be so designed and of suchmaterial and workmanship as to beadequately cleanable, and shall beproperly maintained.

(d) Holding, conveying, andmanufacturing systems, includinggravimetric, pneumatic, closed, andautomated systems, shall be of adesign and construction that enablesthem to be maintained in anappropriate sanitary condition.

Equipment and Utensils

(a) Design and construction.

(1) All plant equipment and utensilsshall be so designed and of suchmaterial and workmanship as to beadequately cleanable, and shall beproperly maintained.

(6) Holding, conveying, andmanufacturing systems, includinggravimetric, pneumatic, closed, andautomated systems, shall be of adesign and construction that enablesthem to be maintained in anappropriate clean condition.

Subpart D--Equipment andUtensils

111.25 What requirementsapply to the equipment andutensils you use?

(a) (1) You must use equipment andutensils that are of appropriatedesign, construction, andworkmanship to enable them to besuitable for their intended use and tobe adequately cleaned and properlymaintained. Equipment and utensilsinclude, but are not limited to, thefollowing:

(i) Equipment used to hold orconvey;

(ii) Equipment used to measure;

(iii) Equipment using compressedair or gas;

iv) Equipment used to carry outprocesses in closed pipes andvessels; and

(v) Equipment used in automatic,mechanical, or electronic systems.

211.65 Equipment construction.

(a) Equipment shall be constructed so thatsurfaces that contact components, in-process materials, or drug products shallnot be reactive, additive, or absorptive soas to alter the safety, identity, strength,quality, or purity of the drug product beyondthe official or other establishedrequirements.

(b) Any substances required for operation,such as lubricants or coolants, shall notcome into contact with components, drugproduct containers, closures, in-processmaterials, or drug products so as to alterthe safety, identity, strength, quality, orpurity of the drug product beyond theofficial or other established requirements.

The design, construction, and useof equipment and utensils shallpreclude the adulteration of food withlubricants, fuel, metal fragments,contaminated water, or any othercontaminants.

(2) The design, construction anduse of equipment and utensils shallpreclude the adulteration of rawmaterials, packaging materials, in-process materials or finished productwith lubricants, fuel, metal fragments,contaminated water, or any othercontaminants.

(2) You must use equipment andutensils of appropriate design andconstruction so that use will notresult in the contamination ofcomponents, dietary ingredients, ordietarysupplements with:

(i) Lubricants;

(ii) Fuel;

(iii) Coolants;

(iv) Metal or glass fragments;

(v) Filth or any other extraneousmaterial;

(vi) Contaminated water; or

(vii) Any other contaminants.

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All equipment should be soinstalled and maintained as tofacilitate the cleaning of theequipment and of all adjacentspaces. Food-contact surfaces shallbe corrosion-resistant when incontact with food. They shall bemade of nontoxic materials anddesigned to withstand theenvironment of their intended useand the action of food, and, ifapplicable, cleaning compounds andsanitizing agents. Food-contactsurfaces shall be maintained toprotect food from beingcontaminated by any source,including unlawful indirect foodadditives.

....(7) Equipment, containers, andutensils used to convey, hold, orstore raw materials, work-in-process, rework, or food shall beconstructed, handled, andmaintained during manufacturing orstorage in a manner that protectsagainst contamination....

(3) All equipment should be soinstalled and maintained as tofacilitate the cleaning of the equipmentand of all adjacent spaces. Processing equipment and utensilsshall be corrosion-resistant when incontact with raw materials, in-process or finished dietary product. They shall be made of nontoxicmaterials and designed to withstandthe environment of their intended useand the action of dietary products,and, if applicable, cleaningcompounds and sanitizing agents. Processing equipment and utensilsshall be maintained to protect dietaryproducts from being adulterated byany source.

(12) Equipment, containers, andutensils used to convey, hold, or storeraw materials, in-process material,rework, or finished product shall beconstructed, handled, and maintainedduring manufacturing or storage in amanner that protects againstcontamination.

(3) All equipment and utensils youuse must be:

(i) Installed and maintained tofacilitate cleaning the equipment,utensils, and all adjacent spaces;

(ii) Corrosion-resistant if theequipment or utensils contactcomponents, dietary ingredients, ordietary supplements;

(iii) Made of nontoxic materials;

(iv) Designed and constructed towithstand the environment of theirintended use, the action ofcomponents, dietary ingredients, ordietary supplements, and, ifapplicable, cleanin

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