What is 21 CFR Part 11 Title 21 in the federal regulations are regulations which regulates the Food and Drugs

in United States of America. Part 11 within this Code of Federal Regulations is related to US Food and Drug Administration (FDA guidelines a!out electronic records and electronic signatures. The regulations in this "art set forth the criteria under which the US FDA considers electronic records# electronic signatures# and handwritten signatures e$ecuted to electronic records to !e trustworth%# relia!le# and generall% e&ui'alent to "a"er records and handwritten signatures e$ecuted on "a"er. 21 cfr Part 11 !ecame effecti'e in August 1(() 21 CFR Part 11# states the re&uirements for "rocedures for creating# modif%ing# maintaining# archi'ing# retrie'ing# and transmitting electronic records and electronic signatures !% 'irtue of which the% can !e considered or rendered to !e trustworth%# relia!le and e&ui'alent to "a"er records. CFR 21 Part 11 re&uires that a drug manufacturer #medical de'ice manufacturer and !iologics de'elo"ers and all other industries regulated !% FDA to im"lement controls for their electronic s%stem# li*e audits# documentation for software # s%stem 'alidations# audit trails# electronic signatures# and for s%stems which are handling the electronic data which is re&uired to !e maintained !% the FDA "redicate rules or the s%stems which "rocess data used for demonstration of com"liance of a re&uirement or a rule. CFR21 "art 11 also a""lies to the electronic su!missions made to FDA li*e A+DA# +DA. ,an% drug manufacturers and felt that the 21CFR11 is !it difficult to im"lement in the wa% it is desired in the regulations and US FDA has listed the "oints wh% the% ga'e rela$ations at some "oints of im"lementation in CFR 21 "art 11 are as follows. 1. Unnecessaril% restrict the use of electronic technolog% in a manner that is inconsistent with FDA-s stated intent in issuing the rule. 2. Significantl% increase the costs of com"liance to an e$tent that was not contem"lated at the time the rule was drafted. .. Discourage inno'ation and technological ad'ances without "ro'iding a significant "u!lic health !enefit. /n an effort towards "ro"er im"lementation US FDA released a guidance document in August of 200. the

US FDA "u!lished the 1Part 11# 2lectronic Records3 2lectronic Signatures 4 Sco"e and A""lication5 guidance which descri!es how US FDA intends to e$ercise enforcement discretion and sets forth the following considerations related to Part 116 US FDA has made an announcement on 789ul%82010 with res"ect to im"lementation of cfr 21 "art 11 as follows The US (FDA will !e conducting a series of ins"ections in an effort to e'aluate industr%5s com"liance and understanding of Part 11 in light of the enforcement discretion descri!ed in the August 200. 1Part 11# 2lectronic Records3 2lectronic Signatures 4 Sco"e and A""lication5 guidance (:uidance . The Agenc% intends to ta*e a""ro"riate action to enforce Part 11 re&uirements for issues raised during the ins"ections that do not fall under the enforcement discretion discussed in the :uidance. 1. CFR 21 Part 11 remains in effect since the issuance of the guidance and the e$ercise of enforcement discretion a""lies as identified in the guidance. 2.The guidance sets out certain conditions related to the 'alidation# audit trail# record retention# record co"%ing# and legac% s%stems where the US FDA sa%s the% do not intend to ta*e enforcement action to enforce com"liance. also FDA mentions that -Con'ersel%# 'iolations of CFR 21 "art 11 re&uirements that do not fall within the guidance5s discretion can lead to enforcement action to enforce com"liance de"ending on the im"ortance of the 'iolation-. ..Records must also !e maintained or su!mitted in accordance with regulator% re&uirements outside of Part 11# and we will enforce all "redicate rule re&uirements# including "redicate rule record and record*ee"ing re&uirements. ;nl% "art so far routinel% enforced is access control# where as 21CFR11 the <"redicate rules< which re&uired the records to !e *e"t in the first "lace are still in effect. /f electronic records are illegi!le# inaccessi!le# or corru"ted the manufacturers are still su!9ect to those re&uirements. Pa"er documents are still considered if a "harma com"an% *ee"s <hard co"ies< of all mandator% records# for regulator% "ur"ose the "a"er documents are also considered as authoritati'e documents.

A drug manufacturer is re&uired to ma*e a claim 'er% carefull% a!out the <hard co"ies< of mandator% records are authoritati'e document. =ence to the <hard co"% should !e an accurate and com"lete co"% of its electronic source and can !e used for regulator% "ur"oses. US FDA is e$"ected to !egin conducting the CFR 21 Part 11 focused ins"ections soon. Definitions of a drug, Radioactive Drug, Radiopharmaceuticals, Investigational New Drug or Device, Drug product, Drug substance, What is an orphan drug. What is a drug: An% chemical com"ound that ma% !e used on or administered to humans to hel" diagnose# treat# cure# mitigate# or "re'ent disease or other a!normal conditions Regulatory definition of drug An article or su!stance that is recogni>ed !% the US Pharmaco"oeia# +ational Formular%# or official =omeo"athic Pharmaco"oeia# or su""lement to an% of the a!o'e intended for use in the diagnosis# cure# mitigation# treatment or "re'ention of disease in man or animals intended to affect the structure or an% function of the !od% of man or animals Su!stance a!use An% medication Radioactive Drug: An% su!stance defined as a drug in 201(! (1 of the Federal Food# Drug and Cosmetic Act that e$hi!its s"ontaneous disintegration of unsta!le nuclei with the emission of nuclear "articles or "hotons ?21 CFR .10..(n @. /ncluded are an% nonradioacti'e reagent *it or nuclide generator that is intended to !e used in the "re"aration of a radioacti'e drug and <radioacti'e !iological "roducts#< as defined in 21 CFR A00..(ee . Drugs such as car!on8containing com"ounds or "otassium8containing salts containing trace &uantities of naturall% occurring radionuclides are not considered radioacti'e drugs. Radiopharmaceuticals: Radioacti'e drugs that are la!eled or tagged with a radioisoto"e. These materials are largel% "h%siological or su!"harmacological in action# and# in man% cases# function much li*e materials found in the !od%. The "rinci"al ris* associated with these materials is the conse&uent radiation e$"osure to the !od% or to s"ecific

organ s%stems when the% are introduced into the !od%. /n'estigational +ew Drug or De'ice6 A drug or de'ice "ermitted !% FDA to !e tested in humans# !ut not %et determined to !e safe and effecti'e for a "articular use in the general "o"ulation# and not %et licensed for mar*eting. Drug product: Drug "roduct means a finished dosage form# for e$am"le# ta!let# ca"sule# or solution# that contains a drug su!stance# generall%# !ut not necessaril%# in association with one or more other ingredients (21 CFR .1B.. (! . Drug substance: Drug su!stance means an acti'e ingredient that is intended to furnish "harmacological acti'it% or other direct effect in the diagnosis# cure# mitigation# treatment# or "re'ention of disease or to affect the structure or an% function of the human !od%# !ut does not include intermediates used in the s%nthesis of such ingredient (21 CFR .1B.. (! . What is a Prodrug 6 A "rodrug is as such a "harmacologicall% inacti'e drug !ut when administered it get con'erted in 'i'o in to a "harmacologicall% acti'e molecule. Prodrugs are intentionall% designed to o'ercome degradation in gut and first "ass meta!olism # and ma*e a drug a'aila!le for action for longer time and also to increase its !ioa'aila!ilit%# some naturall% occurring drugs too are "rodrugs which get con'erted in to "harmacologicall% acti'e form. 2$am"le of "rodrugs 6 Cisde$amfetamine it is a "rodrug C8C%sin is cou"led with de$troam"hetamine molecule form Cisde$amfetamine it get meta!oli>ed in to an acti'e form de$troam"hetamine . What is an orphan drug: An or"han drugs is a drugs which are de'elo"ed s"ecificall% for treating a rare diseases # a rare medical condition or disease s%m"toms such diseases are also termed as or"han disease. Usuall% a disease that affects a!out one indi'idual out 200000 "eo"les. De'elo"ment of or"han drugs are alwa%s encouraged as there is 'er% less mar*et re&uirement for such drugs and de'elo"mental costs too are high # hence some rela$ation in fees and clinical trials is gi'en !%

go'ernments of USA and along with e$clusi'e mar*eting rights to "harmaceutical com"anies ta*ing initiati'es for de'elo"ing or"han drugs# man% 2uro"ean countries too encourage "harmaceutical com"anies for de'elo"ing or"han drugs !% gi'ing similar facilities to "harmaceutical com"anies. What is a Investigational e! Drug "I D#: A drug is said to !e /n'estigational +ew Drug when a "harmaceutical manufacturer want to de'elo" it for treating a disease or an indication # to underta*e research and de'elo"ment such drug # the drug should !e get a""ro'al from US FDA # for which "harmaceutical manufacturer is re&uired to su!mit /n'estigational Drug A""lication ( /+D # after getting an a""ro'al for such drug it can !e then trans"orted and used in a clinical trials normall% it is tested first in "hase 1of a clinical trial. What is Placebo $ Place!o is a su!stance which do not contain an% acti'e ingredient# or an% drug# rather it is designed to 9ust loo* ali*e the actual drug dosage form# it is formulated !% using sugar# or other inert "harmaceutical addaiti'es# it is widel% used in research as control to find out the effect of an actual drug with res"ect to the treatment with "lace!o# some times "lace!o "roduce e&ual effect when used to treat a disease or a condition# which is merel% !ecause of the "s%chological effects and feeling of !eing treated with drug and doctor. Similarl% a treatment and medical "rocedures are designed 9ust to mimic the actual thera"% are also called as "lace!o# some "atients are gi'en treatments which are not actuall% real ones !ut the% 9ust mimic the actual treatments are called as simulated medical inter'ention. =ere is an e$am"le of a /n'estigational +ew drug !eing a""ro'ed for treating a rare disease condition. Process of approval of a drug for mar%ing in &'(: Drugs which has some ho"e for !eneficial effects in treating an% disease# conditions or s%m"toms are first tested in animals . As animal trials do not necessaril% demonstrate com"lete "h%siological# "harmacological# or to$icological effects of a new drug under stud%. Drugs are a""ro'ed for mar*eting onl% after e'aluation of their effecti'eness # efficac% and safet% in human !eings. These e'aluations are usuall% done through clinical trials# and after thorough e'aluation of out come of clinical trial# if it is found that a drug is effecti'e and safe and "ro"erl% la!eled ?21 CFR .12 and 21 CFR .1B@ for use in

conditions indicated # then onl% a drug is a""ro'ed for mar*eting in USA. The Food and Drug Administration (FDA is res"onsi!le for monitoring the testing of new drugs in humans# and all clinical trial are regulated !% US FDA. What is a )rand ame Drug : Dhen drug molecule is com"letel% researched and de'elo"ed in to a drug "roduct for a "articular disease or its s%m"tom or for a indication or when he a""lies new technolog% to an e$isting molecule so as to enhance the efficac% safet% or new route of administration # such drug "roducts then are in'estigated for their safet% and efficac% # and after a""ro'al clinical studies # a manufacturer generall% a""lies for a "atent for the drugs de'elo"ed !% them so as to en9o% the mono"ol% of getting his "roduct-s sale for which he in'ented the drug for a "articular disease. What is a *eneric Drug: Refer this lin* for generic drug we ha'e "ro'ided all details a!out generic drug. Why there are some drugs said to be unapproved and are there available in mar%et+ ,an% of these una""ro'ed drugs are older "roducts introduced well !efore formation of FFDCA in 1(.7 these drug "roducts were a""ro'ed on the !asis of 1(0A Pure Food and Drug Act# that re&uired a drug for getting an a""ro'al onl% to com"l% with some standards of strength and "urit% and not for safet%. Also earlier in 1(A05s drugs were gi'en a""ro'al !ased on onl% as"ects of safet% and efficac% # !ut safet% stud% li*e clinical trials for safet% were not under control !% FDA# until the heroic re9ection of drug containing thalidomide in 1(A0 !% ,adam Dr Frances ;ldham Eelse% an US FDA em"lo%ee then. =er decision actuall% sa'ed millions of American children-s from disa!ilities#which forced US legislation to "ass an act to "ro'ide an additional authorit% to FDA to ma*e it mandator% for a drug to !e "ro'ed that it is a safe !% conducting clinical trials which are com"letel% assessed !% US FDA to get an a""ro'al for mar*eting a drug in USA.

What is a *rand Fathered Drug , Which are the *rand Father Drug Clauses: Under the 1(.7 grandfather clause a drug "roduct that was on the mar*et "rior to "assage of the 1(.7 Act and which contained in its la!eling the same re"resentations concerning the conditions of use as it did "rior to "assage of that Act was not considered a new drug and therefore was e$em"t from the re&uirement of ha'ing an a""ro'ed new drug a""lication. Under the 1(A2 grandfather clause# the Act e$em"ts a drug from the effecti'eness re&uirements if its com"osition and la!eling has not changed since 1(A2 and if# on the da% !efore the 1(A2 Amendments !ecame effecti'e# it was (a used or sold commerciall% in the United States# (! not a new drug as defined !% the Act at that time# and (c not co'ered !% an effecti'e a""lication. The two grandfather clauses in the Act ha'e !een construed 'er% narrowl%. There are 'er% few drugs on the mar*et that are actuall% entitled to grandfather status !ecause the drugs currentl% on the mar*et li*el% differ from the "re'ious 'ersions in some res"ect# such as formulation# dosage or strength# dosage form# route of administration# indications# or intended "atient "o"ulation. /f a firm claims that its "roduct is grandfathered# it is that firms !urden to "ro'e that assertion. -here are three types of unapproved drugs (+D.'I Drugs D2S/ means Drug 2fficac% Stud% /m"lementation Refers to a drug that is a su!9ect of 1(.781(A2 +DAs (safet% onl% and drug which is identical# related# and similar to such drugs. D2S/ drugs are not FgrandfatheredG or generall% recogni>ed as safe and effecti'e (:RASH2 )+Prescription /Wrap0&p1 Refers to drugs that are on the mar*et !ased on a claim of !eing a "re85.7 or "re85A2 "roduct or identical# related# or similar to such a "roduct

C+Post 232 Drugs Drugs initiall% mar*eted after 1(A2 (bbreviated e! Drug (pplication "( D(#+What is an (bbreviated e! Drug (pplication "( D(#$ (bbreviated e! Drug (pplication is also *nown in a!!re'iation as (( D( it is a com"lete set of documents re&uired to !e su!mitted as an a""lication for getting a""ro'al for a drug as a generic drug or generic 'ersion drug of an alread% a""ro'ed !rand name drug to mar*et and sale generic 'ersion of that drug in USA . A+DA is a document referred in conte$t with generic drug a""ro'al a""lication to USFDA. The A+DA is su!mitted for re'iew and a""ro'al to Center for drug e'aluation and research of US FDA. The generic drug "roduct are almost e&uall% safe# effecti'e and com"ara!le to that of an alread% a'aila!le !rand name drug with res"ect to indications of use and "erformance# route of administration# more im"ortantl% their cost too is less com"ared to !rand name drugs. A generic drug while getting an a""ro'al for sale is not re&uired to su!mit "reclinical data (animal safet% and efficac% studies and clinical studies data (=uman clinical trials to esta!lish safet% and efficac% as such clinical studies are alread% conducted !% inno'ator and are re'iewed !% US FDA while granting an a""ro'al for an inno'ator drug a !rand name drug. There for a generic 'ersion of these !rand name drug is re&uired to onl% demonstrate that the% are !ioe&ui'alent with the alread% a""ro'ed inno'ator drug# this is wh% the term Fa!!re'iatedG is used in term F(bbreviated e! Drug (pplicationG for the drug a""lication for a generic drug. A "harmaceutical com"an% can also su!mit A+DA for a drug "roduct electronicall% as electronic su!mission is cost effecti'e and ta*es less time as well. ;nce a generic drug or a drug inno'ated !% a "harma com"an% as their !rand name drug is a""ro'ed !% US FDA it a""ears in the list of a""ro'ed drugs which is also called as orange !oo*. Dhile demonstrating that a drug is !ioe&ui'alent to the alread% a""ro'ed inno'ator drug !ioa'aila!ilit% studies are carried out in com"arison with the alread% a""ro'ed inno'ator drug and !ioa'aila!ilit% of the drug is measured and demonstrated how it is e&uall% a!sor!ed at 'arious inter'als as com"ared to the alread% a""ro'ed inno'ator drug. The generic 'ersion drug should !e a!sor!ed in !lood with the same

rate as com"ared to the alread% a""ro'ed inno'ator drug so as to get a a""ro'al as generic drug "roduct. Dhile a""ro'ing an generic drug onl% !ioe&ui'alence studies are conducted and are re'iewed and clinical studies a'oided so as to a'oid du"lication of the stud% which is alread% done and re'iewed while a""ro'ing a !rand name drug or inno'ator drug. Read where e'er it is written as <we< as US FDA and <agenc%< as or means US FDA and its Regulator% agencies. A+DA C=2CEC/ST F;R CTD or eCTD F;R,AT F;R C;,PC2T2+2SS and ACC2PTAI/C/TJ of an APPC/CAT/;+ F;R F/C/+:. Dhat is Common Technical Document(CTD in "harmaceutical industr% =ow to design a !ioe&ui'alence (I2 studies for s"ecific drug "roducts to su""ort a!!re'iated new drug a""lications (A+DAs . 888888888888888888888888888888888888888888888888888888888888888888888888888 (bbreviated e! Drug (pplication "( D(# An A!!re'iated +ew Drug A""lication (A+DA contains data which when su!mitted to FDA-s Center for Drug 2'aluation and Research# ;ffice of :eneric Drugs# "ro'ides for the re'iew and ultimate a""ro'al of a generic drug "roduct. ;nce a""ro'ed# an a""licant ma% manufacture and mar*et the generic drug "roduct to "ro'ide a safe# effecti'e# low cost alternati'e to the American "u!lic. A ( Pharmaceutical generic drug "roduct is one that is com"ara!le to an inno'ator drug "roduct in dosage form# strength# route of administration# &ualit%# "erformance characteristics and intended use. All a""ro'ed "roducts# !oth inno'ator and generic# are listed in FDA-s A""ro'ed Drug Products with Thera"eutic 2&ui'alence 2'aluations (;range Ioo* . :eneric drug a""lications are termed <a!!re'iated< !ecause the% are generall% not re&uired to include "reclinical (animal and clinical (human data to esta!lish safet% and effecti'eness. /nstead# generic a""licants must scientificall% demonstrate that their "roduct is !ioe&ui'alent (i.e.# "erforms in the same manner as the inno'ator drug .

;ne wa% scientists demonstrate !ioe&ui'alence is to measure the time it ta*es the generic drug to reach the !loodstream in 2B to .A health%# 'olunteers. This gi'es them the rate of a!sor"tion# or !ioa'aila!ilit%# of the generic drug# which the% can then com"are to that of the inno'ator drug. The generic 'ersion must deli'er the same amount of acti'e ingredients into a "atient-s !loodstream in the same amount of time as the inno'ator drug. Using !ioe&ui'alence as the !asis for a""ro'ing generic co"ies of drug "roducts was esta!lished !% the <Drug Price Com"etition and Patent Term Restoration Act of 1(7B#< also *nown as the Da$man8=atch Act. This Act e$"edites the a'aila!ilit% of less costl% generic drugs !% "ermitting FDA to a""ro'e a""lications to mar*et generic 'ersions of ( Pharmaceutical !rand8name drugs without conducting costl% and du"licati'e clinical trials. At the same time# the !rand8name com"anies can a""l% for u" to fi'e additional %ears longer "atent "rotection for the new medicines the% de'elo"ed to ma*e u" for time lost while their "roducts were going through FDA-s a""ro'al "rocess. Irand8name drugs are su!9ect to the same !ioe&ui'alence tests as generics u"on reformulation. For more information on generic drug !ioe&ui'alenc% re&uirements# "lease see the cha"ter entitled <FDA 2nsures 2&ui'alence of ( Pharmaceutical :eneric Drugs< in <From Test Tu!e to Patient6 /m"ro'ing =ealth Through =uman Drugs.< For decades# the regulation and control of ("harmaceutical new drugs in the United States has !een !ased on the +ew Drug A""lication (+DA . Since 1(.7# e'er% new drug has !een the su!9ect of an a""ro'ed +DA !efore U.S. commerciali>ation. The +DA a""lication is the 'ehicle through which drug s"onsors formall% "ro"ose that the FDA a""ro'e a new "harmaceutical for sale and mar*eting in the U.S. The data gathered during the animal studies and human clinical trials of an ( "harmaceutical in'estigational +ew Drug (/+D !ecome "art of the +DA. The goals of the +DA are to "ro'ide enough information to "ermit FDA re'iewer to reach the following *e% decisions6 Dhether the ( "harmaceutical drug is safe and effecti'e in its "ro"osed use(s # and whether the !enefits of the drug outweigh the ris*s. Dhether the ( Pharmaceutical drug-s "ro"osed la!eling ("ac*age insert is a""ro"riate# and what it should contain.

Dhether the methods used in ("harmaceutical manufacturing the drug and the controls used to maintain the drug-s &ualit% are ade&uate to "reser'e the drug-s identit%# strength# &ualit%# and "urit%. The documentation re&uired in an +DA is su""osed to tell the drug-s whole stor%# including what ha""ened during the clinical tests# what the ingredients of the drug are# the results of the animal studies# how the drug !eha'es in the !od%# and how it is manufactured# "rocessed and "ac*aged. The following resources "ro'ide summaries on +DA content# format# and classification# "lus the +DA re'iew "rocess6 *ood 4anufacturing Practices guidelines its importance in "gmp guidelines# For Pharmaceutical Industry+ A drug, medical device can be treated as adultrated even if they pass or comply all the final specifications and are found to be manufactured where in a condition where current good manufacturing practices are not followed properly or cgmp guidelines are found to be violated. cgm" guidelines com"rises of the general re&uirements for manufacturing of a drug or a medical de'ice# food and acti'e "harmaceutical ingredients# diagnostics. :ood manufacturing "ractices guidelines are general guidelines with which manufacturer is re&uired to com"l% with !ut are not how to com"l% with them guidelines# a "harmaceutical manufacturer ma% ada"t their own &ualit% s%stems so as to com"l% with good manufacturing guidlines# good manufacturing guidelines are more or less similar world wide. Regulator% agencies (FDA-s around the world# can ins"ect the manufacturing firms for com"liance of good manufacturing "ractices with or without "rior notice in a reasona!le time (when e'er the firm is o"en for a !usiness or acti'it% . Current good manufacturing practices regulations for combination products+ There is no se"arate cgm" guidelines regulations for com!ination "roducts # !ut the each and e'er% "art of the com!ination "roduct is re&uired to com"l% se"aratel% as a single entit% with res"ecti'e good manufacturing "ractices guidelines# which include 21 cfr "art 210 and 211 good manufacturing guidelines for drugs or "harmaceutical finished

"roduct# and 21 CFR Parts A008A70 which "ro'ides good manufacturing "ractices guidelines for !iological "roducts # 21 CFR Part 720 for Kualit% s%stem (KS regulation for medical de'ices # when a !iological "roduct is de'elo"ed in to a medical de'ice it is re&uired to follow com"l% and follow good manufacturing "ractices guidelines 21 CFR Parts A008A70 as well as 21 CFR Part 720 together. =ow to calculate %ield and sta!ilit% of drug "art in a com!ination "roduct6 The% are re&uired to com"l% with 21 CFR 211.10. regulations as well as 21 CFR 211.1AA for sta!ilit% of the drug. Corrective and preventive actions "C(P(# for combination products: For medical de'ice in a com!ination "roduct 21 CFR 720.100 descri!es Correcti'e and "re'enti'e actions (CAPA and for drug "roduct it is gi'en as a general guidelines in Production Record Re'iew (21 CFR 211.1(2 . 5atest updates by &' FD( on current good manufacturing practices freshly issued guidelines: U S FDA has issued a fresh good manufacturing "ractices guidelines for Transdermal drug deli'er% s%stems# transmucosal drug deli'er% s%stems# and for all other related drug deli'er% s%stems li*e drug s"ra%s and a""lication# where drug affect !% s%stemic a!sor"tion in to !lood . US FDA has now re&uires that the initial drug load in the Transdermal drug deli'er% s%stems !e minimum and rational# and the% re&uire that the residual drug load must !e mentioned along with the logical e$"lanation for getting an a""ro'al for such drugs Read in detail what all about here Good manufacturing practices guidelines on Transdermal drug delivery system We have outlined in brief all the sections of ! "#R part !! topics which of current good manufacturing practices they address. Current *ood manufacturing practices for penicillin and betalactum drugs:

There are following re&uirements for manufacturing as well as re"ac*ing of "enicillin drug "roducts /t re&uires that there must !e com"lete control on all "rocess so as that cross contamination of other drug with !etalactum and "enicillin drug do not occur. US FDA5S 21 CFR 211.B2(d re&uire that there must !e se"aration of facilit% and e&ui"ment for manufacturing of !etalactum and "enicillin drugs. 21 CFR 211.BA(d Re&uire that there must !e se"arate A/R =andling s%stem for manufacturing aria where !etalactum and "enicillin drugs are manufactured 21 CFR 211.1)A6 Re&uire that the tests must !e in "lace to find out a!sence or traces of "enicillin where e'er there are chances of e$"osure. At the same time acti'e "harmaceutical ingredient are also re&uired to !e manufactured with similar re&uirements so as to "re'ent cross contamination Dhen some one is sic* he goes to a doctor and doctor after diagnosis suggest some treatment and some medicines# im"ortance of those few ta!lets and s%ru" or an in9ection is well understood !% the "atient and their *iths and *in# these medicines are some times life sa'ing drugs and medical de'ices# the few milligram dose of the acti'e constituent in the drug and the su""ort of a medical de'ice is 'er% critical for "atient# what will ha""en when those drugs them self !ecome life threatening to them. 2$am"le thalidomide. Therefore along with de'elo"ment of "harmaceutical industr% almost e'er% countr% in world is regulating the drugs and medical de'ices food and acti'e "harmaceutical ingredients# diagnostics# which their citi>ens use or consume. United States Food and Drugs Administration is one of the !est regulator% agenc% amongst all in world in medicine and medical de'ice regulations e$am"le is the re9ection of drug contain thalidomide !% US FDA in 1(A0 while it was a""ro'ed in 2uro"ean and other countries which is one of the !est e$am"le how US FDA ta*e care of

health of American citi>ens# otherwise at that time# 9ust li*e other "art of world# se'eral children would ha'e !een !orn in countr% without lim!s and lim! deformities !ecause of consum"tion of drug thalidomide !% "regnant mothers# (the one who re9ected thalidomide is a women US FDA em"lo%ee at that time . A"art from a""ro'al of an% new drug# regulator% agencies around world form regulations for "harmaceutical and medical de'ices# acti'e "harmaceutical ingredients# diagnostics# manufacturing which guide manufacturers a!out what "recautions the% must ta*e for safe and efficient "roduction of drugs and medical de'ices acti'e "harmaceutical ingredients# diagnostics with which the manufacturer will !e a!le to ensure and assure them sel'es as well as rest of the world that the medicines and medical de'ices# acti'e "harmaceutical ingredients# diagnostics !eing manufactured or !een manufactured at their "remises are com"letel% safe effecti'e# and com"lies to re&uired &ualit% standards at an% gi'en times s"an of the self life of the drug or medical de'ice acti'e "harmaceutical ingredients# diagnostics# these guidelines are called as good manufacturing "ractices which are a!!re'iated as gm" guidelines# gm" guidelines constitute guidelines for ma*ing fool"roof &ualit% assurance s%stems or &ualit% s%stems. /m"ortant constitution of good manufacturing guidelines are more or less similar world wide# with the ultimate goal of achie'ing "roduction of &ualit% drugs . The good manufacturing "ractices guidelines *ee"s on changing with time toward im"ro'ement as and when there is some im"ro'ing or u" gradations ha""ening in the manufacturing and &ualit% assurance s%stems and there for one which is u"dated with such im"ro'ising factors and changes are called as current good manufacturing guidelines. :ood manufacturing "ractices guidelines (gm" guidelines are integral "art of an% &ualit% s%stems therefore failure of the &ualit% assurance s%stem or &ualit% s%stem is critical and damaging to the !asis of the &ualit% assurance in turn &ualit% of drugs and medical de'ices manufactured# and hence would not !e afforda!le and acce"ta!le !% either manufacturer or regulator% agencies. Therefore &ualit% assurance s%stems are rooted u" to the ultimate !ases of the all functions which are related to medical de'ice and

"harmaceutical manufacturing# therefore origin of the &ualit% assurance in a "harmaceutical and medical de'ice com"an% is at almost at e'er% "oint and stages in'ol'ed in medical de'ice and "harmaceutical manufacturing. Therefore the "ersonnel5s res"onsi!le for timel% "roduction must !e trained as "rime &ualit% !uilding "ersonals in to &ualit% assurance s%stems. Some of the !asics common arias of good manufacturing "ractices are as follows. 1.Kualit% assurance general Princi"les # the guidelines outline !asic fundamental re&uirements of &ualit% assurance in a "harmaceutical and medical de'ices food # and acti'e "harmaceuticals manufacturing. 2.Kualit% control "rinci"als # good manufacturing "ractices guidelines gi'es !asic detailed re&uirements of &ualit% control de"artment and what is re&uired and e$"ected functions of the &ualit% control de"artment in a "harmaceutical com"an%. 2. Sanitation and h%giene is one of the ma9or aria of ins"ection !% FDA .. Lalidation# "rocess 'alidations !asic re&uiems we ha'e "u!lished com"lete detailed information a!out "rocess 'alidation and software 'alidation re&uirements # cleaning 'alidation in "harma. B. Com"laints# handling of mar*et com"laints# guides a!out how to handle an% mar*et com"laints a!out drug "roduct. M. Contract "roduction and anal%sis guidelines guide a!out what are the re&uirements when a "harmaceutical manufacturer gets "harmaceuticals or food# medical de'ices # it clearl% s"ecif% the res"onsi!ilities of !oth contract manufacturer and contract gi'er. A. Self8ins"ection and &ualit% audits# which are 'er% im"ortant in !uilding a full "roof &ualit% assurance s%stem. ). Personnel# "ersonnel training# "ersonal h%giene. :uidelines a!out "ersonal h%giene health chec* u"s and 7. Premises. :ood manufacturing "ractice guidelines on "remises s"ecif% how good and se"arated # clean should !e the "remises so as

to "re'ent cross contamination and "ro"er segregation and storage of goods and materials is facilitated. /t also gi'es se"aratel% all re&uirements for sterile dosage forms and ase"tic arias and clean room re&uired in sterile drug manufacturing. (. 2&ui"ments6 :,P guidelines on e&ui"ments gi'es com"lete re&uirement of their cleaning maintenance# "re'enti'e maintenance# 'alidation# and documentations in "roduction as well as in "rocess testing and &ualit% control testing. 10. ,aterials# good manufacturing "ractices guidelines a!out materials guide a!out material including starting material# in "rocess "roduct to finished "roducts in good manufacturing "ractices guidelines great em"hasis is gi'en o material handling # storage and issue and recalled material include all materials including raw material# "ac*aging and finished "roducts. 11.Documentation 6 :ood manufacturing guidelines a!out documentation "ro'ide in details a!out what t%"es of documents# are re&uired and how those should !e generated and how to "reser'es and utili>e them# including documents generated from com"uter s%stem and standard o"erating "rocedures ( so" . The world health organi>ation good manufacturing "ractices guidelines are followed a""ro$imatel% in hundred de'elo"ing countries# while 2U :,P is followed in the countries under 2uro"ean Union# /n US c gm" guidelines issued !% US FDA are followed and in U.E good manufacturing "ractices guidelines are termed as orange guidelines. /C= good manufacturing "ractices are followed !% countries which are signatories to /nternational Conference on =armoni>ation /C= (/n 2uro"ean union countries # US and Na"an # Australia# Canada# Singa"ore ha'e ada"ted the /C= :,P guidelines. /n United States "harmaceutical com"anies are re&uired to com"l% with the 'arious good manufacturing "ractices and regulation for food and drugs.The 21CFR PART 211 "ro'ides in details guidelines a!out current good manufacturing "ractices for finished "harmaceuticals. The !ul* drug and acti'e "harmaceutical ingredients which are not

su!9ect to 21 cfr 210 and 211 regulations !ut must com"l% with general standards of current good manufacturing "ractice Pharmaceutical validation /n "harmaceutical manufacturing industr% 6alidation is 'er% im"ortant "art of Kualit% assurance and in :ood manufacturing Practice acti'ities or guidelines. FDA gi'es s"ecial em"hasis on 'alidation3 also it is one of the "rime re&uirement of all regulator% authorities world wide. /t is of great im"ortance in Pharmaceutical manufacturing as well as medical de'ices manufacturing industr%. Lalidation is a "rocess of collection of documentar% e'idence3 it is a "rocess of demonstration that an% of the "rocedure# "rocess# method# or acti'it% is !eing ada"ted is ca"a!le of "roducing consistent and satisfactor% result in terms of measurements or in terms of "roduct &ualit%. To demonstrate this it is re&uired that the s%stems it self and e&ui"ment are "ro"erl% designed and &ualified. To demonstrate that a "harmaceutical "roduct manufactured with an% "rocess in an% "harmaceutical com"an% it is re&uired to 'alidate man% "rocedures# "rocesses# methods acti'ities associated with "harmaceutical manufacturing including machiner% # s*ills and testing "rocedures # methods. Pharmaceutical 6alidation definition: $alidation can be defined as process of establishing through documented evidence a high degree of assurance that a specific process will consistently produce a product that meets its predetermined specifications and %uality attributes. & validated manufacturing process is one that has been proven to do what it purports or is represented to do. The proof of validation is obtained through collection and evaluation of data, preferably beginning from the process development phase and continuing through the production phase. $alidation necessarily includes process %ualification 'the %ualification of materials, e%uipment, systems, buildings, and personnel(, but it also includes the control of the entire processes for repeated batches or runs. 6alidation In pharmaceutical is classified as follo!s 1+Cleaning 6alidation Cleaning 'alidation is carried out to ascertain the "rocedure and method

ada"ted for cleaning of e&ui"ments # and aria # is ca"a!le of gi'ing desired cleanness # cleanliness of e&ui"ment can !e ascertained !% caring out trace anal%sis of acti'e ingredient of "re'ious "roducts acti'e ingredient trace anal%sis . !% doing rinse water anal%sis or swa! test# this is &uite good method to ascertain the com"lete remo'al of earlier "roducts residue so as to a'oid cross contamination we ha'e "ro'ided a com"lete e$am"le document for cleaning 'alidation here. 2+Process 6alidation Process 'alidation is carried out on the manufacturing "rocess or ste"s # which are ada"ted for during "harmaceutical manufacturing . The "rocess ada"ted in "harma manufacturing should %ield a consistent results with res"ect to &ualit% of "roduct. The laid down "rocess is crosschec*ed for e'idence for efficac% # and the results are documented for each ste". FDA guidelines define "rocess 'alidation as follows Process validation: The collection and e'aluation of data# from the "rocess design stage through commercial "roduction# which esta!lishes scientific e'idence that a "rocess is ca"a!le of consistentl% deli'ering &ualit% "roducts. For e$am"le in manufacturing of ta!lets a final mi$ing ste" is 'alidated !% withdrawing sam"les from all "oints in mi$er at intermittent inter'als # and assa% of acti'e ingredients is done# results are "lotted against res"ecti'e sam"le "oints and time inter'als # the #most efficient time inter'al at which there are consistent and satisfactor% result for desired content at all sam"ling "oint is considered to !e the !est for the "rocess of final mi$ing ste"# and this !est time inter'al "oint is again 'alidated !% crosschec*ing #and documenting on further three !atches. /t is one of e$am"le of "rocess 'alidation # it can e$tend to other "rocesses ada"ted in "harma manufacturing. /f there is an% "ro!lem in the "rocess 9ust !% anal%>ing the 'alidation results one can *now the ste" "oint or e&ui"ment or "rocess which is res"onsi!le for an% untoward result. -ypes of validations in pharmaceutical6 Following are the t%"es in "harmaceutical 'alidations What is prospective validation$ Pros"ecti'e 'alidation is "rocess of gathering of data and documentar% e'idence a!out a "roduct and its "rocess !efore it is sent to mar*et or

for distri!ution# a new "roduct 'alidation or a 'alidation after ma*ing a change in the master formula# to determine if the "roduct meet its "redetermined standards. The "rocess starts with designing of !atch record # raw material s"ecification and in "rocess s"ecifications and limits #esta!lishing sam"ling "lan# and e&ui"ment lists and re&uired en'ironment controls. Concurrent validation /s a 'alidation "rocess where in current "roduction !atches are used to confirm the com"liance of "rocessing "arameters and standards. Concurrent 'alidation is the set of 'alidation "rocedures following "ros"ecti'e 'alidation. Concurrent 'alidation is carried out for ensuring the "roduct !atches "roduced in "ros"ecti'e 'alidation meet the re&uired standards and &ualit% so that those can !e distri!uted in mar*et. Concurrent 'alidation is of great use when the test em"lo%ed is not destructi'e and can determine the "roduct meet "redetermined standards and &ualit%. Concurrent 'alidation is also carried out on "roduct or "rocess which is "re'iousl% 'alidated "rocess to ascertain that the "roduct or the "rocess meets re&uired standards and is 'alidated. What is Retrospective 6alidation$ Retros"ecti'e Lalidation is a t%"e of 'alidation where in the "roduct is alread% and esta!lished "rocess such !atches of "roducts which are !eing sent to mar*et are studied to gather documentar% e'idence a!out the efficac% of the "rocess or an% in "rocess tests and the "roduct it self# such t%"e of 'alidation can !e ada"ted to 'alidate "roduct and the "rocess e'en if the "roduct and "rocess is not 'alidated earlier. /t also ma*es use of data from old !atches to esta!lish the efficac% and com"liance of "roduct or "rocess standards. 7+(nalytical 4ethod 6alidation =ere the method which is ada"ted to estimate the content# assa%# "urit% or standard of a "harmaceutical "roduct# tested for its efficac% and accurac% # that is it is assessed if the method ada"ted is ca"a!le of gi'ing consistent and correct results without an% error # e'en though there is change in chemicals# instrument or "erson . The method ada"ted should !e such that it should !e a!le to detect the content# assa%# "urit% or standard of "harmaceutical "roduct without an%

error e'en if there is a change in change in chemicals# instrument or "erson and this has to !e 'alidated !% crosschec*ing se"aratel% and documented as e'idence for efficac% and efficienc% of method ada"ted. 8+Computer 'ystem 6alidation: The com"uteri>ed s%stem which are ada"ted in manufacturing of "harmaceuticals is tested for their worthiness # if the actual readings o!tained from s%stem # and those o!tained in manuall% in "rocess are !oth matching and are accurate and satisfactor% so as to rel% com"letel% on the com"uter s%stems ada"ted in the "rocess of "harmaceutical manufacturing and &ualit% control # and &ualit% assurance # and stores acti'it%# rules go'erning com"uterised s%stem 'alidation # electronic signature and document generated through com"uterised s%stems are included in 21 cfr Part 11 of the United states code of federal regulations. 6alidation Phases: The acti'ities relating to 'alidation studies ma% !e classified into three "hases6 Phase 16 Pre8Lalidation Phase or the Kualification Phase# which co'ers all acti'ities relating to "roduct research and de'elo"ment# formulation# "ilot !atch studies# scale8u" studies# transfer of technolog% to commercial scale !atches# esta!lishing sta!ilit% conditions# storage and handling of in8"rocess and finished dosage forms# 2&ui"ment Kualification# /nstallation Kualification# master "roduction documents# ;"erational Kualification# Process Ca"a!ilit%. Phase 2: Process Lalidation Phase (Process Kualification "hase designed to 'erif% that all esta!lished limits of the Critical Process Parameters are 'alid and that satisfactor% "roducts can !e "roduced e'en under the <worst case< conditions. Phase 7: Lalidation ,aintenance Phase re&uiring fre&uent re'iew of all "rocess related documents# including 'alidation audit re"orts to assure that there ha'e !een no changes# de'iations# failures# modifications to the "roduction "rocess# and that all S;P-s ha'e !een followed# including Change Control "rocedures and &ualif%ing s%stems #e&ui"ments are re&uired to &ualif% for following Kualifications6 1+Design 9ualification "D:# 2+Component 9ualification "C:#

7+Installation 9ualification "I:# 8+;perational 9ualification ";:# <+Process 9ualification "P:# Design :ualification "D:#8 /t consists "rocess of gathering documentar% e'idence of a "articular instruments or machine5s fundamental o"erational and functional s"ecification of an instrument # and its inherent "rogram # or e&ui"ment and details a!out and its detailed design and its &ualifications # wh% this instrument and is su""lier chosen. Installation :ualification "I:# 8 /t consists "rocess of gathering documentar% e'idence and "rocess of Demonstration that the "rocess or e&ui"ment !eing installed com"lies with all of its &ualifications of successful installation in a "articular aria # so as to com"l% with intended re&uirements of "rocess # with res"ect to its s"ecifications# is it installed correctl%# are all necessar% accessories and com"onents installed correctl% and its documentation re&uired for continued utili>ation are installed "ro"erl%. ;perational :ualification ";:# 8 /t consists "rocess of gathering documentar% e'idence and of Demonstration of all as"ects of a e&ui"ment # "rocess are functioning "ro"erl% and accuratel% so as to %ield intended #measurements# results &ualit% of a "harmaceutical !eing manufactured. Performance :ualification "P:# 8 /t consists "rocess of gathering documentar% e'idence and "rocess of Demonstration of all as"ects of a e&ui"ment # "rocess are functioning "ro"erl% and accuratel% so as to "roduce intended #measurements# results # intended &ualit% of a "harmaceutical manufactured o'er a "eriod of time. in a consistent manner 6alidation 4aster Plan /t is a document which identifies and "ro'ides com"lete ste"s# guide or ma" or guidelines for caring out a "articular 'alidation "rocedure. Dhere e'er there is re&uirement of an% 'alidation # Lalidation "rocedure is first assigned a Lalidation ,aster Plan. -he 6alidation Process

/t is a "rocess of monitoring #testing#and e'aluation of all ste"s and "rocess in'ol'ed in a "harmaceutical manufacturing 6alidation Protocol 6 All ste"s in "harmaceutical "rocess are 'er% im"ortant ste"s# and to ensure the "rocess wor*s with re&uired standard "harmaceutical "rocess 'alidation is carried out# the com"lete details a!out 'alidation "rocess stages# "rocedures# and tests# standards# locations# "ersons res"onsi!le and underta*ing or doing 'alidation "rocedures# etc# the detailed road ma" detailed information of how to do things in a well documented format to carr%out the 'alidation "rocedure is termed as 'alidation "rotocol# 'alidation "rotocol also mentions# what should !e done# if there is an% de'iation from the "rocess# what should !e done when the 'alidation !atches it self are re&uired to !e distri!uted to mar*et and so on. Computer system 6alidation: /t re&uires that the software or "rograms which are utili>ed !% "harmaceutical com"anies in manufacturing of "harmaceuticals should wor* without an% error# it "ro'ides or leads to an accurate measures or acti'it% .2$am"le Dis"ensing of Raw ,aterial using com"uterised s%stem. Process control using a com"uterised s%stem /n 21 CFR Part 11 this to"ic is co'ered in 'er% detail and %ou can read it o'er here =ere screen shot "rints are gathered to 'alidate and document that the "rocedure ada"ted is leads to correct measures or acti'it% Com"lete details a!out Com"uter s%stem Lalidation6 6alidation 5ife cycle: Dhene'er an% s%stem or e&ui"ment is set for its 'alidation to 'erif% that it meets to the re&uired criteria of o"eration # and &ualit%# a com"rehensi'e 'alidation life c%cle is formed to *ee" the integrit% of the s%stems 'alidit%. Re'alidation6 /t is a most im"ortant as"ect in 'alidation # once a 'alidation for a drug "roduct# machiner%# or e&ui"ment# or a water "urification s%stem# re'alidation is mandator% !% current good manufacturing "ractices# here %ou will find when to do re'alidation

We can classify of Revalidation as follo!s 1 Re'alidation after an% change in the "roduct formula# "rocess #method which affect the &ualit% of "roduct. 2 Scheduled "eriodic Re'alidation. Revalidation after changes+ /t is mandator% to carr% out re'alidation if there are changes made in manufacturing "rocess# "rocedures# methods# formula# e&ui"ments# raw material# "ac*aging material# manufacturing aria su""ort s%stems li*e water and steam# and in "rocess controls or an% other changes in an esta!lished &ualit% "roduct which ma% alter or affect the &ualit% of the "roduct. Kualified 'alidation team should re'iew an% re&uested changes in a!o'e mode# and decide a!out the re'alidation and re'alidation "rocedure. Some of the "erformance tests and "rocedures# for "rocess and e&ui"ments ada"ted while carr%ing out first 'alidation ma% !e ada"ted in the re'alidation as well. Which are the ma=or changes !hich re9uire revalidation$ Ra! material, starting material: Drug "roduct and its "rocess should !e re'alidated if there are changes in the starting material# e'en if there are change in the "h%sical "ro"erties of the starting material li*e cr%stal "ro"erties# 'iscosit%# !ul* densit%# s"ecific gra'it%# "article si>e distri!ution of the acti'e as well as e$ci"ients as these "h%sical "ro"erties might ad'ersel% affect the "rocess and then "roduct &ualit%. Pac%aging material: /f there are changes done in "ac*aging material re'alidation must !e done if the "ac*aging material comes directl% in contact with dosage form as well as if the "h%sical "ro"erties of the "ac*aging material !eing changed ma% affect the sta!ilit% and &ualit% of the drug. 4anufacturing process: Re 'alidation must !e done whene'er there are changes in manufacturing "rocess li*e change in the time re&uired for the "rocess li*e mi$ing# homogeni>ation# recirculation cooling time# and tem"eratures a""lied for 'arious "rocesses.

.9uipments: Re 'alidation must !e done whene'er there are changes in e&ui"ment li*e instruments used for 'arious measurements in manufacturing and in "rocess &ualit% assurance# e'en their re"air and changes in the s"are "arts and com"onents must !e considered for re'alidation. 'upport systems and maintenance Re'alidation must !e done whene'er there are changes and re"airing is done in the su""ort s%stems ( water s%stem 'entilation and air handling s%stems and "roduction area these changes ma% !e critical on "roduct &ualit%# for e$am"le if the manufacturing aria is for sterile "roducts which ma% affect "roduct &ualit%# clean room en'ironment and sterilit% of the "roduct in case of sterile "roduct manufactured !% ase"tic "rocess. See also media fill run Why there should be periodic revalidation: A drug "roduct ma% under go changes o'er the time for im"ro'ement in its formulation for efficac% and &ualit%# the e&ui"ment and the su""ort s%stems ma% undergo wear and tear as well# therefore re'alidation !ecomes im"ortant re&uirement hence ada"ting a intentionall% and "re"lanned scheduled re'alidations ena!les a firm to !e re"aired and !e ca"a!le of conducting re'alidation efficientl% and effecti'el%. Re'alidations conducted and "lans are ins"ected !% regulator% agencies world wide during FDA ins"ections. The fre&uenc% and "eriod of re'alidation can !e decided !% stud%ing data collected on regular !asis from all in "rocess &ualit% control "arameters and &ualit% control re"orts of finished "roduct. Important points before revalidation must be verified: /m"lementation of re'ised standard o"erating "rocedures. Anal%tical method# if there are an% changes in the anal%tical methods the% must !e 'alidated !efore the "rocess re'alidation u" on which all results de"end. Scheduled cleaning and saniti>ation "lan com"leted. Pre"aration of master formula if there is an% change in the "roduct formula Change in !atch si>e# rational for change# and its effect on the &ualit% of the "roduct should !e considered !efore im"lementation and then considered for re'alidation. Cali!ration of instruments# which will !e used during the "rocess after a change# is im"lemented.

Pre'enti'e maintenance is com"leted. /t should !e com"leted on schedules.

List of regulation titles

Code of Federal Regulations, seen at the Mid-Manhattan Library. Editions of Title 3, on the President, are kept on ar hi!e. "oti e that for the first year of ea h ne# presiden y, the !olu$e is thi ker. Title %& 'eneral Pro!isions Title (& 'rants and )gree$ents Title 3& The President Title *& ) ounts Title +& )d$inistrati!e Personnel Title ,& -o$eland .e urity Title /& )gri ulture Title 0& )liens and "ationality Title 1& )ni$als and )ni$al Produ ts Title %2& Energy Title %%& Federal Ele tions Title %(& 3anks and 3anking Title %3& 3usiness Credit and )ssistan e Title %*& )eronauti s and .pa e 4also kno#n as the Federal )!iation Regulations, ad$inistered by the Federal )!iation )d$inistration5 Title %+& Co$$er e and Foreign Trade Title %,& Co$$er ial Pra ti es Title %/& Co$$odity and .e urities E6 hanges Title %0& Conser!ation of Po#er and 7ater Resour es Title %1& Custo$s 8uties

Title (2& E$ployees9 3enefits Title (%& Food and 8rugs 4ad$inistered by the :. Food and 8rug )d$inistration and the :. 8rug Enfor e$ent )d$inistration5 Title ((& Foreign Relations Title (3& -igh#ays Title (*& -ousing and :rban 8e!elop$ent Title (+& ;ndians Title (,& ;nternal Re!enue Title (/& )l ohol, Toba o Produ ts and Firear$s Title (0& <udi ial )d$inistration Title (1& Labor Title 32& Mineral Resour es Title 3%& Money and Finan e& Treasury Title 3(& "ational 8efense Title 33& "a!igation and "a!igable 7aters Title 3*& Edu ation Title 3+& Reser!ed 4for$erly Pana$a Canal5 Title 3,& Parks, Forests, and Publi Property Title 3/& Patents, Trade$arks, and Copyrights Title 30& Pensions, 3onuses, and =eterans9 Relief Title 31& Postal .er!i e Title *2& Prote tion of En!iron$ent 4ad$inistered by the :nited .tates En!iron$ental Prote tion )gen y5 Title *%& Publi Contra ts and Property Manage$ent Title *(& Publi -ealth Title *3& Publi Lands& ;nterior Title **& E$ergen y Manage$ent and )ssistan e Title *+& Publi 7elfare Title *,& .hipping Title */& Tele o$$uni ation 4also kno#n as the >FCC Rules>, ad$inistered by the Federal Co$$uni ations Co$$ission5 Title *0& Federal ) ?uisition Regulations .yste$ Title *1& Transportation Title +2& 7ildlife and Fisheries