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GCCD MANUIAC1UkING kAC1ICL IN 1nL

nAkMACLU1ICAL INDUS1k



Worklng paper 3, prepared for Workshop on '1raclng harmaceuLlcals ln SouLh Asla',
2-3 !uly 2007, unlverslLy of Ldlnburgh






lunder: LS8C / uflu
Lead auLhors: eLra 8rhllkova, lan Parper, and Allyson ollock, wlLh lnpuLs from SoumlLa
8asu, SamlLa 8haLLaral, Abhl[lL uas CupLa, SLefan Lcks, aLrlcla !effery, 8oger !effery,
nlLu Slngh, and Madhusudan Sharma Subedl
hLLp://www.healLh.ed.ac.uk/ClP/ourresearch/ulluLS8CLraps.hLm
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
2
1. Cb[ect|ves

1he alm of our sLudy ls Lo map regulaLlon, producLlon, dlsLrlbuLlon and consumpLlon of
pharmaceuLlcals ln Lwo SouLh Aslan counLrles, namely lndla and nepal and Lo undersLand Lhe
conLexLs of pharmaceuLlcal use ln SouLh Asla. 1hls paper ls concerned wlLh Lhe role of regulaLlon
and lLs enforcemenL ln lndla and nepal wlLh respecL Lo one speclflc regulaLory requlremenL -
Cood ManufacLurlng racLlce (CM)
1
- Lhe guldellnes whlch govern Lhe producLlon, dlsLrlbuLlon
and supply of a drug.

Compllance wlLh CM ls a necessary condlLlon for markeLlng auLhorlzaLlon, ln oLher words
domesLlc and forelgn producers of pharmaceuLlcal companles cannoL sell or markeL Lhelr drugs
wlLhouL lL ln Lhe WesL and norLh. Whlle CM compllance has noL been unlversally adopLed ln
Lhe developlng world, governmenLs ln less developed counLrles are under pressure Lo comply
wlLh CM requlremenLs when granLlng markeLlng auLhorlzaLlons Lo domesLlc companles and
Lhe WesL has developed a varleLy of sLraLegles Lo ensure LhaL developlng counLrles adopL Lhe
rules. CM requlremenLs requlre ma[or lnvesLmenL ln upgradlng manufacLurlng faclllLles and
Lhls has lmpllcaLlons for local producers. An lnLeresLlng emplrlcal quesLlon ls Lhe lmpacL of Lhese
changes on local markeLs and on access Lo and affordablllLy of medlclnes ln developlng
counLrles.

1he pharmaceuLlcal lndusLry operaLes ln a mulLl bllllon pound/euro/dollar global markeL place.
lLs operaLlons are hlghly complex and so Loo ls lLs governance or regulaLlon. 1here ls a pleLhora
of cross cuLLlng supranaLlonal and naLlonal regulaLory sLrucLures and legal sysLems Lo navlgaLe,
buL Lhe key Lo undersLandlng Lhese reglmes ls Lhe way ln whlch Lhey llnk Lo Lrade reglmes and
sancLlons. lrom Lhe perspecLlve of developlng counLrles, Lhe WesL has esLabllshed Lhe rules of
Lrade and seL Lhe barrlers for markeL enLry. 1hese rules orlglnaLe ln Lhe Lu and uS buL lf
successfully overcome, are Lhe gaLeway Lo new markeLs. 1he large mulLlnaLlonal lndlan
pharmaceuLlcal companles have now adapLed Lhelr manufacLurlng processes Lo comply wlLh
lnLernaLlonal rules and sLandards. So Loo have Lhelr governmenLs as slgnaLorles Lo Lrade reglmes

1
WlLh respecL Lo pharmaceuLlcal supply chaln, lL ls lmporLanL Lo look also aL Cood ulsLrlbuLlon racLlce (Cu) and
Cood SLorage racLlce (CS). 1he CM sLandards Lyplcally lnclude recommendaLlons on boLh, Lhe Cu and CS, we
wlll need Lo pay aLLenLlon Lo Lhe exLenL Lo whlch CMs cover Cu and CS and Lhe dlfferences ln coverage
beLween developed and developlng counLrles. 1he presenL verslon of Lhe paper deals malnly wlLh CM sLandards.
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
3
Lhrough Lhe W1C and oLher Lrade LreaLles: lndla, for lnsLance, ls currenLly seLLlng up a CenLral
urugs AuLhorlLy of lndla slmllar Lo Lhe uS lood and urug AdmlnlsLraLlon.
2
ln Lhe nexL secLlon we
explore Lhe raLlonale for and Lhe naLure and evoluLlon of Lhese rules from Lhe economlc and Lhe
publlc healLh perspecLlve.

2. 1he ro|e and types of pharmaceut|ca| regu|at|on - |nformat|on asymmetry and consumer
protect|on

1he need for regulaLlon derlves from lnformaLlon asymmeLry beLween Lhe pharmaceuLlcal
producers on one slde and consumers and medlcal pracLlLloners on Lhe oLher slde. 1haL means
LhaL consumers are noL able Lo assess safeLy or observe quallLy and efflcacy of medlclnes on
Lhelr own and nelLher can Lhe medlcal pracLlLloners who declde on Lhelr behalf. 1he
pharmaceuLlcal lndusLry ls Lhe maln knowledge generaLor ln Lhe fleld. 1he response Lo
lnformaLlon asymmeLry ls Lhe requlremenL by Lhe sLaLe for consumer and publlc Lo puL ln place
regulaLory safeguards aL every sLage of Lhe pharmaceuLlcal producLlon cycle Lo ensure LhaL all
drugs are properly LesLed and produced and LhaL LesLs resulLs avallable Lo regulaLory auLhorlLles
are compleLe and unblased. 1here ls no sLage of drug llfe cycle whlch ls noL regulaLed and
documenLed wheLher lL ls Lhe laboraLory phase of a new molecular enLlLy dlscovery, LesLlng ln
cllnlcal Lrlals, or Lhe llcenslng, manufacLurlng, and dlsLrlbuLlon.

ueLalled accounLs of Lhe hlsLory of pharmaceuLlcal regulaLlon can be found ln Lee and PerzsLeln
(1986), ermanand (2006), 8ralLhwalLe & urahos (2000), uanzon & keuffel (2003), and lmmel
(2000). ln brlef, Lhe regulaLlon of pharmaceuLlcals evolved aL Lhe naLlonal level ln response Lo
publlc healLh concerns (Lyplcally, urged by drug dlsasLers LhaL requlred lmmedlaLe changes and
sLrengLhenlng of safeguards). WlLh globallzaLlon of pharmaceuLlcal markeLs, some aspecLs of
regulaLlon, especlally Lhose concernlng quallLy, safeLy and efflcacy, were Laken Lo Lhe
supranaLlonal level. 1he complexlLy of Lhe area means LhaL lL ls noL wlLhln Lhls paper's remlL Lo
provlde an overvlew or comprehenslve accounL of pharmaceuLlcal regulaLlon excepL Lo draw
aLLenLlon Lo a number of areas of lnLeresL. llrsL, as we noLe aL Lhe ouLseL, regulaLlon ls sLrongly
llnked Lo Lrade and markeL enLry. Second, Lhe regulaLory reglmes, enforcemenL mechanlsms and
sancLlons vary conslderably across Lhe drug developmenL and producLlon cycle, dependlng on

2
See lndlan Lmbassy (2007) or 8ureau 8eporL (2007).
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
4
Lhe lnLeresLs and power of Lhe varlous parLles. 1hlrd, Lhe regulaLory codes Lhemselves vary boLh
ln sLrengLh and legal [urlsdlcLlon reflecLlng Lhe power and lnLeresLs of Lhe varlous sLakeholders.

AL one end of Lhe regulaLory specLrum ls Lhe W1C Lrade reglme whlch governs lnLellecLual
properLy and paLenLs. 1hls slLs ln Lhe regulaLory sLrucLure of Lhe W1C Lrade reglme known as
18lS. 1he 1reaLy was developed by and for Lhe pharmaceuLlcal lndusLry buL ls acLlvely
promoLed by governmenLs Lhrough Lhe W1C negoLlaLlng apparaLus. 1hls reglme unllke all Lhe
oLhers has lLs own law enforcemenL and dlspuLe seLLlemenL reglme llnked Lo Lrade sancLlons
and ls aggresslvely pursued. AL Lhe oLher end and by far Lhe weakesL end of regulaLlon ls self-
regulaLlon whlch ls used by pharmaceuLlcal and medlcal professlonal bodles wlLh respecL Lo
pharmaceuLlcal markeLlng and relaLlonshlps beLween medlcal pracLlLloners and pharmaceuLlcal
and oLher lndusLrles (e.g., coJe of ltoctlce of tbe Assoclotloo of tbe 8tltlsb lbotmoceotlcol
loJostty, coJe oo lotetoctloos wltb neoltbcote ltofessloools by Lhe harmaceuLlcal 8esearch
and ManufacLurers of Amerlca, or Aosttolloo lbotmoceotlcol Mooofoctotets coJe of cooJoct).
3


AL Lhe naLlonal level, Lhere are Lhe prlclng resLrlcLlons (lncludlng prlce celllngs for essenLlal drugs
and proflL marglns) and markeLlng agreemenLs (e.g., banns on u1CA ln mosL counLrles). llnally,
Lhere are Lhe quallLy and safeLy sLandards whlch govern Lhe llfecycle of drug producLlon and
dlsLrlbuLlon whlch are developed aL naLlonal level buL whlch are converglng Lhrough
lnLernaLlonal agreemenLs.
4
1able 1 lllusLraLes flve of Lhe key bodles ln Lhe wesL concerned wlLh
developlng lnLernaLlonal guldellnes ln respecL of Lhe drug llfe cycle (we examlne Lhese LogeLher
wlLh monlLorlng and enforcemenL ln laLer secLlons).
1able 1: harmaceuLlcal producLlon sLandards

Drug ||fe cyc|e Gu|de||nes WnC ICn LU Uk US

3
1he lncenLlves for self-regulaLlon mlghL be lnLrlgulng. 8ralLhwalLe (1993) dlscusses lnlLlaLlves of Clba-Celgy,
pharmaceuLlcal company wlLh bad repuLaLlon, Lo lnLroduce more sLrlngenL self-regulaLory sLandards. CerLalnly,
such sLandards or cerLlflcaLlon serves as a shorLcuL Lo a beLLer name. lnsLead of conLlnuous repuLaLlon bulldlng LhaL
Lakes decades of LrusLworLhy pracLlces, companles upgrade Lhelr sLandards aL once, rely on Lhe repuLaLlon of
regulaLory body or assoclaLlon approvlng Lhe sLandards or cerLlflcaLlon and suddenly [ump Lo Lhe hlgh quallLy
producers' club.
4
1he process of developlng Lhese sLandards has been more compllcaLed ln LhaL Lhey had been developed Lo a
cerLaln exLenL aL naLlonal level, Lhen Laken Lo Lhe lnLernaLlonal level Lhrough Lhe WPC, furLher ad[usLed and
sLrengLhened aL naLlonal level and agaln harmonlzed aL lnLernaLlonal level Lhrough Lhe lnLernaLlonal Conference on
ParmonlzaLlon. 1he flnallzed and harmonlzed sLandards are Lhen adopLed aL naLlonal level and posslbly ad[usLed
furLher Lo local condlLlons. See more deLalls ln SecLlon 3 on CM sLandards.
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
3
urug dlscovery Cood LaboraLory racLlce x x x x x
Cllnlcal Lrlals
(phase 1,2,3)
Cood Cllnlcal racLlce x x x x
ManufacLurlng Cood ManufacLurlng racLlce x x x x x
ulsLrlbuLlon Cood ulsLrlbuLlon racLlce x x x x x
osL-markeLlng
survelllance
harmacovlgllance x x x x x

SLandards are noL legal rules Lhey are guldellnes buL neverLheless when llnked Lo enforcemenL
reglmes and sancLlons can be very powerful. lor example, Lhe WPC CM sLandards and
lnspecLlons procedures LhaL are prlmarlly used ln developlng counLrles are llnked Lo markeLlng
auLhorlsaLlon and Lo procuremenL. 1hus Lhe WPC wlll noL procure drugs Lhrough Lhe Cul
unless Lhe company has CM. Slmllarly, Lhe WPC advocaLes for Lhe lmplemenLaLlon of publlc
drug procuremenL sysLems wlLh bullL-ln quallLy conLrol mechanlsms, Lyplcally represenLed by
Lhe requlremenL of CM cerLlflcaLes, ln developlng counLrles.
3
1he WPC also suggesLs sancLlons
LhaL should be lmposed on manufacLurers falllng Lo comply wlLh Lhe CM. 1he responslblllLy of
Lhe lmplemenLaLlon, monlLorlng and enforcemenL of Lhe CM ls however shlfLed Lo lndlvldual
governmenLs whlch ralses lssues abouL Lhelr capaclLy Lo do so.

2.1 1he trend towards harmon|sat|on of pharmaceut|ca| regu|at|on

1he flrsL sLeps Lo regulaLe Lhe pharmaceuLlcal lndusLry were Laken ln Lngland and SwlLzerland aL
Lhe break of Lhe 19
Lh
and 20
Lh
cenLury. ln Lhe uS, Lhe 8lologlcs ConLrol AcL of 1902 lnLroduced
requlremenLs on lnspecLlon and LesLlng of faclllLles and producLs of blologlcs manufacLurers and
Lhe ure lood and urug AcL of 1906 esLabllshed Lhe flrsL governmenL regulaLory agency (now
luA). CuallLy and safeLy conLrol mechanlsms were lnLroduced by naLlonal regulaLory auLhorlLles
ln response Lo healLh dlsasLers such as Lhe ellxlr sulfanllamlde
6
ln 1938 or Lhe Lhalldomlde
7
one
ln Lhe early 1960s (8ralLhwalLe and urahos 2000: 382). 1he uS lnLroduced flrsL safeLy sLandards
for pharmaceuLlcals ln 1938. AfLer Lhe Lhalldomlde Lragedy, Lhe uS lnLroduced even more

3
'uelhl Model' for publlc drug procuremenL ls such a sysLem and has been presenLed by Lhe WPC as an example Lo
follow ln oLher lndlan sLaLes as well as oLher developlng counLrles (see e.g. Chaudhury eL al. 2003).
6
Lllxlr sulfanllamlde was a Loxlc cough syrup LhaL kllled 107 people ln Lhe uS (8ralLhwalLe and urahos 2000).
7
1halldomlle was markeLed ln Lurope as a sleeplng plll and also prescrlbed Lo pregnanL women Lo LreaL mornlng
slckness. AlLhough safe ln adulLs, lL was Loxlc Lo feLuses. More Lhan 10000 bables were born wlLh deformlLles ln Lhe
1960s (8ralLhwalLe and urahos 2000).
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
6
sLrlngenL approval procedures requlrlng a proof of efflcacy ln addlLlon Lo safeLy before
markeLlng pharmaceuLlcal producLs. Luropean CommunlLy and many oLher counLrles followed
Lhe uS example and lnLroduced drug regulaLlon (8ralLhwalLe and urahos 2000: 382, Shadle
2004).

lrom Lhen, pharmaceuLlcal regulaLlon was shaped aL naLlonal level by varlous lncldenLs and Lhe
lnLeresLs of varlous sLakeholders ln pharmaceuLlcal lndusLry and healLh care. CounLrles have
been worklng Loward more complex and coherenL regulaLory requlremenLs, sLrengLhenlng and
addlng conLrol mechanlsms, maklng Lhe documenLaLlon of varlous processes and LesL resulLs
mandaLory. AlLhough Lhe markeL auLhorlzaLlon of new producLs became more cosLly Lo drug
producers, a hlgh level of quallLy and safeLy sLandards has Lwo maln beneflLs for lndusLry. llrsL,
Lhe fulfllmenL of regulaLory requlremenLs makes Lhe lndusLry 'LrusLworLhy'. Secondly, cosLs of
hlgh sLandards creaLe barrlers Lo markeL enLry and compeLlLlon and Lhus resulL ln concenLraLed
markeLs. 1he hlgh cosLs of regulaLlon and drug developmenL are used Lo argue for sLronger l
proLecLlon. SLrlcLly enforced l regulaLlon LogeLher wlLh CM creaLes addlLlonal barrlers Lo enLry
for generlcs producers who mlghL follow Lhe CM sLandards, Lhus susLalnlng monopollsLlc
markeLs.

1he global pharmaceuLlcal lndusLry ls a powerful player ln Lhe evolvlng pharmaceuLlcal
regulaLory landscape. 1here ls no doubL LhaL Lhe pharmaceuLlcal lndusLry ls a ma[or drlver
behlnd Lhe pollcy of harmonlsaLlon. 1hls ls noL Lo say LhaL pharmaceuLlcal companles do noL
Lake advanLage of Lhe dlfferenL sLandards and regulaLlons across dlfferenL counLrles Lo game Lhe
sysLem. lor example, faced wlLh forelgn markeLs wlLh dlfferenL and posslbly sLrlcLer regulaLlon,
Lhe burden of complylng wlLh counLry speclflc requlremenLs mlghL be conslderable. 8ralLhwalLe
(1993) argues LhaL law evaslon raLher Lhan breaklng Lhe law ls Lyplcal for Lhe pharmaceuLlcal
lndusLry. 1he sLraLegy lnvolvlng

an lmpure or undersLrengLh producL LhaL ls forbldden from sale ln one counLry belng
dumped ln anoLher naLlon wlLh looser laws.ls ofLen an elemenL of a much more
sophlsLlcaLed lnLernaLlonal law evaslon sLraLegy whereby Lhe flrm develops an
lnLegraLed plan of where lL wlll do Lhe early LesLlng and where lL wlll do lLs flnal LesLlng,
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
7
where lL wlll seek markeLlng approval flrsL, second, Lhlrd, penulLlmaLely, and ulLlmaLely,
and where lL wlll locaLe manufacLurlng of Lhe new producL" (8ralLhwalLe 1993).

AlLhough game playlng by pharmaceuLlcal companles should be reduced by harmonlzaLlon of
pharmaceuLlcal regulaLlon lL also plays Lo Lhe lnLeresLs of Lhe pharmaceuLlcal lndusLry because
Lhe compllance wlLh harmonlzed rules opens doors Lo several markeLs aL once, e.g. luA
approval glves access Lo Lhe worldwlde markeL.

1he flrsL aLLempL Lo globallze pharmaceuLlcal regulaLlon was made by Lhe WPC Lhrough Lhe
AcLlon rogram on LssenLlal urugs" and Lhe CerLlflcaLlon Scheme on Lhe CuallLy of
harmaceuLlcal roducLs Movlng ln lnLernaLlonal Commerce" ln 1973. ln Lhe CerLlflcaLlon
Scheme, exporLlng counLrles cerLlfy domesLlc pharmaceuLlcal companles as manufacLurers of
drugs LhaL are auLhorlzed for Lhe domesLlc markeL and wlLh producLlon faclllLles regularly
checked for compllance wlLh Lhe WPC CMs AcL (8ralLhwalLe and urahos 2000).

ln parallel, Lhe Luropean lree 1rade AssoclaLlon (Ll1A) lnLroduced a harmaceuLlcal lnspecLlon
ConvenLlon (lC) ln 1970. Members of lC (Ll1A buL also non-Ll1A counLrles) reclprocally
recognlze lnspecLlons of pharmaceuLlcal manufacLurlng planLs based on exchange of lnspecLlon
reporLs Lo ensure credlblllLy, whlch lncludes compllance wlLh Lhe WPC CMs 8egulaLlons"
(8ralLhwalLe and urahos 2000: 377). 1hls move made Lhe Lu Lhe lead ln Lhe harmonlzaLlon
process of pharmaceuLlcal regulaLlon. A furLher exLenslon of Luropean pharmaceuLlcal markeL
was Lhen done Lhrough bllaLeral agreemenLs wlLh Lhe uS, and !apan and from 1999, Lhrough Lhe
lnLernaLlonal harmonlzaLlon of pharmaceuLlcal regulaLlon (lnLernaLlonal Conference on
ParmonlzaLlon, lCP).

1he process of harmonlzaLlon was noL sLralghLforward and easy as lL ls always Lhe quesLlon of
who has Lhe power Lo persuade oLhers and whose rules wlll be followed. ln Lhe 1980s, Lhe uS
luA was relucLanL Lo [oln Lhe Lu and !apan ln Lhe harmonlzaLlon process buL

[g]lven Luropean domlnance ln Lhe lndusLry and !apanese agreemenL Lo cooperaLe, Lhe
uS had llLLle cholce buL Lo agree. Lven Lhen lL heslLaLed. 8uL afLer Lhe uS harmaceuLlcal
ManufacLurers AssoclaLlon (MA) commenced acLlve collaboraLlon, emphaslzlng Lhe
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
8
dangers of exporLlng Lhe uS drug lag Lo Lhe resL of Lhe world, Lhe luA had Lo [oln Lhe
process Lo defend lLs poslLlon" (8ralLhwalLe and urahos 2000: 372).

1o daLe a number of guldellnes and sLandards have been harmonlzed vla Lhe lCP.
8
1he lCP
sLresses Lhe advanLages of unlform guldellnes and muLual recognlLlon agreemenLs adopLed by
slgnaLorles LhaL ellmlnaLe dupllcaLlve LesLlng and documenLaLlon before markeLlng
auLhorlzaLlon ln dlfferenL counLrles, Lhus brlnglng publlc healLh beneflLs, decrease ln regulaLlon
cosLs and speedlng up Lhe approval process.
9


3. Good Manufactur|ng ract|ce (GM) gu|de||nes

CM ls LhaL parL of quallLy assurance whlch ensures LhaL producLs are conslsLenLly produced
and conLrolled Lo Lhe quallLy sLandards approprlaLe Lo Lhelr lnLended use and as requlred by
markeLlng auLhorlzaLlon" (WPC 2004).

CM guldellnes represenL mlnlmal sLandards LhaL are a necessary condlLlon for markeLlng
auLhorlzaLlon. urugs are consldered Lo be adulLeraLed, lf CMs are noL meL. CM sLandards are,
however, only guldellnes and alLernaLlve processes and conLrol mechanlsms can be used under
Lhe condlLlon LhaL equlvalenL assurance ls aLLalned.

CM guldellnes Lyplcally comprlse sLrong recommendaLlons on quallLy managemenL, personnel,
producLlon faclllLles and equlpmenL, documenLaLlon and records, producLlon and ln-process
conLrols, packaglng and ldenLlflcaLlon labelllng, sLorage and dlsLrlbuLlon, laboraLory conLrols,
valldaLlon, complalnLs and recalls, and conLracL manufacLurers.

1he flrsL verslon of CM guldellnes for manufacLurlng, processlng, packlng, or holdlng flnlshed
pharmaceuLlcals was lnLroduced by uS luA ln 1963 (lmmel 2000). lour years laLer, Lhe WPC
verslon of CMs was prepared by a group of consulLanLs aL Lhe requesL of Lhe 1wenLleLh World
PealLh Assembly (WPC 2004). lrom Lhen, Lhere were several amendmenLs and exLenslons of

8
8ralLhwalLe and urahos (2000) menLlon LhaL 19 LrllaLeral guldellnes were flnallzed by Lhe lCP conference of 1993
and anoLher 19 were Lo be flnallzed by Lhe lCP conference of 1997.
9
Abraham and 8eed (2001), however, argue LhaL Lhe harmonlzaLlon process led Lo lower regulaLory sLandards and
Lraded drug safeLy, rlsk assessmenL and publlc healLh for Lhe markeL expanslon of Lhe pharmaceuLlcal lndusLry.
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
9
Lhe guldellnes and many counLrles developed Lhelr own CM guldellnes whlch are based on Lhe
WPC guldellnes:
WPC CM guldellnes are prlmarlly used by pharmaceuLlcal regulaLors ln developlng
counLrles, Lhese are less sLrlcL Lhan Luropean or uS CM sLandards,
lnLernaLlonal Conference on ParmonlzaLlon, lCP-CMs,
Lu-CMs,
luA-CMs,
CM sLandards ln oLher counLrles such as AusLralla, Canada, !apan, Slngapore, 8ussla
10
,
lnLernaLlonal CrganlzaLlon for SLandards (lSC),
harmaceuLlcal lnspecLlon CooperaLlon Scheme (lCS) and
common pracLlces wlLhln Lhe lndusLry, llcense revlews, and crlsls managemenL conLrol
are also sources of CMs (Crazal and Larl 1997).

ln 1991, CM sLandards were harmonlzed aL Lhe Lu level (MP8A 2007). ln 1999, Lhe
lnLernaLlonal Conference on ParmonlzaLlon, a common pro[ecL of Lhe Lu, !apan and Lhe uS,
broughL CMls fot Actlve lbotmoceotlcol loqteJleots, whlch apply ln slgnaLory counLrles, Lhe Lu,
!apan and Lhe uS, and also ln oLher counLrles (e.g., AusLralla, Canada, Slngapore).

1he enforcemenL of CMs resLs on lndlvldual sLaLes: ln Lhe uS, Lhe responslblllLy ls wlLh Lhe luA,
ln Lhe Lu, wlLh naLlonal 8egulaLory Agencles (e.g., MP8A ln Lhe uk), ln AusLralla, wlLh Lhe
1herapeuLlcal Coods AdmlnlsLraLlon, ln lndla, wlLh Lhe MlnlsLry of PealLh.


10
Accordlng Lo Mrazek and lldler (2004) 8usslan CM sLandards are even less sLrlngenL Lhan Lhe WPC CM
sLandards.
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
10

llgure 1: CM developmenL groups


1he nexL subsecLlons focus on lndlvldual naLlonal and supranaLlonal agencles, Lhelr procedures
and relaLlonshlps among Lhem Lo see how CM sLandards are lnspecLed, recognlzed and
enforced. CM ls noL a low cosL exerclse, nelLher for pharmaceuLlcal companles, nor for
governmenLs. AlLhough Lhe sLandards are guldellnes raLher Lhan legally blndlng rules ln pracLlce
Lhey can be enforced ln a number of ways lncludlng procuremenL of drugs ln bulk by
governmenL bodles, nCCs or lnCCs. lor governmenLs Lhls means developlng capaclLy Lo
lmplemenL and enforce Lhe regulaLlon.

3.1 WnC

1he WPC CM guldellnes, complemenLed wlLh guldellnes on Lhe lnspecLlon of pharmaceuLlcal
producers, are prlmarlly used ln developlng counLrles. 1hese guldellnes are, however, also
embedded ln CM sLandards of developed counLrles, where Lhey Lyplcally represenL a subseL ln
more deLalled quallLy and safeLy assurance sysLems. Lven ln developlng counLrles, Lhese
guldellnes are ofLen ad[usLed Lo local condlLlons and Lhelr lmplemenLaLlon, lnspecLlons of
manufacLurlng faclllLles, llcenslng, and enforcemenL ls wlLh governmenL bodles of lndlvldual
sLaLes. ln lndla, for lnsLance, Lhe responslblllLy ls wlLh Lhe CenLral urugs SLandard ConLrol
Lu 27
lceland
LlchLensLeln
norway
AusLralla,
Canada,
Slngapore,
.
ueveloplng
counLrles
ICn:
Lu - LMLA
!apan
uSA - luA
WPC
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
11
CrganlzaLlon, MlnlsLry of PealLh and lamlly Welfare. ln nepal, Lhe naLlonal CM guldellnes are
prepared and enforced by Lhe ueparLmenL of urug AdmlnlsLraLlon.

1he WPC recommends several Lypes of lnspecLlons of manufacLurlng faclllLles Lo check
compllance wlLh Lhe CM. 1hese lnspecLlons are ad[usLed Lo speclflc slLuaLlons (shorL
descrlpLlon of Lhese lnspecLlons can be found ln Appendlx: 33).

lor all companles, conLrols should be regular and accordlng Lo Lhe WPC lnsLrucLlons, ldeally on
annual basls. lor large companles, conLrols mlghL be spllL lnLo several smaller checks durlng a
longer perlod such as valldlLy of manufacLurer's llcense or Lhe CM cerLlflcaLe. AlLhough Lhese
frequencles are menLloned as ldeal, and maybe exacLly because of LhaL, lL ls lmporLanL Lo flnd
ouL/esLlmaLe how far are Lhese ldeals from Lhe reallLy and whaL Lhe consequences of Lhe gap
beLween ldeal sLandards and pracLlce are for Lhe quallLy of drug producLlon ln developlng
counLrles.

1he WPC makes also suggesLlons on regulaLory acLlons ln Lhe case of non-compllance. 1hese
lnclude Lhe requlremenL of correcLlon of unsaLlsfacLory slLuaLlons, producL recall and ln exLreme
cases wlLhholdlng Lhe auLhorlzaLlon and closure of a facLory. 1he flnal declslons abouL correcLlve
acLlons, however, depend on naLlonal regulaLlon of lndlvldual sLaLes.

3.2 Internat|ona| Conference on narmon|zat|on of 1echn|ca| kequ|rements for keg|strat|on of
harmaceut|ca|s for numan Use (ICn)

1he lCP ls a common pro[ecL of regulaLory auLhorlLles and represenLaLlves of pharmaceuLlcal
lndusLrles ln Lu, !apan and Lhe uS Lo dlscuss lssues relaLed Lo approval and markeLlng
auLhorlzaLlon of new medlclnal producLs ln Lhese Lhree reglons. namely, Lhe slx parLles lnvolved
are Lhe Luropean Commlsslon and Lhe Luropean lederaLlon of harmaceuLlcal lndusLry
AssoclaLlons, Lhe !apanese MlnlsLry of PealLh and Welfare and Lhe !apanese harmaceuLlcal
ManufacLurers AssoclaLlon, Lhe uS luA and Lhe uS harmaceuLlcal ManufacLurers AssoclaLlon.
ln addlLlon Lo Lhese prlnclpals, Lhere are Lhree observers represenLlng non-lCP counLrles -
WPC, Lhe Luropean lree 1rade AssoclaLlon and PealLh Canada - and Lhe lnLernaLlonal
lederaLlon of harmaceuLlcal ManufacLurers AssoclaLlons provldes a secreLarlaL for Lhe lCP.
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
12

1he prlmary ob[ecLlve ls Lo harmonlze regulaLory requlremenLs relaLed Lo quallLy, safeLy and
efflcacy of medlclnal producLs and Lo supporL muLual recognlLlons by Lhe Lhree regulaLory
auLhorlLles. MuLual recognlLlons based on Lhe exchange of daLa and assessmenL reporLs
ellmlnaLe dupllcaLlve LesLlng and lnspecLlon procedures and Lhus decrease cosLs of and speed up
Lhe lnLroducLlon of new medlclnal producLs Lo Lhe markeLs.

Among oLher guldellnes, Lhe lCP harmonlzed Lhose applylng Lo human medlclnes, CooJ
mooofoctotloq ltoctlce ColJe fot Actlve lbotmoceotlcol loqteJleots (lCP C7A) whlch were
developed and recommended for adopLlon ln Lhe Lu, !apan and Lhe uS ln 2000. naLlonal
regulaLory auLhorlLles lmplemenL, monlLor and enforce compllance wlLh Lhese sLandards, whlch
are requlred for markeLlng auLhorlzaLlon.

3.2.1 Luropean Med|c|nes Agency (LMLA)

ln Lurope, Lhere are Lhree dlfferenL legal frameworks for Lhe reglsLraLlon of pharmaceuLlcal
producLs as esLabllshed by Lhe Lu: CenLrallzed rocedure, uecenLrallzed rocedure, and MuLual
8ecognlLlon rocedure. 1he CenLrallzed rocedure for Lhe approval of drugs, coordlnaLed by Lhe
LMLA, ls mandaLory for bloLechnology and oLher hlgh Lechnology producLs, orphan drugs, and
new acLlve subsLances noL prevlously auLhorlzed ln Lhe Lu and whlch are for Lhe LreaLmenL of
Plv/AluS, cancer, and dlabeLes or neurodegeneraLlve dlsorders. 1he uecenLrallzed rocedure ls
carrled ouL by Lhe auLhorlzaLlon agency of Lhe sLaLe ln whlch Lhe pharmaceuLlcal manufacLurer
seeks Lhe markeLlng approval for lLs producL. 1hrough MuLual 8ecognlLlon rocedure Lhen, Lhls
manufacLurer can apply for Lhe markeLlng auLhorlzaLlon ln oLher Lu member sLaLes. ln such a
case, Lhe flrsL counLry auLhorlzlng Lhe concerned producL has Lo produce a deLalled assessmenL
reporL whlch ls clrculaLed Lo Lhe oLher member sLaLes.

ln Lhls secLlon we overvlew Lhe cenLrallzed procedure and oLher acLlvlLles of Lhe LMLA and Lhen
focus on one naLlonal auLhorlzaLlon agency ln Lhe Lu, Lhe uk Medlclnes and PealLhcare
producLs 8egulaLory Agency.

aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
13
1he LMLA was esLabllshed by a ulrecLlve LC 2309/93
11
and ln operaLlon slnce 1993 as a
decenLrallzed agency of Lhe Lu. lLs maln responslblllLles concern Lhe sclenLlflc evaluaLlon of
appllcaLlons for markeLlng auLhorlzaLlon of medlclnal producLs and monlLorlng Lhe safeLy of
medlclnes ln Lhe Lu. ln conLrasL Lo Lhe uS luA, Lhe LMLA works as a sclenLlflc body LhaL draws
on resources of naLlonal regulaLory auLhorlLles. lL does noL have any execuLlve power. lLs
evaluaLlons are submlLLed Lo Lhe LC whlch lssues Lhe markeLlng approval or decldes abouL Lhe
wlLhdrawal of speclflc producLs from Lhe markeL. 1he LMLA complemenLs acLlvlLles of naLlonal
auLhorlzaLlon agencles and also serves as an umbrella organlzaLlon of Lhese naLlonal bodles. 1he
agency faclllLaLes Lhe exchange of lnformaLlon on CM cerLlflcaLes vla LudraCM daLabase and
on safeLy of auLhorlzed producLs vla Ludravlgllance reporLlng sysLem (more deLalls are avallable
ln Appendlx: 34).

lor markeLlng auLhorlzaLlons granLed under Lhe cenLrallzed procedure ln Lhe Lu, lnlLlal
lnspecLlon ls carrled ouL under conLracL Lo Lhe LMLA. 1he flrsL lnspecLlon ls Lyplcally carrled ouL
by Lhe Supervlsory AuLhorlLy concerned, l.e. Lhe Member SLaLe ln whlch Lhe producL ls Lo be
made or lmporLed. SubsequenL lnspecLlons are normally carrled ouL rouLlnely by Lhe same
auLhorlLy alLhough Lhere ls provlslon for one Member SLaLe Lo lnspecL ln non-Member SLaLes on
behalf of anoLher (MP8A 2007).

1he LC negoLlaLes MuLual 8ecognlLlon ArrangemenLs (M8As) beLween Lhe CommunlLy and Lhlrd
counLrles, whlch lnclude muLual recognlLlon of sLandards of CM and arrangemenLs Lo ensure
compllance by pharmaceuLlcal manufacLurers. under an M8A, Lhe 8egulaLory AuLhorlLles
accepL each oLher's lnspecLlon 8eporLs and rouLlne lnspecLlons by one auLhorlLy of
manufacLurers ln Lhe oLher's LerrlLory ls noL requlred. ln addlLlon, Lhe re-LesLlng of lmporLed
producLs are normally noL requlred" (MP8A 2007).

8egardlng Lhe lnspecLlon of faclllLles ln Lhlrd counLrles, lL ls noL clear wheLher Lhe lnspecLlon
focuses only on a speclflc drug or drug group LhaL ls Lo be markeLed ln Lhe Lu or wheLher CM
cerLlflcaLlons of planLs are also granLed. Accordlng Lo MP8A, lnspecLlons are drug relaLed buL

11
Crlglnally named as Lhe Luropean Agency for Lhe LvaluaLlon of Medlclnal producLs and renamed as Luropean
Medlclnes Agency ln 2004.
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
14
lndlan companles usually asserL LhaL Lhey have Lu cerLlfled faclllLles. 1hls ls an lssue LhaL needs
Lo be followed up.

3.2.1.1 Uk - Med|c|nes and nea|thcare products kegu|atory Agency (MnkA)

1he MP8A ls an execuLlve body of Lhe MlnlsLry of PealLh. lL assesses quallLy, safeLy and efflcacy
of medlclnes and auLhorlses Lhem for markeLlng ln Lhe uk. lL also carrles ouL posL-markeLlng
survelllance and regulaLes cllnlcal Lrlals for medlclnes and medlcal devlces.

1he MP8A has flve lnspecLoraLes LhaL monlLor Lhe compllance of pharmaceuLlcal companles
wlLh Lhe uk and Lu regulaLlon. 1hese are Cood Cllnlcal racLlce, Cood ulsLrlbuLlon racLlce,
Cood LaboraLory racLlce, Cood ManufacLurlng racLlce, and Cood harmacovlgllance racLlce
lnspecLoraLes.

Compllance wlLh CM and Cu sLandards by all holders of and appllcanLs for manufacLurer's
and wholesaler's llcences ln Lhe uk ls requlred by MP8A. 1he lnspecLlons follow Lhe Lu ulrecLlve
for medlclnal producLs for human use. '8ules and Culdance for harmaceuLlcal ManufacLurers
and ulsLrlbuLors 2002' conLaln deLalls on Lhls dlrecLlve and guldance on lLs lmplemenLaLlon.
(MP8A 2007)

1he MP8A carrles ouL lnspecLlons of all appllcanLs for manufacLurer's or wholesaler's llcence
and Lhen perlodlcally durlng Lhe llfe of LhaL llcence wlLh Lhe maxlmum lnLerval of 2 years for
manufacLurers and 3 years for wholesalers and for overseas manufacLurers. noLe, LhaL Lhe uk
Medlclnes lnspecLoraLe does noL llcence overseas manufacLurlng slLes buL lnspecLlons, pre-
arranged or unannounced, are carrled ouL only for speclflc markeLlng auLhorlsaLlons and focus
on a producL Lo be lmporLed Lo Lhe uk. ln Lhls case sLandards applled musL be Lhe same as Lhose
valld ln Lhe uk.

1he uk lnspecLoraLe currenLly carrles ouL regular lnspecLlons ln a number of counLrles, lncludlng
uSA, lndla, Chlna and !apan boLh ln connecLlon wlLh naLlonal requlremenLs and on behalf of Lhe
Luropean Medlclnes Agency (LMLA).

aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
13
3.2.2 USA - Iood and Drug Adm|n|strat|on (IDA)

AcLlvlLles of Lhe luA are much broader Lhan acLlvlLles of Lhe LMLA and Lhe MP8A ln LhaL lL
focuses on proLecLlon of healLh ln general and regulaLes food, drugs, medlcal devlces, blologlcs,
anlmal feed and drugs, cosmeLlcs and also radlaLlon-emlLLlng producLs. WlLhln Lhese areas,
however, lLs roles are slmllar Lo Lhe LMLA and Lhe MP8A. 1he luA assesses new producLs,
approves Lhelr markeLlng and operaLes posL-markeLlng survelllance. ln addlLlon, Lhe luA has an
execuLlve power and can dlrecLly sancLlon non-compllance wlLh CM sLandards or vlolaLlon of
oLher Lypes of pharmaceuLlcal regulaLlon.

luA uses Lerm 'currenL CM' (cCM) Lo emphaslze LhaL manufacLurers have Lo employ up-Lo-
daLe Lechnologles and sysLems ln order Lo comply wlLh Lhe regulaLlon. luA cCMs lncorporaLe
Lhe lCP C7A guldance for acLlve pharmaceuLlcal lngredlenLs. ln 2002 Lhe luA adopLed sysLems
approach for lLs lnspecLlons (Lhe llsL of sysLems LhaL are lncluded ls provlded ln Appendlx: 34).

lor Lhe lnspecLlon of a speclflc sysLem, several Lypes of Als LhaL use Lhls process/sysLem should
be selecLed for proper check of Lhe sysLem. 1hus, Lhe sLrucLure of lnspecLlons dlffers from Lhe
one applled by Lhe MP8A ln Lhe uk.

ln Lhe case of forelgn manufacLurers, lnspecLlons cover only Als LhaL are Lo be markeLed or
already markeLed ln Lhe uS. 1here are speclal reporLlng lnsLrucLlons for forelgn producers.
CenLre for urug LvaluaLlon and 8esearch's Cfflce of Compllance, lorelgn lnspecLlon 1eam
recelves and evaluaLes all lnspecLlon reporLs and malnLalns a compleLe flle for each forelgn drug
producLlon faclllLy.
3.3 GMs |n deve|op|ng countr|es

Whlle focuslng on pharmaceuLlcal lndusLry and markeL ln lndla and nepal, we can see Lwo
dlfferenL effecLs CM sLandards have on local lndusLrles. 1he flrsL one ls an aLLempL Lo acqulre
CM cerLlflcaLes on Lhe black markeLs and lL would be lnLeresLlng Lo sLudy Lhe effecL of such
companles on compeLlLlon ln Lhe pharmaceuLlcal markeL. 1he oLher lmpacL ls Lhe creaLlon of
barrlers Lo enLry and/or Lo growLh of domesLlc drug manufacLurers (pushlng smaller companles
LhaL cannoL afford Lhe upgrade Lo Lhe hlgher sLandards ouL of Lhe markeL).
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
16

lndlan pharmaceuLlcal lndusLry ls more developed Lhan Lhe nepall one wlLh slgnlflcanL exporL
noL only Lo less developed counLrles buL also Lo developed markeLs. Several lndlan companles
have already overgrown lnLo MnCs wlLh manufacLurlng and markeLlng acLlvlLles abroad. 1hese
companles, ln order Lo reach forelgn markeLs, had Lo upgrade Lhelr producLlon faclllLles Lo
sLandards of developed counLrles long before slmllar sLandards were requlred by lndlan
regulaLory bodles. 1hanks Lo Lhelr scale, Lhese companles do noL have any dlfflculLles Lo meeL
conLlnuously lncreaslng sLandards. 1he process of sLrengLhenlng of requlremenLs ln lndla, and
oLher less developed counLrles, creaLes a pressure on smaller companles LhaL focus on domesLlc
markeLs. AlLhough lL ls lmposslble Lo separaLe effecLs of Lhe recenL changes lncludlng 18lS,
lnLenslfled compeLlLlon and more sLrlngenL CM sLandards, lL ls noL surprlslng LhaL Lhese facLors
accorded ln Lhelr lmpacL on lndlan pharmaceuLlcal lndusLry and resulLed ln lLs consolldaLlon.

ln nepal, pharmaceuLlcal companles are much smaller and less advanced Lechnologlcally. nepall
pharmaceuLlcal markeL ls small, especlally when compared Lo lLs lndlan and Chlnese nelghbor.
uue Lo lLs small slze, producLlon of many drugs ls noL proflLable for nepall pharmaceuLlcal
lndusLry and wlLh hlgh quallLy requlremenLs on exporLs represenLed by CMs, lL ls almosL
lmposslble Lo compeLe wlLh MnCs and lndlan and Chlnese pharmaceuLlcal glanLs. Pere, Lhe
lmposlLlon and sLrlcL enforcemenL of CMs mlghL lead Lo slgnlflcanL barrlers Lo growLh of
domesLlc companles.

ln Lhe presenL verslon of Lhe paper we focus only on nepal. We look aL how governmenL
represenLaLlves and pharmaceuLlcal producers percelve and respond Lo requlremenLs Lo
lmplemenL and enforce CM sLandards. A few noLes on lndlan regulaLory auLhorlLles and CM
sLandards are provlded ln Appendlx: 33.

3.3.1 Nepa|

1hese noLes from nepal and lssues of CM cerLlflcaLlon are LenLaLlve and derlved from lnlLlal
lnLervlews and eLhnographlc research by Lhe nepal research Leam. 1hey are reproduced here Lo
provoke dlscusslon and polnLers for posslble fuLure avenues of lnqulry.

aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
17
AllopaLhlc medlclne ln nepal has a relaLlvely recenL hlsLory ln Lhe conLexL of nepal, lnLroduced
around 1860 wlLh Lhe flrsL hosplLal belng Lhe kaLhmandu 8lr hosplLal bullL ln 1890. 1he llmlLed
supply of medlclnes Lo nepal was vla lndla (and Lhe 8rlLlsh Lmbassy for Lhe ellLe, lnLervlew,
kaLhmandu unlverslLy, Aprll 2007) unLll Lhe flrsL people's movemenL" of 1930. lrom Lhls perlod
was sLarLed Lhe more sysLemaLlc developmenL of Lhe healLh secLor. nepal sLarLed Lo
manufacLure lLs own drugs from Lhe 1930s, focuslng lnlLlally on medlclnal planLs and herbal
forms and was locaLed under Lhe MlnlsLry of loresLs. 1he 8oyal urugs LaboraLory was seL up as a
plloL ln 1963, and Lhen converLed Lo 8oyal urugs LlmlLed (8uL) ln 1972 Lhe flrsL producLlon unlL
ln nepal (lnLervlew, ACn, kaLhmandu, uecember 2006). 1he flrsL prlvaLe company,
Chemldrug lndusLrles vL. LLd. was opened ln 1971 (lnLervlew, kaLhmandu unlverslLy, Aprll
2007). 1he drug AcL of 1978 resulLed ln Lhe ueparLmenL of urug AdmlnlsLraLlon (uuA) belng seL
up ln 1979 (sLlll parL of Lhe mlnlsLry of foresLs). recursors Lo Lhe urug AcL lncluded Lhe 8lack
MarkeLlng & CLher Soclal Cffences AcL, 2032 8S (1973), and Lhe urug Abuse ConLrol AcL, 2033
8S (1976).
12
8y 1979 Lhere were Lwo nepalese companles buL around 1000 lndlan ones, nepal
was an exLenslon of Lhe lndlan markeL. lL wasn'L Llll afLer Lhe laLe 1980s, however, LhaL Lhe
nascenL nepalese lndusLry sLarLed Lo mushroom. 8elocaLed Lo a parL of Lhe MlnlsLry of PealLh,
Lhe uuA has overseen Lhls growLh of Lhe nepal harmaceuLlcal lndusLry Lo lLs currenL slze of 43
reglsLered nepall companles, and been responslble for Lhe regulaLlon of Lhe lndusLry. CurrenLly
Lhe uuA ls locaLed ln 8abar Mahal (no where near Lhe mlnlsLry of healLh), behlnd whlch ls found
Lhe naLlonal Medlclnes LaboraLory (Llll recenLly known as Lhe 8oyal urugs 8esearch LaboraLory),
also esLabllshed as a parL of Lhls acL.
1he ob[ecLlves of Lhe uuA are as follows:
Lo regulaLe all funcLlons relaLlng drug llke mlsuse and abuse of drugs and lLs raw
maLerlals, Lo sLop false and mlsleadlng adverLlsemenL and make avallable safe,
efflcaclous and quallLy drug Lo Lhe general publlc by conLrolllng Lhe producLlon,
markeLlng, dlsLrlbuLlon, sale, exporL-lmporL, sLorage and use of drugs" (uuA 2007).

1he sLraLegles Lo do Lhls lnclude:
SelecLlon of essenLlal drug Lo promoLe raLlonal use of drugs, LsLabllshmenL of reglonal
offlces aL all flve reglons for effecLlve decenLrallzaLlon: SLrengLhenlng of naLlonal
Medlclne LaboraLory as an lndependenL naLlonal urug ConLrol LaboraLory, urug

12
See ulxlL (2000) for a full llsL of all Lhe AcLs perLalnlng Lo healLh, and Lhelr developmenL ln Lhe conLexL of nepal.
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
18
8eglsLraLlon on sclenLlflc facLs, romoLlon of raLlonal drug use, uevelopmenL of an
efflclenL drug lnformaLlon sysLem Lo dlssemlnaLe Lhe relevanL lnformaLlon,
LncouragemenL Lo promoLe and esLabllsh pharmaceuLlcal lndusLrles Lo achleve self-
rellance ln Lhe producLlon of essenLlal drugs, LffecLlve lnspecLlon Lo ensure Lhe quallLy
of markeLed producLs, revenL mlsuse of anLlbloLlc Lo combaL anLlmlcroblal reslsLance,
SLrengLhen naLlonal lndusLry Lo comply wlLh WPC-CM" (uuA 2007).

Slnce 1984 Lhe uuA has lLs own code of manufacLurlng pracLlce, whlch ls wrlLLen ln nepall and
publlshed along wlLh Lhe WPC CM code of pracLlce (ln Lngllsh). 1he WPC CM code was
revlsed and publlshed ln 1998, and desplLe Lhe WPC revlslng Lhelr CM codes ln 2003, Lhls parL
has noL been updaLed ln Lhe uuA's publlcaLlon. We were Lold by a senlor drug admlnlsLraLor
LhaL Lhe uuA ls ln process of publlshlng a new code as Lhe 1984 uuA code does noL explaln
cerLaln Lhlngs clearly, for example, lL ls wrlLLen ln Lhe code LhaL fresh alr ls necessary whlle
produclng drugs buL lL does noL explaln whaL ls meanL by fresh alr." When asked abouL overlap
beLween Lhe uuA code and WPC CM code, he replled ln vague Lerms, saylng LhaL mosL of Lhe
WPC CM sLandards are lncorporaLed ln Lhe uuA code (ConversaLlon, senlor drug
admlnlsLraLor, uuA, !une 2007).

lrom Lhe 1990s Lhe uuA made Lhe upgradlng of faclllLles Lo WPC prescrlbed CM sLandards
mandaLory. 1he deadllne was seL for Aprll 2007, buL Lo daLe only elghL companles have
managed Lhls. 1he currenL dlrecLor of Lhe uuA descrlbed LhaL Lhe WPC CM cerLlflcaLlon for
nepall companles remalns opLlonal" aL presenL, wlLh Lhe uuA's own Code on ManufacLurlng of
urugs Lhe only legally blndlng requlremenL. ln our flrsL lnLervlew wlLh senlor uuA offlclals, we
were Lold Lhe followlng regulaLlons have been developed:

1. urug reglsLraLlon regulaLlons
2. urug sLandard regulaLlon
3. urug lnqulry and lnspecLlon 8egulaLlon
4. urug manufacLurlng code.

1he essenLlal drug llsL was flrsL produced ln 1986, updaLed ln 1992, 1997, and Lhe lasL updaLe
2002. 1he urug 8ulleLln of nepal (u8n) was flrsL publlshed ln nepal ln 1992, and has a serles of
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
19
edlLorlals on regulaLlon, CM, spurlous and fake drugs and Lhe oLher lssues affecLlng Lhe nepal
pharmaceuLlcal lndusLry. LlsLs of reglsLered companles are publlshed as well as banned drugs
and comblnaLlons. CurrenLly Lhelr prlnL run ls 7,000 coples and Lhey dlsLrlbuLe Lo all Lhe pharma
companles, assoclaLlons, mlnlsLrles and hosplLals as well as Lo reLallers and wholesalers vla Lhelr
assoclaLlons. Also ln Lhe uuA are avallable coples of Lhe nepalese naLlonal lormulary, Lhe !une
2000 SLandards for harmaceuLlcal 8egulaLlon and Care", Lhe naLlonal urug ollcy 1993, 1he
naLlonal LlsL of LssenLlal urugs nepal (Lhlrd revlslon, 2002), and Lhe november 2003 urafL of
naLlonal Cood harmacy racLlce Culdellnes".

CM cerLlflcaLlon was descrlbed Lo us by Lhe uuA as necessary only for exporL, alLhough Lhe
WPC does lnspecL for drugs and producLs llnked Lo Lhelr own purposes" (for example
vacclnaLlon programmes, 18 drugs for uC1S, A8vs eLc.). 1he WPC role ls malnly lndlrecL,
Lhrough Lhe uuA. Whlle Lhe AssoclaLlon of harmaceuLlcal roducers of nepal (ACn) are
supposed Lo be asslsLlng wlLh Lhls process, and dolng Lralnlngs around CM Lhey are deemed by
many Lo be of llLLle help (as one company dlrecLor sLaLed: Lhey Lake our money and drlnk
whlsky"!). 1hey have a volunLeer pharmaclsL from !apan currenLly helplng Lhem wlLh Lhls
process of developlng guldellnes and Lralnlngs. ACn ls currenLly more lnvolved ln lobbylng for
dollar raLes for lmporLs from lndla and regulaLlng LhaL all forelgn lmporLs should have Lhelr
baLches labelled ln nepall (LhaL ls ln proLecLlng Lhe lnLeresLs of Lhe nepall manufacLurers).

3.3.1.1 GM |ssues

1he dlrecLor of Lhe uuA descrlbed Lhe CM cerLlflcaLlon process as parL of Lhe LssenLlal urugs
and Medlclnes rogramme. 1he uuA conducLed Lhe lnlLlal Lralnlng ln counLry, wlLh supporL from
Lhe WPC whlch ls Lechnlcal and flnanclal". Powever, Lhe dlfflculLles Lhey face ln lmplemenLlng
Lhe CM process were descrlbed Lo us as Lhree fold. llrsLly, Lhe sLaff lssues and Lhelr lack of
experLlse, Lhls ls noL only uuA sLafflng problems (Lhey have only flve sLaff members who check
LhaL rules are belng followed), buL Lhe lack of experLlse ln Lhe company sLaff. Whlle Lhere are
lncreaslng numbers of graduaLes now comlng ouL of Lhe unlverslLles, Lo daLe Lhey have llLLle
experlence. Secondly Lhere are dlfflculLles wlLh Lhe concepL lLself. Some manufacLurers say LhaL
Lhey already sell well, so why do Lhey need CM? 1hey have a markeL perspecLlve", and as
Lhelr drugs pass Lhelr own producL LesLs, why do Lhey need lL? 1hey complaln abouL Lhe
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
20
lnvesLmenLs requlred for upgradlng when Lhey see llLLle beneflL. 1hlrdly, Lhe CM concepLs
Lhemselves are changlng and becomlng more sLrlngenL. 1he uuA ls responslble for Lhe
evaluaLlon of Lhe company CM cerLlflcaLlon and for glvlng Lhe cerLlflcaLe, and no-one from Lhe
WPC comes Lo evaluaLe Lhls.

Cne group of senlor managemenL workers for one of Lhe CM cerLlfled companles explalned
LhaL Lhere was flexlblllLy ln Lhe Llmlngs of Lhe lmplemenLaLlon because of Lhe recenL dlfflculLles
ln nepal - Lhe recenL pollLlcal envlronmenL, wlLh sLrlkes and oLher lndusLry problems. CLhers
descrlbed Lhe sheer producLlon of paperwork requlred for monlLorlng as overwhelmlng, besldes
Lhe prohlblLlve cosLs. 1he dlrecLor of nL sald LhaL lnlLlally Lhelr producLlon dropped afLer
lmplemenLlng CM sLandards. 1hey used Lo have quallLy conLrol", buL now Lhls has shlfLed Lo
quallLy assurance" wlLh greaLer sLrlngency. 1hls shlfL was descrlbed Lo us by anoLher company's
senlor manager as follows:

CuallLy conLrol ls noL ln common use now. We call lL quallLy assurance. 8efore whlle
checklng quallLy, Lhey used Lo check aL Lhe end. 8uL now Lhey say LhaL lf we check lL
rlghL from Lhe beglnnlng Lhen quallLy ls assured rlghL from Lhe beglnnlng. 1he quallLy of
exclplenL, wheLher Lhe raw maLerlal ls mlxed properly or noL, wheLher lL ls welghed
properly or noL, coaLlng, punchlng, lf everyLhlng ls done properly, all Lhls ls checked. 1hls
ls called SC" (lnLervlew, kaLhmandu, 20 Aprll 2007).

We were furLher Lold LhaL Lhe concepLs Lhemselves have changed a loL slnce nL sLarLed Lo
lmplemenL Lhem, llke for example Lhe APu (alr handllng unlLs) whlch are sLrlcLer, or Lhe use of
reverse osmosls" havlng replaced demlnerallsers" for Lhe waLer Lhey use. 1he cosLs Lo run
Lhese new unlLs have lncreased as well, and Lhe slze of Lhe backup generaLors requlred Lo keep
manufacLurlng sLandards up wlLh Lhe regular power cuLs have lncreased.

C1L pharmaceuLlcals have recenLly upgraded Lo CM cerLlflcaLlon sLandards. 1he dlrecLor of Lhe
company Lold us LhaL Lhe lnlLlal cosL ouLlay had been 4 crore rupees. 1hls had spun Lhem from a
proflL maklng buslness lnLo one wlLh large debLs. An ex-employee of 8oyal urugs sLaLed LhaL
Lhere was no way LhaL Lhls company could afford Lo upgrade Lo CM sLandards. Cne parLlcular
complalnL was LhaL desplLe Lhls lnlLlal ouLlay, Lhe nepal markeL was small and lL would be
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
21
dlfflculL Lo recrulL cosLs (Lhe slze of Lhe nepal markeL ls sLaLed Lo us a parLlcular dlfflculLy for
nepal Lo develop lLs own ln[ecLables, Lhe markeL ls [usL Loo small). noL one person we have
spoken Lo ln Lhe buslness Lhlnks of exporL as a posslblllLy, all concenLraLlng on Lhe nepal markeL.
We have heard repeaLedly Lhe aLLempL by nL (a CM cerLlfled company) Lo exporL Lo lndla as
Lhe cauLlonary Lale, Lhe flrsL baLch was held ln cusLoms on Lhe border wlLh lndla as samples
were senL Lo Lucknow for quallLy conLrol checks. All Lhe drugs explred ln Lhe lnLerlm and had Lo
be desLroyed.

1hls ls how Lhe CM process was descrlbed Lo us by senlor C1L sLaff:

WhaL WPC/CM ls LhaL, Lhe WPC has deflned, a seL of rules, how lL ls Lo be done and
whaL all ls Lo be done. All Lhese checkllsLs should be ln a recorded form. Llke where have
raw maLerlals come from, and Lhen Lhese raw maLerlals have Lo be checked ln CC, LhaL
ls quallLy conLrol lab. now even Lhe packaglng maLerlal ls kepL under survelllance for 24
hours. lf Lhere won'L be any growLh of bacLerla, fungus eLc Lhen lL ls cleared. 1hen only lL
ls senL from ware house Lo sLoreroom. 1hls ls also recorded. ln WPC/CM, lL should be
recorded LhaL Lhls raw maLerlal has come, checked, verlfled, ok, or re[ecLed. 1hen Lhere
are labels: yellow, green and red. llrsL all raw maLerlals have yellow label, whlch means
LhaL lL has [usL arrlved. 1hen lL ls senL Lo lab. lf lL ls verlfled Lhen lL ls labelled as green
and lL ls senL lnslde. lf Lhe maLerlal ls re[ecLed Lhen lL ls labelled as red and ls kepL
ouLslde and reLurned Lo Lhe one who had supplled Lhese raw maLerlals. Lven Lhe
packaglng maLerlals llke carLon, boLLles, caps, sLrlpes, flles eLc are kepL ln a quaranLlne
area. AfLer 24 hours of survelllance, lL ls senL Lo sLore. 1hls ls also recorded. now afLer lL
ls senL Lo sLore Lhere are Lwo areas: one ls grey area and anoLher ls black area.. (he
wenL on Lo descrlbe Lhe parameLers for baLch welghL, LhaL Lhe lndlvldual's names
responslble are recorded, and Lhe percenLage varlaLlon allowed). And lf lL dlffers Lhen
we can flnd ouL exacLly where Lhe problem was. 1hls we call SC, sLandard operaLlon
procedure. 1hls ls also under WPC guldellne. And Lhen flnally afLer Lhls, Lhe Lhlckness,
dlameLer, hardness ls checked. AfLer lL ls ready, lL goes Lo grey area for secondary
packaglng. lor prlmary packaglng llke puLLlng lL ln a boLLle or sLrlpes, lL ls done ln black
area. now Lo pack Lhls ln carLons eLc lL goes Lo grey area (lnLervlew, kaLhmandu, 20
Aprll 2007).
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
22

roud of Lhelr capaclLy Lo do so, and Lhe new faclllLles, we were shown around Lhese. 1helr
dlrecLor and markeLlng manager Lalked of commlLmenL Lo eLhlcal pracLlce, and galnlng CM
cerLlflcaLlon was a parL of Lhls. AfLer a Lour of Lhe producLlon faclllLles, we were Lold by Lhe
producLlon managemenL Leam LhaL CM cerLlflcaLlon conslders many elemenLs: Lhe premlses,
personnel, quallLy conLrol, producLlon, sanlLaLlon and hyglene and flnally, documenLaLlon. As
Lhey phrased lL all Lhe CM process should be done per documenLaLlon and documenLed"
13
.
Lach and every acLlvlLy ls prescrlbed ln deLall Lhrough SLandard CperaLlng rocedures (SCs),
whlch are sLraLeglcally dlsplayed ln nepall and Lngllsh LhroughouL Lhe slLe. 1he uuA was
descrlbed as responslble for Lhe guldellnes LhaL are seL up for Lhls end, and Lhen responslble for
Lhelr lmplanLaLlon.

ln a conversaLlon wlLh a senlor pharmacology professor, he referred Lo Lhe problem ln nepal as
one of quallLy versus cosL. Pe referred Lo amoxlclllln, whlch ls now produced by nearly all Lhe
nepall companles. lL cosLs around 4-3 rupees, buL lf you flnd lL for less Lhan Lhls Lhen ln hls
oplnlon Lhe quallLy musL be compromlsed. Pe reckoned LhaL Lhe currenL dlrecLor aL Lhe uuA ls
good aL hls [ob, and worklng hard aL Lrylng Lo keep prlces low whlle malnLalnlng quallLy, he ls
worklng aL Lrylng Lo geL CM cerLlflcaLlon lmplemenLed. lL ls dlfflculL, he sald, as smaller
companles used Lo send goondas" around Lo hlm Lo ask why CM ls belng puL lnLo place. 1hey
sald LhaL lL ls drlvlng up Lhelr cosLs and Lhe prlces of affordable medlclnes. lL ls Lenslon beLween
cosL and quallLy. 1he currenL uuA dlrecLor ls an advocaLe of unlformlLy of prlce for generlcs, we
were Lold buL currenLly aparL from araceLamol, whlch Lhe governmenL has capped Lhe prlce of,
Lhe lndusLry decldes on Lhe prlces of drugs.

As one wholesaler polnLed ouL Lo us, Lhe sLrlngenL regulaLlons demanded by CM cerLlflcaLlon
has resulLed ln some lndlan companles belng unable Lo lmporL Lhelr producLs, and Lhelr
producLs noL belng re-reglsLered by Lhe uuA. As lL was phrased Lo us: lL dldn'L send some
papers so lL ls noL found ln nepal's markeL" (lnLervlew, wholesaler, kaLhmandu, 12 Aprll 2007).
1he wholesaler ln quesLlon wanLed Lhe parLlcular producL, buL Lhe company sald LhaL Lhey were
now unable Lo geL Lhe producL pasL cusLoms. As anoLher example, Lhe producer of sLrepslls"

13
lan Parper and SamlLa 8haLLaral vlslL Lo C1L harmaceuLlcals, Aprll 2007.
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
23
(8CC1S) enLered lnLo a conLracL wlLh a nepall company Lo make Lhls ln nepal, buL because Lhe
company does noL have CM cerLlflcaLlon SLrepslls are no longer avallable on Lhe nepal markeL.

uoes CMl slqool blqb poollty?

uesplLe some companles havlng CM cerLlflcaLlon, some of Lhose we lnLervlewed remalned
unconvlnced LhaL Lhls lmproves quallLy of drugs. lor example, Lhe pharmaclsL responslble for
Lhe pharmacy aL uhullkhel hosplLal ln kavre dlsLrlcL Look down a boLLle of paedlaLrlc amoxlclllln
(L8lMCx) made by ueurall-!anaLa harmaceuLlcals, a nepall company wlLh CM cerLlflcaLlon.
Pe polnLed ouL LhaL Lhe marker Lo flll Lo was on Lhe label noL on Lhe boLLle, LhaL Lhe sLlcker was
puL on by non professlonals, LhaL Lhere ls no chlld proof Lop, and LhaL Lhe measurlng Lop, made
of plasLlc are noL always correcL. Would you glve Lhls producL CM cerLlflcaLlon he asked
rheLorlcally? Pe Lhen broughL down a boLLle from Sandlp (whlch had been glven as a donaLlon Lo
Lhe hosplLal). 1he llne was marked ln Lhe glass, Lhere was a chlld proof Lop, and every lngredlenL
was menLloned on Lhe label (noL [usL Lhe acLlve lngredlenL). nepall companles have noL yeL
maLured" he sald. Pe sald LhaL he llkes Lo say LhaL pharmaceuLlcal companles klll more people
Lhan 8ln Laden!" When asked how Lhe company could have recelved CM cerLlflcaLlon he [usL
shrugged. As a consequence, when a Medlcal 8epresenLaLlve comes Lo hlm suggesLlng Lhey buy
LhaL companles producL, he does noL LrusL Lhe quallLy of Lhe producL based on wheLher Lhey are
cerLlfled or noL, buL has Lhe producLs lndependenLly checked. 1hls lack of LrusL exLends Lo Lhe
rlfamplcln supplled by Lhe governmenL ln Lhe uC1S programme. Pe doesn'L belleve" ln Lhe
governmenL purchased rlfamplcln. When l menLloned Lhe new global procuremenL sysLem,
requlrlng CM cerLlfled quallLy, he sLlll lnslsLed LhaL Lupln would be geLLlng loLs of commlsslon
and he doesn'L LrusL Lhelr producLs elLher. Pe has cllnlcal evldence from Lhls hosplLal LhaL Lhe
drugs provlded by Lhe uC1S programme don'L work he Lold us. Such ls hls mlsLrusL of Lhe
sysLem, LhaL he based hls oplnlon of Lhe efflcacy of drugs from hls own emplrlcal relaLlonshlp
wlLh LreaLmenL ouLcomes, sLaLlng LhaL Lhe C1L rlfamplcln ls Ck ln hls oplnlon and advlses Lhose
paLlenLs who can afford lL Lo buy Lhelr 18 drugs prlvaLely.

A pharmaclsL who works ln Lhe prlvaLely owned pharmacy ln Lhe MaLernlLy PosplLal explalns Lhe
reglsLraLlon process wlLh Lhe uuA for a new drug (lnLervlew, pharmaclsL, kaLhmandu, 9 Aprll
2007):
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
24

Su: ln nepal, whaL happens ls LhaL, whenever a pharma company has Lo produce a
cerLaln producL, lL has Lo reglsLer lLself ln Lhe uuA Lo geL a manufacLurlng llcense. And
Lhen Lo manufacLure Lhe producLs lL has Lo reglsLer Lhe producL ln Lhe uuA. 8uL flrsL
Lhey have Lo geL a llcense for Lhe lndusLry" (here he means company). llrsLly Lhey have
Lo reglsLer Lhe lndusLry". 1hen afLer LhaL Lhe survelllance wlll be done by Lhe uuA. AfLer
Lhe approval of uuA Lhey geL Lhe manufacLurlng llcense. 1hen Lhey proceed wlLh lL.
1hen Lhey have Lo glve foll deLalls. 1hey need Lo prlnL manufacLurlng llcense on Lhls foll.

lP: So Lhey can'L sell lL wlLhouL Lhls?

Su: 1hey can'L. AfLer Lhls, Lhe uuA agaln check everyLhlng and Lhen only Lhe producL can
be broughL lnLo Lhe markeL. AfLer Lhls Lhey are allowed Lo make Lrlals (Pe meanL raw
maLerlals Lrlals here). llrsL Lhey are allowed Lo lmporL Lhe raw maLerlals. lf lL ls a
conLrolled drug Lhen Lhey are allowed Lo lmporL a llmlLed amounL. AfLer Lhey recelve
Lhese conLrolled/narcoLlc subsLances Lhen Lhey are supposed Lo reporL Lo Lhe uuA LhaL
Lhey have recelved Lhls much amounL of Lhls drug. 1hen Lhey do successlve Lrlals (Lrlals
of raw maLerlals) unLll Lhey geL Lhe good formulaLlon. AfLer havlng Lhe formulaLlon, Lhey
pack Lhe drug and send lL Lo 8u8L (n8 8oyal urugs 8eference LaboraLory), whlch ls [usL
behlnd Lhe uuA. 1here Lhey check Lhe quallLy and see lf Lhe drug has meL Lhe crlLerla.
Slnce we don'L have our own nepalese harmacopoela, we solely rely on lndlan
pharmacopoela or 8rlLlsh harmacopoela. A harmacopoela Lells you how Lo
manufacLure a drug, whaL are Lhe crlLerla for manufacLurlng a drug. lor example, lf you
have Lo make a LableL Lhen, whaL are Lhe raw maLerlals necessary, whaL analysls musL
raw maLerlals pass Lhrough, Lo be lncluded ln Lhe formulaLlon eLc.? 1he harmacopoela
glves a serles of rules and LesLs LhaL has Lo be carrled on raw maLerlals. And afLer LhaL
you can carry on Lo make a drug. Lven afLer maklng a drug, lL has Lo pass Lhrough a
serles of LesLs before lL can come Lo Lhe markeL. lf you refer Lo Lhe lndlan
pharmacopoela ln Lhe beglnnlng Lhen all Lhese sLages musL comply Lo Lhe lndlan
pharmacopoela LhroughouL. lf Lhey fall Lo do LhaL Lhen Lhe whole baLch would fall. lL
cannoL come Lo Lhe markeL. So Lhe 8u8L afLer checklng everyLhlng quallfles. 1hen Lhe
lndusLry submlLs Lhe 8u8L reporL and Lhe drug sample Lo Lhe uuA for Lhe producL
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
23
llcense. AfLer geLLlng Lhe producLlon llcense, Lhey produce lL and Lhen Lhey send lL Lo Lhe
markeL.

lrom an lnLervlew wlLh one wholesaler, hls experlence ls LhaL some docLors are now only
prescrlblng CM cerLlfled company producLs as a way of ensurlng quallLy. Pe suggesLed LhaL Lhls
was Lhe case even wlLh Lhose commonly prescrlbed drugs produced ln nepal (e.g., Amoxyclllln).
1he quesLlon of docLors and prescrlbers LrusLlng cerLaln brands over oLhers ls a complex one,
parLlcularly ln Lhe generlc markeL. lor example, wlLh lluoxeLlne we have been Lold LhaL
resldenLs aL Lhe Leachlng hosplLal are LaughL Lo prescrlbe Lhe drugs from companles Lhey LrusL,
noL wrlLe Lhe generlc name on prescrlpLlons. Clven LhaL Lhe pracLlce of subsLlLuLlon" by
reLallers ls common place, parLlcularly ouLslde hosplLals, and LhaL many medlcal represenLaLlves
for drug companles pay subsLanLlal lncenLlves for docLors Lo prescrlbe Lhelr producLs Lhere are a
number of lssues aL sLake here.

ulJ utoqs Nepol stop ptoJocloq tlfomplclo becoose of tbe stlpolotloo of CMl cettlflcotloo?

1hls lnformaLlon comes from an lnLervlew wlLh Lhe currenL dlrecLor of ACn, kk, who worked
for 8oyal urugs nepal, and was responslble for Lhe producLlon of 8lfamplcln ln Lhe 1990s for Lhe
naLlonal 1uberculosls rogramme. 1hls was prlor Lo Lhe developmenL of Lhe WPC global
procuremenL mechanlsm Lhe Clobal urug laclllLy (Cul), Lhrough whlch nepal ls currenLly
supplled lLs anLl-Luberculous drugs (purchased lnlLlally by uflu, Lhen Lhe Clobal lund). lL
addresses how quallLy conLrol was dealL wlLh ln relaLlonshlp wlLh !apanese supporL, prlor Lo
CM cerLlflcaLlon ln nepal (noLes were Laken durlng Lhe lnLervlew so Lhls ls a summary of whaL
he sald, noL dlrecL quoLaLlon):

8oyal urugs produced 130 and 430 mg LableLs for Lhe nepal 1uberculosls CenLre (n1C).
1hls producLlon sLarLed, he Lhlnks, ln 1990 (n8 - lan: l Lhlnk lL was laLer Lhan Lhls). 1here
was a campalgn ln 18 managemenL called uC1S, a WPC slogan". Cn Lhls ground Lhe
!apanese CovernmenL wanLed Lo help Lhe n1C, by provldlng Lhe medlclnes. 1hey
supplled Lhe capsules for one year, and Lhese were made ln !apan. ur 8am (who was
Lhen Lhe ulrecLor of Lhe n1C) asked why Lhey could noL buy from nepal? lL would be
cheaper and Lhey could susLaln Lhe supply. A group from Lhe !apanese harmaceuLlcal
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
26
ManufacLurers AssoclaLlon (!MA) came Lo nepal, and wlLh some people from !lCA Lhey
vlslLed 8oyal urugs. AL Lhls Llme kk was chlef of Lhe Capsule SecLlon. 1he machlnery Lhey
had for capsule producLlon was manually operaLed and Lhey dld noL have Lhe capaclLy Lo
produce Lhe requlred amounL. 1he group were lnLeresLed and sald Ck, buL Lhey sald
LhaL you need Lo make a plan. 1he new machlne would requlre a new chamber as lL
wouldn'L flL ln Lhe exlsLlng one. 1he manager sald LhaL lf Lhey assure supply Lhen Lhey
would bulld Lhe new secLlon. kk Lhen deslgned lL. 1he WPC also came as well Lo look aL
CM sLandards and he deslgned lL accordlng Lo Lhese norms. lf l vlslL 8oyal urugs Loday
he sald l would sLlll flnd Lhls rlfamplcln secLlon.

1he !MA experL came and sLayed aL Lhls Llme for one monLh. kk was dellghLed and he
learnL much aL Lhls Llme. lor example, say you have a baLch of drugs, 8aLch 1 he
explalned. 1hls ls Lhen dlvlded lnLo LoL A, LoL 8, LoL C, LoL u. lf Lhe machlne produces
one baLch Lhen Lhls ls 200kg (4 x 30 kg LoLs). 1he !MA experL sald Lake 3g from each
loL, mlx Lhem up and LesL Lhls for quallLy. lf lL passes Lhen 8aLch 1 passes. 1hey dld Lhls
for each baLch LhaL Lhey produced. ln Lhls way Lhey produced Lhe flrsL slx baLches and
for each baLch Lhey senL a sample llke Lhls Lo !apan for LesLlng, and 8oyal urugs also
LesLed Lhem. Slx baLches made up abouL 3 monLhs supply for Lhe naLlonal programme.
1hey also had Lo send Lhls quallLy reporL Lo !apan as well, Lhey read Lhese closely and
Lhen Lhey sald LhaL boLh Lhe LesLs Lhey dld, and Lhe 8u LesLs were Ck. lor 4-3 years Lhey
supplled Lhe n1C wlLh Lhese drugs.

1he flrsL loL of acLlve lngredlenLs came from !apan dlrecLly Lo Lhe n1C. 1hen for Lhe flrsL
year LhaL 8u made Lhe rlfamplcln Lhe raw maLerlals came from !apan as well - Lhey
were Lhen confldenL wlLh Lhe quallLy of Lhe producL. 1he capsules came from lndla or
1halland. lor Lhe acLlve lngredlenL, !apanese labour cosLs were hlgh and so Lhe raw
maLerlals were expenslve. 1hey asked 8u lf Lhey could buy Lhe raw maLerlals
Lhemselves. 8u Lhen boughL Lhls from Chlna and Pong kong, as Lhey were on Lhe WPC
approved llsL. 8uL lf a company was new, Lhey would LesL Lhe acLlve lngredlenLs
Lhemselves. 1hls ls vendor managemenL", and whlle Lhey don'L vlslL Lhe company lLself,
Lhey LesL Lhe producL. Cne beneflL was LhaL Lhey could buy ln dollars from Chlna, whlch
meanL less exclse duLy. 1hls was more lf lL was boughL wlLh rupees, be LhaL elLher nepall
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
27
or lndlan. 8u goL Lhe raw maLerlals from Chlna for an lnlLlal Lwo year conLracL, and
procured from Lhere for a LoLal of flve years. AfLer Lhls Llme Lhe managemenL of 8oyal
urugs changed and LhaL of n1C changed as well, and no one wanLed 8oyal urugs Lo
produce Lhe rlfamplcln capsules anymore. Pe Lhlnks LhaL some oLher company probably
provlded ln Lhe pockeL" some lncenLlves Lo Lhe n1C.

ln response Lo dlrecL quesLlonlng lf Lhls was relaLed Lo Lhe Cul, and CM cerLlflcaLlon,
he replled LhaL he dld noL know abouL LhaL buL Lhlnks lL was relaLed Lo brlbery LhaL Lhey
losL Lhe conLracL. 1he change of managemenL ls Lhe cause - Lhen you lose your personal
connecLlons. no-one remembers Lhe hlsLory afLer a whlle. lL was only ln 2002 when Lhe
uuA has glven Lhe mandaLe LhaL every company has Lo have CM cerLlflcaLlon by 2007.
AL Lhe Llme when Lhey were produclng rlfamplcln lL was noL mandaLory, so LhaL was noL
Lhe reason ln hls oplnlon. l asked lf Lhls had anyLhlng Lo do wlLh uflu buylng Lhe drugs,
afLer !lCA sLopped and lf Lhey had dlfferenL rules abouL quallLy, and he relled LhaL !lCA
were happy wlLh Lhe quallLy, buL he does noL know abouL uflu.

CovernmenL regulaLlon currenLly sLaLes LhaL any Lender for Lhe governmenL procuremenL of
drugs musL be accompanled by Lhe approprlaLe paperwork, whlch lncludes CM cerLlflcaLlon.
uesplLe Lhls, and LhaL Lhe old sLaLe run nepal urugs (nu) doesn'L have CM cerLlflcaLlon,
conLracLs for publlc procuremenL are awarded as a prlorlLy Lo nu (Lhls ls descrlbed ln more
deLall ln Lhe nepal drug dlsLrlbuLlon paper).

Ao exomple of tbe polltlcs of CMl

ln a conversaLlon wlLh a senlor advlsor Lo Lhe MlnlsLry of PealLh, lP was Lold Lhe followlng ln
relaLlon Lo Lhe pollLlcs of CM. 1he !-vacclne (for !apanese LncephallLls) for nepal was pald for
by !apan and procured from a company ln Chlna, buL Lhls was noL CM cerLlfled. 1hls year
(2007) Lhey could noL buy lL, desplLe !apan saylng Lhey were happy wlLh Lhe quallLy and wllllng
Lo glve Lhe money. 8uL Lhe money was noL glven dlrecLly Lo Lhe nepal governmenL, buL Lo
unlCLl, and Lhey were unable Lo buy lL Lo Lhen glfL Lo Lhe governmenL because lL was noL CM
cerLlfled. 1he manufacLurer has noL yeL applled for CM cerLlflcaLlon. 1he WPC, or oLher un
agencles, cannoL procure any drugs wlLhouL CM cerLlflcaLlon. Whlle Lhls example ls suggesLlve
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
28
of some of Lhe lssues aL sLake wlLh CM cerLlflcaLlon ln a heavlly ald dependenL sLaLe llke nepal,
lL needs Lo be followed up ln more deLall.

Cettloq otoooJ teqlsttotloo. u1cs?

Some (prlvaLe) hosplLals have esLabllshed urugs and 1herapeuLlcs CommlLLees (u1C). lor
example Lhe norvlc hosplLal dlrecLor explalned LhaL Lhelr commlLLee - esLabllshed ln lebruary
2006 - allows Lhem Lo procure from any parL of Lhe world, even lf LhaL drug ls noL llcensed ln
nepal wlLh Lhe uuA. Pe explalned LhaL Lhe u1C formaLlon has been encouraged by Lhe uuA who
don'L have physlclans", alLhough Lhe governmenL says whaL Lhe makeup of Lhe commlLLee
should be. 1he u1C Lhen can lmporL" medlclnes noL reglsLered, for example lmporLanL drugs
for Lhelr hosplLal cardlac medlclnes (Lhe hosplLal speclallsed lnlLlally ln cardlology - and has
expanded from LhaL). 1hey have Lo produce documenLs" - sLudles and ouLcomes from Lhese
drugs. 1hus Lhey are able Lo provlde daLa for laLer reglsLraLlon.

A recenL communlcaLlon ln Lhe kaLhmandu unlverslLy Medlcal !ournal suggesLed LhaL Lhese
commlLLees have a supporLlve funcLlon for Lhe uuA: ln developlng counLrles llke nepal, where
Lhe pharmacovlgllance programs are ln lLs prlmlLlve sLage, Lhe u1C has lmmense responslblllLy ln
ensurlng drug safeLy. 1hls commlLLee can also acL as an advlsory commlLLee Lo Lhe pollcy makers
and drug regulaLory auLhorlLy of nepal for drug safeLy maLLers based on Lhelr experlences"
(alalan and Mlshra 2003).

CMl ooJ expott

no nepall company yeL exporLs any pharmaceuLlcal producL. Powever, CM cerLlflcaLlon ls also
requlred for Ayurvedlc producLs. ln an arLlcle on Lhe W1C webslLe (Shakya 2003), on Lhe
experlence of a nepall Ayurvedlc company (Corkha Ayurved Co.) Lo exporL medlclnal herbs, Lhe
auLhor expresses surprlse LhaL Lhey requlred CM cerLlflcaLlon. 1he company had no ldea LhaL
Lhls was necessary (or LhaL buyers could also ask for oLher lnLernaLlonally harmonlsed sLandard
of SanlLary and hyLosanlLary Measures (SS). When Lhe company seL abouL Lhe process of
headlng Lowards CM cerLlflcaLlon, Lhey found Lhe 8u8L (and Lhe ueparLmenL for lood
1echnology and CuallLy ConLrol - ul1CC) wlLhouL any plan of pollcy regardlng SS sLandards,
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
29
lncludlng CM cerLlflcaLlon procedures", parLlcularly for Ayurvedlc producLs (Shakya 2003).
AlLhough accedlng Lo Lhe W1C, lL seems LhaL LhaL Lhere were few aLLempLs Lo sLrengLhen Lhe
lnsLlLuLlonal capaclLy Lo pracLlcally develop Lhls. 1he company had no ldea LhaL Lhe uuA had
already called for all pharmaceuLlcal companles (lncludlng Perbal ones) Lo ablde Lo WPC CM
cerLlflcaLlon, as a prerequlslLe for Lhe SS mechanlsm. Shakya ls crlLlcal LhaL Lhe uuA had noL
prepared lLself for accredlLaLlon processes, nor deLermlned Lhe baslc mechanlsms LhaL
companles should Lake. 8uslnesses were preLLy much on Lhelr own, suggesLs Lhe auLhor. 1he
company had huge ouLlays, lncludlng hlrlng a forelgn experL Lo asslsL ln Lhe process.

lL seems apparenL LhaL one consequence of aLLempLlng Lo harmonlse lLs regulaLory capaclLy wlll
be a greaLer dependence on forelgn asslsLance (boLh Lechnlcal and flnanclal) for Lhls process.

4. D|scuss|on and further quest|ons

AlLhough 18lS agreemenL ls presenLed as Lhe maln LhreaL for drug avallablllLy and affordablllLy
ln developlng counLrles, our prellmlnary research hlghllghLs how domesLlc producers flnd
compllance wlLh ever more sLrlngenL CM sLandards a ma[or obsLacle for domesLlc producLlon
of affordable pharmaceuLlcal producLs. MosL ma[or classes of drugs are now off paLenL and so
whlle 18lS affecLs fuLure producLlon of new producLs, CM affecLs generlc compounds.

lrom whaL we have learnL so far, compllance wlLh CM sLandards ls an lmporLanL barrler Lo
enLry, susLalnablllLy and posslbly, markeL expanslon for small drug producers ln boLh nepal and
lndla. ln nepal, Lhe maln preoccupaLlon of local producers ls producLlon for domesLlc markeLs.
Companles do noL alm Lo exporL Lhelr pharmaceuLlcal producLs, Lhey merely sLrlve Lo secure
Lhelr poslLlon on Lhe nepall pharmaceuLlcal markeL. naLlonal healLh programmes are dependenL
on lnLernaLlonal ald, flnanclal and ln klnd, and bulk drug procuremenL usually bypasses naLlonal
governmenL and ls processed by lnLernaLlonal agencles such as Lhe Clobal urug laclllLy. Clven
LhaL such agencles rely on large and CM cerLlfled pharmaceuLlcal manufacLurers, nepall
companles do noL have access Lo slgnlflcanL parL of Lhe domesLlc markeL whlch resLrlcLs Lhelr
posslblllLles Lo recoup cosLs of lnvesLmenLs when producLs are Lled Lo sLrlngenL quallLy
assurance sysLems.

aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
30
We do noL quesLlon Lhe lmporLance of quallLy conLrols. 1he lssue raLher seems Lo be abouL how
much quallLy assurance aL each producLlon and dlsLrlbuLlon sLage ls really requlred and whaL are
Lhe cosLs of Lhese marglnal conLrols Lo pharmaceuLlcals manufacLurers ln developlng counLrles.
lurLher areas for fuLure research are ouLllned below.

We need Lo examlne Lhe capaclLy of regulaLory auLhorlLles ln developlng counLrles Lo develop,
monlLor and enforce manufacLurlng sLandards: sLaff, ln Lerms of numbers and experLlse, and
flnanclal resources.
lL would be useful Lo look from Lhe producers' perspecLlve, aL Lhe cosL of compllance wlLh CM
sLandards and how lL ls reflecLed ln prlce. Pow much does lL cosL Lo lnLroduce quallLy assurance
sysLems? Pow cosLly ls Lhe Lralnlng of sLaff necessary for lmplemenLaLlon of Lhese new sysLems?
WhaL are Lhe fees for audlLlng and CM cerLlflcaLes? Pow are CM cerLlflcaLes lssued and pald
for?

AnoLher serles of quesLlons refers Lo how acLors ln domesLlc markeLs percelve CM
cerLlflcaLlon. uo dlsLrlbuLors and reLallers requlre CM cerLlflcaLes from manufacLurers Lo be
sure abouL producL quallLy? ls CM cerLlflcaLe a sufflclenL proof of quallLy? An eLhnographlc
quesLlon here relaLes Lo Lhe symbollc lmpacL of CM cerLlflcaLlon, and how ldeas around lL
clrculaLe amongsL varlous acLors ln Lhe sysLem. Pow has CM cerLlflcaLlon fed lnLo percepLlons
of quallLy and LrusL of parLlcular companles' producLs, and how does lL feed lnLo how docLors,
reLallers, wholesalers and oLhers percelve quallLy?

lL would be useful Lo undersLand Lhe sLraLegles whlch are belng adopLed Lo overcome CM
regulaLlon and how effecLlve Lhese are from Lhe producer perspecLlve? We also need Lo Lalk Lo
Lhe sLandard seLLers ln Lhe WesL Lo undersLand Lhe sLandard seLLlng process. WhaL are Lhe
lssues LhaL Lhese seLLers of sLandards percelve Lo be aL sLake ln counLrles such as lndla and
nepal?


keferences

aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
31
Abraham, !. and 1. 8eed (2001). 1radlng rlsks for markeLs: Lhe lnLernaLlonal harmonlzaLlon of
pharmaceuLlcals regulaLlon." neoltb, klsks & 5oclety 3(1): 113-128.
8ralLhwalLe, !. and . urahos (2000). Clobol bosloess teqolotloo. Cambrldge, uk, new ?ork,
Cambrldge unlverslLy ress.
8ureau 8eporL (2007). CenLral urug AuLhorlLy wlll be formed ln slx monLhs: ur 8amadoss,"
lbotmoblz.com, Chennal, 13 !anuary.
uanzon, .M. and L.L. keuffel (2003). 8egulaLlon of Lhe pharmaceuLlcal lndusLry," (unpubllshed
paper presenLed aL n8L8 Conference on 8egulaLlon, SepLember 2003).
ueparLmenL of urug AdmlnlsLraLlon, uuA. (hLLp://www.dda.gov.np), LasL on accessed on 22
!une, 2007. kaLhmandu: MlnlsLry of PealLh & opulaLlon, CovernmenL of nepal.
ulxlL, P. (2000). nepal's CuesL for PealLh," (hLLp://www.hdlxlL.org.np/quesL/AnnLx-l.pdf), LasL
accessed on 20 !une, 2007.
Luropean Agency for Lhe LvaluaLlon of Medlclnal roducLs, LMLA. (hLLp://www.emea.eu.lnL),
LasL accessed on 21 May, 2007.
Crazal, !.C. and u.S. Larl (1997). Lu and luA CM 8egulaLlons: Cvervlew and Comparlson",
Ooollty Assotooce Iootool 2: 33-60.
lnLernaLlonal Conference on ParmonlsaLlon of 1echnlcal 8equlremenLs for 8eglsLraLlon of
harmaceuLlcals for Puman use, lCP. (hLLp://www.lch.org), LasL accessed on 18 May,
2007.
lmmel, 8. (2000). A brlef hlsLory of Lhe CMs", keqolototy compllooce Newslettet, W|nter
200S.
lndlan Lmbassy (2007). lndla Lconomlc news,"
(hLLp://www.lndlanembassy.org/Lconomlc_news/2007/lndla Lconomlc news vol.lll
lssue 2.pdf), LasL accessed on 16 May, 2007.
Lee, .8. and !. PerzsLeln (1986). lnLernaLlonal drug regulaLlon," Aooool kevlew of lobllc neoltb
7: 217-233.
Medlclnes and PealLhcare roducLs 8egulaLory Agency, MP8A. (hLLp://www.mhra.gov.uk), LasL
accessed on 18 May, 2007.
----. CooJ Mooofoctotloq ooJ ulsttlbotloo ltoctlce,
(hLLp://www.mhra.gov.uk/home/ldcplg?ldcServlce=SS_CL1_ACL&nodeld=613), LasL
accessed on 16 Aprll, 2007.
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
32
Mrazek, M. and A. lldler (2004). Access Lo pharmaceuLlcals and regulaLlon ln Lhe
CommonwealLh of lndependenL SLaLes," ln: keqolotloq pbotmoceotlcols lo otope.
sttlvloq fot efflcleocy, epolty ooJ poollty, eds Lllas Mosslalos, Monlque Mrazek, 1om
Walley. Cpen unlverslLy ress, 2004.
Shadle, .!. (2004). Cvervlew of CMs," 8lo lbotm lotetootloool,
(hLLp://www.blopharmlnLernaLlonal.com/blopharm/arLlcle/arLlcleueLall.[sp?ld=134223),
LasL accessed 23 Aprll, 2007.
Shakya, 8. (2003). nepal: LxporLs of Ayurvedlc Perbal 8emedles and SS lssues," ln: Moooqloq
tbe cbolleoqes of w1O lottlclpotloo - 45 cose 5toJles, eds eLer Callagher, aLrlck Low,
and Andrew L. SLoler. W1C 2003.
WPC 1992. Annex 2: rovlslonal guldellnes on Lhe lnspecLlon of pharmaceuLlcal
manufacLurers,"
(hLLp://whqllbdoc.who.lnL/publlcaLlons/2004/9241346190_lnLroducLlon.pdf), LasL
accessed on 23 !une 2007.
----. 2004. WPC good manufacLurlng pracLlces: maln prlnclples for pharmaceuLlcal producLs,"
ln: wnO xpett commlttee oo 5peclflcotloos fot lbotmoceotlcol ltepototloos. 1hlrLy-
sevenLh reporL. Ceneva, World PealLh CrganlzaLlon, 2003. Annex 4 (WPC 1echnlcal
8eporL Serles, nC. 908).
(hLLp://whqllbdoc.who.lnL/publlcaLlons/2004/9241346190_parL1.pdf), LasL accessed on
17 Aprll, 2007.


Append|x

A.1. WnC - types of |nspect|ons

8ouLlne lnspecLlons are full lnspecLlons of all componenLs of CM LhaL are carrled ouL when Lhe
producer ls newly esLabllshed, has lnLroduced new producLs, applled for Lhe renewal of llcense,
has noL been lnspecLed ln Lhe lasL 3-3 years, or lf Lhere ls a record of non-compllance. ln
conLrasL, conclse lnspecLlons focus only on selecLed lndlcaLors and ldenLlflcaLlon of slgnlflcanL
changes. 1hey are applled lf Lhere ls a record of compllance wlLh CM sLandards. lollow-up
lnspecLlons are deslgned Lo check wheLher correcLlve acLlons recommended aL Lhe prevlous
lnspecLlons were successfully lmplemenLed. Speclal lnspecLlons are carrled ouL lf Lhere are any
complalnLs or recalls relaLed Lo subsLandard quallLy of producLs or ln case of adverse drug
reacLlons and can be focused on a speclflc producL, group of producLs, or operaLlon. 1he lasL
Lype of lnspecLlons, quallLy sysLems revlews, descrlbes a quallLy assurance sysLem LhaL has been
saLlsfacLorlly lmplemenLed and manufacLurer's pollcy for quallLy assurance.
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
33

Announced lnspecLlons are recommended for regular vlslLs Lo evaluaLe new planLs, producLs,
renewal of llcense. unannounced lnspecLlons are requlred for conclse, follow-up, and speclal
vlslLs. Such lnspecLlons and/or Lhelr varlaLlons are recommended and employed also by
regulaLory auLhorlLles ln developed counLrles.



A.2 LMLA act|v|t|es

lrom May 2007, Lhe LMLA admlnlsLers a CommunlLy CM uaLabase, LudraCM, whlch alms Lo
faclllLaLe Lhe exchange of lnformaLlon on compllance wlLh good manufacLurlng pracLlce wlLhln
Lhe Luropean medlclnes neLwork" (LMLA, 01 May 2007). 1he daLabase ls open only Lo LC, LMLA
and naLlonal medlclnes agencles (Lu member sLaLes, lceland, LlchLensLeln and norway) and lL
conLalns lnformaLlon on all manufacLurlng and lmporLaLlon auLhorlzaLlons and all CM
cerLlflcaLes lssued by Lhe naLlonal medlclnes agencles wlLhln Lhe neLwork and also reporLs on
deflclencles encounLered durlng lnspecLlons conducLed wlLhln Lhe neLwork or ln Lhlrd counLrles.

WlLhln Lhe LMLA, Lhe CommlLLee for Medlclnal roducLs for Puman use (CPM) coordlnaLes
Lhe cenLrallzed procedures, arblLraLes ln cases when member sLaLes do noL agree on markeLlng
auLhorlzaLlon of a speclflc producL, and acLs ln cases when publlc healLh ls aL sLake. 1he
cenLrallzed revlew process works Lhrough a neLwork of Luropean experLs from 27 Lu member
sLaLes and Lhree LLA-Ll1A sLaLes, lceland, LlchLensLeln and norway.

1he CPM also monlLors safeLy of auLhorlzed producLs vla Lhe reporLlng sysLem, Ludravlgllance,
and makes recommendaLlons Lo Lhe LC lf any changes ln markeLlng auLhorlzaLlon of speclflc
producLs or producL's wlLhdrawal from Lhe markeL are necessary (LMLA, 2007).

CM guldellnes for medlclnal producLs are sLaLed ln ulrecLlve 2003/94/LC and have Lwo parLs:
one appllcable Lo Lhe manufacLure of medlclnal producLs and one covers CM for acLlve
subsLances used as sLarLlng maLerlals (LMLA web, 2007). lL ls Lhe second parL LhaL ls based on
lCP C7A guldellnes on acLlve pharmaceuLlcal lngredlenLs. 1he Lu Culdellnes also lnclude a
number of speclflc and deLalled annexes focuslng on parLlcular acLlvlLles.

A.3 US IDA - system approach

ln 2002 Lhe luA adopLed sysLems approach for lLs lnspecLlons, meanlng LhaL Lhe followlng
sysLems (lCP C7A references) need Lo be audlLed:
quallLy (CuallLy ManagemenL, Change ConLrol, 8e[ecLlon and 8euse of MaLerlals,
ComplalnLs and 8ecalls, ConLracL ManufacLurers),
faclllLles and equlpmenL (bulldlngs and laclllLles, rocess LqulpmenL, uocumenLaLlon
and 8ecords),
maLerlal (MaLerlals ManagemenL, SLorage and ulsLrlbuLlon, WaLer, uocumenLaLlon and
8ecords),
producLlon (uocumenLaLlon and 8ecords, roducLlon and ln-rocess conLrols,
valldaLlon, Speclflc Culdance for Als ManufacLures by Cell CulLure/lermenLaLlon),
packaglng and labelllng (packaglng and ldenLlflcaLlon Labelllng of Als and
lnLermedlaLes, AgenLs, 8rokers, 1raders, ulsLrlbuLors, 8epackers, and 8elabellers) and
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
34
laboraLory conLrol sysLem (LaboraLory ConLrols, uocumenLaLlon and 8ecords,
valldaLlon).
lCP C7A secLlons on personnel, uocumenLaLlon and 8ecords apply Lo all sysLems.

luA lnspecLlons are of Lwo Lypes. Survelllance lnspecLlon ls a rouLlne lnspecLlon of
manufacLurlng faclllLles. Compllance lnspecLlons are for-cause conLrols or follow a vlolaLlve
survelllance lnspecLlon Lo verlfy correcLlve acLlons Laken.

lnspecLlon approaches applled by luA lnclude
full lnspecLlon opLlon whlch ls a broad and ln-depLh evaluaLlon of compllance wlLh Lhe
CuallLy SysLem and aL leasL Lhree oLher sysLems (could be boLh survelllance and
compllance lnspecLlon)
abbrevlaLed lnspecLlon opLlon - provldes an updaLe on manufacLurer's conformlLy wlLh
cCMs and lL lncludes an lnspecLlon of Lhe CuallLy sysLem and aL leasL one oLher sysLem
buL alLogeLher noL more Lhan Lhree sysLems (could be also boLh survelllance and
compllance lnspecLlon)
compllance lnspecLlon.

A.4 Ind|a: harmaceut|ca| regu|at|on and GM standards

Ceneral lnformaLlon abouL drug regulaLory requlremenLs are provlded by Lhe CenLral urugs
SLandard ConLrol CrganlzaLlon, MlnlsLry of PealLh and lamlly Welfare. 1he producLlon, lmporL,
dlsLrlbuLlon and sale of pharmaceuLlcals ls regulaLed by Lhe urugs and CosmeLlcs AcL, 1940. 1hls
acL has several schedules LhaL apply Lo pharmaceuLlcal lndusLry:
- Schedule M - speclfles Lhe general and speclflc requlremenLs for facLory premlses and
maLerlals, planL and equlpmenL and mlnlmum recommended areas for baslc lnsLallaLlon for
cerLaln caLegorles of drugs,
- Schedule 1 - CM speclflcaLlons for manufacLure of Ayurvedlc, Slddha and unanl medlclnes,
- Schedule ? - cllnlcal Lrlals leglslaLlve requlremenLs,
- CC guldellnes for research ln human sub[ecLs, based on ueclaraLlon of Pelslnkl, WPC
guldellnes and lCP requlremenLs for CC, drafLed by Lhe MlnlsLry of PealLh, urug ConLroller
Ceneral of lndla and lndlan Councll for Medlcal 8esearch,
- 1he harmacy AcL, 1948.

Chaudhurl (2003) menLlons dlfflculLles of small pharmaceuLlcal companles Lo adhere Lo CM
sLandards, especlally hlgh lnvesLmenLs necessary for upgradlng Lhelr producLlon faclllLles (pp.
248-232).

lndla, Cermany slgns fasL Lrack agreemenL Lo fasLen pharmaceuLlcals exporL" (!. Alexander,
harmablz, !an 02, 2007) - fasL Lrack approvals of drugs from lndlan manufacLurlng faclllLles
approved by Lhe uS luA or Lu, also Lhere ls lndo-Lu worklng group whlch was supposed Lo
meeL ln Aprll 2007 Lo dlscuss muLual recognlLlon of CM cerLlflcaLlon.

CovernmenL of lndla has approved seLLlng up of CenLral urugs AuLhorlLy of lndla (CuA) as an
auLonomous organlzaLlon Lo revamp Lhe drug regulaLory sysLem, brlnglng abouL unlformlLy of
drug llcenslng, and Lo lmprove quallLy and safeLy of drugs. CuA ls envlsaged Lo have separaLe
dlvlslons for regulaLory overslghL of cllnlcal Lrlals, new drugs, medlcal devlces, cosmeLlcs,
vacclnes and blologlcals, good manufacLurlng pracLlce-compllance eLc." (lndlan Lmbassy, 2007)
aper 3 - Cood ManufacLurlng racLlce ln Lhe harmaceuLlcal lndusLry
33
CLher sources of lnformaLlon on CuA: CenLral urug AuLhorlLy wlll be formed ln slx monLhs: ur
8amadoss" ln harmablz, !anuary 13, 2007, PealLh mlnlsLry seeks cablneL nod for CuA, sLaLes
noL keen on cenLrallzlng drug admlnlsLraLlon" by !C MaLhew, 2006, harma lndusLry frowns on
formaLlon of Lhe CenLral urugs AuLhorlLy of lndla" by n vl[ay, harmablz !anuary 13, 2007,
AluCCC approaches M, pollLlcal parLles agalnsL move Lo CenLral llcenslng of pharmaceuLlcals"
by S ShasLrl, harmablz May 14, 2007.

1he much-hyped naLlonal harmacovlgllance rogramme, flagged off by Lhe unlon healLh
mlnlsLer abouL nlne monLhs ago, ls yeL Lo begln ln lLs rlghL earnesL. 1hough Lhe CenLral urugs
SLandard ConLrol CrganlzaLlon (CuSCC) has flnallzed Lhe llsL of coordlnaLlng cenLres aL Lhe
reglonal level, Lhe cenLres are noL fully funcLlonal so far." !C MaLhew, 'naLlonal
hramacovlgllance rogramme yeL Lo Lake off' ln harmablz, AugusL 10, 2003.

Cn CM compllance:
'SLaLe luA cancels llcenses of 163 pharma unlLs for non-compllance of CM' C. 8abu,
harmablz, Aprll 23, 2007,
'kerala lagglng ln Schedule M lmplemenLaLlon, 70 unlLs non-compllanL' v narayanan, harmablz,
Aprll 10, 2007,
'kerala Lo ban Cu players wlLhouL cCM & manufacLurlng llcense' 8 !ayakumar, harmablz,
AugusL 10, 2003,
'CovernmenL mooLs Lo scrap loan-llcenslng sysLem' !C MaLhew, harmablz, AugusL 09, 2003.

Cn reLallers:
1he governmenL proposal Lo lmplemenL Cood harmacy racLlces and a sysLem of
accredlLaLlon of pharmacles ln Lhe counLry should seL ln moLlon a revoluLlon ln pharmaceuLlcal
reLalllng ln Lhe nexL few years." A lrancls 'Changlng pharmacy pracLlces', harmablz,
november 29, 2006,
'Many reLall pharmacles ln kerala flouLlng 8ule 63 of urugs & CosmeLlcs AcL' v narayanan,
harmablz, May 23, 2007.

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