The problems associated with designing clean areas for pharmaceutical manufacturing

lie, to a large extent, in the diversity of requirements of the pharmaceutical

manufacturer . If their requirements are not understood then it will not be possible to
provide suitable clean areas. It is therefore necessary to consider what is produced in
the clean areas and how this affects the design in terms of room layout and environmental
quality.
Solutions: dung djch
Terminally sterilized products
Grade Examples of operation
A Filling of products, when unusually at risk
C Preparation of solutions, when unusually at risk. Filling of products.
D Preparation of solutions and components for subsequent filling
Remarks: Preparation of most products should be done in at least a grade D environment,
where there is an unusual risk, grade C environment should be used.
Aseptic preparations
Grade Examples of operation
A Aseptic preparation and filling
C Preparation of solutions to be filtered
D Handling of components after washing
Cleanroom suite layouts (kin truc dy phong sach)
Filling: nap liu
Hinh 4.1 th hin cu hinh dc trung cua mt dy phong sach d dap ung duoc
yu cu cua vic san xut mt san phm thuc tim ma no duoc v trung giai
doan cui. Nhn vin khi vao khu vuc phong sach phai qua 'phong thay d.
Trong do qun ao thuong duoc thay di, rua tay va mc d chuyn dung cho
phong sach. Nguyn liu th va dung cu nhu d chua truoc khi vao phai qua
phong ngn khng khi. Phong ngn khng khi duoc su dung d giam su nhim
bn tu bn ngoai dua vao phong sach. Dung dich duoc chun bi trong khu vuc
'solution preparation d chuyn di truc tip hoc gian tip boi ng va thung di
dng d nap liu cho qua trinh hoat dng trong phong clean Iilling`. Thung
chua so cp va bao bi dong goi duoc chun bi va rua sach trong phong
component preparation` va chuyn bng tay d dn cng doan dong goi hoc su
dung thit bi truyn tai. Thung chua d dy va kin duoi khu vuc khng khi chay
dng huong trong phong clean Iilling`. Va thung hang roi khu phong sach
thng qua ni hp v trung cui cung.
hinh 4.2 th hin mt cu hinh kin truc dc trung cua phong sach d san xut
mt san phm dung mt k thut nap liu tit trung. Su khac nhau trong yu cu
quy trinh dn dn su khac nhau o mt s dim mu cht: kin truc hoan toan c
lp dn mt phong sach va mt phong v trung. Co su ngn cach giua giua 2
khu vuc duoc tao ra boi lo, ni hp va cua sp cho cac vt co th vao bung v
trung, va vuot qua su ngn cach cua khu vuc chun bi dung dich va phong nap
liu v trung. Nhu tng th mi truong kim soat cua bung sach va v trung la
khac nhau, chia ra va nhiu thay di nghim ngt duoc dua va di voi bung v
trung. No cung co th phu hop khi mt su cach ly bng dong khi dng huong
cua khu vuc lam vic.
Mi truong sach
D dat duoc cht luong khng khi sach cua mi truong bn trong la yu cu kho
nht va duoc xac dinh boi:
- luong cht bn giai phong trong phong
- cht luong khng khi cp vao phong
- luu luong va phuong phap cung cp khng khi trong phong nhu thng gio
thng thuong (dong ri) hoc dong chay tng dng huong hoc kt hop ca hai.
- luong cht bn ra vao tu phong k bn. Khi cach ly duoc su dung, nhiu su
xem xet ging nhau duoc duoc yu cu nhung thng thuong su nhim bn ra
vao tu bn ngoai khu vuc duoc cach ly la ti thiu.
Tao ra cht bn va phat tan no:
Cht bn co th dn tu:
Con nguoi
Dung cu san xut
B mt
Cht bn nghim trong nht trong phong sach duoc phm la vi khun va hu ht
chung dn tu con nguoi (tru nhung vi khun ni tai trong phong). Do do khi bit
duoc s nguoi cn thit d lam vic trong phong tu do suy ra duoc truc tip
luong khng khi yu cu cn cung cp d lam long va loai tru duoc cht bn
phat ra tu con nguoi. Hiu qua cua nhung b qun ao cua ho mc s truc tip
phn tan cht bn boi con nguoi trong phong va tu do suy ra duoc luong khng
khi cn cp. Diu do d duoc lam r trong chuong 1. Loai qun ao cung anh
huong dn tai lanh, nhu hiu qua qun ao cang cao thi tranh duoc su (tan xa), it
su trao di khng khi qua lop vai qun ao. Do do con nguoi s cam thy nong
hon va yu cu nhit d trong phong thp hon.
Nhung thit bi san xut la ngun phat tan cht bn dang k. Chung co th duoc
ngn ngua nu ta lam sach cac hat bn ngay tu luc du truoc khi cho phep
chung vao phong sach. Diu do lam cho gia thanh thit k tng ln.
B mt phong sach co th la ngun cua cht bn do b mt roi ra do khng duoc
lam sach va khng bn vung. Loai b mt su dung trong phong sach duoc thao
lun trong chuong 9 cua quyn sach.
XM NHAP QUA CAC L HO CUA HE THONG LOC
Trong ca thit bi dng huong va thit bi du cui cung cp khi thi b loc HEPA.
B loc nay dat duoc hiu qua loc khng cao bng cac b loc duoc yu cu trong
nganh cng nghip vi din tu. Ly do diu nay la gp ba ln. Du tin, vi khun
thuong khng co o trong khng khi dang don bao nhung duoc tp hop trn b
mt vt liu nhu b mt hat bui va co kich thuoc trung binh trong khng khi vao
khoang 10 dn 15 m. (thu 2, nhung hat vt cht nho boi vi su lng dong cua
chung nho nn it co co hi xm nhp vao khng gian tu khng khi d du s
luong d gy bnh.) cui cung, cac hat vt cht rt nho khng duoc bit dn la
gy hai cho bnh nhn. B loc HEPA voi hiu sut khoang 99.97 di voi hat
bui co kich thuoc tu 0.5m tro ln.
B loc HEPA phai duoc kim tra trong nha may. Tuy nhin mt b loc tt luc o
xuong san xut vn chua du, hiu sut cui cung con phu thuc vao vic bao
quan va tay ngh tho lp dt. (Hiu sut cua nha hoc xuong phu thuc vao b
loc, va khi b loc duoc lp dt vao toa nha thi toan b h thng thu nghim cua
mt bai kim tra tai ch (in situ test) nhu su nong lanh cua du hoc kim tra
binh phun nhn tao d duoc ph duyt khac. mt b loc hiu qua cao va b
khung duoc san xut boi mt nha san xut co uy tin rt co th dam bao mt kt
lun thoa dang.)
Vic lot qua (by-passing) cua cac hat bui do kt cu b loc ti thuong xay ra.
Vic ung dung bai test ap luc DIN 1946 co y nghia lon di voi b loc nhu la
dung cht long d lam kin lam tng suc chiu dung cua nhung kt cu khng phu
hop, va tranh vic phai su dung ap luc cao d chc chn v hiu qua cua ming
dm.
Mt diu quan trong trong vic lp dt dung b loc la chc chn la vo boc cua
b loc duoc lp dt dung noi d kt ni hiu qua dn trn gia cua phong sach.
Vic lp dt chinh xac tai dim kt ni s giup tranh duoc su xm nhp cua bui
bn tu khng gian ngoai va cung tranh duoc bui bn thoat ra tu vt liu kt cu
toa nha hoc la vt liu giua khung b loc va kt cu toa nha.
LOAI BO BUI BAN TRONG PHONG BANG THNG GIO QUA DAY
LUONG (DISPLACEMENT VENTILATION) HOAC THNG GIO LAM
LONG
Phuong an duoc thng gio toan b phong duoc lua chon d loai bo bui bn la h
thng dong dng huong hoc h thng dong khi ri, hoc la kt hop ca hai. Nhu
d cp o trn, phong phong sach nha may duoc ta thuong thy kt hop ca hai
phuong phap thng gio nhung khu vuc chung thi duoc thng gio bng phuong
phap dong ri con phuong phap dong dng huong duoc su dung d bao v
nhung khu vuc san xut noi ma san phm truc tip phat sinh bui bn. Duoc
minh hoa o hinh 4.3
Su kt hop cua hai phuong phap duoc nhc lai boi su xem xet sau:
- kinh t, nhu it khng khi duoc yu cu.
- su kt hop tu nhin cua dy phong duoc sach tht kho d su dung h thng
dng huong cho toan b khng gian lon. Mt kho khn dc trung cua phong
duoc la nu dung san duc l thi co th kinh va cht long co th roi xung va lot
vao san.
- lin quan dn kim soat ap sut phong duoc yu cu. phong co dong dng
huong thuong duoc cung cp boi h thng diu hoa ring. Diu do lam cho
vic cn bng ap sut giua cac phong kho dat duoc
- su tach ring. Nguoi dung thuong yu cu tach ring r rang giua khu vuc
hoat dng san xut va noi nghi ngoi trong phong. Diu do d dang thuc hin nu
dung h thng thng gio dng huong.
Nu mt luong lon bui bn tu do trong khng khi cua phong sach duoc bit, no
la diu co th, trong mt h thng thng gio dong thng thuong, d uoc luong
duoc luong khi cn phai cung cp va do do dat duoc yu cu v tiu chun cua
vic san sinh bui bn. Tuy nhin, thng tin v ti l phn tan cua nhn vin dc
bit la may moc rt kho dat duoc. Do do thng thuong khng khi cn thit duoc
ly tu tiu chun hoc huong dn GMP hoc theo kinh nghim
No cung duoc cn nhc v thit bi cung cp khng khi vi du nhu dung luoi hoc
ming thi, s anh huong dn huong di chuyn cua khng khi thng h thng
thng gio thng thuong va do do no cn phai duoc lam sach. Co nhiu loai thit
bi dua khng khi cp phu hop nhung v co ban co hai loai thit bi. Do la:
Ming gio sot trung hoc loai dang dia duc l d dua dong khi xung
Co nhiu loai canh hoc canh dao ming thi d dua khng khi vao phong tt
hon
Co hai loai ming thi duoc th hin o hinh 4.4 va 4.5. ming gio sot trung, l
hoc
Tinh toan luong gio cp phai nm duoc cac kin thuc sau:
S ln trao di gio ti thiu phu hop voi tiu chun phong sach d co th
loai bo duoc ht bui bn trong phong
Phu tai nhit bn trong
Luong khng khi cn thit d tao ap cho phong
Theo kinh nghim thi trong qua trinh san xut cac san phm thuc tim hin dai,
thi cac thit bi san xut giai phong nhit vao khng gian do do yu cu s ln
trao di gio tu 25 dn 35 ln/gio, do la muc ti thiu cho tiu chun phong sach
con d dat duoc ap sut trong phong co th con lon hon.
Phong nn duoc thit k d qua trinh san xut va mi truong duoc quan ly hiu
qua. D dat duoc tiu chun GMP quan trong la diu kin mi truong khng
duoc dao dng nhiu nu diu kin mi truong khng tt s lam cho san phm
bi nhim bn. Do do rt cn thit d nguoi su dung co th quan ly duoc diu
kin mi truong. Diu kin mi truong nn duoc dinh nghia truoc va duy tri
thuong xuyn trong qua trinh san xut.
Chung ta nn su dung cac thit bi kt hop voi nhau d kim soat duoc tim duoc
li cua h thng. Vi du, dung dung cu do luu luong va cng tc ap sut d xac
dinh nhung thng tin quan trong anh huong dn hiu sut hoat dng cua h
thng. Nhung li cua quat, b loc, diu khin co th dn dn ap sut phong thay
di.
Su cung cp khi cua dong dng huong thuong do mt h thng dc bit. Tuy
nhin, khi su dung cac thit bi dong dng huong dc bit hoc hp tru, no cn
phai co tiu chun ap dung ring cho thit bi. Vn d lon thuong gp voi thit bi
co dong khi dng huong la d xuyn qua cua b loc, lo thn cabin, dong khi mt
cn bng, va su tht bai trong vic kt hop voi cac co so thu nghim thng gio
cua h thng loc cung nhu giam sat hoat dng.
CACH LY MI TRUONG XUNG QUANH: cht luong mi truong ring mi
truong xung quanh cua mt di tuong cach ly hoc t hop cach ly phai duoc xac
dinh. Quyt dinh phai dua vao mt s diu la:
Nguy co qua trinh
Tinh toan ven cua rao can
Cac thao tac k thut
K thut vn chuyn
Ap sut bn trong
K thut cai thin v sinh mi truong
Cac yu cu diu khin
Nguy co qua trinh: D nhay cam cua san phm di voi bui bn la mt diu kin
quan trong d xem xet phn tich d nguy him. Diu du tin cn xem xet la san
phm duoc san xut v trung hay chi tit trung o giai doan cui. (San phm v
trung, dc bit chung tao diu kin cho vi khun phat trin, duoc huong loi tu
vic su dung h thng cach ly. San phm v trung giai doan cui khng duoc
loi tru khi do la mt vn d dc bit voi bui bn trong phong. Kha nng xm
nhp va phat trin cua vi sinh vt trong thung chua phu thuc vao a) thung chua
duoc chuyn dn khu vuc nap liu duoc dong hay mo b) khu vuc c c) thoi gian
mo va d) co hi phat trin cua vi khun trong san phm. Mt danh gia tt ca cc
buoc cua mt qu trnh tu lp rp v trng cua h thng dn vic chuyn giao
san phm s dua ra mt danh gia rui ro.