Critical Plant System

1

Kualifikasi SISTEM untuk pabrik Farmasi



Heating, Ventilation and Air Conditioning System (HVAC)

– Sistem Aliran Udara



Water System – Sistem Air (pengolahan dan distribusi)



Compressed Air and other gases – Sistem Udara

bertekanan dan gas-gas lain

Heating, Ventilation and Air-

Conditioning (HVAC)

HVAC

Tujuan

Untuk dapat memahami

 Perlunya HVAC systems

 peranan HVAC in dalam menjaga /protection:

– Product

– Personnel

– Environment

 peranan HVAC dalam „dust control‟

HVAC

Ruang lingkup

 HVAC systems can have an impact on product quality (HVAC dapat berdampak pada kualitas produk)

 It can provide comfortable conditions for operators (dapat memberikan suasana yang nyaman pada operator)

 The impact on premises and prevention of contamination and cross-contamination to be considered at the design stage

(memberikan perlindungan terhadap Contamination dan cros contamination )

Faktor-faktor yang dapat mempengaruhi

kualitas produk farmasi

Starting materials Personnel Procedures Validated processes Equipment Premises Environment Packing materials

Faktor – faktor yang harus diperhatiakn di area produksi

yang dapat mempengaruhi kualitas produk :

1. Light ( penyinaran / penerangan area produksi )

2. Temperature ( suhu )

3. Relative humidity ( kelembaban )

4. Air movement ( pola aliran udara )

5. Microbial contamination ( kontaminasi mikroba )

6. Particulate contamination ( kontaminasi partikel asing )

 Lingkungan yang tidak terkontrol akan memicu turunnya kualitas produk seperti produk yang terkontaminasi.

Apakah yang dimaksud dengan kontaminasi ?

Adalah tercampurnya bahan kimia lain, mikro organisme, partikel asing kedalam bahan baku, produk antara ataupun produk jadi selama proses sampling, proses produksi, packing ataupun

repacking.

Apakah Cross-contamination /kontaminasi silang?

“Kontaminasi yang disebabkan tercampurnya bahan baku,

produk antara ataupun produk jadi dengan bahan baku produk lain dan atau antar produk selama proses produksi.".

Cross-contamination dapat disebabkan diantaranya oleh :

1. Jeleknya design, operasional ataupun pemeliharaan

(maintenance) dari “ air-handling systems and dust extraction systems “

2. Tidak tersedianya prosedur (SOP) untuk alur personel, material dan peralatan (Inadequate procedures for, and movement of personnel, materials and equipment )

3. Insufficiently cleaned equipment ( peralatan yang tidak / kurang bersih.

Contamination Contaminant from Environment Operators Contaminant from Equipment Cross Contamination Product from Environment Operators Product from Equipment

Cross-Contamination

HVAC

Cross-contamination can be minimized by, e.g.

1. Personnel procedures

2. Adequate premises

3. Use of closed production systems

4. Adequate, validated cleaning procedures

5. Appropriate levels of protection of product

6. Correct air pressure cascade

HVAC

HVAC yang baik akan memberikan perlindungan

terhadap:

 Product protection : melindungi produk dari ;

– Contamination (kontaminasi)

– Cross-contamination (kontaminasi silang)

– Environmental conditions (pencemaran lingkungan)  Personnel protection

– Prevent contact ( melindungi kontak personel dengan produk)

– Comfort conditions ( membuat kondisi lebih nyaman)  Environment protection

HVAC

Protection

: Product and personnel

 Area dimana bahan baku dan produk disimpan harus berada pada ruang dengan klasifikasi bersih ( clean areas ).

 Pencapaian klasifikasi “ clean area “ tergantung pada beberapa faktor diantaranya :

– Building finishes and structure (bangunan dan struktur bangunan )

– Air filtration (sistem penyaringan udara)

– Air change rate (pertukaran udara)

– Room pressure (tekanan udara dlm ruangan)

– Temperature (suhu)

– Relative humidity

– Material and personnel flow (alur barang dan manusia)

– Outside environment (lingkungan luar pabrik)

HVAC

 Air filtration and air change rate merupakan penentu untuk tercapainya klasifikasi ruangan

 Air change rate tergantung pada beberapa faktor diantaranya.

– Spesifikasi / klasifikasi ruangan

– Kualitas sistem filtrasi dari suplai udara – Particulates generated

– Konfigurasi ruangan – Infiltrasi partikel asing – Suhu ruangan

– Tekanan udara ruanga

 Air change rate normally varies between 6 – 20 air changes per hour

HVAC

Pencapaian konsisi ruangan sesuai dg spesifikasinya dilakukan pada kondisi: ( 1 )

 "As built"

– Bare room, without equipment or

personnel

– Ruangan kosong tanpa mesin dan operator

HVAC

(2):

 "At rest"

– Equipment may be operating, but

no operators present

– Mesin dalam keadaan operasi, tanpa operator

HVAC

(3):

 "In operation"

– Normal production process with

equipment and personnel,

– Proses produksi normal dengan orang dan mesin.

– Clean up time validated –

normally in the order of 20 minutes

HVAC

Control of contaminants

 External contaminants dapat dicegah dengan filtrasi yang efektif.

 Internal contaminants dicontrol melalui „flushing, or displacement airflow‟

 Sehingga cemaran partikel diudara dan sistem filtrasi merupakan “critical factor”

Therapeutic risks Manufac turing Environ me nt requi reme nts Clean room Class A / B Clean room Class C Clean rm. Cla ss D Others

HVAC

HVAC

Level of protection and air cleanliness determined

according to (

tingkat proteksi dan kebersihan

udara ditentukan berdasarkan):

 Product to be manufactured (produk yg akan dibuat)

 Process to be used (proses yg akan dilakukan)

 Product susceptibility to degradation (kerentanan produk terhadap degradasi)

Parameter yg berpengaruh pada kualitas udara :

 Jumlah partikel diudara dan jumlah mikroorganisme diudara dan dipermukaan.

 jumlah air changes pada tiap ruangan.

 Air velocity dan airflow pattern

 Filter (type, position)

 Air pressure differentials antar ruangan.

 Temperature, relative humidity (kelembaban relatif)

Selain persyaratan tersebut, ada hal lain yang hrus

diperhatikan :

 appropriate gowning (type of clothing, proper changing rooms)

 validated sanitation

 adequate transfer procedures for materials and personnel

Cleanroom Class

defined by

Critical Parameters

Air Handling

System

Additional Measures

HVAC

Examples of levels of protection

Example of area Condition

Level

Area with normal housekeeping, e.g. warehouse

General Level 1

Area where steps are taken to protect

exposed material/product, e.g. dispensing Protected

Level 2

Area with defined, controlled, monitored environmental conditions to prevent

contamination and degradation Controlled

HVAC

Air Filtration

Penyaringan udara

 Derajad penyaringan merupakan faktor yg penting untuk mencegah kontaminasi.

 Type filters yg akan dipakai tergantung pada kualitas udara lingkungan,return air dan air change rates

HVAC

Levels of protection and recommended filtration

*Filter class should be referenced to the standard test method

Recommended filtration Level of

protection

Primary filters, e.g. EN779 G4* Level 1

Production area with 100% outside air: Primary plus secondary filter (e.g. EN779 G4 plus F8 filters)

Level 2 and 3

Production area with recirculated plus ambient air with a risk of cross-contamination: Primary plus secondary plus tertiary filter (e.g. EN779 G4 plus F8 plus EN1822 H13 filters)

HVAC

Contamination dapat dicegah dengan cara:

 Materials for components and construction (pemilihan bahan dan konstruksi yg baik)

 Design and appropriate access to dampers, filters and other components (desain dan akses aliran udara ke damper, filter dan komponen lainnya)

 Personnel operations

 Airflow direction (arah aliran udara yg baik)

 Type of diffusers (non-induction type recommended)-tipe dari pendorong udara

 Air exhaust (normally from a low level)sistem penghisap udara

HVAC

HVAC

Airflow patterns

Filtered air entering a production room or covering a

process can be

(udara tersaring yang masuk ke

ruang produksi ada dua tipe :



turbulent, or



unidirectional (laminar)



GMP aspect



economical aspect

Unidirectional/laminar

displacement of dirty air

Turbulent

dilution of dirty air

Airflow patterns

Prefilter

Airflow patterns

AHU

Main filter Unidirectional _Turbulent Turbulent 1 2 3

HVAC

Workbench (vertical) Cabin/booth Ceiling

Airflow patterns (4)

HVAC

Unidirectional airflow (UDAF):

Provided where needed over product or material to prevent contamination, or to protect operator

UDAF in weighing areas

 The aim is to provide dust containment (melindungi dari pengaruh debu)

 Airflow velocity should not affect balance (kecepatan alir udara tidak boleh

mempengaruhi timbangan)

 Position of material, balance, operator determined and validated – no

obstruction of airflow or risk (posisi dari material, timbangan dan operator tidah berubah dan tervalidasi tidak menimbulkan gangguan atau resiko).

Pressure cascade solids

Protection from cross-contamination

Note : Direction of door opening relative to room pressure15 Pa15 Pa15 Pa

E

30 Pa

Passage

0 Pa

AirLock Room 3 Room 2 Room 1

15 Pa

Air LockAir Lock

Note : Direction of door opening relative to room pressure

15 Pa 15 Pa 15 Pa E 30 Pa Passage 0 Pa Air Lock Room 3 Room 2 Room 1 15 Pa Air Lock Air Lock

HVAC

Komponen penyusun

HVAC sistem

+

Production Room

Exhaust air treatment

Central air handling unit

Terminal air treatment at production room level

Fresh air treatment (make-up air)

 Weather louvre

 Silencer

 Flow rate controller

 Control damper

 To prevent insects, leaves, dirt and rain from

entering ( mencegahmasuknya serangga, daun, hujan dan cemaran lainnya dari luar )

 To reduce noise caused by air circulation (

mengurangi kebisingan yang timbul karena perputaran udara )

 Automated adjustment of volume of air (night

and day, pressure control)pengendali aliran/volume udara secara otomatis )

 Fixed adjustment of volume of air

Components penyusun terdiri dari

HVAC

 Heating unit  Cooling unit/ dehumidifier  Humidifier  Filters  Ducts

 To heat the air to the proper temperature

(memanaskan udara sampai pada temperatur yg dikehendaki )

 To cool the air to the required temperature or

to remove moisture from the air (mendinginkan dan mengurangi kelambaban udara

 To bring the air to the proper humidity, if too

low ( menjaga kelembaban udara)

 To eliminate particles of predetermined

dimensions and/or microorganisms (mencegah masuknya partikel asing dan mikroorganisme)

 To transport the air

Components (2)

Filter

Silencer

Terminal filter Weather louvre _{Control damper}

Fan

Flow rate controller

Humidifier Heating coil Cooling coil with droplet separator Production Room

Skema komponen HVAC

+

Prefilter

Exhaust Air Grille

Heater

Secondary Filter

Recirculated air

HVAC

Control damper for airflow

De-humidification

Filter Pressure Gauges AHU with fan Variable

Speed Controller

Humid room air

Air heater Regeneration air

Humid room air Adsorber wheel Dry air

Air-handling unit

Humidifier Silencer Heating and

cooling units

Filter classes

Dust filters

Standard Aerosol

Fine

Coarse HEPA ULPA

10 µ m > Dp > 1 µ m Dp > 10 µ m _{Dp < 1 µ m} F5 - F9 G1 - G4 H 11 - 13 U 14- 17 EN 1822 Standard EN 779 Standard

HVAC

Primary panel filter

Secondary filter

HEPA or tertiary filter

Positioning of filters (1)

Filter in terminal position

AHU mounted final filter

Production Room + Production Room HEPA Filter HEPA Filter

HVAC

Prefilter

AHU

Main filter

1 2 3

Low level exhausts

Ceiling exhausts

Positioning of filters (2)

AHU

Prefilter Final filter 2 1

Positioning of filters (3)

HVAC

Swirl Type air diffusors with

terminal filters

1 Filter

2 Tightening frame 3 Register outlet

4 Screw fixation for register

1 2

3 4

Low induction swirl diffusor

(preferred) High induction

office type diffusor (avoid)

Regulation of room pressure – pressure differentials concept

Room pressure gauges

Room pressure indication panel

+ Production Room Exhaust air Return air (recirculated) Fresh air

(make-up air) Supply _air

Air types

Ventilation with recirculated air + make-up air

Central Air-Handling Unit

Return air Exhaust Unit