ASEPTIC PROCESSING FACILITY

3474 3475

4.9.1 System Schematic (Sample) 3476

3477

3478 3479

4.9.2 System Design Considerations 3480

3481

 Considerable background on the design of HVAC systems is covered in 3482

the ISPE Baseline Guide for Sterile Manufacturing Facilities.

3483

 Eliminate contamination introduced through the air conditioning 3484

supply system by utilizing properly installed and integrity tested 3485

ceiling mounted terminal HEPA filters.

3486

 Minimize infiltration of contamination from uncontrolled areas by 3487

the use of room pressure differentials and airlocks between air 3488

classes.

3489

 Continuous room pressure monitoring with alarms and recording 3490

devices that indicate out of spec conditions are recommended.

3491

 Consider automatic pressure controls to keep the spaces within 3492

specified pressure limits where process exhausts change, or where 3493

door and hatch are frequently opened or door seal integrity varies.

3494

 Dehumidification and post cooling coils should be considered for low 3495

humidity room control.

3496

 A dedicated air handling system is recommended, serving only the 3497

aseptic area and remaining operational for required pressure control 3498

redundancy (parallel fans or fan walls) Consider utilizing standby 3504

electric power generating systems to maintain fans and design 3505

pressure differentials in the event of local power failures.

3506

 The air handling system should be of the constant volume terminal 3507

reheat type utilizing industrial grade equipment.

3508

 Ductwork should be designed per SMACNA standards but in no case 3509

should it be constructed for less than 4" water gauge duct static 3510

pressure and seal Class "A".

3511

 Ductwork should be galvanized steel except where exposed (to a 3512

minimum extent) in production areas or subject to moisture, in which 3513

case it should be a minimum 304 stainless steel with cleanable 3514

finish. Cleaning materials used in the room should be considered.

3515

monitor PAO (aerosol) challenge materials upstream on the non-3527

aseptic side of the HEPA diffusers are suggested for filter 3528

integrity testing.

3529

 Air supplied through ceiling mounted terminal HEPA filters should be 3530

life. Recirculation HEPA/fan units mounted below the ceiling are not 3534

recommended as they require service within the aseptic area, do not 3535

normally utilize low returns, and lack adequate pre-filtration.

3536

 The return air openings in the aseptic area should be located near 3537

the floor, preferably on at least two (2) walls and along the long 3538

dimensions of the room to ensure maximum uniformity of airflow. More 3539

return openings are better than too few.

3540

 Differential air pressure should be employed to minimize 3541

infiltration of contaminants from outside the controlled area. The 3542

aseptic area should be designed for a positive pressure with all 3543

doors closed in relation to less clean adjacent areas outside the 3544

controlled area (refer to latest issue of Federal Standard 209).

positive pressure relative to the outside and uncontrolled areas.

3548

Differential pressures are measured ACROSS airlocks (see the ISPE 3549

Baseline Guides for Sterile and Biopharm Facilities.) 3550

leading to this room are to be maintained successively less positive 3555

down to the zero reference level of uncontrolled areas (the general 3556

building). Only high-pressure Grade 7airlocks that have HEPA 3557

filtered supply air may have pressures higher than the aseptic 3558

filling room. A control range should be established for each room 3559

pressure level such that the pressure can float within the range and 3560

still satisfy the specified differentials.

3561

 A remotely operated or automatic damper may be provided in the 3562

return air duct from each room as a means of obtaining and setting 3563

the established pressure differentials. Simple facilities may be 3564

successfully balanced using only manual dampers, especially if 3565

terminal HEPA filters do not load quickly.

3566

 If manual / remotely operated dampers are used, the remote damper 3567

controls should be tamper-proof or concealed in a lockable cabinet 3568

accessible to authorized personnel only. A differential pressure 3569

gauge should be provided for each room adjacent to the remote damper 3570

controls.

3571

 The manual/remote gauges and controls or automatic controls should 3572

be mounted in a common panel outside the controlled area. An audible 3573

alarm may be provided to indicate loss of area pressure control.

3574

This alarm may be manual reset type and equipped with a hard copy 3575

printout that indicates the out-of-range alarm.

3576

 Unidirectional airflow serves as a barrier between product and 3577

microbial and particulate contamination generated by the equipment 3578

and personnel within the aseptic area. Where possible, terminal HEPA 3579

filters should be located directly over the exposed product, 3580

components and equipment that are not protected by UFH.

3581

 When the central system air conditioning air quantity required to 3582

maintain room conditions is not sufficient to provide protection 3583

temperature. The engineer should consider the heat generated from 3589

the local recirculating system fan motor. This particular oversight 3590

is quite common and can lead to serious temperature stratification 3591

and overheating in the aseptic area.

3592

 Airflow patterns within the work space may be uniform with minimum 3593

turbulence. Ambient air may not aspirate into the work areas along 3594

the perimeter of the unidirectional airflow barrier. The heights and 3595

filter area should deliver Class 100 air at a velocity of 90 feet 3596

(27.5 meters) per minute, with uniformity within plus or minus 20%, 3597

measured at the filter face. Velocity at the work height should also 3598

be measured. The optimal filter face velocity should be determined 3599

during qualification of the UFH using airflow visualization (―smoke 3600

testing‖). See the ISPE Sterile Baseline Guide.

3601

 Room temperatures should be controlled by maintaining constant 3602

airflow and modulating a heating coil. Systems in which varying flow 3603

is used as a means of controlling room temperatures are unacceptable 3604

because of their adverse effects on room pressures.

3605

 Where low relative humidity is required, special attention may be 3606

given to sealing the return duct systems to prevent inward air 3607

leakage from uncontrolled areas and resultant high humidity.

3608 3609

4.9.3 Aseptic Potent Compounds:

3610 3611

 Processes should be contained in isolators, with dedicated HVAC for 3612

the containment enclosure.

3613

 Where the process leaks into the room, protect the HVAC system and 3614

other rooms on the system from hazardous compounds by utilizing non-3615

recirculating primary air conditioning systems.

3616

 The exhaust or return air ducts must be fitted with HEPA filters 3617

protected from physical damage with a pre-filter or equivalent.

3618

These filters should be located within the room where they can be 3619

serviced by properly gowned and protected personnel.

3620

 If filters are located remote from the room where open processing 3621

occurs, they should be housed in a high containment bag-in/bag-out 3622

filter housing and identified as such. These filters contain the 3623

potentially hazardous compounds and minimize particulate "fall back"

3624

during fan failure.

3625

 Gowning areas shall be supplied with air and maintained at a 3626

negative pressure relative to the controlled aseptic area and at a 3627

positive pressure relative to the uncontrolled areas. The gowning 3628

area should be separated from the aseptic filling room by a high 3629

pressure airlock.

3630

 The de-gowning area must be separated from the aseptic filling room 3631

by a low pressure airlock. The de-gowning room shall be maintained 3632

negative relative to adjacent spaces on the uncontrolled side.

3633

 Material entering the aseptic filling room must be transferred via a 3634

HEPA filtered, high pressure tunnel, box or sterilizer. Material 3635

leaving the aseptic filling room must be transferred via a low 3636

pressure tunnel or box.

3637 3638

In document ISPE Good Practice Guide - HVAC (Page 91-94)