DEVELOPING THE USER REQUIREMENTS SPECIFICATION (URS)

2563 2564

3.2.1 Introduction 2565

2566

User requirements provide key information that defines the processes, 2567

activities, and environments needed for an operating facility.

2568

lowest Total Cost of Ownership(TCO).

2573 2574

Decisions and commitments made in the early phase of project planning 2575

are often too costly to change as the project advances to final design 2576

significant portion of a facilities cost.

2581 2582

It is important to ensure that user requirements are well understood 2583

and properly applied.

2584 2585

For HVAC systems in a pharmaceutical environment, user requirements are 2586

Quality – Regulatory guidance and quality principles to guide decision 2593

making on HVAC parameters that can have product impact.

2594 2595

Operations – Proper environment for the working conditions that impact 2596

the HVAC design.

2597 2598

Maintenance – Provide input on critical aspects of the HVAC design that 2599

would ensure a low TCO 2600

2601

User requirements have often been associated with qualification, that 2602

is, critical HVAC parameters (e.g., temperature, humidity, differential 2603

pressure, air quality) are segregated from non critical HVAC 2604

parameters. Critical HVAC parameters are part of direct impact systems 2605

while non-critical HVAC parameters are either indirect or no impact 2606

systems. In either case, all HVAC systems are commissioned following 2607

GEP while direct impact systems are further qualified.

2608 2609

User requirements can either be in the form of performance based 2610

information that describes an operation and sets expectations or strict 2611

criteria where critical HVAC parameters are well defined, e.g., 2612

Temperature, Relative Humidity, etc.

2613 2614

In the case of performance based information, the HVAC designer would 2615

gather relevant information and propose the necessary criteria that 2616

would meet the user requirements. It is accepted practice to copy HVAC 2617

criteria from one facility to another (similar) facility – as long as 2618

the rationale for the original criteria is well understood. For 2619

example, determining temperature and relative humidity criteria in an 2620

aseptic environment is dependent on, type of process (closed or open, 2621

powder or liquid), local regulatory expectations, gowning procedures, 2622

environmental monitoring procedures, the level and type of activity in 2623

the area, and alert and alarm limits,. The HVAC designer should 2624

carefully consider each of these variables when proposing criteria and 2625

avoid using "industry norms" or "accepted industry practices" without 2626

an understanding of the variables involved.

2627 2628

Once user requirements are established, the HVAC designer should begin 2629

to consider design strategies and impact. It is desirable to segregate 2630

HVAC parameters that are critical and non-critical under different HVAC 2631

systems rather than mix critical and non-critical HVAC parameters under 2632

the same system. Although there may not be any restrictions from a 2633

process viewpoint, segregating HVAC system components between direct 2634

and indirect impact adds to the complexity of commissioning and 2635

qualification. It could unnecessarily drive up qualification and on-2636

going maintenance costs.

2637 2638

The flow diagrams shown below are a simple model segregating critical 2639

HVAC parameters with separate HVAC systems versus combining critical 2640

and non-critical HVAC parameters, by virtue of a single HVAC system.

2641

Both design approaches would meet user requirements but it illustrates 2642

the potential complexity when using a single HVAC system to serve 2643

direct and indirect/no-impact areas.

2644 2645

The impact assessment methodology evaluates the HVAC system at the 2646

component level to separate out critical and non-critical components, 2647

thus making it possible to have a single HVAC system. Well defined and 2648

accepted procedures should be in-place or agreed upon when defining the 2649

user requirements that would allow the single HVAC system to have a 2650

lower total cost of ownership. If these concepts are not well 2651

understood or established procedures or practices do not recognize this 2652

methodology, the HVAC design may increase the total cost of ownership.

2653

2654

Figure 3-1 User Requirements drive HVAC critical parameters 2655

2656

3.2.2 References for User Requirements 2657

2658

ISPE Baseline Guides provide a framework to understand the different 2659

products and processes within pharmaceutical and biopharmaceutical 2660

manufacturing facility. The baseline guides that would apply to this 2661

section include the following:

2662 2663

 Bulk Pharmaceutical Chemicals 2664

 Oral Solid Dosage Forms 2665

 Sterile Manufacturing Facilities 2666

 Biopharmaceuticals 2667

 Packaging, Labeling & Warehousing Operations (under development) 2668

 Laboratories (draft) 2669

2670

(Include a chart with a timeline and activities to illustrate?.... no) 2671

2672

The following section describes HVAC parameters as covered in the 2673

Baseline Guides listed above and the importance of each parameter in 2674

each type of facility.

2675 2676

3.2.3 HVAC Parameters 2677

2678

HVAC parameters that may have impact on product generally include:

2679 2680

 Temperature 2681

 Relative Humidity 2682

 Airborne contamination (viable and non-viable particles), which is 2683

affected by:

2684 2685

 Room Relative Pressure 2686

 Airflow patterns 2687

 Air Changes 2688

 Air Filtration 2689

2690

Within the context of the baseline guides listed, some parameters are 2691

common to all facility types while other parameters only apply to 2692

specific facilities. The following chart depicts at-a-glance the 2693

typical HVAC parameters that would generally apply to each facility 2694

type.

2695 2696

HVAC Parameter

Facility Type Temperature

Relative Humidity

Room Relative Pressure

Airborne Particles

Air Changes Bulk Pharmaceutical

Chemicals

Oral Solid Dosage Forms

Air

direction Sterile

Manufacturing Facilities

Biopharmaceuticals Pack., Labeling &

Warehousing Laboratories 2697

Table 3-1 Typical HVAC Critical Parameters by facility type 2698

2699

Hatched areas represent the HVAC parameter used to set criteria that 2700

normally would have product impact or is required for creature comfort.

2701

Non-shaded areas are HVAC parameters that do not normally have product 2702

impact and are not used to set criteria. However, there may be other 2703

requirements such as local codes or regulations that may require 2704

certain parameters be considered in the design. For example, room 2705

relative pressure may not have product impact in a Bulk Pharmaceutical 2706

facility, but due to governing codes, the design may implement room 2707

pressurization controls in order to sustain certain safety requirements 2708

due to the high presence of flammable liquids or vapors.

2709 2710

Individual HVAC parameters are discussed in the following section with 2711

an emphasis on establishing the minimum requirements to achieve 2712

"compliance", the importance of the parameter, the impact on design, 2713

and the challenges faced in determining these requirements.

2714

Temperature requirements will vary depending on the application, 2720

product impact, and operator comfort. ………

2721 2722

This looks to be light… why discuss just temperature?

2723 2724

3.2.4 Critical Parameters 2725

2726

Provide typical critical HVAC parameters under a given process or 2727

classification; i.e., Product Type, Solvent Issues, Environmental 2728

Classification, Open/Closed processes, Terminally Sterilized, Oral 2729

Solid Dosage Forms. Discuss assumptions or clarifications 2730

will require additional attention via qualification and may require 2734

higher levels of redundancy to avoid business impact.

2735

be provided in the form of a matrix in which the individual components 2742

the other axis.

2746 2747

Managing HVAC Parameters (Monitoring) – Accountability for alerts and 2748

alarms. Methodology in determining appropriate alarm delays. Guidance 2749

on how to monitor - BAS, procedural means or manual monitoring.

2750

Determining what should be monitored – every room or select rooms.

2751 2752

Table 3-2 (HVAC System Impact Matrix) See Appendix for graphic 2753

2754

3.2.5 Programming and Layout Considerations 2755

project programmer must coordinate their knowledge and experience to 2760

avoid future problems in the construction, verification, operation and 2761

maintenance of the facility. The impact of HVAC on programming and 2762

layout will vary by the type of facility, generally increasing as the 2763

complexity of the facility increases from general administrative office 2764

It is important to establish User Requirements before beginning layout 2768

and design. It is especially important to identify critical parameters 2769

versus controlled parameters, as this is a major factor determining 2770

environmental cleanliness classifications. In general, the larger the 2771

classified area and the more stringent the environmental cleanliness 2772

class the more complex and costly the HVAC system, both first cost and 2773

the ongoing operating cost. Determine if there are there special 2774

requirements for temperature or RH for specific rooms (freezers, chill 2775

rooms, stability storage chambers, R&D suites, etc.).

2776 2777

The flow of materials, equipment and people (unidirectional flow;

2778

gravity flow, etc.) must be understood by the HVAC engineer in 2779

determining area classifications, pressurization strategies, airlock 2780

strategies (the use of airlocks to separate areas of different 2781

requirements for cleanliness, pressure, temperature, and/or RH) and 2782

their classification, HVAC system zoning, etc.

2783 2784

Area functionalities and adjacencies (both horizontal and vertical) 2785

2786

Determine functional/relational adjacencies (i.e., don‘t put large air 2787

compressors adjacent to a laboratory with vibration-sensitive precision 2788

projects employing prefabricated modular construction.

2792 2793

The locations and considerations for HVAC and utilities equipment, 2794

ducting/piping routing, supply/exhaust/return diffusers/grilles.

2795

docks and other loading/unloading facilities. Will major equipment be 2799

located in basement, penthouse, roof or elsewhere? Building 2800

configuration (H x W x L) may affect the location of central services 2801

and how they are distributed.

2802 2803

Understand the requirements for maintenance, testing, repair and/or 2804

replacement. This includes the locations for access doors/panels for 2805

HVAC system inspection, testing and maintenance, including HEPA filter 2806

pathways, hoists/elevators, etc.). Identify the locations and need for 2813

access to BMS/EMS data and control, and what local indications and/or 2814

control features are needed. What are the maintenance philosophies for 2815

the facility (i.e., maintain from inside or outside of room)?

2816

2817

What are the materials to be used in the process (i.e., potent, 2818

solvents, cytotoxic, sterile) and the approaches & technologies for 2819

product containment and for clean/sterile processing. The use of mini-2820

environments (barrier isolators, RABS, biosafety cabinets, etc.) will 2821

usually reduce both the required amount and grade of classified space 2822

compared to traditional ‗ballroom‘ cleanroom processing. The location 2823

of hazardous equipment & ductwork and the need to maintain them may 2824

affect the facility layout.

2825 2826

Issues related to codes and standards:

2827 2828

 What codes and standard apply to this jurisdiction? (ADA, Fire, 2829

OSHA, Energy, IMC, etc.) 2830

 Egress and other safety considerations 2831

 Must understand risks associated with various layout and programming 2832

issues (i.e., area electrical classification, blowout panels, SISPQ 2833

risks…) 2834

 Special considerations with hydrogen operations 2835

2836

The requirements of local codes and standards may need special 2837

attention in the design and construction of prefabricated modules.

2838

When facility modules are fabricated in a different jurisdiction than 2839

the location of the facility, this may become a major problem if not 2840

identified early in the design process.

2841 2842

Within the room: Consider the locations of people, processes and 2843

product with respect to HVAC supplies and exhaust/returns. Consider the 2844

equipment heat loads (where is heat generated and how is it cooled or 2845

extracted?) Consider the location of utilities connection with respect 2846

to the operations to be performed. Room HVAC system must be designed as 2847

3.2.6 Architectural Considerations 2853

previously identified issues for consideration in the programming and 2858

project architect must also coordinate their knowledge and experience 2862

to avoid future problems in the construction, verification, operation 2863

and maintenance of the facility.

2864

sanitization chemicals, suitable for the environment, and be 2870

wear/bump resistant.

2871

2872

 Flooring: The same considerations as for Room Finishes. Selection of 2873

performance in a specific application.

2878

differential is important. If RH is important, then address reducing 2885

moisture migration through unsealed penetrations, door seals, and 2886

porous wall materials. Considerations in the door specifications 2887

need to address seals, windows, interlocks, construction of the 2888

door, actuation and hardware.

2889 2890

Consider a commissioning test to verify room tightness (i.e., room 2891

leakage test or room integrity test).

2892 2893

 The use of prefabricated modular construction techniques might 2894

impose additional restrictions on the HVAC design (design might be 2895

limited to equipment vendors with which the module contractor has an 2896

established relationship; the size of AHUs might be limited to the 2897

size of a standard module; etc.) 2898

2899

Impact of HVAC on programming and layout will vary by the type of 2900

facility. (some of this is redundant) 2901

 Area functionalities and adjacencies (both horizontal and vertical) 2905

 Determine functional/relational adjacencies (i.e., don‘t put large 2906

air compressors adjacent to a laboratory with vibration-sensitive 2907

precision analytical equipment.

2908

 Locations and considerations for HVAC and utilities equipment, 2909

ducting/piping routing, supply/exhaust/return diffusers/grilles.

2910

Major equipment in basement, penthouse, roof or ????

2911

 Requirements for testing, repair and/or replacement (i.e., HEPA 2912

filter scan testing and maintenance) 2913

wheels, coils, filters, 2917

 Environmental cleanliness classifications 2918

 Materials to be used in the process: Potent, solvents, cytotoxic, 2919

sterile?

2920

 Determining User Requirements (critical parameters versus controlled 2921

parameters) 2922

 What codes and standard apply? (ADA, Fire, OSHA, ??) 2923

 Egress and other safety considerations 2924

 Building configuration (H x W x L) may affect the location of 2925

central services and how they are distributed.

2926

 Approaches and technologies for product containment.

2927

 Routing of ductwork & utilities 2928

 Location of Hazardous equipment and ductwork 2929

 Manifolded exhaust systems versus one fan per hood.

2930

 In general, the larger the classified area and the higher the 2931

environmental cleanliness class, the more complex and costly the 2932

HVAC system, both first cost and the ongoing operating cost.

2933

 Room HVAC system must be designed as an integrated system in rooms 2934

with fume hoods, biosafety cabinets (BSCs), LEV systems and process 2935

equipment HVAC systems.

2936

 Must understand risks associated with various layout and programming 2937

issues (i.e., area electrical classification, blowout panels, SISPQ 2938

risks…) 2939

 Special considerations with hydrogen operations 2940

 Location of HVAC inlet air and exhaust stacks 2941

 Special temperature (or RH) rooms (freezers, chill rooms, stability 2942

storage chambers, R&D suites, etc.) 2943

 Use of airlocks to separate areas of different requirements 2944

(cleanliness, pressure, temperature, RH) and their classification 2945

 Location and need for access to BMS/EMS data and control; what local 2946

indications and/or control features are needed 2947

 Access to field instruments (calibration, testing, and repair) 2948

 Special considerations for prefabricated modular construction 2949

 Locations of people, processes and product within the space with 2950

respect to HVAC supplies and exhaust/returns 2951

 Consideration of equipment heat loads (where is heat generated and 2952

how is it cooled or extracted?) 2953

 Location of utilities connection 2954

2955

In document ISPE Good Practice Guide - HVAC (Page 61-69)