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Fundamentals of

BiopharmaceuticalFacility Design

INTAS BIOPHARMACEUTICALS LIMITED

S. BALLAL & M. KODILKAR

Dec 29, 2010

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Program Introduction

Key Design Parameters

Emerging Trends

Design Process

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Introduction Traditional: Single

product facilities 1990s: Multi-

product facilities

introduced GMP evolves to

permit multi-product operationswith sharedequipment

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Key Design Parameters Process Flows / Unit Operations

Process Volumes

Biosafety

Viral Segregation Multi-product V/s Single Product

Regulatory Requirements

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Process Flows Biopharma facilities are built around the process

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Process Flows Segregation

Inoculum prep

Centrifugation: noisy, aerosol generating, difficult toclean

Pre viral & post viral steps in DSP Column packing areas: open, manual operations

Solvent use areas: flame-proof zone

Product changeovers: Segregation in overlapping

batches

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Process Volumes Large (~ >1500L)

Stationary systems

Hard piped

CIP/SIP

Centralized CIP Long pipe runs

Multistoried units

Small Mix of stationary, mobile

CIP hardpiping preferred

COP/SOP possible

Multiple CIP units

Large MALs, corridors Space for clean staging

CNC spaces for less critical operations, closed operations

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Biosafety BL1 preferred.

Exponential rise in capital cost with higher Biosafetylevels

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Viral Segregation Detection of potentially harmful viruses in DS (Porcine

parvovirus in Factor VIII)

Principle concern: Segregation of post-viral material frompre-viral.

Extended to segregation in area, airlocks, washing. Separate AHUs and washing areas

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Multi Product /Singleproduct Multi Product Facility

Need flexibility foraccommodating processes

Equipment more flexible inoperating ranges

Utilities oversized

Pre-determined, multi-directional transfer paths

Larger quantum of extraspace provision

More disposables used

Single Product Facility One/two batch sizes,

defined process

Sizing, flowsstraightforward

Utilities sized to batchvolumes & processschedules

Defined operating range

Fixed equipment preferred

over disposables No additional space

provisions required.

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Regulatory requirements Which regulator will approve the facility? What do they

require?

Are there any key flags to look for?

Talk to the regulators & get a feel of their opinion prior to

basic/detail design.

EU needs Class A in B for inoculum prep.

India does not specify viral segregation.

PICS & others like Indonesia require separate PAL MAL

USFDA open to considering V+, V- process steps in thesame room.

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Emerging Trends in FacilityDesign Disposable/ Single use systems

Use of Controlled Non Classified (CNC) areas

Multi-product facilities with parallel operations

Modular Plants & Superskids

Visual Factories and Open Space concepts

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Single Use Products: Influenceon Facility Design Reducing requirement of

cleaning spaces SIP/CIP/SOP/COP, Staging,tank movement

Reduced Size of Utilities andPiping both Central Utilitiesand within a process room

Easily validatable closedsystems allow use of lower airclassification

Rapid deployment lessplanning due to low cost ofcapital

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Use of CNC Areas

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Multi-product facilities withparallel operations Historically:

Multiproduct Operation = Campaign mode

Newer technologies for closed operations and riskbased approach

Manufacturers pushing for simultaneous multi-productoperations

Regulators more open to concept Ok if segregationand cross contamination issues are addressed

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Modular Plants andSuperskids

Superskids: Reduce sitework, shrinktimelines, offsite Qualification

Modular plants: Designed, constructed,integrated offsite

Reduce sitework Condense Construction Timelines Pre-tested & integrated- no last minute

surprises Higher Cost, Suited for midsized plants,

infrastructural constraints

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Workplaces not Factories To provide better working environment

Moving away from windowsless artificially lighted rooms

Contract manufacturers- key drivers: To attract potentialcustomers

Influence Design room placements, adjacencies

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Designing a Facility Start with defining the process, lay down operational

requirements

Build the facility around the process- add functional areasaround the process

Flexibility comes at a price

Design only for more expected variables Ex. 85% processcoverage of LAMP

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The Facility Design Process

Facility URS

Conceptual Design (3-4 months) Basic layouts, site plan, buildingsizing, utilities-basic plan and sizing, line diagrams, equipment

lists, overall philosophies & budget cost (+ 25%) Basic Design (3-4 months)- Room sizing, utility sizing, detailed

layout, equipment URSs, P & IDs and cost (+ 10%)

Detailed Design (8-12 months): Full/detailed designing of allelements. 1000s of drawings, 2D and 3 D designing

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If you are lucky.

You will end up making THAT product, forwhich you designed the facility!