Biotech. Facility Design

8/13/2019 Biotech. Facility Design

1/17

Biotech Manufacturing Facility DesignMichael Chan

PQC Consulting, Inc., USA

DocumentsPDFCompleteClick Here & Upgrade

Expanded FeaturesUnlimited Pages
http://www.pdfcomplete.com/1002/2001/upgrade.htm


2/17


3/17

An Integrated PlantBulk API productionFill & FinishPrimary & Secondary PackagingQC LabsCentral Utilities Plant

Warehousing & DispensingQA Personnel Administration




4/17


5/17

ISO 14644

To convert from ISO classification to Federal 209 D, divide the particulate concentration by 35.2 to convertfrom cubic meter to cubic feet. Hence, ISO Class 5 is equivalent to 209 D Class 100.


http://www.pdfcomplete.com/1002/2001/upgrade.htmhttp://www.pdfcomplete.com/1002/2001/upgrade.htm


6/17

Rule of Thumb for HVAC Design Criteria

ISO Class Monitoring &Controls

Air Velocity attable level in

feet per minute

Air ChangeRate per hour

HEPACoverage as% of Ceiling

5 Very Strict 70 90 150 400 100

6 Medium 25 40 60 100 33 40

7 Medium 10 15 25 40 10 15

8 Adequate 3 5 10 15 5 - 10




7/17

DSP SuiteAir Flow Diagram

Buffer PrepClass 8

(--)

Material A/L

FillingClass 6

(++)

ComponentPrep

Class 7(+)

ProcessingClass 8

(+)

Personnel A/L

Tank StorageClass 8

(+)

FiltrationClass 7

(+)

A/L

A/L

Corridor Class 8 (-)

Dirty Corridor

Tank CleaningClass 8

(--)

A/L

Filling lineClass 5




8/17

DSP SuiteMaterial Flow Diagram

Buffer Prep

Material A/L

Filling

ComponentPrep

Processing

Personnel A/L

Tank Storage

Filtration

A/L

A/L

Corridor

Dirty Corridor

Tank Cleaning

A/L

CleanDirty

Filling line




9/17

DSP SuitePersonnel Flow Diagram

Buffer Prep

Material A/L

Filling

ComponentPrep

Processing

Personnel A/L

Tank Storage

Filtration

A/L

A/L

Corridor

Dirty Corridor

Tank Cleaning

A/L

CleanDirty

Filling line




10/17

Functions of Biotech Manufacturing PlantCore Processing

Upstream Processing Media prep Seed reactors Fermentation/Recovery, centrifugation, homogenization Tank storage & cleaning Unclassified to Class 100,000

Downstream Processing Buffer prep Buffer storage Purification, chromatography systems, microfiltration, ultrafiltration Equipment storage, cleaning Class 100,000 to Class 10,000

Filling & Filtration Component prep: wash, sterilization

Vials, stoppers & seals Lyophilization Filling & Inspection Class 10,000 to Class 100



Cli k H & U d


11/17

Support Functions Utilities

Central vs. dedicated utities WFI & USP Purified water storage Skid based systems: WFI, RO, Clean steam, CIP, SIP, columns, UF/DF Dirty utilities: steam, potable water, compressed air, nitrogen Media and buffer storage in unclassified areas Interstitial space

Administration Management & Staff Batch records, SOPs, Validation, Maintenance, etc. storage

QA/QC Management & Staff Samples Lab space

Warehousing/Raw Material Incoming, quarantine, released products Sampling and dispensing



Cli k H & U d


12/17

Design Considerations Transfer Panels

Minimize valving and direct tank-to-tank piping Use non-classified areas for media and buffer holding tanks Gravity Feed

Requires use of elevators for material and personnel transfer Minimize pressurization transfers

Interstitial space & catwalk for maintenance access HEPA filter accessibility from interstitial space Sanitary piping

Sloped and minimize deadlegs Ensure maintenance accessibility for valving and instrumentation

Reduce visitor intrusions by building in viewing windows



Click Here & Upgrade


13/17

Project PhasesScope Definition

Design Development

Detailed Design

Construction

Start-up

Validation

Sets the Project s Founda t ion Establish Project Scope & DriversDefine Capacity & Through-put Set Design CriteriaPrepare Budget Form Project TeamDefine roles and responsibilities

Agree upon Project Schedule





14/17

Project Drivers, Scope & Objectives Define the Project s Drivers

Why is the project needed? What happens if the project is not implemented? Increasing product pipeline Higher market demand for product Redundancy/Back-up capacity

Set Project Limits and Scope Products to be manufactured in the facility Clinical vs. commercial

Compliance with US, EU, Japan, Middle-East regulatory requirements Included functions: Manufacturing, QA, QC, Fill & Finish, Packaging, Administration, etc

What will the Project achieve at the end?





15/17

Key Elements of Design Development Production capacity must be tied to marketing or product development

requirements Expansion capabilities Redundancy requirements

Multi-product vs. single product train Operating assumptions (shifts) Product and personnel flows Centralized warehousing/dispensing vs. localized Methods for material transfers Regulatory Compliance (U.S., EMEA, e Local and national building code review Process and unit ops descriptions Utility systems Environmental constraints Level of automation Equipment list and identify long lead time items Incorporation of PAT





16/17

Case Study Existing Facility

Microbial fermentation Scale-up reactors 50L, 200L and 800L Cell harvest and protein recovery in fermentation hall using portable media

tanks Separate purification suite using portable systems/skids 8,000 s.f. facility

Expansion Additional 10,000 s.f. Use 800L as scale-up bioreactor New 2,500L media prep tanks New 2,500L convertible microbial/cell culture bioreactor New dedicated cell harvest and recovery suite with fermentation broth hold

tanks New buffer prep suite with fixed tanks New purification suite with 3 skid stations





17/17

Lessons Learned Expansion did not consider large scale material handling Too much piping in too little space resulting in difficult maintenance Facility contamination due to personnel crossover from under

construction areas to existing facility Should have had better personnel segregation

Plan for utility tie-ins well in advance Involve current plant personnel early in design phase and integrate

into project team Integrate new plant SOP s and validation documentation into existing

system Incorporate over-arching change control for new plant

All validations must be completed and QA approved

DocumentsPDFCompletepg


Biotech. Facility Design

Documents

Transcript of Biotech. Facility Design