ASME BPE 2009

New Requirements & Resources for BioProcess Equipment Design

David M. Marks, P.E.
ASME BPE Design Subcommittee Chair President and Senior Consultant

June 17, 2009

What is ASME BPE and Why is it Important???

ASME

BioProcessing Equipment
standard or ASME BPE

ASME BPE Scope

This Standard deals with the requirements of the bioprocessing, pharmaceutical, and personal l care product d t industries i d t i as well ll as other applications with relatively high levels of hygienic requirements, covering directly or indirectly the subjects of materials, design, fabrication, inspections, testing, and certification.

Familiar BPE Topics:

New publication every 2 years that address current system and facility topics:

BPE 2009 Addresses Biopharm Business Needs with New Content!

Fermentor & Bioreactor Design CIP Distribution Systems Process Gas System Design Steam Sterilizers / Autoclaves Hygienic Pump Design CIP Skid Design Single-Use Product Requirements Compendial Water Pump Seals Electropolishing & Passivation Rouge & Stainless Steel Polymer Surface Finishes Metallic Materials of Construction Corrosion Testing Elastomer Performance Hygienic Hose Assemblies Process Instrumentation ASME Certification Program

Voluntary Consensus Standard

Developed and maintained by a balanced group of experts Multiple stages of approval before publication Continuously updated to support y accepted p practices p industry Corrections and clarifications can be requested by anyone

ASME BPE Committee Structure

BPE Standards Committee (Main Committee)

Meets 3 times annually to:
Review Subcommittee Progress Coordinate Efforts Between Subcommittees Delegates from Europe and Japan participate Liaison Reports with other Organizations
ISPE P3-A DIN ASTM 3-A SSI EHEDG

Next Meeting October 5-8, 2009

Radisson Hotel Boston, Boston, MA

Whats New???
The most extensive revision i i to date! d ! New Process Systems Design Requirements! New Sections!
Process Instrumentation Metallic Materials

New Supplier Certification Program!

BPE Certification Program (Part CR)

Certificate of Authorization issued to qualified component suppliers. ASME BPE Symbol Stamp will mark components in compliance compliance. Program is starting with tubing and fitting manufacturers.
BPE

Dimensions & Tolerances (Part GR)

GR-4 (Inspector Delegates)
New section defining the qualifications of personnel involved in inspection of BioProcessing, Pharmaceutical and other systems involving a high degree of bioburden control.

bioburden
mechanical seal biofilm
corrosion

Inspector I t Delegates D l t
(4 levels of qualification):

rouge g

Trainee QID-1 QID-2 QID-3

passivity

Dimensions & Tolerances (Part DT)

New Design Criteria for Hygienic Clamps. New Nominal one inch fitting design. Reducing the length on eccentric i & concentric i reducing fittings.

Metallic Materials of Construction (Part MMoC)

Metallic materials commonly used in hygienic service
Testing standards Mechanical & chemical properties Surface finish Fabrication guidelines

Material Joining (Part MJ)

New Content:
Use of duplex alloys Sample weld criteria Welding Operator Qualification Requirements

Polymers and Elastomers (Part PM)

New subsection on Single-Use Components & Assemblies New appendix on Interpretation of Elastomer Material Property Changes Other new content:
Hose assemblies Elastomer performance Surface finish of polymers in product contact

Surface Finishes (Part SF)

New acceptance criteria for passivated product contact surfaces New section SF-P on Polymer Product Contact Surfaces New Non-mandatory Appendices
Electropolishing Procedure Qualification Passivation Procedure Qualification Rouge & Stainless Steel
(Rouge Remediation)

Equipment Seals (Part SG)

New Standardized Process Test Conditions for Seals fitness for use.
Simulated SIP & CIP conditions

New Application Data Sheet for seal specification New section i on seals l for f compendial water pumps.

Design for Cleanability and Sterility (Part SD)

New Design Content
Hygienic Pumps Spray Spra Devices De ices Ball Valves O-ring connections Top-entering mixers Steaming for bioburden control

New Process Systems

Bioreactors Autoclaves CIP Distribution Process Gas Systems

Steam Sterilizers / Autoclaves (SD-4.14)

Cycle Capabilities Materials/Finish Elastomers Door Design Sterile filters Loading carts/trays Jacket design Instrumentation

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CIP Systems and Design (SD-4.15)

System Functionality & Operating Capabilities CIP Skid Design Flow Rate Guidelines Guidelines for Cleaning Vessels Spray Device Design CIP Distribution Design
Supply & Return Looped Headers Zero Static Chains Multiport Valves Transfer Panels Swing Elbows & Transfer Spools CIP Return Pumps CIP Return Eductors

Bioreactors and Fermentors (SD-4.17)

Vessel Internals S Sampling li System S t Sterile Boundary Inlet Gas Assembly
Inlet filters Sparger design
OPTIONAL

EXHAUST

Indicates Sterile Boundary

OPTIONAL

CIP

INOCULUM

LIQUID ADD

OPTIONAL

FIC

COMP. AIR

NUTRIENT

PROBE (TYPICAL)

FIC

COMP. GAS

OPTIONAL

Exhaust Gas Assembly

CLEAN STEAM

SAMPLE ASSEMBLY AGITATOR SEAL

Note: Design May Vary

Vent filters Vent heaters & condensers

Feed lines & Diptubes Harvest valves Agitators & foambreakers CIP/SIP requirements

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Process Gas Distribution Systems (SD-4.18)

Materials of Construction Process Requirements Piping Design Filtration

Gas systems are not designed G d i d or configured with the intent or provisions to be cleaned, passivated or chemically treated after installation. SD 4.18(d) BPE 2009 (pending)

Hot Topics under Development

Science-based L/D requirements Chromatography & Filtration Systems Project 2012
2.5 2.0

D Cleanable

Flow Rate (m/s)

1.5

L/D has no significant effect

1.0

0.5

L/D has significant effect

Un-cleanable

A0

B Dead End Length (L/D)

model residue: BSA+glycerol pipe size: 10A to 1.5S

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What are the current trends in the BioPharm industry?

How is the ASME BPE used to address these trends?

Trend #1 Multi-Product, Contract Manufacturing Facilities

One facility has to be accepted by:
Several operating companies Several regulatory agencies from around the globe. g International Standards are CRITICAL to address this trend

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Trend #2 Better yields Higher titers than ever before

Equipment size is generally ll staying t i about b t the same size or getting smaller.
Better use of current designs and materials The demand for larger and d larger l equipment i t has decreased. Higher energy efficiency. Limited by downstream processing equipment.

Trend #3 Focus on quality Fittings, Tubing, and Valves is being replaced by todays demand for better performing Materials (ie: Alloys, Thermoplastics, Elastomers)
2 year lifespan Resistance to steam and corrosives Consistent (Repeatable) Material Performance is CRITICAL End Users just expect fittings, tubing, and valves to meet the standards.

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Internationally accepted Acceptance Criteria is required for all 3 trends.

Science-Based Requirements q Not too restrictive or expensive Consideration for the 5-10 year old system Not just the e new ew system sys e ( (they ey are e only new for a short time) Updated regularly to reflect the current acceptance criteria.

Regulatory Update
State of California to Adopt the ASME BioProcessing Equipment (BPE) Standard by Reference The State of California has developed an L (Laboratory) Occupancy designed for R&D Laboratories, which has been proposed for use in all areas by the State Fire Marshal, Chief Kate Dargan. Part of the L Occupancy adoption was the reference to supporting standards, one of which is the ASME BPE Standard. The L Occupancy has been approved by the State Fire Marshal as well as the State Building Fire and Other Uses Committee. It has been advanced to the Building Standards Commission for ratification and then to the Legislature for inclusion in Title 19 Code of California Regulations (CCR). Visit http://www.fire.ca.gov or http://osfm.fire.ca.gov for further updates.

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How do I get involved in the ASME BPE?

Go to a meeting and listen to the Subcommittee Sessions. Determine where your technical strengths would help. Participate in a Task Group. Speak up and be an active participant in the Subcommittee Sessions.

Should I become a member?

If y you have the time and interest to be an active participant. If your company will support your ASME BPE work. If you want to vote on changes and updates to an international standard. You do not have to become a member to participate in ASME BPE.

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Questions?
You may also contact after the meeting at: David.Marks@dmealliance.com
Presentation Contributors: Jay Ankers Chair, BPE Standard Committee Principal, P i i l Lifetek Lif t k Solutions S l ti Rick Zinkowski Vice-Chair, BPE Standard Committee

BPE 2009: New Requirements & Resources for BioProcess Equipment

ASME BPE has emerged as the definitive international standard on bioprocessing equipment and facilities, , covering the subjects of materials, design, fabrication, inspections, testing, and certification. The BPE 2009 edition will be the most extensive revision of ASMEs BioProcess Equipment Standard since it was first published in 1997. This presentation will summarize the new BPE resources and requirements for the design and delivery of components and process systems for use in bioprocessing, pharmaceutical, and personal care product industries. This publication will include new content on the design of process systems such as bioreactors, fermentors, autoclaves, process gasses, CIP distribution and single-use equipment. New resource material will be provided on electropolishing, passivation, elastomer performance, metallic materials of construction, polymer surface finishes, corrosion testing and stainless steel rouge. The BPE has also been expanded to include new sections on process instrumentation, hygienic pumps, hygienic hose assemblies and rotary spray devices.

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