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
1
ASME BPE Scope
This Standard deals with the requirements
of the bioprocessing, pharmaceutical, and
personall 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:
2
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
3
Voluntary Consensus Standard
• Developed and maintained by a
balanced group of experts
• Multiple stages of approval before
publication
• Continuously updated to support
p practices
p
industryy accepted
• Corrections and clarifications can
be requested by anyone
ASME BPE Committee Structure
4
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
What’s 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!
5
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.
• Inspector
I
t Delegates
D l t
(4 levels of qualification):
–
–
–
–
Trainee
QID-1
QID-2
QID-3
bioburden
corrosion
mechanical seal
rouge
g
biofilm
passivity
6
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
7
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
8
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 Seal’s 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.
9
Design for Cleanability and Sterility
(Part SD)
•New Design Content
•Hygienic Pumps
•Spra Devices
•Spray
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
10
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
SAMPLE
ASSEMBLY
CLEAN STEAM
Note: Design May Vary
AGITATOR
SEAL
– Vent filters
– Vent heaters & condensers
•
•
•
•
Feed lines & Diptubes
Harvest valves
Agitators & foambreakers
CIP/SIP requirements
11
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
2.5
D
2.0
L
Cleanable
Flow Rate (m/s)
• Science-based L/D
requirements
• Chromatography &
Filtration Systems
• Project 2012
1.5
L/D has no significant effect
1.0
A0
Un-cleanable
L/D has significant effect
0.5
3
4
5
6
B
Dead End Length
(L/D)
7
8
model residue: BSA+glycerol
pipe size: 10A to 1.5S
C
12
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
13
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
andd 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 today’s 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.
14
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
thee “new
ew system”
sys e ((they
ey aree
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 yyou 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.
16
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 ASME’s
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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