A

next

generation

pilot-scale

continuous

sterilization

system

for

fermentation

media

A

new

continuous

sterilization

system

was

designed

constructed

started

up

and

qualified

for

media

sterilization

for

secondary

metabolite

cultivations

bioconversions

and

enzyme

production

An

existing

Honeywell

Total

Distributed

Control

control

system

was

extended

using

redundant

High

performance

Process

Manager

controllers

for

I/O

-LRB-

input/output

-RRB-

points

This

new

equipment

was

retrofitted

into

an

industrial

research

fermentation

pilot

plant

designed

and

constructed

in

the

early

Design

strategies

of

this

new

continuous

sterilizer

system

and

the

expanded

control

system

are

described

and

compared

with

the

literature

-LRB-

including

dairy

and

bio-waste

inactivation

applications

-RRB-

and

the

weaknesses

of

the

prior

installation

for

expected

effectiveness

In

addition

the

reasoning

behind

selection

of

some

of

these

improved

features

has

been

incorporated

Examples

of

enhancements

adopted

include

sanitary

heat

exchanger

-LRB-

HEX

-RRB-

design

incorporation

of

a

flash

cooling

HEX

on-line

calculation

of

Fo

and

Ro

and

use

of

field

I/O

modules

located

near

the

vessel

to

permit

low-cost

addition

of

new

instrumentation

Sterilizer

performance

also

was

characterized

over

the

expected

range

of

operating

conditions

Differences

between

design

and

observed

temperature

pressure

and

other

profiles

were

quantified

and

investigated

Introduction

Continuous

sterilization

also

is

known

as

high-temperature

short-time

-LRB-

HTST

-RRB-

sterilization

A

continuous

sterilizer

heats

non-sterile

-LRB-

raw

-RRB-

medium

to

the

desired

sterilization

hold

temperature

-LRB-

typically

°C

-RRB-

maintains

it

at

constant

temperature

in

an

adiabatic

holding

loop

-LRB-

consisting

of

a

long

length

of

insulated

stacked

piping

connected

with

U-bends

for

compactness

-RRB-

then

cools

it

to

°C

before

transferring

flow

to

a

fermenter

that

has

been

previously

sterilized

empty

or

with

a

minimal

amount

of

water

The

residence

time

that

medium

is

held

at

sterilization

temperature

tR

-LRB-

min

-RRB-

-LSB-

calculated

from

the

adiabatic

retention

loop

volume

Vs

-LRB-

L

-RRB-

divided

by

the

system

volumetric

flowrate

Q

-LRB-

lpm

-RRB-

-RSB-

is

varied

by

adjusting

flowrate

and/or

length

of

the

holding

loop

Energy

is

recovered

by

pre-heating

incoming

cold

medium

from

°C

-LRB-

worst

case

-RRB-

to

°C

with

outgoing

sterilized

medium

that

is

cooled

from

its

sterilization

temperature

of

to

°C

prior

to

entering

the

process

cooler

where

it

is

cooled

further

to

°C

Medium

is

recycled

back

to

a

circulation

tank

-LRB-

also

called

a

surge

or

recycle

tank

-RRB-

or

diverted

to

the

sewer

during

start

up

or

process

upsets

-LRB-

such

as

a

decrease

in

sterilization

temperature

or

an

increase

in

system

flowrate

-RRB-

This

circulation

tank

can

be

pressurized

or

non-pressurized

with

the

non-pressurized

design

approach

requiring

a

second

flash

cooler

before

returning

flow

to

the

recycle

tank

to

avoid

flashing

Heating

is

accomplished

indirectly

using

steam

or

hot

water

via

a

heat

exchanger

-LRB-

HEX

-RRB-

or

directly

by

mixing

steam

with

incoming

medium

-LRB-

steam

injection

-RRB-

Cooling

HEXs

can

use

cooling

tower/chilled

water

but

also

may

use

vacuum

to

reduce

temperature

and

draw

off

any

accumulated

water

from

direct

steam

injection

Continuous

sterilization

systems

typically

are

pre-sterilized

with

steam

by

direct

injection

and/or

with

hot

water

After

attaining

steady

state

with

water

flow

non-sterile

medium

feed

is

introduced

Various

media

components

are

sterilized

in

aliquots

and

sent

to

the

receiving

fermentation

vessel

with

water

flushed

between

them

A

next

generation

pilot-scale

continuous

sterilization

system

was

designed

installed

started

up

and

validated

Demolition

as

well

as

retrofit

was

accomplished

within

an

actively

operating

industrial

pilot

plant

Despite

prior

experience

with

a

stick-built

internally

designed

system

a

skid-mounted

vendor

design

was

selected

consisting

of

five

skids

-LRB-

recovery

and

heating

exchangers

hot

water

loop

and

exchanger

retention

loop

process

and

flash

cooling

HEXs

and

switching

valve

station

-RRB-

Sterilized

medium

obtained

from

the

system

at

lpm

typically

was

aliquoted

into

L

scale

fermenters

with

lower

flowrates

being

most

appropriate

for

lower

fermenter

volumes

The

design

accommodated

a

range

of

different

media

types

including

low

solids

levels

below

wt

and

concentrated

nutrient

solutions

The

design

evaluated

features

from

related

industrial

applications

of

continuous

sterilization

including

sanitary

design

advances

in

spiral

HEX

fabrication

that

were

considered

helpful

Valued

design

characteristics

were

flexibility

reliability

and

straightforwardness

in

operation

and

maintenance

Although

some

general

papers

describing

continuous

sterilizer

design

are

available

-LSB-

-RSB-

there

have

been

few

if

any

publications

linking

design

and

operation

despite

the

considerable

and

varied

industrial

applications

of

high

temperature

short

time

-LRB-

HTST

-RRB-

sterilization

This

paper

describes

the

design

and

testing

of

a

next

generation

HTST

continuous

media

sterilization

system

along

with

the

technical

rationale

behind

its

features

and

flexibility

Background

Advantages

Advantages

of

continuous

sterilization

have

been

outlined

in

several

reports

-LSB-

-RSB-

By

far

the

most

noted

benefit

is

energy

conservation

since

continuous

sterilization

consumes

up

to

less

steam

and

cooling

water

for

large-scale

fermenter

media

volumes

This

economy

lies

at

the

high

end

of

this

range

when

continuous

sterilization

utilizes

heat

recovery

via

indirect

heat

exchange

to

pre-heat

incoming

cold

medium

with

hot

medium

leaving

the

sterilization

hold

loop

It

thus

requires

less

energy

-LRB-

as

well

as

generates

a

more

uniform

demand

without

peak

draws

-LSB-

-RSB-

-RRB-

than

the

alternative

batch

sterilization

process

involving

sterilizing

the

fermenter

vessel

and

its

non-sterile

contents

together

Batch

sterilization

becomes

less

efficient

with

scale

since

heating

and

cooling

portions

of

the

cycle

are

longer

than

the

constant

hold

temperature

portion

-LSB-

-RSB-

and

heat

transfer

coefficients

decrease

with

scale

up

-LSB-

-RSB-

Prior

to

receiving

continuously

sterilized

medium

the

fermenter

is

sterilized

empty

or

with

a

small

volume

of

water

covering

the

pH

and

dissolved

oxygen

probes

Heat

up/cool

down

times

are

substantially

shorter

decreasing

overall

turn-around

time

-LSB-

-RSB-

Continuous

sterilization

results

in

gentler

treatment

of

medium

compared

to

batch

sterilization

which

tends

to

overheat

medium

to

ensure

that

vapor

space

vessel

internals

achieve

sterilization

temperatures

-LSB-

-RSB-

Sterilization

at

higher

temperatures

for

a

shorter

time

generates

less

degradation

of

heat-sensitive

medium

components

since

spore

destruction

rates

increase

faster

than

nutrient

destruction

rates

as

temperature

rises

-LSB-

-RSB-

The

activation

energy

for

nutrient

degradation

ranges

from

to

kJ/mol

which

typically

is

smaller

than

activation

energies

for

the

thermal

death

of

microorganisms

which

range

from

to

kJ/mol

-LSB-

-RSB-

Consequently

Fo

increases

more

than

Ro

as

temperature

rises

-LSB-

-RSB-

Similarly

amino

carbonyl

or

Maillard

browning

reactions

which

form

objectionable

color

and

tastes

to

consumers

for

pasteurization

and

adversely

affect

medium

quality

-LRB-

destroy

growth

factors

-RRB-

for

fermentation

are

minimized

-LSB-

-RSB-

In

the

case

of

polymerized

poly

-LRB-

l-lactide

-RRB-

rod

implants

lower

molecular

weight

decreases

also

have

been

found

for

autoclave

cycles

at

higher

temperatures

and

shorter

times

-LSB-

-RSB-

Continuous

sterilization

results

in

more

uniform

heat

treatment

of

medium

than

batch

processes

since

the

system

operates

at

steady

state

-LSB-

-RSB-

Proteins

and

carbohydrates

can

be

separately

sterilized

in

multiple

sections

using

several

mix

tanks

with

a

sterile

water

flush

between

them

-LSB-

-RSB-

Since

there

is

no

need

to

agitate

unaerated

-LRB-

ungassed

-RRB-

large

liquid

volumes

during

batch

sterilization

fermenter

agitator

design

can

be

based

on

drawing

full

load

during

gassed

conditions

-LSB-

-RSB-

Some

feel

that

continuous

sterilization

offers

a

lower

contamination

rate

relative

to

batch

sterilization

since

fermenter

internals

are

more

easily

sterilized

in

an

empty

rather

than

full

fermenter

-LSB-

-RSB-

others

believe

that

batch

sterilization

has

a

lower

risk

since

there

is

no

need

to

transfer

aseptic

media

-LSB-

-RSB-

HTST

systems

have

a

high

degree

of

flexibility

since

a

large

range

of

time/temperature

combinations

can

be

selected

within

equipment

design

limits

Scale

up

is

linear

with

media

flowrates

of

L/h

reported

for

HTST

systems

-LSB-

-RSB-

and

up

to

L/h

for

pasteurizers

-LSB-

-RSB-

Time/temperature

exposure

profiles

accurately

reflect

sterilization

conditions

for

the

media

of

interest

and

can

be

readily

modeled

Finally

the

ability

to

design

heat

exchange

equipment

to

minimize

fouling

reduces

cleanability

and

maintenance

concerns

Disadvantages

of

continuous

sterilization

primarily

are

that

process

control

performance

is

critical

since

it

is

necessary

to

immediately

divert

flow

of

any

inadequately

sterilized

medium

halt

any

further

medium

sterilization

and

resterilize

the

system

In

contrast

for

a

batch

sterilization

system

upset

often

additional

hold

time

can

be

readily

added

to

the

sterilization

Continuous

sterilizer

systems

also

use

dedicated

equipment

that

usually

is

not

well

suited

for

other

purposes

Applications

Several

relevant

background

papers

on

applications

of

continuous

heat

treatment

of

liquids

have

been

published

in

the

food

biowaste

and

fermentation

fields

Applications

of

continuous

sterilization

to

dairy

and

other

food

pasteurization

are

prevalent

in

the

literature

A

continuous

pasteurization

process

with

a

hold

temperature

of

°C

and

hold

time

of

s

replaces

a

batch

process

with

a

lower

hold

temperature

of

°C

for

min

-LSB-

-RSB-

Ultra

high

temperature

-LRB-

UHT

-RRB-

treatment

-LRB-

°C

-RRB-

using

either

direct

steam

injection

or

indirect

heating

is

used

to

obtain

longer

preservation

-LRB-

specifically

greater

log

reduction

-RRB-

than

pasteurization

at

°C

-LSB-

-RSB-

Temperatures

of

°C

produce

extended

shelf

life

milk

with

a

product

shelf

life

of

days

at

°C

-LSB-

-RSB-

Direct

steam

injection

for

heating

feed

to

its

hold

temperature

for

UHT

treatment

causes

less

destruction

to

other

milk

components

owing

to

rapid

heating

using

injected

steam

and

rapid

cooling

using

a

vacuum

-LSB-

-RSB-

For

dairy

applications

often

the

lethality

achieved

during

heat

up

and

cool

down

periods

is

similar

in

magnitude

to

that

achieved

during

isothermal

hold

time

-LSB-

-RSB-

and

thus

needs

to

be

considered

in

evaluating

exposure

The

integrated

pasteurization

effect

-LRB-

PE

-RRB-

is

calculated

to

convert

the

time

t

-LRB-

min

-RRB-

at

different

temperatures

T

-LRB-

t

-RRB-

-LRB-

K

-RRB-

in

various

sections

of

the

pasteurizer

-LRB-

specifically

the

heat

up

holding

and

cooling

sections

-RRB-

to

the

equivalent

time

at

a

reference

temperature

To

of

C

-LRB-

K

-RRB-

and

a

reference

time

to

of

s

-LRB-

min

-RRB-

-LRB-

Eq

-RRB-

where

Ea

is

the

activation

energy

cal/mol

and

R

is

the

universal

gas

constant

of

cal/mol-K

A

PE

of

one

corresponds

to

complete

pasteurization

at

°C

for

s

-LSB-

-RSB-

The

effectiveness

of

heat

treatment

in

the

food

industry

is

established

indirectly

since

it

is

undesirable

to

introduce

indicator

organisms

into

production

equipment

An

indicator

enzyme

such

as

alkaline

phosphatase

is

used

to

test

proper

milk

pasteurization

after

first

establishing

its

relation

to

pathogen

load

-LSB-

-RSB-

and

pasteurization

effect

-LSB-

-RSB-

The

behavior

of

indicator

organisms

also

is

examined

and

rigorously

modeled

since

obtaining

accurate

kill

kinetics

at

operational

conditions

can

be

problematic

-LSB-

-RSB-

Continuous

sterilization

also

is

used

for

biowaste

destruction

and

decontamination

of

spent

broth

the

major

byproduct

from

biotechnology

plants

-LSB-

-RSB-

Typical

sterilization

temperatures

vary

from

as

low

as

°C

up

to

°C

for

usually

short

hold

times

of

min

Less

aggressive

conditions

are

warranted

since

organisms

being

sterilized

are

active

cultures

and

not

dormant

spores

Batch

systems

involve

heat

up

sterilization

and

cool

down

of

waste

all

in

the

same

jacketed

vessel

and

often

with

direct

steam

sparging

for

heating

and

an

external

HEX

used

for

cooling

to

shorten

the

time

cycle

-LSB-

-RSB-

Owing

to

its

higher

throughput

continuous

sterilization

has

been

applied

to

biowaste

treatment

-LSB-

-RSB-

and

the

prediction

that

it

eventually

would

be

the

preferred

method

of

biowaste

inactivation

-LSB-

-RSB-

has

been

realized

for

larger

facilities

Operational

concerns

for

biowaste

treatment

are

opposite

those

for

media

sterilization

Although

both

processes

require

achievement

of

the

desired

log

reduction

of

live

organisms

in

the

feed

biowaste

treatment

is

concerned

with

live

organism

leakage

into

either

previously

sterilized

effluent

broth

and/or

uncontained

cooling

water

In

contrast

media

sterilization/pasteurization

is

concerned

with

live

organisms

leaking

into

sterilized

media

from

non-sterile

cooling

water

-LSB-

-RSB-

and/or

non-sterile

incoming

feed

For

fermenter

media

sterilization

applications

continuous

sterilization

complements

continuous

fermentation

which

can

be

more

productive

for

certain

fermentation

processes

since

it

substantially

reduces

fermenter

turn-around

time

between

successive

runs

-LSB-

-RSB-

Systems

are

able

to

be

maintained

on-line

and

ready

so

that

they

can

continuously

sterilize

and

deliver

mid-cycle

medium

additions

directly

into

active

fermentations

Typical

sterilization

temperatures

range

from

to

°C

with

hold

times

of

min

Similarly

to

the

PE

value

for

pasteurization

the

Fo

value

-LRB-

min

-RRB-

is

used

to

characterize

sterilization

effectiveness

for

fermentation

medium

-LSB-

-RSB-

It

is

the

time

for

the

actual

sterilization

hold

temperature

that

is

equivalent

to

exposure

to

a

saturated

steam

environment

of

°C

according

to

Eq

where

T

-LRB-

t

-RRB-

is

the

sterilization

hold

temperature

K

t

is

the

incremental

sterilization

hold

time

min

integrated

over

the

start

time

ti

to

finish

time

tf

and

Z

is

the

temperature

difference

-LRB-

K

or

°C

-RRB-

for

a

one

log

change

in

DT

-LRB-

min

-RRB-

the

time

for

a

one

log

reduction

in

spore

concentration

A

similar

expression

can

be

developed

for

the

analogous

impact

on

nutrient

degradation

Ro

-LRB-

min

-RRB-

-LSB-

-RSB-

High

temperature

short

time

continuous

heat

treatment

also

has

been

evaluated

for

the

viral

inactivation

of

mammalian

cell

culture

medium

-LRB-

hold

temperature

of

°C

and

hold

time

of

s

-RRB-

to

minimize

nutrient

degradation

-LSB-

-RSB-

and

of

blood

plasma

-LRB-

hold

temperature

of

°C

and

hold

time

of

s

-RRB-

to

maintain

protein

structure

and

activity

-LSB-

-RSB-

Kill/degradation

kinetics

Relative

to

Escherichia

coli

the

heat

resistance

of

bacterial

spores

is

million

mold

spores

is

and

viruses

and

bacteriophages

is

-LSB-

-RSB-

As

a

first

pass

the

kinetics

of

kill

and

degradation

are

based

on

the

Arrhenius

equation

for

the

thermal

death

constant

k

-LRB-

t

-RRB-

min

-LRB-

Eq

-RRB-

as

a

function

of

the

incremental

sterilization

holding

time

t

where

T

-LRB-

t

-RRB-

Ea

and

R

are

defined

as

in

Eq

and

A

is

the

frequency

factor

of

the

reaction

min

Adherence

to

strict

first

order

kinetics

is

not

always

the

case

-LSB-

-RSB-

and

this

model

does

not

incorporate

partial

germination

and/or

heat

activation

of

dormant

spores

prior

to

media

sterilization

reducing

their

heat

resistance

-LSB-

-RSB-

Nevertheless

this

simple

model

is

employed

for

the

validation

of

media

sterilization

conditions

in

the

fermentation

industry

Using

the

Arrhenius

model

the

non-temperature

dependent

activation

energy

can

be

calculated

from

the

regressed

slope

of

log

of

reaction

rate

constant

versus

the

reciprocal

of

absolute

temperature

-LSB-

-RSB-

Typical

values

for

Bacillus

-LRB-

Geobacilllus

-RRB-

stearothermophilus

an

indicator

organism

commonly

used

to

evaluate

heat

treatment

effectiveness

are

min

for

A

and

cal/mol

for

Ea

-LSB-

-RSB-

The

D

value

DT

-LRB-

min

-RRB-

or

decimal

reduction

time

is

the

time

to

decrease

the

population

to

one-tenth

its

original

number

at

a

specified

temperature

-LSB-

-RSB-

The

Z

value

-LRB-

K

or

°C

-RRB-

is

number

of

degrees

of

temperature

rise

that

causes

a

tenfold

increase

in

D

value

-LSB-

-RSB-

It

is

obtained

by

plotting

the

log

of

the

D

value

versus

the

corresponding

temperature

and

calculating

the

Z

value

obtained

from

the

reciprocal

of

the

slope

of

the

least

squares

regression

line

-LRB-

Bigelow

model

-RRB-

-LSB-

-RSB-

The

QΔT

value

is

the

death

rate

increase

for

a

specified

change

in

temperature

ΔT

-LSB-

-RSB-

and

it

is

calculated

from

the

dependence

of

the

D

value

-LRB-

specifically

k

-RRB-

on

temperature

Both

D

and

Z

values

are

affected

by

the

physicochemical

and

biochemical

properties

of

the

solution

to

be

sterilized

-LRB-

e.g.

composition

pH

-RRB-

-LSB-

-RSB-

The

Z

value

for

B.

stearothermophilus

in

water

is

°C

vs.

°C

for

vitamin

and

°C

for

vitamin

-LRB-

riboflavin

-RRB-

-LSB-

-RSB-

both

notably

higher

Correspondingly

the

value

for

B.

stearothermophilus

is

vs.

for

vitamin

for

vitamin

-LRB-

riboflavin

-RRB-

and

for

the

Maillard

reaction

-LSB-

-RSB-

all

notably

lower

Two

models

-LRB-

Arrhenius

or

Bigelow

-RRB-

can

be

used

to

extrapolate

death

rates

for

higher

temperatures

than

those

measured

experimentally

since

it

is

difficult

to

measure

kill

and

degradation

kinetics

at

temperatures

above

°C

with

existing

equipment

-LSB-

-RSB-

Using

the

overall

sterilization

hold

time

or

residence

time

tR

the

log

reduction

may

be

obtained

according

to

Eq

where

N

-LRB-

t

-RRB-

is

the

number

of

spores

surviving

heat

treatment

at

incremental

sterilization

time

t

No

is

the

initial

number

of

spores

and

DT

is

defined

below

Eq

Assuming

min

and

Z

°C

-LRB-

typical

values

for

B.

stearothermophilus

spores

in

water

-LSB-

-RSB-

-RRB-

then

log

reductions

for

continuous

sterilization

at

°C

range

from

to

for

the

system

residence

times

of

min

substantially

higher

than

what

is

obtainable

via

batch

sterilization

Actual

sterilization

conditions

are

selected

based

on

specific

medium

properties

and

fermentation

process

requirements

Retention

loop

flow

behavior

and

its

impact

Flow

through

a

pipe

is

characterized

by

the

Reynolds

number

NRe

given

by

DVρ/η

which

is

the

ratio

of

inertial

to

viscous

forces

Since

the

system

flow

tube

diameter

D

-LRB-

cm

-RRB-

does

not

change

NRe

varies

with

sterilization

fluid

velocity

V

-LRB-

controlled

by

system

flowrate

-RRB-

fluid

viscosity

η

-LRB-

cp

-RRB-

and

density

ρ

-LRB-

-RRB-

which

is

fixed

for

the

selected

medium

As

flow

becomes

more

turbulent

-LRB-

higher

NRe

-RRB-

flow

behavior

approaches

ideal

plug

flow

There

is

considerable

disparity

in

the

literature

regarding

the

Reynolds

numbers

associated

with

laminar

and

turbulent

flow

through

a

tube

for

various

continuous

flow

sterilization

applications

For

flow

through

a

tube

laminar

flow

was

below

and

turbulent

flow

was

above

-LSB-

-RSB-

Laminar

flow

was

below

and

turbulent

flow

above

according

to

another

study

-LSB-

-RSB-

A

minimum

velocity

which

gives

turbulent

flow

is

recommended

with

a

Reynolds

number

of

about

-LSB-

-RSB-

or

at

least

-LSB-

-RSB-

but

preferably

above

-LSB-

-RSB-

For

a

retention

loop

in

a

dairy

application

Reynolds

numbers

of

were

considered

laminar

-LSB-

-RSB-

and

Reynolds

numbers

of

were

considered

transitional

-LSB-

-RSB-

Substantially

higher

Reynolds

numbers

of

were

considered

transitional

for

the

heating

and

cooling

sections

of

tubular

HEXs

for

a

dairy

application

-LSB-

-RSB-

Differences

in

tube

roundness

and

entrance

effects

may

have

an

influence

-LSB-

-RSB-

System

design

for

NRe

well

above

particularly

in

the

holding

tube

minimizes

potential

for

inadvertent

operation

in

the

laminar

flow

regime

One

potential

design

approach

is

to

incorporate

flow

disturbances

to

induce

turbulence

at

lower

NRe

Confirmation

of

turbulent

flow

based

on

the

deviation

between

ideal

and

non-ideal

plug

flow

behavior

for

specific

operating

conditions

can

be

determined

experimentally

Continuous

thermal

treatment

is

most

uniform

when

the

flow

through

the

retention

loop

is

turbulent

since

residence

times

of

individual

streamlines

become

less

variable

The

parabolic

velocity

profile

associated

with

laminar

flow

leads

to

variable

residence

times

-LSB-

-RSB-

Specifically

for

laminar

flow

the

mean

velocity

of

a

viscous

fluid

through

a

pipe

is

one-half

of

the

maximum

velocity

along

the

axis

and

for

turbulent

flow

the

mean

velocity

is

of

the

maximum

value

-LSB-

-RSB-

Thus

there

are

concerns

about

laminar

flow

for

viscous

solutions

in

pasteurization

-LRB-

e.g.

ice

cream

mix

egg

nog

and

liquid

egg

products

-RRB-

-LSB-

-RSB-

Non-ideal

flow

behavior

is

problematic

since

each

fluid

element

spends

different

lengths

of

time

in

the

sterilizer

hold

phase

and

thus

receives

different

levels

of

sterilization

Consequently

it

is

necessary

to

characterize

the

residence

time

distribution

to

accurately

predict

lethality

-LSB-

-RSB-

specifically

the

spectrum

of

times

spent

in

the

sterilizer

hold

tube

for

different

fluid

elements

The

extent

of

the

distribution

dictates

the

degree

of

axial

or

Taylor

dispersion

i.e.

concentration

gradients

along

the

length

of

the

retention

loop

-LSB-

Radial

gradients

are

assumed

negligible

-RSB-

The

holding

efficiency

tmin/tm

is

evaluated

by

comparing

the

minimum

holding

time

tmin

-LRB-

min

-RRB-

to

the

mean

holding

time

tm

-LRB-

min

-RRB-

and

the

extent

of

product

overheating

tmax/tm

can

be

calculated

using

the

ratio

of

the

maximum

tmax

-LRB-

min

-RRB-

to

mean

holding

times

-LSB-

-RSB-

Stimulus-response

measurement

techniques

and

data

analysis

to

determine

the

extent

of

non-ideal

flow

have

been

described

comprehensively

-LSB-

-RSB-

After

a

pulse

or

step

change

is

introduced

tracer

concentration

is

measured

as

a

function

of

time

by

sampling

effluent

at

the

system

outlet

The

total

area

under

the

concentration

versus

time

curve

then

is

calculated

and

used

to

normalize

concentration

measurements

so

they

can

be

readily

compared

for

different

tracer

tests

The

exit

age

distribution

E

-LRB-

t

-RRB-

delineates

the

fraction

of

fluid

elements

exiting

the

system

having

a

particular

hold

time

t

It

characterizes

instantaneous

pulse

changes

-LRB-

delta

function

-RRB-

in

tracer

concentration

This

curve

is

normalized

by

dividing

measured

C

-LRB-

t

-RRB-

values

by

the

area

under

the

resulting

concentration

versus

time

curve

to

obtain

E

-LRB-

t

-RRB-

for

which

the

area

under

the

E

-LRB-

t

-RRB-

curve

is

always

one

-LSB-

-RSB-

For

E

-LRB-

t

-RRB-

curves

the

mean

time

tm

is

the

sum

of

individual

products

of

time

normalized

tracer

concentrations

and

time

interval

Δt

-LRB-

min

-RRB-

which

is

assumed

constant

-LSB-

-RSB-

The

distribution

variance

σ2

is

given

by

Eq

where

The

dimensionless

variance

can

be

used

to

estimate

the

dispersion

coefficient

based

on

experimental

data

Another

concentration

versus

time

curve

F

-LRB-

t

-RRB-

is

the

probability

that

a

fluid

element

left

the

system

within

time

t

or

the

volume

fraction

of

the

outlet

stream

that

has

remained

in

the

system

for

a

time

less

than

t

-LSB-

-RSB-

It

characterizes

behavior

resulting

from

step

inputs

of

tracer

with

an

initial

entering

concentration

Co.

The

ratio

of

C

-LRB-

t

-RRB-

Co

versus

time

produces

a

normalized

F

-LRB-

t

-RRB-

curve

for

which

the

axes

range

from

to

-LSB-

-RSB-

These

distributions

are

related

mathematically

according

to

Eqs

and

Integration

of

E

-LRB-

t

-RRB-

curve

to

obtain

the

corresponding

F

-LRB-

t

-RRB-

curve

via

Eq

is

accomplished

graphically

for

various

Δt

-LSB-

-RSB-

Both

the

E

-LRB-

t

-RRB-

and

F

-LRB-

t

-RRB-

curves

also

can

be

made

dimensionless

in

time

by

normalizing

by

the

mean

hold

time

tm

Normalization

with

respect

to

time

is

helpful

to

compare

conditions

at

different

residence

times

and

normalization

with

respect

to

concentration

assists

in

comparing

data

from

different

tracer

experiments

The

sterilization

efficiency

for

a

given

residence

time

distribution

is

given

by

Eq

This

equation

permits

quantitative

assessment

of

the

sterilization

impact

from

non-ideal

flow

patterns

The

Bodenstein

number

-LRB-

or

Peclet

number

or

Peclet-Bodenstein

number

-LSB-

-RSB-

-RRB-

NBs

is

given

by

VL/Dz

where

Dz

is

the

axial

dispersion

coefficient

V

is

the

flow

velocity

m/s

and

L

is

the

retention

loop

length

m

This

dimensionless

group

is

the

ratio

of

convective

transport

to

axial

dispersion

-LSB-

-RSB-

and

it

is

used

to

quantify

the

extent

of

axial

dispersion

For

NBs

there

is

plug

flow

with

minimal

axial

mixing

and

sterilization

efficiency

is

the

highest

possible

-LSB-

-RSB-

For

NBs

axial

dispersion

is

at

its

worst

with

retention

loop

contents

completely

mixed

along

the

tube

length

and

sterilization

likely

is

incomplete

Actual

operating

conditions

fall

between

these

two

extremes

-LSB-

-RSB-

The

flow

system

should

be

designed

so

that

dispersion

is

minimized

with

high

NBs

and

high

NRe

-LSB-

-RSB-

preferably

NRe

NBs

of

have

been

reported

as

typical

for

continuous

sterilizers

-LSB-

-RSB-

The

current

system

's

NBs

of

about

is

much

higher

than

this

range

most

likely

due

to

its

longer

retention

loop

Experimental

distribution

data

may

be

used

to

calculate

NBs

and

then

Dz

-LSB-

-RSB-

using

Eqs

and

For

Dz/VL

and

a

normal

-LRB-

Gaussian

-RRB-

distribution

for

the

E

-LRB-

t

-RRB-

curve

Alternatively

the

dispersion

coefficient

and

residence

time

distribution

may

be

inferred

from

correlations

For

turbulent

flow

Eq

applies

where

the

Fanning

friction

factor

f

for

the

retention

loop

pipe

is

obtained

from

correlations

based

on

the

ratio

of

surface

roughness

ε

to

pipe

diameter

D

-LSB-

-RSB-

An

experimental

correlation

for

water

where

Dz/VD

for

NRe

and

Dz/VD

for

NRe

-LSB-

-RSB-

was

used

to

assess

the

reasonableness

of

measured

Dz/VL

values

and

to

compare

NBs

values

obtained

using

Eqs

and

Friction

factors

for

the

retention

loop

pressure

drop

applicable

for

both

laminar

and

turbulent

flow

were

calculated

using

Eq

-LSB-

-RSB-

and

shown

in

Table

where

Alternatively

these

friction

factors

can

be

estimated

using

the

Colebrook

equation

Eq

-LSB-

-RSB-

and

solving

iteratively

but

this

approach

was

not

used

Rule-of-thumb

conditions

generating

a

narrow

residence

distribution

and

low

dispersion

coefficient

for

flow

through

a

pipe

are

L/D

and

NRe

-LSB-

-RSB-

Influence

of

solid

content

of

media

For

sterilizer

feed

medium

that

contains

solids

ranging

from

small

amounts

to

in

excess

of

vol

-LSB-

-RSB-

solids

must

be

adequately

wetted

and

dispersed

without

clumps

Particles

flow

at

different

velocities

through

the

retention

loop

and

temperature

distribution

within

a

particle

is

challenging

to

monitor

Although

it

is

somewhat

straightforward

to

determine

residence

time

distributions

partial

differential

equations

using

finite

differences

are

required

to

model

convective

conductive

heat

transfer

between

the

fluid

and

particles

-LSB-

-RSB-

Thermal

properties

of

the

surrounding

fluid

are

less

critical

for

heat

transfer

to

particles

since

the

heat

transfer

coefficient

h

-LRB-

cal/s-cm

°C

-RRB-

between

the

fluid

and

particle

is

limiting

-LSB-

-RSB-

Its

effectiveness

is

shown

by

the

Nusselt

number

-LRB-

ratio

of

total

heat

transfer

to

conductive

heat

transfer

-RRB-

NNu

given

by

hDp/K

where

Dp

-LRB-

cm

-RRB-

is

the

particle

diameter

and

K

-LRB-

cal-cm/s-cm

°C

-RRB-

is

the

thermal

conductivity

of

fluid

at

the

processing

temperature

-LSB-

-RSB-

If

the

predicted

particle

temperature

profile

is

hotter

than

the

actual

one

it

is

possible

to

obtain

incomplete

inactivation

-LSB-

-RSB-

The

sterilization

challenge

of

large

diameter

solids

is

to

avoid

selecting

hold

times/temperatures

that

sterilize

solids

but

damage

liquid

medium

components

-LSB-

-RSB-

The

time

required

for

particles

to

attain

sterilizing

temperature

is

on

the

order

of

microseconds

for

particles

several

microns

in

size

-LRB-

i.e.

media

bioburden

-RRB-

and

seconds

for

solids

several

millimeters

in

size

-LRB-

i.e.

raw

material

particles

-RRB-

highlighting

the

need

to

clarify

raw

materials

-LSB-

-RSB-

Time-temperature

integrators

have

been

developed

to

quantify

the

heating

impact

on

spores

within

the

entire

particle

These

indicators

are

spores

immobilized

in

alginate

cubes

or

polymethylmethacrylate

designed

to

have

a

mechanical

resistance

to

flow

through

the

system

similar

to

that

of

actual

particles

-LSB-

-RSB-

Other

tracers

have

been

found

to

mimic

the

flow

behavior

of

microbial

cells

except

when

the

flow

is

laminar

-LSB-

-RSB-

As

the

solid

content

increased

from

to

w/w

the

mean

residence

time

of

the

liquid

phase

increased

by

and

flow

less

resembled

plug

flow

which

indicated

that

the

presence

of

solids

can

significantly

influence

liquid

phase

flow

patterns

-LSB-

-RSB-

Consequently

a

safe

design

approach

for

solids-containing

medium

sterilization

uses

the

maximum

rather

than

average

fluid

velocity

-LSB-

-RSB-

Residence

time

distributions

for

solid

particles

also

often

have

more

than

one

peak

representing

different

groups

of

particles

Experimental

methods

to

quantify

axial

dispersion

Testing

of

dispersion

has

been

done

using

a

variety

of

tracers

most

commonly

salts

and

dyes

Experimental

mean

residence

times

calculated

from

salt

tracer

measurements

in

skim

milk

were

close

to

the

average

holding

time

-LSB-

-RSB-

A

salt

tracer

was

found

to

be

adequate

for

low

viscosity

and

Newtonian

fluids

only

it

overestimated

thermal

exposure

in

more

viscous

fluids

-LSB-

-RSB-

Salt

tracers

can

be

saturated

sodium

chloride

solutions

but

chloride

exposure

is

not

desirable

for

stainless

steel

-LSB-

-RSB-

thus

other

salts

with

high

aqueous

solubilities

-LRB-

sodium

sulfate

sodium

citrate

and

magnesium

sulfate

-RRB-

and/or

sodium

hydroxide

can

be

substituted

Dye

tracers

include

fast

green

FCF

-LRB-

Sigma

St.

Louis

MO

USA

-RRB-

and

basic

Fuchsin

-LRB-

no

vendor

given

-RRB-

-LSB-

-RSB-

Other

tracers

have

been

based

on

chemical

reactions

specifically

sucrose

inversion

-LRB-

hydrolysis

to

glucose

and

fructose

-RRB-

when

heated

in

an

HCl

solution

at

pH

or

sulfuric

acid

at

a

pH

of

to

avoid

exposure

of

stainless

steel

to

chlorides

Changes

in

optical

rotation

and

freezing

point

were

used

to

quantify

reaction

extent

-LSB-

-RSB-

Another

tracer

used

has

been

the

pulse

injection

of

w/w

citric

acid

and

subsequent

pH

measurement

-LSB-

-RSB-

Finally

temperature

spikes

also

have

been

effective

tracers

in

scraped

surface

HEXs

-LSB-

-RSB-

Overview

of

operation

A

comparison

of

major

changes

between

the

prior

and

next

generation

pilot-scale

continuous

sterilization

systems

as

well

as

expected

benefits/risks

or

potential

drawbacks

are

summarized

in

Table

A

schematic

of

major

equipment

components

and

their

arrangement

is

shown

by

Fig.

System

specifications

and

design

criteria

are

listed

in

Table

After

system

design

was

completed

for

water

its

effectiveness

was

evaluated

for

concentrated

nutrients

typically

sterilized

separately

from

the

base

medium

to

avoid

Maillard

reactions

or

sterilized

just

prior

to

delivery

to

active

fed-batch

fermentations

to

avoid

storage

in

a

holding

tank

The

nutrients

and

concentrations

selected

were

wt

cerelose

-LRB-

glucose

monohydrate

CPC

International

Argo

IL

USA

-RRB-

and

vol

glycerol

-LRB-

Superol

glycerine

Proctor

and

Gamble

Chemicals

Cincinnati

OH

USA

-RRB-

Physical

properties

for

these

test

media

at

various

temperatures

were

estimated

for

water

from

-LSB-

DIPPER

database

tables

-LRB-

dippr.byu.edu

-RRB-

-RSB-

Physical

properties

for

vol

glycerol

and

wt

cerelose

were

modeled

using

Aspen

Plus

-LRB-

AspenTech

Cambridge

MA

USA

-RRB-

process

simulation

software

with

physical

properties

database

information

Table

of

major

changes

in

large

continuous

sterilization

systemItemPrior

designNew

designExpected

benefit/Risk

or

potential

drawbackFinal

heating

method

to

attain

sterilization

temperatureDirect

steam

injectionIndirect

heating

loopLess

dilution

improved

stability

with

respect

to

source

steam

fluctuations

no

adulteration

from

plant

steam

additives/higher

costFlowmeterMagneticCoriolisAbility

to

sense

deionized

water/position

of

flag

criticalNumber

of

different

retention

loop

lengthsAble

to

increase/decrease

by

two

tubes

for

tubes

-LRB-

tR

min

-RRB-

removable

connections

at

both

ends

of

all

tubesFive

configurations

from

to

tubes

-LRB-

tR

min

-RRB-

removable

jumpers

at

same

end

of

selected

tubesFewer

fittings/limited

visual

inspectionFlowrate

turn

lpmAvoids

separate

smaller

unit/multiple

ranges

for

tuning

controlPressure

safety

deviceSafety

valve

onlyRupture

disc

and

safety

valve

with

tell-tale

pressure

gaugeSanitary

disc

in

process

contact

evident

when

disc

blown/added

cost

and

maintenanceSecond

cooler

of

same

size

as

process

cooler

-LRB-

flash

cooler

-RRB-

AbsentPresentAbility

to

conduct

water

sterilization

installed

marker

for

process

cooler/extra

expenseBooster

pump

with

pressure

control

on

recuperator

outletAbsentPresent

-LRB-

used

with

centrifugal

feed

pump

only

-RRB-

Sterile

media

at

higher

pressure

than

non-sterile

media/increased

complexity

of

tuning

and

operationRetention

loop

insulationInsulated

box

without

packing

°C

temperature

dropInsulated

box

with

packing

°C

temperature

dropMore

adiabatic

and

isothermal/modest

additional

expenseHEX

plate

Lower

cost

and

higher

surface

area

per

unit

volume/higher

risk

of

breachHEX

aspect

ratioHigher

velocities/increased

effect

of

channeling

due

to

gap

and

drain

-LRB-

horizontal

cross

flow

for

condensing

service

-RRB-

HEX

process

side

channel

-LRB-

coolers

-RRB-

-LRB-

coolers

-RRB-

Higher

surface

area

per

unit

volume/higher

pressure

dropHEX

utility

side

channel

thickness

-LRB-

coolers

-RRB-

Higher

surface

area

per

unit

volume/higher

pressure

dropAspect

ratio

is

the

HEX

diameter

divided

by

its

widthFig

of

sterilizer

system

a

major

components

b

switching

stationTable

specifications

and

design

criteriaParametersDesign

range

-LRB-

min

max

-RRB-

Sterilization

hold

temperature

-LRB-

T

-RRB-

°C

Retention

loop

hold

up

volume

-LRB-

Vs

-RRB-

LFlowrate

-LRB-

to

achieve

design

recuperator

HEX

heat

recovery

-RRB-

-LRB-

Q

-RRB-

lpm

at

°C

-LRB-

water

-RRB-

lpm

at

°C

-LRB-

wt

cerelose

-RRB-

lpm

at

°C

-LRB-

wt

cerelose

-RRB-

lpm

at

°C

-LRB-

vol

glycerol

-RRB-

lpm

at

°C

-LRB-

vol

glycerol

-RRB-

Flow

rates

lpm

may

not

achieve

sufficient

back-pressure

for

the

selected

sterilization

temperature

to

avoid

flashingFeed

temperature

-LRB-

Tin

cold

ext

-RRB-

°C

-LRB-

water

vol

glycerol

-RRB-

°C

-LRB-

wt

cerelose

-RRB-

Feed

temperature

of

°C

for

wt

cerelose

insufficient

to

maintain

a

solutionResidence

time

-LRB-

tR

-RRB-

minBack-pressure

-LRB-

P

-RRB-

-LRB-

typically

-RRB-

Sufficient

pressures

used

to

avoid

flashing

for

°C

for

°C

Retention

loop

temperature

drop

-LRB-

L

volume

and

inlet

temperature

of

°C

-RRB-

°C

for

lpm

°C

for

lpm

°C

for

lpm

and

°C

for

lpmHeat

recovery

-LRB-

HR

-RRB-

depending

inlet

feed

temperature

media

type

and

flowrate

-LRB-

lpm

water

°C

-RRB-

-LRB-

lpm

wt

cerelose

°C

-RRB-

-LRB-

lpm

vol

glycerol

°C

-RRB-

The

sterilizer

had

several

distinct

phases

that

are

depicted

by

Fig.

and

described

briefly

below

System

start

up

included

-LRB-

-RRB-

leak

tests

of

the

cold

system

under

pressure

-LRB-

-RRB-

flowrate

and

totalizer

accuracy

checks

versus

a

decrease

in

feed

tank

volume

and

-LRB-

-RRB-

leak

re-check

after

raising

the

system

to

sterilization

temperature

Proper

operation

and

reliability

of

instrumentation

was

assured

by

evaluating

all

pressure

and

temperature

transmitter

and

gauge

readings

for

consistency

Prior

to

system

sterilization

and

before

introducing

steam

or

superheated

water

draining

of

process

water

supplemented

by

evacuating

with

psig

air

was

necessary

for

preventing

stress

corrosion

cracking

of

HEXs

-LSB-

-RSB-

Fig.

of

sterilizer

phases

The

next

phase

was

steam

sterilization

using

four

high

point

steam

injection

points

one

of

which

was

located

at

the

outlet

of

retention

loop

and

setting

the

hot

water

heating

loop

to

°C

slightly

above

the

corresponding

steam

sterilization

temperature

of

°C

for

the

psig

-LRB-

-RRB-

steam

supplied

After

h

of

steam

sterilization

the

system

was

transitioned

from

steam

to

water

carefully

-LRB-

over

a

period

of

h

-RRB-

to

maintain

sterility

or

with

less

care

assuming

that

water

sterilization

was

planned

next

Steam

sterilization

could

be

conducted

for

the

system

up

through

the

process

cooler

as

well

as

up

through

the

flash

cooler

-LRB-

Fig.

-RRB-

Use

of

the

flash

cooler

was

the

preferred

configuration

since

it

provided

an

extra

buffer

during

steam

collapse

During

this

next

phase

of

steam-to-water

transition

the

system

flowrate

was

started

with

lpm

water

flowing

to

the

sewer

after

the

flash

cooler

using

the

Moyno

pump

All

steam

injection

points

such

as

the

medium

distribution

system

were

closed

and

the

hot

water

generated

by

the

heater

provided

sufficient

back-pressure

The

system

was

set

up

for

water

sterilization

-LRB-

i.e.

recuperator

non-sterile

side

bypassed

and

the

flash

cooler

used

to

cool

sterilizing

water

so

that

the

process

cooler

could

be

sterilized

-RRB-

and

the

hot

water

loop

was

set

at

°C

in

cascade

-LRB-

set

point

for

water

sterilization

-RRB-

As

water

entered

the

system

the

temperature

of

the

retention

loop

rose

from

to

°C

while

the

temperature

of

the

process

cooler

fell

from

to

°C

-LRB-

The

temperature

drop

of

the

process

cooler

was

not

a

sterility

risk

since

the

entering

lpm

water

flowrate

sterilized

at

°C

resulted

in

a

sufficient

Fo

of

min

to

assure

sterility

of

the

retention

loop

effluent

-RRB-

Loss

of

incoming

water

due

to

boiling

while

the

system

was

at

a

lower

backpressure

was

believed

minimized

by

the

nearly

closed

flash

cooler

backpressure

valve

-LRB-

expected

fill

volume

L

actual

volume

L

-RRB-

During

water

sterilization

incoming

cold

water

was

circulated

for

two

passes

-LRB-

one

pass

if

system

was

already

hot

from

steam

sterilization

-RRB-

at

lpm

using

the

centrifugal

inlet

feed

pump

after

it

rose

to

the

sterilization

inlet

hold

temperature

of

°C

It

required

previously

steamed-through

system

block/drain

valves

since

users

were

not

comfortable

that

conduction

adequately

sterilized

through

them

when

closed

The

non-sterile

side

of

the

recuperator

HEX

was

bypassed

to

ensure

that

the

sterile

side

reached

sterilization

temperature

Cooling

water

was

applied

to

the

flash

cooler

to

ensure

that

the

process

cooler

attained

sterilization

temperature

For

the

target

sterilization

temperature

of

just

below

°C

and

a

lpm

water

flowrate

the

temperature

reached

about

°C

at

the

sterile

side

of

the

recuperator

and

°C

for

the

sterile

side

of

the

process

cooler

Water

sterilization

was

redone

during

medium

sterilization

if

medium

diversion

was

necessary

owing

to

system

sterility

upset

After

taking

immediate

action

to

divert

media

away

from

the

production

vessel

water

re-sterilization

was

conducted

by

-LRB-

-RRB-

diverting

flow

through

the

flash

cooler

and

enabling

its

pressure

control

loop

-LRB-

-RRB-

fully

opening

the

process

cooler

back-pressure

valve

-LRB-

-RRB-

conducting

water

re-sterilization

-LRB-

-RRB-

enabling

the

process

cooler

pressure

control

loop

-LRB-

-RRB-

fully

opening

the

flash

cooler

back-pressure

valve

and

then

-LRB-

-RRB-

resuming

medium

sterilization

When

switching

from

the

flash

to

the

process

cooler

it

was

necessary

to

maintain

sterile

conditions

After

the

system

was

sterilized

and

running

on

water

typically

in

recirculation

mode

or

emptying

into

the

system

sewer

the

switching

valve

station

was

used

to

divert

flow

to

distribution

Water

now

flowed

to

a

waste

vessel

or

the

process

sewer

located

near

the

eventual

medium

receiving

vessel

After

conditions

stabilized

sterilizer

inlet

feed

was

switched

from

water

to

medium

Again

after

conditions

stabilized

flow

was

switched

to

the

receiving

vessel

When

the

receiving

vessel

was

filled

sufficiently

sterilizer

effluent

was

switched

back

to

the

waste

tank

sterilizer

inlet

feed

was

switched

back

to

water

and

then

effluent

switched

back

to

either

the

recirculation

vessel

or

system

sewer

After

media

sterilization

a

thorough

water

rinse

was

conducted

at

sterilization

temperature

and

the

system

was

cooled

to

°C

for

cleaning

Alkaline

and/or

acid

cleaning

solutions

were

used

depending

on

the

nature

of

the

soil

After

cleaning

the

system

was

cooled

and

drained

completely

Equipment

design

The

system

's

five

skids

were

designed

and

fabricated

at

the

vendor

's

shop

and

delivered

with

only

field

installation

of

interconnecting

piping

required

To

minimize

design

miscommunications

three-dimensional

piping

models

were

used

for

skid

piping

plans

which

were

able

to

be

reviewed

remotely

by

the

customer

Ball

valves

were

used

instead

of

diaphragm

valves

for

hot

temperature

service

Hazardous

energy

control

was

carefully

considered

with

locking

devices

installed

and

valve

placement

selected

for

facile

equipment

isolation

and

operability

Equipment

was

citric

acid-passivated

after

installation

Each

relief

device

on

the

process

side

consisted

of

a

flanged

rupture

disc

-LRB-

RD

-RRB-

with

a

pressure

indicator

and

telltale

as

well

as

a

pressure

safety

valve

-LRB-

PSV

-RRB-

that

reseated

after

the

source

of

excessive

pressure

was

removed

These

devices

were

placed

directly

after

the

positive

displacement

Moyno

-LRB-

Robbins

and

Myers

West

Chester

PA

USA

-RRB-

system

inlet

feed

pump

recuperator

outlet

and

booster

pump

Discharges

were

piped

to

return

to

the

feed

tank

for

safety

as

well

as

for

medium

recovery

Piping

was

designed

such

that

no

PSV

devices

were

required

on

the

process

side

to

minimize

risk

of

system

integrity

disruption

Sample

points

were

located

on

the

inlet

feed

-LRB-

pre-sterilization

prior

to

recuperator

-RRB-

and

sterilized

medium

outlet

-LRB-

post-sterilization

after

process

cooler

-RRB-

lines

Heat

exchangers

The

chief

goals

of

HEX

design

are

to

optimize

cost

heat

transfer

size

and

pressure

drop

-LSB-

-RSB-

The

type

of

HEX

selected

was

a

spiral

which

was

preferred

over

alterative

shell

and

tube

plate

and

frame

or

concentric

double

pipe

designs

A

spiral

HEX

consists

of

two

long

flat

preferably

seamless

sheets

of

metal

plate

separated

by

spacers

or

studs

wrapped

around

a

center

core

or

mandrel

which

forms

two

concentric

spirals

Alternate

ends

are

welded

-LRB-

both

by

machine

and

manually

-RRB-

to

create

separated

flow

channels

Hot

fluid

enters

the

center

-LRB-

flows

inside

to

outside

-RRB-

and

cold

fluid

enters

on

the

exterior

-LRB-

flows

outside

to

inside

-RRB-

to

achieve

countercurrent

flow

Details

of

spiral

HEX

design

are

described

elsewhere

-LSB-

-RSB-

Advantages

of

spirals

are

chiefly

that

they

require

less

space

per

unit

of

heat

transfer

surface

area

-LSB-

-RSB-

Their

continuously

curved

channel

unrestricted

flow

path

and

presence

of

spacers

increases

turbulence

due

to

secondary

flow

effects

which

maintain

solids

in

suspension

-LSB-

-RSB-

Fouling

is

lower

than

shell

and

tube

designs

since

cross-sectional

velocities

increase

as

channel

size

decreases

creating

a

scrubbing

effect

-LSB-

-RSB-

-LRB-

In

contrast

as

individual

tubes

of

shell

and

tube

exchangers

plug

flow

is

diverted

into

unplugged

tubes

-RRB-

Spirals

are

particularly

well

suited

for

slurries

and

many

viscous

fluids

-LSB-

-RSB-

Specifically

slurries

can

be

processed

at

velocities

as

low

as

ft/s

-LRB-

m/s

-RRB-

-LSB-

-RSB-

Periodic

thorough

cleaning

can

be

conducted

by

simply

removing

the

cover

to

expose

the

spiral

cavities

and

cleaning

with

a

high

pressure

water

source

Evaluation

of

thermal

effectiveness

can

be

done

by

calculating

the

number

of

thermal

transfer

units

NTU

-LSB-

-RSB-

using

Eq

where

AHEX

is

the

heat

transfer

area

QM

is

the

mass

flow

rate

-LRB-

kg/s

-RRB-

U

-LRB-

W/s

-RRB-

is

the

overall

mean

heat

transfer

coefficient

between

the

fluid

streams

and

Cp

-LRB-

J/kg-K

-RRB-

is

the

specific

heat

capacity

of

the

fluid

at

constant

pressure

This

quantity

also

can

be

obtained

from

individual

stream

temperatures

where

Tin

hot

ctr

is

the

temperature

of

the

incoming

hot

stream

entering

in

the

center

Tin

cold

ext

is

the

temperature

of

the

incoming

cold

stream

entering

on

the

periphery

Tout

hot

ext

is

the

temperature

of

the

outgoing

hot

stream

exiting

on

the

periphery

and

Tout

cold

ctr

is

the

temperature

of

the

outgoing

cold

stream

exiting

in

the

center

In

this

case

the

temperature

rise

of

the

cold

stream

is

divided

by

the

log

mean

temperature

difference

-LRB-

LMTD

-RRB-

for

the

HEX

An

NTU

of

correspond

to

a

shell

and

tube

HEX

NTU

represents

overlap

of

hot

and

cold

side

temperature

ranges

indicative

of

spiral

HEXs

Thermal

effectiveness

also

can

be

evaluated

using

Eq

to

calculate

the

thermal

effectiveness

factor

TE

-LSB-

-RSB-

Overall

Eq

represents

the

change

in

recuperator

cold

side

stream

temperature

divided

by

the

temperature

difference

of

streams

flowing

through

its

center

connections

-LRB-

i.e.

incoming

sterilized

hot

medium

exiting

retention

loop

and

outgoing

pre-heated

non-sterile

medium

-RRB-

Finally

thermal

effectiveness

can

be

evaluated

by

calculating

the

heat

recovery

heat

recovery

-LRB-

HR

-RRB-

using

Eq

which

represents

the

heat

gained

by

the

incoming

cold

medium

after

passing

through

the

recuperator

divided

by

total

heat

gained

by

the

cold

medium

after

passing

through

both

the

recuperator

and

heater

HEXs

Heat

recoveries

improve

with

clean

HEXs

-LRB-

higher

heat

transfer

coefficient

-RRB-

lower

flowrates

-LRB-

permitting

more

time

for

heat

transfer

-RRB-

and

higher

inlet

feed

temperatures

-LRB-

lower

medium

viscosity

which

improves

heat

transfer

coefficient

-RRB-

When

the

temperature

difference

on

both

sides

of

the

recuperator

is

the

same

then

NTU

is

replaced

by

TE

and

Eq

can

not

be

used

since

ΔTln

-LSB-

-RSB-

For

consistency

in

comparing

design

and

observed

performance

over

the

entire

sterilizer

system

the

value

of

Tin

hot

ctr

-LRB-

retention

loop

outlet

temperature

-RRB-

used

for

calculating

design

values

in

Eqs

and

was

assumed

to

be

identical

to

the

retention

loop

inlet

temperature

-LRB-

T

-RRB-

i.e.

the

retention

loop

was

assumed

to

be

isothermal

-LRB-

adiabatic

-RRB-

The

sensitivity

of

these

three

parameters

to

small

temperature

measurement

errors

of

°C

for

the

expected

temperature

change

of

each

HEX

stream

was

estimated

for

NTU

for

TE

and

for

HR

Specific

limiting

performance

case

scenarios

depend

on

media

type

and

inlet

feed

temperature

Higher

inlet

feed

temperature

-LRB-

°C

-RRB-

is

worst

case

for

the

cooling

HEX

since

the

recuperator

removes

less

heat

from

sterile

medium

Lower

inlet

feed

temperature

-LRB-

°C

-RRB-

is

worst

case

for

the

recuperator

since

it

represents

the

greatest

challenge

to

HR

Heat

exchanger

design

and

material

selection

is

important

to

extending

the

unit

's

lifetime

A

pressure

rating

of

psig

was

selected

to

match

piping

specifications

specifically

flange

connections

Thicker

gauge

material

permitted

wider

spacing

of

studs

directly

affecting

cost

-LSB-

-RSB-

minimized

corrosion

without

significantly

reducing

heat

transfer

-LSB-

-RSB-

but

decreased

HEX

surface

area

per

unit

volume

-LRB-

Table

-RRB-

All

HEXs

underwent

hydrostatic

as

well

as

helium

leak

tests

Studs

for

spacing

were

only

partially

welded

around

the

base

so

a

small

crack

existed

These

crevices

were

considered

unavoidable

and

they

were

accepted

since

they

were

shallow

enough

to

permit

adequate

contact

with

sterilizing

and

cleaning

fluids

Heat

exchanger

diameter

width

and

channel

spacing

were

designed

to

minimize

fouling

and

deposits

by

ensuring

channel

velocities

were

sufficiently

high

during

operation

Channel

widths

of

were

used

except

for

the

utility

sides

of

cooler

HEXs

where

a

channel

width

of

was

selected

to

minimize

plugging

due

to

cooling

water

deposits

and

to

reduce

pressure

drop

Bulk

velocities

for

each

process

fluid

are

shown

in

Table

A

sanitary

design

was

utilized

with

a

continuous

sheet

for

coil

formation

a

tapered

channel

transition

for

the

medium

inlet

and

outlet

external

bracing

of

shell

connections

back-welding

of

the

center

pocket

stiffener

as

much

as

possible

elimination

of

additional

center

stiffeners

and

polishing/cleaning

of

all

internal

welds

Process

connections

were

psig

bolted

milled

lap-joint

flanges

possessing

a

right

angle

rather

than

a

bevelled

edge

to

line

up

directly

with

the

gasket

and

avoid

crevices

A

solid

L

stainless

steel

door

eliminated

a

process

side

weld

around

the

center

nozzle

required

to

attach

a

stainless

steel

skin

to

a

carbon

steel

door

Heat

exchangers

initially

were

designed

to

include

a

gap

between

the

spiral

face

and

cover

to

minimize

gouging

of

the

door

due

to

distortion

or

telescoping

Spirals

can

grow

during

thermal

cycling

and

cut

into

full-face

gaskets

if

present

-LSB-

-RSB-

or

door

covers

if

annular

gaskets

were

utilized

without

a

sufficient

gap

Telescoping

also

was

minimized

by

not

applying

pressure

to

one

HEX

side

without

either

the

opposite

door

bolted

closed

or

suitable

bracing

installed

on

the

open

side

An

annular

gasket

initially

was

selected

which

when

placed

in

its

groove

provided

a

gap

between

the

exchanger

spiral

surface

and

the

door

At

first

this

gap

was

considered

small

enough

so

that

any

short-circuiting

negligibly

impacted

performance

particularly

the

recuperator

HR

Subsequently

the

gap

size

was

realized

to

be

critical

especially

for

high

aspect

ratio

-LRB-

pancake

type

-RRB-

HEXs

like

the

recuperator

The

smoothness

and

straightness

of

the

spiral

and

door

faces

-LRB-

tolerance

of

-RRB-

also

assured

a

consistent

gap

minimizing

bypassing

and

maximizing

heat

transfer

HEXs

were

modified

to

be

within

this

tolerance

Observed

pressure

drops

during

operation

-LRB-

°C

inlet

retention

loop

temperature

lpm

water

-RRB-

approached

design

values

for

cases

where

this

gap

was

minimized

through

installation

of

compressible

gaskets

Both

an

annular

gasket

-LRB-

Gylon

Garlock

Sealing

Technologies

Palmyra

NY

USA

-RRB-

and

a

full-face

gasket

-LRB-

Gylon

-RRB-

were

used

to

implement

a

full-face

gasket

installation

with

gasket

material

compressed

so

as

to

cut

into

the

spiral

face

Low

point

drains

were

installed

to

permit

complete

system

drainage

with

steam

barriers

applied

to

sterile

process

side

drain

valves

to

reduce

sterility

risk

These

drains

were

fed

by

small

U

shaped

notches

in

each

wind

of

the

spiral

from

the

center

down

to

the

door

drain

These

notches

were

expected

to

negligibly

impact

performance

relative

to

the

gap

The

extent

that

gaps

or

notches

remained

when

a

pliable

full-face

gasket

was

installed

was

estimated

by

qualitative

assessment

of

HEX

gravity

draining

rates

which

corresponded

to

measured

pressure

drops

closer

to

design

values

For

the

HEX

gaskets

selected

the

remaining

water

after

gravity

drain

was

of

the

entire

HEX

hold

up

volume

suggesting

only

very

small

gaps

This

water

was

removed

by

subsequent

blow-down

using

a

psig

air

supply

A

second

cooling

HEX

was

required

for

water

sterilization

conducted

without

a

pressurized

recirculation

vessel

This

HEX

was

cooled

with

chilled/cooling

water

and

not

by

flashing

and

it

is

referred

to

as

a

flash

cooler

throughout

this

paper

Since

this

pilot

scale

system

was

used

intermittently

a

sterilized

system

was

not

continuously

maintained

by

recirculating

sterile

water

between

media

runs

which

often

is

done

in

production

facilities

This

flash

cooling

HEX

also

was

sized

to

directly

replace

the

process

cooling

HEX

Since

process

coolers

experienced

the

highest

extent

of

thermal

cycling

they

were

more

likely

than

the

other

HEXs

to

fail

based

on

previous

experience

In

addition

it

was

desirable

to

avoid

using

chlorine

treatments

to

reduce

bioburden

in

chilled

and

tower

cooling

water

since

this

adversely

affected

stainless

steel

integrity

-LSB-

-RSB-

Other

causes

of

stress

cracking

and

pitting

corrosion

during

normal

operations

and

cleanouts

also

existed

-LSB-

-RSB-

and

their

impact

needed

to

be

minimized

Chilled/cooling

water

flowrates

to

cooling

HEXs

were

sized

for

reasonable

exit

temperatures

to

minimize

load

on

the

chiller/cooling

tower

and

reduce

deposits

that

formed

at

higher

outlet

cooling

water

temperatures

above

°C

-LSB-

-RSB-

The

peak

design

condition

was

for

water

sterilization

of

the

system

and

not

production

of

sterile

media

The

observed

rise

in

chilled

water

temperature

was

within

design

values

when

full

cooling

was

applied

but

not

when

the

control

valve

restricted

flow

to

attain

the

desired

outlet

temperature

set

point

-LRB-

Table

-RRB-

Less

water

was

used

for

cooling

when

under

control

than

was

assumed

in

the

design

since

-LRB-

-RRB-

process

and

flash

coolers

were

oversized

and

-LRB-

-RRB-

media

outlet

temperature

and

chilled

water

flowrate

can

not

both

be

specified

Hot

water

heating

loop

A

hot

water

or

tempered

heating

loop

involves

indirect

heating

without

direct

steam

contact

and

it

utilizes

a

HEX

expansion

tank

and

circulation

pump

to

heat

water

to

above

°C

It

is

more

expensive

than

direct

steam

injection

since

additional

equipment

is

required

but

hot

water

loops

have

some

key

advantages

Direct

steam

injection

can

be

accomplished

with

a

specialized

steam

water

mixing

valve

for

example

a

Pick

heater

-LSB-

-RSB-

Although

it

is

more

energy

efficient

since

heat

up

is

almost

instantaneous

its

ability

to

provide

accurate

temperature

control

has

been

debated

It

has

a

faster

response

time

can

be

used

with

solids-containing

media

and

is

easier

to

clean

and

maintain

-LSB-

-RSB-

but

it

is

sensitive

to

source

steam

pressure

and

media

composition

changes

Limited

theoretical

design

information

is

established

for

these

mixers

although

detailed

photographic

examination

of

injected

steam

characteristics

in

water

as

a

function

of

flow

Reynolds

number

is

available

-LSB-

-RSB-

The

key

drawback

to

direct

steam

injection

is

process

stream

dilution

which

can

be

up

to

vol

-LSB-

-RSB-

Excess

water

must

be

removed

by

subsequent

flashing

elsewhere

in

the

system

or

the

initial

feed

concentration

must

be

adjusted

Also

since

medium

is

exposed

directly

to

steam

it

may

accumulate

any

additives

or

iron

present

in

the

steam

-LSB-

-RSB-

Finally

there

can

be

additional

noise

from

direct

steam

injection

into

flowing

liquid

in

some

applications

There

is

higher

energy

in

steam

-LRB-

kJ/kg

energy

released

from

condensing

steam

-RRB-

versus

the

heat

capacity

Cp

of

water

of

kJ/kg

K

making

condensing

steam

heat

content

higher

than

hot

water

heat

content

on

a

per

degree

basis

-LSB-

-RSB-

In

addition

injected

steam

heat

transfer

coefficients

are

higher

than

indirect

condensing

steam

heat

transfer

coefficients

-LSB-

-RSB-

and

are

not

reduced

by

fouling

as

in

a

HEX

-LSB-

-RSB-

Consequently

there

are

advantages

of

direct

steam

injection

due

its

higher

steam

utilization

efficiency

-LSB-

-RSB-

for

high

temperature

sterilization

of

milk

-LSB-

-RSB-

and

beer

mash

heating

-LSB-

-RSB-

Based

on

its

advantages

for

media

sterilization

indirect

heating

via

a

hot

water

loop

was

implemented

A

shell

and

tube

L

stainless

steel

HEX

was

selected

for

this

application

since

a

spiral

HEX

was

not

found

to

be

cost-effective

for

the

size

required

The

hot

water

loop

utility

piping

originally

carbon

steel

exhibited

substantial

amounts

of

iron

oxide

corrosion

due

to

its

operation

at

higher

temperatures

This

build-up

throughout

the

hot

water

loop

was

subsequently

removed

by

a

citric

acid

wash

and

piping

was

replaced

by

stainless

steel

The

hot

water

loop

was

designed

for

an

operating

temperature

of

up

to

°C

and

pressure

of

psig

using

compressed

air

-LRB-

psig

-RRB-

applied

to

the

expansion

tank

Installation

of

a

computer

limit

of

°C

for

the

loop

temperature

was

necessary

to

avoid

inadvertent

system

over-pressurization

since

the

steam

control

valve

opened

fully

during

initial

loop

heat

up

Inlet

retention

loop

temperature

was

controlled

for

these

loops

rather

than

outlet

temperature

commonly

used

in

pasteurization

applications

-LSB-

-RSB-

owing

to

longer

loop

residence

times

for

medium

sterilization

applications

Sterilization

inlet

temperature

was

controlled

in

either

automatic

or

cascade

mode

In

automatic

mode

a

single

loop

was

used

to

modulate

hot

water

temperature

to

control

retention

loop

inlet

temperature

at

the

outlet

of

the

heater

In

this

single

loop

feedback

control

wider

periodic

fluctuations

have

been

found

but

response

time

is

quicker

-LSB-

-RSB-

In

cascade

mode

inlet

temperature

was

used

for

primary

control

and

hot

water

temperature

input

was

used

as

the

secondary

control

loop

Using

cascade

control

the

slave

inner

or

secondary

loop

manipulated

the

steam

control

valve

to

control

water

outlet

temperature

from

the

hot

water

HEX

The

master

outer

or

primary

loop

manipulated

the

secondary

-LRB-

slave

-RRB-

loop

set

point

to

control

medium

outlet

temperature

on

the

final

heating

HEX

prior

to

medium

entry

into

the

retention

loop

This

control

has

been

found

to

be

smoother

and

more

accurate

-LSB-

-RSB-

but

it

has

about

a

twofold

longer

response

time

-LSB-

-RSB-

Steam

valve

signals

were

more

stable

under

cascade

control

with

more

constant

steam

flows

instead

of

oscillating

between

high

and

low

steam

supply

flow

rates

as

in

single

loop

control

An

alternative

feed

forward

control

algorithm

also

has

been

used

in

other

systems

to

anticipate

process

upsets

due

to

load

changes

and

to

ensure

tight

control

of

product

outlet

temperature

from

the

retention

loop

-LSB-

-RSB-

but

this

strategy

was

not

implemented

in

the

current

system

The

hot

water

loop

temperature

controllers

initially

were

tuned

using

the

Ziegler

Nichols

closed

loop

method

-LSB-

-RSB-

for

both

primary

and

secondary

loops

Tuning

constants

for

the

secondary

loop

were

first

determined

from

the

ultimate

gain

-LRB-

specifically

controller

gain

that

causes

continuous

cycling

-RRB-

and

ultimate

period

-LRB-

specifically

cycle

period

-RRB-

Next

the

primary

loop

was

tuned

with

the

secondary

loop

placed

in

cascade

using

these

constants

The

speed

of

the

slave

-LRB-

secondary

-RRB-

loop

was

slowed

down

considerably

and

reset

minimized

-LSB-

-RSB-

to

gain

more

precise

control

-LRB-

°C

-RRB-

of

inlet

temperature

in

cascade

mode

Together

with

low

heat

loss

over

the

insulated

retention

loop

this

tuning

strategy

permitted

operation

at

more

uniform

sterilizing

temperatures

Thus

sterilization

temperature

effects

on

subsequent

production

media

performance

were

quantified

more

precisely

and

operation

with

a

safety

factor

of

several

degrees

was

avoided

Retention

loop

The

retention

loop

-LRB-

holding

tube

or

box

-RRB-

was

composed

of

thirty

diameter

tubes

-LRB-

schedule

pipe

with

an

ID

of

and

wall

thickness

of

-RRB-

each

with

only

one

weld

over

the

ft

straight

length

plus

connecting

U-bends

These

U-bends

were

fabricated

from

pipe

bent

by

machine

that

resulted

in

a

minimum

thickness

at

the

bend

slightly

less

than

normal

schedule

pipe

The

total

length

was

ft

-LRB-

m

-RRB-

The

L/D

was

suggesting

that

a

narrow

residence

time

distribution

-LRB-

and

low

axial

dispersion

-RRB-

was

achievable

with

sufficient

turbulent

flow

Also

additional

mixing

at

each

U-bend

owing

to

its

curvature

might

further

reduce

axial

concentration

gradients

although

this

effect

has

not

been

mentioned

specifically

in

the

literature

The

retention

loop

was

designed

to

be

drainable

and

tubes

were

arranged

in

two

banks

in

an

accordion-type

fashion

on

a

incline

Pipe

supports

were

designed

to

permit

expansion

-LSB-

-RSB-

A

high

point

vent

valve

was

installed

in

the

loop

for

draining

and

for

bleeding

of

air

during

steaming/filling

-LRB-

This

vent

valve

did

not

appear

to

be

required

since

a

negligible

amount

of

air

exited

the

system

when

it

was

opened

-RRB-

Jumpers

were

configurable

for

variable

retention

loop

volumes

of

-LRB-

L

-RRB-

-LRB-

L

-RRB-

-LRB-

L

-RRB-

-LRB-

L

-RRB-

or

-LRB-

L

-RRB-

tubes

All

of

the

jumpers

were

located

on

the

same

end

of

the

retention

loop

with

a

removable

insulation

cover

Removable

U-bends

were

attached

using

pipe-to-I-line

ferrule

fitting

adaptors

with

minimal

welds

and

maintaining

the

inner

diameter

so

that

flow

was

not

constricted

The

retention

loop

was

required

to

operate

as

close

to

isothermally

-LRB-

adiabatically

-RRB-

as

possible

Improved

insulation

was

installed

by

packing

fiberglass

blankets

inside

thick

fiberglass

board

surrounding

the

faces

between

the

frame

and

tubes

This

method

was

preferred

over

insulating

individual

tubes

since

the

large

insulation

thickness

required

around

each

tube

adversely

enlarged

overall

loop

dimensions

The

temperature

profile

along

the

length

of

the

retention

loop

was

assumed

to

be

linear

-LSB-

-RSB-

For

this

improved

insulation

observed

retention

loop

temperature

drops

as

a

function

of

flowrate

compared

favorably

with

design

values

Flow

and

pressure

control

Flow

and

pressure

control

was

composed

of

five

loops

that

although

not

related

by

software

linkages

were

closely

related

operationally

Two

flow

control

valves

were

installed

with

one

located

after

the

centrifugal

inlet

feed

pump

and

one

after

the

centrifugal

booster

pump

-LRB-

Fig.

-RRB-

The

system

was

designed

to

utilize

either

a

positive

displacement

-LRB-

Moyno

-RRB-

or

centrifugal

inlet

feed

pump

When

the

positive

displacement

pump

was

used

both

flow

control

valves

were

held

fully

open

and

flow

was

controlled

using

the

Moyno

pump

's

variable

speed

drive

When

the

centrifugal

feed

pump

was

used

with

the

booster

pump

booster

pump

suction

pressure

was

controlled

just

prior

to

the

booster

pump

suction

and

flow

was

controlled

at

the

booster

pump

discharge

only

-LRB-

The

flow

control

valve

after

the

centrifugal

feed

pump

was

not

used

since

this

starved

the

booster

pump

suction

-RRB-

Three

pressure

control

valves

also

were

installed

One

pressure

control

valve

located

on

the

recuperator

inlet

piping

on

the

booster

pump

suction

side

was

set

to

maintain

a

positive

pressure

differential

to

avoid

leakage

on

non-sterile

feed

should

a

HEX

breach

develop

-LSB-

sterile

side

at

higher

average

pressure

-LRB-

-RRB-

than

the

non-sterile

side

-RSB-

The

second

and

third

valves

were

located

after

the

process

and

flash

coolers

respectively

-LRB-

Fig.

-RRB-

to

maintain

system

pressure

above

the

boiling

point

which

eliminated

noise

and

potential

damage

from

hammering

-LSB-

-RSB-

To

avoid

leakage

of

non-sterile

cooling

fluids

the

pressure

on

the

utility

side

of

the

process

cooler

can

be

operated

slightly

below

that

of

the

sterile

process

side

-LSB-

-RSB-

by

raising

the

system

back-pressure

or

by

reducing

the

chilled

water

supply

pressure

-LRB-

i.e.

by

opening

the

supply

to

the

nearby

flash

cooler

-RRB-

Piping

and

HEX

pressure

drops

were

designed

to

be

low

so

that

sufficient

back-pressures

were

attainable

at

the

system

outlet

to

provide

adequate

protection

against

flashing

There

were

limits

to

the

range

of

suitable

temperature

and

back-pressure

combinations

that

avoided

operating

close

to

the

fluid

flashing

point

-LRB-

Table

-RRB-

In

addition

sufficient

system

flowrate

-LRB-

lpm

-RRB-

was

necessary

to

maintain

back-pressure

and

flow

consistency

to

avoid

flashing

The

tuning

strategy

for

the

system

began

with

tuning

each

flow

and

pressure

loop

individually

and

then

operating

them

together

slowing

down

the

response

of

the

pressure

loops

as

necessary

to

eliminate

interactions

Loops

were

tuned

using

the

Ziegler

Nichols

method

-LSB-

-RSB-

however

the

loop

response

with

these

settings

excessively

oscillated

even

before

approaching

set

point

For

flow

and

liquid

pressure

loops

large

proportional

bands

-LRB-

i.e.

small

gain

-RRB-

and

fast

reset

action

-LRB-

i.e.

small

reset/integral

time

-RRB-

are

recommended

-LSB-

-RSB-

Proportional

and

integral

constants

only

are

recommended

for

most

liquid

flow

control

with

only

integral

constants

-LRB-

i.e.

floating

control

-RRB-

recommended

for

noisy

loops

-LSB-

-RSB-

Consequently

gain

and

reset

time

were

reduced

so

that

integral

control

was

the

dominant

action

which

reduced

oscillations

In

addition

booster

pump

suction

pressure

control

was

deliberately

detuned

to

have

a

slow

response

so

as

not

to

interact

with

flow

and

system

back-pressure

controllers

-LRB-

which

themselves

did

not

interact

with

each

other

-RRB-

Thus

both

booster

pump

flow

and

suction

pressure

controllers

could

be

used

together

with

no

instability

Table

shows

the

tuning

constants

selected

Table

tuning

constants

for

sterilization

of

test

-LRB-

min/repeat

-RRB-

-LRB-

min

-RRB-

Flow

control

valve

after

centrifugal

feed

pump

-LRB-

lpm

-RRB-

Pressure

control

valve

on

suction

of

booster

pump

Flow

control

valve

after

centrifugal

booster

pump

-LRB-

lpm

-RRB-

Hot

water

temperature

control

of

retention

loop

inlet

sterilization

temperature

of

°C

cleaning

temperature

of

°C

-LRB-

lpm

-RRB-

Primary

-LRB-

outer

-RRB-

Secondary

-LRB-

inner

-RRB-

Pressure

control

after

process

cooler

Moyno

or

centrifugal

inlet

feed

pump

Pressure

control

after

flash

cooler

Moyno

or

centrifugal

inlet

feed

pump

Temperature

control

of

process

cooler

cooling

to

°C

Temperature

control

of

flash

cooler-during

sterilization

cooling

to

°C

and

with

°C

inlet

feed

-LRB-

lpm

-RRB-

Temperature

control

of

flash

cooler-during

cleaning

solution

cooling

to

°C

and

with

°C

inlet

feed

-LRB-

-RRB-

Zero

values

were

used

for

faster

-LRB-

relative

to

temperature

loop

-RRB-

pressure

and

flow

control

loops

-LRB-

-RRB-

Slightly

different

tuning

constants

required

for

-LRB-

a

-RRB-

Moyno

and

centrifugal

feed

pumps

and

-LRB-

b

-RRB-

and

lpm

flowrates

to

remain

within

desired

back-pressure

variation

Tuning

constants

for

lpm

worked

up

to

lpm

-LRB-

-RRB-

At

lpm

slower

tuning

required

for

flash

cooler

when

cooling

to

°C

for

cleaning

-LRB-

inlet

feed

of

°C

-RRB-

than

cooling

to

°C

-LRB-

inlet

feed

of

°C

-RRB-

during

sterilization

-LRB-

-RRB-

Higher

value

for

primary

hot

water

loop

relative

to

its

value

minimized

variations

of

slower

secondary

temperature

control

loop

Switching

valve

station

The

switching

valve

station

was

comprised

of

several

diverter

valves

to

direct

the

flow

of

steam

water

or

medium

to

distribution

recycle

condensate

trap

or

system

sewer

as

desired

-LRB-

Fig.

-RRB-

The

system

switched

according

to

the

following

valving

arrangements

-LRB-

Fig.

b

-RRB-

-LRB-

-RRB-

system

recycle

to

circulation

tank

-LRB-

after

passing

through

flash

cooler

used

for

clean-in-place

-LRB-

CIP

-RRB-

and

water

sterilization

-RRB-

-LRB-

-RRB-

transfer

-LRB-

feed

-RRB-

of

sterilized

medium

to

fermenters/waste

tank

-LRB-

-RRB-

system

flow

to

sewer

after

process

cooler

-LRB-

-RRB-

system

flow

to

sewer

after

flash

cooler

-LRB-

-RRB-

steam

sterilization

through

process

cooler

to

its

condensate

trap

and

-LRB-

-RRB-

steam

sterilization

through

flash

cooler

to

its

condensate

trap

Simultaneously

with

pathway

switch

a

steam

barrier

was

applied

to

the

pathway

not

being

used

to

maintain

sterility

Isometric

design

of

the

switching

station

was

challenging

since

several

automatic

valves

with

actuators

were

located

in

close

proximity

to

reduce

dead

legs

Actuator

size

was

minimized

by

sizing

appropriately

with

little

excess

buffer

for

the

facility

instrument

air

pressure

Limit

switches

were

avoided

to

save

additional

space

as

well

as

to

streamline

installation

and

maintenance

costs

Instrumentation

Sterilizer

instrumentation

is

described

in

Table

In

general

instrumentation

mounting

was

important

both

for

sanitary

operation

and

for

accurate

instrument

measurements

Remotely

mounted

transmitters

were

used

where

needed

to

extend

temperature

range

suitability

of

instrument

sensors

-LRB-

e.g.

flowmeters

-RRB-

and

where

helpful

for

space

and

access

reasons

Wherever

possible

locally

indicating

transmitters

were

selected

which

permitted

operation

by

a

single

person

since

the

human/machine

interface

-LRB-

HMI

-RRB-

was

upstairs

in

the

facility

control

room

Transmitters

were

mounted

either

in

a

panel

-LRB-

drawback

of

additional

wiring

but

able

to

be

factory

tested

-RRB-

or

on

the

skid

-LRB-

drawback

of

crowding

skid

access

but

avoids

cost

of

a

separate

panel

-RRB-

Table

°C

-LRB-

hot

water

loop

-RRB-

°C

-LRB-

all

others

-RRB-

FlowMicromotion

lpmPressureRosemount

-LRB-

feed

and

booster

pumps

-RRB-

-LRB-

post-cooler

HEXs

-RRB-

ConductivityRosemount

MS/cm

triclamp

connectionRosemount

μS/cm

triclamp

connectionTemperature

controlFisher-Rosemount

limit

of

°C

for

hot

water

loopFlow

controlFisher-Rosemount

control

valves

usable

with

either

transmitterPressure

controlFisher-Rosemount

adjustment

to

prevent

full

closing

of

system

back-pressure

valveSteam

controlFisher-Rosemount

psig

unregulated

plant

steam

supplyI/P

transducerMarsh-Bellofram

psig

compactSolenoidAsco

series

multifunction

ISO

mono

stableSpring-return

piston

actuators

Accurate

measurement

of

temperature

was

critical

to

ensuring

that

adequate

medium

sterilization

was

achieved

and

permitting

reliable

Fo

and

Ro

calculations

Typical

accuracies

reported

in

HTST

pasteurization

equipment

are

°C

at

°C

between

indicating

and

recording

temperature

devices

and

°C

at

°C

between

test

and

indicating

devices

-LSB-

-RSB-

This

compared

favorably

with

the

loop

accuracy

of

°C

for

this

system

estimated

based

on

stated

vendor

accuracy

for

matched

sensors

-LSB-

-RSB-

Pressure

loop

accuracy

was

The

system

back-pressure

valve

was

capable

of

controlling

pressure

for

flowrates

ranging

from

to

lpm

using

a

computer-controlled

maximum

output

of

closure

to

prevent

unintentional

shut

off

when

operating

with

the

positive

displacement

Moyno

pump

In

contrast

a

closure

of

at

least

was

required

when

operating

with

the

centrifugal

pump

since

the

pump

output

pressure

was

lower

A

pressure

and

temperature

gauge

or

transmitter

was

installed

on

the

inlet

and

outlet

of

both

sides

of

all

HEXs

for

assuring

adequate

heat

transfer

performance

and

determining

when

HEXs

required

cleaning

These

instruments

also

were

important

to

evaluate

individual

unit

performance

for

systems

of

interrelated

HEXs

during

trouble-shooting

-LSB-

-RSB-

Accurate

measurement

of

volumetric

flow

was

critical

to

ensuring

that

medium

was

properly

sterilized

for

the

appropriate

residence

time

A

back-up

flowmeter

was

installed

for

confirmation

Coriolis

meters

-LRB-

Micromotion

Rosemount

Chanhassen

MN

USA

-RRB-

with

a

meter

accuracy

of

of

flowrate

-LRB-

loop

accuracy

of

of

flowrate

-RRB-

were

selected

rather

than

magnetic

meters

Since

flow

measurements

were

based

on

fluid

density

Coriolis

meter

readings

were

similar

for

both

deionized

and

process

-LRB-

city

-RRB-

water

-LRB-

lpm

at

lpm

-RRB-

and

within

expected

variations

Coriolis

meters

also

were

insensitive

to

media

composition

changes

specifically

the

switch

from

media

to

water

assuming

these

changes

negligibly

affected

fluid

density

and

were

not

affected

by

the

hydraulics

of

medium

to

water

switches

However

volumetric

flow

rate

readings

were

up

to

higher

after

the

recuperator

than

before

it

owing

to

density

decreases

with

temperature

for

specific

medium

types

-LSB-

Mass

flowrate

-LRB-

kg/min

-RRB-

readings

were

similar

-RSB-

Finally

since

air

bubble

entrainment

altered

density

readings

and

thus

Coriolis

flowmeter

readings

a

variable

speed

agitator

-LRB-

turndown

-RRB-

was

installed

on

the

larger

non-sterile

medium

feed

tanks

For

soluble

media

shutting

off

the

agitation

also

minimized

air

entrainment

Proper

Coriolis

flowmeter

installation

was

critical

to

performance

The

preferred

orientation

was

in

a

vertical

upward

flow

section

of

pipe

so

that

the

flag

filled

and

drained

completely

Alternatives

were

not

attractive

in

the

horizontal

position

pointing

downwards

the

flag

does

not

drain

in

the

horizontal

position

pointing

upwards

the

flag

incompletely

fills

due

to

air

entrapment

and

in

the

vertical

position

in

a

downward

flow

section

of

pipe

the

flag

incompletely

fills

owing

to

gravity

drainage

It

also

was

necessary

to

secure

the

surrounding

pipe

to

minimize

interfering

vibrations

Conductivity

sensors

were

used

on-line

to

measure

changes

in

the

composition

upon

switching

inlet

feed

stream

contents

and

between

inlet

and

outlet

streams

One

conductivity

meter

with

a

range

of

μs/cm

detected

DIW

with

typical

conductivities

of

μs/cm

during

cleaning

Two

other

conductivity

meters

each

with

a

range

of

Ms/cm

were

located

on

feed

-LRB-

after

the

inlet

feed

pump

-RRB-

and

outlet

-LRB-

after

the

process

cooling

HEX

-RRB-

of

the

sterilizer

system

-LRB-

Fig.

-RRB-

Similarly

to

the

flowmeters

they

were

mounted

in

the

vertical

flow

section

to

ensure

no

adverse

effects

on

readings

Conductivity

monitoring

at

the

cooling

water

exit

may

enable

instant

detection

of

a

cooling

HEX

breach

-LSB-

-RSB-

but

this

leak

might

have

to

be

fairly

substantial

since

cooling

water

and

media

conductivities

are

similar

in

magnitude

Control

system

Strategy

The

control

system

strategy

utilized

minimal

sequencing

with

manual

operation

preferred

both

to

reduce

installation

expense

and

maximize

flexibility

The

system

was

composed

of

about

I/O

-LRB-

input/output

-RRB-

with

about

analog

input/output

-LRB-

AI/AO

-RRB-

and

digital

input/output

-LRB-

DI/DO

-RRB-

The

controls

were

interfaced

to

an

existing

Honeywell

Total

Distributed

Control

hybrid

system

using

newly-installed

dual

-LRB-

redundant

-RRB-

Honeywell

High

performance

Process

Manager

controllers

Field-mounted

-LRB-

remote

-RRB-

I/O

was

installed

inside

a

Nema

enclosure

Calculated

values

by

the

control

system

Several

calculated

values

were

displayed

on

the

HMI

to

permit

alarming

and

trending

These

parameters

included

the

temperature

difference

-LRB-

inlet

minus

outlet

-RRB-

across

the

insulated

retention

loop

flowrate

difference

across

the

recuperator

-LRB-

upstream

minus

downstream

-RRB-

conductivity

difference

-LRB-

inlet

minus

outlet

-RRB-

and

pressure

difference

across

the

recuperator

-LRB-

outlet

of

hot

side

minus

inlet

of

cold

side

-RRB-

In

addition

the

totalized

volumetric

flowrate

was

calculated

based

on

flowmeter

readings

rather

than

using

the

flow

transmitter

totalizer

signal

since

implementation

of

the

former

was

more

straightforward

Values

of

Fo

and

Ro

were

obtained

based

on

on-line

calculation

of

system

residence

time

The

flowrate

measured

after

the

recuperator

HEX

was

used

in

the

calculation

Activation

energies

Ea

of

cal/mol

used

for

Ro

generally

were

lower

than

those

of

the

various

spore

types

of

cal/mol

used

for

Fo

-LSB-

-RSB-

An

Ea

of

cal/mol

was

used

for

Fo

-LSB-

-RSB-

and

an

Ea

of

cal/mol

was

used

for

Ro

-LSB-

-RSB-

An

adjustable

filtering

function

-LSB-

-RSB-

could

be

applied

to

final

calculated

Fo

and

Ro

process

variable

values

-LRB-

PV

-RRB-

to

smooth

fluctuations

caused

by

pulsations

in

flow

and

temperature

readings

This

function

-LRB-

Eq

-RRB-

had

only

one

user

adjustable

parameter

for

the

filter

value

-LRB-

FV

-RRB-

With

FV

set

to

-LRB-

i.e.

no

filtering

-RRB-

variations

of

Fo

and

Ro

were

less

than

In

addition

a

user

adjustable

input

permitted

entry

of

proper

retention

loop

volumes

Vs

to

ensure

accurate

residence

time

tR

calculations

Three

methods

were

used

to

evaluate

this

on-line

calculation

for

a

simulated

continuous

sterilization

run

-LRB-

Table

-RRB-

-LRB-

a

-RRB-

calculation

for

min

residence

time

intervals

along

the

loop

length

and

summation

of

values

over

the

entire

length

of

pipe

-LRB-

b

-RRB-

use

of

the

average

of

retention

loop

inlet

and

outlet

temperatures

in

the

calculation

and

-LRB-

c

-RRB-

averaging

of

two

separate

calculations

using

inlet

and

outlet

temperatures

Although

method

a

was

most

accurate

method

b

was

selected

since

the

error

was

sufficiently

small

and

implementation

was

more

straightforward

In

general

errors

were

smaller

for

Ro

than

Fo

This

approach

was

in

contrast

to

the

dairy

industry

where

a

worst

case

lethality

has

been

calculated

using

the

outlet

temperature

of

the

insulated

retention

loop

-LSB-

-RSB-

Table

of

calculation

methods

for

Fo

and

Ro

for

a

simulated

continuous

sterilization

run

with

a

°C

temperature

drop

across

the

insulated

retention

loop

and

tR

min

-LRB-

error

calculated

relative

to

method

a

-RRB-

MethodFo

-LRB-

min

-RRB-

Error

-LRB-

-RRB-

Ro

-LRB-

min

-RRB-

Error

-LRB-

-RRB-

aIntegrate

at

min

residence

time

BasisbUse

average

of

inlet

and

outlet

loop

cAverage

separate

calculations

using

inlet

and

outlet

loop

Tuning

constants

and

control

variation

For

all

control

loops

proportional/integral/derivative

-LRB-

PID

-RRB-

control

in

the

fast

mode

-LRB-

PID

calculation

updated

every

s

-RRB-

was

utilized

based

on

three

parameters

-LRB-

definitions

are

specific

to

the

Honeywell

control

system

-RRB-

the

proportional

gain

KP

unitless

-LRB-

reciprocal

of

the

proportional

band

-RRB-

the

integral

constant

min

per

repeat

and

the

derivative

constant

min

Control

tuning

constants

were

developed

for

water

-LRB-

Table

-RRB-

then

tested

and

found

to

be

acceptable

for

different

media

-LRB-

wt

cerelose

vol

glycerol

-RRB-

Slightly

different

values

were

optimal

for

flowrates

of

lpm

than

for

lpm

with

lower

flowrate

range

constants

performing

somewhat

better

than

higher

flowrate

range

constants

between

and

lpm

Variations

in

these

control

loops

characterized

under

various

operating

conditions

were

found

to

be

acceptable

Hot

water

loop

control

performance

did

not

change

significantly

with

media

type

since

system

disturbances

expected

for

media

were

likely

to

be

dampened

relative

to

water

System

performance

Water

and

media

testing

The

three

types

of

media

tested

were

water

-LSB-

both

deionized

-LRB-

DIW

-RRB-

and

process

-LRB-

city

-RRB-

-RSB-

wt

cerelose

and

vol

glycerol

Heating

of

non-sterile

feed

tanks

by

external

jacket

platecoils

and

recycling

of

cooled

effluent

back

to

the

system

inlet

permitted

system

testing

with

feeds

of

differing

temperatures

over

the

range

of

°C

Once-through

testing

was

used

only

for

cerelose

to

reduce

Maillard

reactions

which

were

feared

to

soil

sterilizer

internals

Water

and

glycerol

were

recycled

by

setting

the

flash

cooler

temperature

to

the

desired

inlet

temperature

permitting

testing

of

process

cooler

performance

at

or

above

inlet

feed

temperatures

The

manner

in

which

readings

were

taken

affected

assessment

of

their

variability

readings

were

observed

for

a

few

seconds

then

a

mental

average

was

taken

and

evaluated

to

determine

whether

the

bounce

was

within

reasonable

limits

Computer

system

historical

trends

which

recorded

data

every

min

also

were

used

to

assess

variability

Pressure

drops

were

calculated

for

each

HEX

for

various

media

considering

the

temperature

effect

on

the

inlet

feed

stream

density

The

vendor

's

proprietary

software

was

used

which

did

not

account

for

gaps

between

spiral

face

and

HEX

door

and

assumed

a

tighter-than-actual

stud

spacing

Thus

the

design

HEX

pressure

drop

was

likely

overestimated

Re-calculation

-LRB-

data

not

shown

-RRB-

using

published

equations

for

the

pressure

drop

across

the

spiral

HEX

-LSB-

-RSB-

which

also

did

not

account

for

the

gap

impact

resulted

in

estimates

somewhat

closer

to

measured

values

The

retention

loop

pressure

drop

was

calculated

using

a

retention

loop

equivalent

length

of

ft

-LRB-

including

elbows

and

pipe-to-tube

adapters

-RRB-

and

f

values

according

to

Table

Calculated

pressure

drops

were

compared

to

measured

values

-LRB-

data

not

shown

-RRB-

For

the

lpm

flowrate

most

measured

values

were

about

lower

than

calculated

values

with

the

exception

of

the

heater

's

cold

side

which

was

to

higher

For

the

lpm

flowrate

observed

values

were

substantially

higher

-LRB-

to

-RRB-

than

calculated

values

for

the

heater

's

cold

side

These

results

may

indicate

difficulty

in

predicting

pressure

drops

for

the

lower

aspect

ratio

heater

HEX

-LRB-

Table

-RRB-

particularly

at

its

higher

operating

temperatures

relative

to

the

other

HEXs

Measured

pressure

drops

for

various

test

media

were

reasonably

similar

System

temperatures

were

calculated

for

each

media

type

and

compared

with

observed

values

-LRB-

Tables

-RRB-

Design

HR

NTU

and

TE

were

calculated

assuming

no

temperature

drop

across

the

retention

loop

-LRB-

i.e.

retention

loop

inlet

temperature

equal

to

hot

side

recuperator

inlet

temperature

-RRB-

Negligible

heat

loss

for

the

retention

loop

HEXs

and

piping

also

was

assumed

design

values

would

be

higher

if

these

losses

were

included

Table

performance

using

water

at

lpm

-LRB-

L

retention

volume

unless

noted

otherwise

-RRB-

ParameterFeed

inlet

of

°C

Feed

inlet

of

°C

Feed

inlet

of

°C

DesignObserved

Moyno/centrifugalDesignDesignObserved

Moyno/centrifugalObserved

Moyno

LRecuperator

cold

side

inlet

feed

-LRB-

°C

-RRB-

cold

side

outlet/heater

hot

side

inlet

-LRB-

°C

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

hot

side

outlet/retention

loop

inlet

-LRB-

°C

-RRB-

Retention

loop

outlet/recuperator

hot

side

inlet

-LRB-

°C

-RRB-

Recuperator

hot

side

outlet/process

cooler

hot

side

inlet

-LRB-

°C

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

cooler

hot

side

outlet

-LRB-

°C

-RRB-

Process

cooler

cold

side

inlet

-LRB-

°C

-RRB-

N/AN/AProcess

cooler

cold

side

outlet

-LRB-

°C

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

ARecuperator

heat

recovery

-LRB-

HR

-RRB-

-LRB-

Eq

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Recuperator

NTUs

-LRB-

Eq

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Recuperator

thermal

efficiency

-LRB-

TE

-RRB-

-LRB-

Eq

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Water

not

tested

at

°C

but

design

is

included

for

comparison

-LRB-

-RRB-

Process

cooler

inlet

temperature

reading

taken

from

building

chilled

water

supply

temperature

-LRB-

-RRB-

Design

numbers

calculated

based

on

intermediate

temperatures

needed

to

reach

°C

at

the

retention

loop

inlet

assuming

that

most

of

the

load

was

undertaken

by

the

heating

HEX

based

on

a

maximum

heating

loop

temperature

of

°C

Thus

less

than

the

maximum

area

of

the

recuperator

was

utilized

in

some

cases

-LRB-

-RRB-

Design

numbers

in

bold

calculated

based

on

utilization

of

the

recuperator

surface

area

and

permitting

the

hot

water

loop

to

operate

at

values

less

than

°C

Table

performance

-LRB-

L

retention

loop

volume

-RRB-

using

wt

cerelose

at

-LRB-

°C

inlet

temperature

-RRB-

and

lpm

-LRB-

°C

inlet

temperature

-RRB-

ParameterFeed

inlet

of

°C

Feed

inlet

of

°C

DesignObserved

Moyno/centrifugalDesignObserved

lpmRecuperator

cold

side

inlet

feed

-LRB-

°C

-RRB-

Recuperator

cold

side

outlet/heater

hot

side

inlet

-LRB-

°C

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

hot

side

outlet/retention

loop

inlet

-LRB-

°C

-RRB-

Retention

loop

outlet/recuperator

hot

side

inlet

-LRB-

°C

-RRB-

Recuperator

hot

side

outlet/process

cooler

hot

side

inlet

-LRB-

°C

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

cooler

hot

side

outlet

-LRB-

°C

-RRB-

Process

cooler

cold

side

inlet

-LRB-

°C

-RRB-

-LRB-

est

-RRB-

Process

cooler

cold

side

outlet

-LRB-

°C

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

est

-RRB-

heat

recovery

-LRB-

HR

-RRB-

-LRB-

Eq

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Recuperator

NTUs

-LRB-

Eq

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Recuperator

thermal

efficiency

-LRB-

TE

-RRB-

-LRB-

Eq

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Est

estimation

by

using

data

for

lpm

case

as

a

basis

-LRB-

-RRB-

Cerelose

after

sterilization

was

dark

brown

at

°C

lighter

brown

at

°C

-LRB-

-RRB-

At

°C

wt

cerelose

forms

a

cloudy

dispersion

in

feed

tank

with

entrained

air

-LRB-

requiring

several

minutes

to

dissipate

after

agitation

is

stopped

-RRB-

compared

to

wt

cerelose

at

°C

where

solution

in

feed

tank

is

clear

-LRB-

-RRB-

Design

numbers

in

bold

-LRB-

see

note

of

Table

-RRB-

for

lpm

interpolated

from

and

lpm

casesTable

performance

-LRB-

L

retention

loop

volume

-RRB-

using

vol

glycerol

at

lpm

using

flowmeter

after

inlet

feed

pump

-LRB-

°C

inlet

temperature

-RRB-

and

lpm

-LRB-

°C

inlet

temperature

-RRB-

ParameterFeed

inlet

of

°C

Feed

inlet

of

°C

DesignObserved

MoynoDesignObserved

lpmRecuperator

cold

side

inlet

feed

-LRB-

°C

-RRB-

cold

side

outlet/heater

hot

side

inlet

-LRB-

°C

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

hot

side

outlet/retention

loop

inlet

-LRB-

°C

-RRB-

Retention

loop

outlet/recuperator

hot

side

inlet

-LRB-

°C

-RRB-

Recuperator

hot

side

outlet/process

cooler

hot

side

inlet

-LRB-

°C

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

cooler

hot

side

outlet

-LRB-

°C

-RRB-

-LRB-

est

-RRB-

Process

cooler

cold

side

inlet

-LRB-

°C

-RRB-

Process

cooler

cold

side

outlet

-LRB-

°C

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

est

-RRB-

heat

recovery

-LRB-

HR

-RRB-

-LRB-

Eq

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Recuperator

NTUs

-LRB-

Eq

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Recuperator

thermal

effectiveness

-LRB-

TE

-RRB-

-LRB-

Eq

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Glycerol

at

°C

inlet

feed

temperature

cooled

to

°C

outlet

temperature

-LRB-

-RRB-

Est

estimation

by

back

calculating

heat

transfer

coefficient

for

cooling

using

tower

water

performance

data

for

similar

test

media/conditions

Chilled

water

flowrate

varies

which

alters

heat

coefficient

which

changes

chilled

water

outlet

temperature

Chilled

water

flowrate

and

outlet

temperature

solved

iteratively

by

balancing

heat

transferred

-LRB-

U

A

ΔTln

-RRB-

with

heat

absorbed

-LRB-

QMCp

ΔT

-RRB-

-LRB-

-RRB-

Design

numbers

in

bold

-LRB-

see

note

of

Table

-RRB-

for

and

lpm

interpolated

from

and

lpm

cases

Observed

temperature

profiles

HRs

NTUs

and

TEs

generally

met

or

were

somewhat

lower

than

design

depending

upon

which

design

basis

was

utilized

The

primary

factor

causing

under-performance

was

believed

to

be

lack

of

allowance

for

the

gap

that

was

likely

present

even

with

pliable

full-face

gaskets

installed

owing

to

unavoidable

variations

in

flatness

of

the

HEX

spiral

and

door

faces

The

observed

hot

side

recuperator

inlet

temperature

from

the

non-adiabatic

retention

loop

was

lower

than

the

isothermal

design

assumption

and

thus

raised

measured

values

compared

with

design

HR

NTU

and

TE

Viscosity

decreases

with

higher

temperature

resulted

in

improved

performance

System

draining

hold

up

volume

The

system

's

hold

up

volume

was

established

by

running

process

water

into

a

completely

drained

and

air-blown

system

It

was

determined

when

water

reached

a

certain

section

by

opening

the

adjacent

downstream

drain

valve

Measured

hold

up

volumes

agreed

with

calculated

ones

within

reasonable

limits

but

may

have

been

affected

by

the

ability

to

fill

the

system

completely

at

the

lower

flowrates

used

to

obtain

these

measurements

Overall

the

impact

on

design

residence

times

of

these

differences

was

negligible

however

Inlet

feed

stream

and

outlet

distribution

stream

switching

Prior

to

testing

all

instrument

air

connections

to

the

switching

skid

were

checked

for

leaks

and

proper

venting

When

switching

to

the

distribution

manifold

-LRB-

sterilizer

feed

to

fermenters

-RRB-

from

either

the

sewer

or

recycle

flow

paths

transient

flow

and

pressure

spikes

and

their

effect

on

inlet

and

outlet

retention

loop

temperatures

were

observed

and

found

to

be

negligible

When

sterilizer

distribution

was

switched

from

the

receiving

waste

tank

to

the

desired

fermenter

vessels

pressure

spikes

also

had

a

negligible

effect

on

temperature

Minimal

disturbances

were

observed

for

actual

water-to-media

switch

over

when

the

system

feed

was

changed

from

water

to

wt

cerelose

and

back

again

In

all

of

these

instances

an

acceptable

temperature

spike

was

considered

to

be

less

than

the

variation

observed

during

normal

flow

operation

Since

these

spikes

were

negligible

it

was

not

necessary

to

flush

the

system

appreciably

after

a

switch

to

regain

steady

performance

In

addition

sewer

to

recycle

waste

to

sewer

and

fermenter

to

waste

transitions

were

not

potential

sterility

risks

since

these

typically

occurred

after

sterilized

medium

transfer

was

completed

Heat

losses

For

this

system

the

target

retention

loop

temperature

drops

-LRB-

Table

-RRB-

were

met

or

exceeded

for

the

test

media

at

residence

times

of

min

In

another

study

for

a

retention

loop

of

mm

-LRB-

-RRB-

diameter

the

temperature

drop

was

negligible

for

short

residence

times

of

s

-LRB-

hold

temperature

of

°C

and

room

temperature

of

°C

-RRB-

regardless

of

whether

the

retention

loop

was

insulated

-LRB-

°C

-RRB-

or

not

insulated

-LRB-

°C

-RRB-

-LSB-

-RSB-

For

longer

residence

periods

of

s

the

temperature

drop

was

°C

for

insulated

and

°C

for

non-insulated

cases

These

temperature

drops

are

expected

to

increase

with

higher

residence

times

and

higher

holding

temperatures

Extrapolating

from

these

data

assuming

operation

at

°C

a

change

of

°C

min

was

expected

translating

to

an

expected

drop

of

°C

for

a

residence

time

of

min

Since

the

actual

operating

temperature

was

substantially

higher

at

°C

the

observed

drop

of

°C

appears

consistent

with

these

earlier

studies

Infrared

pictures

-LRB-

Inframetrics

model

Thermocam

Flir

Boston

MA

USA

-RRB-

of

the

retention

loop

and

HEXs

were

taken

to

evaluate

retention

loop

insulation

effectiveness

-LRB-

particularly

the

removable

jumper

end

-RRB-

and

HEXs

heat

losses

due

to

lack

of

insulation

-LRB-

Radiant

heat

loss

due

to

thermal

radiation

was

considered

negligible

-RRB-

These

pictures

showed

that

the

retention

loop

was

adequately

insulated

Typical

HEX

surface

temperatures

were

consistent

with

the

temperature

profile

of

Table

Since

cold

fluids

enter

the

HEX

on

the

periphery

and

hot

fluids

enter

in

the

center

there

was

minimal

heat

loss

to

the

surroundings

-LSB-

-RSB-

In

addition

during

water

sterilization

temperature

drops

were

measured

for

the

recuperator

's

hot

media

side

-LRB-

with

the

inlet

cold

side

bypassed

-RRB-

and

the

process

side

of

the

process

cooler

-LRB-

without

chilled/cooling

water

flow

-RRB-

These

drops

were

°C

for

the

recuperator

-LRB-

aspect

ratio

of

-RRB-

and

about

°C

for

the

process

cooler

-LRB-

aspect

ratio

of

-RRB-

Lower

heat

losses

were

expected

for

thicker

lower

aspect

ratio

HEXs

and

HEXs

with

more

turns

-LSB-

-RSB-

In

addition

full-face

gaskets

minimized

heat

transfer

rates

to

the

HEX

cover

faces

which

reduced

heat

loss

System

sensitivity

Variations

in

inlet

retention

loop

temperature

-LRB-

°C

-RRB-

system

flowrate

-LRB-

Moyno

feed

pump

lpm

centrifugal

feed

pump

lpm

-RRB-

and

back-pressure

-LRB-

-RRB-

generally

were

negligible

across

the

operating

range

and

for

the

various

test

media

As

expected

flowrate

variations

were

somewhat

greater

for

the

centrifugal

than

for

the

positive

displacement

Moyno

feed

pump

The

relative

sensitivities

of

retention

loop

inlet

and

outlet

temperatures

to

changes

in

system

back-pressure

were

found

to

be

negligible

This

behavior

was

improved

from

the

prior

direct

steam

injection

design

since

steam/water

mixing

was

more

volatile

and

pressure-sensitive

Fo

and

Ro

For

a

hold

temperature

of

°C

Fo

magnitudes

were

acceptable

ranging

from

min

at

lpm

to

min

at

lpm

At

°C

Fo

was

substantially

lower

at

min

but

still

representing

a

reduction

for

spores

with

a

D

value

of

min

For

a

hold

temperature

of

°C

Ro

magnitudes

ranged

from

to

min

at

lpm

to

min

at

lpm

at

°C

Ro

was

substantially

lower

at

min

Acceptability

of

these

Ro

values

depends

on

the

degree

and

impact

of

media

degradation

for

the

specific

process

Reproducibility

was

high

at

for

the

same

inlet

feed

pump

Fo

and

Ro

differences

were

between

the

two

inlet

feed

pumps

using

the

same

medium

type

residence

time

and

sterilization

hold

temperature

these

differences

were

presumed

due

to

small

volumetric

flowrate

changes

thus

slightly

altering

residence

times

Different

flowmeters

controlled

flowrate

depending

on

the

inlet

pump

utilized

but

the

flowmeter

after

the

recuperator

was

used

for

the

calculation

regardless

Dimensionless

groups

and

axial

dispersion

For

the

retention

loop

NRe

and

NBs

were

calculated

for

each

type

of

media

at

various

system

flowrates

and

at

a

sterilization

temperature

of

°C

-LRB-

Table

-RRB-

starting

with

velocity

estimation

Process

bulk

velocities

for

the

retention

loop

as

well

as

HEXs

ranged

from

m/s

at

lpm

and

m/s

at

lpm

-LRB-

Table

-RRB-

The

velocity

at

lpm

was

of

the

value

for

lpm

Over

the

wt

cerelose

feed

temperature

range

of

°C

and

the

vol

glycerol

feed

temperature

range

of

°C

there

was

only

a

very

slight

change

in

calculated

velocity

-LRB-

data

not

shown

-RRB-

Table

calculated

parameters

for

the

retention

loop

for

an

inlet

feed

temperature

of

°C

sterilization

hold

temperature

of

°C

and

process

cooler

set

point

of

°C

-LRB-

L/D

of

for

L

retention

loop

volume

-RRB-

ParameterWater

-LRB-

lpm

-RRB-

wt

cerelose

-LRB-

lpm

-RRB-

vol

glycerol

-LRB-

lpm

-RRB-

V

-LRB-

m/s

-RRB-

f

-LRB-

Eq

-RRB-

Dz/VD

-LSB-

-RSB-

Eq

Dz

-LRB-

-RRB-

NBs

-LRB-

VL/Dz

-RRB-

correlation

-LSB-

-RSB-

-LRB-

NRe

-RRB-

-LRB-

NRe

-RRB-

Dz

-LRB-

-RRB-

-LRB-

NRe

-RRB-

-LRB-

NRe

-RRB-

NBs

-LRB-

VL/Dz

-RRB-

-LRB-

NRe

-RRB-

-LRB-

NRe

-RRB-

-LRB-

-RRB-

Surface

roughness

assumed

to

be

equivalent

to

commercial

steel

-LRB-

ε

m

D

m

ε/D

-RRB-

-LSB-

-RSB-

-LRB-

-RRB-

Inlet

temperature

variation

from

to

°C

only

slightly

affects

NRe

-LRB-

-RRB-

based

on

density

change

of

volumetric

inlet

flow

rate

-LRB-

-RRB-

NBs

for

L

retention

loop

volume

is

about

of

that

for

L

retention

loop

volumeTable

bulk

velocities

of

HEXs

for

various

test

media

-LRB-

based

on

lpm

process

flowrate

sterilization

temperature

of

°C

process

cooler

set

point

of

°C

-RRB-

HEXProcess

side

velocity

-LRB-

m/s

-RRB-

Utility

side

velocity

-LRB-

m/s

-RRB-

Water

-LRB-

°C

inlet

feed

-RRB-

wt

cerelose

-LRB-

°C

inlet

feed

-RRB-

vol

glycerol

-LRB-

°C

inlet

feed

-RRB-

Interconnecting

N/ARecuperator

-LRB-

both

sides

-RRB-

Retention

N/AProcess

and

flash

Calculated

system

velocities

were

compared

to

expected

settling

velocity

for

a

solids-containing

media

such

as

cottonseed

flour

-LRB-

Pharmamedia

Traders

Protein

Memphis

TN

USA

-RRB-

According

to

the

manufacturer

of

the

particles

are

μ

-LRB-

i.e.

pass

through

a

mesh

screen

-RRB-

and

particle

density

ρp

is

The

particle

settling

velocity

at

°C

based

on

a

specific

gravity

of

for

a

g/L

solution

at

°C

-LRB-

measured

using

a

Fisherbrand

Category

No.

hydrometer

-RRB-

was

estimated

at

m/s

for

μ

particles

m/s

for

μ

particles

and

for

μ

particles

These

values

were

to

lower

-LRB-

depending

on

the

particle

size

assumed

-RRB-

than

the

lowest

system

velocities

Settling

velocities

were

expected

to

be

even

lower

as

the

temperature

decreased

owing

to

the

higher

specific

gravity

of

water

NRe

ranged

from

regardless

of

media

type

-LRB-

Table

-RRB-

Equation

was

used

to

obtain

f

values

ranging

from

to

regardless

of

media

type

or

flowrate

resulting

in

Dz

values

-LRB-

Eq

-RRB-

ranging

from

to

over

the

flowrate

range

from

to

lpm

NBs

values

ranged

from

to

and

were

relatively

insensitive

to

either

medium

type

or

flowrate

-LRB-

Table

-RRB-

Using

the

experimental

correlation

and

applying

it

to

water

-LSB-

-RSB-

NBs

values

were

somewhat

higher

than

the

calculated

values

-LRB-

Table

-RRB-

but

reasonable

considering

the

data

scatter

of

the

correlation

itself

Thus

NBs

for

expected

operational

ranges

Dips

for

disturbances

were

shallower

for

the

retention

loop

outlet

than

for

the

inlet

and

were

observed

about

tR

minutes

later

For

example

at

lpm

an

inlet

temperature

dip

to

°C

-LRB-

from

°C

-RRB-

resulted

in

an

outlet

temperature

dip

to

only

°C

Based

on

the

°C

steady-state

temperature

loss

observed

an

outlet

temperature

dip

to

°C

was

expected

but

not

realized

most

likely

due

to

axial

dispersion

Direct

qualitative

examination

of

axial

dispersion

was

accomplished

using

step

change

and

spike

tests

for

flowrates

of

and

lpm

For

the

step

change

test

water

flowed

through

the

sterilizer

then

the

step

change

was

performed

quickly

by

switching

from

one

feed

tank

at

ambient

temperature

to

a

second

tank

at

a

higher

temperature

-LRB-

°C

-RRB-

The

system

was

not

heated

and

was

operated

without

backpressure

For

the

spike

-LRB-

delta

or

pulse

-RRB-

change

a

temperature

spike

in

the

hot

water

loop

was

created

by

quickly

opening

the

steam

valve

fully

and

then

returning

it

to

its

original

output

setting

taking

care

to

maintain

the

peak

temperature

below

°C

For

both

types

of

tests

the

non-sterile

side

of

the

recuperator

was

by-passed

to

avoid

heat

transfer

as

well

as

reducing

the

piping

length/volume

-LRB-

relative

to

that

of

the

retention

loop

-RRB-

between

the

switching

point

and

the

retention

loop

entrance

-LRB-

about

ft

excluding

spiral

loops

vs.

ft

L

vs.

L

-RRB-

It

was

difficult

operationally

to

perform

step

and

spike

changes

with

sufficient

rapidity

owing

to

this

hold

up

The

dispersion

results

are

shown

in

Fig.

and

b.

Clearly

the

degree

of

dispersion

increased

at

the

lower

flowrate

of

lpm

-LRB-

versus

lpm

-RRB-

for

both

types

of

tests

However

the

absolute

value

of

the

dispersion

coefficient

suggested

by

these

data

appears

artificially

higher

than

that

predicted

from

the

calculations

Fig.

dispersion

a

pulse

b

step

change

Steam-in-place

testing

The

use

of

biological

indicators

-LRB-

BIs

-RRB-

and

thermocouples

-LRB-

TCs

-RRB-

was

avoided

in

steam-in-place

-LRB-

SIP

-RRB-

testing

since

-LRB-

-RRB-

fittings

had

to

withstand

higher

pressures

up

to

and

-LRB-

-RRB-

the

system

was

physically

large

precluding

use

of

TCs

with

attached

wires

-LSB-

although

Valprobe

-LRB-

GE

Kaye

Instruments

Inc.

North

Billericia

MA

USA

-RRB-

wireless

TCs

were

one

alternative

considered

-RSB-

TCs

commonly

have

been

used

in

pasteurization

applications

with

a

lower

hold

temperature

of

°C

-LSB-

-RSB-

and

correspondingly

lower

pressure

BIs

-LRB-

in

the

form

of

feed

inoculated

with

indicator

organisms

-RRB-

were

not

considered

desirable

for

contact

with

production

equipment

for

pasteurization

-LSB-

-RSB-

although

studies

are

underway

to

determine

if

non-indicator

organisms

can

be

used

-LSB-

-RSB-

Simulations

have

been

conducted

-LRB-

-RRB-

using

laboratory

or

pilot

scale

test

apparatuses

with

inoculated

spore

solutions

-LRB-

-RRB-

by

tracking

an

indicator

enzyme

-LSB-

-RSB-

and/or

-LRB-

-RRB-

utilizing

rigorous

temperature

distribution

monitoring

on

laboratory

and

production

equipment

obtaining

spore

inactivation

kinetic

data

in

parallel

then

developing

models

to

estimate

lethality

-LSB-

-RSB-

Installation

of

several

temperature

and

pressure

indicators

for

in

process

monitoring

along

with

a

functional

sterility

test

was

the

preferred

approach

to

demonstrate

proper

operation

Operational

testing

was

performed

to

test

both

the

steam

sterilization-to-water

transition

and

water

sterilization

modes

Regardless

of

the

sterilization

method

used

prior

steam

sterilization

of

the

empty

system

and

subsequent

switching

back

pressure

control

from

the

flash

to

process

cooler

was

required

Each

method

had

key

points

requiring

extra

care

the

initial

water

introduction

for

the

steam

sterilization-to-water

transition

and

placing

the

empty

non-sterile

side

of

the

recuperator

on-line

for

the

water

sterilization

Thus

the

time

and

attention

required

to

execute

either

method

was

reasonably

equivalent

Using

the

steam

sterilization-to-water

transition

and

a

min

residence

time

three

sterility

tests

employing

soluble

medium

were

successfully

completed

at

°C

and

one

at

°C

to

test

the

Fo

range

of

min

One

sterility

test

was

successfully

completed

using

the

water

sterilization

method

Changes

between

non-sterilized

and

sterilized

sterility

medium

were

minimal

for

total

dissolved

solids

-LRB-

-RRB-

and

conductivity

-LRB-

decrease

-RRB-

confirming

minimal

medium

dilution

since

all

heating

was

done

indirectly

Glucose

concentration

-LRB-

measured

enzymatically

by

a

YSI

analyzer

Yellow

Springs

OH

USA

-RRB-

decreased

by

likely

reflecting

glucose

complexing

with

nitrogen

during

sterilization

and

not

medium

dilution

Further

tests

for

different

media

-LRB-

vol

glycerol

wt

cerelose

wt

Pharmamedia

-RRB-

are

to

be

done

as

process

development

requirements

dictate

Clean-in-place

-LRB-

CIP

-RRB-

testing

Cleaning

of

HEXs

to

remove

fouling

and

solid

accumulations

was

required

both

to

maintain

heat

transfer

performance

and

avoid

system

sterilization

problems

After

medium

was

run

through

the

sterilizer

the

system

was

flushed

with

water

while

at

sterilization

temperature

for

at

least

one

system

volume

then

flushing

was

continued

as

the

system

cooled

An

alkaline

cleaning

agent

-LRB-

typically

vol

low

heat

Oakite

Products

Bardonia

NY

USA

-RRB-

was

added

to

dissolve

medium

components

as

well

as

any

denatured

proteins

Besides

alkaline

cleaning

agents

acid

cleaning

agents

-LRB-

typically

wt

sulfamic

acid

-RRB-

were

used

to

dissolve

mineral

deposits

Also

a

high

pressure

water

stream

-LRB-

psi

pressure

-RRB-

can

be

used

to

clean

the

spiral

HEX

channels

-LSB-

-RSB-

although

this

required

opening

HEXs

doors

which

was

costly

on

a

routine

basis

The

system

was

heated

to

°C

rather

than

sterilization

temperatures

of

°C

which

past

experience

indicated

to

be

sufficient

for

cleaning

An

additional

set

of

tuning

constants

was

implemented

for

these

lower

cleaning

temperatures

-LRB-

Table

-RRB-

but

overall

control

was

not

required

to

be

as

tight

as

during

sterilization

Contact

of

the

cleaning

solution

with

all

internal

wetted

sterilizer

parts

at

a

minimum

required

velocity

of

m/s

-LRB-

m/s

recommended

-RRB-

-LSB-

-RSB-

was

desirable

Although

these

high

velocities

were

not

achievable

in

the

process

side

-LRB-

Table

-RRB-

system

cleanability

was

acceptable

There

were

significant

concerns

about

cleaning

HEXs

with

full-face

gaskets

installed

due

to

the

potential

for

accumulated

residue

where

the

spirals

contacted

the

door

and

underneath

the

gasket

at

the

center

nozzles

since

the

gasket

hole

was

braced

only

by

the

spiral

face

System

cleanliness

was

evaluated

by

-LRB-

-RRB-

examining

inlet

and

outlet

conductivity

differences

and

comparing

values

to

those

for

DIW

-LRB-

-RRB-

analyzing

rinse

water

samples

for

total

solids

filtered

solids

color

and

ultraviolet

absorbance

and

-LRB-

-RRB-

visual

inspection

and

swabbing

internal

surfaces

for

total

organic

carbon

-LRB-

TOC

-RRB-

including

the

HEXs

There

were

no

appreciable

differences

between

source

and

rinse

water

in

these

measurements

Residue

accumulation

was

negligible

on

the

process

sides

of

all

spiral

HEXs

and

swab-testing

results

were

less

than

ppm

TOC

for

each

location

examined

Cleaning

approaches

utilized

in

the

dairy

industry

for

continuous

pasteurization

applications

are

consistent

with

the

above

approach

After

processing

in

certain

milk

pasteurization

applications

systems

are

rinsed

with

cold

water

flushed

with

w/v

caustic

detergent

at

°C

for

min

cooled

drained

then

flushed

with

water

a

second

time

-LSB-

-RSB-

For

other

dairy

applications

the

nature

of

the

soil

was

primarily

protein

butter-fat

and

minerals

-LSB-

-RSB-

In

this

latter

case

an

acid

detergent

first

dissolved

minerals

and

loosened

burned

on

accumulation

which

increased

soil

solubility

in

subsequent

caustic

detergent

solution

Instead

of

draining

and

rinsing

the

system

between

detergent

switches

caustic

has

been

added

directly

to

the

acid

solution

to

minimize

energy

costs

associated

with

a

second

heating

of

the

cleaning

solution

-LSB-

-RSB-

However

this

short

cut

can

result

in

soil

particles

already

dissolved

in

acid

or

caustic

solution

potentially

re-depositing

on

system

surfaces

as

the

pH

changes

Conclusion

Improvements

implemented

for

a

next

generation

pilot-scale

continuous

sterilization

system

span

the

design

fabrication

and

testing

project

phases

and

have

been

described

Advantages

and

disadvantages

of

various

system

features

were

evaluated

based

on

literature

analysis

from

fermentation

as

well

as

other

related

applications

Successful

realization

of

these

requirements

depended

on

the

adoption

of

an

effective

project

strategy

The

selected

system

vendor

had

experience

primarily

with

the

food

industry

since

there

were

few

new

media

sterilizers

for

manufacturing

being

constructed

and

even

fewer

for

pilot

plant

process

development

use

Thus

it

was

critical

to

devote

sufficient

time

to

comprehensively

determining

system

requirements

Development

of

a

detailed

sequence

of

operation

as

the

piping

and

instrument

diagram

-LRB-

P&ID

-RRB-

itself

was

developed

ensured

alignment

of

performance

expectations

In

addition

selection

of

a

system

-LRB-

as

well

as

HEX

-RRB-

vendor

who

was

located

nearby

facilitated

interim

progress

examinations

prior

to

delivery

The

worst

case

design

scenarios

were

determined

carefully

ensuring

that

they

did

not

create

unnecessary

additional

costs

Agreement

on

the

design

assumptions

and

performance

requirements

was

critical

particularly

for

calculated

quantities

Specifically

the

entire

system

operation

needed

to

be

evaluated

when

developing

the

HEX

performance

requirements

Interim

temperatures

and

pressures

were

estimated

based

on

the

system

's

flow

connections

and

not

simply

considering

each

HEX

separately

Since

the

temperature

rise

in

each

HEX

stream

depended

on

actual

flowrate

design

calculations

were

done

using

expected

flowrates

and

not

solely

the

maximum

flowrates

that

the

HEX

can

support

Finally

a

check

of

calculations

for

the

various

design

cases

ensured

they

were

internally

consistent

Performance

testing

was

devised

to

quantify

actual

operation

versus

design

expectations

Intermediate

pressure

and

temperature

measurements

within

the

system

were

compared

to

design

calculations

to

identify

performance

issues

Communication

of

acceptable

variability

to

the

control

and

instrument

system

designer

upfront

ensured

proper

test

criteria

were

met

and

steady

state

variations

were

acceptable

Tests

were

performed

and

documented

for

all

operational

phases

These

system

tests

were

considered

critical

to

effectively

characterizing

the

system

's

capabilities

prior

to

placing

the

equipment

in

service

high temperature short time
spiral heat exchanger
start-up