aseptic processing operation

7/24/2019 Aseptic Processing Operation

1/44

Seminar on

Aseptic Processing operation


2/44

Schedule (contents)

Introduction to aseptic processing,

Aseptic Processing vs. Terminal Sterilization

contamination:

Sources and control,

Microbial environmental monitoring

Microbiological testing o air and !ater

"haracterization o aseptic process,

Media and incubation conditions.

"onclusion

#eerences


3/44

Aseptic Processing

Aseptic Processing is the processing o

drug components ( drug product,

containers, e$cipients, etc.) in a manner

that ma%es impossibleo microbiological

contamination o the inal sealed product.


4/44

Progression o S&mptoms

'ever

ecreased lood Pressure

#apid reathing and *eart #ate

S%in +esions

Spontaneous lood "lotting

rgan 'ailure

eath

Sepsisis a serious medical condition characterized b& a

!hole-bod& inflammatorystate caused b& infection.
http://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/Infectionhttp://en.wikipedia.org/wiki/Infectionhttp://en.wikipedia.org/wiki/Inflammation


5/44

"auses o sepsis

Sterile drug manuacturers should have a %een

a!areness o the public health implications odistributing a non-sterile product. Poor cMP

conditionsat a manuacturing acilit& can

ultimatel& pose a lie-threatening health ris% to a

patient.


6/44

Asepsisis the practice to reduce or eliminate

contaminants (such asbacteria, viruses, ungi, and

parasites) rom entering the ield to prevent inection.

Ideall&, a ield is /sterile/ 0 ree o contaminants 0 a

situation that is diicult to attain. *o!ever, the goal iselimination o inection.
http://en.wikipedia.org/wiki/Bacteriahttp://en.wikipedia.org/wiki/Virushttp://en.wikipedia.org/wiki/Fungihttp://en.wikipedia.org/wiki/Parasiteshttp://en.wikipedia.org/wiki/Infectionhttp://en.wikipedia.org/wiki/Infectionhttp://en.wikipedia.org/wiki/Parasiteshttp://en.wikipedia.org/wiki/Fungihttp://en.wikipedia.org/wiki/Virushttp://en.wikipedia.org/wiki/Bacteria


7/44

Producing drug products b&

Terminal sterilization

Product containers are illed and

sealed under high-1ualit&

environmental conditions designed tominimize contamination, but not to

guarantee sterilit&.

Product in its inal container is

sub2ect to a sterilization process such

as heat or irradiation.

Aseptic processing

rug product, container, and

closure are sub2ect to sterilization

separatel&, and then broughttogether.

ecause there is no process to

sterilize the product in its inal

container, it is critical that

containers be illed and sealed in an

e$tremel& high 31ualit&environment.


8/44

Terminal Sterilization

DrugProduct

Container/ Closure

Excipiants

SterilizationProcess Sterile Drug Product !


9/44

Aseptic ProcessingDrug

Product

Sterilization

Process

Container

Closure

Excipient

Sterilization

Process

Sterilization

Process

Sterilization

Process

Sterile

Closure

Sterile

Excipient

Aseptic

Processin

g

Sterile

DrugProduct

SterileContaine

r

Sterile

Final

Product

Can use multiple sterilization processes each optimized for the individual compon


10/44

acteria, virus, ungi and other viable microbes cause a

serious contamination.

acterial spores and endoto$ins

4on viable Particles li%e dust, ibers, or other material are

suspended in the air and ma& contaminate product.

"ontaminating agents


11/44

*umans and bacteria

ver 566 dierent species o bacteria are ound

associated !ith humans.

acteria are ound in the intestines, e&es, nares, mouth,

hair and s%in.

r& s%in can have 76668s o microbes 9 mm5

Staphylococcus epidermidis

Scanning ;M. "".


12/44

Sources of Contamination:

Personnel born contaminants

Poor or improper Sanitization:Procedures deicient, or poorl&e$ecuted

Air born contaminants. Inadequate HEPA seal(over ariable velocities bet!een

ilters. Inade1uate laminar lo! resulted. +o! or undetectablevelocit& at !or% surace.

!echanical failure o illing tan%? main pump ailure? coolings&stem lea%s at 2oints.


13/44

"ontrol

"ststep # eliminating the source of

contamination$ndStep % &educe the &is' of

contamination through:Sterile barriers

Surace monitoringAseptic techni1ue


14/44

o!ning (sterile barrier)

I people are a ma2or source

o contamination !e avoidcontaminating the product

!hile !e process it.


15/44

Surace Monitoring

Touch or Contact plates

- RDAC Plates

(#eplicate rganismetection

and "ounting)

Sa"s


16/44

Aseptic Techni1ue (s%ill)

Contact sterile materials only (ith sterile instruments:

perators should not contact sterile products, containers,

closures, or critical suraces !ith an& part o their go!n or

gloves

@eep the entire bod& out o the path o unidirectional airlo!

Approach a necessar& manipulation in a manner that does not

compromise sterilit& o the product


17/44

#hat$s rong ith this picture%


18/44

CORRECT


19/44

&orizontal air'lo (ertical air'lo

.ors.od.nih.go)/ds/pu"s/"sc/graphics/'ig*.gi'

)nidirectional airflo(

The operator should

never come between the

air source and the

product.

pressure dierential b9ncritical area rom e$ternal environment

(7.B-B6 Pa)


20/44

*isinfectants

IS+P&+P,- A-C+H+- ./012 Po!erul disinectant

;ectivel& %ills bacteria and ungi

Mode o action: denatures proteins, dissolves lipidsand can lead to cell membrane disintegration.

ut does not inactivate spores

e.g., phenols, Alcohols, Aldeh&des etc.,


21/44

Sporicidal agents

lutaraldeh&de

'ormaldeh&de

sodium h&pochlorite

Iodine and iodophors

Pero$&gens

;th&lene o$ide

P- Propiolactone


22/44

Isolators

Ad3antage:

4o direct contact

bet!een operator C

product.


23/44

Microbial identiication should

e$tend to the species level.

#outine traditional techni1ues

phenot&pic and

biochemical. enot&pic techni1ues are

suggested or ailure

investigations.

Microbial ;nvironmental Monitoring:

Identiication


24/44

Phenotypic technique

4ram Stain

Identi&ing Microbes


25/44

Staphylococcus xylosus

&eduction of

5etrazolium Violet

iochemical Assa&s


26/44

enot&pic Methods

Dse 4A se1uence (oten ribosomal #4A genes

r4A) to identi& organism

'aster, and more accurate then traditional

biochemical and phenot&pic techni1ues


27/44

QC Micro: +denti',ing icro"es

enot,pe ased Assa,0PCR0 Pol,1erase Chain Reaction


28/44

;$tremel& heat stable 3 recommended conditions or

inactivation are 7E66

" or F hours.

Endotoxin: a p,rogenic 2'e)er inducing3 su"stance 2e.g. lipopol,saccharide3

present in the "acterial cell all. Endotoxin reactions range 'ro1 'e)er to death.

;ndoto$in Testing

+A+ Assa&(+imulus amoeboc&te l&sate)

E6*+5+7I6 -I!I5 +& WFIIS08$9 E)ml


29/44

Microbiological testing o !ater Dniversal solvent ,Dsed as >ehicle and used to rince and cleaning o

apparatus

Gater should also be tested or presence o coliorms and9or

pseudomonads i appropriate (ma& cause bioilm)

Gater should be tested using #5A agar (lo! nutrient or the recover&o !ater borne organisms) incubated or at least B da&s at F6-FBH"

Sampling procedures should ollo! those used in production


30/44

Microbiological testing o air

Co1pressed Air/4itrogen/C5 Air sampling should be done and tested or the presence

o non-viables and viables b& e$posure to the environment.

Pressure control oriices should be used to provide astead& stream o air.

'all out plate

Slit sampler

(slit-to-agar sa1pler3

Slit Sampler

.6e( ;runs(ic' Scientifics !odel S5A%$


31/44

"haracterization o aseptic process

The our pillars o a robust aseptic process

Personnel training C monitoring

;nvironmental monitoring 'acilities design

Media ills


32/44

Personnel Training C Monitoring

Avoiding contamination means %no!ing the potential sources

o contamination Personnel

;1uipment

Air9li1uids rug product

"ontainers9closures

utside environment

An&thing rought in contact !ith, or in the vicinit& o, the product

is a potential source o contamination


33/44

;nvironmental Monitoring

The goal o the environmental monitoring program is to

provide meaningul inormation on the 1ualit& o the

aseptic processing environment during production as

!ell as environmental trends.


34/44

6.

5.

*.7.

8.

9.:.

;.


35/44

'acilities: eneral "lean room esign

*;PA9D+PA ilters on ceiling

;$haust vents on loor

Airloc%s and interloc%ing doors to control air balance

Seamless and rounded loor to !all 2unctions

#eadil& accessible corners

'loors, !alls, and ceilings constructed o smooth hardsuraces that can be easil& cleaned

+imited e1uipment, i$tures and personnel

+a&out o e1uipment to optimize comort and movemento operators


36/44

'acilities: "lean room "lassiication


37/44

Class 6=>=== clean roo1

http0//.a1ericancleanroo1s.co1/a1/photogaller,?=;.ht1l

Class 6== clean roo1

acilities:"lean room "lassiication


38/44

'acilities: *;PA 'ilters

http0//people.deas.har)ard.edu/@ones/la"?arch/nano?'acilities/hepa.gi'

*igh ;icienc& Particulate Air ilters

Minimum particle collection eicienc&:


39/44

Media 'ill test

Dsed to validate the aseptic process

Dse microbial gro!th media instead o drug

product-an& contamination !ill result in

microbial gro!th.

It doesn8t provide a direct relation or sterilit&

but gives an ade1uate evaluation or operationalprocessing steps.


40/44

Media and Incubation conditions

So&bean casein digest medium (S")

'luid thiogl&collate medium ('TM) or anerobes

Inoculated !ith K 766 cu challenge At least 7L da&s incubation F6-FBH" or S", 56-5BH" or 'TM temperatures should be monitored product produces suspension, locculation or deposit in

media, suitable portions (5-B=) should be transerred toresh media, ater 7L da&s, and incubated or a uther da&s


41/44

Theoretical ;valuation

Gh&te mathematical model

contamination is due to air borne microbes

d e1uivalent particle diameter

A area o container opening (cm5)

t time (sec)

"ont rate (c) 6.66F5.d5.A.t


42/44

PostScript (conclusion)

The challenge in aseptic processing is ala,s

personnel0

B As a source o' 1icro"ial and

Particle conta1ination.BAs a "rae on the i1ple1entation o'

+1pro)ed technolog,.


43/44

#;';#;4";S

;nc&clopedia o pharm.technolog&

#DSS;++ A. .. acterial Spores and "hemical Sporicidal Agents.clinical microbiology reviews. F(5):


44/44

ThanQ

aseptic processing operation

Documents