2020 PDA Aseptic Processing of Biopharmaceuticals

2020 PDA Aseptic

Processing of

BiopharmaceuticalsFilling systems for Injectables

From stainless steel to a single use filling path

Tobias Goettler

Head of Product Management Pharma Liquid

Syntegon Technology GmbH

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Overall trend in pharmaceutical production

COPYRIGHT © PDA 2020

Trend to personalized

medicine

e.g. Oncology

High value drugs

e.g. Biologics

Therapeutic niche

applications

Orphan drugs

Smaller batch size

Smaller patient target

group per drug

Cost pressure

Capital investment,

flexibility, utilization

Patent expiry

Major drugs run out

off patent

Time pressure

Speed to market, time

to patient

Flexible filling

concepts

Small footprint

(cleanroom),

multiple containers

Required

technology

Pre-sterilized

containers

ready to use

Single use

processing

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Overview of filling systems


Mass flow

metering

Rolling

diaphragm

pump

Time pressurePeristaltic

pumpPiston pump

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Product parameters


- Not possible / not reasonable 0 possible with restrictions + possible solution ++ preferred solution

High

Viscosity

Similar

to Water

Protein /

BiotechSuspension Warm /

Cold

Crystalizing Min.

Product Loss

Piston pump

Peristaltic pump

Time pressure

Mass flow metering

Rolling diaphragm

pump

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Overview of single use filling systems


Rolling diaphragm pumpPeristaltic pump Piston pump

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Peristaltic pump

Peristaltic pumps are displacement pumps. The product is pushed through the filling hoses by

means of mechanical hose deformation (typically generated by rollers at the outside).


Rotary pump

shown with 2 rollers

Suction side

Pressure side

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Rolling diaphragm pump


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Drivers for disposables in pharma drug production


FlexibilityEconomic benefits

Saftey

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The interaction between the product and product contact surface (such as

adsorption, or the formation of leachables

and extractables).

The fragile nature of the system compared to

fixed reusable systems.

The increase in the number and complexity of manual operations

(including inspection and handling of the system) and connections made.

The complexity of the assembly.

The performance of the pre-use integrity test for sterilizing grade filters.

The potential for compromising the

system at the point of opening the outer

packaging.

The risk of holes and leakage.

The risk of particulate contamination.

Risks according to Annex 1


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Comparison


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Comparison


Single Use

• batch-to-batch cleaning

• no cleaning validation (only verification)

• supplier qualification (audit, report)

• specification (CoA)

• validation data (leachables, extractables)

• lower investments, higher running costs

• faster set up

Multi Product Use

• product-change-over cleaning (e.g. CIP)

• full cleaning validation

• system qualification incl. supplier

evaluation

• higher investments costs, lower running

costs

• time-consuming

versus

• not reusableSingle use disposables

• multiple use in same process step for different batches or in different process steps of one batchMulti-batch (one product)

• multiple use with same equipment for different productsMulti-product (multi purpose)

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Comparison


~10min

None

None

None

~6min

Plastic with product

residues

~40min

~3h

10kg steam, 150 Nl PW,

500l WFI, 12,000 Nl air/N2

Expensive

~30min

Waste water with

product residues

Preparing the filling system

Cleaning, sterilization, cooling

Media consumption

Cleaning validation

Dismantling the filling system

Disposal

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Application possibilities for Single Use


Single Use

RTP

packedTriple packed

Isolators cRABS Cleanroom RABSIsolators cRABS RABS

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Elements of the single use disposable system

• Filling needles

• Disposable RDP

• Peristaltic Pumps

– Tubing inside pump

– Suction & filling tubing

• Bag with

– Single connectors

– Venting

– Gassing


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Example for system setup in isolator


Sterile connector

Vent bag

Flush bag

Beta-port for insertion

Bag

Product header with weighing cell

Gassing

Venting

Peristaltic pumps

Disposable filling needles

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Key:

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Installation in clean room and RABS


Remove 1st packaging in class C

Spray 2nd packaging in class C in a material lock

Transfer the 2nd packaging from material lock to class

B

Open the 2nd packaging under LAF and slide it

inside the RABS

Open the last packaging with gloves in the desinfected RABS

Install the system

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Example for system setup in isolator


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No need for decision


Combi filling station

Combi filling „Selection“

Peristaltic pump

Time pressure

Combi filling „Performance“

Piston Pump

Peristaltic pump

Time pressure

Rolling diaphragm

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From TPF to Peristaltic pump


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Conclusion

• Single use technologies help to answer pharmaceutical trends

• Plenty of components and filling technologies are available

• Major benefits in combination with numerous batch changes

• Risks coming from material and manual handling


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THANK YOUPROCESSING AND PACKAGING FOR A BETTER LIFE.

Tobias Goettler – Product Management

2020 PDA Aseptic Processing of Biopharmaceuticals

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