MODERN PARENTERAL PACKAGING - pharmtech-expo.ru · PDF fileextrusion blow molding dedicated to...

2017-11-23

MODERN PARENTERAL PACKAGING -

NEW POLYMERS & INNOVATIVE DESIGNS

FOR BOTTELPACK CONTAINERS

PHARMTECH MOSCOW 2017

Thomas Obenauer

2

1. Introduction

2. Materials for BFS

3. Material selection by using test kits

4. Soft Polypropylene material

5. New LVP container development - Easy Empty

6. New Polypropylene material

7. Modification of existing machines

NEW POLYMERS & INNOVATIVE DESIGNS FOR BOTTELPACK

CONTAINERS

НОВЫЕ ПОЛИМЕРЫ & ИННОВАЦИОННЫЙ ДИЗАЙН ДЛЯ

ФЛАКОНОВ BOTTELPACK

New Parenteral Packaging and Innovative Container Design 2017-11-23

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Blow-Fill-Seal Definition

BFS is a production process based on

extrusion blow molding dedicated to aseptic

pharma packaging.

Key steps include:

1. Blow the polymer tube to form a container

2. Fill the formulation into the container

3. Seal the container immediately after filling

BFS IS HIGHLY INTEGRATED ASEPTIC PHARMA PACKAGING

BFS - ЭТО ВЫСОКОИНТЕГРИРОВАННАЯ

АСЕПТИЧЕСКАЯ ФАРМАЦЕВТИЧЕСКАЯ УПАКОВКА

New Parenteral Packaging and Innovative Container Design

Bottelpack machine

Examples of BFS containers

2017-11-23

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Some figures

established since 1964

1st application for IV Solutions sold in 1965

1st application for Eye drops sold in 1971

1st application for Single dose Eye drops sold in 1976

1st application for Inhalation Therapy sold in 1981

1st application for Cough Syrup sold in 1982

more than 2’000 BFS machines sold worldwide

Approx. 7 billion of BFS containers per year

BFS IS WORLDWIDE WELL ESTABLISHED FOR PHARMACEUTICAL

PACKAGING

BFS – ШИРОКО ИЗВЕСТНАЯ ВО ВСЕМ МИРЕ

ФАРМАЦЕВТИЧЕСКАЯ УПАКОВКА


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WITHIN SECONDS BFS PRODUCES FILLED AND CLOSED

CONTAINERS FROM POLYMER GRANULATE

ЗА СЧИТАННЫЕ СЕКУНДЫ BFS ПРОИЗВОДИТ НАПОЛНЕННЫЕ

И ЗАКРЫТЫЕ ФЛАКОНОВ ИЗ ПОЛИМЕРНЫХ ГРАНУЛ


Blow-Fill-Seal (BFS) - processing

3 sec* to 15 sec

EXTRUSION FILLING** SEALING DEMOULDING BLOWING

*3 sec. cycle time for Rommelag's proprietary 460 rotary technology for SVP containers

2017-11-23

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BFS CONTAINERS USE MEDICAL GRADE POLYMERS

ФЛАКОНЫ BFS С ИСПОЛЬЗОВАНИЕМ ПОЛИМЕРОВ

МЕДИЦИНСКОГО НАЗНАЧЕНИЯ


LDPE, HDPE & PP

from e.g. LyondellBasell (Purell®),

Borealis (Bormed®), etc.

Autoclavable PE 106-115ºC; PP 121ºC

Extractables dossiers (approx. 40 pages)

available for selected PE & PPs (by Toxikon)

PET mainly used for cosmetic applications & for

Japanese products

Soft PPs new developments by Borealis* &

Sumitomo with low flex modulus (400-500 MPa)

and modern additive packages

Typical BFS materials

PET HDPE PP LDPE

Soft PP 2017-11-23

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BOREALIS SUPPORTED BY ROMMELAG HAS DEVELOPED A SOFT PP FOR

BLOW-FILL-SEAL-APPLICATIONS

НАПРИМЕР: ТЕСТОВЫЙ КОМПЛЕКТ ПОЗВОЛЯЕТ БЫСТРО И

ЭФФЕКТИВНО ПРОВЕСТИ ТЕСТ СОВМЕСТИМОСТИ


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CO-EXTRUSION OF POLYMERS TO PRODUCE MULTILAYER CONTAINERS

HAS A LONG TRADITION IN AUTOMOTIVE & FOOD INDUSTRY

СО-ЭКСТРУЗИЯ ПОЛИМЕРОВ ДЛЯ ПРОИЗВОДСТВА

МНОГОСЛОЙНЫХ ФЛАКОНОВ ИМЕЕТ ДАВНИЕ ТРАДИЦИИ В

АВТОМОБИЛЬНОЙ И ПИЩЕВОЙ ПРОМЫШЛЕННОСТИ


Principle Extrusion Examples

EVOH, …

COC, COP,

PP, …

PE, PP, …

2017-11-23

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CO-EX BLOW-FILL-SEAL ALLOWS THE IMPROVEMENT OF BARRIER

PROPERTIES TO MINIMIZE ADSORPTION / PERMEATION

ВЫДУВ-НАПОЛНЕНИЕ-ЗАПАЙКА С СО-ЭКСТРУЗИЕЙ

ПОЗВОЛЯЕТ УЛУЧШИТЬ БАРЬЕРНЫЕ СВОЙСТВА, ЧТОБЫ

МИНИМИЗИРОВАТЬ АДСОРБЦИЮ / ИНФИЛЬТРАЦИЮ


Cross sections of a

5 layer BFS-ampule

b

CoEx barrier materials

EVOH - excellent O2 barrier properties

for food and pharmaceutical packaging

PA - good gas barrier properties and

chemical resistance, used for packaging

of cosmetics and chemicals

Cycloolefinpolymers COP (Nippon Zeon)

inner layer for low adsorption used for

parenteral packaging

Cycloolefincopolymers COC (Topas)

inner layer for low adsorption & low

moisture vapor transfer used for parenteral

packaging 2017-11-23

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ROMMELAG CMO OFFERS CONTRACT MANUFACTURING IN CO EX BFS

UNDER GMP CONDITIONS

ОТДЕЛ КОНТРАКТНОГО ПРОИЗВОДСТВА РОММЕЛАГ ПРЕДЛАГАЕТ

КОНТРАКТНОГО ПРОИЗВОДСТВО НА УСТАНОВКАХ BFS С СО-

ЭКСТРУЗИЕЙ В СООТВЕТСТВИИ С ПОЛОЖЕНИЯМИ GMP


Co-Extrusion Bottelpack: 321-079 GMP

EVOH, …

COC, COP,

PP, …

PE, PP, …

2017-11-23

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Definition of core requirements

Design concepts Lab-scale

manufacturing Verification tests

Scale-up

ROMMELAG R&D SUPPORTS FAST PHARMACEUTICAL DEVELOPMENT BY TEST KIT, CALCULATIONS & SIMULATION

ОТДЕЛ R&D (ИССЛЕДОВАНИЯ И РАЗРАБОТКИ) РОММЕЛАГ

ПОДДЕРЖИВАЕТ БЫСТРОЕ ФАРМАЦЕВТИЧЕСКОЕ РАЗВИТИЕ С

ПОМОЩЬЮ ТЕСТОВЫХ КОМПЛЕКТОВ, КАЛЬКУЛЯЦИИ И РАСЧЁТНОГО

МОДЕЛИРОВАНИЯ


chemical • sorption

• degradation

• light sensitivity

• extractables and leachables

• etc.

physical • loss of water

• oxygen permeation

• opening force

• etc.

functional • filling volume

• delivered volume

• terminal sterilization

• cap / connector

• etc.

mathematical

assessment

technical construction

simulation

preliminary compatibility

study with BFS test kit

design concept

pilot tool

material

selection

design concept

production tool functional tests

handling studies

loss of water

oxygen permeation

opening force

preliminary stability

study

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EXAMPLE: TEST KITS ALLOW FAST & EFFICIENT COMPATIBILITY TESTING

НАПРИМЕР: ТЕСТОВЫЙ КОМПЛЕКТ ПОЗВОЛЯЕТ

БЫСТРО И ЭФФЕКТИВНО ПРОВЕСТИ ТЕСТ

СОВМЕСТИМОСТИ


Available Standard Polyolefines (PE and PP)

Plastic Manufacturer Resin Type Extractables

Dossier Available

LDPE LyondellBasell Purell PE 1840H X

LDPE LyondellBasell Purell PE 3020 D X

LDPE LyondellBasell Purell PE 3040 D X

LDPE LyondellBasell Purell PE 3420 F X

LDPE Borealis Bormed LE6609-PH

HDPE LyondellBasell Purell PE GF 4750 X

PP LyondellBasell Purell RP 270 G X

PP Total Petrochemicals PPM R021

PP Borealis Bormed SB815MO

PP Flint Hills PP 23M2A

Closed & empty 10 ml BFS containers

produced under GMP 2017-11-23

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EXAMPLE: USING TEST KITS IN YOUR R&D LAB IS EASY

НАПРИМЕР: ЛЁГКОЕ ПРИМЕНЕНИЕ ТЕСТОВЫХ

КОМПЛЕКТОВ В ВАШЕЙ ЛАБОРАТОРИИ R&D


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COST EFFECTIVE PP BOTTLES, THAT EMPTY WELL, NEED AN IMPROVED

DESIGN

УЛУЧШЕННЫЙ ДИЗАЙН РЕНТАБЕЛЬНЫХ ФЛАКОНОВ ИЗ

РР, КОТОРЫЕ ЛЕГКО ОПУСТОШАЮТСЯ


1. Self standing BFS infusion bottle

2. Standard head design

3. Administration similar to LDPE-bottles

4. 121°C / 20 min autoclaving

5. minimal height / weight (i.e. minimal air head space)

6. Design for high numbers of cavities

Easy Empty - key cost & performance targets

2017-11-23

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THE RELEVANT PARAMETERS FOR AN EFFICIENT INFUSION HAVE BEEN

IDENTIFIED

БЫЛИ ОПРЕДЕЛЕНЫ СООТВЕТСТВУЮЩИЕ

ПАРАМЕТРЫ ДЛЯ ЭФФЕКТИВНОЙ ИНФУЗИИ


efficient

infusion

medical

requirements

environment

material BFS-process

container

design

wall thickness costs

autoclaving

cap size

various

no venting*

shape

Ishikawa - Analysis

flow rate

softness

material BFS-process

container

design

headspace / fill ratio

pressure

needle size

2017-11-23

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A ROBUST EMPTYING METHOD HAS BEEN DEVELOPED TO MIMIC

MEDICAL PRACTICE

НАДЁЖНЫЙ МЕТОД ОПУСТОШЕНИЯ БЫЛ РАЗРАБОТАН

ДЛЯ ИМИТИРУЮЩЕЙ МЕДИЦИНСКОЙ ПРАКТИКИ


In vitro infusion – set up

1. Strict temperature control : 22 +-2 °C

2. Infuset: US-IV Set, 12664-28 without filter

3. Needle BBraun: 0,6 x 30mm

4. Non-vented container

5. End:

• Last drop from bottle or

• no weight change within 30 sec

2017-11-23

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ANALYSIS OF STANDARD BOTTLES INDICATED LIKELY IMPROVEMENTS

BY EXPLICIT FOLDING PATTERNS

АНАЛИЗ СТАНДАРТНЫХ ФЛАКОНОВ ПОКАЗАЛ

ЗНАЧИТЕЛЬНЫЕ УЛУЧШЕНИЯ ЧЁТКО СЛОЖЕННЫХ

КОНТУРОВ


• Hinges

• Folding triangle

• Folding edges

2017-11-23

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FINITE ELEMENT MODELING REFLECTS THE FOLDING PROCESS

МОДЕЛИРОВАНИЕ КОНЕЧНЫХ ЭЛЕМЕНТОВ ОТРАЖАЕТ

ПРОЦЕСС СКЛАДЫВАНИЯ


Simulation of folding behavior

Start t0 End tend

time

2017-11-23

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FEM(FINITE ELEMENT METHOD) SIMULATION RESULTS CONFIRM LAB EXPERIMENTS &

SUPPORT BEST APPROACH TO IMPROVE DESIGN FOR NEXT VERSIONS

FEM (МЕТОД КОНЕЧНЫХ ЭЛЕМЕНТОВ) РЕЗУЛЬТАТЫ РАСЧЁТНОГО

МОДЕЛИРОВАНИЯ ПОДТВЕРЖДАЮТ ЛАБОРАТОРНЫЕ

ЭКСПЕРИМЕНТЫ И ПОДДЕРЖИВАЮТ ЛУЧШИЙ ПОДХОД ДЛЯ

УЛУЧШЕНИЯ ДИЗАЙНА ДЛЯ СЛЕДУЮЩИХ ВЕРСИЙ


Approach:

1. X-Ray-CT-Scanning EE100v1 for

real wall thicknesses

2. FEM modelling based on scan

3. Verification of simulation results

by experiments

4. Simulation of different critical

design attributes

5. Verification of best simulation

results by experiments

FEM grid

Example 100ml version 1

Collapsing over time

2017-11-23

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THE EASY-EMPTY DESIGN SUPPORTS PRE-DEFINED FOLDING DURING

EMPTYING; PATENT APPLICATIONS HAVE BEEN FILED

ДИЗАЙН EASY-EMPTY ПОДДЕРЖИВАЕТ

ПРЕДУСТАНОВЛЕННОЕ СКЛАДЫВАНИЕ ВО ВРЕМЯ

ОПУСТОШЕНИЯ; ПАТЕНТНЫЕ ЗАЯВКИ ПОДАНЫ


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500 ML EASY EMPTY SOFT PP BOTTLES PERFORM WELL; OPTIMIZATION FOR

100 ML EE IS ONGOING

ФЛАКОН 500 МЛ EASY EMPTY ИЗ МЯГКОГО РР ВЫПОЛНЕН

ОТЛИЧНО; ОПТИМИЗАЦИЯ ДЛЯ 100 МЛ ПРОДОЛЖАЕТСЯ


Easy empty design & soft PP allow bottles that:

• Collapse well without venting

• Minimize head space

• Minimize height / weight

• Maximize the number of cavities

• FEM by university of Heilbronn will support fast

optimization of EE-Designs

Easy Empty - current results

EE-100 ml EE-500 ml 2017-11-23

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MODERN PARENTERAL PACKAGING:

NEW POLYMERS & INNOVATIVE DESIGNS FOR BOTTELPACK CONTAINERS

СОВРЕМЕННАЯ ПАРЕНТЕРАЛЬНАЯ УПАКОВКА:

НОВЫЕ ПОЛИМЕРЫ И ИННОВАЦИОННЫЕ РАЗРАБОТКИ ДЛЯ

КОНТЕЙНЕРОВ BOTTELPACK


1. BFS is the modern advanced aseptic technology for

liquid formulations from ophthalmics to parenterals

2. BFS uses dedicated medical grade polymers

and high performance barrier materials

3. Rommelag supports fast galenic development

by test kit and modern simulation tools

4. Easy empty Soft PP infusion bottles offer key benefits.

Summary

2017-11-23

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NEWLY DEVELOPED POLYPROPYLENE MATERIAL FROM SIBUR


• First contact in October 2016

• First trials on R&D bottelpack 312 machine on

2017-12-14 good results

• Trial on a bottelpack 360 production machine on

2017-05-10 good results

• Available from approx. Q2/2018

Sibur Polypropylene R015 BM

2017-11-23

MODIFICATION OF

EXISTING MACHINES

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NEW „TECHNICAL MODIFICATIONS“

DEPARTMENT

• Siemens S5 PLC not supported any more. Several

hundred bp machines still in operation with S5.

• Mould overhauls, fast and cost effective, either in

Germany, Switzerland or India. Original

manufacturers warranty certificate.

• Detailed discussions and technical expertise to

develop custom made upgrades from just a few

critical parts to complete overhauls.

• Replacement of hydraulic drives with servo driven

technology.

• Assistance of service engineers from Germany,

Switzerland, France, Egypt, Australia, China,

Pakistan, India, USA, Canada, Brazil,… More than

120 Rommelag SERVICE employees worldwide.

• Rommelag Pharma Service assistance in re-

validation activities after upgrade/modification.

• From old make new


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ROMMELAG MODIFACTION TEAMS

• Kocher Plastik Sulzbach-Laufen, Germany

• Rommelag Sales Waiblingen, Germany

• Rommelag Sales Buchs, Switzerland

• Maroplastic Reitnau, Switzerland


DEPARTMENT


27

BEFORE YOU DO THAT …

LET’S TALK …


DEPARTMENT


28 New Parenteral Packaging and Innovative Container Design

Большое спасибо за Ваше внимание

Thank you very much for your attention

2017-11-23

MODERN PARENTERAL PACKAGING - pharmtech-expo.ru · PDF fileextrusion blow molding dedicated to...

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