Process of Packaging Development

By Saurav Anand,+91-8511773466

Packaging Development, IIP, MBA

Meaning of First Packaging IntentPreferred range of pack/material options to be used for new productsAgreed between R&D and factory Identical global materialsFully aligned with Procurement sourcing strategiesSecure/robust sourcingMinimised R&D resourceSupports supply site transfers (like for like; identical)

PACKAGING: First Intent

Blister Pack has two component • Lidding foil – Alu Foil, Pet-Alu foil, Paper Alu foil, Glasin paper foil• Forming Material – PVC, PVC-PVdC, PP, PVC-Aclar, Alu-Alu etcMaterial choice (hierarchy of choice based on product stability)

• Material should preferably be opaque white unless clear is a specific market requirement (e.g. US, Japan)

• Aclar® should be restricted to applications where cold form is not technically or commercially acceptable due to product or pack size, ie larger products (further guidance to be defined)

1. PVC 250m

2. PVC/PVDC 250m/60gsm

4. PVC/Aclar® UltRx 2000

3. Cold Form 25 OPA/45 Al/ 60 PVC

Aclar® is registered trademark of Honeywell Inc

PACKAGING: First Intent – Blister Pack

• Reduction of complexity• Standardisation and rationalisation

of components• Reduced number of change-overs

at factory sites• Reduction in resource demand• R&D, Pack Dev, Procurement,

Sites use ‘off the shelf’ solution for majority of products.

• Flexibility across factory sites without increased Regulatory activity.

• Risk Mitigation• Commercial Leverage

Reduced ComplexityMaintaining Flexibility

Current

Future

First Intent: Bottles and Closures - Benefits

Phase I – FTIH & Phase II Clinical Supply Objective

Selection of packs for clinical supply Our approach:

Will generally use Limited range of standard, characterised packs, e.g. HDPE

bottles for solid dose forms Inert packs, e.g. fluororesin laminated injection stoppers

Packs and materials chosen to ensure pharmacopoeial and regulatory compliance is well understood

Material performance is well characterised or known Pack selection is supported by stability testing for each product

Phase II – III, Commercial Pack Development Objective:

Identification, development and testing of commercial pack options Approach:

Identify Pack Options

Material Selection & Testing

Development Stability Testing

Controls Defined

Pack Selection

Pivotal Stability Testing

BASIC REQIRMENT

Packaging: Choosing the most appropriate pack

Protection • stability test conditions

Compatibility Safety and performance

RegulatoryLegislation• E. g. E C Packaging and

Packaging Waste Directive

Some factors are territory-specific, e.g.

Packaging : Choosing the most appropriate pack

Child resistance requirements US

Legal requirement with few exceptionsEU/RoW

Legal requirement in only for EU member states & for very limited

list of products.

Pack options are identified to meet:

Product attributes, e.g. dosage form, physical and chemical robustness Product protection needs, e.g. moisture & gas sensitivity, thermal stability,

photostability, chemical compatibility, etc Clinical requirements, e.g. dosing regimen, titration dosing, route of

administration, need for dosing device Patient requirements, e.g. specific handling requirements, patient handling

studies Commercial requirements, e.g. market presentation, pack sizes, market specific

needs, patient handling needs Manufacturing requirements, e.g. equipment capability, critical process

parameters, Regulatory requirements, e.g. material compliance, pharmacopeial monographs

1. Identify Pack Options

• Product contact materials chosen to meet global and local regulations. • Product contact materials, particularly, plastics confirmed as compliant with

relevant food contact regulations, e.g. US, EU etc• Pharmacopoeial compliance established, e.g. USP, Ph Eur, JP • Performance testing conducted, e.g., moisture permeation, light transmission• Chemical characterisation, e.g. extractables and leachables studies, especially

for parenteral, ophthalmic and inhalation products• Toxicological assessment of extractables and leachables conducted• Maximise pack and product knowledge and understanding and achieve

commercial efficiency by using a limited range of First Intent, preferred pack materials, wherever possible.

2. Material Selection & Testing

• Development stability testing used to • Understand and explore stability in selected pack option• Predict long term stability• Confirm product protection or need for more protective packs, e.g. need for

Inclusion of desiccants for moisture protection Higher barrier blister films or need for foil/foil blisters protective overwrap

• Confirm compatibility• Identify and explore pack/product interaction

These are key data used to make a final pack selection.

3. Development Stability Testing

Data from material and product testing used to identify critical quality and processattributes for pack and packaging process, e.g.

• Need for RH controls during packing• Need for inert gassing of pack headspace• Seal integrity testing• Need for extractables testing as a routine control• Manufacturing controls/specifications for the pack components and

suppliers, e.g. dimensional and performance specifications, need for clean room manufacture, etc.

• Manufacturing controls for the packaging process

4. Controls Defined

• Data from the previous steps, together with the clinical, patient, commercial and manufacturing requirements, are used to identify and agree the intended market packs.

• Pivotal stability testing conducted in the selected markets packs, to

• Confirm compatibility and product stability• Support product registration submission

5. Pack Selection

6. Pivotal Stability Testing

Phase 3 – Launch : Market Introduction

Between Phase 3 and LaunchSecondary packaging is defined

note, if needed for product protection, this will be defined with the primary pack and included in pivotal stability

Define market presentations, graphics, patient information leaflets

Conduct line, engineering and technical trials on pack components and equipment

Conduct any necessary validation of packaging processes

Pack Changes if Required

Recommended aim: To avoid pack changes between pivotal stability and launch by ensuring a

Quality-by-Design approach to pack selection and understanding of product stability and packaging.

However, changes can occur at late stage due to, for example… Unpredictable outcome in pivotal stability assessment

Newly identified impurities Requirement for tighter specification limits

These tend to drive need for more protective packs, e.g. Inclusion of desiccant in bottle packs Need for higher barrier (e.g. foil/foil) blister packs

By use of First Intent pack materials and packs, we aim to have a thorough understanding of our materials to minimise impact of change and have readily available, well characterised pack options.

Example of Essentials of “Integrated Blister Cartoning Line” of Today High Level of Automation (w/o Human intervention) Reliability Safety to Product High Operational Efficiencies Quick Change Over cGMP Norms Ease of Line Clearance Ease of Validation Flexibility to handle various Packaging films.

Thermo Forming Cold Forming

Flexibility to handle Multi Products in a Blister

Example of Essentials of “Integrated Blister Cartoning Line” of Today Online Printing on Lidding Foils.

Child Resistant Foil Print Registration

Online Checks for Inserts and Cartons... Camera Systems for Products Pharma Code Readers 2 – D Matrix Code Pin Hole Detector for both Cold Forming & Lidding Reject Verification OCR / OCV 2 – D Matrix Code Track & Trace with Serialization / Random Online Check Weighing Online Bundler