This document discusses packaging development for pharmaceutical products. It outlines the process of selecting packaging, including identifying options, testing materials, development stability testing, defining manufacturing controls, selecting the intended market pack based on testing results, and conducting pivotal stability testing. The goals are to choose packs that ensure product stability and compatibility while meeting regulatory requirements and minimizing complexity. First intent packaging aims to standardize materials to reduce costs and variability across sites.

1. By
Saurav Anand,
+91-8511773466
Packaging Development, IIP, MBA

2. Meaning of First Packaging Intent
 Preferred range of pack/material options to be used for new products
 Agreed between R&D and factory
 Identical global materials
 Fully aligned with Procurement sourcing strategies
 Secure/robust sourcing
 Minimised R&D resource
 Supports supply site transfers (like for like; identical)
PACKAGING: First Intent

3. 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 etc
Material 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 250m
2. PVC/PVDC 250m/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

4. • 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 Complexity
Maintaining Flexibility
Current
Future
First Intent: Bottles and Closures - Benefits

5. 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

6. 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

7. BASIC REQIRMENT
Packaging: Choosing the most appropriate pack
Protection
• stability test
conditions
Compatibility
Safety and
performance
Regulatory
Legislation
• E. g. E C Packaging and
Packaging Waste Directive
Commercial
• Image
• market re q uirements/trends
• dosing/patient compliance
• security/tamper evidence
• Manufacturing
• economics - COGCorporate
• Global Quality
Policies

8. Some factors are territory-specific, e.g.
Packaging : Choosing the most appropriate pack
Presentation
e.g. for solid dose
US prefers bottles
E U /RoW prefer blister packs
Environment
EU Packaging and Packaging Waste
Directive
US - no direct equivalent
Child resistance requirements
US
Legal requirement with few exceptions
EU/RoW
Legal requirement in only for EU member states
& for very limited list of products.

9. 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

10. • 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

11. • 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

12. Data from material and product testing used to identify critical quality and process
attributes 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

13. • 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

14. Phase 3 – Launch : Market Introduction
 Between Phase 3 and Launch
Secondary 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

15. 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.

16. 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

17. 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