Key Operational Considerations for Validation and Packaging in Support of a Product Launch

Rebecca Tumelty

Client Team Leader

Almac

22 May 2019

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Overview

• Highlight key operational areas to consider in the countdown to an EU Product Launch

- Planning - Validation - Launch Phase

• Importance of understanding lead times to ensure all preparation and key operational milestones are met in a timely manner

• Case Study

- EU Launch Product in Blister / Wallet Presentation- Key operational decisions and outcomes- Additional considerations for alternative projects

• Final Presentation Decision

• Patient Functionality and Compliance

• Regulatory Requirements

• Technical Review of Pack Design

• Confirm Specification of Materials e.g. Foil, Base, Desiccation

• Source Primary Packaging Supplier Options

• Approval of Suppliers

• Specific Requirements- Print Registration - Child Resistance

• Additional packaging solution or impact on facility

• Modification to Existing Line

• Printing and Serialization Solutions

• Specific Design Requirements - Embossing - Perforation - Blister Pocket - Dimensions

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Early Phase Considerations

Pack format & Design

Primary and Secondary Packaging Materials

Tooling Requirements

Case StudyEU Product Launch in Blisters and Wallets - 2018

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Information available to Almac Prior to EU Submission

- Dosage Form (Tablet x 2 Strengths) and Tablet Dimensions

- Dosage Regimen – Daily

- One tablet strength in the morning, second tablet strength in the evening.

- Projected Commercial Batch Size

- Material Specifications for Foil and Base Material, and preferred supplier for Tamper Evident Seal – To meet Falsified Medicines Directive (FMD)

- Specific Requirements on Blister cavity dimensions (re. stability / shelf life)

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Case Study Overview

Pack Format

Option 1 – Blister → Blister Print → Finished Pack in Carton

Option 2 – Blister → Blister Print → Wallet Card → Carton

- Option 2 was selected by the Client. Blister, wallet and pack dimensions were confirmed enabling Almac to order specific toolsets for blister line and wallet press

- Pack Design of a wallet was best suited for patient use. This enabled clear instruction to be added to the pack regarding timing and dosage strength for administration on a daily basis – 4 weeks of medication in a pack.

Similar decisions pre-submission at the project kick-off phase can lead to considerations for bottles / sachets / vial labelingetc

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Initial Operational and Technical Decisions

Tooling & Processes

- Lead Time of 3 months for tooling manufacture at supplier site.

- Considerations for perforated blisters / desiccant feeders etc

- Considerations for new production line (lead time of 1+ years)

- Specific Printers requested for Serialization – 12-14 Weeks

- Drug Categorisation led to containment requirements for blister line and humidity control in the primary packaging room

- Subsequent updates to Almac SOPs

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Critical Path Items – Preparation to ensure operational milestones are met

Packaging Materials

- Foil lead time for primary packaging was 16 weeks as Client requested US supplier.

- New supplier required an audit and qualified to be considered ‘Approved’

- Ensuring all materials on site (inc. DP) for initial Engineering Work (FAT if req.)

Drug Product Availability

- DP manufacture of Validation batches was delayed– alternative agreement was reached to receive engineering batches to perform Engineering Study and Process Qualification.

- Key to agree batch sizes and QTY of available product

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Critical Path Items – Preparation to ensure operational milestones are met

FMEA / Project Risk Assessment

- Planning Stage - A FMEA Risk Assessment was carried out with input from several key Subject Matter Experts

- Handling of Drug Product: Initial receipt → Storage → In and out of production operations → Distribution

- Workplace Exposure Limits (WEL’s) reviewed- Containment Strategy during Primary Packaging- Cleandown Assessment and Strategy- Additional SOP Requirements / Update to Existing SOPs

Each Product will require a separate detailed assessment … i.e if the Client is launching a Vial product there will need to be an assessment for how operations should approach a vial breakage

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Detailed Assessment of the Product and Process – Operational Input

Strategy and Validation Plan

1) Specifications of primary packaging materials decided at an early stage

2) Defined standard batch quantity of tablets to be blistered in a commercial campaign – with engineering batches available.

3) Timely decisions made on tooling and pack design to allow ordering of equipment and mock up secondary packaging materials

• As a result, in the interim period awaiting delivery of the above, Almac was able to clearly define a Validation strategy with the Client. This was reviewed and approved by Quality and Operational personnel at Almac and the Client pre Validation activities commencing.

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Validation Planning

Blistering → Blister Printing → Walleting

- FAT / SAT – Impact on Project Timelines

- Toolset Qualification (Blistering Only) - Anything from 2-4 months before a

commercial batch is processed- Carry out extensive checks on new

parts, including fitting tooling to blistering unit ensuring no issues with format parts

- Detect and resolve any issues before Engineering work commences

- Produce blister samples for checks re. Forming / Dimensions / Orientation

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Validation Execution

- Engineering Study- Determine proven acceptable range and

proposed fixed settings for a number of variables including; forming and sealing temperatures, sealing pressure, line speed etc that resulted in an acceptable blister (relevant tests applied to printing and walleting)

- Challenged critical devices; e.g Vision system and reject systems including fail safe sensors

- Further appearance tests on blisters produced for Engineering Study

For a cold chain vial product, studies would be carried out conditioning of vials and adhesion of labels / tamper evident seals via in-fridge studies. Smudge checks on overprinted information also completed.

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Validation Execution

- Process Qualification- 2 production runs carried out by

operational staff, following protocol and draft Master Batch Record emulating a repeatable packaging run.

- Due to availability of product each PQ ran half a batch of tablets to ensure overall there was a representation of a full commercial batch.

- Operational extremes of line speed and temperature tested, increased In Process Checks carried out at PQ

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Validation Execution

- Process Validation- Post PQ close out, 3 Commercial scale

batches were then completed, on this occasion with commercial product.

- Ranges established were inputted into a fully approved commercial batch record for blistering.

- Blister Printing and Walleting PV was completed using trial components representative of commercial packaging.

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Validation Execution

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• Ensure all DP Manufacturing Batch Records and Certification is available for review by CDMO QP

• CofA Available if DP Release is the responsibility of an external QPDrug Product Release

• Finalise Batch Number and Expiry Details• Commercial Master Batch Records Approved• QC Approval of Packaging Materials

Process Validation →Commercial Batches

• Review and Approval of Executed Batch Records• Post Approval of Executed Validation Protocols• Validation Release Memo

Validation Close Out

• QP Review of Executed Batch Records / Validation Protocols / Serialized Data / DP Paperwork and CertificationQP Release of Product

Shipment and Product Launch

Commercial Product Launch – Final Steps

Importance of Planning and Understanding Timeline Requirements

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Operations – Key Considerations

Accurate assessment and early decisions made of tooling requirements

Timely sourcing and purchasing of primary packaging materials

A clear picture of proposed commercial batch sizes and availability of DP to allow operations to plan Validation activities was available

Detailed and early assessment of the product, project and processes ensured any risks were addressed proactively and solutions in place

Importance of Planning and Understanding Timeline Requirements

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Operations – Key Considerations

Both the CDMO and the Client were clear on the responsibilities and timelines for the review and approval of all batch records and Validation protocols

Operational team ensured that late stage details were available early in the project, e.g batch numbering format, expiry calculation and format were obtained to ensure operators were aware of over printing requirements

Client provided DP certification in a timely manner to enable QP review and successful release and launch of the product

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Rebecca Tumelty

Client Team Leader

Almac Group

E: rebecca.tumelty@almacgroup.comT: +44 (0) 28 3836 3363

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