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1 Incorporate packaging early in the product development lifecycle

Without firsthand experience in packaging, many team members think packaging as a simple last step in getting a product to mark. Have you ever heard someone say “just put it in a pouch and a box”? Unfortunately, packaging development can be a lot more complicated, costly, and time consuming than originally thought causing disruption late in the game.

Major considerations:

 Packaging design (time, resources, complexity)  Manufacturing planning (demand, capacity, layout, personnel)  Lead times for tooling and materials (dies, molds)  Lead times for equipment (sealer, printer, test equip)  Screening, benchmarking, and challenging  Validation activities such as sealing qualification, transportation testing  Sterilization validation  Labeling development and UDI compliance  Accelerated and real time aging  Training / implementation

Planning, scheduling, and budgeting appropriately can mean the difference in a successful product launch or significant delay.

2 Perform a Product Package Assessment (PPA)

Engaging the packaging team early is half the battle – making the most of the opportunity is the other half. This step is about asking the right questions, capturing key information up front, and feeding that into the project plan, schedule, and budget.

Have you considered?

 Countries of Sale  User needs  Marketing requirements  Sterilization  Product morphology  Device sensitivities  Shelf life  Product mix and volume  Distribution channel  Manufacturing environment  Labeling strategy

Responses to these questions create design inputs that can be used to establish design requirements, design constraints, and subsequent design verification/validation requirements. These also are pertinent to risk management activities such as DFMEA, Hazard Analysis, etc. While these topics may not have an

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answer up front, or may evolve with time, it is important to start the dialogue and plan accordingly. The PPA is just one of the many tools that PCL uses to deliver “Speed to Market with Confidence.”

3 Evaluate several types of packaging systems and sealing equipment

Unfortunately there isn’t a one system fits all when it comes to medical device packaging. Many varieties exist including pouches, trays, sleeves, bags, tubes, cartons and more. Equipment can range with tray sealers, bar sealers, band sealers and form-fill-seal machines all that do something unique. Many companies mistakenly revert back to what was used on previous projects, which may be expensive, inadequate, or not applicable to the next project. It is critical to evaluate each product- packaging system uniquely, containing its own unique challenges.

During this “Design Concept” or “Napkin Sketch” phase (that’s what we call it at PCL) it is imperative to compare alternative designs side by side and evaluate for:

 Fulfillment of design requirements identified during the PPA  Capital requirements including equipment, tooling  Staffing / personnel requirements  Manufacturing capacity / throughput  Total packaging system cost including materials, protective packaging, waste, labor, sterilization, other soft costs  Schedule  Project complexity and risk

4 Create Prototypes and perform feasibility testing

Feasibility studies are the key to optimizing packaging design for performance and cost.

Blindly selecting a packaging design, making the investment in materials and tooling, and moving into validation without upfront due diligence can be a recipe for disaster – we call it the Hail Mary approach. There is not a crystal ball that will give you insights on the success or failure of your project, but feasibility testing is the next best thing!

We encourage our clients to make data driven decisions on packaging design by prototyping and verifying performance before moving forward on a project. This doesn’t have to be a costly exercise, get creative! Hand-cut larger Tyvek pouches down to size, create 3-d printed parts, mock up corrugated designs using scrap boxes, use nuts/bolts to simulate weight. Many packaging material suppliers have ways to quickly and efficiently create prototype parts and are happy to support this effort at your request. Take those prototypes and challenge them. Perform screening and benchmarking studies and simulate worst case conditions. Results of feasibility testing can uncover potential failure modes, highlight areas of concern, or provide confidence in a package design before initiating qualification/validation activities. A simple drop and vibration simulation on your proposed packaging system will make for a good night’s sleep.

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5 Create a Risk Management strategy and stick to it.

It may be surprising to learn that the FDA considers packaging to be an element of the product itself. This means that packaging development activities require the same design control and risk management scrutiny that accompany device development.

Design Control ensures that there are clear design & performance requirements, tracks the evolution of designs as they progress through a project; and covers the verification / validation of designs through services offered at PCL such as package integrity, simulated distribution and shelf life testing.

Risk management is how risks in designs and processes are identified, what effects those risks might have (especially on patient safety), and how those risks are mitigated through the use of design improvements or process controls.

PCL has developed many tools and templates that can be used during packaging development to ensure that key requirements are not forgotten.

Outputs of these deliverables will drive decisions on validation strategy, sample sizes, process controls, and many other important considerations that keep your project audit-friendly.

6 Evaluate Labeling requirements

Labeling is critical for safe and effective product use. Key elements include reference numbers, product description, lot numbers, expiration dates, quantities and identifiers that healthcare professional rely on prior to using a device. Additionally, the FDA is rolling out the Unique Device Identification (UDI) program that requires all medical devices to be uniquely registered in a public database and be labeled with specific content

Key aspects for successful UDI implementation:

 Procurement: all products must have a UDI which can be obtained from several FDA-accredited issuing agencies.  Identification: The UDI must be added to the product label and include Device Identifier (DI) and the Production Identifier (PI). This is displayed as a barcode and human readable text.  Registration: It is required to register the UDI with FDA’s Global UDI Database (GUDID).  Implementation: The final step is to adhere to FDA established timelines.

PCL has developed a quick-implement program for companies seeking UDI compliance.

7 Be aware of key requirements for packaging OQ / PQ activities

Many medical device manufacturers mistakenly treat packaging process qualification (e.g. forming and sealing validation) the same as other assembly qualifications. But there are some key differences:

 Define Package Families: It is vital to properly plan. It is not sufficient to perform a process qualification on a PET/Tyvek pouch and then assume a Nylon/Tyvek pouch is also qualified. Differences in materials, size, process settings, and sealing technologies may drive multiple process qualification activities.

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 Define the Critical Process Parameters: The focus of validation efforts should be on to the defined parameters. Usually this consists of time, temperature, and pressure but others may be identified depending on the unique nature of the process.  Optimize Process Window: Before entering OQ / PQ, properly optimize the process window using engineering studies such as Design of Experiments (DOE). ISO16775 Annex Q provides some excellent tools and discussion.  Define Quality Attributes: Per ISO11607-2, critical to quality characteristics for sealing include seal integrity, seal width, punctures/tears, wrinkles/creases, peel-open characteristics, and process repeatability/reproducibility. Don’t miss them.  Be Production Representative: PQ should be treated as production-representative, meaning the use of trained operators, following written work instructions, producing typical lot sizes, and incorporating product or simulated product.  Have a Plan: Establish Lower Process Limits (LSLs) for seal strength and film thickness. Auditors are beginning to ask “why is that 1.0lbs/inch the LSL”. It is best to develop your own LSLs uniquely based on capability of the process and subsequent validation of worst case process limits during transit testing and aging studies.

Defending your protocols in front of an FDA auditor is never a welcomed task but being equipped with rock solid IQ/OQ/PQ documents will give you the confidence that all details have been accounted for.

8 Properly define “Worst Case”

ISO11607-1 addresses “worst case” in three areas and in each case, it means something slightly different. Start by understanding these key definitions:

 Sterile Barrier System – this is minimum package which prevents ingress of microorganisms  Protective Packaging – configuration of materials designed to prevent damage to the sterile barrier system and contents.  Packaging system – combination of sterile barrier system and protective packaging

Typically “worst case” scenarios fall under three areas and the elements within them must be defined.

Medical Device

Within medical device product families, a common sterile barrier system can be used to protect a variety of devices. The worst-case is established by identifying the device(s) that applies the most stress to the packaging system. This may be the bulkiest/heaviest, or an item with the greatest number of fitments or features. It may be necessary to test more than one device to ensure that a packaging system has been fully challenged.

Sterile Barrier System

ISO11607-1 requires validating sterile barrier systems produced at the worst case limits of forming and sealing (e.g. samples sealed at “Low” or “High”) run conditions. Typically the parameters used during OQ are selected. The key is to make the final closure seal at or beyond specified process limits to ensure that a worst-case sterile barrier system has been produced.

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Packaging System Configuration

Consider package families, such as chevron pouches, rigid trays, FFS, etc. Identify the worst case configuration from each one, perhaps this is a final shipping unit containing the most sealed pouches in the largest/heaviest box. Or it may be a partial shipper where there is excess room for movement of parts. A bracketing approach may be used to ensure that extremes are challenged.

Selecting worst case is a careful balance between pushing the limits of your packaging system while also being aware of practical real world scenarios. Create a defensible plan and be prepared for the introduction of additional variation to ensure the full spectrum of possibilities is accounted for.

9 Understand YOUR distribution channel.

The purpose of a transit validation is to ensure that products arrive to the hospital while maintaining efficacy, including maintenance of the sterile barrier. To be successful in this effort, it is necessary to first map your Finished Goods distribution channel.

Helpful Scenarios to Consider:

 Does product travel from the plant, to the sterilizer, to a DC, then small parcel to a supply room? Or does product get stacked in an ocean container and travel for months baking in the sun or the cold on the ocean?  Is product placed in the cargo hold of an airplane traveling through the Arctic Circle on an Alaska-Norway route?

Transit testing should be tailored accordingly. This will ensure that packaging systems are challenged in a manner representative of real world scenarios.

FDA consensus standards for transit testing include ASTM D4169 and ISTA 1, 2, 3 series. Review the options within these standards to customize a representative test plan for your product.

10 Don’t forget Real-time Aging!

ISO 11607–1:2006 clause 6 states that “stability testing shall demonstrate that the sterile barrier system maintains integrity over time. Stability testing shall be performed using real-time aging. Stability testing using accelerated aging protocols shall be regarded as sufficient evidence for claimed expiry date until data from real time aging studies are available.”

The FDA understands that delaying a product launch while waiting for real-time aging testing slows down innovation in the market. Accelerated aging allows for faster market introduction as long as the data from real-time aging studies continues to demonstrate maintenance of key performance requirements over time. Too many companies forget to include this important step and find themselves in difficult audit situations.

PCL can help structure your stability test plan ensure that your validation has the best chance for success.

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ABOUT US Packaging Compliance Labs, LLC is an independent packaging engineering partner. We provide design, development, and validation services for sterile packaging systems on behalf of medical device and pharmaceutical manufactures. Our focus is always on sound engineering discipline and regulatory compliance.

Your packaging engineering partner:

 We are an extension of your product development team  We bring the people, systems, and capabilities to create innovative, cost effective packaging solutions for your healthcare products.  We offer precision expertise to address breaking developments in the healthcare industry.  We have extensive experience across a variety of industries to serve additional sectors such as food, consumer products, and technology packaging.

WHAT WE DO We get your product to market quickly by fusing packaging design and validation into one streamlined experience.

 Packaging Design – Our expert team of engineers will design and develop a custom packaging solution for your healthcare product.  Packaging Validation – We offer a suite of package testing services in our state-of- the-art ISO17025 accredited and ISTA certified package testing laboratory. If you need a custom packaging solution for your healthcare product, or if you are simply looking for a trustworthy packaging laboratory to meet your testing needs, we can help.

OUR SPECIALTIES

Project Services Package Technologies Equipment Specialties  FDA & ISO Regulations  Flexible & Rigid  Form-Fill-Seal (FFS)  Design Control  Pouches & Bags  Bar Sealing  Program Management  Trays & Lidding  Tray Sealing  Process  Rollstock  Induction Sealing Characterization  Blisters  Thermoforming  IQ/OQ/PQ  Bottles & Caps  Injection Molding  Transit and Aging  Labels, Printing &  Capping & Labeling  Root Cause Analysis Inks  Printing Systems  Documentation  Cartons & Boxes

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PACKAGING ENGINEERING SERVICES Packaging Compliance Labs typically works with clients in three ways:

1. Program Management

2. Consulting

3. Packaging Laboratory

Program Management

Many times our clients have a defined project scope, objectives and budget that could be derailed by packaging. They come to PCL looking for solutions. We sit down with the client and create a plan of action, from napkin sketch to market launch. PCL then takes the reigns and manages the packaging effort start-to-finish. We don’t work in a vacuum – we are an extension of our client’s product development team. We schedule routine office hours, weekly project updates, and formal stage-gates to ensure that all stakeholders are engaged and the team’s efforts are all pointed in the same direction. Our contribution can be throttled by our client’s needs, from supervision of project activities to direct, hands on execution.

Program costs are determined on a case-by-case basis uniquely for each project. We start with a “Discovery” phase to learn about your product, project, and objectives. From there, we put together a high level project plan and price the plan based on the number of hours we expect it to take. Invoices are issued on a monthly basis. Here’s the caveat – we don’t charge more than we quoted, as long as there have been no changes to scope. We know it’s important for you to count on hitting a budget.

Consulting

Other times our clients just want an expert on the other end of the phone. We arrange a blanket PO for a capped amount. Throughout the year, our clients rely on us to help make key decisions, troubleshoot, diagnose failures – whatever we can do to be a resource.

Packaging Laboratory

Packaging Compliance Labs is proud to offer a full service, ISO17025 healthcare packaging laboratory in West Michigan. A suite of capabilities ranging from material, labeling, strength / integrity, transit, accelerated and real time aging ensure that your next testing need is covered. In addition to our commitment to Quality, we offer responsive service, quick lead times, and fast turnaround on reports.

GET STARTED Packaging Compliance Labs fuses design, development, and validation into one streamlined experience to get your products to market on time and on budget. What can PCL do for you? Let’s sit down together and discuss your needs. We look forward to working with you!

4334 Brockton Dr SE Suite E Kentwood, MI 49512 www.pkgcompliance.com 616.227.4540