Article Ken Shagagi of Life Science Outsourcing, Inc

Boxed to Perfect Standards The complex art of getting medical packaging right

of use, safety and product protection. The materials used in packaging devices play as important a role as the colours and design, protecting the device as much as providing quality packaging. The used to make folding packaging is an important part of manufacturing.

The four main types of substrates used in folding are: unbleached kraft ; bleached kraft paperboard; recycled paperboard; and small flute corrugate.

– Unbleached kraft paperboard is the most common material used for folding cartons – Bleached kraft, also called solid bleached sulfate, is the highest quality and most expensive paperboard substrate – Recycled paperboard is made from recovered paper, and represents the single largest market for recovered paper in the United States – Small flute corrugate has added strength and rigidity due to its construction, but this also adds cost to the converting process. It is usually used in high-end packaging where strength and stiffness are important Packaging for

The creation and design of medical packaging The primary standard governing medical terminally sterilised is a highly specialised profession, and medical device packaging and validation medical devices device manufacturers are called upon to is ISO 11607-1. The intent behind this obtain approval on each individual medical standard is “To provide designers and The process of developing and constructing device package. Ken Shagagi of Life Science manufacturers of medical devices with a a packaging system for terminally sterilised Outsourcing, Inc talks readers through the framework of tests and evaluations medical devices is a convoluted and pressing design, creation and validation testing for that can be used to qualify the overall endeavour. The definitive nature of the medical medical packaging and the numerous performance of the package used to protect device, the intended sterilisation methods, the standards that apply. the device components during handling, intended use, expiration date, transport, and distribution, and storage.” storage all influence the packaging system Background design and choice of materials. The The importance of combination of the medical device and the Packaging for medical devices, related products packaging system should perform efficiently, and materials is highly regulated and must meet material and design safely, and adequately in the end user’s hands. very specific requirements. The most critical There is more to medical device packaging ISO 11607 details the requirements from the factor for medical device packaging is product than simply creating a flashy package that gets International Organization for Standardization sterility, which must be maintained throughout consumers’ attention. Package design, while (ISO) for this process. The standard is broken distribution and storage, allowing for safe and being cost effective to the manufacturer, should into two parts. Below is a summary of each effective use of the device. be tailored to the end user for optimum ease of the two sections of the standard.

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3. Stability testing/accelerated ageing - Includes to a test plan involving , compression, accelerated ageing and real-time ageing. These vibration and drop tests as per the guidelines tests are conducted to determine that the set by ASTM D4169 and ISTA standards. packaging configuration is sufficient to maintain product sterility for the intended shelf life period. It may also be necessary to expose the medical packages and products to atmospheric – Accelerated Aging per ASTM F1980 conditioning in order to simulate particular – Conditioning per ASTM D4332 field conditions that a packaged product or Let’s delve into each of these in more detail. component may encounter during its expected ISO 11607-1 details the elemental attributes life cycle or testing cycle. The ASTM D4322 demanded of materials and pre-formed systems Standards and standards cover this. intended for use in packaging systems for terminally sterilised medical devices. It takes regulations ASTM D4169 into consideration the vast array of potential Distribution simulation testing assesses ASTM D4169 lists the ‘Standard Practice for materials, medical devices, packaging system a medical package’s ability to protect and Performance Testing of Shipping designs, and sterilisation methods. maintain the sterility of the products within. and Systems’ as per current industry/ There are numerous variables that medical ISO 11607-2 describes the validation government practises and experience. The packages and products will encounter when requirements for forming, sealing and assembly ’s performance level is determined by traveling from the point of manufacture to processes. The development and validation putting it through a specified order/sequence of the sterilisation facility, distribution centre of packaging processes are crucial to ensure tests, throughout which the shipping unit must or healthcare facility. A medical package that sterile barrier system integrity is withstand the distribution environment. falling from a fork lift, swaying around maintained until opened by the users a truck during transit, or being stacked of sterile medical devices. ISTA on top of other packages or containers Beyond ISO there are also ASTM in a storage warehouse are all examples The International Safe Transit Association (Association for Testing and Materials) and of distribution occurrences. (ISTA) is the author of test procedures that ISTA (International Safe Transit Association) define how packages should perform to ensure Distribution simulation is a systematic and standards which must be followed, especially protection of their contents. ISTA test repetitious way of testing shipping containers, if you intend to achieve FDA ( and Drug procedures are internationally recognised using testing equipment which exposes these Administration) approval. because they are based on leading technology packaging systems to genuine, real life hazards and the most current global transport Medical package testing can be broadly that may ensue within the forthcoming environment . categorised into: distribution environment. The organisation provides the final validation of 1. Distribution simulation testing - Involves a series Distribution simulation is a large and package revisions through its packaged-product of tests specifically designed to measure the quintessential component that complies performance test procedures. The ISTA test sturdiness of the outer/secondary packaging. This is with the ISO 11607-1 standard. The package procedures are acceptable in complying with to ensure that the packaging can meet industry or container and its contents are subjected the ISO 11607-1 standard. 4 standards and can safely contain the devices during shipping, handling and storage. Major standards involved are:

– ISTA Procedure 1A – ISTA Procedure 2A – ISTA Procedure 3A ASTM D4169-05, DC=13 - Testing sequence and types

– ASTM D4169 Sequence Test Type Standard Schedule Description 2. Package integrity testing - Focuses on the device’s 1 Drop ASTM D5276 A Handling primary packaging/pouch. Tests are designed to check the pouch’s ability to maintain sterility and 2 Compression ASTM D642 C Vehicle stacking its robustness. Standards utilised here are: 3 Vibration ASTM D999 F Loose-load – Bubble Leak Test per ASTM F2096 Altitude simulation (non porous 4 Low Pressure ASTM D6653 I – Peel Test per ASTM F88 packages) – Burst Test per ASTM F1140 5 Vibration ASTM D4728 E Vehicle – Dye Penetration Test per ASTM F1929 6 Drop ASTM D5276 A Handling – Visual Inspection per ASTM F1886

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ISTA Procedure 1A - Testing sequence and types

Sequence Test Type Standard Description

1 Vibration ASTM D999 Fixed displacement, rotary, vertical linear motion

2 Drop ASTM D5276 Free fall

ISTA Procedure 2A - Testing sequence and types

Sequence Test Type Standard Description

1 Atmospheric preconditioning ASTM D4332 Ambient and humidity

2 Atmospheric conditioning ASTM D4332 Controlled temperature and humidity

3 Compression ASTM D642 Machine apply and release

ASTM D999 4 Vibration Fixed displacement or random or D4728

5 Shock ASTM D5276 Drop

ASTM D999 6 Vibration Fixed displacement or random or D4728

ISTA Procedure 3A (Standard Package) - Testing sequence and types

Sequence Test Type Standard Description

1 Atmospheric preconditioning ASTM D4332 Ambient temperature and humidity

2 Atmospheric conditioning ASTM D4332 Controlled temperature and humidity

3 Shock ASTM D5276 Drop

4 Vibration ASTM D4728 Random with and without load

5 Vibration (optional) ASTM D4728 Random vibration under low pressure

6 Shock ASTM D5276 Drop

ISTA testing standards include the following: be used to validate that the package integrity has been maintained throughout the package’s – ISTA-1A: Non-Simulation Integrity Performance Tests processing, expected shelf life, and handling. – ISTA-2A: Partial Simulation Performance Tests Testing includes, but is not limited to, the following: – ISTA-3A: General Simulation Performance Tests – ASTM F1886: Visual Inspection Test - Standard Package integrity testing for determining integrity of seals for medical packaging by visual inspection Package validation testing is vital to ensure integrity of the package’s seal. Validation will – ASTM F88: Peel Strength Test - Standard test provide assurance and security that a package method for seal strength of flexible barrier materials is sealed properly, leak free, and secure from – ASTM F1140: Burst Test - Standard test methods any number of outside contaminants. for internal pressurisation failure resistance of Accelerated ageing should take place after unrestrained packages the integrity of the product and package – has been determined. ASTM F1929: Dye Penetration Test - Standard test method for detecting seal leaks in porous The main culprit for feeble package strength medical packaging by dye penetration is the seal heat-sealing parameters. If a formal – ASTM F1140: Creep Test - Standard test methods validation of the is not carried out, for internal pressurisation failure resistance of the medical device manufacturer can expect unrestrained packages sterile barrier failure. Packages may also lose their integrity as a result of the various events – ASTM F2096: Bubble Leak Test - Standard test that occur during processing and/or method for detecting gross leaks in packaging by distribution. Package validation testing may internal pressurisation

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Finally, remember that although the ISO 11607-1 standard is the benchmark, each customer may have particular requests which exceed these standards, so it’s best to remain flexible and prepared for further testing if necessary.

For detailed knowledge on each standard and test procedure visit: http://lso-inc.com/

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Author

Ken Shagagi is the Business Development Manager of the Medical Package Testing Division at Life Science Outsourcing, Inc. Ken has been operating in this capacity for four years, and has worked on more than 750 package validations during this period.

Ken has worked with large medical device companies that are part of the Fortune 500, as well as small, just off the Stability testing or half time change in the rate of a chemical ground, startup companies, and everything in between. reaction. For example, at 55° C, 6.5 weeks Ken holds an MS in Mechanical Engineering from Stability testing is done through accelerated is equivalent to one year on-the-shelf, two years University of Wisconsin-Madison. ageing and real-time ageing tests. Accelerated would be equivalent to 13.0 weeks and five ageing is a testing method used to estimate the years would be 32.5 weeks (assumes ambient About Life Science Outsourcing Inc useful lifespan of a product when actual lifespan temp = 25° C, and Q10=2). data is unavailable. This occurs with products Life Science Outsourcing is a FDA registered and Testing includes, but not limited to, that have not existed long enough to have gone ISO 13485 certified full service Medical Device Contract the following: through their useful lifespan. Manufacturer, located in Brea (Orange County), California. – ASTM F1980 Our services and capabilities provide clients with an A product can be released to market based opportunity to focus on running their business, while we Standard Guide for Accelerated Aging of Sterile upon successful accelerated ageing of the provide turnkey manufacturing, testing, validation, Barrier Systems for Medical Devices package/product that simulates the period sterilisation and distribution services. claimed for product expiration (e.g. one or two – ASTM D4332 LSO has worked with more than 250 start-ups since its years). Accelerated ageing data is recognised Standard Practice for Conditioning Containers, inception 15 years ago, resulting in more than 2.6 billion by regulatory bodies as an acceptable means Packages, or Packaging Components for Testing dollars in acquisitions for our clients. Regardless of the size to generate data quickly, but is only accepted of your company, we can address all of your specific until those tests can be repeated on real Summary outsourcing needs. We are able to provide clients with cradle time samples. to grave outsourcing solutions through our six divisions. The entire testing process is both costly An accelerated ageing test is carried out by To learn more about the various standards and processes and time consuming, lasting anywhere from subjecting the packaged product to unusually required to meet FDA/industry standards visit our website. 30 days to several months, so time and high levels of stress (controlled temperature finances should be planned accordingly. Divisions and humidity) designed to mimic the effects of normal storage. Before sterile medical device packaging Medical Device Manufacturing Medical Package Testing validation begins, an ISO 11607-1 compliant Accelerated ageing techniques are based on Sterilisation Validation Testing protocol should be developed and signed-off. the assumptions that the chemical reactions Fulfillment and Distribution Services involved in the deterioration of materials follow After testing is complete, a final report is Offshore Manufacturing Services the Arrhenius reaction rate function. This submitted which documents all test results, any LSO Incubator Services function states that a 10° C increase or corrective actions which were taken, and any 830 Challenger St, Brea, CA 92821 decrease in the temperature of a homogenous other pertinent information regarding testing T: (714) 672-1090 process, results in approximately a two times and packaging. W: www.lso-inc.com

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