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Before you set out to validate a package design or 10 Things You Should process, you’ve got to do your homework. “You need to understand what is critical so you build the proper foundation,” explains Scott Levy, senior packaging engineer for DDL, a testing that Do Before You Validate serves the medical device packaging community. If your company is marketing a sterile medical device, “your goal is to develop a Your Next Package sterile barrier system and avoid a breach of that system,” he says. With DDL for nearly 20 years, Levy helps medical device packaging professionals with package testing programs to support package design and process validation. He offers the following 10 points to consider before beginning any validation effort.

Understand the requirements for a specific intended 1 regulatory requirements use can be consistently fulfilled.” It (FDA, EU, etc.) defines process validation as “es- In general, regulators expect you to tablishing by objective evidence that prove that your packaging system a process consistently produces a ensures sterility maintenance of that result or product meeting its prede- device and to confirm the consistency termined specifications.” of your processes, explains Levy. Expectations for device packag- Quality System Regulation in the ing are described under 21 CFR Part United States defines validation (un- 820.130: “Each manufacturer shall Package integrity testing is important in determining the sterility and the of der 21 CFR Part 820.3) as “confirma- ensure that device packaging and a medical device or product. Package integrity testing includes dye leak, vacuum tion by examination and provision of shipping are designed and leak, and bubble leak testing. objective evidence that the particular constructed to protect the device from

1 alteration or damage during the cus- Read and familiarize device development,” says Levy. For tomary conditions of processing, stor- 2 yourself with ISO 11607 instance, “get the geometry of the age, handling, and distribution.” It also so you understand your product and work toward the ship- outlines expectations for medical device validation responsibilities ping configuration. A lot of times this design controls (21 CFR Part 820.30), To obtain a CE mark for marketing happens at the end, and then you run including design validation. If your med- your medical device in the EU, you into problems. Get involved early and ical device is intended to be labeled as must be in compliance with ISO work closely with your entire team— sterile, you are expected to establish 11607. The good news is that ISO these professionals can help you fur- and maintain procedures for validating 11607 is also recognized by the U.S. ther understand the risk assessment the sterile barrier system for that device. FDA as a consensus standard, so if of the device so you can plan sample Process validation is outlined under you are in conformance with it, you sizes accordingly.” Accelerated aging is performed on 21 CFR Part 820.75, which explains will have a much easier time comply- Also, during product design verifi- materials, products, and packaging “where the results of a process cannot ing with the FDA. “It’s fantastic—it cation, “conduct feasibility testing to systems including packaged medical be fully verified by subsequent inspec- spells out exactly what you need to understand the product and package devices to provide a theoretical tion and test, the process shall be vali- do for sterility maintenance,” explains interactions,” he says. “You can then equivalent to real time shelf life. dated with a high degree of assurance Scott Levy. “Part 1 covers materials, avoid later problems during testing.” and approved according to established and Part 2 covers processes.” Part 1 procedures.” The European Union’s 3.28 defines validation in general, and Perform a risk Talk to your suppliers Medical Device Directives state (in 3.29 defines process validation. And 4 assessment of the 5 and service providers Annex I 8.3) that “devices delivered in a the document goes into greater depth medical device you sterile state must be designed, manu- throughout both parts, particularly on are packaging “Your vendors have a lot of knowl- factured, and packed in a non-reusable installation qualification, operational Determine the specified attribute edge about materials and processes, pack and/or according to appropriate qualification, and performance qualifi- for your package, identify all potential especially when it comes to materials procedures to ensure that they are cation (IQ/OQ/PQ). failure modes that could cause (or for packages such as pouches and sterile when placed on the market and result from) an out-of-specification trays, for instance,” he says. Get as remain sterile, under the storage and Get your package package, and then determine the much data as possible from mate- transport conditions laid down, until 3 professionals involved sample size needed to catch those rial providers, thermoformers, and the protective packaging is damaged upfront in the product failures. “The chosen sample size and package , and don’t forget or opened.” The directives also state design process resulting confidence level will depend to work closely with machinery pro- (in Annex I 8.4) that “devices delivered “Packaging professionals should be upon the overall risk assessment viders, who in addition to providing in a sterile state must have been manu- working with colleagues in regulato- (Failure Mode Effects Analysis; FMEA) process validation support might also factured and sterilized by an appropri- ry, product development, and quality that the MDM puts in place for any consult on material performance. ate, validated method.” as early as possible during medical given device,” says Levy. “The last step would be to work with

2 PMP News SmartGuide a qualified and knowledgeable test Know your worst cases I need a shelf ? Or are there other laboratory that not only understands 7 “Review your product fami- elements within that box to help miti- the regulatory requirements, but can lies to define all worst- gate the potential for abrasion issues, further guide and partner with you scenarios,” says Levy. “For instance, etc.?” He also cautions against folding to make sure that specific regulatory for a family of catheter products, pouches to make them fit properly requirements are being met,” he says. decide which catheter you feel is into a pre-existing configuration. “If a the worst case. You then may not package is folded, consider what may Write your packaging need to test the other family members happen with that particular product at 6 protocol and establish that are similar. When identifying a that folded intersection,” he says. clear acceptance criteria worst case, look for the heaviest, the “Your protocol should have the follow- lightest, the largest, and the smallest. Understand the ing: a purpose, a scope, a reference It is a hard question to answer, but 8 differences between section listing all standards and test you are looking for what potentially package seal strength procedures, descriptions of all mate- can cause the most adverse effects and whole package integrity as rials and equipment, all attribute data, to the package.” You’ll also want to well as stability testing and Medical device manufacturers obtaining 510(k) approval on medical a sequence of events or a flow chart ensure that the product materials are package performance devices use a variety of testing to of what will transpire, and a summary the same, he adds. “People start using test methods ensure the integrity of the medical of the chosen sample size and accep- You should also consider how the before they understand the stan- device packaging and compliance tance criteria,” says Levy. “It is import- particular package would be packed dards,” says Levy. “For instance, they with ISO standards, such as ISO ant to document everything. And the out in your shipping configuration. “Will start using ASTM F88 [Standard Test 11607. protocol can help you manage your Method for Seal Strength of Flexible processes with outside vendors. We Barrier Materials] before they realize can help customers put it all together.” that there are three different methods Gross Leaks in Packaging by Internal Levy adds that some companies within this procedure. Or they test for Pressurization [Bubble Test]), says have long-established protocols that a 1-lb minimum seal strength without Levy. Engineers should also consider may appear to be “set in stone.” Such even knowing where that specification the microbial barrier properties of the an approach may help packaging came from.” materials selected for their sterile bar- professionals meet minimum quality In addition, engineers cannot rier system. It is important to note that system thresholds, but “it is important solely test packages for seal strength. validated physical package integrity to stay on top of all new standards Packaging engineers also need to test methods can sufficiently demon- and allow the potential use of them,” test for whole package integrity, us- strate sterility maintenance (instead of he says. In addition, it could be miss- ing a method such as ASTM F2096 using whole package microbial chal- Photo of bubble immersion. ing “new key attributes.” (Standard for Detecting lenge testing).

3 PMP News SmartGuide Another major issue, says Levy, is package integrity. Separating these How does the new standard In addition, “Use your suppliers “you cannot just use the tests without evaluations allows you to identify the an older validation? Am I still in com- and leverage their knowledge and use going through test method validation. causes of seal failure or compromised pliance? And a gap analysis is also them as a sounding board,” Levy ad- The difference between ‘guides and integrity. necessary if there is a change in vises. “As I tell my customer, we are all standards’ is the guides provide a road- Bottom line: understand what you packaging materials or processes.” in this together to help bring safe and map, and the standards tell you how to are testing, look for test methods that effective devices to market. We need drive. Following the standard allows you have been validated, and then validate Make sound technical to get this right.” to compare your own results to those in that you can perform them according 10 science-based the precision and bias statements.” to the standardized methods. “We justifications if needed In the end, medical device pack- Testing will also likely be performed challenge our customers a lot to justify If making a justification, you need to aging professionals simply need to in stages. ISO 11607 separates why they are performing a given test,” take a look at all factors for a partic- understand what they are putting stability testing from performance he says. ular justification and make it science into packages, says Levy. “If they testing, unless you don’t have enough based and defendable, Levy advis- do their homework with materials samples for testing, advises Levy. Do a gap analysis of the es. “When making any justification, and processes and understand what Stability testing looks at the effects of 9 test standards that you you need to look further at all risks they need to do before validation, aging on seal strength and package have previously utilized involved, whether it is product based they’ll build a successful validation integrity and helps you determine to what is current or packaging based. Too many times, program.” a shelf life, whereas performance You’ll want to do a gap analysis when organizations are trying to meet a testing looks at the effects of handling any new standards are released, he timeline and utilize loose justifications and distribution on seal strength and adds. “Ask yourself these questions: in order to meet that timeline.”

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