If you are reading this, from one perspective or another, you probably know all too well the sentiment of “it’s just packaging” or “just put it in a pouch and box” without a deeper appreciation for the regulatory agency expectations on packaging development and validation. It’s not until the dreaded response from FDA comes back, filled with challenging comments about packaging, is it truly realized how technically complex a packaging project can be. We work with clients to develop a sound path forward and help to accelerate the process of getting their products to market.
Our team is in a unique position to see FDA feedback across a range of projects. For the benefit of industry, we want to highlight some of the recent feedback we have seen from FDA on new product submissions.
FDA Agency Thoughts on Sample Size
“The Agency recommends that the number of samples used in package integrity and shelf life test be large enough to provide for statistically significant analysis with a high degree of reliability; for example, 95% confidence at 95% reliability or greater. Accordingly, a minimum sample size of 60 is recommended for package integrity testing such as dye penetration, and a minimum sample size of 30 is recommended for testing such as seal strength. The Agency further recommends that a full set of data be generated for both inner and outer sterile barriers.”
FDA Agency ASTM vs ISTA Position
“The Agency recommends the use of FDA recognized consensus standards for conducting package integrity and shelf life validation testing (e.g., shipping and aging simulations, as well as package integrity and seal strength testing).
Your submitted materials cite ISTA Schedule 2A for testing. Please note that ISTA standards are not considered to be consensus standards and are not FDA-recognized. Please provide results from testing that conform to FDA-recognized standards, or provide a side-by-side comparison of your methods with FDA-recognized standards, and provide a scientifically valid rationale that supports the acceptability of any deviation(s) from FDA-recognized standards.”
FDA Agency Comment on Assurance Level I vs II
“You indicate the intended use of ASTM D4169, Distribution Cycle 13, and Assurance Level II. Please provide a scientifically valid justification for your selection of Assurance Level II.”
FDA Agency Input: Seal Strength Minimum Value
“While the Agency does not recognize an industry standard acceptance criterion for package seal strength; in general, packages with lower seal strengths may be more practical for smaller, lighter devices, whereas packages designed with greater seal strength may be more practical for containing devices of greater mass. Please provide a scientifically valid justification for your test acceptance criterion for seal strength for your packages.”
FDA Agency on Seal Strength Sampling
“The Agency recommends that data points for seal strength analysis be derived from individual packages. That is, multiple samples from a single unit packages will likely represent the same sealing process redundantly while sampling different packages will provide a more accurate representation of the variability within the process, between packages, and will provide more meaningful test data. For pouches that incorporate seals from the pouch manufacturer, as well as seals created by the medical device manufacturer, the Agency recommends that both be adequately represented in the final validation data – with no more than one data sample from each seal type.”
FDA Agency Advice Seal Strength Before and After Aging
“You provided dye penetration testing of the package seals following sterilization, environmental conditioning, distribution simulation, and accelerated aging. While this test demonstrates that the seals are intact, they do not demonstrate the strength of the seal and therefore, it is not possible to determine from the data whether the seals are decreasing in strength over time. As is stated in FDA’s Guidance for Sterility Information in Premarket Notification for Devices Labeled as Sterile, seal strength testing is recommended to demonstrate that the packaging is capable of maintaining a sterile seal both before and after aging. Please provide peel testing of the packages seals before and after aging.”