[3] ISO 11607-1:2019 Packaging for terminally sterilized medical devices — Part 1: Requirements for materials, sterile barrier systems and packaging systems

ISO 13485:2016, 7.5.6 – Validation of processes for production and service provision requires the organization in bullet point d) to, as appropriate, document statistical techniques with rationale for sample sizes [2].

ISO 13485:2016, 4.1.2 requires in bullet point b) that the organization shall apply a risk-based approach to the control of the appropriate processes needed for the quality management system.

ISO 16269-6 provides k-values for the statistical tolerance interval analysis based on the type of distribution (attribute or variable), confidence levels (90%, 95%, 99%), probability (also reliability) levels (again 90%, 95%, 99%), and sample sizes.

Other standards such as the ISO 11607:2019 have similar requirements. ISO 11607:2019 Part 1, 4.3 – Sampling requires that sampling plans are based upon statistically valid rationales [3].

But not only do ISO standards require valid statistical rationale, but the U.S. FDA also has a similar requirement in TITLE 21 CFR 820.250 – Statistical techniques – and a very serious about it, as seen here.

A sample is representative when it represents the population being studied and can either be a random sample, stratified or periodic sample.

[1] Taylor, Wayne (2017). Statistical Procedures for the Medical Device Industry. Taylor Enterprises, Inc., www.variation.com

Wait… you don't know how? This does not ring a bell, and you still have no clue how you should do it? No worries, we'll explain this further....

To answer the above question: Again, it depends – Evaluate the risk of factors affecting the process, relate the average and standard deviation to the specifications, and do some math!

Again, something you do not know what it is? Check out our blog post about "Statistical Tolerance Intervals – Explained simply and practically based on ISO 16269-6".

The confidence level (C) and probability level (P) allow us confidence statements like “With C% confidence, more than P% of units conform to requirements”.

3 samples will most likely not be representative for an injection molding process to allow temperatures, pressures speeds, etc., to vary over their entire range, nor can you prove a normal distribution with 3 samples.

While this definition connects certain probability (also reliability) levels with product risks, a minimum of 95% confidence must be used unless a justification is provided [1].

In a stratified sample, an equal number of units are selected from each collection tray, and every nth unit is selected in a periodic sample.

ISO 16269 is a standard that talks about statistical interpretation of data, part 6 of this standard explain the “Determination of statistical tolerance intervals”.

A valid rationale (sometimes referred to as justification) is based on the risk (or severity) and thus on the intended use of the product we are considering – easy, right?

To explain the connection to Medical Device Risk Management, we first need to look at the common approach used for the statistical interpretation of data.

According to ISO 14971, an organization must define its risk acceptability for individual and overall residual risks [6].