Validation Sample Size for Tray Seal

#1
I'm working on a tray seal validation for a sterile medical device. We have already qualified this packaging system on a single nest sealer, but we are moving it to a multi-cavity sealer and it is causing quite a debate about sample sizing.

We are taking 8 peel strength samples from defined locations around the tray and have a nest that can process 4 trays simultaneously. The debate is whether each peel location of each tray should count as 1 sample, or if due to lack independence between sample locations, each "run" of 4 trays really only counts as 1 sample, or somewhere in the middle.

What have you all done to address validation of multiple units per machine cycle and with multiple measurements per unit?
 
Elsmar Forum Sponsor

William55401

Quite Involved in Discussions
#2
Do you have very good existing variable data on the capability of your existing process? Can you leverage these variable stats to minimize sample size? IMHO: If you sampled 4 locations on your one up sealer and had a sample size for that, you need to do the same on each 4 up. The opportunity here is if you can leverage variable stats to perform a difference test (t test) on the 4 up version. Hope this helps.

Said differently... you should have the same (or better) statistical confidence / reliability in the 4 up as the 1 up. Leverage your experience to get there and potential reduce sample size from the initial one up qualification.
 

SylvieS

Starting to get Involved
#3
I'm working on a tray seal validation for a sterile medical device. We have already qualified this packaging system on a single nest sealer, but we are moving it to a multi-cavity sealer and it is causing quite a debate about sample sizing.

We are taking 8 peel strength samples from defined locations around the tray and have a nest that can process 4 trays simultaneously. The debate is whether each peel location of each tray should count as 1 sample, or if due to lack independence between sample locations, each "run" of 4 trays really only counts as 1 sample, or somewhere in the middle.

What have you all done to address validation of multiple units per machine cycle and with multiple measurements per unit?

... did you have an answer - I am facing the same issue currently. My initial assumption is that counting each cavity as a sample will not provide me sufficient confidence of quality within a batch - but I can't seem to explain it statistically.
 
#4
I never got a satisfactory answer, but the approach I took was to base the sample sizing on the number of sealer runs, but then to sample tray/peel locations randomly from within each run (I did three, but somewhat arbitrarily). That gave us an overall peel strength sample size of 59 * 3 = 177 rather than the 59 * 4 * 8 = 1888 samples it would have taken to measure every location of every cavity.

The idea with the approach we took being that if all the stats pass, then the cavities must be similar enough (or at least not different enough relative to the spec limits). I don't know for certain that it is statistically kosher, but it kind of makes sense in my head and hasn't raised any flags with auditors so far. If it didn't pass, we would have then supplemented with a peel strength test from one randomly sampled location from each cavity of each run and analyzed each cavity in isolation.

I also did an on the side analysis for my personal amusement to see if I could map strength values across the whole nest. I did find (weakly at the number of samples I had) that one area of one cavity generally had the highest seal strength, and a particular position in two cavities tended to have the lowest peel strength across each sealer run. Based on that, I rolled out control charts using those 3 locations plus 2 more randomly as our ongoing process monitoring samples. So far so good on that front as well.
 

MSterling

Starting to get Involved
#5
I'm working on a tray seal validation for a sterile medical device. We have already qualified this packaging system on a single nest sealer, but we are moving it to a multi-cavity sealer and it is causing quite a debate about sample sizing.

We are taking 8 peel strength samples from defined locations around the tray and have a nest that can process 4 trays simultaneously. The debate is whether each peel location of each tray should count as 1 sample, or if due to lack independence between sample locations, each "run" of 4 trays really only counts as 1 sample, or somewhere in the middle.

What have you all done to address validation of multiple units per machine cycle and with multiple measurements per unit?
Hello Joe,
WARNING: Exercise extreme caution when changing from single nest to multiple nests. Tray sealing is a pressure-dependent process, so if you're changing the total seal area by a factor of 4, you need to address the pressure requirements to pull it off. It's complicated, and not a no-brainer. Work with your sealer supplier to ascertain what this additional need will be. (Also, what else is sharing your air pressure supply line?)

As far as sampling, I suggest you take one tray from each cavity and do an ASTM F88 seal strength perimeter study around the whole tray for all four. It will give you a profile that will inform further decisions. It's best practice to know as much about your tray and seal as possible, so it gets down to metrology. How this is done is this:
1. Decide on a corner to start on. Mark off 1.5" all around the tray seal flange and number them. These will be what you cut your 1" sample from for F88.
2. Carefully cut them from the tray using shears, razor blade or heavy duty scissors, maintaining tray and location ID always.
3. From these sections, carefully cut out your test strips. Precision counts in all things F88.
4. Peel test each test strip and from the data, create your profile. When you plot the data, certain things will pop to the top.
5. You can determine at which area of the tray you get your lowest seal strength (likely at your deepest draw). Here is where you test your tray for minimum seal strength. And it may be different for each nest (one would hope not).

Happy trails! Cheers,
Michael
 
Thread starter Similar threads Forum Replies Date
P Unrealistic Packaging Validation Sample Size 21 CFR Part 820 - US FDA Quality System Regulations (QSR) 41
T Sample Size for Design Validation Design and Development of Products and Processes 4
R Sample size for clinical validation/investigation EU Medical Device Regulations 4
R Process Validation sample size selection Statistical Analysis Tools, Techniques and SPC 0
R Determining Sample Size for Medical Device Component Validation Inspection, Prints (Drawings), Testing, Sampling and Related Topics 0
P Cleaning and Disinfection Validation Sample Size of 3? Other Medical Device Related Standards 2
G Sampling Plan - Sample Size Justification for a Bottling Cleaning Process Validation Qualification and Validation (including 21 CFR Part 11) 2
P Sterile Medical Packaging and Shelf Life Validation Sample size ISO 13485:2016 - Medical Device Quality Management Systems 10
G Sample Size for Design Verification and Validation 21 CFR Part 820 - US FDA Quality System Regulations (QSR) 6
E Determining Sample Size for Design Verification and Design Validation Other Medical Device and Orthopedic Related Topics 20
L Sample size for validation run with product users 21 CFR Part 820 - US FDA Quality System Regulations (QSR) 1
M Sample Size in Design Verification & Process Validation Inspection, Prints (Drawings), Testing, Sampling and Related Topics 2
Q Determining Sample Size for FDA Verification and Validation Activities Inspection, Prints (Drawings), Testing, Sampling and Related Topics 41
Q Determining the Appropriate Sample Size for Process Validation/Qualification Inspection, Prints (Drawings), Testing, Sampling and Related Topics 13
N Design Verification & Process Validation - Statistical sample sizes Design and Development of Products and Processes 2
N ETO Sterilisation Validation - EO Residual Minimum Sample Requirement ISO 13485:2016 - Medical Device Quality Management Systems 2
M Validation Sample Sizes and Selection: An Example Inspection, Prints (Drawings), Testing, Sampling and Related Topics 10
B Sample Sizes for In-Vivo Design Validation Testing Other Medical Device and Orthopedic Related Topics 1
S Which sample to use for PV (Production Validation) or DV (Design Verification) tests Manufacturing and Related Processes 4
Q Differences between Sample Sixes for Design Verification vs. Process Validation ISO 13485:2016 - Medical Device Quality Management Systems 2
A Sample Sizes for Process Validation - Medical device manufacturer ISO 13485:2016 - Medical Device Quality Management Systems 6
L Validation of mixers Qualification and Validation (including 21 CFR Part 11) 0
B How to satisfy clause 5.7.1.5 process validation for valve production API 6D Oil and Gas Industry Standards and Regulations 13
A Applying agile model for Computer system Validation Medical Device and FDA Regulations and Standards News 2
H Production Validation- CE Mark ISO 13485:2016 - Medical Device Quality Management Systems 3
Watchcat Software validation vs design V&V? Other US Medical Device Regulations 27
M Initial Importer/Distributor and Software Validation IEC 62304 - Medical Device Software Life Cycle Processes 1
P Test Method Validation (TMV) for all Measurement Methods in Rec/Inspection Gage R&R (GR&R) and MSA (Measurement Systems Analysis) 0
M Validation of Data verification tool per 21 CFR 820 Quality Assurance and Compliance Software Tools and Solutions 1
G Number of Destructively Tested Devices Needed for Ethylene Oxide Validation Other Medical Device Related Standards 4
E ISO 13485 software validation ISO 13485:2016 - Medical Device Quality Management Systems 7
R SAP B1 Computer System Validation Qualification and Validation (including 21 CFR Part 11) 0
A GAGE R&R Binomial with master list (for method validation) Gage R&R (GR&R) and MSA (Measurement Systems Analysis) 0
Y ISO 13485:2015 Software Validation IQ/OQ/PQ ISO 13485:2016 - Medical Device Quality Management Systems 13
N Validation of special processes - thread closed Oil and Gas Industry Standards and Regulations 3
L Validation without Tolerance Qualification and Validation (including 21 CFR Part 11) 0
shimonv Test Method Validation ISO 13485:2016 - Medical Device Quality Management Systems 10
R Debug mode in software/device validation IEC 62304 - Medical Device Software Life Cycle Processes 2
M Software verification and validation AS9100 AS9100, IAQG, NADCAP and Aerospace related Standards and Requirements 4
Melissa Process Validation of Rotary Heat Sealer Speeds Design and Development of Products and Processes 4
C Validation of process for releasing the UDI EU Medical Device Regulations 4
C Validation of process for production and servicing 5.7.1.5 API Spec Q1, 9th Edition Oil and Gas Industry Standards and Regulations 9
W Transport validation Qualification and Validation (including 21 CFR Part 11) 4
M Is validation required when consumables are changed Qualification and Validation (including 21 CFR Part 11) 7
C 8.3.4 Verification and Validation ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 4
W Transport validation Qualification and Validation (including 21 CFR Part 11) 12
mustomutlu Process Validation Final Report Other Medical Device and Orthopedic Related Topics 2
P Software verification and validation procedure IEC 62304 - Medical Device Software Life Cycle Processes 6
Y SaMD Verification and Validation SOP and Plan IEC 62304 - Medical Device Software Life Cycle Processes 8
C Spreadsheet Validation and Release Qualification and Validation (including 21 CFR Part 11) 2

Similar threads

Top Bottom