Validation of widefield microscope for ISO compliance help!

[Kelly Lundsten-2]

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Hi,
 
I was hoping someone in the community who has had to go through ISO 9001:2008 and ISO 1345:2003 certification could give us some feedback on what was required by their auditors to verify/validate the widefield microscopes in your facility.  We have an IX83 scope with an LED.  I assume we can use calibration slides, but which parameters are required?  Intensity, chromatic aberrations, spherical, etc??  How many parameters are enough to call an instrument "verified"?  We also have questions about how often you are required to calibrate and/or validate the scope?  Monthly, quarterly, yearly?  Is there anything about instrument validation for ISO compliance that we are overlooking?  Very open to experienced input.  
 
Anybody out there in industry that can help?
Thanks,
Kelly
 
 
Kelly Lundsten
Business Segment Manager, Advanced Cytometry
Email: [hidden email]
Telephone: [phone]
Website: www.biolegend.com
BioLegend
9727 Pacific Heights Blvd., San Diego, CA 92121, USA
 
This message (including any attachments) may contain confidential, proprietary, privileged and/or private information. The information is intended to be for the use of the individual or entity designated above. If you are not the intended recipient of this message, please notify the sender immediately, and delete the message any attachments. Any disclosure, distribution or other use of this message or any attachments by an individual or entity other than the intended recipient is prohibited.

[Jerry (Gerald) Sedgewick]

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Hi Kelly,
From my understanding, not every piece of equipment has to be validated in
ISO settings. Often microscopes and microscope labs are excluded from
validation as research areas. As long as there is a rationale that makes
sense, you can exclude instruments. Anyway, the ISO understanding is that
companies source from ISO compliant companies that have done internal
validation/qualification, and that is uncommon among microscope
manufacturers with some exceptions.

I, too, would like to hear from someone who has been audited, and not just
on the microscope, but the microscope system (microscope, camera,
acquisition software). If I were writing the regulatory documentation to
verify a microscope. it would only make sense to validate it for ways in
which you use it. If, for example, you are using it to screen small parts
for quality control on a visual basis, then you would validate the
microscope for its ability to resolve the components. You could use a
resolution standard on a microscope slide to validate resolution, or simply
go with the manufacturer's chart for resolution, especially when its
resolution isn't at a critical point. I'd go with the latter, because if you
use a slide for resolution, then it would have to be NIST certified, etc.

It wouldn't make sense to find lens characteristics such as coma, flare,
chromatic aberration, etc. if these do not significantly apply to what you
are doing. It would be like validating the characteristics of a motor inside
an instrument in a manufacturing setting.

As far as cleaning is concerned, that's your call. Quarterly is generally
enough, but it really depends on how you're using it. If you're using an oil
immersion lens, you'd also want to have a procedure for cleaning between
uses. Again, it depends on how it's being used.

If you are evaluating digital images, or if images are a part of your
procedure, then validation with a calibration system would be ideal. If I
were auditing, that would be something I'd want to see, even if the
procedure has some drawbacks that can't be addressed (such as the
consistency of stain colors in histology, limited by a visual evaluation of
color from the qualifying Biological Stain Commission versus something that
could be measured with a calibrated colorimeter). That doesn't mean,
however, that calibration can't be done. On the digital imaging end a
calibration slide can be used for chromatic stains, such as the slide
available through Datacolor (ChromaCal). The same for fluorescence. Some
means for calibrating even to a reference standard would have to be
included, or, as an auditor, I'd penalize. Plastic fluorescent standards are
available from several companies, and uranium slides can still be obtained
(can't remember the glass manufacturer at the moment).

Hope that provides some food for thought.

Jerry Sedgewick









-----Original Message-----
From: Kelly Lundsten
Sent: Tuesday, November 10, 2015 5:27 PM
To: [hidden email]
Subject: Validation of widefield microscope for ISO compliance help!

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Hi,

I was hoping someone in the community who has had to go through ISO
9001:2008 and ISO 1345:2003 certification could give us some feedback on
what was required by their auditors to verify/validate the widefield
microscopes in your facility.  We have an IX83 scope with an LED.  I assume
we can use calibration slides, but which parameters are required?
Intensity, chromatic aberrations, spherical, etc??  How many parameters are
enough to call an instrument "verified"?  We also have questions about how
often you are required to calibrate and/or validate the scope?  Monthly,
quarterly, yearly?  Is there anything about instrument validation for ISO
compliance that we are overlooking?  Very open to experienced input.

Anybody out there in industry that can help?
Thanks,
Kelly


Kelly Lundsten
Business Segment Manager, Advanced Cytometry
Email: [hidden email]
Telephone: [phone]
Website: www.biolegend.com
BioLegend
9727 Pacific Heights Blvd., San Diego, CA 92121, USA

This message (including any attachments) may contain confidential,
proprietary, privileged and/or private information. The information is
intended to be for the use of the individual or entity designated above. If
you are not the intended recipient of this message, please notify the sender
immediately, and delete the message any attachments. Any disclosure,
distribution or other use of this message or any attachments by an
individual or entity other than the intended recipient is prohibited.

[Jerry (Gerald) Sedgewick]

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Added Clarification. To clarify the Biological Staining Commission's (BSC)
quality control:  I made a blanket statement about BSC's method for
determining color in the last email to the confocal listserv. From a phone
call to BSC, I was told
that hematoxylin was evaluated after oxidation by comparing colors visually
between a reference and the new batch of hematoxylin. I didn't inquire about
other stains.

Jerry Sedgewick

-----Original Message-----
From: J. Sedgewick
Sent: Wednesday, November 11, 2015 6:59 AM
To: Confocal Microscopy List
Subject: Re: Validation of widefield microscope for ISO compliance help!

Hi Kelly,
From my understanding, not every piece of equipment has to be validated in
ISO settings. Often microscopes and microscope labs are excluded from
validation as research areas. As long as there is a rationale that makes
sense, you can exclude instruments. Anyway, the ISO understanding is that
companies source from ISO compliant companies that have done internal
validation/qualification, and that is uncommon among microscope
manufacturers with some exceptions.

I, too, would like to hear from someone who has been audited, and not just
on the microscope, but the microscope system (microscope, camera,
acquisition software). If I were writing the regulatory documentation to
verify a microscope. it would only make sense to validate it for ways in
which you use it. If, for example, you are using it to screen small parts
for quality control on a visual basis, then you would validate the
microscope for its ability to resolve the components. You could use a
resolution standard on a microscope slide to validate resolution, or simply
go with the manufacturer's chart for resolution, especially when its
resolution isn't at a critical point. I'd go with the latter, because if you
use a slide for resolution, then it would have to be NIST certified, etc.

It wouldn't make sense to find lens characteristics such as coma, flare,
chromatic aberration, etc. if these do not significantly apply to what you
are doing. It would be like validating the characteristics of a motor inside
an instrument in a manufacturing setting.

As far as cleaning is concerned, that's your call. Quarterly is generally
enough, but it really depends on how you're using it. If you're using an oil
immersion lens, you'd also want to have a procedure for cleaning between
uses. Again, it depends on how it's being used.

If you are evaluating digital images, or if images are a part of your
procedure, then validation with a calibration system would be ideal. If I
were auditing, that would be something I'd want to see, even if the
procedure has some drawbacks that can't be addressed (such as the
consistency of stain colors in histology, limited by a visual evaluation of
color from the qualifying Biological Stain Commission versus something that
could be measured with a calibrated colorimeter). That doesn't mean,
however, that calibration can't be done. On the digital imaging end a
calibration slide can be used for chromatic stains, such as the slide
available through Datacolor (ChromaCal). The same for fluorescence. Some
means for calibrating even to a reference standard would have to be
included, or, as an auditor, I'd penalize. Plastic fluorescent standards are
available from several companies, and uranium slides can still be obtained
(can't remember the glass manufacturer at the moment).

Hope that provides some food for thought.

Jerry Sedgewick









-----Original Message-----
From: Kelly Lundsten
Sent: Tuesday, November 10, 2015 5:27 PM
To: [hidden email]
Subject: Validation of widefield microscope for ISO compliance help!

*****
To join, leave or search the confocal microscopy listserv, go to:
http://lists.umn.edu/cgi-bin/wa?A0=confocalmicroscopy
Post images on http://www.imgur.com and include the link in your posting.
*****

Hi,

I was hoping someone in the community who has had to go through ISO
9001:2008 and ISO 1345:2003 certification could give us some feedback on
what was required by their auditors to verify/validate the widefield
microscopes in your facility.  We have an IX83 scope with an LED.  I assume
we can use calibration slides, but which parameters are required?
Intensity, chromatic aberrations, spherical, etc??  How many parameters are
enough to call an instrument "verified"?  We also have questions about how
often you are required to calibrate and/or validate the scope?  Monthly,
quarterly, yearly?  Is there anything about instrument validation for ISO
compliance that we are overlooking?  Very open to experienced input.

Anybody out there in industry that can help?
Thanks,
Kelly


Kelly Lundsten
Business Segment Manager, Advanced Cytometry
Email: [hidden email]
Telephone: [phone]
Website: www.biolegend.com
BioLegend
9727 Pacific Heights Blvd., San Diego, CA 92121, USA

This message (including any attachments) may contain confidential,
proprietary, privileged and/or private information. The information is
intended to be for the use of the individual or entity designated above. If
you are not the intended recipient of this message, please notify the sender
immediately, and delete the message any attachments. Any disclosure,
distribution or other use of this message or any attachments by an
individual or entity other than the intended recipient is prohibited.

[Julien CAU-2]

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Hi Kelly,

Our facility is ISO9001 compliant since 2009. I guess you are referring to ISO 13485:2003 rather than ISO 1345:2003. The picture depicted below is probably much different for ISO13485.

As for ISO9001 compliance, it is up to you to consider what will impact the users results and its subsequent satisfaction. What the auditors then checks is whether all the quality checks you run make sense with respect to what you defined as important for final result/satisfaction. For instance, we wrote at some point that room temperature was an important parameter (for system or LASER alignment stability), then the Lloyds auditor requested us to save all temperature recordings and define the number of measurements over/under temperature thresholds that will engage some action.
In this respect, Jerry is absolutely right : there is no need to run tests that do not make any sense for the final user. As you have to prove that you run the tests you defined, you don't want to go too far if this makes no sense.

If you mine the list archive, you will find many discussions about the quality insurance tests.

The quality check we run here are (widefield or other systems) :
- temperature (room, incubator),
- C02 concentration,
- visual inspection of objectives and filters
- microscope realignment,
- field homogeneity (BF and fluorescence),
- pinhole adjustment,
- LASER power measurements,
- Chromatic aberration correction,
- FWHM measurements for all channels,
- detector behavior (CV, linearity, etc...),
- hot pixels, cold pixels, dead pixels for CCDs/sCMOS,
- detector/dichroics comparisons (see below),
- fluorescence source stability over time,
- scanner linearity,
- AOTF/AOM behavior (linearity/calibration),

Whenever you use a meter (CO2, powermeter, etc...), you need to prove the auditor this is calibrated, otherwise that would not make so much sense. We compare meters to each other, to some calibrated source and send them for calibration whenever needed.

More tests would probably be useful, but at some point this is highly time-consuming and you have to consider the added value of a new test and whether this is worth it.

We use various beads and slides (fluosphere of various diameters, inspeck beads, focal check beads, fluorescent plastic slides - aka chroma slides - we get from The Microscopy and Imaging Place, sample tests slides from Leica/Zeiss/Molecular Probes, mirrors, rulers such as USAF1951/Richardson test slides). We considered SIPCharts as well. We tested different slides from Argolight, and are still considering using them. As for today, their slides however would not replace all our test slides nor are the tested slides suitable for all LASER lines (this is no fluorescence). In the best world, we could run all automatized tests with a single slide. We have not yet reached this. That would make life obviously easier and reasonable quality check frequency higher.

We use in-house adaptations of an ImageJ Plugin designed by Fabrice Cordelières and colleagues (MetroloJ) for most of the tests. This plugin is used by tens of imaging facilities (most of them in France I guess!). We run the test analysis while acquiring next step, new test images, so that no time is lost between test images acquisition and final test result. We defined acceptance thresholds for all these parameters. These threshold were either defined from the manufacturers acceptance values or from theoretical values. Whenever the system is running under these thresholds, we call the service.

Among these tests the frequency varies :
- monthly check for the first parameters (up to chromatic aberration),
- yearly check for the rest. It would make more sense to run these tests more often but at some point with >10 systems, this is highly time consuming,
- we run any test at any time we consider there might be a problem with a given system.
We adapt the frequency to the microscope actual usage.

We also request some external servicing of all systems (either through the PM included in our confocal service contracts, or through a third party company) so that we get an external overview of the system.

As for light path/detectors comparisons, we compare detectors/dichroic (aka any light path combination) using arbitrary parameters so that we have an idea of what are the best parameters that users can adopt. This is more a global measure that many parameters can affect (pinhole position, dichroic, detector, etc...) but at the end, this is what the users are looking for). Here are also considered sample test slides. User don't look at beads and don't care our beads. The use real sample. We thus use some real, stable samples so that we are closer to what they care about.

Some of our systems have dedicated maintenance schemes/tests obviously (such as our SIM microscope or FLIM systems for instance) and we run more tests, more often (up to every day for some tests), use the manufacturers routines or ImageJ plugins (SIMCheck plugin from our MicronOxford colleagues for instance). Obviously, FLIM systems use specific standards, etc...

Conclusion : as for ISO9001 compliance in the context of microscopy or any other context, it is up to you to say what you do, do what you say, prove it and improve it!
Best
Julien

--
____________________________________________
Julien Cau, PhD.
Montpellier RIO Imaging Facility /plate-forme d'imagerie Montpellier RIO Imaging
Montpellier BIOCAMPUS, UMS3426
Arnaud de Villeneuve Campus
Institut de Génétique Humaine-CNRS
141, rue de la Cardonille F-34396 Montpellier cedex 5 (France)
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phone: [phone]
mobile: [phone]
fax: [phone]
URL: http://www.mri.cnrs.fr/
____________________________________________

-----Message d'origine-----
De : Confocal Microscopy List [mailto:[hidden email]] De la part de Kelly Lundsten
Envoyé : mercredi 11 novembre 2015 00:27
À : [hidden email]
Objet : Validation of widefield microscope for ISO compliance help!

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*****

Hi,
 
I was hoping someone in the community who has had to go through ISO 9001:2008 and ISO 1345:2003 certification could give us some feedback on what was required by their auditors to verify/validate the widefield microscopes in your facility.  We have an IX83 scope with an LED.  I assume we can use calibration slides, but which parameters are required?  Intensity, chromatic aberrations, spherical, etc??  How many parameters are enough to call an instrument "verified"?  We also have questions about how often you are required to calibrate and/or validate the scope?  Monthly, quarterly, yearly?  Is there anything about instrument validation for ISO compliance that we are overlooking?  Very open to experienced input.  
 
Anybody out there in industry that can help?
Thanks,
Kelly
 
 
Kelly Lundsten
Business Segment Manager, Advanced Cytometry
Email: [hidden email]
Telephone: [phone]
Website: www.biolegend.com
BioLegend
9727 Pacific Heights Blvd., San Diego, CA 92121, USA
 
This message (including any attachments) may contain confidential, proprietary, privileged and/or private information. The information is intended to be for the use of the individual or entity designated above. If you are not the intended recipient of this message, please notify the sender immediately, and delete the message any attachments. Any disclosure, distribution or other use of this message or any attachments by an individual or entity other than the intended recipient is prohibited.