Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

We are submitting our DV module of the PMA in February 2022 and manufacturing module of the PMA in June 2022. 

1. Do we need to submit the Test Method Validations (TMV) as a part of these modules? 
2. Would FDA review the TMV during their inspection audit?

Please educate me on this topic as I don't have experience about this.

Hello Anon,

To answer your questions simply:
1. Yes
2. Sometimes

For test method validations we typically included this in the design information and if this was something performed as part of manufacturing testing would included or reference there as well.  We would especially include this if the test method was unique to the device where we had developed our own acceptance criteria.  This of course depends on the type of device and type of testing because if fairly straightforward or a modification of existing testing maybe is not so critical.

During the PAI they are typically reviewing the quality management system and manufacturing activities.  Depending on the testing method and level of detail they get into depends on if they review the test method validation.  I have experienced they want to see results of testing as part of the manufacturing process for validation lots and initial lots, but typically the methodology would have already been reviewed.  The approach I would take is look at this from the perspective of someone not knowing anything about your device and product (and testing).  If the information associated with the test methods needs to be provided or more clear to an external person, then include to ensure no mis-understanding or delay in request for additional information.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs
------------------------------

Original Message:
Sent: 02-Sep-2021 01:28
From: Anonymous Member
Subject: Test Method Validations

This message was posted by a user wishing to remain anonymous

We are submitting our DV module of the PMA in February 2022 and manufacturing module of the PMA in June 2022.

1. Do we need to submit the Test Method Validations (TMV) as a part of these modules? 
2. Would FDA review the TMV during their inspection audit?

Please educate me on this topic as I don't have experience about this.

This message was posted by a user wishing to remain anonymous

Hi Richard,

I shared the TMV requirement with my quality and R&D team and there is some push back to understand if having TMVs is a true FDA requirement or it is nice to have. I tried to look into the regulations (CFR) but could not find anything which specifically broach the topic of method validation. It alludes to it in equipment qualification, statistical methods, process validation, design controls, and other sections. 

Would you be able to direct me to the actual FDA regulation which I can use to back my reasoning? 
Any help is highly appreciated. 
Thanks
Original Message:
Sent: 03-Sep-2021 03:58
From: Richard Vincins
Subject: Test Method Validations

Hello Anon,

To answer your questions simply:
1. Yes
2. Sometimes

For test method validations we typically included this in the design information and if this was something performed as part of manufacturing testing would included or reference there as well.  We would especially include this if the test method was unique to the device where we had developed our own acceptance criteria.  This of course depends on the type of device and type of testing because if fairly straightforward or a modification of existing testing maybe is not so critical.

During the PAI they are typically reviewing the quality management system and manufacturing activities.  Depending on the testing method and level of detail they get into depends on if they review the test method validation.  I have experienced they want to see results of testing as part of the manufacturing process for validation lots and initial lots, but typically the methodology would have already been reviewed.  The approach I would take is look at this from the perspective of someone not knowing anything about your device and product (and testing).  If the information associated with the test methods needs to be provided or more clear to an external person, then include to ensure no mis-understanding or delay in request for additional information.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs

Original Message:
Sent: 02-Sep-2021 01:28
From: Anonymous Member
Subject: Test Method Validations

This message was posted by a user wishing to remain anonymous

We are submitting our DV module of the PMA in February 2022 and manufacturing module of the PMA in June 2022.

1. Do we need to submit the Test Method Validations (TMV) as a part of these modules? 
2. Would FDA review the TMV during their inspection audit?

Please educate me on this topic as I don't have experience about this.

Hello,

You will not find any specific requirements or statement in a regulation for test method validation.  The closest you will get is in topics which you stated like process validation and design controls.  Maybe you could reference ASTM E2857 for analytical methods.  What you will find is different books and papers on the subject, but nothing which would be specific to the regulations.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs
------------------------------

Original Message:
Sent: 13-Sep-2021 12:37
From: Anonymous Member
Subject: Test Method Validations

This message was posted by a user wishing to remain anonymous

Hi Richard,

I shared the TMV requirement with my quality and R&D team and there is some push back to understand if having TMVs is a true FDA requirement or it is nice to have. I tried to look into the regulations (CFR) but could not find anything which specifically broach the topic of method validation. It alludes to it in equipment qualification, statistical methods, process validation, design controls, and other sections.

Would you be able to direct me to the actual FDA regulation which I can use to back my reasoning?
Any help is highly appreciated.
Thanks
Original Message:
Sent: 03-Sep-2021 03:58
From: Richard Vincins
Subject: Test Method Validations

Hello Anon,

To answer your questions simply:
1. Yes
2. Sometimes

For test method validations we typically included this in the design information and if this was something performed as part of manufacturing testing would included or reference there as well.  We would especially include this if the test method was unique to the device where we had developed our own acceptance criteria.  This of course depends on the type of device and type of testing because if fairly straightforward or a modification of existing testing maybe is not so critical.

During the PAI they are typically reviewing the quality management system and manufacturing activities.  Depending on the testing method and level of detail they get into depends on if they review the test method validation.  I have experienced they want to see results of testing as part of the manufacturing process for validation lots and initial lots, but typically the methodology would have already been reviewed.  The approach I would take is look at this from the perspective of someone not knowing anything about your device and product (and testing).  If the information associated with the test methods needs to be provided or more clear to an external person, then include to ensure no mis-understanding or delay in request for additional information.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs

Original Message:
Sent: 02-Sep-2021 01:28
From: Anonymous Member
Subject: Test Method Validations

This message was posted by a user wishing to remain anonymous

We are submitting our DV module of the PMA in February 2022 and manufacturing module of the PMA in June 2022.

1. Do we need to submit the Test Method Validations (TMV) as a part of these modules? 
2. Would FDA review the TMV during their inspection audit?

Please educate me on this topic as I don't have experience about this.

In FDA/industry joint training programs (like AAMI's process validation courses) I've seen FDA repeatedly, and as a general rule, categorize test method validation under FDA's process validation regulation in 21 CFR 820.75.  A test process,  like any other production process, is to be screened for the need for process validation.  For example, in a February 19, 2002 Warning Letter, FDA states, "...[we]...collected information that revealed serious regulatory problems...as follows:...Failure to validate with a high degree of assurance a process that cannot be fully verified by subsequent inspection and test as required by 21 CFR 820.75(a). For example:...The testing procedure used for...has not been validated..."

------------------------------
Kevin Randall, ASQ CQA, RAC (U.S., Europe, Canada)
Principal Consultant
Ridgway, CO
United States
© Copyright 2021 by ComplianceAcuity, Inc. All rights reserved.
------------------------------

Original Message:
Sent: 13-Sep-2021 12:37
From: Anonymous Member
Subject: Test Method Validations

This message was posted by a user wishing to remain anonymous

Hi Richard,

I shared the TMV requirement with my quality and R&D team and there is some push back to understand if having TMVs is a true FDA requirement or it is nice to have. I tried to look into the regulations (CFR) but could not find anything which specifically broach the topic of method validation. It alludes to it in equipment qualification, statistical methods, process validation, design controls, and other sections.

Would you be able to direct me to the actual FDA regulation which I can use to back my reasoning?
Any help is highly appreciated.
Thanks
Original Message:
Sent: 03-Sep-2021 03:58
From: Richard Vincins
Subject: Test Method Validations

Hello Anon,

To answer your questions simply:
1. Yes
2. Sometimes

For test method validations we typically included this in the design information and if this was something performed as part of manufacturing testing would included or reference there as well.  We would especially include this if the test method was unique to the device where we had developed our own acceptance criteria.  This of course depends on the type of device and type of testing because if fairly straightforward or a modification of existing testing maybe is not so critical.

During the PAI they are typically reviewing the quality management system and manufacturing activities.  Depending on the testing method and level of detail they get into depends on if they review the test method validation.  I have experienced they want to see results of testing as part of the manufacturing process for validation lots and initial lots, but typically the methodology would have already been reviewed.  The approach I would take is look at this from the perspective of someone not knowing anything about your device and product (and testing).  If the information associated with the test methods needs to be provided or more clear to an external person, then include to ensure no mis-understanding or delay in request for additional information.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs

Original Message:
Sent: 02-Sep-2021 01:28
From: Anonymous Member
Subject: Test Method Validations

This message was posted by a user wishing to remain anonymous

We are submitting our DV module of the PMA in February 2022 and manufacturing module of the PMA in June 2022.

1. Do we need to submit the Test Method Validations (TMV) as a part of these modules? 
2. Would FDA review the TMV during their inspection audit?

Please educate me on this topic as I don't have experience about this.

Test method validation addresses a specific issue. It is not always required. You need to test some product characteristic, say product verification for acceptance, and you have to develop a specific method, a test method, to perform the verification. Then, how do you the test method is correct? In other words, does the test method correctly classify the item under test as conforming or nonconforming with the necessary accuracy and precession. Test method validation answers this question.

A simple measurement of a voltage or dimension using standard IM&TE doesn't require a test method. Rely on the IM&TE and its stated precision and accuracy. However, if you want to measure the concentration of an analyte and need to develop the test, then test method validation is essential.

Test method validation is not process validation. Process validation addresses the problem of making only conforming product when you cannot test or inspect the output. In the extreme case, there is no test method. In other cases, there is a sampling plan with a test method.

------------------------------
Dan O'Leary CQA, CQE
Swanzey NH
United States
------------------------------

Original Message:
Sent: 13-Sep-2021 12:37
From: Anonymous Member
Subject: Test Method Validations

This message was posted by a user wishing to remain anonymous

Hi Richard,

I shared the TMV requirement with my quality and R&D team and there is some push back to understand if having TMVs is a true FDA requirement or it is nice to have. I tried to look into the regulations (CFR) but could not find anything which specifically broach the topic of method validation. It alludes to it in equipment qualification, statistical methods, process validation, design controls, and other sections.

Would you be able to direct me to the actual FDA regulation which I can use to back my reasoning?
Any help is highly appreciated.
Thanks
Original Message:
Sent: 03-Sep-2021 03:58
From: Richard Vincins
Subject: Test Method Validations

Hello Anon,

To answer your questions simply:
1. Yes
2. Sometimes

For test method validations we typically included this in the design information and if this was something performed as part of manufacturing testing would included or reference there as well.  We would especially include this if the test method was unique to the device where we had developed our own acceptance criteria.  This of course depends on the type of device and type of testing because if fairly straightforward or a modification of existing testing maybe is not so critical.

During the PAI they are typically reviewing the quality management system and manufacturing activities.  Depending on the testing method and level of detail they get into depends on if they review the test method validation.  I have experienced they want to see results of testing as part of the manufacturing process for validation lots and initial lots, but typically the methodology would have already been reviewed.  The approach I would take is look at this from the perspective of someone not knowing anything about your device and product (and testing).  If the information associated with the test methods needs to be provided or more clear to an external person, then include to ensure no mis-understanding or delay in request for additional information.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs

Original Message:
Sent: 02-Sep-2021 01:28
From: Anonymous Member
Subject: Test Method Validations

This message was posted by a user wishing to remain anonymous

We are submitting our DV module of the PMA in February 2022 and manufacturing module of the PMA in June 2022.

1. Do we need to submit the Test Method Validations (TMV) as a part of these modules? 
2. Would FDA review the TMV during their inspection audit?

Please educate me on this topic as I don't have experience about this.

As defined by the Code of Federal Regulations Title 21, Part 820.3(z) - Validation means confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use can are fulfilled.  Since Test Methods have specified intended uses (i.e., verify design or process specifications are met), they must be validated for their intended use.  Therefore, you must establish test method performance characteristics and limitations, identify what factors may change these characteristics, and when revalidation is required.

The extent of validation depends on the type of test, test characteristics, and risk to users if nonconforming product is released.  I recommend you consult FDA Guidance - Analytical Procedures and Methods Validation for Drugs and Biologics (July 2015) and ICH guidance Q2(R1).  They contain key principles and guidelines that can be readily applied to medical devices. 

If you need additional backing for your position, consider that FDA cites firms for inadequate TMV in warning letters and 483s. The following from 2019 and 2020 Warning Letters:

"Your firm has not conducted or documented installation, operational or test method validation for your measuring equipment to ensure that it is capable of producing valid results."  
"...test report from [date] does not appear to be performed in conformance to any standard or include sufficient test method validation to ensure the suitability of the test method."
"Your firm failed to develop a suitable test method for..."



------------------------------
Wayne Schrier
------------------------------

Original Message:
Sent: 13-Sep-2021 12:37
From: Anonymous Member
Subject: Test Method Validations

This message was posted by a user wishing to remain anonymous

Hi Richard,

I shared the TMV requirement with my quality and R&D team and there is some push back to understand if having TMVs is a true FDA requirement or it is nice to have. I tried to look into the regulations (CFR) but could not find anything which specifically broach the topic of method validation. It alludes to it in equipment qualification, statistical methods, process validation, design controls, and other sections.

Would you be able to direct me to the actual FDA regulation which I can use to back my reasoning?
Any help is highly appreciated.
Thanks
Original Message:
Sent: 03-Sep-2021 03:58
From: Richard Vincins
Subject: Test Method Validations

Hello Anon,

To answer your questions simply:
1. Yes
2. Sometimes

For test method validations we typically included this in the design information and if this was something performed as part of manufacturing testing would included or reference there as well.  We would especially include this if the test method was unique to the device where we had developed our own acceptance criteria.  This of course depends on the type of device and type of testing because if fairly straightforward or a modification of existing testing maybe is not so critical.

During the PAI they are typically reviewing the quality management system and manufacturing activities.  Depending on the testing method and level of detail they get into depends on if they review the test method validation.  I have experienced they want to see results of testing as part of the manufacturing process for validation lots and initial lots, but typically the methodology would have already been reviewed.  The approach I would take is look at this from the perspective of someone not knowing anything about your device and product (and testing).  If the information associated with the test methods needs to be provided or more clear to an external person, then include to ensure no mis-understanding or delay in request for additional information.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs

Original Message:
Sent: 02-Sep-2021 01:28
From: Anonymous Member
Subject: Test Method Validations

This message was posted by a user wishing to remain anonymous

We are submitting our DV module of the PMA in February 2022 and manufacturing module of the PMA in June 2022.

1. Do we need to submit the Test Method Validations (TMV) as a part of these modules? 
2. Would FDA review the TMV during their inspection audit?

Please educate me on this topic as I don't have experience about this.

The most direct regulation I'm aware of is actually 21 C.F.R. 820.72 Inspection, measuring, and test equipment (which is in the Production and Process Controls subpart of the QSR), where it states "Each manufacturer shall ensure that all inspection, measuring, and test equipment, including mechanical, automated, or electronic inspection and test equipment, is suitable for its intended purposes and is capable of producing valid results" [emphasis added]. I take this to include both the testing equipment as well as the method itself (since producing valid results requires both aspects; this section goes on to discuss calibration and maintenance of said equipment).

While this does not explicitly apply to Design Validation (which would be within the Design Controls part of the regulation, 21 C.F.R. 820.30), I concur with others who have stated that it is generally expected and also aligns with drug/biologic applications where justification/validation of analytical test methods are required.

So, I would recommend for either including a summary of said validations in a PMA submission or having those in the DHF ready and available for an inspection or request during review.

------------------------------
Jonathan Amaya-Hodges
Sr. Principal Consultant
jamaya-hodges@suttonscreek.com
Suttons Creek, Inc.
United States
https://suttonscreek.com/
------------------------------

Original Message:
Sent: 16-Sep-2021 14:06
From: Wayne Schrier
Subject: Test Method Validations

As defined by the Code of Federal Regulations Title 21, Part 820.3(z) - Validation means confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use can are fulfilled.  Since Test Methods have specified intended uses (i.e., verify design or process specifications are met), they must be validated for their intended use.  Therefore, you must establish test method performance characteristics and limitations, identify what factors may change these characteristics, and when revalidation is required.

The extent of validation depends on the type of test, test characteristics, and risk to users if nonconforming product is released.  I recommend you consult FDA Guidance - Analytical Procedures and Methods Validation for Drugs and Biologics (July 2015) and ICH guidance Q2(R1).  They contain key principles and guidelines that can be readily applied to medical devices.

If you need additional backing for your position, consider that FDA cites firms for inadequate TMV in warning letters and 483s. The following from 2019 and 2020 Warning Letters:

"Your firm has not conducted or documented installation, operational or test method validation for your measuring equipment to ensure that it is capable of producing valid results."
"...test report from [date] does not appear to be performed in conformance to any standard or include sufficient test method validation to ensure the suitability of the test method."
"Your firm failed to develop a suitable test method for..."



------------------------------
Wayne Schrier

Original Message:
Sent: 13-Sep-2021 12:37
From: Anonymous Member
Subject: Test Method Validations

This message was posted by a user wishing to remain anonymous

Hi Richard,

I shared the TMV requirement with my quality and R&D team and there is some push back to understand if having TMVs is a true FDA requirement or it is nice to have. I tried to look into the regulations (CFR) but could not find anything which specifically broach the topic of method validation. It alludes to it in equipment qualification, statistical methods, process validation, design controls, and other sections.

Would you be able to direct me to the actual FDA regulation which I can use to back my reasoning?
Any help is highly appreciated.
Thanks
Original Message:
Sent: 03-Sep-2021 03:58
From: Richard Vincins
Subject: Test Method Validations

Hello Anon,

To answer your questions simply:
1. Yes
2. Sometimes

For test method validations we typically included this in the design information and if this was something performed as part of manufacturing testing would included or reference there as well.  We would especially include this if the test method was unique to the device where we had developed our own acceptance criteria.  This of course depends on the type of device and type of testing because if fairly straightforward or a modification of existing testing maybe is not so critical.

During the PAI they are typically reviewing the quality management system and manufacturing activities.  Depending on the testing method and level of detail they get into depends on if they review the test method validation.  I have experienced they want to see results of testing as part of the manufacturing process for validation lots and initial lots, but typically the methodology would have already been reviewed.  The approach I would take is look at this from the perspective of someone not knowing anything about your device and product (and testing).  If the information associated with the test methods needs to be provided or more clear to an external person, then include to ensure no mis-understanding or delay in request for additional information.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs

Original Message:
Sent: 02-Sep-2021 01:28
From: Anonymous Member
Subject: Test Method Validations

This message was posted by a user wishing to remain anonymous

We are submitting our DV module of the PMA in February 2022 and manufacturing module of the PMA in June 2022.

1. Do we need to submit the Test Method Validations (TMV) as a part of these modules? 
2. Would FDA review the TMV during their inspection audit?

Please educate me on this topic as I don't have experience about this.