Applying for 510K - What is a significant process change and what is not

J

JasonDanner13

#1
I wasn't sure how to make another thread so I added it in here. I am part of a startup company who got a 510K as a contract manufacturer. We sent a design to our predecessor company, they built the medical device, and sent it back to us for packaging and sterilization.

Now, we have deemed our manufacturing process superior to our predecessor and want to manufacture the piece ourselves. The process changes we instituted do not change the product in terms of looks or function. It may make the device safer in a worst case scenario, but I wouldn't say our device is superior in safety either. Rather, we just optimized the process to create better flow, shorten the manufacturing process, and minimize the amount of raw materials we use in the process.

We do have information that could support our product being safer than the predecessor, but not significantly safer.

My question is: Do we need to get another 510K since we did alter the manufacturing process? I've read some of the FDA's wording on this and they tend to use the adjective "significant" changes to the manufacturing process. But, I don't know how to categorize what is significant and what is not. And because of this confusion, I am not sure if we need to apply for another 510K or not.

If anyone could help I'd appreciate the input!
 
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QAengineer13

Quite Involved in Discussions
#2
I wasn't sure how to make another thread so I added it in here. I am part of a startup company who got a 510K as a contract manufacturer. We sent a design to our predecessor company, they built the medical device, and sent it back to us for packaging and sterilization.

Now, we have deemed our manufacturing process superior to our predecessor and want to manufacture the piece ourselves. The process changes we instituted do not change the product in terms of looks or function. It may make the device safer in a worst case scenario, but I wouldn't say our device is superior in safety either. Rather, we just optimized the process to create better flow, shorten the manufacturing process, and minimize the amount of raw materials we use in the process.

We do have information that could support our product being safer than the predecessor, but not significantly safer.

My question is: Do we need to get another 510K since we did alter the manufacturing process? I've read some of the FDA's wording on this and they tend to use the adjective "significant" changes to the manufacturing process. But, I don't know how to categorize what is significant and what is not. And because of this confusion, I am not sure if we need to apply for another 510K or not.

If anyone could help I'd appreciate the input!
Hi Jason,

I am presuming you are aware and read this FDA guidance document https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm514771.pdf

My recommendation would be to follow the flow chart in this guidance document and document the rationale as part of the 510K product file, the decision whether it triggers another 510k or its a Letter to File, depends on the detail about the manufacturing change and its impact to product safety and effectiveness.

Also I noticed that you mentioned :
" It may make the device safer in a worst case scenario, but I wouldn't say our device is superior in safety either. Rather, we just optimized the process to create better flow, shorten the manufacturing process, and minimize the amount of raw materials we use in the process. "

My 2'c here for your comment above would be that you need to be very specific about the product safety case, manufacturing process changes...for example with the change in the raw materials, the detail that needs to be documented would be, what is the impact to the existing product 510k file's existing Process validation?

Another example would be with the "shorter manufacturing", what does this change means in terms of impact to the existing Process validation , end of line testing , Manufacturing work instruction, Manufacturing supporting Software tool validation etc which was submitted for previous 510k clearance? [Note: term " existing" refer to the submission made earlier for 510k clearance]

So in summary you have to use the Flowchart from FDA guidance document and document all the changes and assess their change to the safety and effectiveness of the cleared 510k file, please note: the devil is in the details and its all about the details in your change which would help you to make the determination whether its Significant or not....if you need further recommendation please complete the flowchart and if you have any particular question, be specific and the forum members can offer some guidance from their experience.

Albeit this guidance is FDA draft https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM467414.pdf Please read this draft guidance as well so you can get some insight about the FDA thinking related to the Manufacturing site change. Good Luck!
 
Last edited:
J

JasonDanner13

#3
Gotcha for the most part. The reason I say it doesn't "really" effect safety is that the device in it's intended use is made to be a solid component. During our 510K we did cytox testing (MEM Elution) that did not pass. We remedied this by changing the process to more extensively cure the device, which lead to reduction in toxic by products formed. The predicate piece was not subject to this type of cytox testing but rather agar overlay I believe. But, the MEM Elution was based around our product being cut up which allowed the toxic by products to become available in the serum. But in real life, our product will never be broken up and therefore is no more safe than the predicate unless a patient would get hit in the head with a baseball, and in that situation they'd have more problems than some cytoxic events in their head, and the surgery would dictate that our implant removed either way. Previous to your message, I had gone through the flow-chart and I believe that it lead to just a Letter to file.

But, I wanted to make sure I was on the same page as you. So, the change in our manufacturing process is just a shorter, but warmer cure cycle. This also functioned within our process validation. We knew we could cure at different rates, we choose the lower rate because our ultimate goal is to also have electronics in our device and therefore we wanted a lower curing temperature. But the OQ validation showed that the equipment could operate within the range we asked it to. However, we did qualify it under the old manufacturing parameters. So maybe this is a significant enough change to warrant a new 501K?
It doesn't change dimensions, use, or function of the product. All elements of the process our the same. We use less raw materials now because there was an overflow factor in our original process that we changed to reduce cost. The function and results of the product are exactly the same and again no change to the function or use of the implant occurred.

But as for safety, it is harder for me to move forward because technically I'd say yes we are safer than the predicate, because we can pass the MEM Elution, however in a sense of functionality and safety in terms of how the device is to be used, there should be no difference between the two products.

Not sure if this clarifies anything or just makes it hazier. I am leaning towards filing documentation rather than a new 510K. But that safety issue is concerning to me.
 

QAengineer13

Quite Involved in Discussions
#4
Gotcha for the most part. The reason I say it doesn't "really" effect safety is that the device in it's intended use is made to be a solid component. During our 510K we did cytox testing (MEM Elution) that did not pass. We remedied this by changing the process to more extensively cure the device, which lead to reduction in toxic by products formed. The predicate piece was not subject to this type of cytox testing but rather agar overlay I believe. But, the MEM Elution was based around our product being cut up which allowed the toxic by products to become available in the serum. But in real life, our product will never be broken up and therefore is no more safe than the predicate unless a patient would get hit in the head with a baseball, and in that situation they'd have more problems than some cytoxic events in their head, and the surgery would dictate that our implant removed either way. Previous to your message, I had gone through the flow-chart and I believe that it lead to just a Letter to file.

But, I wanted to make sure I was on the same page as you. So, the change in our manufacturing process is just a shorter, but warmer cure cycle. This also functioned within our process validation. We knew we could cure at different rates, we choose the lower rate because our ultimate goal is to also have electronics in our device and therefore we wanted a lower curing temperature. But the OQ validation showed that the equipment could operate within the range we asked it to. However, we did qualify it under the old manufacturing parameters. So maybe this is a significant enough change to warrant a new 501K?
It doesn't change dimensions, use, or function of the product. All elements of the process our the same. We use less raw materials now because there was an overflow factor in our original process that we changed to reduce cost. The function and results of the product are exactly the same and again no change to the function or use of the implant occurred.

But as for safety, it is harder for me to move forward because technically I'd say yes we are safer than the predicate, because we can pass the MEM Elution, however in a sense of functionality and safety in terms of how the device is to be used, there should be no difference between the two products.

Not sure if this clarifies anything or just makes it hazier. I am leaning towards filing documentation rather than a new 510K. But that safety issue is concerning to me.
From the first paragraph of your comment it give me an impression that you have exercised the due diligence of following the FDA flow chart and it directed you to LTF which is a good starting point, so I am presuming you used sections B (Tech. Engg and performance) and C( Materials), if its IVD its Section D..Also please note in your case B5.4 is very relevant " If the manufacturer determines after an initial assessment that submission of a new 510(k) is not required, the manufacturer should conduct routine verification and validation activities to ensure that no new issues of safety or effectiveness are raised. If successful application of routine verification and validation activities confirms the initial assessment, manufacturers should proceed with the design change and document their assessment. Occasionally, routine verification and validation activities may either produce unexpected results or otherwise prove to be inadequate to verify and/or validate the modified design.In such instances, the manufacturer likely is required to submit a new 510(k). ......."

I was a bit lost because I don't know your product nor your process well, but from a external perspective with limited knowledge about your product/process , this comment " However, we did qualify it under the old manufacturing parameters. So maybe this is a significant enough change to warrant a new 501K?" since you used the same parameters for Process validation as your previous cleared product it does seem like its going to trigger the 510k.

However, the part about the "Safety/ Safer" is want you should be mindful because if you were to state the modified device is safer than previous one, then the next question you need to answer would be " Is the predicate not any safer and what is the CA for the field device" so be very careful with your rationale and the supporting reasons for LTF, if you go down that path.....

I am afraid , I can only give reco based on what you mentioned in the comment but there is a technical know-how about your device which I am not across! :-(, it looks like you are doing the right thing, now its all about Documentation, rationale about the change in comparison of modified device to most recently cleared version.
 
J

JasonDanner13

#5
Thanks for your help! I know I can't list too much about our product, and I am sorry about that! But, with the manufacturing process, we know we have changed it from the predicate device. However, if we do the same testing cytotox, bioburden, endotoxin, leachables, etc. and show that we pass the same test as the predicate, could this be used to show "substantial equivalence? We are prepared to document a LTF we have a lot of data to support and we rather go that route than submitting another 510K, but we are trying to do some due diligence now to show that the process and product aren't significantly altered.
 

QAengineer13

Quite Involved in Discussions
#6
Thanks for your help! I know I can't list too much about our product, and I am sorry about that! But, with the manufacturing process, we know we have changed it from the predicate device. However, if we do the same testing cytotox, bioburden, endotoxin, leachables, etc. and show that we pass the same test as the predicate, could this be used to show "substantial equivalence? We are prepared to document a LTF we have a lot of data to support and we rather go that route than submitting another 510K, but we are trying to do some due diligence now to show that the process and product aren't significantly altered.
Jason, that sound like a perfect plan, yes you are absolutely correct, document all due diligence activities you have performed to state that the modified device with this individual change and if there are any cumulative changes made before has not changed the safety and effectiveness of the predicate device. This change is part of continuous improvement made to the manufacturing process to improve efficiency, cost reduction initiative with no changes to the existing design, performance, safety, effectiveness end of line (EOL)testing, raw materials,batch release etc.........
 
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