California FDA inspection

Since we moved the company we're waiting around for a state of California FDA inspection so we can manufacture medical devices for clinical use. We waited until we were mostly all set up before telling them about the move, which was way too conservative because they are doing inspections 3-4 months after they receive the application (like it says on the website...), we should have told them immediately about the move. Our previous state FDA inspections were nothing more than top level SOP reviews, although I talked to a QA at a large pharmaceutical company in the area and they said their state FDA inspectors looked at everything.

In the meantime, I think I've convinced everyone to build samples for a full sterilization validation and some other bonus testing. This way we can stop screwing around with lot to lot validation which takes a lot of time and money. Plus I think product workmanship will improve with practice and we'll be ready to go more quickly when we do get approval.

510(k) response received

A while back we received our 510(k) response, about 60 days after the submission, and if a 10 was as good as could reasonably be expected we ended up with a solid 8, so we're all pretty happy. We had one hardware comment, a couple labeling comments, around six software comments and a couple non-software V&V testing comments. Nothing actually that hard to respond to or that left us scratching our heads, "How do we do that!?". If we kept key parts within the company we could probably respond in the 30 days given.

I'm trying to think of something useful I could pass on, but most of it boils down to little things we forgot to include in the submission even though they are clearly documented on the FDA website. The FDA obviously spent a lot of time reading the Software V&V and requested some more typical condition testing instead of the worse case testing that we focused on. Everything they requested was very reasonable though. Same with the non-software V&V testing, out of the 20 or so reports the FDA only commented on two, I missed a standard and tested to the wrong limit, and for one test they wanted more typical condition testing. They probably can't use the words "brilliantly done" in the letter, but they did use the phrase "generally acceptable" which is good enough I think.

Anyway, it is good to receive a response and now we have something to focus on. We'll get the work done ASAP and hopefully the next letter we get from the FDA is an approval.

Heat sealing bags

In the comments, Mike asks:

I am trying to seal 4 x 6 3 mil poly bags and currently having some problems. The sealer that we have is a AIE 310FDA impulse sealer that can handle up to 20 mil. The problem we have seen is either the seal is too weak or melts when the sealing time is turned up. It is hard to regulate and get consistent seals. I just think this too much sealer for these bags. I like the looks of the Bocsh Dough Boy. Do you have any thoughts or advice to help?

Sorry, about the delay, but I don't always see the comments from old posts. I looked up your sealer here, and I don't know if is "too much" sealer for your bags, but I suspect, with never having used or seen this particular sealer that you need a fairly major upgrade in sealer if you want more consistent results. I've had much better results with sealers that use air pressure to seal (although its not clear to me how yours works). You might be able to use that sealer for some applications, but for medical devices I'm doubtful, ours cost $11,000 new, it is a base model, and I'm still not completely happy with it.

If you want to make sure that your sealer is the problem, the first thing I would do is call the bag manufacturer and get their settings and the test data for the lot you have, make sure you are getting a decent bag. The other thing to check is there is probably (again I'm not completely sure about your sealer) Teflon tape that goes over the heated metal of the sealer, make sure that is in good condition and replace it if not- that tape drives me crazy. Once the possibility of the those being problems is ruled out, make a grid of time/temp/pressure and see if you can find a suitable setting, one degree or 0.1 seconds can make a difference, use one inch peel tests to the ASTM standard to test the strength.

ISO 13485 vs GMP

We had an ISO 13485 audit a few weeks ago, one thing I learned is that ISO is much stricter about management review meeting content than GMP. 820.20(3)(c):

Management review. Management with executive responsibility shall review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure that the quality system satisfies the requirements of this part and the manufacturer's established quality policy and objectives. The dates and results of quality system reviews shall be documented.

That is pretty broad, while ISO 13485 5.6.2 has more specific requirements that auditors look for in a management review, like confirming if any major regulatory standards referenced in the Quality Manual have been updated or not, customer feedback, non-conformances, etc. GMP doesn't even state CAPAs must be reviewed (I suppose you could argue 820.20(3)(i or ii), but it isn't specific). A good auditor knows about 20 of these ISO/GMP differences and can focus in on them and find them in about 15 minutes. It would be a long day for the Quality department if they had any pride!