Medical Device Design History File

After much kicking and screaming, I spent a couple days this week making sure the Design History File (DHF) was adequate and up to date. The QSR (820.30) is pretty open ended regarding the requirements:

Each manufacturer shall establish and maintain a DHF for each type of device. The DHF shall contain or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and the requirements of this part.

Some more details are available here. Thankfully, it says "or reference" so we can throw in the Engineering Change Notices (ECN - sometimes called change control records or orders), which contain a reason and description of changes, and not worry too much about the all of the actual product requirements (design input) and specifications (design output) going in there. Obviously, testing protocols and reports including V&V, biocompatibility, sterilization, etc., go in there. Our company SOP also has design meeting notes listed, which has been interpreted as pretty much every meeting that I attend is a design meeting. I think the strategy is to err on the side of completeness instead of usability. We also have some goofy things required to be in there like marketing and competitor information.

As an engineer its hard for me to efficiently maintain the DHF since I do not see every finalized ECN. I did badger the QA to run everything going into the master file by me before filing for the time being. This way the DHF shouldn't get out of date, but hopefully I can turn it over to the DHF quality department soon as they can maintain it more efficiently because they have final sign off. However, right now no one in the company outside of engineering is able to make the distinction of which documents are necessary to show "that the design was developed in accordance with the approved design plan."

Other than that we are going to miss another filing deadline, part of it due to some consultants falling behind, part of it due to management doing some things that caused a bit of a delay, but it also crushed morale, it was so bad that they tried to make amends on Friday by offering lunch and not a single person outside of management took them up on their offer of free lunch. Ouch.

I am web published!

Medical device blogger addresses technical questions

The picture looked less geeky when I picked it out.

Our packaging design went fairly smoothly and was validated. There are couple cosmetic problems related to workmanship that need ironed out, and a few tweaks to the packaging could help that, but nothing serious. Of course, I blamed all of the problems on manufacturing not following the drawing precisely and QA for not inspecting correctly. Just kidding, I'll make the changes when I have time.

Anyway, I spent about 6 hours editing a software requirements document today and will spend about 6 more hours tomorrow because we thought it would be a good idea to let the software guy rewrite and make pretty the requirements before we submitted to the FDA. Instead of taking the already released document and editing it, he made a brand new one, and I get to reconcile the old with the new, both of which are missing major components. The joys.

End of the 510(k) line

I know how Creo Quality (sorry to post off of Creo so much, but I can't find many other device blogs) feels, the closer you get to your deadline, the more you think, we should (or think we should) have discovered these problems months ago. Our device incorporates an air detector to ensure air doesn't enter the patient's bloodstream, it is a fairly common accessory for any device with an extracorporeal circuit. We just discovered recently that the software was set up to check the air detector every half second, at our flow rates more than 50 ml of air could have gone by in half a second. Thats is why we do the validations. It is a relatively simple job to change the scan rate and then retest that it works correctly this time, probably takes about a week overall, but at this stage every delay is painful and they start to add up.

I've been fairly lucky this week though and haven't caught much flak, management has been occupied with self inflicted problems that I'm not part of. The 510(k) checklist hasn't had many tasks crossed out the last few weeks though, most of it is due to contractors or consultants having one problem or other. Unfortunately it ripples back and other stuff has to be put on hold. A big piece is due tomorrow (No MLK day break for us!), the final software V&V, we'll see how it looks. Until we have that we haven't been able to finish a lot of traceability documentation and a bit of testing that was waiting for the final software version to be signed off on.

Biomedical Engineer?

Shreya asks for comments if you're a biomedical engineer and how to advance in a medical device career. I'm a chemical engineer, but as usual that won't stop me from giving my opinion. My boss prefers to hire mechanical or chemical engineers over biomedical engineers because he thinks they have a more solid understanding of engineering fundamentals- I have no idea if this is true or not. So, our company certainly wouldn't value a biomedical engineer more than the other two when it came to hiring time. I obviously can't speak for all companies, that just what I'm used to, but I think with a mechanical engineering degree you would still have a very decent chance in getting into the medical device field, and if that didn't work out you'd have many more options than a biomedical degree.

You can give yourself a further leg up by just working at any position in a medical device or drug company. Really understanding GMP/GLP is a huge leg up on a new graduate. Any position would help and many companies have a high turnover in starting positions because people move on and up quickly.

The other thing to keep in mind is that this country has a dozen or less biotech clusters and if you are not willing to move or live near one your chances of getting a biotech job are slim.

IDE expectations

Creo Quality has a good post up about expectations and a list of unrealistic ones:

From a regulatory and clinical perspective, there were other expectations, including:

• A pre-IDE meeting with the FDA would happen before the close of 2007.
• Animal testing would be simple and straight-forward to adequately demonstrate product safety.
• An IDE submission should be ready for FDA submission in early February 2008.
• An IDE clinical trial should only require a single site with limited # of patients.
• The clinical site IRB and enrollment process should be quick and easy.

I’ve known all along that every one of these expectations were not and are not realistic.

I can't comment on the expected schedule items, but I agree with the rest. I'll detail some of my experience below.

Animal testing would be simple and straight-forward to adequately demonstrate product safety.

I worked at a company that thought this at one time too, the product performance testing on animals and bench was all wrapped up, from this we had some safety data, but nothing clean, so additional safety tests had to be performed. Eight months and an unfortunate number of pigs later it was finally locked down. Some of the difficulties were due to differences in anatomy, to get to the femoral vein in a pig you have to do a cut down through muscles and fat, while most humans you don't. Also, you can expect a critically ill patient to lie relatively still for 5 days, the same can't be said for a healthy pig. Another major problem was we didn't realize that a 100 ml blood loss was an adverse event until very late in the game, it was never a problem in animal tests where losing the blood isn't going to matter to a healthy pig. Surgeons are much more concerned about the blood loss than large animal vets. All of these issues required significant amounts of time and money to work through, it is difficult to anticipate all problems with a new test.

An IDE clinical trial should only require a single site with limited # of patients.

We actually asked for and got this at my company, but it was to our detriment. A single site with a 10 patient safety study required, after the 10 patients a review to see if a larger study was needed. The single site was a killer, the surgeon involved was a champion for our device, but other hospital personnel involved with patient sign up for clinical trails were much more cautious and frequently and strongly voiced doubts to the people that the surgeon had convinced to sign up. We thought the surgeon was on board so it was all good, we didn't find out what was really happening for a year- a year with no patients. There was also limited patient population at the hospital our surgeon could approach due to some internal hospital politics that we weren't told about when we started. We had previously amended our request to the FDA and were granted additional sites, but thinking we could do it at one was a mistake that cost us a lot of time.

The clinical site IRB and enrollment process should be quick and easy.

The hospital Internal Revue Board (IRB) meetings I've been part of (all of two), or ordered to produce something as a result of, have been tough, but fair. I don't think that most people not in the industry know this, but IRBs can be tougher to get past than the FDA and can require extra testing as well. The ones I've dealt with met once a month and generally set the meeting agenda the previous month, so it required 3 months to get approval, one month to get on the agenda for the next, the initial discussion of the device and request for more information, and the third month was approval after discussion of the requested information.

I don't think you can ever say patient enrollment will be quick and easy. Its amazing that you can spend so much time on selection criteria and then someone always shows up with something unexpected.

Anyway, I hope it all turns out well for Creo's client companies!