Contract Manufacturing Pre-Qualification? How much 'due diligence' to satisfy the FDA

[Scott Catron]

For the first time I've been in this job we're going to use a contract manufacturer. We will supply the bulk solution and they will package it in one-time-use applicators. This comes at the request of a customer who previously had supplied the bulk solution to this third party, but now they just want to buy the complete package from us. The specifications are all in place, the third party has been doing this for about five years for our customer and has been through a couple FDA inspections without an FDA-483 being issued. From all indications, they have a solid operation.

My question is what sort of pre-qualification is required - how much 'due diligence' do we need to do to satisfy the FDA should they look into the arrangement? Is a review of procedures sufficient? Do we need an on-site inspection before we even ship them material to use? Should we be on-site when they start up? Being on-site does add some non-trivial costs to the arrangement - they're in Connecticut, we're in Utah.

I didn't find any FDA guidance documents addressing this. Anybody have experience is something like this?

Thanks in advance.

Scott

[Aaron Lupo]

Originally Posted by Scott_Catron

For the first time I've been in this job we're going to use a contract manufacturer. We will supply the bulk solution and they will package it in one-time-use applicators. This comes at the request of a customer who previously had supplied the bulk solution to this third party, but now they just want to buy the complete package from us. The specifications are all in place, the third party has been doing this for about five years for our customer and has been through a couple FDA inspections without an FDA-483 being issued. From all indications, they have a solid operation.

My question is what sort of pre-qualification is required - how much 'due diligence' do we need to do to satisfy the FDA should they look into the arrangement? Is a review of procedures sufficient? Do we need an on-site inspection before we even ship them material to use? Should we be on-site when they start up? Being on-site does add some non-trivial costs to the arrangement - they're in Connecticut, we're in Utah.

I didn't find any FDA guidance documents addressing this. Anybody have experience is something like this?

Thanks in advance.

Scott

The FDA part 820.50 states that you need to evaluate your suppliers, establish the requirements (including quality requirements). It is up to your orginization to determine what or how much control you need to have over this supplier. So it is up to your orginization to determine if you need to perform an on-site audit of your suppliers or if can evaluate them through your inspection process/records. IMHO I would not audit unless you really feel it necessary.

[Wes Bucey]

Originally Posted by ISO GUY

The FDA part 820.50 states that you need to evaluate your suppliers, establish the requirements (including quality requirements). It is up to your orginization to determine what or how much control you need to have over this supplier. So it is up to your orginization to determine if you need to perform an on-site audit of your suppliers or if can evaluate them through your inspection process/records. IMHO I would not audit unless you really feel it necessary.

When I last dealt with FDA, the guideline from the FDA guy who visited us about "contract manufacturers" was simply:

You are responsible for assuring they have "Good Manufacturing Practices."
If we (FDA) get an "itch" or a "tickle" about the product, WE will launch an inspection of them and hold you responsible. You make the decision about what gives you confidence in the contract manufacturer.

In Scott's case, I think the very minimum would be a questionnaire completed by the contractor about his methods. If it does not seem straightforward enough to you, it seems you may have to travel out east to confirm statements in the questionnaire. If you feel comfortable, talking to your customer, ask them how they confirmed the GMP of the contractor. Maybe they have on-site audit reports to give you copies.

$$$The cost of an on-site visit and audit is pertinent to the equation ONLY if the sums involved on your contract with your customer are very small (value judgement.) That is, what is your financial exposure if the contractor screws up?

[Al Rosen]

Scott,

I agree with both ISO and Wes. You might want to get a copy of their procedures for the product they are supplying and perhaps perform a review of the records that they supply with the first shipment. Periodic evaluations can be done subsequently.

[Gerry Quinn]

I agree with Wes. Do yourself a favor. Put the maximum controls on every supplier that are comensurate with your exposure. We it hits the fan, you won't be able to say, "Oh it wan't me it was my supplier." If you said that to me, I'd have the cuffs on before you finished the last word.

Gerry

[Wes Bucey]

Originally Posted by Gerry Quinn

I agree with Wes. Do yourself a favor. Put the maximum controls on every supplier that are comensurate with your exposure. We it hits the fan, you won't be able to say, "Oh it wan't me it was my supplier." If you said that to me, I'd have the cuffs on before you finished the last word.

Gerry

By an interesting coincidence, one of my ASQ Sections had an absolutely riveting presentation last night concerning FDA visits, 483 letters, etc. right on up through criminal prosecution.

The presenters were a consultant and a recently retired FDA inspector. The gist of the presentation was that FDA has a strong agenda to be consistent in its enforcement activity globally. It is much quicker to pull the trigger on civil and criminal prosecution.

Top changes in methods include

1. Holding top executives personally responsible. No more "passing the buck" to the Quality guy who gets fired while the company continues its bad old ways.
2. refusal to allow goods from foreign suppliers to enter the US, thereby crippling US owner/operators (it seems the FDA overseas inspections have no need to "prove" a case against a foreign manufacturing site, "suspicion" is sufficient grounds to debar product.)
3. Final seller is responsible and accountable for everyone in the supply chain.
4. The time table between steps in an FDA action are considerably truncated from even 2 years ago, thanks to an improved computer-tracking system which enables every district to act uniformly with every other district
5. Absolute willingness to do "perp walks" (execs in handcuffs before TV cameras) if the FDA senses "footdragging."

Fines have escalated drastically. A fine is a combination of "disgorgement" of any profits plus the penalty for the category of nonconformance. Recent cases have shown willingness to pursue monster fines ($600,000,000 for one!) and to get court orders padlocking entire plants.

The balance of the presentation was about strategies to pursue for companies at any stage in the continuum from first FDA visit to criminal trial.

Previous to this presentation, I had sensed an upswing in FDA presence and activity, based on gossip among many of our Section members who work for big pharmaceutical companies in our area. As a comparative industry outsider, I was pretty much stunned at the attack dog mentality described.

Before you ask, I do not think these guys were on a campaign to scare up business. If they were, it was the wrong audience. Our audience for the most part seemed to know and accept the step-up. They were most interested in the kind of documentation FDA would expect at the various stages in the continuum. This was the kind of stuff to chill the bones of any executive.

[Sidney Vianna]

For an index and access to the FDA warning letters, check http://www.accessdata.fda.gov/script.../indexdate.cfm.

Some interesting reading.

[Wes Bucey]

Originally Posted by Sidney Vianna

For an index and access to the FDA warning letters, check http://www.accessdata.fda.gov/script.../indexdate.cfm.

Some interesting reading.

Folks not involved in FDA should know these warning letters are only issued after time has been granted to cure observations reported by the FDA inspector. The issuance of a warning letter means the organization has failed to figure out how to fix the problem or just plain stonewalled.

This one boilerplate paragraph is not a bluff:

Originally Posted by FDA Warning Letter

You should take prompt action to correct these deviations. Failure to promptly correct these deviations may result in regulatory action being initiated by the Food and Drug Administration against you or your product without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil penalties

The FDA, like the FAA, does not listen to b---s---; if you can't document a cure for your Quality breakdown, don't waste your breath.

I can understand some mom and pop food operations getting in over their heads, but not major medical device manufacturers. What can those executives be thinking?