Molding Press and Tooling V&V Continued ...

In response to additional ques on above subject:

STATEMENT: In the OQ phase; process parameters that yield acceptable product are found; process windows are determined (via DOE’s) and backed-up by statistical data. In the PQ phase, you recommend using worst-case settings – at the edge of the now-determined process window.  While I can see that this is the most thorough way to ensure the process window is appropriately set, there are two questions:

Ques:  Is this necessary in the eyes of the FDA or other governing bodies that you have run into?   Or, is running the PQ at a nominal setting acceptable by the FDA and other governing bodies?

Ans:  The FDA has always questioned the upper and lower limits on SOPs, set-up cards, et al, wanting to see the proof for the values chosen.  I address by a min of three PQs, one at nominal for all values, one at the higher (and/or lower), and one at the lower (and/or higher) for all the values, mixing and matching to get "worst case allowable" with the three minimum PQs.

Ques:    When validating a process that has many variables, are there rules of thumb to determining how many “worst case” settings or scenarios should be run?  I can see how a machine could be forever in the PQ phase if we were constantly exercising worst case scenarios. I can’t imagine a business “making money” let alone shipping product if they are spending time in a constant PQ phase.

Ans:  Again, I try to hold my initial PQs to 3-5 max. (this would not include the additional PQs required for additional tooling, different lots of resin, etc.)  You combine as many as practical and can omit some if the patient risk is minimal to non-existent.  You as the manufacture decide, and document your rationale.  I sometimes use a matrix to combine, much like a factorial for DOE.

To add to my previous response (see previous blog) -- An Alternative to V&V of Press and Tools:

1. V&V the press as described (machine states plus other key settings / operations -- heating, cooling, pressure ...);

2.  Do 1. with the next tool scheduled, with min of 3 PQs, to V&V the press and qualify the tool;

3.  At completion of three PQs, et al, release that lot;

4. That will Validate the press (and qualify that tool);

5.  Remove the press machine states and other press related elements from the PQ template, and leave those pertaining to the molded part (fill, stress (polorized light / destructive testing ...), dims, et al);

6.  Do a min of 1 PQ for each new tool and/or each new lot of problematic resin as an addendum to the original Press/Tool V&V and after approval release that lot of molded parts. 

7.  Repeat for each new part until all tools are qualified.

8.  Each part / tool PQ can be done as part of a normal run if no problems are anticipated, and when passed, signed off so the lot can be released.

9.  Do the same with additional lots of problematic resins if an issue.

Of course, all the above assumes the same as mentioned in the previous blog, that there are downstream 1st articles / QC performed in molding and assembly, as further verification activities, documented (SOPs referenced, results included ...). 
It further assumes that variations in input variables are basically well known and controlled.  To the degree that they aren't, additional PQs may be required.

This is not as hard as it appears.  And not that obstructive to a business' operation.


-- John E. Lincoln        jel@jelincoln.com

Molding Press and Tooling V&V

A recent webinar on V&V Planning I conducted resulted in the following questions (and my answers):

 We are planning on performing Validation(s) for mold tooling that  will produce parts that go into a Medical Device. We are not making the completed device here (as yet) but simply making some of

the molded components.

Ques:  As such, do our molding machines need to first be validated? I am presuming so.

Ans:  Yes.  Even if you do 1^st articles and additional QC on the molded parts. One of the adversary

 audit remediations I performed dealt with this, meaning the mandate came from an FDA District

Office after review of the 483.

Ques: Does this mean a full validation of the machine(s) themselves;   IQ, OQ, PQ?

Ans:  Yes.  IQ would include leveling, water, hydraulics, and electrical.

Ques:  If yes, what constitutes the OQ and PQ portion of such a validation?

Ans:  OQ would verify general operation.  Specific parts are validated separately to address resin, establish set-up card information / parameters et al.

I did a 550 T C-M press, HW and SW, and used a fold-out schematic addressing “machine states”

to develop many of my test cases.  The OQ verified the initialization, operation of the software –

“black box” – by the hardware’s performance for each of the states, as well as temperature,

pressure, et al, that everything cycled as expected or as set.  The PQ’s ran thru each of the above (machine states et al)  for n=?  with ? determined by the variability in the process (an existing

sampling SOP and/or industrial statistician or similar can provide sample sizes, or see Juran and

Gyrna’s Quality Planning And Analysis Text, any edition for rationales for sample sizes down to

=10.

Although mine involved a dedicated press (one tool), in your case I would determine the most

difficult one or two parts / tools and use that with a well thought out and documented rationale.   Include an explanation of your downstream verifications / QC required for any

molded part, e.g., 1^st articles, other QC in Molding and/or Production / Assembly in your Test

Report justifications for any reduction in test cases / sample sizes, which such would allow.

In my case, a review of the press manufacturer’s  C++ module list (which I obtained by a call to

their tech support) showed the company did a FAT, so I requested a copy, and incorporated most

 in my V&V, reducing some of the additional V&V.  

Ques:  Can you use "any old mold" or does it require a specific mold to be used?

Ans: See above.

Ques:  Doesn't this constitute the "chicken or the egg" syndrome if using  a mold that is yet to be qualified?

Ans:  A common occurrence.  Do some qualification before, e.g., flow studies, part dimensional,

part stress,

venting, shot / fill and similar, which may have been done on another press -- document.  Then do

the above, if this is your most troublesome molded part.

Ques:  You spoke of software/hardware validations;  We rely upon the SPC and Parameter software

 that is part of the molding machine(s) themselves to provide us with consistent molded parts; do

we need  to have this built in software validated?

Ans:  Yes.  And it might also involve 21 CFR Part 11, depending upon how the SPC data is used.  This could be a separate V&V.

Ques:  If so, how does one go about doing such; generally speaking?

Ans:  As addressed briefly in the webinar, but I would also add something similar to an Excel macro

V&V, where you compare data so generated by your equipment with an independent source,

gauges (cal’d) and a calculator using a  textbook formula or similar independent source, all recorded

 in the Test Report.

As mentioned.  If the above seem intimidating, start simpler and address high [patient] risk items,

then later add others as CAPA feed back or other CGMP requirements require and your experience

with the system dictate.

--  John E. Lincoln       jel@jelincoln.com