As a contract manufacturer, it is understood by our clientele that we are experts in our manufacturing discipline. That said, as medical device OEMs respond to the current requirements described in the EMDR (European Medical Device Regulations) or by the FDA, the topic of process validation is more and more common. Most OEMs simply do not have a validation plan for a contract manufacturer to follow. The engineers are fully aware that it is a requirement for releasing their product in the market and they simply want to “check the box” that this has been completed. This is a current need in the marketplace and SiMEDEx has developed a program to move projects from the process development phase of manufacturing to a fully validated process.

Prior to jumping into a validation discussion, it makes sense to touch on the topic of verification versus validation.   Verification is typically performed while a product or process is being developed. It is a means by which to determine if a product (or process) meets the dimensional or visual requirements set forth by the product specification. 21 CFR part 820.75(a) stipulates that if process results cannot be fully verified during routine production by inspection and testing (i.e.: in-process dimensional checks) then the process must be validated according to established procedures. That being stated, OEM’s want to be certain when they order a particular component, that it arrives in-spec each time.

As with all projects there are many moving pieces. Some steps move in parallel whilst others move in series. The backbone in the development of a validated process are the 3Q’s otherwise known as IQ/OQ/PQ. Each step towards the validated process builds on the previous step. Let’s break these down in greater detail:

IQ- Installation Qualification – This is the verification that your manufacturing equipment is installed correctly.   For example, is the electrical power correct for the input of the machine? The same questions must be asked about all equipment in the process. Ovens and temperature set points, puller wheels and their respective speeds. This step is easily overlooked but the list for validating equipment must be complete. The important distinction to be made in this step is that all measurements are performed with calibrated inspection equipment. Examples of calibrated equipment used during this step are digital multi-meters and a calibrated stopwatch.

To process silicone, we require scales (analytical balance) to weigh raw materials, 2 roll mills for raw material preparation, extruders, curing ovens with some means of conveying the extrudate through the ovens and possibly a post cure oven for normalization. Each piece of equipment needs to have completed its own IQ and have it documented for review. For example, to qualify our oven, we placed 12 thermal couples in the oven (4 on the top shelf, 4 on the middle shelf, and 4 on the bottom shelf) spaced equidistant from one another. We brought the oven up to temperature (392 degrees F / 200 degrees C) for 4 hours and showed that the oven held +/- 5 degrees F at each location during the duration of the heat soak. Another example would be showing that the extruder screw speed reacts accordingly to the inputs received by the operator. When you power up the extruder and input a screw RPM does the machine react accordingly? This is all documented in a protocol established by our engineering group and in some instances, reviewed by the customer. Additionally, any preventative maintenance steps would also be established in this step of bringing on a piece of equipment on-line.

OQ – Operation Qualification – This is the verification that the installed equipment is working properly. It is also in this step of the validation that we perform engineering studies for process development. Die and mandrel sizes are selected based on historical performance of the raw material specified. How much die swell do we anticipate for this raw material? How much draw down do we anticipate for the processing of a particular raw material? It is at this point that tooling is modified to ensure a stable manufacturing process. Once tooling dimensions are determined, we begin a series of engineering studies to establish processing windows (minimums and maximums) for the critical processing variables. Some customers have referred to these processing windows as the “worst case” for manufacturing product that meets dimensional and visual specifications. For silicone extrusion those key variables are processing temperature (to insure proper vulcanization) and line speed.

PQ – Process Qualification – The process qualification is really where the rubber hits the road (Yes! Pun intended!) Building on the previous engineering runs, these runs are performed at the nominal settings for the process. For example, if the worst case OQ runs showed that product could be manufactured at 25 feet per minute and 15 feet per minute, we would most likely select 20 feet per minute as the feed rate for the process qualification lots. In most instances our clients have agreed that we need to perform a minimum of 3 different set-ups with 2 distinct lots of raw material. This shows repeatability of the process set-up while also considering lot-to-lot variability.

It is becoming more and more common for manufacturing engineers to look at statistical process control to ensure that a manufacturing process is stable. We use a minimum CpK value of 1.33 on the critical dimensional attributes to illustrate that our process is in control. This statistical work is typically performed on a minimum of 30 samples and the CpK is calculated from this data set. A report summarizing our findings is presented to the customer showing that our process meets the minimum CpK requirements and is routed with for appropriate signatures.

Link to FDA Quality System Registration (21 CFR Part 820):

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