Pharma/Medical Extrusion, The Devil is in the Details V - Process Input Materials

For any extrusion process, the input materials will need some method of control. From what is purchased to handling the components once they come off the extrusion line it is important to develop the proper processes around these needs. Above is a simple breakdown of the steps normally seen in medical/pharma applications. I will attempt to walk through these and try to supply some helpful information (not intended to be all inclusive) in each step. In the end what we all want to avoid is to (quoting former colleague and consultant Mike Ferrandino) "do no harm to the material".

I will try to break this up into smaller sized 'bytes" whenever possible to keep the article size short. Today I'd like to cover the "Material Specification" portion of the process.

Material Specifications

The material specification is where it all starts. What is specified should be derived from objective data and not through using standard jargon from a table. Use rheological and thermal data as your tools whenever possible. Some general things to consider;

Is it a natural resin from the manufacturer?

Does the vendor's specification work for you (not the TDS)? If so, have you tested and/or validated your process around as much variation you might see from the vendor as possible? While it may be impossible to test the entire range, the more variation you input into your process development and validation strategy the better off you will be. I've been asked to perform validations with a single lot of material a few times, and each time I have pushed back, hard.

Does the supplier offer support for the Med/Pharma industry?

Using "non medical friendly" vendors should be avoided. At some point support will be needed. Also, if you do require a narrower range for a specific attribute then what the vendor offers, the vendor will need to agree to supply you with it. A caveat to this will always be to make sure what you ask for is necessary for reasons already discussed. Some vendors are very good about this, some are not. As a (real world) example, if the manufacturer's MFI range is 3 to 15 and your process data shows that you need something less, a supportive vendor will supply you with historical data. If their data shows that 75% of their lot distribution meets a 5-9 MFI and that fits what you need, you would at least know your risk level and have an action plan in place to mitigate it (inventory levels vs. use, etc.). If their data shows that only 20% of their lots meets the requirements you need, you might want to redevelop the process with a much wider range or rethink the material choice, or else manufacturing will be backed into a corner at some point.

Is it a compounded resin?

Now there are three or more vendors nested. Just as above, have you tested and validated as much of the range one is expected to see as possible? Everything noted above applies, and then some. Does your compounding partner have the proper controls in place for their vendors? Do they have the engineering bandwidth to institute the proper controls in their processes to deliver what you need on a regular basis? Can they conduct the proper tests for release of materials based on specification? My recommendation is to use a compounding vendor that will minimize your risk. There are some very good ones out there. I recommend that when it comes time for a vendor quality audit that an engineering audit be conducted at the same time if they'll let you (you should already have the proper NDA's in place). If they won't let you, you might want to wonder why.

Is it a high cost resin?

Some natural resins are high cost. Bio-absorbables and implantable resins comes to mind. Add to that the compounding of fillers and/or API's and the costs escalate quickly. Compounded polymers with the usual radiopaque fillers are of course expensive and prevelant in the industry as well. Tantalum and Tungsten fills escalate those costs by 300% or more. What is specified for these materials will be important, as consistency will be one of the keys to success. Don't guess at what you need, test limits (and materials) as much as possible and determine what is best for the process and product. Testing is inexpensive when compared to the long term cost of scrap of high cost materials and there is nothing worse then processing thousands of dollars per hour of scrap material on the extrusion floor. The cost is even higher the further up the manufacturing chain it goes and can be disaster if it makes to the patient.

Of course there are other factors but when putting together a material specification, one needs to put a lot of thought into it as there is the balance of the higher the cost and potentially the higher risk there is of supply issues. Test the range limits whenever possible, even off spec materials, and you might be surprised when developing a "process window" at what can be accounted for. It's better for the organization to put the effort in up front.

These are just some general thoughts around materials and considerations for specifications. I keep reminding myself of a time in my career while in contract manufacturing when a salesman mentioned that he sold a specific order for $32k. My response was that it used $30k in tungsten filled PUR resin. No one had addressed the raw material or thought out the process. Of course, it became my next project.