Introduction
In the pharmaceutical and medical device arena, each passing year brings tighter tolerances (micron to sub-micron), smaller features, and more complex assemblies. These assemblies are getting more complex because of their need to fit, for example, into pencil-lead sized pumps or catheters, or endoscopes with actual working micro components inside. They are often combination components with challenging geometries, maybe once drawn in CAD as two components, but due to cost implications reduced to one. Perhaps in the case of a powder inhaler they were once 22 micro components and have been redesigned into 6 total components. Some devices also require pharmaceutical drugs directly compounded with or added to polymers, metals, or membranes. Others have working gears, levers, and drive mechanisms to make the device function repeatedly and with robust longevity.
With all these possible attributes in mind, and in consideration of the fact that these devices are juxtaposed to or directly implanted into the body, it is important that they are developed in such a way that they are robust, and tried and true before they are “thrown over the production wall”. This article explores the challenges, solutions, and pitfalls when manufacturing and assembling medical and pharmaceutical devices.
What’s New and Exciting?
Many cutting-edge products start with some element of the impossible. Someone’s hair-brained idea on the back of a napkin during a sales meeting has been sent to engineering for a quick review. These drawings are sent (many times still on the napkin) to the micro developers of the world for an initial look. Rarely are they manufacturable as received, but often they are just scaled-down versions of something similar on the market, just several magnitudes smaller and requiring some novel material for strength purposes due to their thin walls, or some funky material due to a drug-releasing agent or similar characteristic.
Some examples of these exciting micro-sized medical and pharmaceutical devices include pharmaceutical induced stents, anchors, needles, and sheaths; pharmaceutical powder inhalers; diabetic pumps with onboard valving; hydrogel and collagen implants; micro aspirators; micro MIM (metal injection moulding) biopsy forceps, sensors, and gears; neurosurgical coil assemblies; transdermal patches with injection moulded polymer needles; silicone 2-shot micro ophthalmic implants; hearing aids; cranium reconstruction screws; and resorbable polymer implants. An example of a working inhaler component can be seen in Figure 1. These 16 micro moulded orifices are 152 microns (0.006”) in diameter and dispense the powder in a centrifugal and extremely accurate fashion.
Proof of Concept
It’s all about timing in this business. It’s critical for medical device and pharmaceutical manufacturers to be first to market and first in the surgeon’s hands for them to see, feel, and test. Once the prototypes are out there and the surgeons are supportive of the product, the device can be budgeted for clinical trials. It’s not uncommon to have micro components (micro moulded or micro machined) deliverable in 1–2 weeks. Some take longer because of the need to procure materials we comically refer to as “unobtainium” or “non-inventorium”. Custom compounds or custom blends with drug formulations typically take 4–6 weeks or longer to obtain, creating an opportunity for processing with another similar material until the real stuff arrives. This is commonly the practice with resorbable polymers due to them being $3k per pound. Micro moulding them in polypropylene, nylon, or TPE will allow a rough estimate match in dimension and shrink factor until such time as the costly materials can be utilised.
Multiple Material and Processing Platforms
It’s important for medical device and pharmaceutical companies to choose a micro developer that has multiple material and processing platforms under one roof. As shown in Figure 2, these micro processes are all-important in choosing the best process for the product being developed. It is common to employ a variety of these micro processing and material platforms for a multiple component assembly. Micro assembly is an art form on its own and requires its own article (stay tuned next month).
At times, the material is driving the process choice and at times the process drives the material choice. In any case, it’s a luxury to have them all in one place to choose the best material and process combination that fits the leading-edge application. At the bare minimum, micro machining represents the roots of the micro tree in which all of these processes thrive. With this truly enabling technology which can create hair-sized core pins and micro channels and cavities, all silicone, thermoplastic, and metal injection moulding is possible.
Micro Moulding
Not only should the product be delivered as drawn (and usually dust-specked size or featured), it should be prototyped in the exact process with which it will scale up. In other words, if the product will ultimately be micro injection moulded, it should be prototyped as a micro moulded component. The reason for this is that micro moulding will add very slight parting lines, draft requirements, gate vestige, and flow lines that may have different strength characteristics than their machined polymer counterparts. It’s best to figure these out in the initial prototyping stages than to go all the way through clinical trials with geometry and functional strengths that will not be replicated in the scaled-up micro moulded version.
Micro Machining
If the product is to stay micro machined as a ramped-up, high volume component, such considerations are equally relevant. Proving that the product can be machined with less than hair-sized end mills, and determining the costs for machining it — including the breakage of end mills — is a critical step in validating the machining process. Proper tool paths must be designed and tweaked to obtain the best surface finish and tolerance balance possible. Features/surfaces achievable in micro milling are: surface finish to 8 micro inches; 50 micron holes in 1/16” block without drill breakage; 12 micron wide microfluidic channels within 1 micron tolerance of one another. An example of these channels can be seen in Figure 3. The channels are 100 microns (0.004”) wide by 25 microns (0.001”) deep and the cutter seen in Figure 4 that is used for these channels is 98 microns (0.0039”).
Micro machining has come a very long way in just the last couple of years. The technology has flourished by leaps and bounds from hard milling with 0.002” (50 micron) end mills to hard milling with 0.0004” (10 micron) end mills! Machining pockets (channels, v-grooves, dimples) in microfluidic chip devices is measured in microns.
Micro Etching/Micro Embossing
Thousands of through holes in inkjet nozzles are electroformed to 10 microns in size and perfectly coiffed without burrs to insure straight nozzle flow. This same technology is used in pharmaceutical aspirators with nozzle orifices that have five micron holes in polymer cones.
Intellectual Property
Okay, let’s face it, this is our least favorite subject. We have had our legal counsels read, review, and process countless non-disclosures, and promised secrecy (including not telling our spouses about all of the cool technology we have seen over the years). It’s not fun, but it is critical to the success of our clients and our success too. Micro product developers and micro prototyping houses see their fair share of the most secretive, tiniest, leading-edge technology component and designs from all sorts of different medical and pharmaceutical companies, all competing against each other. It’s our job to really understand the Intellectual Property (IP) of each device we help develop, and to make sure that signing the agreements doesn’t hinder any of our existing client relationships. Good practices incude keeping scores of files on different micro subjects such as micro sharps/skin piercing materials/processes (required for moulded needles, transdermal devices); thin walled devices/materials/processes (required for cannuals, sheaths); deep draw orifices/materials/processes (required for balloon catheters, etc); and class VI materials/processes (required for all medical devices and implants).
These files should include the patents and “prior art” that can and cannot be used in medical devices, microfluidic devices, and pharmaceutical devices. Micro device product developers are cognisant of the nuances that create differential advantage in the marketplace. For example, patent searches on skin piercing in either metal or polymers will yield thousands of patents, however the geometry that actually pierces skin and is manufacturable is represented by two different entities. New patents and trade secrets are created every year on this one subject alone and if developers aren’t keeping track of where they may be stepping on IP, they won’t last very long in the business.
On the other hand, those who keep good records and keep track of prior art that is useable will save countless hours for themselves and their clients in the long run. An important file of note is Class VI Materials and Processes. This file should include all pertinent materials that have been classified for use in medical devices and pharmaceutical devices. All of the above files are invaluable to medical and pharmaceutical device client and developer alike.
Development to Production Cycle
Speed to market is so very critical, and micro product developers have quick, nimble, and accurate methods to create micro components and features in micro assemblies. Quick and nimble micro developers and production-minded contract manufacturers are separate entities for a reason — they are geared to different aspects in the development cycle. On one hand, micro developers are typically creative thinkers, lean and mean in overhead and personnel, and not typically ISO or FDA certified. These formal systems would hamper their meaningful existence for speed, accuracy, and agility in designing and manufacturing a highly iterative design to make quick, nimble, and low-cost changes to their client’s designs.
On the other hand, contract manufacturers are geared to high-volume production of micro devices, handling proven processes and tweaking them to fit their needs for speed and efficiency. They are extremely focused on getting their processes under control and running 24/7 without a hiccup. A very challenging feat is finding both a micro developer and a micro contract manufacturer that can be both or can work closely together to hand off the micro processing and material platform created by the micro developer for the client.
Working together on Gage R&R studies, DOE material studies, and quantifiable and repeatable material characterisation analysis for pharmaceutical implants creates huge value to the medical and/or pharmaceutical device manufacturer. It’s also important for the micro developer to understand scaling-up devices such that they can build this knowledge base into a robust process in the first place. These two very different entities working closely together can develop a highly robust, statistically valid, and repeatable micro process.
Donna Bibber is President/CEO of Micro Engineering Solutions, a micro product development company serving small to Fortune 50 companies. Ms Bibber has written and lectured hundreds of technical papers on micro manufacturing associated topics worldwide and was recently voted onto the List of 100 Notable People in Medical Devices.
