Tomorrow’s world today: automating medical device manufacture

The earliest medical devices are centuries old: the magnifying glass, invented in 1250 by Roger Bacon; the flexible catheter, invented in 1752 by Benjamin Franklin; and René Laennec's stethoscope from 1815. Sanctorius of Padua's pulsilogium, a device used to measure pulse rate with the help of a pendulum made from a cord and a weight, represents the first interaction between man and a medical device for the purpose of measuring a physiological parameter; it dates from the 17th century.

Much related to medical devices and their manufacture has changed in the intervening centuries; indeed, much has changed in the past two decades.

The manufacture of devices has been affected dramatically in the past two decades by many factors: advances in technology; regulatory demands; changes in the practice of medicine related to screening, diagnosis, and therapy; increased understanding of existing diseases and emergence of new ones; concerns for patient safety; competitive demands (time to market and cost); the need for uniformity across what are sometimes millions of units of simple, single-use medical devices; the ability to assemble ever-more-complex devices; developments in device miniaturisation; cost pressures from payers; the need for greater flexibility due to shorter product life cycles and small batch runs; and, as devices more frequently become a part of us, the need for devices built in clean rooms.

These factors, taken together, have contributed to the accelerated growth of medical device manufacturing automation, which offers opportunities for higher quality, greater consistency and lower costs than traditional worker-staffed assembly lines can produce. Manufacturing automation includes a wide range of technologies, including robotics and expert systems, telemetry and communications, electro-optics, cybersecurity, process measurement and control, sensors, wireless applications, systems integration and test measurement. Manufacturing automation can also exist in a smaller footprint and in environments not so conducive to humans.

Furthermore, automated manufacturing helps companies meet regulatory requirements and standards expectations, such as the US FDA's quality system regulation under 21 CFR part 820; EU medical device quality requirements under ISO 13485; and ISPE's good automated manufacturing practice. It also enables medical device companies to readily meet statistical process controls; in-process visual inspections; packaging, shipping, component and finished goods warehousing and control; component/product identification and finished goods inspection.

Examples of current manufacturing automation

In today's $330-billion global medical device market, a wide variety of medical devices of different levels of complexity are produced by automated manufacturing methods, including hearing aids, miniaturised devices, orthopaedic implants, cardiac stents, catheters, cardiac pacemakers, insulin pumps and blood dialysers.

At the cutting edge of automated manufacture is 3D printing, which works by building an object layer upon layer. While many of us are familiar with research into the 3D printing of tissue-based heart valves, ears, artificial bone, joints, menisci, vascular tubes and skin grafts (a field known as 'bioprinting'), it may be surprising to learn that there are already an estimated ten million 3D-printed hearing aids in use worldwide. And automated manufacturing via 3D printing is fast: the German company EnvisionTEC has a system that can print 65 hearing-aid shells in 60-90 minutes.

3D printing is also used in the automated manufacture of medical devices for dentistry. 3D printers can produce surgical drill guides tailored to individual patients, ensuring precise drilling for the placement of dental implants. They can also manufacture porcelain crowns and braces - Align Technology printed 17 million Invisalign braces last year alone.

MEMS (micro-electromechanical systems), miniaturised devices too small to be assembled and tested by humans, are also at the forefront of automated medical device manufacturing. These tiny mechanical devices include sensors, motors, nozzles and valves, some of which fit onto the surface of computer chips. According to Yole Développement, the MEMS market is valued at approximately $12.5 billion and is expected to reach $19.5 billion by 2017. While such devices may seem futuristic, some are already being marketed, while others are undergoing clinical trials.

For example, Proteus Digital Health manufactures a wireless system named Helius, which features an ingestible MEMS sensor used to monitor pill ingestion. After the tagged pill is taken and reaches the stomach, an RF signal is generated and sends a unique number to a wearable patch receiver, which stores the number and time of detection. The patch then transmits the data wirelessly to the user's mobile phone. The device is currently cleared by the FDA for use with placebo drugs.

Currently in clinical trials, Senseonics' continuous glucose monitoring system uses an implantable MEMS device that measures the fluorescent change in a glucose-indicating polymer on its external surface; an embedded LED is used to excite the polymer. Second Sight's Argus II retinal prosthesis system, used by people with inherited blindness, features a MEMS electrode array that emits small pulses of electricity to stimulate the retina's remaining cells using information from a video camera, helping the user in the recognition of doors and pavements. Finally, Given Imagings' PillCam SB is a welcome advance in endoscopy - it's a pill-sized camera that can be ingested by the patient to allow clinicians to have a look inside the small bowel.

MEMS devices are also used in drug delivery devices, neurosignal detection and neurostimulation applications. Lab-on-a-chip and miniaturised biochemical analytical instruments are being marketed as well. MEMS pressure sensors are quite common and are used in a wide variety of applications including:

• monitoring blood pressure in the IV lines of patients in intensive care
• measuring intrauterine pressure during childbirth
• blood pressure and respiration monitoring
• measuring and controlling vacuum level during eye surgery
• measuring the pressure on hospital beds used for burn victims
• monitoring the patient's breathing cycle and releasing medication in inhalers at the proper time
• measuring input and output pressures in dialysis
• monitoring the flow rate, and detecting obstructions and blockages in drug infusion pumps that indicate that the drug is not being properly delivered to the patient.

Automated manufacturing has brought improvement in form and function to more common medical devices. For those familiar with the look and feel of the user interfaces of devices of old, current devices will come as a surprise. For example, the Tandem Diabetes Care t:slim insulin pump sports a smartphone look, touch screen and a wide range of smartphone-like accessories (cases, screen protectors, charger cables and so on). As concerns function, most (if not all) knee and hip implants have been manufactured using automated processes since the late 1990s, with manufacturers experiencing improved product quality, tighter tolerances and greater product consistency.

Challenges to automation

The current challenges to the automation of medical device manufacturing are numerous. They include:

• The capital investment required for a switch from traditional to automated medical device manufacturing. For example, one hearing aid manufacturer reports that, while using 3D printing has streamlined production and introduced consistency, it has also increased capital costs. A hearing aid 3D printer can cost anything from $20,000-$150,000.
• An ever-changing regulatory environment in which regulators try to keep pace with technology. The FDA is currently grappling with cybersecurity in medical devices, and has two laboratories studying 3D printing of medical devices; guidance on 3D printing is expected in two years. However, the FDA has not shown significant success in introducing guidance for cutting-edge topics in a timely fashion; mobile medical applications guidance finalisation took more than two years after closing the comment period on the draft version.
• The perception that robots are complicated and require experts to operate them, when in fact they are simply a form of automation.

The future

Three areas are likely to dominatethe future of medical device manufacturing automation:

3D printing: the 3D printing of medical devices is expected to play a huge role in the future of medical device manufacturing automation, with prosthetics, orthotics and implantables being produced from a wide variety of materials, including synthetic, human and animal tissue .

MEMS: with promising applications around the convergence of health information technology and medical devices such as the aforementioned Helius system, MEMS looms large in the future of smart devices. Specialised automated manufacturing equipment will be necessary to bring these new devices to market on the scale anticipated.

Nanotechnology: while definitely a technology of the future, molecular manufacturing - manufacturing from the molecular level up - holds promise for automated medical device manufacturing. Molecular manufacturing can be carried out by nanorobots. Envisioned are everything from cheap implantable sensors for monitoring to devices able to cure diseases by repairing the body at the molecular level.

Conclusion

While early medical devices have the charm of the antique and the whiff of the bespoke, their inventors would scarcely have been able to imagine the revolution in quality and innovation brought about by today's advances in medical device manufacturing automation. It's safe to say that the future is now for automated manufacturing of medical devices. Current automated manufacturing capabilities related to 3D printing and MEMS will advance as technology develops further, and nanotechnology will bring science fiction-like tools to clinicians.