David HessHow will 3D printing impact key players in the pharma supply chain (suppliers, manufacturers, distributors, etc.)?
3D printing has a true potential to disrupt the generic pharmaceutical supply chain, giving local pharmacies and hospitals the ability to create their own medicines. API suppliers could ship directly to those endpoints, shipping to regions where their consumers will have their drugs rendered. Hospitals or large regional pharmacies could simplify their storage into larger containers for filler and common ingredients like acetaminophen, with smaller containers for less common APIs.
Contract manufacturers could diversify their customers’ utilization of production lines, providing smaller batch runs a more cost-effective solution than the traditional molded offering. For a slimmed down pharmaceutical startup, those savings can be directed into their clinical trial efforts.
While it’s doubtful that consumers will have in-home printers, it is feasible that their mainstream corner pharmacies will adopt the technology.
What are the benefits of 3D printing drugs vs.using traditional molds?
3D printing in general allows for several key benefits: customization in scale and density/infill, internal composition and rapid prototyping. Each of these transitions directly to pharmaceutical creation.
Being able to generate a dosing specific to a patient, with a certain subset of each compound in the drug, assembled for a precise time-release schedule means better treatment for a patient. Imagine a drug with a monitoring device at the core, able to transmit a patient’s vitals immediately post-absorption.
Rapid prototyping allows new mixtures to be tested on an extremely small batch, without the need to place an order with a CMO or set up a full production run. Not having to buy time on a 24/7 CMO line translates into direct savings that can be spent elsewhere.
What are the risks of 3D printing drugs for pharma manufacturers specifically?
As with any 3D print, even under perfect conditions, the opportunities to deviate from spec are infinite. Calibration and preventive maintenance are already painstaking efforts for pharmaceutical manufacturers, with teams assembled to follow consistently scrutinized SOPs and work instructions for every piece of equipment on their production line; this is just as evident with a printing device, where things like bed leveling, material extrusion and retraction, surface adhesion and any number of other factors are accounted for.
Physical production complications aside, there are a number of other risk factors that may lose visibility in the transition to 3D printing.
• Was the printer sanitized properly after the last batch was printed? There would be serious adverse events if testosterone therapy medication was produced prior to prenatal pills, for example.
• Was the batch created with a single lot of API, or did the print run out halfway through, requiring a refill from a different supplier’s stock?
• Did the printer operate at temperatures above the permissible limits of the ingredients?
Inconsistency in finished goods is an easy target for 483s, so do not expect larger, risk-averse, publicly traded corporations to pick up the technology while unproven. For smaller firms, balancing the budget may mean taking on a bit more risk.
How can pharma manufacturers ensure quality when leveraging 3D printing technologies?
Pharmaceutical manufacturers will need to step up their game with regard to automatic detection of deviations; instead of random sampling, each pill can be measured for weight, size, and appearance during the printing process.
If drug production is more distributed, the traditional large manufacturer model goes out the window - each printing group would need specifications from their suppliers on how best to assemble the medication.
Regardless of the method used for manufacturing these medications, manufacturers should employ Good Manufacturing Practices, with full traceability in a 21 CFR Part 11 Compliant quality management system.
How will 3D printing drugs impact drug delivery?
Aprecia’s ZipDose is a huge leap in rapid release medication. Have you ever tried to get a toddler to keep a dissolvable medicine in their mouth without chewing or swallowing it? Being able to give them their dose in under 10 seconds means closer adherence to a physician’s treatment plan.
We will likely see that technology extend to any number of pain management drugs, where instant relief is typically only available intravenously. Orally administered naloxone to counter heroin overdoses could find its way into the kits of EMS staff the world over.
What would you expect to see in a FDA draft guidance on additive manufacturing for pharmaceuticals?
Given the variance in styles of additive manufacturing, expect a greater level of scrutiny regarding machine calibration/preventive maintenance.
The FDA may require manufacturers to fulfill specific pill tests:
• Variable time release schedules of the same size tablet
• Different density at the same size
• Same density at variable size
• Pausing a printing run, restarting the run and comparing those pills with normal batches
The FDA should specify which entities maintain the responsibility for adverse event reporting as manufacturing is shifted. Third-party additive manufacturing outside of major manufacturing is comparable to that of compounding facilities. In 2012 we saw a fungal meningitis outbreak stem from the New England Compounding Center’s packaging of methylprednisolone. The incident killed 64 people, resulting in 2013’s Drug Quality and Security Act, which added provisions for compounding pharmacies and supply chain security. Based on that act, a pharmacist is still required to oversee the production of those medications outside of a manufacturer’s site. The push toward printed pills will need some federal oversight, lest we risk more lives unnecessarily.