Kristin Brooks, Contract Pharma03.03.17
While the medical device segment is no stranger to 3D printing, this technology represents a relatively new approach for the pharmaceutical industry. Back in August 2015, the FDA approved the first drug product manufactured using 3D printing technology—Aprecia Pharmaceuticals’ SPRITAM, a prescription pill for the treatment of certain types of seizures caused by epilepsy in adults and children. The drug utilizes Aprecia’s ZipDose 3D printing technology platform to produce a porous formulation that rapidly disintegrates.
3D printing technology not only offers great potential to create drugs that are easier to consume and more effective, but also potential efficiencies throughout the research, development, and manufacturing process—even the supply chain.
Efficient manufacturing can be achieved since the active ingredients are added via 3D printers, offering the ability to produce high dosages and knowing that every dose will be exactly the same. This also implies that drugs can be customized for specific patients, with each dosage individually measured and printed.
Additionally, 3D printing technology may improve R&D, making the process less costly and more efficient. For example, the possibility to test drugs using 3D print sample tissues and organs instead of animals or synthetic models. Moreover, this technology might allow for new types of drug compounds based on new geometries and configurations made possible with 3D printing.
3D printing is estimated to grow into an $8.9 billion industry, with 21% projected to be spent on medical applications in the next 10 years.1 While this technology has many potential benefits, it also presents many complications for the pharmaceutical industry, and of course, the FDA approval process is critical to its success. While, the FDA seems quite open to the idea of 3D printing, the regulatory hurdles could be considerable.
Discussing the future of 3D printing in the pharmaceutical industry, David Hess, Solutions Consultant at Sparta Systems, also provides insights on benefits and challenges, safety concerns, and regulatory hurdles. –KB
Contract Pharma: What are the advantages of using 3D printing technology for drug products and what are the challenges? (development, approval, manufacturing)
David Hess: Rapid prototyping, customization, eliminated shipping costs and time: the benefits of 3D printing can translate to huge savings for startups and virtual companies, which sink or swim by the management of those core expenses. Established pharma groups can afford to drop tens of millions of dollars on a new production line or can take advantage of existing relationships with contract manufacturing organizations (CMOs).
Buying time at a CMO to produce test batches is expensive, requires collaboration from a number of groups from either company (R&D, QC, legal), and involves shipping to-and-from the facility. If that first batch isn’t up to spec, those rework costs rise exponentially. Printing that same small batch in-house saves on a ton of time, effort, and cost, and affords the company room for trial and error.
Any printing enthusiast that's tried to get their additive printer to level properly and print a halfway decent 'Benchy' (www.3dbenchy.com) knows that it takes time and intricate tweaks to get things to come out JUST right. And even when you do everything right, sometimes you just end up with plastic spaghetti.
When it comes to pharmaceutical manufacturing, those calibrations and preventive maintenance are defined for every piece of equipment that product comes in contact, with SOPs and work instructions detailing every step of the process. Managing that cycle for a full production line takes a team of full time employees to manage. These stringent policies and procedures are required regardless of the manufacturing model, meaning little to no savings on effort.
CP: What are some of the quality and patient safety concerns as manufacturing technologies continue to evolve?
DH: With the proliferation of newer manufacturing technology, we may see a swing from centralized rendering to local pharmacy or automated ‘vending-machine’ manufacturing. In that situation, there are glaring questions for any patient:
• What group is responsible for handling complaints and adverse events that arise?
• What group is responsible for product quality?
While the FDA regulates drug manufacturers, regulation of pharmacies is left to the state. 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 towards printed pills will need some federal oversight, lest we risk more lives unnecessarily.
CP: What impact would 3D printing of pharmaceutical products have on the supply chain?
DH: For specialty drugs that wouldn’t find benefits from patient-adjusted doses, anticipate business as usual. Generics may see a shift, however, especially if hospitals or corner chain pharmacies adopt the printers. There will always be a shipping cost associated with getting API to those printing locations, then into the hands of patients. In the end, active ingredient providers may be able to ship directly to regions of end users. 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.
CP: How might the FDA help or hurt innovation in the life science industry in regard to compliance?
DH: Unfortunately, compliance and innovation tend to be opposing forces; as one is dialed up, the other dials down. Given the FDA’s focus on patient protection and product consistency, submissions will have to cater to those topics. If a printed drug can provide a more accurate, faster acting dose to a patient, it serves that the FDA will fast track the approval over a standard tablet; this transition could potentially use the abbreviated new drug application (ANDA) to utilize newer technology.
For study directors, keeping a clinical trial on program with minimal deviations means cutting out risk; skewed results due to an improperly tuned printer could mean the rejection of that study, and, ultimately, the drug approval.
CP: What do you anticipate for 3D printing in the pharmaceutical industry in the near term and the future?
DH: With the quick turnaround on Aprecia's ZipDose FDA approval, we will likely see that technology licensed to a number of pain management pharmaceuticals, or for nutrient absorption medication such as pancrelipase. In addition, the current heroin epidemic could push for a fast-dissolving oral naloxone to counteract overdoses.
We will likely see more use with 3D printing regarding the creation of customized doses and release schedules for individual patients, or combination pills to simplify dosing. Elderly patients can struggle with keeping their pill schedules correct – combining them may streamline that experience.
Longer term could see the production of generics with common APIs at the major local pharmacies or from vending machines around the corner.
References:
1. Schubert C, van Langeveld MC, Donoso LA. Innovations in 3D printing: a 3D overview from optics to organs. Br J Ophthalmol 2014; 98(2):159–161.
David Hess is a Solutions Consultant at Sparta Systems. He has spent the past seven years in the Life Sciences industry, guiding Life Sciences organizations in implementations of Quality success practices. He holds a B.S. in Computer Science from Rutgers University, and is an avid FDM and SL 3D printing enthusiast.
3D printing technology not only offers great potential to create drugs that are easier to consume and more effective, but also potential efficiencies throughout the research, development, and manufacturing process—even the supply chain.
Efficient manufacturing can be achieved since the active ingredients are added via 3D printers, offering the ability to produce high dosages and knowing that every dose will be exactly the same. This also implies that drugs can be customized for specific patients, with each dosage individually measured and printed.
Additionally, 3D printing technology may improve R&D, making the process less costly and more efficient. For example, the possibility to test drugs using 3D print sample tissues and organs instead of animals or synthetic models. Moreover, this technology might allow for new types of drug compounds based on new geometries and configurations made possible with 3D printing.
3D printing is estimated to grow into an $8.9 billion industry, with 21% projected to be spent on medical applications in the next 10 years.1 While this technology has many potential benefits, it also presents many complications for the pharmaceutical industry, and of course, the FDA approval process is critical to its success. While, the FDA seems quite open to the idea of 3D printing, the regulatory hurdles could be considerable.
Discussing the future of 3D printing in the pharmaceutical industry, David Hess, Solutions Consultant at Sparta Systems, also provides insights on benefits and challenges, safety concerns, and regulatory hurdles. –KB
Contract Pharma: What are the advantages of using 3D printing technology for drug products and what are the challenges? (development, approval, manufacturing)
David Hess: Rapid prototyping, customization, eliminated shipping costs and time: the benefits of 3D printing can translate to huge savings for startups and virtual companies, which sink or swim by the management of those core expenses. Established pharma groups can afford to drop tens of millions of dollars on a new production line or can take advantage of existing relationships with contract manufacturing organizations (CMOs).
Buying time at a CMO to produce test batches is expensive, requires collaboration from a number of groups from either company (R&D, QC, legal), and involves shipping to-and-from the facility. If that first batch isn’t up to spec, those rework costs rise exponentially. Printing that same small batch in-house saves on a ton of time, effort, and cost, and affords the company room for trial and error.
Any printing enthusiast that's tried to get their additive printer to level properly and print a halfway decent 'Benchy' (www.3dbenchy.com) knows that it takes time and intricate tweaks to get things to come out JUST right. And even when you do everything right, sometimes you just end up with plastic spaghetti.
When it comes to pharmaceutical manufacturing, those calibrations and preventive maintenance are defined for every piece of equipment that product comes in contact, with SOPs and work instructions detailing every step of the process. Managing that cycle for a full production line takes a team of full time employees to manage. These stringent policies and procedures are required regardless of the manufacturing model, meaning little to no savings on effort.
CP: What are some of the quality and patient safety concerns as manufacturing technologies continue to evolve?
DH: With the proliferation of newer manufacturing technology, we may see a swing from centralized rendering to local pharmacy or automated ‘vending-machine’ manufacturing. In that situation, there are glaring questions for any patient:
• What group is responsible for handling complaints and adverse events that arise?
• What group is responsible for product quality?
While the FDA regulates drug manufacturers, regulation of pharmacies is left to the state. 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 towards printed pills will need some federal oversight, lest we risk more lives unnecessarily.
CP: What impact would 3D printing of pharmaceutical products have on the supply chain?
DH: For specialty drugs that wouldn’t find benefits from patient-adjusted doses, anticipate business as usual. Generics may see a shift, however, especially if hospitals or corner chain pharmacies adopt the printers. There will always be a shipping cost associated with getting API to those printing locations, then into the hands of patients. In the end, active ingredient providers may be able to ship directly to regions of end users. 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.
CP: How might the FDA help or hurt innovation in the life science industry in regard to compliance?
DH: Unfortunately, compliance and innovation tend to be opposing forces; as one is dialed up, the other dials down. Given the FDA’s focus on patient protection and product consistency, submissions will have to cater to those topics. If a printed drug can provide a more accurate, faster acting dose to a patient, it serves that the FDA will fast track the approval over a standard tablet; this transition could potentially use the abbreviated new drug application (ANDA) to utilize newer technology.
For study directors, keeping a clinical trial on program with minimal deviations means cutting out risk; skewed results due to an improperly tuned printer could mean the rejection of that study, and, ultimately, the drug approval.
CP: What do you anticipate for 3D printing in the pharmaceutical industry in the near term and the future?
DH: With the quick turnaround on Aprecia's ZipDose FDA approval, we will likely see that technology licensed to a number of pain management pharmaceuticals, or for nutrient absorption medication such as pancrelipase. In addition, the current heroin epidemic could push for a fast-dissolving oral naloxone to counteract overdoses.
We will likely see more use with 3D printing regarding the creation of customized doses and release schedules for individual patients, or combination pills to simplify dosing. Elderly patients can struggle with keeping their pill schedules correct – combining them may streamline that experience.
Longer term could see the production of generics with common APIs at the major local pharmacies or from vending machines around the corner.
References:
1. Schubert C, van Langeveld MC, Donoso LA. Innovations in 3D printing: a 3D overview from optics to organs. Br J Ophthalmol 2014; 98(2):159–161.
