PC1 -Relax -your 3D printer is doing your work for you
3D medicines printing: adding an extra dimension to personalised precision medicine
Patrick van Oirschot, MSc March 24th 2021 Disclosure • PCJM van Oirschot works in 2DP/3DP projects as implementation partner with several (academic) hospital pharmacies, pharmacy university departments and Digital Health Systems GmbH Self assessment questions 1. Are more than two technologies suitable in 3D medicines printing? Yes or No 2. Is lowering production cost the main goal of 3D medicines printing? Yes or No 3. Does it only take a 3D printer to get going? Yes or No Learning objectives • Reasons for 3D medicines printing • 3DP technology categories • Applications of 3DP • Steps towards clinical 3DP WHY
HOW
WHAT One size doesn’t fit all
What to prevent! “3D printing over the years”
Madla C.M., Trenfield S.J., Goyanes A., Gaisford S., Basit A.W. (2018) 3D Printing Technologies, Implementation and Regulation: An Overview. In: Basit A., Gaisford S. (eds) 3D Printing of Pharmaceuticals. AAPS Advances in the Pharmaceutical Sciences Series, vol 31. Springer, Cham. https://doi.org/10.1007/978-3-319-90755-0_2 Gartner 3DP Hype Cycle
https://www.3dnatives.com/en/gartner-hype-cycle-3dprintingpredictions-150120194/ Why using 3DP?
Better pharmacotherapy Economic results • Specific personalised dosage • Reduce cost due to less • Precise dose API use • Tailored release schedules • Less process cost • Faster product development
Increased Compliance Adherence Concordance • Ease of administration through: Other • Fast dissolving • Drug shortages • Easy swallowing • Trial medication: (small) batch • Patient centred design production • Form, size, colour, taste • Personalised drug tapering & • Convert intravenous to oral titration • Polypill • Decentralised production Areas of application
Pediatrics Neurology Geriatrics Oncology § Polypill, Polypharmacy § ACE inhibitors: Enalapril, § M. Parkinson § Breast cancer § Antihypertensive API, CSE Ramipril, Captopril § Ropinirol, Entacapone, § Tamoxifen inhibitors, etc § Methylphenidate Levodopa, Carbidopa, etc § Reason: low long term § Reason: individual API, § Reason: no suitable dose § Reason: individual API adherence due to side kidney dysfunction, available/dose combination, frequent effects, dose adherence, avoidance of adjustments necessary. dose adjustments personalisation waste
Immunosupressive drugs Cardiology NTI Depression § Ciclosporin, Everolimus, § Anticoagulation: § Digoxin, Digitoxin, § Sertraline Sirolimus Phenprocoumon, DOAC, Flecainide, Rifampicin, § Reason: standards doses § Reason: Blood level ARNI Valproic acid, L- not suitable for tapering measurement necessary; § Reason: individual dosage, Thyroxine, Iodide, individual dose to be adherence, waste Theophylline adjusted, adherence, avoidance § Reason: small avoidance of waste therapeutic window WHY
HOW
WHAT 3DP technologies
Vithani, K., Goyanes, A., Jannin, V. et al. An Overview of 3D Printing Technologies for Soft Materials and Potential Opportunities for Lipid-based Drug Delivery Systems. Pharm Res 36, 4 (2019). https://doi.org/10.1007/s11095-018-2531-1 2DP
2D Inkjet Printing Drug Printing on Individualised solution polymer film film 2DP concepts
Preis et al. (2015), Perspective: Concepts of printing technologies for oral film formulations. Int. J. Pharm. 494(2): 578-584. Oral Dispersible Film (ODF) essential advantages for patients
Oral Dispersible Film is a well established and monographed dosage form
Advantage of ODF
• Convenient dosing with high acceptance by elderly and children • On-The-GO dosage form / no water needed • Immediate release profile • Individual colour and taste Scalable 2D Drug Printing
Table-top for Pharmacies Production scale 3DP concepts
• Additive manufacturing • Rapid manufacturing/prototyping • Building up solid objects layer by layer
3D Printing Techniques
Fused Selective (Semi Direct Binder Stereolith Depositio Laser Solid) powder Jetting ography n Sintering Extrusion extrusion Modeling Dose variation by digital manufacturing
Ø Sizes Ø Geometries
Ø Amounts of infill Ø Infill patterns
• User interface easy and safe input • Printer setting only by supervisor • Process data are automatically transferred by inserting cartridge 3D Drug Printing: Polypill by 3DP
Khaled et al. (2015) 3D printing of tablets containing multiple drugs with defined release profiles. Int. J. Pharm. 494: 643-650. Examples of personalised medicines 3D Printing scalability API’s 2DP/3DP in research API(s) Medical use 4-Aminosalicylic acid (4-ASA, para-aminosalicylic acid (PAS), brand Paser) antibiotic primarily used to treat tuberculosis 5-Fluorouracil (Adrucil) cancer Dactinomycin (Actinomycin D) chemotherapy medication used to treat a number of types of cancer Acyclovir antiviral medication Amlodipine (Norvasc) high blood pressure and coronary artery disease Amoxicillin antibiotic used to treat a number of bacterial infections Anastrozole (Arimidex) breast cancer Aripiprazole (Abilify) atypical antipsychotic Ascorbic acid (hexuronic acid) chemotherapeutic and biological response modifying agent. ⋮ ⋮ Vancomycin antibiotic used to treat a number of bacterial infections high blood pressure, angina (chest pain from not enough blood flow to the heart), and supraventricular tachycardia.[5] It may also be used for the prevention of migraines and Verapamil cluster headaches Warfarin (Coumadin) anticoagulant (blood thinner) Zotarolimus (INN, codenamed ABT-578, sirolimus, rapamycin). immunosuppressant, It was designed for use in stents with phosphorylcholine as a carrier
PVO:166 API’s identified Where to find 3DP studies?
Countries with reported initiatives in 2DP/3DP medicines printing
PVO: 24 countries Mogelijk gemaakt met Bing © DSAT for MSFT, GeoNames, Microsoft, Navinfo, Navteq, TomTom In publications WHY
HOW
WHAT Conversion into daily practice? … my personal experience …
Inspiration To what is congresses / Literature Believers From possibility needed class
Set-up: Scope Project proposal Supplier Team API, excipients
1.Compatibility 3. Substrate Development 2.Ink/Filament study development Conversion into daily practice? … my personal experience …
Reporting Hardware Software 4. Printing trials Packaging (inspection) placement development
Operational ... Funding Approval Stability testing GMP support sourcing
Handover in Reimbursement Study/publication ... practice Impact on stakeholders managing different needs
Legislative bodies Necessities Pharma • Research industry • (Pilot) projects
Doctor Compounding Wholesalers Health insurers Pharmacist • Investments / budget • "Players"
IT Patient • Laws and regulations Nurse • Reimbursement Caregiver • IT systems Board of • Patient data directors • Acceptance Politics Requirements Project mandate Partners
Business case Suppliers
Funding Legislative approval
Project organisation And if you thought you had it all ... Adding another dimension at 3DP • Morphology Adjustments • By time or external stimuli such as: – light – Temperature – Water – pH 4DP - Bio adhesion device • Attach to intestines • 3-layered muco- adhesive DDS • >> More drug traverse
Firth J., Gaisford S., Basit A.W. (2018) A New Dimension: 4D Printing Opportunities in Pharmaceutics. In: Basit A., Gaisford S. (eds) 3D Printing of Pharmaceuticals. AAPS Advances in the Pharmaceutical Sciences Series, vol 31. Springer, Cham. https://doi.org/10.1007/978-3-319-90755-0_8 Take home messages • 3DP facilitates a paradigm shift in pharmacotherapy • We are only at the beginning of the curve ... … but it is not a distant future • The possibilities are endless ... the obstacles also they say ... • 3DP is ready for clinical practice
• 3DP does not come naturally, but we make it happen! I would like to recommend
• Frost & Sullivan: New Paradigm Shift in Treatment • Glady, Gilbert. (2019). The Bio Immune(G)ene Medicine or How to Use a Maximum of Molecular Resources of the Cell for Therapeutic Purposes. Edelweiss Applied Science and Technology. 26-29. 10.33805/2576-8484.164 • Madla C.M., Trenfield S.J., Goyanes A., Gaisford S., Basit A.W. (2018) 3D Printing Technologies, Implementation and Regulation: An Overview. In: Basit A., Gaisford S. (eds) 3D Printing of Pharmaceuticals. AAPS Advances in the Pharmaceutical Sciences Series, vol 31. Springer, Cham. https://doi.org/10.1007/978-3-319-90755-0_2 • Gartner Hype Cycle: 3D Printing Predictions for 2019 https://www.3dnatives.com/en/gartner-hype-cycle-3dprintingpredictions-150120194/ • Vithani, K., Goyanes, A., Jannin, V. et al. An Overview of 3D Printing Technologies for Soft Materials and Potential Opportunities for Lipid-based Drug Delivery Systems. Pharm Res 36, 4 (2019). https://doi.org/10.1007/s11095-018-2531-1 • Preis M, Breitkreutz J, Sandler N. Perspective: Concepts of printing technologies for oral film formulations. Int J Pharm. 2015 Oct 30;494(2):578-584. doi: 10.1016/j.ijpharm.2015.02.032. Epub 2015 Feb 13. PMID: 25683143 • Khaled et al. (2015) 3D printing of tablets containing multiple drugs with defined release profiles. Int. J. Pharm. 494: 643-650 • Firth J., Gaisford S., Basit A.W. (2018) A New Dimension: 4D Printing Opportunities in Pharmaceutics. In: Basit A., Gaisford S. (eds) 3D Printing of Pharmaceuticals. AAPS Advances in the Pharmaceutical Sciences Series, vol 31. Springer, Cham. https://doi.org/10.1007/978-3-319-90755-0_8 • Trenfield SJ, Awad A, Goyanes A, Gaisford S, Basit AW. 3D Printing Pharmaceuticals: Drug Development to Frontline Care. Trends Pharmacol Sci. 2018 May;39(5):440-451. doi: 10.1016/j.tips.2018.02.006. Epub 2018 Mar 11. PMID: 29534837.