What Does Pharmaceutical 3D Printing Cost? A Framework and Case Study with Hydrocortisone for Adrenal Insufficiency

Overview

Journal Pharmacoecon Open

Date 2024 Dec 31

PMID 39739242

Authors

Sejad Ayyoubi

Liesbeth Ruijgrok

Hugo van der Kuy

Renske Ten Ham

Frederick Thielen

Affiliations

Soon will be listed here.

Abstract

Background: Pharmaceutical three-dimensional printing (3DP) technology offers an automated platform that can be utilized to manufacture personalized medicine, improving pharmacotherapy. Although 3D-printed products have entered clinical trials, no costing studies have been performed yet. Cost insights can aid researchers and industry in making informed decisions about the feasibility and scalability of 3DP.

Objective: The aim of this research was therefore to develop a framework that can be utilized to estimate the manufacturing cost of one 3D tablet in a hospital pharmacy setting.

Methods: To develop the costing framework, general manufacturing phases were identified, consisting of (i) pre-printing, (ii) printing, and (iii) post-printing. For each phase, cost categories were defined, including personnel, materials, equipment, facility, and quality assurance. The three phases combined with the categories formed the base of the costing framework. An earlier developed 3D-printed hydrocortisone formulation (M3DICORT) was used as a case study. Costs were expressed in 2022 euros (€). The framework was applied to M3DICORT in four scenarios: a base case scenario, worst-case scenario, best-case scenario, and a scaling scenario. In the scaling scenario, we assumed that 3D inks were mass produced.

Results: Costs of manufacturing a single M3DICORT tablet were €1.97-3.11 (best-case-worst-case) and €1.58-2.26 for the scaling scenario.

Conclusion: Manufacturing costs of 3D-printed pharmaceuticals were thus far unknown. The framework is translated into an open-access costing tool to facilitate adoption by other parties, and is also applicable for other pharmaceutical 3DP techniques.

References

Robles-Martinez P, Xu X, Trenfield S, Awad A, Goyanes A, Telford R . 3D Printing of a Multi-Layered Polypill Containing Six Drugs Using a Novel Stereolithographic Method. Pharmaceutics. 2019; 11(6). PMC: 6630370. DOI: 10.3390/pharmaceutics11060274. View

Beer N, Hegger I, Kaae S, De Bruin M, Genina N, Alves T . Scenarios for 3D printing of personalized medicines - A case study. Explor Res Clin Soc Pharm. 2022; 4:100073. PMC: 9031080. DOI: 10.1016/j.rcsop.2021.100073. View

Ayyoubi S, van Kampen E, Kocabas L, Parulski C, Lechanteur A, Evrard B . 3D printed, personalized sustained release cortisol for patients with adrenal insufficiency. Int J Pharm. 2022; 630:122466. DOI: 10.1016/j.ijpharm.2022.122466. View

Konta A, Garcia-Pina M, Serrano D . Personalised 3D Printed Medicines: Which Techniques and Polymers Are More Successful?. Bioengineering (Basel). 2017; 4(4). PMC: 5746746. DOI: 10.3390/bioengineering4040079. View

Nowotny H, Ahmed S, Bensing S, Beun J, Brosamle M, Chifu I . Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis. Endocrine. 2021; 71(3):586-594. PMC: 7929907. DOI: 10.1007/s12020-021-02649-6. View

Neumann U, Burau D, Spielmann S, Whitaker M, Ross R, Kloft C . Quality of compounded hydrocortisone capsules used in the treatment of children. Eur J Endocrinol. 2017; 177(2):239-242. DOI: 10.1530/EJE-17-0248. View

Bury D, Wolfs T, Ter Heine R, Muilwijk E, van der Elst K, Tissing W . Pharmacokinetic investigations of isavuconazole in paediatric cancer patients show reduced exposure of isavuconazole after opening capsules for administration via a nasogastric tube. J Antimicrob Chemother. 2023; 78(12):2886-2889. DOI: 10.1093/jac/dkad324. View

Pandey M, Choudhury H, Lau Chui Fern J, Kee A, Kou J, Jing J . 3D printing for oral drug delivery: a new tool to customize drug delivery. Drug Deliv Transl Res. 2020; 10(4):986-1001. DOI: 10.1007/s13346-020-00737-0. View

Pietrzak K, Isreb A, Alhnan M . A flexible-dose dispenser for immediate and extended release 3D printed tablets. Eur J Pharm Biopharm. 2015; 96:380-7. DOI: 10.1016/j.ejpb.2015.07.027. View

10.

Verkerk K, Veenendaal H, Severens J, Hendriks E, Burgers J . Considered judgement in evidence-based guideline development. Int J Qual Health Care. 2006; 18(5):365-9. DOI: 10.1093/intqhc/mzl040. View

11.

Lee K, Kassab Y, Taha N, Zainal Z . Factors Impacting Pharmaceutical Prices and Affordability: Narrative Review. Pharmacy (Basel). 2020; 9(1). PMC: 7838942. DOI: 10.3390/pharmacy9010001. View

12.

Trenfield S, Awad A, Goyanes A, Gaisford S, Basit A . 3D Printing Pharmaceuticals: Drug Development to Frontline Care. Trends Pharmacol Sci. 2018; 39(5):440-451. DOI: 10.1016/j.tips.2018.02.006. View

13.

Ayyoubi S, Cerda J, Fernandez-Garcia R, Knief P, Lalatsa A, Healy A . 3D printed spherical mini-tablets: Geometry versus composition effects in controlling dissolution from personalised solid dosage forms. Int J Pharm. 2021; 597:120336. DOI: 10.1016/j.ijpharm.2021.120336. View

14.

Grissinger M . Life-Threatening Errors With Flecainide Suspension in Children. P T. 2018; 43(5):258-286. PMC: 5912238. View

15.

Hill S, Olson L, Falck-Ytter Y, Cruz A, Atkins D, Baumann M . Incorporating considerations of cost-effectiveness, affordability, and resource implications in guideline development: article 6 in Integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report. Proc Am Thorac Soc. 2012; 9(5):251-5. DOI: 10.1513/pats.201208-059ST. View

16.

Maniruzzaman M, Nokhodchi A . Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters. Drug Discov Today. 2016; 22(2):340-351. DOI: 10.1016/j.drudis.2016.11.007. View

17.

Chabre O, Goichot B, Zenaty D, Bertherat J . Group 1. Epidemiology of primary and secondary adrenal insufficiency: Prevalence and incidence, acute adrenal insufficiency, long-term morbidity and mortality. Ann Endocrinol (Paris). 2017; 78(6):490-494. DOI: 10.1016/j.ando.2017.10.010. View

18.

Binson G, Sanchez C, Waton K, Chanat A, Di Maio M, Beuzit K . Accuracy of Dose Administered to Children Using Off-Labelled or Unlicensed Oral Dosage Forms. Pharmaceutics. 2021; 13(7). PMC: 8308974. DOI: 10.3390/pharmaceutics13071014. View

19.

Seoane-Viano I, Januskaite P, Alvarez-Lorenzo C, Basit A, Goyanes A . Semi-solid extrusion 3D printing in drug delivery and biomedicine: Personalised solutions for healthcare challenges. J Control Release. 2021; 332:367-389. DOI: 10.1016/j.jconrel.2021.02.027. View

20.

Goyanes A, Madla C, Umerji A, Duran Pineiro G, Giraldez Montero J, Lamas Diaz M . Automated therapy preparation of isoleucine formulations using 3D printing for the treatment of MSUD: First single-centre, prospective, crossover study in patients. Int J Pharm. 2019; 567:118497. DOI: 10.1016/j.ijpharm.2019.118497. View