Regulatory Perspectives on 3D Printing in Pharmaceuticals

  • Akm KhairuzzamanEmail author
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 31)


The genomic revolution and the age of personalized medicine has exponentially increased in interest and understanding since its introduction in the last decade. Embracing innovation, the United States Food and Drug Administration (FDA) approved the first three-dimensional (3D) printed drug product and thus, has set the benchmark for an industrial revolution in pharmaceutical manufacture. Regulatory standards, however, require each product of each batch to be within specifications with respect to purity, impurities and quality. The regulatory environment of individual countries, however, differ in terms of manufacturing, distribution and compounding of drug products and thus, need to be fundamentally considered for on-demand and industrial pharmaceutical 3D printing. In the past, it would have seemed like science fiction to design and produce our medicines with 3D printing technology, but it is now certainly becoming reality that will only grow further. This chapter aims to discuss the current regulatory environment for 3D printing mass production and the regulatory gaps and challenges that need to be acknowledged to advance the modern manufacture of medicines.


3D printing Personalized pharmaceuticals Additive manufacturing Process validation Medical devices Drug delivery systems 


  1. 1.
    United States Food and Drug Administration. Highlights of prescribing information – Spritam. 2015. Available from:
  2. 2.
    Norman J, Madurawe RD, Moore CMV, Khan MA, Khairuzzaman A. A new chapter in pharmaceutical manufacturing: 3D printed drug products. Adv Drug Deliv Rev. 2017;108:39–50.CrossRefPubMedGoogle Scholar
  3. 3.
    Trenfield SJ, Awad A, Goyanes A, Gaisford S, Basit AW. 3D printing pharmaceuticals: drug development to frontline care. Trends Pharmacol Sci. 2018;39(5):440–5.CrossRefPubMedGoogle Scholar
  4. 4.
    Awad A, Trenfield SJ, Goyanes A, Gaisford S, Basit AW. Reshaping drug development using 3D printing. Drug Discov Today. 2018;
  5. 5.
    Prima MD, Coburn J, Hwang D, Kelly J, Khairuzzaman A, Ricles L. Additively manufactured medical products – the FDA perspective. 3D Print Med. 2016;2:1.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    United States Government Accountability Office. 3D printing: opportunities, challenges, and policy implications of additive manufacturing. 2015. Available from:
  7. 7.
    Chhaya MP, Poh PS, Balmayor ER, van Griensven M, Schantz JT, Hutmacher DW. Additive manufacturing in biomedical sciences and the need for definitions and norms. Expert Rev Med Devices. 2015;12(5):537–43.CrossRefPubMedGoogle Scholar
  8. 8.
    International Standards Organization. ISO/ASTM 52900 Additive manufacturing – General principles – Terminology. [under development] Available from:
  9. 9.
    Prasad LM, Smyth H. 3D printing technologies for drug delivery: a review. Drug Dev Ind Pharm. 2016;42(7):1019–31.CrossRefPubMedGoogle Scholar
  10. 10.
    Yu DG, Yang XL, Huang WD, Liu J, Wang YG, Xu H. Tablets with material gradients fabricated by three-dimensional printing. J Pharm Sci. 2007;96(9):2446–56.CrossRefPubMedGoogle Scholar
  11. 11.
    Alhijjaj M, Belton P, Qi S. An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersion prepared via fused deposition modeling (FDM) 3D printing. Eu J Pharm Biopharm. 2016;108:111–25.CrossRefGoogle Scholar
  12. 12.
    Wang J, Goyanes A, Gaisford S, Basit AW. Stereolithographic (SLA) 3D printing of oral modified-release dosage forms. Int J Pharm. 2016;503:207–12.CrossRefPubMedGoogle Scholar
  13. 13.
    Goyanes A, Martinez PR, Buanz A, Basit A, Gaisford S. Effect of geometry on drug release from 3D printed tablets. Int J Pharm. 2015;494:657–63.CrossRefPubMedGoogle Scholar
  14. 14.
    Okwuosa TC, Pereira BC, Arafat B, Cieszynska M, Isreb A, Alhnan MA. Fabricating a Shell-Core delayed release tablet using dual FDM 3D printing for patient-centred therapy. Pharm Res. 2017;34:427–37.CrossRefPubMedGoogle Scholar
  15. 15.
    Acosta-Vélez GF, Wu BM. 3D pharming: direct printing of personalized pharmaceutical tablets. Pol Sci. 2016;1:2.Google Scholar
  16. 16.
    Goyanes A, Wang J, Buanz A, Martinez-Pacheco R, Telford R, Gaisford S, et al. 3D printing of medicines: engineering novel oral devices with unique design and drug release characteristics. Mol Pharm. 2015;12(11):4077–84.CrossRefPubMedGoogle Scholar
  17. 17.
    Yi HG, Cho YJ, Kang KS, Hong JM, Pati RG, Park MN, et al. A 3D printed local drug delivery patch for pancreatic cancer growth suppression. J Control Release. 2016;238:231–41.CrossRefPubMedGoogle Scholar
  18. 18.
    Khaled SA, Burley JC, Alexander MR, Yang J, Roberts CJ. 3D printing of tablets containing multiple drugs with defined release profiles. Int J Pharm. 2015;494(2):643–50.CrossRefPubMedGoogle Scholar
  19. 19.
    Katstra WE, Palazzolo RD, Rowe CW, Giritlioglu B, Teung P, Cima MJ. Oral dosage forms fabricated by three dimensional printing. J Control Release. 2000;66(1):1–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Sun Y, Soh S. Printing tablets with fully customizable release profiles for personalized medicine. Adv Mater. 2015;27(47):7847–53.CrossRefPubMedGoogle Scholar
  21. 21.
    Wu BM, Borland SW, Giordano RA, Cima LG, Sachs EM, Cima MJ. Solid free-form fabrication of drug delivery devices. J Control Release. 1996;40(1–2):77–87.CrossRefGoogle Scholar
  22. 22.
    Vogel BJ. Intellectual property and additive manufacturing/3D printing: strategies and challenges of applying traditional IP Laws to a transformative technology. Minn J L Sci Tech. 2016;17(2):880–906.Google Scholar
  23. 23.
    Beck RCR, Chaves PS, Goyanes A, Vukosavljevic B, Buanz A, Windbergs A, et al. 3D printed tablets loaded with polymeric nanocapsules: an innovative approach to produce customized drug delivery systems. Int J Pharm. 2017;528(1-2):268–79.CrossRefPubMedGoogle Scholar
  24. 24.
    Alhnan MA, Okwuosa TC, Sadia M, Wan KW, Ahmed W, Arafat B. Emergence of 3D printed dosage forms: opportunities and challenges. Pharm Res. 2016;33(8):1817–32.CrossRefPubMedGoogle Scholar
  25. 25.
    Fina F, Goyanes A, Gaisford S, Basit AW. Selective laser sintering (SLS) 3D printing of medicines. Int J Pharm. 2017;529(1-2):285–93.CrossRefPubMedGoogle Scholar
  26. 26.
    Fina F, Madla CM, Goyanes A, Zhang J, Gaisford S, Basit AW. Fabricating 3D printed orally disintegrating printlets using selective laser sintering. Int J Pharm. 2018;541(1-2):101–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Fina F, Goyanes A, Madla CM, Awad A, Trenfield SJ, Kuek JM, et al. 3D printing of drug-loaded gyroid lattices using selective laser sintering. Int J Pharm. 2018;
  28. 28.
    Genina N, Boetker JP, Colombo S, Harmankaya N, Rantanen J, Bohr A. Anti-tuberculosis drug combination for controlled oral delivery using 3D printed compartmental dosage forms: from drug product design to in vivo testing. J Control Release. 2017;268:40–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Gioumouxouzis CI, Katsamenis OL, Bouropoulos N, Fatouros DG. 3D printed oral solid dosage forms containing hydrochlorothiazide for controlled drug delivery. J Drug Deliv Sci Technol. 2017;40:164–71.CrossRefGoogle Scholar
  30. 30.
    Goyanes A, Chang H, Sedough D, Hatton GB, Wang J, Buanz A, et al. Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing. Int J Pharm. 2015;496(2):414–20.CrossRefPubMedGoogle Scholar
  31. 31.
    Goyanes A, Det-Amornrat U, Wang J, Basit AW, Gaisford S. 3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems. J Control Release. 2016;234:41–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Goyanes A, Kobayashi M, Martínez-Pacheco R, Gaisford S, Basit AW. Fused-filament 3D printing of drug products: microstructure analysis and drug release characteristics of PVA-based caplets. Int J Pharm. 2016;514(1):290–5.CrossRefPubMedGoogle Scholar
  33. 33.
    Goyanes A, Fina F, Martorana A, Sedough D, Gaisford S, Basit AW. Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing. Int J Pharm. 2017;527(1-2):21–30.CrossRefPubMedGoogle Scholar
  34. 34.
    Goyanes A, Scarpa M, Kamlow M, Gaisford S, Basit AW, Orlu M. Patient acceptability of 3D printed medicines. Int J Pharm. 2017;530(1-2):71–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Goyanes A, Fernández-Ferreiro A, Majeed A, Gomez-Lado N, Awad A, Luaces-Rodríguez A, et al. PET/CT imaging of 3D printed devices in the gastrointestinal tract of rodents. Int J Pharm. 2018;536(1):158–64.CrossRefPubMedGoogle Scholar
  36. 36.
    Awad A, Trenfield SJ, Gaisford S, Basit AW. 3D printed medicines: A new branch of digital healthcare. Int J Pharm. 2018;548(1):586–96.Google Scholar
  37. 37.
    Goyanes A, Buanz AB, Hatton GB, Gaisford S, Basit AW. 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets. Eur J Pharm Biopharm. 2015;89:157–62.Google Scholar
  38. 38.
    Melocchi A, Parietti F, Maroni A, Foppoli A, Gazzaniga A, Zema L. Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling. Int J Pharm. 2016;509(1-2):255–63.CrossRefPubMedGoogle Scholar
  39. 39.
    Okwuosa TC, Stefaniak S, Arafat B, Isreb A, Wan KW, Alhnan MA. A lower temperature FDM 3D printing for the manufacture of patient-specific immediate release tablets. Pharm Res. 2016;33(11):2704–12.CrossRefPubMedGoogle Scholar
  40. 40.
    Muwaffak Z, Goyanes A, Clark V, Basit AW, Hilton ST, Gaisford S. Patient-specific 3D scanned and 3D printed antimicrobial polycaprolactone wound dressings. Int J Pharm. 2017;527(1–2):161–70.Google Scholar
  41. 41.
    Sadia M, Sośnicka A, Arafat B, Isreb A, Ahmed W, Kelarakis A, et al. Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets. Int J Pharm. 2016;513(1-2):659–68.CrossRefPubMedGoogle Scholar
  42. 42.
    Skowyra J, Pietrzak K, Alhnan MA. Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing. Eur J Pharm Sci. 2015;68:11–7.CrossRefPubMedGoogle Scholar
  43. 43.
    Solanki NG, Tahsin M, Shah AV, Serajuddin ATM. Formulation of 3D printed tablet for rapid drug release by fused deposition modeling: screening polymers for drug release, drug-polymer miscibility and printability. J Pharm Sci. 2018;107(1):390–401.CrossRefPubMedGoogle Scholar
  44. 44.
    Goyanes A, Buanz AB, Basit AW, Gaisford S. Fused-filament 3D printing (3DP) for fabrication of tablets. Int J Pharm. 2014;476(1-2):88–92.Google Scholar
  45. 45.
    Kollamaram G, Croker DM, Walker GM, Goyanes A, Basit AW, Gaisford S. Low temperature fused deposition modeling (FDM) 3D printing of thermolabile drugs. Int J Pharm. 2018;545(1-2):144–52.CrossRefPubMedGoogle Scholar
  46. 46.
    Zhang J, Yang W, Vo AW, Feng X, Ye X, Kim DW, Repka MA. Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: structure and drug release correlation. Carbohydr Polym 2017;177:49-57.Google Scholar
  47. 47.
    Martinez PR, Goyanes A, Basit AW, Gaisford S. Fabrication of drug-loaded hydrogels with stereolithographic 3D printing. Int J Pharm. 2017;532:313–7. Scholar
  48. 48.
    Martinez PR, Goyanes A, Basit AW, Gaisford S. Influence of geometry on the drug release profiles of stereolithographic (SLA) 3D printed tablets. AAPS PharmSciTech. 2018;

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  1. 1.Office of Pharmaceutical QualityThe US FDASilver SpringUSA

Personalised recommendations