3D-printed personalized drug-device combination products : Manufacturing requirements in the EU and US
Sipola, Elisa (2026)
2026
Bioteknologian ja biolääketieteen tekniikan maisteriohjelma - Master's Programme in Biotechnology and Biomedical Engineering
Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology
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Hyväksymispäivämäärä
2026-05-13
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202605115370
https://urn.fi/URN:NBN:fi:tuni-202605115370
Tiivistelmä
Combination products play an increasingly important role in the development of advanced medical solutions. By integrating drug and device components, these products may improve therapeutic efficacy, safety, tolerability, and patient adherence, while also enabling personalized treatment approaches. However, their hybrid nature and the use of advanced manufacturing technologies increase regulatory and manufacturing complexity. Ensuring that such products are suitable for their intended use and do not compromise patient safety requires compliance with Good Manufacturing Practices (GMP) and navigation of multifaceted regulatory pathways. While previous studies have addressed regulatory classification challenges of combination products, the applicability of existing GMP frameworks to novel, technology driven manufacturing approaches remains insufficiently explored.
This thesis evaluates the applicability of GMP requirements in the European Union (EU) and the United States (US) to personalized drug–device combination (DDC) products manufactured using 3D-printing technology. The central research question of this study is: To what extent do EU and US GMP guidelines provide clear and sufficient regulatory guidance for the manufacturing of personalized 3D-printed drug–device combination products?
A drug eluting round window niche implant (RNI) was used as a case example to illustrate the manufacturing process. First, a systematic literature review was conducted to identify manufacturing related risks associated with patient specific 3D-printed DDCs. Second, a Hazard and Operability (HAZOP) analysis was performed to map these risks to specific processing steps. Third, the identified risk control actions systematically mapped against EU and US GMP frameworks using a binary regulatory compliance mapping approach to assess the presence or absence of explicit regulatory guidance.
The results indicate that most identified manufacturing risks can be mitigated through existing GMP principles, particularly those related to process validation, documentation, traceability, and quality risk management. However, differences in regulatory interpretation and specificity were observed between jurisdictions. The US regulatory framework provides more explicit guidance related to additive manufacturing and process validation, whereas EU guidance remains more principle based. The findings highlight both the adaptability of current GMP frameworks and the need for clearer regulatory interpretation in the context of personalized, digitally driven manufacturing processes.
This thesis evaluates the applicability of GMP requirements in the European Union (EU) and the United States (US) to personalized drug–device combination (DDC) products manufactured using 3D-printing technology. The central research question of this study is: To what extent do EU and US GMP guidelines provide clear and sufficient regulatory guidance for the manufacturing of personalized 3D-printed drug–device combination products?
A drug eluting round window niche implant (RNI) was used as a case example to illustrate the manufacturing process. First, a systematic literature review was conducted to identify manufacturing related risks associated with patient specific 3D-printed DDCs. Second, a Hazard and Operability (HAZOP) analysis was performed to map these risks to specific processing steps. Third, the identified risk control actions systematically mapped against EU and US GMP frameworks using a binary regulatory compliance mapping approach to assess the presence or absence of explicit regulatory guidance.
The results indicate that most identified manufacturing risks can be mitigated through existing GMP principles, particularly those related to process validation, documentation, traceability, and quality risk management. However, differences in regulatory interpretation and specificity were observed between jurisdictions. The US regulatory framework provides more explicit guidance related to additive manufacturing and process validation, whereas EU guidance remains more principle based. The findings highlight both the adaptability of current GMP frameworks and the need for clearer regulatory interpretation in the context of personalized, digitally driven manufacturing processes.