Assessment Patterns in Clinical Trial Applications for Advanced Therapy Medicinal Products : Analysis of Consolidated Part I Considerations where Sweden or Denmark acted as Reporting Member State (2022-2025)

Abstract

Advanced therapy medicinal products (ATMPs) are complex biological products that present specific scientific and regulatory challenges during clinical development. This thesis aimed to analyse consolidated Part I considerations raised during assessment of investigational ATMP clinical trial applications (CTAs) under the Clinical Trials Regulation (CTR) to identify recurring scientific and regulatory assessment patterns.
Consolidated Part I considerations were extracted from the Clinical Trials Information System (CTIS) for investigational ATMP CTAs submitted between 2022 and 2025, where Sweden or Denmark acted as Reporting Member State (RMS). A structured classification framework was developed to classify considerations into assessment categories, themes and specific issues. The considerations were subsequently analysed across assessment categories, request for further information (RFI) stages and exploratory subgroup characteristics.
The analysis included 22 CTAs and 907 consolidated Part I considerations. Quality represented the largest assessment category, followed by clinical, regulatory, non-clinical and statistical considerations. Across categories, considerations focused mainly on product and process understanding, control of manufacturing and materials, patient safety, treatment justification, risk management, and documentation requirements. The findings also suggested that similar underlying scientific and regulatory challenges often appeared across multiple assessment categories from different regulatory perspectives. The exploratory analysis fur-ther suggested that assessment patterns may be influenced by overlapping factors such as sponsor type, trial phase, ATMP subtype and dossier maturity.
Overall, the findings showed that CTA assessment of investigational ATMPs mainly focused on how sponsors identified, justified and controlled uncertainties and potential risks before investigational ATMPs were authorised for administration to patients in clinical trials. The results support the view that investigational ATMP assessment under the CTR is product-specific, risk-based and case-by-case. By examining recurring assessment patterns at an earlier stage of ATMP development during clinical trial assessment, this study may contribute to a better understanding of the scientific and regulatory challenges while development strat-egies and supporting documentation are still evolving. Earlier identification of such recurring challenges may help sponsors address critical issues more proactively before late-stage marketing authorisation applications. The classification framework developed in this thesis may also support future analyses of larger CTIS datasets.

Popular Abstract

Before a patient can receive an experimental gene or cell therapy in a clinical trial, regulators must answer a difficult question: is enough known about the treatment and its potential risks to justify testing it in humans? This is especially challenging for advanced therapy medicinal products (ATMPs), which, unlike traditional medicines, use living cells or genetic material to repair, replace or modify biological functions and may involve uncertainties regarding manufacturing, safety, and treatment effects. Some ATMPs are being developed for diseases such as cancer, genetic disorders and tissue damage, where conventional treatments may be limited or unavailable.
Before these advanced therapies can be authorised for administration in patients, regulators review clinical trial applications. They evaluate whether the product is sufficiently characterised, consistently manufactured and supported by adequate quality, non-clinical and clini-cal data. During this assessment, regulators frequently ask sponsors for clarifications or additional information regarding different scientific and regulatory aspects of the application. This project investigated which scientific and regulatory questions most frequently arose during the assessment of investigational ATMP clinical trial applications submitted between 2022 and 2025 where Sweden or Denmark acted as Reporting Member State (RMS).
To analyse these recurring assessment questions, the European Clinical Trials Information System (CTIS) was used. In the system, these questions, requests for clarification, and objections raised by regulators are called considerations. Consolidated Part I considerations from ATMP clinical trial applications were grouped into categories and analysed for recurring patterns. The analysis included 22 clinical trial applications and 907 considerations.
The results showed that quality and clinical considerations were the most common during assessment. Frequent quality-related considerations concerned product characterisation, manufacturing processes, materials, and control strategies, while clinical considerations mainly focused on trial population, safety and treatment strategy. The findings also showed that similar scientific and regulatory challenges often reappeared across several assessment areas, although viewed from different regulatory angles. The analysis also suggested that assessment patterns may differ depending on factors such as ATMP type, sponsor type, de-velopment stage and trial scope.
By examining recurring assessment patterns at an early stage of ATMP development, the study may contribute to a better understanding of the common scientific and regulatory challenges associated with investigational ATMPs. Earlier identification of such challenges at the clinical trial stage may help sponsors prepare more proactively for later stages of clinical development and future marketing authorisation applications.

• author: Stanoevska, Aleksandra
• supervisor: Stephen Burleigh; Ann Marie Janson Lang
• organization: Food Technology and Nutrition (M.Sc.)
• course: KLGM06 20261
• year: 2026
• type: H2 - Master's Degree (Two Years)
• subject: Medicine and Health Sciences
• keywords: advanced therapy medicinal products (ATMPs), regulatory, consolidated Part I, assessment patterns, pharmaceutical formulation
• language: English
• id: 9230679
• date added to LUP: 2026-06-10 14:24:01
• date last changed: 2026-06-10 14:24:01