The European Medicines Agency (EMA) on Monday released for comment a revised guideline on the quality, non-clinical, and clinical data required to support a clinical trial application for investigational advanced therapy medicinal products (ATMPs).
The multidisciplinary guideline addresses gene therapy medicinal products, somatic cell therapy medicinal products, tissue engineered products, and combined ATMPs.
It revises a previous guideline published in February 2019.
EMA made several changes to the guideline to accommodate public comments, according to an overview summary of the responses. Some of the changes include the addition of a glossary section, the adoption of a different structure in section S.2.2 on process controls, and revisions in the testing of replication competent viruses (RCVs).
There is also greater alignment with the US Food and Drug Administration (FDA) on certain concepts and terminologies related to ATMPs. Additionally, EMA has reworked the structure of the quality portion of the guideline to address commenters’ concerns.
EMA states that it endorses a risk-based approaches to support these clinical trials. The document states that “the extent of quality, non-clinical and clinical data to be included in the clinical trials submission should be commensurate with the level of risk. The application of a risk-based approach can facilitate compliance with the guidelines on good clinical practice specific to ATMPs but does not obviate the applicant’s obligation to support the quality and safety of the product to enable the generation of reliable and robust data.”
The quality documentation is the largest portion of the document and addresses controls of the active substance, controls of the excipients, and the of reference standards or reference materials.
The guidance states that “an immature quality development may compromise the use of the clinical trial data in the context of a marketing authorization application (e.g. if the product has not been adequately characterised). A weak quality system may also compromise the approval of the clinical trial if deficiencies are apparent from the submission that pose a risk on the safety of trial subjects and the robustness of data.”
The non-clinical section addresses the use of non-clinical models, and the minimum non-clinical data necessary to support first-in-human studies.
The guidance states that “the non-clinical development pathway for ATMPs is significantly different from other medicinal products. The sequential non-clinical development in which the amount of data required and the duration of dosing increase by the phase of clinical development is not generally applicable for ATMPs. Instead, in many cases, the majority of non-clinical data may need to be available before human exposure.”
The clinical section covers the documentation necessary to support exploratory clinical trials and long-term efficacy and follow-up. The guideline states that there are some distinctive characteristics and features of ATMPs that are expected to have an impact on the clinical trial design in early phases of development.
Yet it notes that “in later phases, for clinical trials aiming to demonstrate efficacy and safety of medicinal products in specific therapeutic areas, the general principles and methodology are similar to those for the development of other medicinal products.”
The deadline for submitting comments is 31 May.
To continue reading this article please go to RAPS .