Advanced Therapies

Advanced therapies represent the most innovative frontier of pharmaceutical and medical development. Under this designation — encompassed in European regulation by the concept of advanced therapy medicinal products (ATMPs) — are grouped those therapeutic products that use genes, cells or tissues as active substance, with the aim of treating, preventing or diagnosing disease through mechanisms of action fundamentally different from those of conventional medicines.

Unlike small molecule drugs or even conventional biologics, advanced therapies intervene directly in the genetic or cellular mechanisms of disease: they correct defective genes, introduce functional genetic material into target cells, modify the patient’s own cells to equip them with new therapeutic capabilities, or use RNA as a tool to transiently modulate gene expression. This transformative potential is accompanied by analytical demands of unprecedented complexity in the history of pharmaceutical development.

The regulatory framework for advanced therapies is specific and constantly evolving: in Europe, Regulation (EC) No 1394/2007 governs ATMPs and establishes specific quality, safety and efficacy requirements. The EMA and FDA have also published numerous specific guidelines for the different types of advanced therapies, including guidance on gene therapy, cell therapy and mRNA vaccines. AMSbiopharma provides specialised analytical services to support the development of these therapies under the scientific rigour and regulatory compliance that their complexity demands.

Advanced therapies present one of the most demanding and specific quality regulatory frameworks in the pharmaceutical landscape. The analytical services applicable to these modalities may be conducted under Good Laboratory Practice (GLP) for support of preclinical and clinical studies, under Good Manufacturing Practice (GMP) for CMC characterisation and quality control services for the drug substance and the product, or in non-regulated environments for exploratory research and development studies. Given the specificity of quality requirements in this area, we recommend contacting our team to define the most appropriate regulatory strategy for your project.

Types of advanced therapies

Advanced therapies comprise several main categories with specific characteristics and analytical challenges:

Gene therapy medicinal products (GTMPs) are products containing a recombinant nucleic acid — DNA or RNA — or a genetically modified microorganism, administered with the aim of regulating, repairing, replacing, adding or silencing a gene sequence. They may use viral vectors — such as adeno-associated vectors (AAV), lentiviruses or adenoviruses — or non-viral vectors, including lipid nanoparticles (LNPs) for the delivery of mRNA or DNA plasmids.

Cell therapy medicinal products use living cells — autologous, from the patient, or allogeneic, from a donor — as active substance. They include tissue-engineered medicines and, most notably, therapies using genetically modified cells such as CAR-T cells, in which patient T-lymphocytes are modified to express chimeric antigen receptors capable of recognising and destroying tumour cells.

Therapeutic mRNA medicines use messenger RNA strands that, upon introduction into the patient’s cells, direct the transient production of a protein of therapeutic interest. This modality experienced unprecedented momentum with the development of mRNA vaccines against SARS-CoV-2, and is now being actively explored in oncology, rare diseases and other indications.

Analytical complexity of advanced therapies

The analytical characterisation of advanced therapies faces unique challenges arising from the biological nature of their active components. Viral vectors such as AAV are complex biological particles whose characterisation requires titre determination, capsid integrity assessment, confirmation of the identity and purity of the encapsidated genome, quantification of the ratio of full to empty particles, and control of process-related impurities.

Plasmid DNA — used both directly as the drug substance in some gene therapies and as starting material for the production of viral vectors and mRNA — requires rigorous characterisation of its isoforms (supercoiled, open circular and linear) and control of impurities related to the fermentation and purification process.

mRNA therapies require confirmation of the integrity and identity of the RNA strand, assessment of stability against nuclease degradation, control of 5’ cap and poly-A tail modifications, and evaluation of the potential immunogenicity of the product.

An evolving regulatory landscape

The regulation of advanced therapies is in continuous development, with the EMA and FDA regularly publishing new guidelines and updating existing ones to address the specific challenges of these modalities. This regulatory dynamism requires development teams and analytical laboratories to remain permanently up to date and to be capable of adapting their analytical strategies to the most recent requirements. AMSbiopharma closely follows this regulatory evolution and adapts its services to ensure that the analytical data generated for our clients’ advanced therapy programmes meet the most demanding standards of current regulation.