Can ADA be considered biomarkers?
Robust and reliable analytical procedures are critical in the life sciences industry. In today’s complex regulatory landscape, where major treatments are developed and approved across different countries, changing an analytical procedure can be cumbersome and costly.
Global pharmaceutical companies fear facing significant delays and additional costs when an essential analytical method fails, especially for methods used to control critical quality attributes (CQA) such as purity and potency.
The adoption of ICH Q14 can help avoid these regulatory hurdles, ensuring reduced compliance risks and faster market access.
FDA recently published a guidance to discuss risk-based tools that are available to facilitate implementation of changes for CCS consisting of glass vials and stoppers.
The suitability and compatibility of a CCS depends not only on the properties of a container, but also on the properties of other CCS components and their interactions with the drug product formulation over its intended shelf life.
It is expected that Sponsors validate the effects of the change before distribution of the drug, and, as appropriate, conduct additional qualification tests or submit information to address product-specific risks as part of that assessment.
ATMP/CGT Development
Cell and Gene Therapy Products (CGT), regulated as Advanced Therapy Medicinal Products (ATMP) in the European Union (EU), represent a novel and varied group of biotherapeutics developed to treat specific conditions for which there are limited or no effective treatments.
The novelty and complexity of this product modality demands a regulatory risk-based approach to define a sound development plan, particularly, as most developers aim to target more than one market area simultaneously for clinical development and registration.
This regulatory strategy should be built on solid scientific data that also addresses general regulatory recommendations to enable a benefit:risk analysis that is aligned with the particularities of each CGT product.
CAR T and secondary cancers
A recent perspective article by Nicole Verdun and Peter Marks in NEJM suggests that controlling insertional mutagenesis risk during CART T generation may help elucidate the risk of T cell lymphoma development in CAR T treated patients.
Genetic sequencing has shown detection of the CAR transgene in the malignant clone in some cases. Could this be due to the LV-mediated insertional mutagenesis or to the survival of CAR T expressing cells in conditions with elevated IL-7/IL-15 conditions?
PTM of AAV capsids
The use of adeno-associated virus (AAV) as delivery vectors for cancer, genetic disorders, in vivo gene editing and infectious diseases treatment. However, concerns over the immunogenicity of the AAV capsid in humans were raised in clinical trials limiting the therapeutic success of some FDA regulated products.
AAV vectors have been shown to engage both the innate and adaptive arms of the immune system with direct and indirect impact on the safety and efficacy of the gene therapy
This paper by Bing et al. shows that naturally occurring in vivo deamidation of AAV9 capsid residues results in inhibition of T cell cellular responses and discusses experimental approaches to limit the risk of reporting false negative data.
Take on ICH Q14
Robust and reliable analytical procedures are critical in the life sciences industry. In today’s complex regulatory landscape, where major treatments are developed and approved across different countries, changing an analytical procedure can be cumbersome and costly.
Global pharmaceutical companies fear facing significant delays and additional costs when an essential analytical method fails, especially for methods used to control critical quality attributes (CQA) such as purity and potency.
The adoption of ICH Q14 can help avoid these regulatory hurdles, ensuring reduced compliance risks and faster market access.