3D Bio-Printed Products: ICMRA Members Discuss Potential Regulatory Frameworks

As part of a project on emerging technologies, six regulators involved in the International Coalition of Medicines Regulatory Authorities (ICMRA) recently published a case study delving into the challenges of regulating 3D bio-printed products.

In this hypothetical case, the regulators evaluated 3D bio-printed knee meniscus tissue and discussed how they would tackle similar products. The case study was conducted by Australia’s Therapeutic Goods Administration (TGA), Brazil’s Agência Nacional de Vigilância Sanitária (ANVISA), Health Canada, the European Medicines Agency (EMA), Japan’s Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency (MHLW/PMDA) and Singapore’s Health Sciences Authority (HSA).

Three out of the six agencies said they were developing new regulatory frameworks (ANVISA and HSA) or implementing new legislation (Health Canada) to better facilitate innovative product development, and 3D bio-printed products would be addressed under these new frameworks and legislation.

“There are many components of 3D bio-printing that could require regulatory oversight. These may include the printer itself, software, production processes, living and non-living printing material, and the deployment of the technology. 3D bio-printing technology challenges regulators with respect to classification of the output, and regulating different models of manufacturing (centralized model versus point-of-care production),” the ICMRA report summarizing the regulators’ discussions says.

As far as what the various regulators would classify 3D bio-printed knee meniscus tissue as, TGA said it would classify the product as a biologic class 4 product that would be subject to the biologics framework, since the product would contain human cells and tissues and the primary mode of action would be taken mainly by the cells, while ANVISA would classify the product as an advanced therapy medicinal product (ATMP) subject to the resolution for market authorization of ATMPs (under development) in Brazil, as the primary mode of action would be taken by the cells.

Health Canada would classify the product as a complex product subject to its Advanced Therapeutic Products Pathway, which is in development to create tailored requirements for biologics and medical device components as well as the production process.

EMA would potentially classify the product as a tissue engineered ATMP combined with a device. But EMA also said it requires a mandatory European certification for any device (CE mark), including for ATMP manufacturing by the 3D printer, although the main criterion would be the quality of the product.

“EMA and MHRA [the UK’s Medicines Healthcare products Regulatory Agency] both discussed the thinking around a manufacturing master file for providing proper regulatory oversight to the point-of-care production.
This is a concept where one licensed master site would be responsible for ensuring its satellite sites are qualified for, and comply with, the licensed procedures and requirements. Japan has a system that provides oversight for decentralized regenerative therapies. The agencies also mentioned that the Pharmaceutical Inspection Co-operation Scheme (PIC/S) is currently looking into point-of-care manufacturing models and considerations,” the report says.

PMDA would classify the product as a regenerative medicine that would be subject to the Pharmaceuticals and Medical Devices (PMD) Act in Japan, as the primary mode of action would be taken mainly by the cells. For the point-of-care production, Japan’s MHLW would regulate the meniscus as per the Act on Securing Safety of Regenerative Therapies.

And HSA said it will be promulgating the new Cell, Tissue and Gene Therapy Product (CTGTP) regulations (in draft form) under the Health Products Act in Singapore, and the product would be regulated under this new framework when implemented.

The regulators also said a qualified operator of the 3D printer and site requirements should be subject to certain GMP standards.

In addition to the 3D bio-printed product, ICMRA also will publish case studies on artificial intelligence and gene editing as emerging disruptive technologies that will challenge traditional health product regulatory systems.

ICMRA Innovation Project 3D Bio-Printing Case Study