Four Things That Need to Happen to Make ATMPs More Accessible
Advanced therapy medicinal products (ATMPs) are innovative medicines for human use that are based on novel gene therapies, tissue-engineered products, or cell therapies1 . They have the exciting potential to offer new treatment avenues for rare diseases and injuries that couldn’t be adequately treated with conventional medicine. That’s why the European Medicines Agency (EMA) published that ATMPs have real long-term value and benefits for patients and all of society.
Several new therapies have already been approved for spinal muscular atrophy and severe combined immunodeficiency with good clinical results. Plus, many more are in the pipeline for tumors, neurological disorders, pain, and other conditions. A total of 21 ATMPs have been approved so far in the EU; although seven ATMPs have been withdrawn, and two of them remain in the evaluation stage.
One of the concerns about ATMPs in healthcare is the low number of ATMPs that have gained approval from regulatory authorities.
So what are the reasons for the slow approval process of ATMPs?
ATMP manufacturers are encountering some pitfalls because of lengthy, complex assessments and long negotiations with agencies and payers. This makes it difficult to bring ATMP to market.
Let’s look into what can be done to accelerate ATMP development and facilitate patient access!
Supporting Payer Decision-Making
The principal concern for payers is the high cost of ATMPs and the uncertainty of approval by health authorities. Therefore, according to the European Federation of Pharmaceutical Industries and Associations (FPIA), support to payers is one viable solution to promote patient access to ATMPs.
Nevertheless, new therapies, like ATMPs, must first be rigorously tested in-vitro and subjected to pre-clinical investigations in accordance with regulatory guidelines to ensure they are safe and efficacious prior to clinical trials. The European Union adopted a centralized procedure for this in 2004. This procedure is valid in all member states and enables a fast authorization of medicinal products based on a benefit/risk assessment made by health technology assessment bodies (HTAs).
HTAs are public organizations that provide assessment and appraisal on ATMPs that can be paid for or reimbursed. They check the relative effectiveness and cost-effectiveness of ATMPs that have been authorized. It is critical that regulators and HTA bodies interact closely to facilitate patient access to important new ATMPs for the benefit of public health.
Sometimes the lack of sufficient data from clinical trials of ATMPs provides incomplete evidence to HTA bodies. What is the reason for this pitfall? The weakness of ATMP is that the length of patient follow-up required to demonstrate its efficacy is far greater than a typical trial duration, while the ATMP value proposition is based on long-term benefits.
Improving Pricing and Reimbursement
Once an ATMP is finally granted, each country is responsible for deploying access to it, which makes pricing and reimbursement a complex issue.
This uncertainty is enhanced by an ATMP’s high cost due to the complexity of manufacturing, which makes the pricing and reimbursement decisions challenging for national healthcare systems. Additionally, other treatments may be displaced in order to fund ATMPs.
Therapies like ATMPs are usually associated with a single upfront payment, although their benefits extend many years into the future. And this fact, unfortunately, creates uncertainty.
The research and development of ATMPs are mainly conducted by public bodies - such as academic institutions, research organizations, and hospitals - and by partnerships with small and medium-sized enterprises.
The costs of ATMPs from research, development, manufacturing, and distribution are high. And the financial burden of upfront costs undermines the availability of ATMPs for patients unless big companies provide financial support.
Greater collaboration between the different stakeholders, academic institutions, industry, payers, and regulatory bodies would ease the financial and legislative barriers. One paradigm change in how ATMPs are valued and financed would ensure sustainable ATMP access for healthcare systems and patients. Here, regulatory authorities should adapt their assessment procedures and lawmakers should adjust legislation without compromising patient safety and hampering innovations.
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Helping ATMPs Developers and Manufacturers with Regulatory Burdens at Early Stages
Academic institutions and small and medium-sized enterprises encounter more challenges in understanding and complying with regulatory requirements during development compared with large pharmaceutical companies.
There are key issues that developers should consider even at early stages to succeed in the Quality-related regulatory requirements of ATMPs.
Organizations should work on these issues in advance to avoid bigger problems appearing at late stages.
Regarding Quality-related issues they should:
Regarding the non-clinical development phase, they should:
Regarding clinical development, they should:
The example lists above obviously show that there are many issues to solve in these early stages. Disregarding this until later stages immediately before the marketing authorization evaluation poses a clear risk to the success of an ATMP project.
Understanding and Training of ATMP Delivery Processes
ATMPs are biological medicinal products based on living cells that have very short shelf lives at ambient temperature. They are classified into three different types: cell therapy medicinal products (CTMP), gene therapy medicinal products (GTMP), and tissue-engineered products (TEP). The source of the cells can differ: they may come from patients themselves or from one or several healthy donors.
Proper logistics of ATMPs is one of the major challenges that the industry is facing today. Patient trials need to be managed depending on logistics feasibility. The site selection for a clinical study depends on the proximity of the investigators, the selected patients, and the manufacturing site. Specific conditions are needed for transportation to extend the shelf life, including liquid nitrogen, dry ice, special containers, isolated boxes.
The procedures for collecting, storing, and supplying cells and tissues may affect the clinical development and the Quality of the final product.
The short shelf life of ATMPs (24-96 hours at ambient temperature), storage, labeling, traceability, packaging, and shipment conditions challenge the logistics procedure.
Traceability poses an additional requirement for packages and containers. There are specific obligations that need to be understood and followed for correct assignment and handling to protect ATMPS from external environmental influences.
In conclusion, it is essential that all parties involved in the supply of ATMPs receive the training and knowledge to understand the requirements of ATMPs to ensure a correct delivery that ensures their safety and efficacy.
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