Donor Eligibility (DE) determination is a central aspect of how FDA and other regulatory authorities ensure that a product from a single allogeneic donor has acceptable very low risk of transmitting disease agents to a large patient population.
In the US, the requirement for DE is clearly described in 21 CFR 1271 Subpart C1. It involves not only donor testing for certain adventitious agents, but more importantly, involves donor screening, which includes review of donors’ medical history and performing a thorough medical questionnaire.
US FDA requires companies to perform each test an Agency cleared kit. Further, a CLIA-certified lab must perform the test. Our latest survey did not reveal many CLIA-certified labs outside the US. There are many reasons for these requirements, but their main purpose is to ensure tests are conducted according to validated procedures and tests FDA has reviewed and found to be suitable for use.
For example, FDA-cleared kits describe, in most cases, exact requirements for collecting, storing and treating donor samples prior to analysis. In the US, there is also a requirement as to how much time you have between collection of the donor materials, such as blood from tissue donors which is used for testing, and tissue recovery. For leukocyte-rich material, companies have a maximum of 30 days. But, for tissue like skin, donor blood must be collected for testing within 7 days before or after tissue recovery.
You might be wondering how these regulations compare with the requirements in Europe. Well, the answer can be found in the ARM report2 that we came across just recently. This is a wonderful resource for companies that would like to follow a single or standard set of requirements that could fulfill the requirements worldwide. Today, this goal is not achievable, as there are major differences in international requirements. In fact, there are additional differences more regionally as well.
You may also ask: Why are there so many differences among requirements? The answer is quite simple. Each regional authority has a different perspective on what are relevant diseases that each donor should be screened and tested for and how to best protect their citizens.
Donor eligibility determination remains the most important step in protecting the public from transmission of adventitious and infectious agents from one donor to thousands of patients. So, this is a matter of public health. Today, the requirements differ regionally and internationally, which creates a major obstacle to development of products that are intended to have a global footprint.
The requirement for DE determination is very complex internationally. But it uniquely impacts products that are allogeneic, such as Induced Pluripotent Stem Cells (iPSC) derived products. Because of this, establishing new iPSC lines that comply with all local requirements may be necessary when market authorization is requested in different global regions. But this is quite costly and challenging.
Clearly, a harmonized global approach to DE is highly desirable but this goal remains today to be extremely complex and aspirational.