As personalized therapies have become a reality rather than a distant promise, the tools needed to ensure the quality of these medicines grow increasingly important. Regulatory guidances for personalized medicines are frequently a “work in progress,” evolving over time as the body of knowledge grows for ensuring that these therapies are safe and beneficial.
Regulatory considerations for personalized medicines are often related to complex scientific and implementation challenges that span the entire production and distribution process. In our current approach for developing standards for biologics—which includes personalized therapies—we are helping to meet some of these challenges by prioritizing the development of standards for raw materials, as well as performance standards, which apply to classes of biologics rather than individual products. Scientists can use these performance standards to evaluate the performance and suitability of analytical tools used to test these therapies through their product lifecycle—which are especially important with autologous therapies where cells must be removed, then manipulated and administered to a patient within a matter of hours or days.
The number of cells collected and subsequently administered to the patient is one of many factors related to the effectiveness of the treatment of certain types of cancer. Performance standards can be used to enumerate blood stem cells, also known as hematopoietic stem cells (HSCs). Getting an accurate count relies on the measurement of a marker called CD34+ which is present on the surface of HSCs. The number of cells expressing CD34+ correlates with engraftment potential to repopulate the patient’s blood and immune system.
USP’s standard method (and associated reference standard) for enumerating CD34+ cells was developed in collaboration with laboratories from academia, industry and the practitioner community. USP’s publicly available standard is an important tool for ensuring consistency in CD34+ measurement across different laboratories and clinical centers. Other USP standards that play important roles in the personalized medicine space include general chapters published in the United States Pharmacopeia–National Formulary (USP–NF) on sterility, endotoxins, biocompatibility, mycoplasma, method validation and bioassays.
Controlling transport conditions
Once produced, autologous therapies must be transported to the recipient. These treatments are very sensitive to changes in their environment, so conditions must be tightly controlled. USP’s General Chapter <1046> CELL AND GENE THERAPY PRODUCTS is currently being revised to include a statement on acceptable conditions for shipping containers and procedures for cell- and tissue-based products, including temperature extremes inside and outside a shipping container and other shipping challenges such as x-rays or mechanical vibration.
To learn more about USP’s development process for performance standards, go to http://biologics.usp.org.