How Tightly Should Stem-Cell Therapies Be Regulated by FDA?

Medi-Post, a Korean-based biopharmaceutical company, announced on Jan. 10, 2017 that it has secured a patent from the United States Patent and Trademark Office protecting a method for culturing mesenchymal stem cells. The patent itself was issued on Nov. 22, 2016 and focuses on the treatment of lung disease in newborn or premature babies via cells proliferated from umbilical cord blood. The patent is being used to develop a therapy called Pneumostem, which was granted an Orphan Drug designation in 2013 by FDA (1). The patent is co-owned by Samsung Life Public Welfare Foundation and is already issued in Canada. The underlying belief about stem-cell treatments is that precursor cells will differentiate into the tissue of interest (in this case, new lung tissue) and will help heal patients through use of autologous cells.

Despite the advances in the field of regenerative therapies, there are some regulatory sensitivities that plague the industry. Direct-to-consumer stem cell therapy clinics are increasingly popping up, and FDA is tasked to monitor each processing or “manufacturing” site in a piecemeal fashion. In the beginning of 2016, FDA issued a stern warning to three stem-cell clinics selling stem-cell treatments purported to treat a variety of chronic conditions (2). Many of the violations listed in the letters were largely related to failing to follow proper cGMP procedures and failing to safeguard against potential microbiological contamination of sterile products.

Shutting these types of clinics down one by one may prove to be a daunting task for the agency. According to an August 2016 article in Cell Stem Cell, there are 351 businesses currently offering unapproved stem-cell treatments across 570 clinics in the United States. Separated out by state, California had the largest number of stem-cell clinics (3). The available interventions were mostly derived from autologous cells, approximately 21% of the therapies offered were from allogenic cells sourced from umbilical cord blood, amniotic material, and placental tissue (3).

Support for stem-cell therapies
Development of Medi-Post’s Pnemostem is backed by the Translational Stem Cell & Regenerative Medicine Consortium Grant as a part of Public Health and Medicinal Technology R&D Project funded by the Ministry of Health and Welfare of Korea and the Korea Health Industry Development Institute. In Japan, conditional approval for stem-cell treatments is granted by the Pharmaceuticals and Medical Devices Agency after Phase II trials if the investigative agent is deemed effective for a very small number of subjects-in other words, companies can be exempt in some cases from conducting Phase III trials. This is alarming, considering that a recent analysis found that 70% of drugs fail to advance from Phase II to Phase III (4).

The Medi-Post product is one of many stem-cell therapies under clinical investigation, and the science behind the use of these therapies is promising. Investigators have shown that multipotency of these types of cells remains after amplification and the stem cells that are extracted are capable of turning into various types of tissue. As Medi-Post says in its patent application, “Methodologically, the umbilical cord blood extracted from the real placental tissue is an ideal source for autologous and allogeneic stem cells, and such stem cells obtained thereby can be used directly or after amplifying stage whenever and as many as required” (5).

Support for investigative cell-therapy products in the US, however, is a little more convoluted. Although many scientists see the value of the research, they think the therapies should be held to rigorous efficacy and safety standards. FDA issued a letter in 2012 warning consumers of the dangers of stem-cell treatments (6). As yet, FDA has not finalized its drafts on guidance documents relating to the regulation of human cells, tissues, or cellular or tissue-based products (HCT/Ps). As of Sept. 27, 2016 (when the comment period closed), there were 6957 public comments in the FDA docket on these guidance drafts. A public hearing occurred in September 2016 to discuss the draft guidance items, and many in the scientific community communicated that the guidance documents required significant amendments.

A piece of legislation introduced in March 2016 seeking to lower standards for the approval of cell-therapy products, the REGROW (Reliable and Effective Growth for Regenerative Health Options that Improve Wellness) Act, is opposed by prominent industry groups such as the International Society for Stem Cell Research, the International Society for Cellular Therapy, and the Alliance for Regenerative Medicine. It seeks to allow marketing of a conditionally approved cellular therapy prior to the approval by FDA. Language from the REGROW Act snuck back into the final text of the 21^st Century Cures Act prior to its final passage (7).

References
1.  Medi-Post, “Medipost receives US Patent for ‘PNEUMOSTEM’ for Treating Lung Disease, Medi-Post.com, www.medi-post.com/2016/05/13163/, accessed Jan. 10, 2016.
2. R. Hernandez, “Stem Cell Treatment Centers Receive FDA Warning for Not Following cGMP Procedures,” BioPharmInternational.com, www.biopharminternational.com/stem-cell-treatment-centers-receive-fda-warning-not-following-cgmp-procedures, accessed Jan. 10, 2016.
3. L. Turner and P. Knoepfler, Cell Stem Cell 19 (2), pp. 154–157 (Aug. 4, 2016).
4. R. Hernandez, “Clinical Development Success Rates Examined in New BIO Report,” BioPharmInternational.com, www.biopharminternational.com/clinical-development-success-rates-examined-new-bio-report, accessed Jan. 10, 2016.
5. Y.S. Chang, W.S. Park, and Y.S. Yang, "Method of treating lung diseases using cells separated or proliferated from umbilical cord blood," US patent PCT/KR2007/000535, Nov. 2015.
6. FDA, "FDA Warns About Stem Cell Claims," FDA.gov, www.fda.gov/ForConsumers/ConsumerUpdates/ucm286155.htm, accessed Jan. 10, 2016.
7. K. Servick, “Under 21st Century Cures legislation, stem cell advocates expect regulatory shortcuts,” Sciencemag.org, www.sciencemag.org/news/2016/12/under-21st-century-cures-legislation-stem-cell-advocates-expect-regulatory-shortcuts-0, accessed Jan. 10, 2016.