Compliant STEM Cell Therapy & HCT/Ps: Beginner’s Guide

By: Susan St. John

Many practitioners or establishments looking to enhance their practice and offer more treatment options to their patients are considering HCT/P and Stem Cell Therapy in addition to other traditional treatment options. However, before embarking on offering HCT/P or STEM Cell Therapy, a practitioner or establishment needs to carefully consider protocol and procedure for offering HCT/Ps or STEM Cell Therapy.

The FDA defines HCT/Ps as “articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion or transfer into a human recipient.” 21 CFR 1271.3(d). HCT/Ps include bone, ligament, skin, dura mater, heart valve, cornea, hematopoietic stem/progenitor cells derived from peripheral and cord blood, manipulated autologous chondrocytes, epithelial cells on a synthetic matrix, and semen or other reproductive tissue.

HCT/Ps (from which STEM Cells may be derived) are regulated pursuant to Section 361 of the Public Health Services (PHS) Act and 21 CFR 1271 of the Food, Drug & Cosmetics Act, or may be regulated as a drug or biologic under Section 351 of the PHS Act. Regardless of which is the appropriate regulatory law, a practitioner or establishment needs to understand the regulations governing the processing, manufacture and use of HCT/Ps and Stem Cells and must have written policies and procedures, that are implemented and followed to ensure the safety of the manufactured HCT/P or Stem Cells.

If a practitioner or establishment seeks to provide HCT/Ps, it needs to be understood, that by law to qualify as only an HCT/P – and not a drug or biologic – the following criteria must be met:

1. The HCT/P is only minimally manipulated;
2. The HCT/P is intended for homologous use only;
3. THE HCT/P has not been combined with the cells or tissues of another article except water, crystalloids, or a sterilizing, preserving or storage agent that does not raise new clinical safety concerns of the HCT/P; and
4. The HCT/P does not have a systemic effect and is not dependent on the metabolic process of living cells for its primary function; or the HCT/P does have a systemic effect or is dependent on the metabolic process of living cells, but is for autologous use, or is for allogeneic use in first or second degree blood relatives, or is for reproductive use.

Homologous use of HCT/Ps include the repair, reconstruction, replacement, or supplementation of a recipient’s cells or tissues with an HCT/P that performs the same basic function or functions in the recipient as in the donor (recipient and donor may be one and the same). For example, a heart valve transplant to replace a dysfunctional heart valve is homologous use; healthy cornea is used to replace a damaged cornea; skin grafts. Ground adipose tissue that is defatted and decellularized is more than minimally manipulated, thus not homologous, because the processing alters the original relevant characteristics of the adipose tissue’s utility for reconstruction, repair, or replacement.

HCT/Ps that meet the criteria above do not need pre-market approval from the FDA in order for the practitioner or establishment to market these products. HCT/Ps that go beyond the four criteria listed above will very likely be viewed as a drug or biologic or both by the FDA, and any marketing for non-homologous use would require pre-approval from the FDA.

Typically, if a practitioner or establishment processes HCT/Ps that are regulated solely under Section 361 of the PHS Act, the practitioner or establishment must register with the FDA and list the HCT/Ps with the FDA’s Center for Biologics and Evaluation Research. However, there are exceptions to registration which include:

1. HCT/Ps used solely for non-clinical, scientific purposes;
2. HCT/Ps are removed from an individual and implanted back into the same individual during the same surgical process;
3. You are a carrier of HCT/Ps that accepts, receives, carriers or delivers HCT/Ps in the course of business as a carrier;
4. If you only receive or store HCT/Ps for implantation, transplantation, infusion, or transfer in your facility; or
5. You are an individual under contract, agreement, or other arrangement with a registered establishment and engaged solely in recovering cells or tissues and sending the recovered cells or tissues to the registered establishment.

Based on the above criteria, there are only limited exceptions where registration and listing of HCT/Ps will not be required. Removing cells or tissue from an individual to be implanted later during a subsequent procedure will require registration with the FDA.

In addition to registration and listing of HCT/Ps, a practitioner or establishment must be prepared to follow the regulations for processing of HCT/Ps. These regulations include establishing and implementing policy and procedure to determine: donor eligibility; donor screening; donor testing; maintaining HCT/P records for 10 years (includes identifying code, donor eligibility, testing and screening for communicable diseases); HCT/P quarantine prior to donor eligibility determination; urgent medical need use; HCT/P storage; HCT/P labeling; Current Good Tissue Practice, including handling, labeling, equipment, environment, processing, facilities, personnel, supplies and reagents, storage, and distribution; Quality Assurance or Quality Control; Tracking, Adverse Reactions, and Complaints. Not only will appropriate policies and procedures need to be implemented and followed, a practitioner or establishment must maintain appropriate records for each phase of processing an HCT/P, and such records must be readily available to the FDA upon request or investigation.

Keep in mind, that even if you do not need to register with the FDA or provide a list of your HCT/P with FDA’s Center for Biologics and Evaluation Research, you are still required to comply with all remaining requirements under Section 361 of the PHS Act and 21 CFR 1271. Thus, it is imperative that if you as a practitioner or establishment wish to offer HCT/P, you must have appropriate written policies and procedures in place that have been implemented and followed. You must keep adequate records demonstrating adherence to your written policies and procedures to assure compliance with the Food Drug and Cosmetic Act and the PHS Act.

Additionally, if you wish to offer Stem Cell Therapy, you will need to comply with the requirements of Section 361 of the PHS Act (and 21 CFR 1271) as well as Section 351 of the PHS Act and 21 CFR 210 and 211. If your Stem Cell Therapy product is a drug or biologic, as defined by the FDA, you will need to obtain a valid biologics license (issued after proving safety and efficacy of the Stem Cell’s intended use). In addition to needing to implement the policies and procedures listed above for HCT/Ps, you will need to have written policies and procedures that are implemented and followed for Current Good Manufacturing Practice for Manufacturing, Processing, Packing or Holding of Drugs, and Current Good Manufacturing Practice for Finished Pharmaceuticals.

Stem cells, used in cell-based therapies, may be used to treat diseases such as macular degeneration, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis. The FDA approval process needed in order to offer Stem Cell Therapy is a long, arduous and costly process, and may take several years unless the Stem Cell Therapy is used in regenerative medicine (regenerative advanced therapy) that addresses a serious disease and has the potential to alleviate currently unmet medical needs. Further, unless properly vetted by the FDA, it is unlawful to advertise treatment using Stem Cell Therapy.