This article is part of a series The Conversation Africa is running on stem cell research and therapy. Read the rest of the series here.
Exploration into the use of stem cells has created a cauldron where scientists and regulators are increasingly pressurised to find ways of fast-tracking promising research into novel therapies.
Many countries are developing guidelines and legislation to balance the provision of stem cell therapies as quickly as possible, while still ensuring the safety and efficacy of treatments.
At the centre of this is the accelerated, or conditional, approval of medicine still under clinical development. This is opposed to medicine already proven to be safe and effective in humans, formally approved by the relevant regulatory authority and legally available for sale to the public.
Although the South African legal systems do not provide for any accelerated or conditional approval, heed should be taken of global developments. This will ensure that legal systems allow local scientific innovation to keep up with global pace setters and that patients are protected.
Stem cells and investigational medicine
The use of investigational medicine, as we know it today, came about in the late 1980s. In an attempt to address lengthy drug development cycles and a growing AIDS epidemic, the US was forced to reconsider its strict guidelines around investigational medicine. It eventually amended them to allow access to investigational medicine under certain conditions.
This developed into the Food and Drug Administration’s (FDA) system of expanded access. This allows patients with serious conditions to receive investigational medicine that has not yet undergone formal product approval.
There are three prescribed categories of people who can get expanded access to investigational medicine:
intermediate-size patient populations; and
widespread use under a treatment protocol.
For individual patients, the decision lies with a physician. They need to confirm that the medicine does not pose a greater risk to the patient’s health than the disease itself.
When large numbers of patients are involved, the FDA must still find evidence that it is safe to use. To qualify, the FDA must determine whether the condition is serious or immediately life-threatening, and that there are no alternative satisfactory treatments available. Access to investigational medicine must also not interfere with the necessary clinical trials required to receive formal product approval.
Similar to all other therapeutics that qualify as biological medicine, stem cells must go through lengthy clinical trials to prove their safety and efficacy before they can be approved by the relevant regulatory authority for public use. Before they received the final approval, stem cells remain investigational medicine.
This should not be confused with the countless bogus stem cell treatments often advertised online. Many of these treatments have not:
undergone clinical trials;
passed the first phase of these trials; or
received the go-ahead from authorities to be used as an investigational medicine.
Expanded access is gaining momentum
In many countries, access to stem cell treatments still classified as investigational medicine, is gaining momentum.
In addition to the US’s expanded access guidelines, the Right to Try Act was introduced in July this year. If passed, the bill, which is complementary to similar state laws, will stop the federal government from taking action to stop expanded access of investigational drugs to terminally ill patients. This will severely limit the FDA’s regulatory authority over expanded access in these instances.
Although federal laws trump state laws, twelve states have already enacted so-called “right-to try” legislation. This has created enormous legal ambiguity as these state laws are not really enforceable. But, in practice, the fear of violating the FDA’s requirements causes a reluctance to actually use these state laws.
Similarly, the European Medicines Agency has started a public consultation process of revised guidelines to implement accelerated access and conditional marketing authorisation. These are based on less complete clinical data. This will also accelerate patients’ access to medicines and address unmet medical needs.
The guidelines are specifically aimed at innovative medicines and target diseases where no treatment is available. It could provide patients with a major therapeutic advantage over existing treatments.
This public consultation process is hot on the heels of the highly debated Stamina Foundation debacle. This involved an Italian court ruling that unproven stem cell therapy on a three-year-old child with Krabbe disease, an incurable neurological condition, could continue.
The decision was based on the compassionate use of the therapy in patients with severe incurable diseases as a last resort. It also followed an official endorsement by the Italian Government in March 2013. The government decreed that the Stamina Foundation were allowed to continue stem cell therapy on 32 terminally ill patients. Their permission came without proof that the cell-based therapies were manufactured according to Italy’s legal safety standards.
In Japan, the revised Pharmaceutical, Medical Devices and other Therapeutic Products Act came into effect in November 2013. It contains a specific section for regenerative medical products and allows for conditional, time-limited marketing authorisation to be given. The authorisation will only happen if a product’s safety is ensured.
The available clinical trial results should also predict likely efficacy. But the authorised products will still be subject to further safety and efficacy tests between conditional and final approval.
Covering South Africa’s landscape
Stem cell therapy holds the possibility of curing a large number of diseases. However, almost all of these therapies are still in early development and clinical trial stages.
Access to these therapies prior to regulatory approval might not only relieve human suffering, but will also legally enable scientists to test and prove their efficacy via an alternative means (other than in the clinical trial setting).
Although the benefits from the developer’s perspective are apparent, the patient’s safety and best interest must remain top-of-mind. Most importantly, the expectations of potentially vulnerable patients should be managed sensitively and accordingly.
The universal nature of stem cells therapy begs for harmonised international regulation, and South Africa can learn and benefit from current global developments.
This article based on a paper published in a special South African Medical Research Council flagship edition of the South African Journal of Bioethics and Law.
Marco Alessandrini has received funding from National Research Foundation (NRF) of South Africa and the National Health Laboratory Services (NHLS) Trust.
Marietjie Botes does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond the academic appointment above.
Authors: The Conversation