Access to plant (phyto) medicines to prevent or treat illnesses or health conditions both acute and chronic, is an ethical obligation. Many factors impact on this, including their costs and affordability, their quality and availability in efficacious dosage forms, and how they are regulated

Termed Complementary Medicines in Australia, Herbal Medicinal Products in Europe, Botanical Drugs in the U.S.A, and Natural Health Products (NHP’s) in Aotearoa New Zealand and Canada, the products themselves are all used in some way to support human and animal health. How the population of each country regards and uses them, and what checks and balances governments decide to put on their safety and accessibility, is influenced by relevant legislation.

Plant medicines are however, a complex and diverse group of products. In practice, many countries have more than one regulatory agency (generally that responsible for foods, plus that responsible for medicines), involved in overseeing their compliance to what is often a rather confusing legislative framework.

NHP Regulations In Aotearoa New Zealand

In Aotearoa New Zealand, successive governments have struggled for more than 25 years to develop suitable new legislation to replace the hopelessly outdated 1981 Medicines Act, and bring regulations of medicines and NHP’s into the 21^st century⁽¹⁾.  

The Australia New Zealand Therapeutic Products Agency (ANZTPA) was an attempt initiated by the New Zealand and Australian governments in 1996 to develop a joint trans-Tasman scheme for regulating therapeutic products. Government officials and industry representatives worked for eleven years on the detail of this new agency until 2007, when the New Zealand government postponed further legislation.

The next attempt was the Natural Health and Supplementary Products (NHSP) Bill, on which the government worked from 2011 until dropping it at the end of 2017.

The Therapeutic Products Bill was the third attempt to regulate all medicines and medical devices as well as NHP’s, and was introduced by the current government in November 2022. In July of this year it passed its third reading in the House, and subsequently became the Therapeutic Products Act (2023). Regulations as provided for in the Act are now being developed, and need to be in place by September 2026⁽²⁾.

Regulatory Challenges

The huge plethora and diversity of brands and product types, digital marketing, ongoing incorporation of new technologies and supply chain disruptions, are driving constant changes in the availability of products in the marketplace.

The important issue of sustainability of some medicinal plants used as raw materials, is largely left to companies themselves to commit to, and voluntarily opt into secondary regulatory agencies such as the Union for Ethical Biotrade, EcoCert, Rainforest Alliance, FairWild and B-Corp.

Many medicinal plants are also foods, and well known culinary foods and spices such as beetroot, garlic, ginger and turmeric are incorporated into capsule and tablet dosage forms. Whether something is in fact a food or ‘dietary supplement’, or is actually ‘medicinal’, is a 6 million dollar question which extracts different answers depending on who is asked.

Many companies in the industry have leveraged this situation to their advantage, and the terms ‘dietary supplement’ or ‘food supplement’ are widely used as descriptive terms when selling products. Most plant-based NHP’s are safe and fulfill a nutritive or functional dietary need when taken in small doses as a supplement to the diet. Food regulations, while having some obligations on manufacturers and sponsors, also tend to have a lower regulatory bar and thus cost, than those for medicines.

Language however, and the terminology used to describe something can greatly influence one’s perception. By referring to most NHP’s as supplements rather than as pharmacologically active medicines, their perceived ability in the eyes of many to produce tangible health improvements, is somewhat compromised. In many ways it fosters an impression that NHP’s are pawns, rather than knights or rooks, kings or queens. As such their status or ‘mana’ (a Māori word that signifies the presence or intrinsic influence or power of something), is lessened.

Personally, since training in medical herbalism after several years working as a pharmacist, I’ve always regarded well manufactured and properly used plant extracts as medicines. The name of the company I founded 25 years ago, and the title of this blog, extols this principle.

Taking the right approach is a minefield for regulators though, and it is impossible to please everyone. Many parameters require consideration when trying to distinguish between a food or dietary supplement and a medicine. They include the product potency, therapeutic claims made for it, the medical condition(s) or intended application, the presence or absence of a qualified practitioner’s oversight, and the manufacturing standards and pharmacovigilance systems in place.

In practice, a more tiered and evolved approach to classification of NHP’s, to include categories apart from dietary supplements and medicines alone, would have much merit.

While alcohol is alcohol regardless of the form it is presented in, low alcohol beer and gin are poles apart, in terms of their alcohol content. Their accessibility, packaging, effects on the user and thus safety, therefore also vary significantly. The same enormous diversity exists in strength, efficacy and safety of many NHP’s being produced and sold today.  Logically therefore, as with drug-based medicines, it is appropriate that certain products should only be able to be prescribed, by suitably trained and registered practitioners⁽³⁾.

Appraising traditional preparations versus modern pharmaceutical manufacturing methods for their relative risks, and ensuring evidence is sufficient to support therapeutic claims, are other challenging areas. For this and other regulatory tasks, adequate knowledge and training in NHP’s is an important capability need for the regulator. A well resourced regulator in budgetary and human expertise terms, and one built upon principles of good science, public safety, consultation and accountability, is therefore essential.

Prevention better than a cure

A more preventative and self help approach to personal health is critical to reduce the dual burden on governments and future taxpayers of aging populations and increasing resource needs of mainstream healthcare systems. Evidence suggests a vast number of plants can either enhance our resistance to and reduce our risks of a wide range of illnesses, or reduce our dependence on drug and hospital treatments. However, to utilise them as prophylactic and safe selfcare interventions, research, education, and a regulatory environment that facilitates this, needs to continue.

Additionally though, there is in fact a growing recognition of the ability of plant derived medicines to provide efficacious treatments for a whole host of serious illnesses and diseases for which conventional medicine is struggling to make more headway.  

Treatment of serious conditions

The incorporation of medicinal plants into mainstream healthcare including for serious conditions such as sepsis, post-stroke and kidney failure, has been a part of Chinese medicine for a long time^(4-6). Also in Japan, Germany and other countries, parenteral products are manufactured from plant extracts and licenced with regulatory authorities for the treatment of specific conditions.

Results from a recent clinical trial in China have put the potential role of phytotherapy for the treatment of sepsis into the spotlight, with a significant reduction in mortality being reported following administration of a polyherbal parenteral preparation⁽⁷⁾.  Sepsis is a seriously dysregulated host response to infection, and more than 19 million cases of severe sepsis occur globally each year, leading to at least 5 million deaths⁽⁸⁾.

The study was a multicentre, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites in China. It included 1817 randomized patients aged 18 to 75 years with sepsis present for less than 48 hours, nearly half of whom had septic shock. Patients received either an intravenous infusion of the herbal preparation at a dose of 100 mL or volume-matched saline placebo every twelve hours for five days, alongside usual hospital care in either an ICU or medical ward. The primary outcome was 28-day all-cause mortality.

Of the 1760 patients who completed the trial, the 28-day mortality rate was significantly lower in the treatment than in the control group. Within the herbal and conventionally treated group, 165 of 878 patients (18.8%) had died, whereas in the control group who received conventional treatment alone, 230 of 882 patients (26.1%) had died after 28 days. The incidence of adverse events was very similar in both groups^{(7, 9)}.

With plant extracts containing multiple phytochemicals including some which may impede absorption, achieving adequate bioavailability from their oral administration can sometimes be a challenge, just as it is for some drugs.  Parenteral dosage forms are often life-saving in modern medicine, as intravenous or intramuscular injections can achieve much higher plasma and tissue levels, and thus enable better, faster and a more protracted efficacy to be achieved.

However, as every pharmacist knows, parenteral medicines need to be manufactured using a high level of Good Manufacturing Practice (GMP) standards, far greater than those in place for dietary or food supplements, to avoid serious adverse events or treatment failure that may result in death.

Leveraging the potential of phytotherapy

Studies such as this one, highlight the potential contribution of medicinal plants to modern healthcare, as being a whole lot more than that of ‘dietary supplements’ alone.

It is encouraging to see that in some countries of the world, companies, clinicians, governments and regulators have for some time now been actively embracing and researching new potential applications for their traditional plant medicines, including their parenteral (injectable) use for serious or difficult to treat conditions.

Incorporating these and other medicinal plants into current treatment protocols for serious and expensive to treat conditions such as acute infections, sepsis, diabetes, cancer and mental unwellness, is an ambitious aspiration, but an essential one. Additionally for most of these applications, adequate regulatory oversight and adherence to medicine-manufacturing standards, will also be required.

The current New Zealand government has now passed legislation to replace our hopelessly outdated 1981 Medicines Act, which was no easy task. However, many challenges exist with preparation of the subsequent regulations. These include providing a regulatory model that continues to allow self-selected NHP’s both as a safe self-help intervention, but also recognizes and fosters greater research into their potential applications for the prophylaxis or treatment of more serious conditions, and extends the clinical reach of our many highly trained NHP practitioners.

References:

1. Rasmussen PL, NZ Politicians continue to let the Natural Health Products Industry and Practitioners Down. www.herbblurb.com Jun 19, 2020.
2. https://www.health.govt.nz/our-work/regulation-health-and-disability-system/therapeutic-products-regulatory-regime
3. Rasmussen PL, Statutory regulation of medical herbalists and naturopaths: an essential step towards a more cost and outcome beneficial future healthcare system. www.herbblurb.com 26 April, 2019.
4. Cheng C, Yu X. Research Progress in Chinese Herbal Medicines for Treatment of Sepsis: Pharmacological Action, Phytochemistry, and Pharmacokinetics. Int J Mol Sci. 2021;22(20):11078. 
5. Zhang L, Yang L, Shergis J, et al. Chinese herbal medicine for diabetic kidney disease: a systematic review and meta-analysis of randomised placebo-controlled trials. BMJ Open. 2019;9(4):e025653.
6. Wei M, Wang D, Kang D, et al. Overview of Cochrane reviews on Chinese herbal medicine for stroke. Integr Med Res. 2020;9(1):5-9.
7. Liu S, Yao C, Xie J, et al. Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial. JAMA Intern Med. 2023;183(7):647-655.
8. Fleischmann C, Scherag A, Adhikari NK, et al. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit Care Med. 2016;193(3):259-272
9. Rasmussen PL, Chinese parenteral phytomedicine reduces mortality from sepsis. Pharmacy Today, October 2023. ISSN 1170-1927