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434 Herbal Pharmacopeia
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Regulatory Considerations
21
forHerbal Products
Saleem Ur Rahman, Ehtisham Shaque, Afsheen Tajummal, Mashaal Nageen, Asma Zahoor, Nasir Ali, and Farakh Javed
Department of Biological and Health Sciences, Pak-Austria Fachhochschule: Institute of Applied Sciences and Technology, Haripur, Pakistan

21.1 INTRODUCTION

Preparations which contain plant materials exclusively are called herbal products [1]. Similarly, the knowledge, skills, beliefs and practices which are used to diagnose and treat diseases to main­tain the health of individuals are dened as traditional medicines (World Health Organization) [1]. According to the literature, herbal medicines are described as the preparations made according to the therapeutic knowledge and experiences of different generations over the centuries and the systems of medicines practiced indigenously in societies. These rm believes that there is a high demand for such medicines in many developing countries not only because they are less expensive but also as a result of better cultural acceptability and minimal side effects on the human body, along with better compatibility [2]. Herbal products are utilized to treat various ailments such as depression and mental health disorders as well as to achieve weight loss, and to operate as analgesics and cold and allergy treatments [2]. Serious health conditions such as diabetes, asthma, heart diseases, and endometriosis are also treated through the use of herbal medicines. This suggests that whatever the disease condition, there is always a herbal remedy which can alleviate it. Food supplements are classied by Food and Drug Administration (FDA) as one aspect of herbal medicine [3]. The FDA does not usually govern the production of new herbal supplements through strict protocols of drug approval process, meaning that no pre- market approval is required [3]. One of the current FDA­approved drugs is Veregen® (sinecatechins ointment) [4]. Both benets and risks of herbal supple­ments are discussed widely on various platforms and strong opinions both in favor and against their use are noted. Although this debate will focus on their use, healthcare professionals do need to acknowledge that people around the world use them commonly, considering them to be safe and appropriate sources for healthcare products [5].
In addition, to improve general health and well- being, various phytochemicals, along with other herbal remedies, are useful in treating ailments. In the local market, there is a concern that there is no scientic basis for believing the fact that herbal remedies are non- hazardous although they have a high success rate. In today’s world of social and electronic media, due to the online marketing of such drugs by manufacturers, there has been an exponential increase in both their use and the related demand. Thus, there is a requirement for the introduction of regulations, which will develop­ing legislation to regulate the manufacturers of herbal products and to regulate the sale of herbal medicine. These should be used to ensure that herbal remedies should be proven safe before enter­ing the market and made freely available to the public. Some such regulations are already in place: In India, for example, the laws of 1945 and the Drug and Cosmetics Act of 1940 regulate herbal medicines [6]. For so long various controversies, suspicions and doubts led to increased use of herbal medicine [7, 8].
440
Regulatory Considerations for Herbal Products 441
TABLE 21.1 Traditional and Complementary Medicine (TMC/CM) Products
Country Terminology Description
China Classic Chinese medicines Refers to Chinese medicines documented and established
through historical texts and practices.
Taiwan Standard formula of Chinese medicine Refers to established formulas that are widely recognized and
used within the framework of Chinese medicine.
Hong Kong Established medicine Refers to recognized and standardized herbal formulations used
within traditional Chinese medicine.
Japan Kampo medicine Derived from ancient Chinese medicine and standardized in
Japan for modern use.
Korea Herbal drug Refers to herbal medicines that are standardized and used within
the practice of Traditional Korean medicine.

21.2 GLOBAL REGULATORY LANDSCAPE

Under the mentorship of the US Food and Drugs Administration (FDA), in 2013 the Global Coalition for Regulatory Science Research (GCRSR) was established. The GCRSR was established in 2013. At present, it has around 10 member countries or organizations, including the European Union (EU). The GCRSR has gone on to collaborate and start partnerships with international bodies and agencies to utilize bid data sciences and emerging technologies in order to improve the safety and efcacy of foods and drugs as well as their improved regulatory structure [9]. As noted earlier, the individuals using herbal products as medicine are continuing to increase in many countries. In addition, the regulation of herbal products varies from country to country; in some places, however, herbal products are only allowed for general health matters rather than being used for broader medi­cal purposes [10]. Globally, the use of herbal medicines (HM) derived from natural sources as well as their usefulness in dietary or medicinal terms has increased substantially [11, 12]. Even though HMs have been present for thousands of years, their jurisdictions and regulation has varied across countries, and some of them have also begun to be regulated recently. Psychological binding is also involved in such practices as for example, if a drug is being used in families over centuries, then the consumers will have blind faith in it as a remedy. . Hence the knowledge of the previous practices can serve as a guide for the current use of dietary supplements.
Table 21.1 offers a summary of the terminology and description of traditional and complemen­tary medicine (TMC/CM) products across ve regions, highlighting their unique regulatory and cultural contexts.

21.3 REGULATORY AGENCIES AND THEIR ROLES

21.3.1 United StateS

Products marketed as dietary supplements are regulated by the US FDA under the umbrella of the Federal Food, Drug and Cosmetic Act (FD&C act), which was later amended by the Dietary Supplement Health and Education Act (DSHEA), 1994 [13–15]. Herbal products (HPs) make up a major part of US dietary supplements. Statistically, in the year 2000, it has been reported that about 591 billion USD have been spent by American consumers on herbal products [4]. Similarly, the practice of Complementary and Alternative Medicine (CAM) has risen dramatically in recent years. In order to explore unconventional medical practices, in 1992 the US Congress introduced the Ofce of Alternative Medicine (OAM). The term CAM comprises a vast range of healthcare practices, therapies and products that differ from conventional or allopathic medicine. With the increase in practice of CAM in the US, the confusion has been seen by the FDA, whether or not
442 Herbal Pharmacopeia
some of products enlisted in CAM are subjected to regulations by the FFDCA or the PHSA. Under the Federal Food, Drug and Cosmetic Act/Public Health Service Act, certain products being utilized in CAM are subjected to regulations. According to the FDA, several CAM products being imported into the US have had guidance issued indicating which types of products would be subjects under the Act. These guidelines made two fundamental points. Firstly, the CAM product would be sub­jected to regulations as a cosmetic, device, food along with additives, dietary supplements, and drug or biological product under the PHS Act. Secondly, the CAM products are neither exempted from PHS nor from the Act. This means, for example, that if a person wants to produce and sell juice extracted from raw vegetables as a therapy for optimal health, then the product would be subjected to the regulation by the Act as well as the FDA, along with the Hazards Analysis and Critical Control Point (HACCP) system for juices. In addition, if the seller looks to retail this as a treatment option for any disease, the juice will also be subject to the regulations of FDA as a drug under the Act. The FDA is supposed to regulate products and preparations containing botanical ingredients in a differ­ent method, as will the products of those botanical ingredients, which intend to diagnose, mitigate, or cure the disease. All of the products should follow the pre- market approval process that fall under this category [16].
21.3.1.1 Key Responsibilities of the FDA
The FDA is a government body that lies within health and human services (HHS) department.
It regulates the safety, security, and effectiveness of various products, including:
• Food (food additives, dietary supplements, infant formula and bottled water)
• Vaccines
• Microwaves and other equipment that radiate etc.
• Cosmetics and beauty items
• Animal and veterinary products
• Tobacco products.

21.3.2 Canada

In Canada, most of the natural products are classied as medicine. They are known as Natural Health Products (NHPs) and are regulated by Health Canada (HC), specically under the Natural Health Products Regulations (NHPR), which were enacted in 2004 [17]. The government planned to balance the safety of the consumers with their freedom of choice in terms of accessing traditional medicines. The NHPs must be licensed by Health Canada in order to be sold in the market in order to ensure the safety and effectiveness of the products. The product is considered to be safe by the department if the benets of the product outweigh its risks and it is intended to be used according to the directions. Simultaneously, it is considered to be effective if the department is presented with evidence supporting the described benets. Since 2004, more than 91,000 licenses have been issued by Health Canada for NHPs. In general, herbal products are regulated either as foods or as drugs according to the Food and Drugs Act. Various factors such as an ingredient’s pharmacologi­cal activity, product’s purpose, representation regarding uses, and the medicinal claims dene its designation. Responsibility for the NHPs has blurred boundaries between the Directorate of Drugs Protection and the Directorate of Food Safety within Health Canada. Various products such as khat and cannabis are controlled drugs pursuant to the Controlled Drugs and Substances Act [5]. Several public attempts have been made by Health Canada to address the issues related to the regulation of herbs. On two occasions in recent decades, 1986 and 1993, expert advisory committees have reviewed the issues of herbs which is provided for food. More recently, in 1997, an advisory panel on herbal medicines was established to advise the development of a framework for the regulation of herbal products. In addition, Health Canada has also issued guidelines, information letters, and policy statements on these issues.
Regulatory Considerations for Herbal Products 443

21.3.3 eUrope

21.3.3.1 European Medicine Agency
On behalf of the European Medicine Agency (EMA), the Herbal Medicinal Products Committee (HMPC) regulates and issues guidelines regarding the preparation, use, and safe conditions of herbal substances and medicinal product. It gives companies and national authorities a reference and standard point for the registration of herbal products and the assessment of their applications and intended usage in the European Union (EU) and its member states [6]. Such products fall into two categories under EU classication criteria, i.e. supplements or medicine. The products which are regulated as food are called supplements under directive 2002/46/EC of the European Commission [18]. Similarly, scientic guidelines on herbal medicinal products help in the development and prep­aration of market authorization for human and veterinary medicines under the European Medicine Agency. The EMA has categorized the guidelines into various sections, as discussed below.
21.3.3.2 Key Responsibilities of the European Medicine Agency
In the European Union, for the benet of animal and public health, the EMA aims to foster the evaluation and supervision of medicines and herbal products in the light of scientic excellence. It is responsible for the following major responsibilities:
1. To facilitate access to medicines and their development.
2. The regulation and evaluation of applications for marketing.
3. The portrayal of information regarding humans and veterinary medicines in simple language.
4. Check and balance maintenance about the safety of medicines throughout their lifecycle [6].
21.3.3.3 Quality Guidelines of the European Medicine Agency
21.3.3.3.1 The Declaration of Herbal Preparations in Traditional Herbal Medicinal Products
Th proper description of different types of herbal substances, along with the preparation steps and qualitative and quantitative particulars, shall ensure clear differentiation as a common criterion for the declaration. As a result, precise, consistent, and clear information is to be provided to the com­munity about all of the active compounds in the herbal products.
In order to conrm the identication and to help with the differentiation of herbal preparations, various factors which determine the complex composition of herbal products are to be stated. These factors include the production process, the genuine drug extract ratio (DER), extraction solvent and the type of herbal substances. However, in order to keep the declaration precise and short, it is not possible to include all characteristics. The purpose of the declaration is to ensure the quality and to identify the quantity of herbal preparations, the active compounds present in the preparations, and the useful substances that ensure the effectiveness and safety of the herbal products.
In order to achieve this, a system has been established that focuses on and reects the character­istics and specications of herbal products as described. Therefore, the general guidance, as outlined in the European Pharmacopeia, should be followed. This should draw, in particular, on the mono­graph Extracts/Herbal Drugs/Herbal Drug Preparations, as well as the guidelines listed under the references (EMEA/HMPC/CHMP/CVMP/287539/2005).
21.3.3.3.2 Practices for Materials Collection from Herbal Origin
Wild or cultivated land areas could be a source for herbal medicinal plants. Greenhouse and indoor cultivation are the principal sources for these plants. At present, there is an increase in indoor cul­tivation because this allows for the control of various environmental factors such as light, tempera­ture, and humidity.
Active Pharmaceutical Ingredients (API) are directly inuenced by the process of cultivation, production, and primary processing. For this purpose, an adequate quality assurance system is needed to cultivate, harvest, and for primary processing.