Quality Control, Quality Assurance Certification for Phytopharmaceuticals
M N V Prasad Department of Plant Sciences, University of Hyderabad

If phytopharmaceuticals are to be regarded as rational drugs, they need to be standardised and pharmaceutical quality has to be approved. This article will shed light upon the criteria of quality assurance and quality control of phytomedicines.

India has a very rich diversity of medicinal and aromatic plants (MAP). However, due to undesirable contaminants, export is negatively affected. The transfer of trace elements by MAPs could be beneficially used in bio-fortification programmes to increase human uptake of essential micronutrients such as Se, Fe and Zn.

India has 15 agro climatic zones and about 18,000 species of flowering plants of which nearly 7,000 are believed to have healing properties and are used in Indian System of Medicine viz., folk medicine, ayurveda, siddha, unani and homoeopathy including modern medicine. There are about 7000 ?rms manufacturing traditional medicines with or without standardisation (Dubey et al 2004). In the recent past there has been considerable interest in drugs obtained from plants than at any time in history. About 960 species of medicinal plants are estimated to be in trade both nationally and internationally of which 178 species have annual consumption level exceeding 100 tons per year. It is being observed that there is a global resurgence in traditional and alternative health care systems resulting in growing world herbal trade which stands currently at USD 120 billion and is expected to reach USD 7 trillion by 2050.

In order to attract international and national market they must have “good quality tag”.

To implement this Government of India very recently launched the quality control and assurance jointly by the National Medicinal Plants Board (NMPB) and the Quality Council of India (QCI). According to QCI, the scheme has been designed keeping best international practices in view – the standards are based on WHO standards. The compliance checking will be done by independent, third party agencies conforming to international standards. Any producer/collector or group of producers/collectors can obtain certification from the designated certification body (CB). The notified CB will undertake surveillance and monitor the herbal materials and products. In the recent past there has been interest in the development of new commercial drugs from herbal materials and to reestablish traditions of yesterday as drugs of tomorrow (Gurib-Fakim 2006).

The two commonly used terms related to herbal products quality are:

Quality Assurance [QA], it is a wide-ranging concept that covers all matters that individually or collectively influences the quality of a drug. It is the total of the organised arrangements made with the objective of ensuring that drugs are of the quality required for their intended use. Quality Assurance therefore incorporates Good Manufacturing Practices, along with associated factors.

Quality Control (QC) is the part of Good Manufacturing Practices [GMP] that is concerned with sampling, specifications, testing, documentation and release procedures. This approach ensures that materials are not released for use, and that drugs (are not) released for sale or supply, until their quality has been deemed satisfactory.

Good Manufacturing Practices (GMP) are the part of Quality Assurance that ensures that drugs are consistently produced and controlled in such a way as to meet the quality standards appropriate to their intended use, as required by the marketing authorisation.

Owing to the great variability in plant chemical composition that results from factors to which plants are exposed during their growth, storage and different stages of manipulation, characterisation and/or standardisation of phytopharmaceuticals are necessary. Standardisation of herbal preparations should allow the knowledge of their composition and prevent, or at least make less likely, the consumption of drugs of questionable quality. The latest pharmacopoeias, attempts at standardisation, prescribe methods, usually chromatographic, for the analysis and quality control of medicinal products of plant origin (Prasad 2008).

Microbiological contamination and foreign materials are important quality criteria in the testing of medicinal plants. As with any product from agricultural or wild sources, medicinal plants can be contaminated by organic or inorganic substances of natural or synthetic origin, such as insects, microorganisms, eg, fungi and their mycotoxins heavy metals (Chizzola and Franz 1996; Figura et al., 1998, Prasad 2008, Sathiyamoorthy et al., 1997; Wong and Koh 1986; Wong et al., 1993; radioactive materials (Karavaeva and Molchanova, 1998).

Glocal demand (global +local = glocal) for plant raw materials (medicinal value) is increasing : Safety (undisclosed toxic contaminants), efficacy, affordability, availability of bioactive molecules and nutraceuticals as per consumer choice, promising plant products for the treatments for major diseases HIV/Malaria/TB/Cancer/Diabetes etc. is gaining momentum. Several of the bioactive molecules and nutraceuticals act as: Adaptogen, Anticancer, Antidiabetic, Antidiarrhoeal, Bioavailability enhancers. Brain tonics, Antiasthmatic, Antihypertensive, Antiulcer, Antiurolithiatic, Hepatoprotective, Carminative stomachic and Purgative. However, there is a vast gap between demand and supply due to plan material availability becoming rare. Since agro-technology is not known for many of the important plants, I vitro methods are to be established. Several of these plants are to be collected from nature.

Some of the Existing Framework for QC/QA
The World Health Organisation (WHO): The WHO recognises that the traditional use of herbal medicines with long historical use and that these may be accepted by national authorities WHO plays a greater role in reducing the undesirable side effects and morbidity especially among impoverished populations.

European Union (EU): The EU directives 2001/83/EC on the Community code relating to medicinal products for human use lays down a general framework for pharmaceutical products requiring pre-marketing approval before gaining access to the market and laying down the requirements for the documentation of quality, safety and efficacy. This framework has effectively been in operation and additionally the European Agency for the Evaluation of Medicinal Plant Products acts as a central agency for European medicines. However, individual Member States (UK, Germany, France, Italy etc.) have taken different approaches in reviewing herbal medicines.

The United States (US): In the US, the Food and Drug Adminsitration (FDA) has responsibility for food and drug products. Drugs are regarded as products that claim to treat, cure, mitigate or prevent a disease. Herbal medicines follow the same procedures as those for a chemical drug. Otherwise natural products are regulated as foods under a requirement for ingredients to be generally recognised as safe (GRAS). Natural products generally have GRAS status, provided that this is supported by expert concensus. Hence dietary supplements and herbs are considered to be foods provided that they are generally regarded as safe and do not make medicinal claims. Furthermore, the ingredients and the plants or parts of the plants must be quanti?ed and where, ingredients are listed with a pharmacopeial reference, they must meet the standard laid down in the pharmacopeia. There are also speci?c requirements for food additives that do need a pre-market approval by the authority.

Unless certified by the national and international standards marketing of phytoproducts in international market will not be possible under the current regulations.

References
  1. Chan, K. (2003) Some aspects of toxic contaminants in herbal medicines, Chemosphere 52: 1361–1371.
  2. Chizzola, R., and Franz, C. (1996). Metallic trace elements in medicinal and aromatic plants from Austria. J. Appl. Bot.Angew. Bot. 70, 52-56.
  3. Dubey NK, Kumar R, Tripathi P (2004). Global promotion of herbal medicine: India’s opportunity. Current Science; 86(1):37–41.
  4. Ernst, E., (2004). Risks of herbal medicinal products. Pharmacoepidemiology and Drug Safety 13, 767–771.
  5. Figura, B., Pluta, J., and Lorenz, K. (1998). Assessment of the level of certain heavy metals in Polish galenic preparations. Pharmazie 53, 458-462.
  6. Gurib-Fakim, A., (2006). Medicinal plants: traditions of yesterday and drugs of tomorrow. Molecular Aspects of Medicine 27, 1–93.
  7. Karavaeva, E. N., and Molchanova, I. V. (1998). Accumulation of radionuclides by medicinal plants in the zone of impact from the Beloyarskaya nuclear power plant. Russ. J. Ecol. 29, 357-359.
  8. Prasad M.N.V. (2008) Trace elements in traditional healing plants - remedies or risks, In. M.N.V. Prasad (ed) Trace elements as contaminants and nutrients: consequences in ecosystems and human health. John Wiley and Sons Inc. New York. pp. 137-160
  9. Sathiyamoorthy P, Vandamme P, Oven M, Gologoldhirsh A. (1997) Heavy metals in medicinal and fodder plants of the Negev desert. J Environ Sci Health;32:2111-2123.
  10. Wong, M. K., and Koh, L. L. (1986). Mercury, lead and other heavy-metals in Chinese medicines. Biol. Trace Elem.Res. 10, 91-97.
  11. Wong, M. K., Tan, P., and Wee, Y. C. (1993). Heavy-metals insome Chinese herbal plants. Biol. Trace Elem. Res. 36,135-142.

Contact: prasad.heavymetal@gmail.com