Quality Control and Regulation of Herbal Medicine

Quality Control of Medicinal Plants

1) Production of Medicinal Plants and GACP 

To minimize the variance and improve the quality of herbal medicine, the Good Agricultural and Collection Practices (GACP) guidelines were established to determine how to cultivate and obtain medicinal plants of the highest possible quality.
The main objectives of GACP guidelines are to : (WHO GACP, 2003)

1. contribute to the quality assurance of medicinal plants used as the source for herbal medicine to improve the quality, safety and efficacy of finished herbal products

2. guide the formulation of national and/or regional GACP guidelines and GACP monographs for medicinal plants and related standard operating procedures; and 3. encourage and support the sustainable cultivation and collection of medicinal plants of good quality in ways that respect and support the conservation of medicinal plants and the environment in general.
In Korea, Office of Rural Development has established GACP and SOP(Standard Operating Procedure) guidelines to set the standard on collection, maintenance and primary processing process on good medicinal plants.

Standards for Good Agricultural Product Control:b
1. Agricultural Product Traceability Management System
2. Selection of seed and seedling Soil management before cultivation: testing Farming utensil management
5. Fertilizer and nutrient management
6. Water management: water quality examination
7. Crop protection and use of agrochemicals (Pest control and crop-dusting, Pesticide residue analysis and presentation, Agrochemical storage and maintenance)
8. Collection process
9. Management after collection
10. Post-collection management facility(Selection standard of GAP management facility) 11. Waste and hazardous substance management
12. Laborers’ health, safety, welfare
13. Environmental issues
14. Education

Currently, the agricultural product quality control standards differ from the control standards of medicinal plants. Therefore medicinal crops are not certified as standard medicinal plants even if they are produced according to GAP, and must be processed according to standards of herbal medicine manufacturers.

2) Medicinal Plants Standard Manufacturing Process Guideline

This refers to the standard manufacturing process implemented from collection to small packaging. It applies to the primary processing of 409 of the 546 herbs listed in the official compendium of the Korean Pharmacopoeia by medicinal herbs material manufacturers, with the remainder undergoing a more specialized process called “Pojae”.
 This guideline categorizes medicinal plants by the part used and describes their collection period, medicinal properties, process of screening for impurities and packaging in detail.

3) Manufactures of Medicinal Plant Material and hGMP 

GMP is short for Good Manufacturing Practice, a system in which the government screens and evaluates the manufacturing process of drugs for certification. Quality control is strictly applied to the whole process of drug material purchase, manufacturing and packaging and supervised by the government for the enhancement of overall drug quality.

GMP standards on biological formulas were first established in 2000, applied to generic drugs in 2008, then began to cover medicinal plants in 2012, with the latter being referred to as hGMP.
hGMP is a mandatory certification authorized by Food and Drug Administration on good medicinal plants materials for the health and safety of citizens.

GMP systems share these three important functions:

 1. Minimize man-made error by fully equipping facilities

 2. Prevent contamination and quality deterioration by educating workers

 3. Establish a quality assurance system with standard documentation of maintenance
 Manufacturers of medicinal plant material are evaluated on their conformance to the guidelines through both questionnaires and on-site inspections by the Food and Drug Administration.
As of January 2015, a total of 82 herbal manufacturers in Korea were certified and registered as hGMP. (KFDA, 2015)

4) Herbal Standard Product and Quality Inspection Standard

Products with this label have been manufactured from materials that passed inspection for quality as well as the hazardous substance inspection. It is certifiably safe from heavy metal and other hazardous substances.
Since April 1st, 2012, only those medicinal plants manufactured by qualified manufactures can be distributed, so as to guarantee the safety of herbal medicine.
Therefore, herb retailers cannot process, pack or sell domestic or imported herbs that have not passed a strict inspection with the proper guidelines. Obligation to use the Standard Herb Product designation is applied not only to institutions of Korean Medicine, but to Korean Medicine pharmacies and apothecaries so that consumers can safely buy herbal medicine.
Quality inspections for herbal standard products are conducted either on the spot or in the lab, depending on the need for a standard, in-depth, or hazardous material inspection.
Summaries of each test are as follows (FDAD of CDA, 2007) : 1. Morphology 2. Verification 3. Hazardous substances 4. Purity Test 5. Loss on drying 6. Ash 7. Acid-insoluble ash 8. Extract content 9. Oil dose 10. Quantity

5) Imported Medicinal Plants and Herbal Medicine Quality Inspection Agency

To assure the safety of medicinal plants imports, the Food and Drug Administration’s Regulation of Imported Drug legislates on Article 5 Clause 3 that “Importers of medicinal plants must submit an application for quality inspection to the director of National Institute of Food and Drug Safety Evaluation, or to the head of herbal medicine quality inspection agency designated by the Food and Drug Administration. They must undergo an inspection according to the inspection method for imported herbal medicine specified in annexed table 1 for customs.”
 As of May 2015, eight research centers and private agencies are designated as inspection agencies for the quality of medicinal plants, for customs tests on imported medicinal plants or for self-quality inspection on domestic herbs.



6) Regulation of Wonoi Tangjeonsil 

Medical Act Enforcement Rules amended in September 2008 enforces regulations that long-term care hospitals, Korean medicine hospitals and clinics must all install Wonoi Tangjeonsil (outside-decoction rooms) for the decoction of herbal medicine, and supervise the facility in accordance with the pertinent guidelines for the safe supply of herbal medicine. Each Wonoi Tangjeonsil should be declared to the jurisdictional health center before its establishment in its medical institution.   
Facility standards for medical institutions establish that facilities such as dispensary rooms and medicinal plants storage facilities needed for decoction be stationed in a separate decoction room.
if herbal medicine is dispensed in the separate decoction room, relevant paperwork including a prescription from a Korean Medicine doctor, a record of preparations, stored and released medicinal plants and shipping bills of dispensed herbal medicine should be stated and stored.

 Quality Control of Herbal Medicine

1) Established Korean Medical Classics and Herbal Medicine

Established Korean medical classics refer to “established Korean medical classics” in Pharmacy Law, Article 45 (Approval of drug sales), Paragraph 4, that “The herbal pharmacist approved by Clause 1 may mix and sell herbal medicine according to prescriptions in established Korean medical classics or a Korean medicine doctorʼs prescription at the patientʼs demand.”
 Currently, “established Korean medical book” is defined as either “Treasured Mirror of Eastern Medicine (東醫寶鑑), Compilation of Formulas and Medicinals (方藥合編), Emergency Prescriptions for the Countryside (鄕藥集成方), Complete Works of Jingye (景岳全 書), Introduction to Medicine (醫學入門), New Edition of Universal Relief (濟衆新編), Secret Works of Universal Relief (廣濟秘編), Longevity and Life Preservation in Eastern Medicine (東醫壽世保元), the Compendium of Materia Medica (本草綱目), or Longevity and Life Preservation (壽世補元).”

When an herbal medicinal preparations is based on a Korean medical book, the usage, dosage, efficacy and effects found in the book are directly applied. Additionally, prescriptions found in Korean medical books or similar prescriptions are exempt from safety or efficacy screening so that herbal medicine prescriptions may easily receive drug-related permissions.

2) Herbal Preparations and GMP 

“Regulations on manufacture and quality control of drugs,” which require GMP regulation on 16 medical products, was newly established according to PIC/S GMP regulations in Korea.
In particular, regulations for manufacturing herbal medicine (crude drugs) are stated, which classifies; Principle, Facility (storage, shed, device), documentation (starting material standard, official compendium), and Quality control (specimen collection). Additionally, the management, storage and processing of “starting materials” in the manufacturing procedure are stressed.
A crude drug (herbal medicine) must be of appropriate quality, and manufacturers of herbal extractions (herbal powder, extracts) and herbal medicine (crude drugs) must be provided with evidence-based data.
An herbal medicine (crude drug) manufacturer must only use a starting material that is manufactured by (material) drug manufacturing and quality control standards and drug item approval (report) and must appraise starting material providers and prepare the necessary papers. Manufacturers must verify whether the suppliers of origin crude drug or crude drug (herbal medicine) comply with the correct herbal medicine (crude drug) manufacture and management guidelines or supervise appropriately, according to quality risk control (QRM) if necessary.