Assuring Quality of T/HMP: Challenges and Key Issues

Question 1

What are the different terminologies for T/HMPs?

Answer 1

• Traditional Medicines, Herbal Medicines
• Natural Products, Botanicals
• Complementary Medicines, Complementary Health Products (CHP), Complementary & Alternative Medicines (CAM)

Question 2

What are the general agreements on the definition of T/HMP?

Answer 2

1. A herbal medicine is a medicinal product.
   - Not a food or dietary supplement or cosmetic product.
   - Contains 1 or more herbal substances as active ingredients.
   - Active ingredients are not synthetic.
2. A traditional medicine is a medicinal product.
   - Not a food or dietary supplement or cosmetic product.
   - Contains 1 or more “traditional” substances as active ingredients.
   » “Traditional” substances include those of herbal, mineral or animal origin.
   - Active ingredients are not synthetic.
3. Products that are not T/HMP

Question 3

Name products that are not T/HMP

Answer 3

• Drug products (chemically synthesized)
• Biologicals and biotechnology-derived medicinal products
• Food, dietary or nutritional supplements
• Cosmetic products
• Medical devices

Question 4

What is the current regulatory status of T/HMP?

Answer 4

1. Lack of harmonized GMP standard for T/HMP
2. Minimal product quality requirements
   - Limits of micro-organisms (bacteria, fungi) in finished T/HMP
   - Limits of toxic-heavy metals (Hg, As, Pb, Cu) in finished T/HMP
3. Product quality attributes which are not mandatory include:
   - Control of herbal active ingredients (i.e. identification and assays)
   - Control of other starting materials (e.g. water, preservatives, excipients)
   - Control of container-closure systems
   - Stability (shelf-life) testing and process validation
   - Control of herbal contaminants – pesticides and fumigants

Question 5

What are the challenges and issues concerning T/HMP?

Answer 5

Need for:

1. Harmonisation of GMP standard for T/HMP
2. Harmonisation of quality standard for T/HMP
3. Combating adulterated T/HMP
4. Levelling up of (cottage) T/HMP industry
5. Implementation of GACP (Good Agricultural and Collection Practice) - but not in detail

Question 6

Strategies for harmonising the GMP standard for T/HMP

Answer 6

• PIC/S GMP Standard (Annex 7) – good starting point for global harmonisation
• Collaboration with 52 PIC/S Participating Authorities

Question 7

Strategies for harmonisation of quality standard for T/HMP

Answer 7

• Based on the philosophy that “quality is independent of traditional use”.
• Manage contents of EMA document
• control water quality

Question 8

What are the contents of EMA document?

Answer 8

• QC of herbal active ingredients
• QC of other starting materials (including water)
• Control of container-closure systems
• Stability (shelf-life) testing
• Control of herbal contaminants, including pesticides, fumigants, heavy metals, microbial limits

Question 9

Why is the control of water quality important?

Answer 9

• Main starting material in (oral) liquid T/HMP, has to meet pharmaceutical quality standards
• Quality of feed water is variable depending on source of water and seasonal variations
• Contains chemical and mineral impurities
  » Affect stability profile and quality of T/HMP in liquid dosage forms.
• Contains microbiological impurities
  » Good potential medium for microbial growth
  » Affects product stability/quality and poses health risks
• Why do we need to purify potable (tap) water?
  » Potable water has a much higher (alkaline) pH than purified water.
  » Potable water has an unknown concentration of heavy metals which may be much higher than the concentration in purified water (<0.1ppm).
  » Potable water has unknown TOC and oxidisable substances, as compared to known quantities in purified water.
  » Potable water has electrical conductivity significantly higher than that of purified water at room temperature.
  » Potable water may have a higher microbial limit (hence higher microbial concentration) than purified water.

Question 10

Who makes adulterated T/HMP?

Answer 10

Backyard manufacturers

• In backyard facilities with improper equipment
• With deliberate intent to cheat (criminal in nature)
• Cause acute toxicity to patients
• Adulterants often present in large amounts

Question 11

What are the suspected adulterants for the following claims/indications?

1. Slimming
2. Baldness
3. Arthritis
4. Fever, cold, flu, typhoid
5. Epilepsy
6. Erectile dysfunction, decreased libido

Answer 11

1. Fenfluramine, thyroxine, sibutramine and analogues
2. Minoxidil
3. Steroids, NSAIDs
4. Paracetamol, aminopyrine, chlorpheniramine
5. Phenytoin
6. Slidenafil, tadalafil and analogues

Question 12

What do backyard manufacturers do to avoid detection of adulterants?

Answer 12

• Incorporate the adulterants into capsule shells, which are not usually tested for purity.
• Adulterants are created using analogues of the API and other ED drugs.

Question 13

What are some multi-prong strategies to avoid the sale and consumption of adulterants in the market?

Answer 13

• Educating consumers and public
• Increased industry vigilance
• Exchange of information and alerts amongst regulators (internationally)
• Sharing of test methods and reference standards for testing adulterants, including new analogues
• Inspectors: robust GMP/GDP audit and tight supply chain control

Question 14

What are the balancing interests of stakeholders involved in the T/HMP industry?

Answer 14

Fast market access public safety/quality issues

Trade/Commercial Interests societal interests

National Considerations globalisation & harmonization

T/HMP Regulation Pharmaceutical Regulation