Essence of quality control


  • Health
  • Sunday, 11 May 2003

What is involved in manufacturing herbal supplement?s HOOI YOU CHING looks at the issue in light of the recall of health supplements in Malaysia manufactured and supplied by Pan Pharmaceuticals Limited. 

 

WHEN you go to the local pharmacy for health supplements, do you know exactly what you’re buying? How certain are you that the bottle you hold in your hand contains the ingredients stated in the label? Or how credible are the therapeutic claims made by the manufacturers? 

Obviously, if herbal medicine weren’t safe, it wouldn’t have survived the test of time. Today, Chinese medicine shops continue to sell a repository of herbal roots and plants. Similarly, the pharmacy has its shelves decked with herbal concoctions. So why did the Drug Control Authority (DCA) last week issued notices to recall immediately all batches of 219 products of health supplements from stores without implicating the Chinese sinsehs when both were in the same business?  

The DCA ruling came after Australian health authorities urgently recalled various products including health supplements manufactured and supplied by Pan Pharmaceuticals Limited. The recall was undertaken because of the cancellation of these goods from the Australian Register of Therapeutic Goods for quality and safety reasons, which subsequently led to the suspension of the company’s licence for six months. Pan Pharmaceuticals is Australia’s largest contract manufacturer of herbal, vitamin, mineral and nutritional supplements. 

The action by Australia’s medicines watchdog, Therapeutic Goods Administration (TGA), came hot on the heels of an investigation that found people who took the travel sickness pill Travacalm suffered from serious and life threatening adverse reactions, including hallucinations that made some people try to jump out of planes.  

Of the 87 who took ill, 19 were serious enough to require hospitalisation. As a result, two Travacalm products (Travacalm Original and Travacalm HO), both made by Pan Pharmaceuticals, were blacklisted and recalled in January 2003.  

According to a statement posted at the TGA website, further inquiry showed a series of serious safety and quality breaches by the company which included “substitution of ingredients, manipulation of test results and substandard manufacturing processes.” 

For instance, an audit revealed manufacturing infringements like changing the status of 270 raw materials from Quarantine to Pass whose samples had not been tested. Some seven raw ingredients without clearance were used in the manufacture of 34 batches of products. Assay results of finished products were manipulated and fabricated in order to comply with specifications.  

For two and a half years, beef cartilage was used to substitute shark cartilage and vice versa. More alarming were the release and distribution of products whose raw materials did not undergo prior testing. 

As at press time, the final list of medicines affected by the Pan Pharmaceuticals recall totals 1,546. If such a manufacturing violation can happen in a country with regulatory controls, what more a country like the US where herbal products are not subjected to safety evaluation and quality control.  

In the US, a 1994 Federal Law provides that a dietary supplement is considered to be a food which does not need pre-market approval by the Food and Drug Administration (FDA). In this context, herbs and other botanical products, vitamins and minerals fall under the definition of a dietary supplement. 

According to a World Health Organisation (WHO) report on Effective drug regulation: A multi-country study, under the provisions of the Australian TGA, all goods including herbal and traditional complementary medicine, which have therapeutic claims must be registered. It says that Malaysia has made registration of traditional medicines compulsory since 1992, but largely for safety and quality and only partially for efficacy.  

This controversy has brought under scrutiny the importance of regulatory controls with regards to the herbal medicine industry. According to WHO, 80% of the world's population self-medicate with herbal remedies. Therefore, why can’t the same pharmaceutical standards of practice be applied to the manufacturing of herbal medicine? By subjecting herbal manufacturing to rigorous and systematic scientific research that is evidence-based, wouldn’t it solve the problem of inferior quality products? 

Here’s the tricky part. The difference between an herb and a pharmaceutical drug lies in its preparation. According to the World Wildlife Fund (WWF), the former is derived from plants or parts of plants (bark, roots, leaves, flowers, fruits) in which the mixture of individual constituents within plants are “balanced” in terms of medicinal properties. Although some modern pharmaceutical drugs are still derived directly from plants, they are typically based on single chemicals with “active” properties. For example, the chemical digitalin, used to treat heart disease, is obtained from foxglove while acetylsalicylic acid combined with active ingredients in the willow bark gives us aspirin. 

According to Chen Kin Fah, a pharmacist with Herbal Revival, a Malaysian distributor and manufacturer of herbal medicine, herbs have very complex compounds. “Herbs in its original form contain a multitude of active ingredients that are synergistic in nature. That means some can enhance absorption of the bio-active ingredients by the body whereas others can cancel the toxic effects of other compounds,” he says. 

With the Chinese sinseh, herbal medicine is as natural as it gets. On the other hand, herbal medicine in the pharmacies have gone through the finer manufacturing processes, where they are later sold as capsules or tablets. For example, solvents used to extract active ingredients in the herb can also change its potency profile. With strong organic solvents like acetone and methylene chloride, some toxic and non-water soluble residues are extracted along with the active ingredients in the herb. Recent reports in Europe showed that the herb kava kava, which used acetone as an extracting solvent, can cause liver toxicity.  

In contrast, traditional methods like water decoction is considered a much safer method where sliced raw herbs are blended then boiled in water according to controlled conditions.  

Although not all herbs can be tested, manufacturers can still determine the composition and quality of the active ingredients based on the monographs through methods like high pressure liquid chromatography (HPLC).  

Herbal revival managing director Michael Lim agrees that the lack of standardisation in herbal preparations has led to sub-standard manufacturing practices. “In herbal medicine, manufacturers can offer a cheaper substitute easily. Without proper standards of measurement and quality control, the amount of active ingredients can be either too much or too little.  

Contamination of equipment poses another major problem to herbal manufacturers. To eliminate the risk of contamination, Lim says that production lines should be cleaned and disinfected with alcohol after every batch. Powder left over on the production line is removed using a High Efficiency Particulate Arrestor (HEPA) filter vacuum cleaner where it is then dissolved and discarded.  

During tabletting and encapsulation, in-process quality control such as weight uniformity, disintegration, hardness and friability tests are conducted before they are released for packaging. Samples are retained and tested periodically to determine their stability.  

Lim explains that it is important to have an in-house quality control laboratory to test and verify raw materials and finished products. Qualified personnel like biochemists, microbiologists, nutritionists and pharmacologists are equally essential.  

For example, raw materials are analysed for active ingredients, heavy metals like lead, mercury and arsenic, microbial and physical conditions like moisture, appearance, odour and pH level through various testing methods.  

A high-pressure liquid chromatography (HPLC) is used to identify and determine concentrations and ratios of the respective compounds. These are shown as a sequence of peaks and valleys and documented into a monograph. Monographs are to herbs what fingerprints are to humans. They include composition, toxicology, side effects, cautions, drug interactions, dosage, methods of extraction and manners of use.  

The German Commission E Monographs is one of the most comprehensive reference with over 300 monographs on herbs and phytomedicines. Other quality control measures are microbiology, Atomic Absorption Spectrophotometry (AAS), disintegration and dissolution testing to ensure quality, efficacy, safety and reliability.  

Microbiology testing is to verify the microbial limits in a finished product. For example, a total plate count should not exceed 10,000 cfu/gm (colony forming unit per gram). The AAS is used to detect the presence of heavy metals.  

Disintegration tests are done to determine the time it takes for the pills to disintegrate under controlled temperature and activity. Generally, it should take less than 30 minutes to break up in the body. A dissolution test ensures that the dosage formula meets appropriate standards and easily dissolved in the gastrointestinal tract.

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