On September 5th and 6th of 2012, mainland China and Taiwan held their first-ever cross-straits conference on granules and herbal pharmacopoeia standards. Sponsored by Taiwan’s Department of Health with assistance from a Chinese medicine trade association and two local TCM universities, the conference was an important political milestone featuring phenomenal presentations. As an herb nerd with a love for both granules and herbal quality assessment, it was an unbelievable stroke of fortune to have the opportunity to attend this historic conference.
The conference opened up with a full-day of amazing presentations on herbal standards and quality control. Topics included updates on current developments in the official pharmacopoeia standards of each region, which provided a thorough overview of the number of medicinals recorded in each pharmacopoeia, as well as the testing methods used to ensure their safety, identity, and quality. An overview of the newly emerging Hong Kong Chinese Materia Medica Standards was presented, and the topics ranged from discussions of official reference standards from the Chinese Pharmacopoeia to the newly established case-by-case heavy metal limits for medicinals that are being developed in Taiwan. The first day closed with a fantastic presentation on the importance of macroscopic identification and other methods of assessing herbal authenticity, and no simple review could hope to capture the elation of my inner herb nerd as the day progressed.
Herbal quality discernment and standards are central themes in my academic life, and having lived in both mainland China and Taiwan I was thrilled to see the enhanced cooperation and cutting-edge knowledge that was in evidence at the pharmacopoeia meeting. However, when it comes to raw herbs, the few experts that delve deep into the topic tend to travel all over China anyway, and their knowledge base is already largely built without borders. Granules, on the other hand, differ dramatically between Taiwan and mainland China, and a cross-straits conference on granules was a totally unprecedented event that I’d dreamed of seeing for years, so I will devote the majority of my brief review to the adventures of day two.
Granules
Granules are made and prescribed slightly differently in mainland China and Taiwan, yet until recently there has been minimal academic exchange on the topic of granules between the two regions. When I first started studying in a Chinese medicine hospital in Taiwan, I immediately noticed that the local granule prescribing style was different than anything I’d been exposed to in the U.S., and over time I came to realize that the prescribing style in mainland China was totally different as well. There were no cross-straits conferences at the time, and no books had been written that explored the cultural variations in granule prescribing and manufacturing. As a student hungry for knowledge, the only way that I could research the topic in-depth was to systematically visit factories and talk to clinical experts about their prescribing styles one-on-one, and I found that many experts in both regions remained poorly informed about the granule trends of their neighbors. Almost ten years later, I was fascinated to see experts from mainland China and Taiwan come together to discuss the very questions that I’d struggled for years to find answers to.
If we look at the clinical trends in granule prescribing today, we find that there are several broad differences between how granules are made and used in mainland China vs. Taiwan. However, even in the Chinese world, relatively few people understand the scope of the differences and the factors behind these differences. In addition to lack of familiarity with the different regional prescribing styles, most practitioners have never seen the actual granules used in the other locale, because no granules that are produced in mainland China are permitted to be sold in Taiwan and vice versa. As in most cross-straits conferences, finding ways to harmonize standards and reduce barriers to trade was a central topic, but the conference was notable in that it was the first academic forum to dedicate space to the differences in the prescribing styles of the two regions. While the differences in prescribing styles cannot be resolved in a single forum, it was fantastic to see people asking all the right questions, and the day was full of rare facts and hard-to-find statistics that illustrate many interesting details of the granule world.
In Taiwan, most practitioners build custom formulas for patients by starting with one or more pre-made, whole formulas, and then add single herb extracts for additional customization. By contrast, in mainland China most practitioners build a granule formula purely from single-herb extracts. The prescribing style used in a given area is influenced by the products that are available in that region, and the different regulatory systems of Taiwan and mainland China have influenced their respective clinical styles when it comes to granules.
In mainland China, granules only became commercially available in the mid-1990s, and they remain available only as single-herb extracts that are prescribed by doctors in hospitals. Chinese law currently regulates whole formula extracts as experimental new drugs, which requires evidence of safety and efficacy similar to the process of developing a new drug. This process is extremely expensive and cumbersome given the wide range of formulas that are used in TCM, so very few pre-made whole formulas are available in granule form on the Chinese domestic market. While the Chinese Pharmacopoeia is rumored to be working on whole formula standards that will allow whole, pre-made classical formulas to be used as traditional drugs by TCM doctors, at present the granule market in mainland China revolves around single herb extracts, which are classified in a manner more akin to decoction pieces or raw materials (i.e., the products are not “medicine” until they are customized by a doctor for a patient, which gets around the regulatory burden).
In mainland China, over 1000 hospitals currently use granules, and six factories are nationally licensed to produce granules for the hospitals. By law, granule companies must manufacture at least 400 single herb extracts in order to supply hospitals, although hospitals can make their own granules for research with approval from the provincial level of the Chinese SFDA. While granules are found in nearly every herbal pharmacy in Taiwan, granules are not permitted to be sold in non-hospital pharmacies in mainland China.
Estimates of the current market volume of granules in mainland China were given at the cross-straits conference, and the already enormous current estimate of 4 billion RMB in annual granule sales is expected to increase up to tenfold or more after smaller, regional hospitals are permitted to use granules. A presentation given by one TCM hospital director from Jiangsu province indicated a steady rise in the proportion of patients using granules relative to raw herbs, and a stunningly large number of single-herb extracts exist on the Chinese domestic market (around 600 single herb extracts are sold, with numerous different processed forms of common medicinals).
In Taiwan, the regulatory situation is somewhat different, which in turn has influenced the products that are available there and the clinical style of prescribing them. The first batch of granules was made in Taiwan in 1963, and granules began to be covered by insurance in 1983. Taiwan and Japan were closely aligned in terms of granule manufacturing in the early era, and many factories in Taiwan made whole formula granules for export to the Japanese market.
From the beginning of its industry development, Taiwan began producing whole-formula granule extracts, and the regulations in Taiwan permit unmodified classical formulas to be prepared as traditional TCM drug products. 337 traditional formulas are currently registered, and the process of harmonizing the source texts and ingredient proportions used in these formulas began in the 1990s (at present, 200 formulas are formally harmonized and the final 137 are being completed). Clinically, most doctors in Taiwan tend to prescribe whole formulas as a base, and use single herb extracts as well as pre-made classical formulas to modify their prescriptions. About 400 single herb extracts are produced in Taiwan, but there are fewer choices of medicinals with multiple processed forms (fewer choices of the same herb with different pao zhi). In Taiwan, the most commonly prescribed single herb addition to formulas is yan hu suo (Corydalis Rhizoma) and the most commonly prescribed formula is jia wei xiao yao san (Supplemented Free Wanderer Powder).
In an assessment from 2010, over 90% of 3000 Chinese medicine clinics and hospitals in Taiwan accepted insurance reimbursement (the only herbal products permitted for insurance reimbursement in Taiwan are granule products). 47 factories in Taiwan are registered to produce granules, and around 20 of these factories produce 200 or more products; of these, 5 large companies are estimated to produce about 72% of the total product used. Additionally, several new regulations have been developed in recent years to implement realistic industry-wide standards for heavy metals; these have already been established for all formulas and 89 single herbs, and standards for the remaining single herbs will be completed in the coming years.
Ultimately, a single conference can only scratch the surface on the complex clinical questions and trade issues that currently divide the granule worlds of Taiwan and mainland China. Many excellent suggestions were raised regarding ways to enhance cross-straits cooperation, including practical suggestions such as removing current export limits that restrict the amount of licorice that may be sent from China to Taiwan. Nonetheless, substantial regulatory barriers will continue to prevent direct trade in granules between the two regions for the foreseeable future, so only practitioners in overseas markets such as the U.S. and Singapore will have the chance to directly compare the granules made in mainland China vs. Taiwan on an everyday clinical basis.
As for us in the West, we still have a long way to go in terms of practitioner education about the clinical trends in granule use in Asia, and I was saddened to see that my small herb company was the only Western granule company in attendance at this historic event. At the same time, I was phenomenally excited to see a whole room full of granule experts and I’m thrilled that the academic discussions are finally beginning to take off in earnest. I guess I always see the glass as half-full.
This article was originally published in PCOM’s newspaper Oriental Medicine, in the Spring 2013 edition.