By Zhejiang Zhenxiong Fiber Technology Co., Ltd.

I. Current Development Situation of New Vacant Capsules

• International development of vacant capsules

Standards for new vacant capsules are being gradually set and improved, with application of new materials of vacant capsules and people’s understanding of characteristics of the new vacant capsules.

The USP issued a draft for comment for HPMC vacant capsules in 2016, with comment deadline of September 30, 2016, mainly including articles on identification, loss on drying, disintegration time, microbes, and storage conditions, etc.

The Japanese Pharmacopoeia, 17^th Edition adds quality standards for HPMC vacant capsules and Pullulan vacant capsules.

• Development of vacant capsules in China

The Chinese Pharmacopoeia 2015 Edition has added the quality standard for hydroxypropyl starch vacant capsules. The Chinese Pharmacopoeia 2015 Edition supplement plans to add quality standards for HPMC vacant capsules and Pullulan vacant capsules, and the Pharmaceutical Capsule Committee of China National Pharmaceutical Packaging Association is currently drafting the association standards for HPMC vacant capsules and Pullulan vacant capsules.

• Development trend in China

Seen from the world, China, a big producer and consumer of TCM and health products, is a big demander for capsule products. Seen from the category, the HPMC vegetarian capsules especially will have bright market prospects.

For pharmaceutical and functional food enterprises, having vegetarian capsules enter the Chinese pharmaceutical product and functional food markets will not only improve the brand value of products in China, and more importantly, accelerate the internationalization of Chinese-produced preparations. Manufacturers ranking high in the Chinese capsule industry have competed to start vegetarian capsule development and production, besides production of gelatin capsules.

II. Comparison between Vegetarian Capsules and Gelatin Capsules

1. The hydroxypropyl methylcellulose (HPMC) in vegetarian capsules has stable chemical properties, and has no chemical reaction with air and water; the cellulose therein has metabolic inertness, and is not absorbed in vivo but directly excreted from the body; microbes are not liable to grow in vegetarian capsules, therefore, there will be no decomposition and deterioration when they are placed under normal conditions for a long time.

2. Compared to the traditional vacant gelatin capsules, vegetarian capsules have advantages such as wide adaptability, no risk of crosslinking reaction, and high stability; vegetarian capsules have relatively stable drug release rate and small individual difference, and are not absorbed after disintegration in vivo and can be excreted from the body with the excrement. Regarding storage conditions, numerous experiments show that vegetarian capsules are not friable under low humidity, their shell characters are still stable under high humidity, and various indicators of the HPMC vacant capsules are not affected under extreme storage conditions, while vacant gelatin capsules easily become adhesive under high humidity, lose water and harden or become friable under low humidity, and strongly depend on the storage environment temperature and humidity, and packaging materials.

3. The main ingredient of the traditional vacant gelatin capsules is protein, therefore, the dividing bacilli and microbes are liable to grow, and preservative shall be added during the production, leading to the possibility that a small amount of preservative remains on capsules; ethylene oxide shall be used for sterilization during product packaging, to guarantee the control indicator of capsule microbes. Chloroethanol is an indicator that shall be strictly controlled for vacant gelatin capsules. However, the vegetarian capsules require no preservative during the production, or ethylene oxide for sterilization, which fundamentally solves the chloroethanol residue problem.

4. The demand for vegetarian capsules will show a rapid growth trend in the future, as they have advantages such as wide adaptability, no risk of crosslinking reaction, high stability, and no moisture absorption. The market demand for vegetarian capsules will rapidly grow, with people’s gradual understanding of vegetarian capsules and changes of concepts of Chinese and foreign people in using drugs.

III. Company Profile - Zhejiang Zhenxiong Fiber Technology Co., Ltd.

Established in September 2014, Zhejiang Zhenxiong Fiber Technology Co., Ltd. is a large vacant capsule manufacturer specialized in producing HPMC vacant capsules and vacant gelatin capsules. The Company is located at Haiyan, a coastal ancient town by Hangzhou Bay, and is about 1h drive to Shanghai, Hangzhou, Suzhou or Ningbo, etc.

The company covers a total area of 48,000m², and have a total building area of 58,000m², with Phase I plant area covering 5,300m², and Phase I building area put into production and use of 17,000m², wherein, the production workshop reaches 9,000m², with clean standard reaching grade D, total investment of RMB 150 million, and able to product 00#, 0#, 1#, 2#, 3# and 4# vacant capsules, etc., with the inspection equipment and warehouse area commensurate with the production scale. As the company scale further expands and degree of specialization continues to increase, the company overall plans 120 automatic production lines, to reach annual production of 40 billion capsules, and can provide a series of solutions according to customers’ filling and packaging equipment, process characteristics, and product consistency, etc. to render custom services to them, to ensure the normal operation and production of customers.

The company has established a quality management system in strict accordance with provisions of the Drug Administration Law of the People's Republic of China, Good Manufacturing Practice for Excipients and other relevant legal documents, developed quality control standards for institution, personnel responsibilities, plant facilities, equipment and material management, hygiene and validation, and file management, and formed standard operating procedures that cover raw and auxiliary material purchasing, production control, quality inspection, finished products’ entry into and exit from warehouse, and product sales, etc., to effectively ensure the continuous and stable proceeding of the production. The laboratory of the Quality Department has been equipped with disintegration tester, gas chromatograph, UV-visible spectrophotometer, atomic absorption spectrophotometer, electronic analytical balance (0.00001), and electronic analytical balance (0.0001), etc., to meet the needs for inspection of raw and auxiliary materials, intermediate products, and finished products of HPMC vacant capsules and vacant gelatin capsules.

The entire workshop is designed according to GMP standard, with reasonable process layout, strong technical strength, and complete testing equipment; there is also strict quality control network and quality assurance system, automatic control operation, strict indoor cleanliness standard, quality monitoring, and other advanced production processes and conditions, to strongly guarantee the production of quality capsule preparations for customers at any time.