While China has grown to become the world’s second-largest consumer of pharmaceutical products, it currently has relatively few pharmaceutical excipients. Recent market research reports indicate that China has less than 600 types of excipients – a number that pales in comparison to the over 1,500 types in the U.S. and nearly 3,000 types in the EU.
Excipients are the components of a finished drug product—other than the active pharmaceutical ingredient (API)—that do not augment the therapeutic action of the active ingredients. Excipients, also referred to as inert or inactive ingredients, are often added as a coloring, flavoring agent, or binding material. Common types of excipients include diluents, disintegrants, glidants, lubricants, and binders.
While the U.S. FDA does not require that manufacturers register excipients, the China FDA (CFDA) has laid out a number of specific rules and regulations governing both generic and unique excipients. Listed below are the regulations that foreign excipient manufacturers must follow in order to sell their products in China.
Regulations and Procedures for Registering an Excipient in China
In order to apply for an import pharmaceutical excipient license (IPEL), foreign manufacturers must first appoint a local Legal Registration Agent who will handle document submission and direct interactions with the CFDA. Once foreign manufacturers have found a local agent, new applications for the IPEL follow the same general procedure, as outlined below:
- Submit an application to the CFDA. If the application was appropriately submitted with the necessary documents and information, it will be approved within 10 to 12 months of the original submission.
- Unique pharmaceutical excipients must also undergo in-country clinical trials before the final application dossier can be submitted. Foreign producers with unique excipient products will have to apply for Clinical Trials Permission (CTP). Unique excipients can expect to wait between 10 to 12 months for CTP. Applicants registering generic excipients generally do not need to go through the clinical trial process. However, in some instances, the CFDA may require bioequivalence trials for foreign generic excipients.
- If full clinical trials are required, the entire clinical trial process will take between 12 and 18 months to complete. If the CFDA requires bioequivalence trials, then the process will only take around 3 to 6 months.
- On average, generic excipient applications take between 18 and 24 months for final approval. Unique excipient applications need between 3 to 4 years for final approval.
Pharmaceutical Excipients Application Documents
29 different application documents must be collected and submitted to the CFDA in order to obtain an IPEL. Two copies of each document must be submitted: one copy written in the original language or English, and the second copy with the Chinese translation. The required documents are divided into four different categories and listed below1:
- Drug names
- Basis, objectives, and reasons
- Summary of the main clinical studies
- Draft of insert packaging and instructions
- Sample of packaging and labeling draft
- Pharmaceutical Data
- Summary of pharmaceutical research
- Research data and literature of the production process
- Experiment data and related literature that confirm chemical structure and components
- Experiment data and related literature on quality research
- Experiment data and related literature on drug compatibility
- Experiment data and related literature on stability research
- Draft of standards and instruction with standard product and test product provided
- Test report for three continuous batches of samples
- Information on the direct packaging materials and containers along with quality specifications and testing methods for these same materials
- Pharmacology and Toxicology Study Information
- Summary of pharmacology and toxicology study
- Primary pharmacodynamics study and literature
- General pharmacology study and literature
- Acute/single dose toxicity study and literature
- Chronic toxicity study and literature
- Special safety study and literature regarding hypersensitive reactions
- Mutagenicity test results
- Reproductive toxicity information
- Carcinogenicity test information
- Clinical study information (if required)
- Summary of domestic and international clinical studies
- Investigational plan and clinical study protocol
- Investigatory brochure
- Sample of informed consent form and approval of the ethics committee
- Clinical study report
Given the growing demand for new pharmaceuticals in China, foreign companies are increasingly looking to sell and register their excipients there. Some foreign excipient companies that have operations, offices, or joint ventures in China include Colorcon, Roquette, and Meggle.
1 Source: CFDA Website