China to Release Its First In-Vitro Diagnostic Reagent Regulation
Chang-Hong Whitney
 Chang-Hong Whitney |
In-vitro diagnostics use methodologies in immunology, microbiology, cell biology and other analytical theories and techniques to detect antigens, antibodies, enzymes, DNA, cancer markers and other indicators that are representative of certain diseases or conditions in the human body. In China, healthcare facilities routinely use IVD testing for diagnosis, measurement of treatment efficacy and post-treatment monitoring.
An IVD system typically consists of an instrument and reagents used to perform each test. Many manufacturers design special reagents specifically for their instruments. This practice allows companies to ensure product and performance quality (and protect the delicate components of the instrument). Furthermore, it provides a competitive advantage to suppliers, who can capture the reagent trail and lock in end users. Indeed, these instruments and the captive reagents have created unique business scenarios in which manufacturers can leverage their investment and costs through the balance of instruments and reagent trails.
Because IVD instruments have been classified as medical devices, the China registration process has been standardized along with the device regulations set by the State Food and Drug Administration (SFDA). However, reagents—due to their technical complexity—have been a difficult subject for Chinese regulators.
The SFDA published two IVD regulations in 2001 and 2002, separating instruments and reagents. For reagents, the agency had stipulated that chemistry reagents were to be registered as a medical device, whereas other reagents for antigen or antibody detection were to be registered as drugs. The latter group, therefore, had been subject to in-country clinical trials, product testing and the release of extensive reviews.
It became apparent that these regulations were too broad and vague and that the implementation of the regulations was almost impossible. Instead of streamlining the market and the regulatory process—as was intended by the SFDA—these regulations had added confusion and heavy burdens to manufacturers and created conflicts to this marketplace.
Burdens and Conflicts
Because registration for a drug requires in-country clinical trials, type testing and a lengthy review process, the registration process for some of these reagents often took one to two years to complete. For a product that has a life cycle of only two to three years, that problematic timing jeopardized a product’s potential in the market. In addition, many IVD manufacturers are device producers and do not have a drug license, which is a registration requirement for pharmaceutical products. Drug registration also requires disclosure of extensive product and production information, which threatens a manufacturer’s trade secrets and intellectual property. Furthermore, drug import regulation requires batch testing at each importation, putting time-sensitive reagent products at risk.
On another front, the SFDA requires a special license for drug distribution. The “drug” nature of the IVD registration permits only drug distributors to sell IVD products. As a result, device distributors that IVD manufacturers depend on to sell the instruments cannot distribute reagents.
In addition, because most IVD reagents are captive, hospitals often demand discounts or free equipment but sign multi-year reagent contracts. Cutting off the reagent trail prevented instrument distributors from creating the best sales package for the end users. Drug distributors usually are not interested in IVDs, because the sales volume of IVD products is low compared with that for drugs. And the customers of IVD technology are not the hospital pharmacies or drug stores that pharmaceutical dealers do business with on a daily basis.
The demand for IVD products (given that doctors are using these products heavily in their practices), combined with the poorly formulated regulations, drove many IVD sales “underground.” Many products were sold without SFDA registrations or were labeled as “research products” but actually sold to a clinical environment. For the past two years, few companies even submitted any registration, fearing the new regulation would send them on a different direction and further delay the registration process.
New Regulation Drafted
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The newest release of the IVD regulation sounds very much like a drug registration again—although products now are to be considered as medical devices. In-Vitro Diagnostic Reagent Registration Management Methods (Trial Version), released April 19, outlines the key components in the IVD reagent registration process. This regulation covers all reagents except those that are used for blood selection or those that use radioisotope markers.
In this new regulation, IVD reagents are classified into three categories, based on risk. Class III products (the highest risk level) include reagents for testing of disease antigens, antibodies and enzymes; human genetic testing; drug target identification; cancer markers; and drug allergy testing reagents. Class I reagents (the lowest risk products) include growth media and sample preparation reagents, such as solvents or diluting fluids. Any reagents that are not clearly identified as Class III or Class I are in the Class II category.
Class II and III products are required to have completed in-China clinical studies and reports prior to registration. (Class III products must be tested in three clinical trial sites prior to registration.) In addition, these products must undergo type testing at SFDA authorized laboratories. Samples of three consecutive batches are to be submitted for testing.
As for registration itself, the following information is required:
1. Product information
• General description of the product, such as intended use, the product’s technical theory, key raw material source and manufacturing process, biosafety and information on similar products already on the market
• User’s manual
• Product standard
• Type testing report
2. Production and analysis information
• Information on raw materials
• Key production processes and analysis reports
• Performance evaluation
• Stability report
• Clinical study reports
• Production report for three consecutive batches
• Product packaging and label samples
3. Manufacturer’s credentials, China agent information and statements
• Manufacturer’s licenses
• Home market product release information
• Quality system certification
• China agent’s authorizations and approvals (service agent, legal representative, registration agent)
• Statement of truthfulness and guarantees
While the SFDA has made a big step in the right direction by grouping IVD reagents into the medical device category, its registration requirements seem to be quite extensive. Discussions with the agency on this new issue have been difficult, as SFDA members are trying to refine the details. It is believed (as of press time) that the June 1 implementation is a set target for all IVD products to be registered. This regulation is bound to evolve, and more developments will be reported as they come up. Stay tuned...
Chang-Hong Whitney is president of Whitney Consulting Ltd. in Massachusetts. With an MBA from Babson College (Wellesley, MA) and undergraduate degrees in electronic engineering and international business, she has been consulting for western companies on doing business in China since 1994, focusing on the medical device market. Her services include China regulatory affairs, market research, sourcing and logistics programs and China business strategies. She can be reached at changhong@whitneyconsulting.net.
