Product Registration in Taiwan

*Please note that some of the regulations listed in this report are direct translations from the Chinese.

Taiwan’s per capita GDP was estimated to be $14,700 in 1996, and its real GDP growth rate was about 6.4% in 1997. Its fast-growing service sector now provides a 61.1% share of the island’s $274.6 billion GDP, while the industrial sector has shrunk to about 35.6%.

Taiwan’s economy suffered little from the Asian Financial Crisis, maintaining low inflation (1.6%) and unemployment (2.6%) rates. Most analysts credit Taiwan’s continuing growth to the government’s encouragement of foreign investment and trade, and to its strong economic fundamentals. Because it has achieved high trade surpluses for the past 20 years, the Taiwanese government has raised its foreign exchange reserve level to $82.9, the second highest in the world. With these reserves as insulation, Taiwan ensures that it will not be seriously affected by the regional crisis.

HEALTH BUREAUCRACY STRUCTURE

The Department of Health (DOH), directly under the Executive Yuan determines national health policies, formulates programs, and supervises and coordinates health services at all levels.

Established in 1971 and then expanded in 1982, the DOH has five technical bureaus and an office that oversees medical affairs.

Bureaus and Agencies Under the DOH at the National Level

• Bureau of Pharmaceutical Affairs
• Bureau of Food Sanitation
• Bureau of Medical Affairs
• Bureau of Health Promotion and Protection
• Bureau of Communicable Disease Control
• National Narcotics Agency
• National Institute of Preventive Medicine Agency
• National Laboratories of Foods and Drugs Agency
• National Quarantine Service Agency
• Provisional Bureau of National Health Insurance Agency

Just below the central DOH are the provincial/special municipality government departments, which are responsible for planning and supervising medical care programs within their jurisdictions. This area encompasses the Taiwan Provincial Department of Health, the Taipei City Department of Health and the Kaohsiung City Health Department. The city/county government level provides its own health bureau for each of the 21 cities and counties, and each township has a health station. Remote mountain and island areas have also established health facilities and group practice centers.

REGULATIONS FOR MEDICAL DEVICE PRE-REGISTRATION

The following medical devices must obtain pre-marketing registration before they may export to Taiwan:

1. Anesthesia Apparatus (ventilators, blood analyzers, monitors, etc.)
2. Respirator Apparatus (ventilators, oxygen chambers, resuscitators, etc.)
3. Implantable Appliances (pacemakers, heart valves, stents, grafts, prostheses, orthopedic implants, etc.)
4. Blood Pressure and Pulse Appliances (venous blood pressure manometers)
5. C.C.U. or I.C.U. Equipment (monitoring systems, catheters, incubators, oxygenators, cardiographs, blood cell separators, pacemaker programmers, etc.)
6. Lithotritors
7. Injection Needles
8. Injection Syringes
9. Diagnostic Appliances (NMR-MRI, manometer and motility systems, etc.)
10. Blood Transfusion and Intravenous Administration Appliances
11. Biopsy Needles or Apparatus
12. Suture Needles
13. Surgical Sutures
14. Contact Lenses
15. Physical Therapy Units
16. Medical Coagulating Devices (cyrosurgical and cyromedical systems, electrosurgical equipment, vitreous aspiration and cutting equipment, etc.)
17. Storage Solutions for Transplant Organs
18. Medical Laser Apparatus
19. Diagnostic Acupuncture
20. Therapeutic Acupuncture
21. Computerized Tomography Scanners
22. Nuclear Medicine and Radiation Isotope Equipment
23. Contraceptive Devices
24. Health Materials (surgical skin closure, porcine dressing, hemostatic dressing, collagen sponges, etc.)

Foreign manufacturers must have an agent in Taiwan to apply to the DOH for a pre-marketing registration license. This agent may be the manufacturer’s Taiwan branch office, a qualified importer of medical devices, or a registered seller of medical devices.

The following documents must be included with the application:

1. Letter of authorization (1 copy)
• Must be authorized by a Taiwanese representative in the product’s country of origin.
• Must state product name and model/type, manufacturer name and address, and agent name and address.
• Must state that agent is authorized to register the product.
• This letter will be considered valid for one year after its issue date.
• All documents must be originals.

2. Certificate of Free Sales (1 copy)
• Must be issued by the highest health authority.
• If the highest health authority does not have jurisdiction over such devices, the highest appropriate authority must issue the certificate.
• Must state product name and model/type and manufacturer name and address.
• Must state that device is freely sold in its home market.
• Must be authorized by a Taiwanese representative in the product’s country of origin.
• This certificate will be considered valid for two years after its issue date.
• All documents must be originals.

3. Leaflet, company profile, brief history (7 copies)
• Must state product’s name, structure, specification usage, and administration
• Must state manufacturer name and address.
• Eight copies are required for radioactive equipment.

4. Quality control records (2 copies)
• Must state testing methods and testing results.

5. General information (1 copy)
• Must state device form, structure, dimensions, raw materials and/or ingredients, as well as quantity, performance, purpose of use, indication and/or effect.

6. Product sample (1 copy)
• If the medical device’s construction is relatively heavy, complicated, bulky, large, or possesses other exceptional features, photographs may be submitted in place of a sample. Photographs must allow for identification of the product’s structure, properties, and functions.

7. Clinical reports (2 copies)
• Required for some newly developed devices, some special devices (such as implantable appliances), and contact lenses.

8. Electric insulation and duration circuit and testing records (2 copies)
• Required for electronic equipment.

9. Operating Instructions (2 copies)
• Required for electronic equipment.

10. Operation records for automatic measurement adjustment (2 copies)
• Required for automatic temperature adjusting equipment.

11. Testing records and certificate of radiation leakage (2copies)
• Required for radioactive equipment.

Additional Information concerning Pre-Marketing Registration
• The agent who files the pre-registration license application shall be the license-holder, not the manufacturer.
• After obtaining the product license, the agent may begin to import the product.
• The product license will remain valid for five years.
• The DOH usually does not revoke the license unless the product or the license holder is in violation of regulations.
• The license holder may transfer the license to another agent, with the manufacturer’s consent.
• The manufacturer may authorize additional agents to register the same product concurrently.

• Separate applications must be filed for manufacturers at different locations who have the same company name (e.g. branch manufacturers).

SITE REGISTRATION

Recently, US medical companies applying for device registration have been concerned by a site registration requirement, which has now come under some contention. The Chinese language version of the registration regulations requires that the plant information (i.e. the plant master file) be submitted along with the device application, while the English version makes no mention of this requirement. Although the Ministry of Health has not clearly stated which version it views as the correct one, it is hoped that the DOH’s upcoming revisions to these regulations will settle the issue. Starting in 2004, the DOH will require Taiwanese companies to comply with Taiwan’s Good Manufacturing Practice (GMP) guidelines, while similar requirements for foreign manufacturers will come into effect January 1, 1999. At this time, imported products will also be required to submit a plant master file (PMF), which will be reviewed by Taiwan’s Industrial Technology Research Institute (ITRI).

The US medical industry is dissatisfied with the discrepancy that allows Taiwanese companies five more years than foreign companies to operate outside of GMP guidelines. In addition, the industry holds that the PMF requirement will not demonstrate GMP compliance. US manufacturers, including the Health Industry Manufacturers Association (HIMA), are lobbying to change the requirement to a certificate of compliance, such as the ISO 9001/2 and the U.S. FDA inspection report.

Site registration has also brought up intellectual property concerns. Although the Taiwanese government does not ensure the confidentiality of any information it receives, companies may submit a request for confidentiality to the American Institute of Taiwan (AIT), who will then send it to the DOH. While this procedure does create a delay of several months, if applied for before January 1, 1999, the company will likely receive official approval to keep its PMF confidential. If a foreign company wants to avoid the red tape and the delay, it may also gamble on heavy bureaucratic workloads, and leave out the crucial plant details in its application. The DOH does not always examine foreign plant information closely, and small exclusions may not affect the application’s chances of approval.
Even with these precautions, however, foreign companies always risk piracy when they operate in Taiwan, especially if their products are based on advanced technology. The medical device industry has an advantage, however, as pirated goods would yield few profits in such a specialized market. In addition, the government is strengthening its intellectual property law, and companies with patented products now have recourse to legal action. It is therefore vital that the foreign company apply for a patent before operating in Taiwan.

REGULATIONS FOR PHARMACEUTICAL REGISTRATION

Documentation Required for Registration

The DOH issues separate pharmaceutical pre-marketing licenses for factories and products. Two laws cover this regulatory process for all manufacturers and purveyors: Pharmaceutical Affairs and the Cosmetics Sanitary Control Law. As mentioned for medical devices above, all imported and locally produced pharmaceuticals must register with the DOH and receive product licenses before they may be marketed in Taiwan. Figure 3 below contains an overview of pharmaceutical registration procedures.

Drugs manufactured domestically must undergo testing for drug stability and GMP standard compliance as part of the registration process. Registration and market approval applications for new drugs require documentation of side effects, toxicity tests, physical and chemical characteristics, clinical reports, etc.

Registration Requirements for Pharmaceutical Importation

* Pre-Registration Requirement: Company Profile
• Required only for manufacturers exporting products to Taiwan for the first time.

1. Certificate of Free Sales (CFS)
• Must be issued by the highest health authority.
• A total of 3 CFSs must be submitted, one from three of the following countries: Australia, Belgium, Canada, France, Germany, Japan, Sweden, Switzerland, UK, and US.
• Must be authorized by a Taiwanese representative.
• Must certify that the product is manufactured and freely sold in its original country.
• Must contain descriptions of the following:
• Product name, dosage form and formula; and
• Manufacturer’s name and address.
• This document will be considered valid for two years after its issue date.

2. Letter of Authorization for Registration
• Must be issued by the pharmaceutical’s manufacturer.
• Must include the authorized agent’s name and address.
• Must describe the authorized product (name, dosage, and content).
• This document will be considered valid for one year after its issue date.

3. Specification and method of analysis for raw materials of each ingredient used for manufacturing (including coloring agents and excipients) (2 copies)
• If the specification is based on pharmacopoeia, the referenced copy should be attached.

4. Certificate of Analysis
• Analysis results must be provided for each raw material mentioned above.
• The following must be listed:
• Manufacturing date;
• Lot number;
• Analysis date; and
• Signature of responsible analyst.

5. Specification and method of analysis for finished products (2 copies)
• If the specification is based on pharmacopoeia, the referenced copy should be attached

6. Certificate of Finished Products
• Analysis results must be provided for every item in the specification.
• Lot number should correspond to that of the sample submitted for analysis.
• Must include manufacturing date, analysis date, and signature of responsible analyst.

7. Samples for analysis (12 samples)

8. GMP Master File for the product
• Manufacturing Method: must contain description of batch size, quantity added for each ingredient, bulk, and detailed procedure.
• In-Process Control: must contain detailed description of control items, control method (including sampling method), control frequency, control range, and control result.
• Stability Test Reports for three different lots in market-available packaging:
• Must indicate lot number and manufacturing date of the tested sample.
• Must describe test conditions (temperature, humidity, package of testing sample), test items, and test results.
• Must indicate analysis date for each test.
• Must include conclusion of effective shelf life.
• Must be signed by person responsible.

9. Packaging material, including carton, label and package insert (12 copies)
• If foil or tube packaging is used, the empty foil or tube must also be submitted.

Remarks
• For new pharmaceutical ingredients approved after 1988, where the generic products are not of the original manufacturing, the application of their oral or muscular injection preparations for approval must be accompanied by information on the bioavailability or bioequivalence tests.
• If a new product’s major ingredient has never been registered in Taiwan, the following documents should be submitted along with the application:
• Documents on Physical/Chemical properties, pharmacology, toxicology, etc.
• The original paper for the study should be included.
• If the paper is not issued in English, the English or Chinese translation should be attached.
• The translator’s name should be stated on the copy.
• Pharmacokinetics data
• Bioavailability data
• Clinical Study Report
• Only papers published in “List of Journals Indexed” of Medicus Index, Jan. 1985, Vol. I are acceptable.
• A double blind and control study is necessary.
• CFS
• A total of 3 CFSs must be submitted, from three of the following countries: Australia, Belgium, Canada, France, Germany, Japan, Sweden, Switzerland, UK, and US.
• Must be issued by the highest health authority.
• Must be authorized by a Taiwanese representative in the product’s country of origin.

A. Dossier Requirement for Plant Registration

1. Company Basic Information
• Brief History
• Must include company name and address.
• Capital statement
• Registered capital; and
• Capital amount in original currency.

2. Plant Master File
• Organization
• Must include organizational chart.
• Must include total number of employees.
• Product Category
• Must be classified by dosage form.
• Must specify preparations of penicillin, antibiotics and biological products.
• Building and Facility
• Must include blueprint of floor plan.
• Must indicate thoroughfares for people and materials.
• Must include information describing sanitation, cleanliness, humidity, and temperature control conditions in production areas.
• If penicillin, antibiotics, or biological products are manufactured in the facility, they should have a separate and specially designated area.
• Production Equipment
• Must include detailed list.
• Control of Raw Materials
• Must include written procedures for the receiving, identifying, storing, handling, sampling, testing and approving of raw materials.
• Production and In-Process Control
• Must include written procedures.
• The procedures must include dosage forms manufactured by the plant.
• Control of Packaging and Labeling Materials
• Must include written procedures describing in sufficient detail the processes of receiving, identifying, storing, handling, sampling, testing, labeling and packaging materials.
• Practice of Stability Study
• Must include a written protocol of the stability study for each dosage form.
• Quality Control
• Must include established responsibility and operation procedures for the quality control department.
• Laboratory Equipment
• Must itemize all equipment (e.g. chemical balances, PH meters, microscopes, and disintegration apparatus).

3. Notarization and Legalization
• All the above documents must be:
• Notarized by the highest health authority or chamber of commerce of the manufacturer’s country of origin.
• Authorized by a Taiwan official or trading representative in the product’s country of origin.
• Compiled into one dossier.

B. Clinical Trials

Local clinical trials must be conducted for certain drugs, such as new and unique drugs, and these trials must follow GCP (Good Clinical Practice) standards. If an imported pharmaceutical has already begun sales in its country of origin and a Free Sales Certificate for the product has been issued, foreign manufacturers are generally allowed to proceed with their clinical trials. The procedure of a clinical trial normally takes 2 – 3 years and is as follows:

1. Designate a Taiwanese medical center or hospital doctor to monitor the trials as an investigator.
2. Design trial protocol, and submit it to the hospital’s ethical committee for approval.
3. Submit the ethical committee approved trial protocol to the DOH to obtain its ethical committee’s approval.
4. Conduct clinical trial under the designated investigator’s control.
5. Submit a report of the trial to the hospital’s ethical and drug committees for approval.
6. Submit the trial results to the DOH for approval to obtain a license.

C. Reimbursement

The Bureau of National Health Insurance (BNHI) governs reimbursement issues. Although hospitals must apply for reimbursement in the case of laser techniques, in general generic manufacturers or licensed owners of origin must submit pharmaceutical applications to the BNHI.

Taiwan’s National Health Insurance (NHI) system uses foreign reference prices for foreign product reimbursement. Generic pharmaceutical producers’ reimbursements are a fixed percentage of the price set for proprietary drugs without consideration for quality. Because they lack R&D and testing fees and receive a high price for their generics, this system benefits local Taiwanese manufacturers, while the NHI’s gives imported, leading brand products artificially low price ceilings.

D. Safety Surveillance System for New Drugs

The DOH has sought to encourage new import patent rights protection and domestic R&D through its drug safety surveillance system. This system requires local agents to conduct safety surveillance of their new drugs in designated teaching hospitals within seven years of introducing the product. Agents must report upon any new information concerning side effects discovered in the procedure. No generic applications by a third country (other than Taiwan and the country of origin) will be accepted during this surveillance period.

The surveillance period is divided into 2 stages:

  1. 1st Stage (5 years): Any application to manufacture or import common-name medicines must contain additional reports of domestic clinical trials equivalent to those of the original manufacturer.
  2. 2nd Stage (2 years): Any report of bioequivalence tests that have been conducted by either domestic or DOH-authorized foreign laboratories must be submitted.

The DOH expects new drug safety surveillance will detect any adverse side effects previous clinical trials may have missed, gain further information about the drugs, and to aid in assessing whether to permit them to enter the market. By July 1995, 241 chemical entities and 412 new drug formulations had been placed under surveillance.

E. Supervision and Inspection

The DOH, the National Laboratories of Food and Drugs, and local health agencies all perform regular and unscheduled factory inspections to check that GMP standards are being followed. Factories that meet GMP standards receive a “P”, and those who seriously violate them, a “C”. Owners must correct their mistakes within two months, during which time a list of C-grade factories is published, and their application for registration and market approval is suspended. Factories failing to improve may be shut down.

F. Specific Medical Product Examples

Some medical products must also undergo medical testing. All imported contact lenses, for example, must pass clinical testing before they may enter the market. The DOH has asked dealers, major medical care institutions and the Ophthalmology Society to aid in determining clinical testing regulations. The DOH has waived local clinical testing for products with the same product name and same manufacturer as an already approved product.

Special regulations govern cosmetics, which are classified as either medicated or general. Imported general cosmetics do not require pre-market approval, though they must be reviewed by the DOH. The registration and market approval of cosmetics are handled according to the regulations stipulated in the Law for the Sanitary Control of Cosmetics, Regulation for the Registration and Market Approval of Cosmetics, and Standards of Medicated Cosmetics.

NEW TRENDS IN PHARMACEUTICAL REGULATIONS

US manufacturers often complain about Taiwan’s complex regulatory environment and its discriminatory practices against foreign manufacturers. Although the Taiwanese government does not evaluate applications through quality standards, like ISO 9000, most foreign companies using a third party manufacturer must still submit a complex PMF. Foreign companies must re-submit the PMF if production shifts to other plants not on file with the DOH. Furthermore, foreign manufacturers must re-register second or third generations of previously approved products. Despite the hassles involved in registering the product, foreign manufacturers receive little to no intellectual property protection. Imported generic products may not receive licenses, and new patent laws only address pharmaceuticals currently in development.

Reforms in Taiwan’s medical product regulations are attempting to address these concerns. In January 1998, representatives of the Taipei Economic and Cultural Representative Office (TECRO) and AIT began a “mutual exchange of information” concerning medical devices. This agreement permits US and Taiwan to compare medical device inspection and reporting techniques, in the hopes of building a mutual understanding of their quality assurance programs. The US Medwatch Program, a vigilance system providing information from manufacturers concerning device failures and malfunctions, will advise the Taiwanese government in medical device approval.

Preparation for Taiwan’s entry into the WTO is also sparking new developments in medical regulations. Taiwan must eliminate several trade restrictions that are precluded by WTO rules, such as import license restrictions on generic drugs that can be produced locally. In addition, review criteria for ten over-the-counter imported drugs have been relaxed. Pharmaceutical associations, rather than physicians and pharmacists, are now responsible for inspecting and reviewing these products.

The Taiwanese government is exploring further ways of deregulating the medical industry. The upcoming Trade and Investment Framework (TIFA) talks will explore possibilities for change in Taiwan’s “five principles” on pharmaceuticals, which outline pricing, original brands, and patent protection issues. Health authorities have established a grievance system to deal with drug-related complaints, and are currently considering a 301 petition filed by HIMA concerning fair market practices and discriminatory pricing.

CONCLUSION

Taiwan is the third largest emerging market in Asia for US medical device manufacturers, who command about 40% of the country’s import market for medical devices. In 1995, Taiwan’s medical technology market was estimated at $630 million, and is expected to grow at an annual rate of about 15% through the year 2000. US pharmaceutical companies’ growth rates have extended well over the industry’s annual average of 13%. With the market’s expected boost in demand for quality medical products, US pharmaceutical companies will continue to occupy a large market share in Taiwan for years to come.

Sources:

  1. CIA World FactBook, 1997.
  2. US Department of Commerce, 1998.
  3. The Republic of China Yearbook, 1998.