The terms used in this chapter are defined as follows:
1.New drugs: the new drugs described in Article 7 of the Pharmaceutical Affairs Act.
2.Generic drugs: pharmaceutical preparations identical to a drug already approved in Taiwan in the aspects of ingredients, dosage form, contents and efficacy.
3.Bio-pharmaceuticals: serum, antitoxin, vaccines, toxic, bacteria sap and products manufactured based on the theories of microbiology and immunology.
4.Substances (Active pharmaceutical ingredients): An active substance or ingredient manufactured through physical and chemical processes or bio-tech procedures and with pharmacological effects that are often used for the manufacturing of drugs, bio-pharmaceuticals or bio-tech products.
5.Radiopharmaceutical drugs: drugs meeting the definition given in Article 6, containing radioactive substances for human uses. After being administrated to humans, the drug can diagnose, monitor, treat, alleviate disease conditions or achieve other medical effects.

The term “authorization letter” mentioned in this Chapter refers to the documents issued by the foreign manufacturer, headquarters or the license holder of an imported drug to authorize the application of drug registration.
The above-mentioned authorization letter is effective for one year from the issuance date. The authorization letter should include the names and addresses of the manufacturer and the agent, as well as drug name, dosage form and contents. The information should be consistent with those stated in the application form. If the authorization letter is in neither Chinese nor English, a Chinese or English translation should be provided additionally.
If the original license holder has a branch office in Taiwan, the authorization letter can be issued by either the manufacturer’s headquarters or the head office in Asia.

The FSC (Free Sales Certificate) from the country of origin mentioned in this Chapter means the original document issued by the highest health competent authority of the country of origin, therein justifies the manufacture and sale of the product in that country. The following conditions should be met:
1.If the required document is in neither Chinese nor English, a Chinese or English translation should be provided additionally.
2.The document is effective for two years from the issuance date, and it should be authenticated by the embassy, representative office or agencies authorized by the Ministry of Foreign Affairs of R.O.C (hereafter the R.O.C foreign affairs offices).The authentication requirement is waived for documents issued by A10 countries, which include Germany, US, UK, France, Japan, Switzerland, Canada, Australia, Belgium, and Sweden.
3.Information of the product name, manufacturer’s name and address, drug formulation, dosage form and contents stated on the document should be consistent with the information on the application form. The product name of exporting drug should be stated in this document; otherwise, a letter issued by the original manufacturer should be provided to explain and to give the product name of exporting drug, as well as to certify that the product is consistent with every description on the CPP (Certificate of Pharmaceutical Product) except for the product name. For capsules, in addition to the full formulation of the drug, the full formulation of soft capsule, or the coloring agents of hard capsule should be described accordingly. In cases where the CPP does not state the coloring agents of hard capsule, the original manufacturer should issue a letter to explain.
4.The CPP should specify the drug manufacturer and state the fact that the product has been approved for free sale in that country. The description of manufacturing and free sale should be clear.
The following documents can substitute for the above-mentioned FSC from the country of origin:
1.FSC issued by the selling countries approved by the central health competent authority;
2.For drugs listed in the United States Pharmacopeia Drug Information (USPDI) or in the Approved Prescription Drug Product with Therapeutic Equivalence Evaluations (Orange Book) published by the US FDA, applicants may submit a photocopy of the pages of the product (printouts from the Internet or the electronic version are acceptable), as well as the FSC issued by the health authority of the State Government as a replacement for the one issued by the US FDA;
3.For products manufactured in Germany, the FSC can be issued by the health authority of a state government. Notarization from the Federal Government would not be necessary;
4.For products manufactured in any of the EU countries, the FSC issued by the European medicinal Agency (EMA) is acceptable; and
5.For toll-manufactured products that have not been sold in the country where the toll-manufacturers are located, the FSC from the country where the commissioner is located together with the manufacturing license from the country where the manufacturing takes place are acceptable substitute. Another acceptable alternative is the FSC from the country where the commissioner is located, on which states the manufacturer’s name and address.
Except as otherwise regulated in the Regulations, Paragraph 1 Item 1 to Item 4 are applicable to the above-mentioned alternative documents and the certificate of changes issued by the country of origin.

Except as otherwise regulated in the Regulations, the CPP said in this Chapter should be issued by the highest health competent authority of the issuance country and authenticated of any one of the A10 countries or the EMA.
CPP can be replaced with the following documents:
1.The package insert approved by the reference country or a photocopy of the reference country’s pharmacopoeia (as listed below, as “official formulary”); printouts from the Internet or the electronic version are also acceptable. It does not have to be issued by the highest health competent authority of the reference country, nor be authenticated by the R.O.C. foreign affairs offices. The edition of the cited official formulary should be indicated, and has to be published within 5 years from the citation.
(1) US: Physicians’ Desk Reference (PDR);
(2) UK: British National Formulary (B.N.F.), Medicines Compendium (published by Association of British Pharmaceutical Industries, ABPI);
(3) Japan: Drugs in Japan, the most recent new drugs in Japan;
(4) Switzerland: Arzneimittel-Kompendium der Schweiz;
(5) Canada: Compendium of Pharmaceuticals and Specialties;
(6) France: Dictionnaire VIDAL;
(7) Australia: MIM’S;
(8) Germany: Rote Liste;
(9) Belgium: Repertoire Commente des Medicaments;
(10) Sweden: Farmaceutiska Specialiteter i Sverige (FASS);
2.The approval letter and the approval information on the website of the highest health competent authority of any one of the A10 countries or the EMA.

Except as otherwise regulated, the formulation basis mentioned in this Chapter refers to the pharmacopoeia or official reference books published in the A10 countries of editions published within 5 years from the date of application.
Formulation basis should meet the following criteria; its title, edition, year of publication and page numbers should all be indicated. A photocopy of complete reference pages should be provided. If the reference is in neither Chinese nor English, a word for word Chinese translation should be provided; but proper names or technical terms can be listed in English.
1.If USP is submitted, then the USPDI shall also be provided for assessment. Extra pharmacopoeia, which is not an official reference book, is for reference only.
2.If the applied formula is not completely consistent with the submitted reference and some alternations have been made, a statement explaining the alternation should be provided. Information in relation to the actual changes should be submitted as appropriate.
3.Tablets, film-coated tablets and sugar-coated tablets can use the same formulation basis, but not for enteric-coated tablets.
4.The formulation basis of ointment and cream can be used interchangeably, provided that the products are not under pharmacovigilance.
5.If the formulation basis or the CPP is of tablets, the reasons for the application of double-layered tablets should be given. Moreover, the package inserts and labels shall not include exaggerated therapeutic effects associated with the dosage form. Any boost of effects due to dosage forms should be approved and justified by clinical data before they can be indicated in package inserts or labels.
6.If the formulation basis submitted by local manufacturers for drug registration is not pharmacopoeia or reference books published by the A10 countries, the Orange Book or USPDI published by the US FDA can be used instead.
New drugs, new dosage forms, new administration doses or new unit strength developed in Taiwan do not need to submit formulation basis. However, the researches of formulation design and technical data in relation to this drug should be submitted.

The testing specifications, methods and certificate of analysis of raw materials mentioned in this Chapter refer to those for active pharmaceutical ingredients (API) and every substance of the formula (including auxiliary materials and coloring agents added during the manufacturing process).
The testing specifications, methods and certificate of analysis of raw materials said in the preceding paragraph should comply with the following regulations:
1.If using a pharmacopoeia as a reference for raw materials, the applicant should indicate the pharmacopoeia’s titles, publication year and editions. The pharmacopoeia is restricted to the Chinese Pharmacopoeia, pharmacopoeias published by the A10 countries, or pharmacopoeias approved by the central health competent authority. The cited edition should be the latest from the date of application. This requirement also applies to any post-approval change of raw materials except excipients.
2. New chemical entities (NCE) are subject to the regulations set by the manufacturers.
3. The reference standards for tests should be indicated whether they are Primary Standard or Working Standard. For Primary Standard, the source should be specified. For Working Standard, the source, batch number, labelled content (or potency), testing specifications, certificate of analysis and calibration procedures should be specified.
4. For coloring agents, testing specifications and methods should be indicated. Testing specifications are not required for aromatics.
5. The certificate of analysis justifying every formulation substance should be the certificates about the substances of the same lot as the finished products.
6. Raw materials should be tested against each specification item. Documented operational procedures of items exempted from tests should be submitted, along with the certificates of analysis of the batch subject to full tests.
7. If test results are in numerical figures, then keep the original data in the document; if the test is a comparison with reference standard, then use “pass” to indicate a satisfactory result.

The testing specifications, methods and certificate of analysis of finished products mentioned in this Chapter refer to those performed on pharmaceutical preparations.
The regulations of testing specifications, methods and certificate of analysis of finished products said in the preceding paragraph are as follows:
1.If the applied drugs are listed in pharmacopoeias, the testing specifications attached to the application form should include the pharmacopoeia’s titles, publication year and editions. Such reference is restricted to the Chinese Pharmacopoeia, pharmacopoeia published in the A10 countries or acknowledged by the central health competent authority in Taiwan. The cited edition should be the latest from the date of application. This requirement also applies to any post-approval change of finished products. The publication year has to be within 5 years from the date of application. If the item in the pharmacopoeia includes more than two esters or salts, or contains ingredients with crystallized water or anhydride, the applicants should clearly specify which one is applicable to this application. In vitro pyrogen test methods should be considered alternatives for animal tests.
2.For each active ingredient, the applicant should state its standard test scopes and methods in the testing specifications. Denotation of the identification and assay of the contents should not be simply summarized as “operated according to certain pharmacopoeias”.
3.If necessary, upon the request of the central health competent authority, the applicant should provide test records, including the information listed below and all test data to justify whether current regulations and criteria have been met:
(1) Sampling venues, quantity, batch numbers or other specific codes, the date of sampling and the date when tests were completed;
(2) References to justify every test method;
(3) The weight or volume of samples for each test;
(4) The reference standards for each test should be indicated whether they are Primary Standard or Working Standard. For Primary Standard, the source should be specified. For Working Standard, the source, batch number, content (potency), test specifications, certificate of analysis and calibration procedures should be specified;
(5) Complete data records produced from each test, including equipment output charts and spectrums, etc. All data should be clearly described to avoid confusion;
(6) All calculation records associated with tests;
(7) Conclusions on the comparison between test results and existing specifications;
(8) For every test, the names of the persons performing the test and the date of the test;
(9) Signatures from reviewers who have checked the original records for accuracy, safety and the compliance with existing specifications.
4.Provisions set out in Paragraph 2 Item 5 to Item 7 of the preceding article are applicable to the certificate of analysis of finished products.
For toll-manufactured pharmaceutical products, the tests of finished products should comply with the Guidelines on Toll-Manufacturing and Contract Testing of Pharmaceutical Products. The purpose of those tests is to ensure drug quality. Tests can be performed by the commissioned toll-manufacturers.

The Manufacturing and Control Standard mentioned in this Chapter refers to the Manufacturing and Control Standard in compliance with Part 2 of Good Manufacturing Practice Regulations (Good Manufacturing Practices for Pharmaceuticals), including data of the actual amount of material used in batch records.
The manufacturing records mentioned in this Chapter refer to the manufacturing records of the same lot as the samples submitted for tests. In the case where the data of the same lot is not available or the products are exempt from testing, the applicant can submit the manufacturing records of any batch produced within two years from the date of application or a representative batch.
The representative batch is a batch of drug product that is manufactured using the same formulation, manufacturing process, and in-process controls, etc. as the application for drug registration or post-approval changes. The applicant should provide proof of the unaffected product quality for the change of the manufacturing process and in-process controls, and should be approved by the central health competent authority.

The term “changed licenses” mentioned in this Chapter includes supporting documents of factory registration, drug company licenses and certificates or official documents of company registration and business registration.
Photocopies or photos of the following documents shall be affixed on the form:
1.Drug company license;
2.Supporting documents of factory registration (imported drugs are exempted); and
3.Certificates or official documents of company registration or business registration.
The affixing form can be exempted, if the documents said in the preceding paragraph are submitted via the electronic submission platform.

The original references of data submitted to support the application should be provided, including physicochemical characteristics, pharmacological and toxicological test data, pharmacokinetic data, bioavailability rate, documents of clinical usage and other research reports. They can not be substituted by general descriptive information, summarized data or case reports. If the original references are in neither Chinese nor English, then a translation version in Chinese or English should be submitted along with the translators’ names.

Product names should comply with the following regulations:
1.Do not use the other manufacturer’s name or trademark as a product name, except in the case the use has been authorized;
2.Products named after items in pharmacopoeias, common names or conventional formulas should include the company’s name or trademark or any distinguishable title as a prefix; but, this naming rule does not apply to export only products;
3.Product names can not be identical to any other exiting product names. Counterfeiting or insinuation is not allowed;
4.Product names should not be deceitful or exaggerated, nor should they give any misinterpretation on product efficacy;
5.Chinese product names should not include any foreign letters or numbers, unless therein lies real meanings;
6.For drugs whose licenses have been revoked pursuant to the Acts, their product names are banned from use for two years; but, this two-year ban does not apply to the following situations: the application is a re-submission according to the condition stated in Article 72 Paragraph 1; or, the original license is changed to export-only license; or, the reasons of the revocation or cancellation of an export-only license are irrelevant to drug safety or effectiveness. With the central health competent authority’s approval, the manufacturer can name the drugs with identical ingredients, dosage form, dose and efficacy for the original names.
7.If a manufacturer gave compounds with different formulas the same product name, then their Chinese product names should contain proper words or terms to clearly distinguish their differences in efficacy; and
8.Names that are inappropriate for pharmaceutical products shall not be used.
In order of priority, whether product names are identical or similar is judged on trademarks, the manufacturer’s name and other distinguishable names. However, in the situation described in Item 3 in the preceding paragraph, the manufacturer’s name and trademark will not be included in the comparison.
For drug items already granted with market licenses, the central health competent authority may reassess their product names pursuant to the previous two paragraphs.

Drug packaging materials and the data field of packaging on the application form should comply with the following regulations:
1.The quantity, materials and types of the drug packaging should be specified;
2.Except for oral nutrient liquids, all bottled solutions for oral internal use and syrups, shall not be packed in ampoule. The volume should be indicated on each bottle; and
3.The unit recorded in the data field of packaging on the application form should be identical to the unit dosage form of the formula.
The maximum package size for drugs should follow the standards in the Table of Maximum Package Size. If there are any special purposes for the maximum package size, the purposes should be stated on the packaging. For common pharmaceutical preparations, the minimum package size is the two-day dose for an adult. For syrup containing codeine (phosphate) as an instruction drug, the maximum package size is the three-day dose. Tablets or capsules containing ephedrine or pseudoephedrine should only be packed in aluminium blister foils and boxes. For instruction drugs, the maximum package size is the seven-day dose for an adult. For drugs for the cold, fever, pain relief and for the cough liquid, the package size should be between one single adult dose and 4000 ml. The restrictions do not apply to sickness drugs and pesticides.
Please see Appendix 1 for the Table of Maximum Package Size as mentioned above.
In the situation where the packaging is over its maximum package size, an application to change the registration should be made by providing documents of purchasing orders from health care providers or academic institutes. The application for changes does not apply to instruction drugs containing ephedrine or pseudoephedrine.

• Appendix1：Maximum Drug Package Size Dosage.pdf

The applicant should honestly and completely fill out the application form, including the company name, code, address, telephone number, drug company license number, the person in charge of the business, the pharmacist in charge of the management or manufacturing, and the pharmacist’s address, and license number. The information should be confirmed by using private signets. The signets can be exempted, if the application is submitted via the electronic submission platform.
The same signets or stamps used in the application form should be used for any follow-up applications. The applicant should report to the authority if the signet or stamp is lost.
In the situation of toll-manufacturing, the names, codes and addresses of all manufacturers involved in the manufacturing processes should be listed in the data field of manufacturers on the application form.

The information given in the data fields for raw materials and contents on the application form should comply with the following regulations:
1.The contents of the formula should be indicated per minimum unit;
2.The contents should be in International System of Units (SI), without including the increasing rate;
3.For pharmaceutical preparations containing ingredients of crude drug, the active ingredients in the formula should be listed in the order of chemical ingredients and the ingredients of crude drugs;
4.Solvent, auxiliary solvent, stabilizers and other excipients used for injections should be described in detail and be suitable for injection. The contents of the formula should be indicated per minimum unit. However, for powder or lyophilized injections, the contents can be indicated per minimum package size;
5.The English names and contents of aromatics, coloring agents, preservatives and other excipients should be indicated;
6.Artificial flavouring may be added if the use is medically justified, but it shall not be added to the nutrient liquid;
7.For capsules, in addition to the full formula of the drug, a description of the full formula of soft capsules, and coloring agents of hard capsules should be described accordingly;
8.The ingredient and contents of active pharmaceutical ingredients should be described in a way consistent with the method used in a pharmacopoeia;
9.If the item includes more than two esters or salts or contains ingredients with crystallized water or anhydride, the applicant should clearly specify which one is relevant to this application;
10.The sources of active ingredients of drug products (manufacturers’ names, manufacturers’ addresses and the country of origin) should be specified. Source data can be declared electronically after the approval of the registration.

The information given in the data field of indications on the application form should be based on the drug efficacy or indications approved by the central health competent authority, including the drug re-categorization, drug re-evaluation results, and the Guidelines on the Review of Instruction Drugs.
When filling in the information of drug efficacy and indications, in addition to following the regulations stated in the preceding paragraph, the applicant can also provide a summary by taking references from information on new drugs and new indications and formularies of the A10 countries. If there are any changes in efficacy, related information should be provided for review.

Assurance Statements (A) and (B) attached to the application form should include the company name, address, person in charge and the date of signature. The information should be confirmed by using the same signets or stamps as those for the application form. In the situation of toll-manufacturing, assurance statements from both the appointer and the appointee are required.

Drug labels, package inserts and packaging are subject to Article 75 of the Regulations, and can contain only the information approved by the central health competent authority. The statutory contents and presentation should comply with the following regulations and the print should be easy to read:
1.Package inserts should include information on drug category, packaging, storage and all compulsory matters required by other regulations;
2.The outer packaging of imported drugs should meet the following conditions:
(1) The Product name, active ingredients and contents, and the name and address of the manufacturer or company should be printed by the original manufacturer. If the manufacturer’s name and address is not printed on the outer packaging, this information should be printed on a sticker adhering to the outer packaging;
(2) The company name, address and license number of the drug company, drug category and Chinese product name can be provided on a sticker;
(3) If the information of the manufacturer’s name and address is not printed on the outer packaging by the original manufacturer, it may be printed on a sticker with the information as stated above in the preceding item (2); and
(4) For toll-manufactured products, with approval from the central health competent authority, the appointee’s name and address can be substituted by the country from where the appointee is located.
3.For generic drugs under pharmacovigilance, the package inserts should follow that of the first approved drug. For the registration or the changes in package inserts of generic drugs not under pharmacovigilance, the package inserts should follow the approved drug of the same active ingredient, same dosage form, same contents and same indication. The supplemented information on product characteristics and drug safety also can submit scientific evidence. It is not limited to those who have supplemented information on product characteristics and drug safety, and submitted scientific evidence for the contents of the supplement. The central health competent authority may ask for revising the package inserts if it is necessary.
4.The process of labelling is deemed a part of the manufacturing process and is subject to GMP Guidelines. For imported drugs, labelling should be done by the original manufacturer. Packaging and labelling can be commissioned to a GMP manufacturer or a GMP medical product distribution center in Taiwan, pursuant to the Guidelines on Drug Toll-Manufacturing and Contract Testing. Information about the GMP manufacturer or GMP medical product distribution center in Taiwan which packages and labels drugs in accordance with this paragraph may be exempted from the stickers.
5.Outer packaging and the immediate packaging have to be labelled in Chinese and English, pursuant to this article. If the immediate packaging does not have enough space to include information in both languages, at least product name and contents in Chinese should be provided. Labels listed below are deemed in compliance with this Paragraph.
(1) Injections that are packed in one injection per box for single use with Chinese information printed on outer packaging;
(2) Drugs that are sold or dispensed in original packaging with the outer boxes remaining intact, on which Chinese information is printed; or
(3) Drugs that are classified by the central health competent authority to be used only by physicians with outer boxes printed with Chinese information.
6.For the following drug items, if Chinese information is provided on outer boxes, then only the Chinese or English product name and contents are required on the immediate packaging to meet the regulations in the preceding paragraph.
(1) Drugs for rare diseases;
(2) In situations where special storage conditions are required, i.e. drugs that need to be refrigerated or frozen; or
(3) Special cases that the central health competent authority’s approval on drugs is required.
7.In principle, the information on package inserts should be within the pharmacological scope of its active ingredients and major efficacy. For compound preparations, the scope should be within the scope of the major pharmacological functions of mixed active ingredients. Exaggerated terms and wordings are not allowed.
8.Contraindications, warnings, side effects, and precautions stated on package inserts should be indicated in detail and printed in red, framed in red line, or in boldface to attract the special attention of users.
9.Chinese characters should not be smaller than font size seven.
10.Drugs sold on the market may only provide approved Chinese package inserts. However, if both Chinese and English package inserts are provided, the contents of the English version should be consistent with that of the Chinese one. Manufacturers may of their own accord modify the contents of the English version to fit the Chinese version.
11.Package inserts, labels and packaging materials should not include photos or wordings that are indecent, offensive or exaggerated.
12.If the distributor’s name is printed on the package inserts, labels or packing materials, the font size of the distributor’s name should not be bigger than that of the manufacturer (license holder). A photocopy of the distributor’s business license should be submitted for reference.
13.The font size of the Chinese product name should not be smaller than that in foreign language. The printing should be clear. As a standard for comparison, the height of the printing of product name in Chinese should not be lower than that in foreign language.
14.For OTC (Over-the-counter) drugs, the labels and packaging should include significant prints of the product category, i.e. OTC drugs or Class B OTC drugs. In principle, printing should be in regular fonts.
15.Whereas the active ingredients, dosage form, dose and administration route of a licensed drug remain unchanged, the appearances or shapes of its aromatics, coloring agents or corrective agents without any pharmacological effects are altered but do not affect drug quality or medication safety, then it can be justified by applying for post-approval changes for excipients as the addition of new contents. Appropriate descriptions should be given on labels, package inserts and outer packaging for clear differentiation. Graphic designs and colors may be changed to suit the new descriptions.
16.For drugs packed in aluminum blister foils, each sheet of foil should be printed with the drug name using Chinese as the main language. Manufacturer’s name and license number can be provided. The following conditions are deemed to meet the criteria of this Paragraph:
(1) The product name in Chinese has been printed on (or adhered to) the immediate packaging of each aluminum blister foil sheet;
(2) Drugs are dispensed or sold in original packaging with the outer boxes remaining intact, on which information in Chinese is printed.
17.Drug labels and packaging should contain information of batch number, manufacturing date, effective period and expiry date in any of the following format:
(1) batch number, manufacturing date and effective period;
(2) batch number and expiry date; or
(3) batch number, manufacturing date and expiry date.
18.The manufacturing date and expiry date as mentioned in the preceding paragraph should be written with Arabic numbers using four-digit format for year. When only month and year are shown for the expiry date, either year-month or month-year format is accepted. For manufacturing date and expiry date containing all three components (year, month, day), the date should be written in the year-month-day format (from left to right). If other date notations are used due to unavoidable circumstance, the format used (e.g., dd/mm/yyyy, day/month/year, etc.) should be clearly expressed on the outer box. But, for products whose validity period is over 2 years, the manufacturing date and expiry date can include year and month only and set at the last day of that labelled month as the expiry date.
19.Information of the materials that have direct contact with pharmaceutical products should be labelled on plastic containers of L.V.P. (large volume package) for infusion.
20.The active ingredient(s) and excipients should be labelled respectively in the package inserts. The excipients may be written in chemical name or trade name, and the excipients not existing in the final product may not be listed.
21. For new drug registration or change in package inserts of prescription drugs, the drafts of package inserts should follow the format (prescription drug’s package insert format in Appendix 1-1).
Concerning locally manufactured drugs for exportation, shall not be subject to the limitations set forth in the preceding paragraph Subparagraph 1-3,5-10,12-14 and 16-21.
Statutory package inserts, labels, outer boxes, aluminum blister foils and other materials or graphic for labelling purpose should comply with the additional items required to be printed as announced by the central health competent authority, as well as the drug re-evaluation results, Guidelines on the Review of OTC Drugs, drug re-categorization and regulations of standardized package inserts.
In addition to the regulations set out in previous three paragraphs, the additional printings on labels and packaging of controlled drugs should also comply with the Regulations Governing Controlled Drugs as well as other related regulations.
Color drafts of outer boxes, package inserts, labels, aluminum blister foils and other labelling materials should be adhere to the form for sticking label and package insert. The affixing form can be exempted, if the documents said in the preceding paragraph are submitted via the electronic submission platform.
When collecting license, applicant should submit the electronic files of the image of drug appearance, labels, package insert and packaging as approved by the central health competent authority. For applications of post-approval changes in drug appearance, labelling, package insert or packaging, electronic files of the new contents approved by the central health competent authority should be submitted.

• Appendix 1-1：Prescription Drug’s Package Insert Format.pdf

Validation requirements for medicinal product are described as follows:
1.When applying for drug review and registration, the applicant may firstly prepare the analytical method validation report and the protocol of the validation of critical manufacturing processes. After receiving approval, the manufacturer should conduct validation studies on three consecutive batches of products. If the results meet all specified criteria, the product can therefore be marketed.
2.The validation studies should be able to assure drug effectiveness and safety and comply with the Guidelines on GMP Validation Requirements as announced by the central heath competent authority.
3.The contents and schedule of a drug validation process are as follows:
(1)Manufacturers should submit the validation documents of the supporting system, equipment and facility, critical manufacturing processes (including cleaning validation) and analytical method of at least one product to the central health competent authority for inspection. The submission deadlines were 31 December 2000 for local manufacturers and 10 June 2002 for license holders of imported drugs. For those failing the submission or the assessment, the authority will make a public list of their company names and all their approved drug licenses in Taiwan, and give a deadline for improvement. These companies are not allowed to file any applications of new drug registration. Companies missing the deadline for improvement will be denied the rights to apply for license extension.
(2)Manufacturers should submit the validation documents of the critical manufacturing processes (including cleaning validation) and analytical method of all products to the central health competent authority for inspection. The submission deadlines were 30 June 2002 for local manufacturers and 10 December 2003 for license holders of imported drugs. Companies failing the submission or the assessment will be handled according to the proceedings stated in item (1).
(3)Manufacturers should fully implement all validation processes and submit the documents to the central health competent authority for inspection. The deadlines for submission are 30 June 2004 for local manufacturers and 10 December 2005 for license holders of imported drugs. Companies failing the submission or the assessment will be handled according to the proceedings stated in Item (1).
(4)Validation would not be necessary for license holders that do not manufacture or import drugs to sell. This exemption took effect from 1 July 2002 for local drugs and from 11 December 2003 for imported drugs. However, licenses of imported drugs may be extended without validation, if the license holder submits the drug license and an assurance statement certifying that the drug will be imported for sale only after all validation documents have been submitted and approved. The license will be stamped, noting that the drug can not be imported due to deficiency of required documents. After all documents are submitted and approved, the license will be re-stamped, indicating that the drug can now be imported for sale on the grounds that full compliance has been met with the DOH’s requirements.
(5)Penalties will be imposed on license holders pursuant to the Pharmaceutical Affairs Acts, if drugs have been produced or imported to sell without validation.

The information and local clinical data required for the application of drug registration or post-approval changes should comply with the following regulations:
1.Clinical trials conducted in Taiwan should follow the Regulations for GCP (Good Clinical Practice), as well as the Notices for the Application of Clinical Trials and the Guidelines on Bridging Studies as announced by the central health competent authority.
2.Before conducting a clinical trial, the manufacturer should submit a protocol, a protocol summary and an application form to the central competent health authority for assessment.
3.After the application is approved by the central health competent authority and an official approval letter is issued, the manufacturer should carry out the clinical trial according to the comments provided with the assessment results. After the completion of the clinical trial, the results should be submitted for inspection.
Clinical data from foreign countries submitted together with the application should have a comparison with a control group or a double-blind test design. This data cannot be substituted by a general descriptive document, summarized data or individual case report. The regulations set forth in the preceding item are applicable to the technical data of local clinical trials.

Except for drugs with relevant local clinical trial data to justify drug efficacy and safety in Taiwan, alone with pharmacokinetic data on ethnic groups in East Asia, the following drug items are subject to a bridging study assessment:
1.New chemical entities and new biologics;
2. Items announced by the central health competent authority as requiring a bridging study assessment.
Drugs received designations of treatment of pediatric or rare severe disease from the central health competent authority, cellular and gene therapy products are exempted from the bridging study assessment.
When applying for a bridging study assessment, manufacturers should fill out the checklist for bridging study assessments and provide a complete clinical data package, preferably with data on ethnic groups in East Asia. Applications of bridging study assessments can be filed prior to or together with the applications of drug registration.
Bridging study data would not be required for the applications of drug registration that have been approved by the central health competent authority to be exempt from bridging studies. However, there should still be sufficient clinical data to justify drug efficacy and safety.
If the assessment result suggests that a bridging study is necessary, the applicant should prepare an appropriate protocol according to the comments from the assessment and submit the protocol to the central health competent authority for assessment. After the protocol is approved, the applicant should conduct the bridging study and submit study reports and related data to the central health competent authority for inspection.
In situation where a license is granted to a new drug with the submission of bridging study data, if in the next 5 years any generic manufacturer intends to manufacture or import generics with ingredients, dosage form and contents identical to this new drug, then the generic manufacturer should submit all required data and a bridging study report up to the standards set by the first license holder.

For drugs other than the categories listed in the preceding article, whether an application of a bridging study assessment shall be filed is left to the discretion of manufacturers. For applications without bridging study data, if the central health competent authority considers that a bridging study is necessary, the manufacturer is obliged to conduct a bridging study.

If the application for drug registration concerns about a drug involved in toll-manufacturing or contract analysis, then the applicant should submit data required by the Guidelines on Drug Toll-Manufacturing and Contract Analysis and all related information required by Article 64 and Article 66.

Except as otherwise regulated, all applications covered in this Chapter are subject to a parallel assessment of dossier review and drug testing. If the submitted dossiers pass the assessment, then the applicant should follow the notice issued by the central health competent authority to collect the license. Once the test specifications are approved, the applicant should follow the notice issued by the central health competent authority to proceed with drug testing.
The following applications only require dossier review, while drug testing can be exempt except for those cases deemed by the central health competent authority as drug testing being necessary.
1.Drug registration:
(1)Pharmaceutical preparations classified as OTC drugs (including Class B OTC drugs);
(2)Vitamins meeting the criteria for products containing vitamin substances;
(3)Generics;
(4)Pharmaceutical preparations meeting the criteria set out by the Guidelines on the Review of Over-the-counter Drugs;
(5)General active pharmaceutical ingredients; and
(6)Pharmaceutical preparations and active pharmaceutical ingredients for exportation only.
2.Post-approval changes
As mentioned in the preceding paragraph, for those drugs that only abide by dossier review, the applicant should submit color photos or scanned images of a sample product for assessment. If necessary, a reference standard should be provided for comparison.

Except for radiopharmaceutical drugs, cell-based preparations and biopharmaceutical drugs needed to be tested by registration, the applicants should provide samples of new chemical entities, new compound medicine and the first active pharmaceutical ingredient to the central health competent authority for future inspection prior to be on the market.
If the above-mentioned new chemical entities and new compound medicine are applied for a change in the dosage form of Article 52, a change in the formula of Article 53, a change in the excipient of article 56, a change in product appearance of Article 57, a change in the site relocation or the place of production of Article 62 Paragraph 1 Item 2, a change in the pharmaceutical toll-manufacturing of Article 64, and self-manufacturing retrieval after outsourced of Article 65, the applicants should also follow the preceding paragraph.

In any of the following situations, applications will be rejected:
1.Applicants don’t have the qualifications required, or manufacturing equipment does not meet the standard, e.g. hardware, software or dosage form equipment does not comply with GMP Guidelines; or there has been no submission of evidence to support compliance with related regulations;
2.No application fees have been paid, or the submitted data is insufficient or does not fit with the contents of the application;
3.The major efficacy of the applied drug is unclear or insignificant; or the drug fails the drug re-evaluation;
4.The applied drug has severe side effects or safety concerns;
5.The contents of toxins or controlled substances contained in the applied drug do not conform to regulated doses;
6.The applied drug contains unapproved coloring agents, preservatives or anti-oxidants;
7.The applied drug contains forbidden ingredients;
8.The applied drug has inappropriate formula, manufacturing method or dosage form;
9.The ingredients of an oral liquid product are not nutrients, or contain Caffeine-like substance;
10.Hormone (including anabolic hormones, steroid), stomachics, pesticides, sickness drugs or pharmaceutical preparations with effects of anti-sleep, antipyretic, antitussive, expectorants or other medical efficacy, that are registered in the dosage form of oral liquid;
11.Amino acid and multi-vitamin nutrition that in total contain over 8% w/v of alcohol;
12.Syrup containing codeine (phosphate) with the content of sucrose less than 55 w/v; or syrup categorized as Over-the-counter (OTC) drugs with the content of codeine less that 1g per 100ml and in compliance with the following rules about the content of codeine:
(1)The maximum daily dose is 9 mg for syrup for the cold and 18mg for syrup for antitussive or expectorants;
(2)For concomitant use with Ephedrine Hydrochloride, dl-Methylephedrine Hydrochloride, the dose should be reduced by 20%;
(3)The single dose for an adult should be at least 5ml; and the formula’s unit strength should be adjusted accordingly.
13.Pharmaceutical preparations combined with Chinese traditional medicine and western pharmaceutical medicines that contain substances affecting the central nerve system, poisons or powerful drugs;
14.Inappropriate testing specifications or data references;
15.Failing to collect licenses or proceed with drug testing within the specified deadline; or the drug testing results fail the assessment due to discrepancy between the results and the data submitted for the application or due to other reasons;
16.Failing to produce, change or modify the product packaging, labels or package inserts in accordance with the approved items; and
17.Any other situations not in compliance with the Regulations, related regulations, or announcements made by the central health competent authority.

In situations where fees have not been paid, application forms not submitted, data insufficient or other matters not in accordance with the Regulations, the applicant should take corrective actions before the deadline specified by the central health competent authority. A two-month period is given for correction.
If the applicant is not able to meet the deadline, a written statement should be submitted to support the application of an extension. The extended deadline is one month after the expiry date of the original correction period. Only one extension will be allowed.
If the applicant fails to make correction within the original or the extended deadline, then the central health competent authority can reject the application based on the currently available information.

Upon the receipt of the notice of license collection, apart from proceeding with drug testing, the applicant should pay the fees within the deadline for license collection. The procedure for license collection is as follows:
1. Two copies of actual printing materials or color drafts each of drug labels, package inserts and packaging materials that are printed in accordance with the approved draft should be provided. The application submitted via the electronic submission platform may only provide one copy of actual printing materials or color drafts.
2.The notification letter stamped with the applicant’s official seal and the signet of managing director;
3.The approved draft copy of labels, package inserts and outer packaging that were attached to the license collecting notice should be returned.
4.The photocopy of the application form of drug registration that was attached to the license collecting notice should be returned.
5.A photocopy of drug license that was attached to the license collecting notice should be returned.
License should be collected within three months of the notice date. If the applicant is requested to make corrections due to mistakes in the information on the labels, package inserts, packaging or other related materials required for license collection, the applicant should make corrections within the deadline specified by the central health competent authority before the license can be collected.
Except for the reissuance of damaged or lost drug licenses, all approved post-approval changes will be certified by the central health competent authority through noting down the changes on the original drug license with date and official stamps, then returned to the license holder. Fees for the reissuance of a new license copy will be charged.
After the license was collected, if the applicant does not follow related regulations to proceed with drug testing, or the test results are not in accordance with the contents of the application or are disqualified for some reasons, then the license has to be returned according to the central health competent authority’s notice.

Upon receipt of a drug testing notice, the applicant should pay the test fees and send the following samples and information to the central health competent authority for testing before the deadline specified in the notice:
1.Three portions of drug samples. Each portion should be quantity sufficient for carrying out specification analysis for all items;
2.Appropriate quantity of reference standards, if they are needed for the test;
3.Form for sample delivery for drug testing;
4.Fee schedule for drug testing charged by the central health competent authority;
5.Color photos or scanned images of drug samples.
For applications of drug registration or post-approval changes filed during the pharmacovigilance period, if the central health competent authority has concerns regarding quality or other issues, then the following procedures should be taken:
1.If the submitted dossiers are complete, the central health competent authority will inform the applicant to send samples for testing.
2.If the sample passes the tests, but the Bioequivalence (BE) test report or clinical trial report has not yet been reviewed, the central health competent authority shall issue a notice, conceal the data submitted for drug registration in a sealed envelope and return it to the applicant. The applicant should keep the envelope safe and should not open it without permission. If the sample fails the test, punishment will be given pursuant to the Act.
3.After being informed by the central health competent authority of the approval of BE test report or clinical trial report, the applicant should return the sealed envelope along with a photocopy of the notice to the central health competent authority to proceed with the application.
Cases or re-testing will be charged testing fees again.

In situations where the applicant proceeds with drug testing prior to the acquirement of license, if the dossiers later fail the review, the applicant shall not request for a refund or return of drug samples.
In situations where the applicant receives a drug license and starts selling the products before the applicant proceeds with drug testing or before the test results are through, the applicant should make an exact list of the manufacturing dates, batch numbers, trading parties and quantities for each batch of products. The list should be submitted to the central health competent authority and local health authorities at 10-day intervals.
In the above-mentioned situations, if the applicant does not comply with related regulations to proceed with drug testing or if the test results are not in accordance with the contents of the applications or for any other reasons it fails the assessment; then, upon receipt of the notice, the applicant should stop manufacturing the products involved and return the drug license immediately. The applicants shall be punished according to the Act.

For the application for drug registration of imported drugs, the regulation of testing samples, their quantity and custom clearance procedure are as follows:
1.In principle, the quantities of samples of testing drugs and reference standards for custom clearance should be consistent with the quantities stated on the letter of notice issued by the central health competent authority. However, to have the packaging remain intact, the applicant may request the custom office to deliberate over the factual packaging and release one single complete package.
2.Manufacturers should follow the Regulations Governing Controlled Drugs and the corresponding implementation rules in compliance with the central health competent authority for approval of the importation and exportation of controlled drugs (including the importation of active pharmaceutical ingredients of controlled drugs for trial manufacturing). This requirement also applies to drugs not classified as controlled drugs in Taiwan but an importation permit is required by the manufacturing country.
The above regulations for testing samples and their quantities and custom clearance procedures are also applied to the applications of post-approval changes of imported drugs.

The following procedures apply to drugs already granted with licenses but that have failed the efficacy and safety assessment and to drugs whose formulas should be re-evaluated:
1.If an applicant fails yet again in the appeal after submitting clinical data, then the drug license shall not be extended after its expiration.
2.For those formulas subject to re-evaluation, if the clinical data submitted by the license holder fails the assessment, the drug license shall not be extended after its expiration.
3.For formulas failing the original assessment or those subject to re-evaluation, if the clinical data submitted for re-evaluation passes the assessment, then the post-approval changes or extension of the drug license will be approved. However, if the clinical data is incomplete or the applicant did not resubmit data, the drug license shall not be extended after its expiration.
4.For formulas failing the assessment or those subject to re-evaluation, licenses in relation to the drugs are still valid during the appeal period or before the resubmission of data for re-evaluation. However, if manufacturers do not make appeals or resubmit data, the licenses in relation to the drugs shall not be extended after its expiration.