The stability studies, required for the application of post-approval changes, should comply with the following regulations of execution and data submission:
1.For any changes in drugs subject to the submission of the stability study report, the applicant needs to conduct 6-month accelerated stability studies on a batch of changed products, as well as a long-term stability study that tests through the expiration date. Data of at least 3-month accelerated stability studies should be submitted when applying for post-approval changes. The manufacturer should retain the documentation of operational details and test figures of other accelerated studies and long-term studies.
2.For changes in drug expiration date, manufacturers should conduct long-term stability studies on 3 marketed batches of drugs that tests through the expiration date, and analyze the results. For drugs applied for registration before 1 January 2001, manufacturers can decide whether to conduct storage tests or long-term tests based on the Guidelines on Stability Studies. Manufacturers should retain historical documentations of the operational details and original testing results and other related data for inspection; however the applications for post-approval expiration date changes would not be required.
For the documents that should be retained by manufacturers as mentioned above, the applicant has the obligation to provide relevant information upon the central health competent authority’s request. If the authority finds any discrepancy in the information, the applicant has to recall all products from the market and receive punishment according to the related regulations in the Act.

Applications for Post-approval change should be conducted in compliance with the following regulations:
1.Definitions of major changes and minor changes are as announced by the central health competent authority.
2.The following information should be provided for changes in manufacturing of drugs:
(1) For major changes: BE study reports should be submitted;
(2) For minor changes: a drug dissolution profile comparisons should be submitted.
3. The following information should be provided for changes of the manufacturing site of drugs:
(1) A comparison between the formula and the manufacturing process, including the sources of raw materials, specifications and manufacturing equipment;
(2) A drug dissolution profile comparison;
(3) If it is determined that a major change is occurred or the data is insufficient to determine a minor change, a BE study report should be submitted.
4. If the application of post-approval changes involves multiple changes in the formula and manufacturing processes, it shall be followed in accordance with its respective scope of change.
5. BE studies can be substituted by BA studies along with clinical trial reports.
6. BA/ BE studies should be conducted in compliance with the Regulations of Bioavailability and Bioequivalence Studies.
7.Post-approval changes involve the bioavailability and bioequivalence test, the waiver or replacement of the test can follow Article 8 of the Regulations of Bioavailability and Bioequivalence Studies, or contents approved or relevant regulations promulgated by central competent health authority.
For drugs already approved on the market, if the manufacturer, of their own accord, conducts a BE study and the report has been approved by the central competent health authority, and subsequent changes involved in the manufacture and manufacturing sites are subject to the regulations in the preceding paragraph.
Unless otherwise provided, the requirement for the bioequivalence study or the bioavailability and clinical study report may be waived for drug products that category in the Guidelines on the Review of Over-the-counter Drugs or in the category of the preparations of inherited formulation.

Applications of post-approval changes of imported drugs should provide a notice of changes issued by the original manufacturer. The notice should be issued by the registered original manufacturer or its headquarters, or authorized license holders in other countries; and the notice should be within its one-year validity. The manufacturer’s name and address stated on the notice should be identical to those on the approval. The notice should not be issued by affiliates, agencies or distributors or in the form of telegram, price quotation statement, or electronic media.

In any of the following situations, manufacturers may, of their own accord, change package inserts, labels, or packaging. However, these changes have to comply with the GMP Guidelines; and the relevant modified operational procedures shall be documented accordingly. Records shall be retained for future inspection. Notification of the post-approval changes in package inserts, labels, and packaging may be declared electronically the approval. Products on the market shall be handled according to the relevant regulations.
1. No changes in the originally approved text:
(1) Only changing the graphic design or colors of labels, package inserts, or outer boxes. The graphic design may not be offensive, indecent, or misleading;
(2) Resizing the approved graphic design or text to fit a different size of packaging, or repositioning the approved graphic design or text;
(3) Changing the fonts of the approved text. However, the font size of English text may not be larger than that of Chinese text;
(4) Changing or adding the corporate identification system (CIS) or anti-counterfeiting labels;
(5) Adding printings on outer boxes or using new outer boxes to replace the labels. The design of text and graphs shall be identical to those approved; or
(6) If an injection is available in different doses, the graphic design and the text on the labels and the outer packaging can be presented in different colors for differentiation.
2. Changes in text without affecting drug quality or medication safety:
(1) Only adding or changing bar-codes, National Health Insurance (NHI) codes, ID codes, “GMP” before the manufacturer’s name, copyright registration number or company trademark approved by the competent authority, trademark registration number, or patent number;
(2) Adding or changing the anti-counterfeiting hotline. Adding or changing the suggested retail price or customer service telephone line of medicines designated by physicians, pharmacists and/or assistant pharmacists, and over-the-counter drugs;
(3) Changing the drug company’s name, the manufacturer’s name or address, or excipients as approved by the central competent health authority, or adding or changing the telephone number, fax number and contact;
(4) Adding or changing the distributor’s name or address. The font size of the distributor’s name may not be larger than that of the license holder’s name. Distributors have to be a qualified pharmaceutical agent;
(5) Adding seal labels (outer boxes) or the changing labels (including price labels);
(6) Adding items on the labels or package inserts of export products upon the request of importing countries;
(7) Adding notes on the approved packaging to indicate that the product is exclusively for the use of certain hospitals or for inpatient use, including other appropriate terms such as “not for resale”;
(8) Adding, deleting, or changing the manufacturer’s name added to the name of the product in English;
(9) Changing the measurement unit of formulas in order to comply with the Chinese Pharmacopoeia;
(10) Changing the terms used in describing the storage conditions without altering the original requirements. The usage of the phrases shall be consistent with the Chinese Pharmacopoeia.
3. Changes in the text of the methods of administration in order to ensure drug quality and medication safety.
The adjustment of the manufactiring date and/or expiry date format of Article 20 paragraph 1 item 18, is not a label or packaging label change.

For drugs with licenses and categorized as medicines designated by physicians, pharmacists and/or assistant pharmacists or in the category subject to the Guidelines on the Review of medicines designated by physicians, pharmacists and/or assistant pharmacists, the central competent health authority’s announcements shall be followed. Missing the deadlines shall be punished according to the relevant regulations in the Act.

For active pharmaceutical ingredients or active pharmaceutical ingredients of drug products with licenses, the data involving the changes of technical documents shall be submitted in accordance with Appendix 12.
When applying for addition or change of the source of active pharmaceutical ingredients of the drug products, the following documents shall be submitted:
1. Application form for post-approval changes;
2. Original drug license;
3. A GMP compliance certificate for the active pharmaceutical ingredients newly added or changed;
4. The approvals of the technical documents of the active pharmaceutical ingredients issued by the central competent health authority. However, the technical documents of active pharmaceutical ingredients can be substituted by other dossiers as promulgated by the central competent health authority.
5. Description of the differences in specification between the new and old source of active pharmaceutical ingredient and the evidence;
6. Comparison and evaluation data of the finished preparations according to the characteristics of the dosage forms;
7. If the results compared according to the preceding paragraph are inconsistent, a dissolution test shall be conducted. If the comparison results of dissolution curves are dissimilar (f2<50), a drug BE test report shall be submitted.

• Appendix 12.PDF
• Appendix 12.doc

The following documents are required for the application of changes in the Chinese or English product name.
1.Application form of post-approval changes;
2.The original copy of drug license;
3.An assurance statement (A) should be submitted to certify the changes in the Chinese or English product names of a locally manufactured drug, or the change in the Chinese product name of an imported drug. If available, a photocopy of the trademark registration certificate or approval letter issued by the Bureau of Intellectual Property of the Ministry of Economic Affairs (MOEA) should be submitted; and
4.The application of the change in the English product name of an imported drug should be accompanied with a notification letter of post-approval changes issued by the original manufacturer and the CPP from the manufacturing country.

The following documents are required for the application of changes in drug categorization:
1.Application form of post-approval changes;
2.The original copy of drug license;
3.The safety test, clinical references and the pharmacopoeia or formularies of the A10 countries; and
4.A notification letter of post-approval changes issued by the original manufacturer for imported drugs.
5. If the first applicant applying for the category change of prescription drug, the global adverse drug reaction notification report and the plan of pharmacist training are required.
If the change in drug category is ordered by the central health competent authority based on an assessment result, then Items 3-5 in the preceding paragraph can be exempt.
If a license reissue is required, the original copy of the application form for drug registration should be provided.

The change of dosage form is restricted to changes among tablets, sugar-coated tablets and film-coated tablets; between cream and ointment or among gel, cream and ointment for external use provided that drugs with identical ingredients, dosage form and dose have been approved by the central health competent authority.
The following documents are required for the change of dosage forms:
1.Application form for post-approval changes;
2.The original copy of drug license;
3.Manufacturing and Control Standard, or the batch records of the same lot as the finished products;
4.Stability study results;
5.For locally manufactured drugs, the testing specifications, methods and certificate of analysis of the finished products, as well as the assurance statement (A) and supporting documents of factory registration;
6.For imported drugs, the testing specifications, methods and certificate of analysis of the finished products and active substances used for the batch, as well as a notification letter of post-approval changes issued by the original manufacturer and the CPP issued by the country of origin are needed.

No active pharmaceutical ingredients can arbitrarily be changed. Re-application for drug registration is required for such changes. In any of the following situations, the application of post-approval changes can be filed:
1. Adding declaration of salt forms in vitamin preparations, if those salts are not listed on the license;
2. Changing the measurement units of the antibiotic preparations from weight to potency;
3. Modification is required according to the central competent health authority’s concerns over safety or ban on certain ingredients in the formula;
4. Imported drugs certified by the supreme competent health authority of the country of origin wherein the formula change is necessary. The manufacturing methods, testing methods, specifications, stability, or drug re-evaluation reports from the original manufacturer shall be submitted.
The following documents are required for the application of changes of formula.
1. Application form for post-approval changes;
2. Original drug license;
3. Standard Manufacturing and Control Procedures and the amount of all starting materials in the batch record or the batch record of the same lot as the finished product;
4. Data on the stability test;
5. Declaration (A);
6. For locally manufactured drug products, the testing specifications, testing methods, and certificates of analysis for the finished products;
7. For imported drugs, the testing specifications, testing methods, certificates of analysis for the finished products and the raw materials of the same lot as the finished products, a notification letter of post-approval changes issued by the original manufacturer, and CPP from the manufacturing country.
In any of the following situations, reapplication of drug registration is required, but it is not applicable to post-approval change.
1. Same active pharmaceutical ingredients with different doses;
2. The original manufacturer no longer manufactures the originally approved drug product, which is to be replaced by a new preparation whose product name and formula are different from those of the approved drug.

The following documents are required for changes in indications:
1.Application form for post-approval changes;
2.The original copy of drug license;
3.Two copies of complete clinical trial report or related references of the claimed indications;
4.For locally manufactured drugs, an official reference book recording the new indications is needed. For imported drugs, approval of new indications issued by the central health competent authority of the country of origin and authenticated by the R.O.C foreign affairs offices is needed. If these documents are not available at the time of filing, the applicant shall provide the required documents before approval. The authentication requirement is waived for documents issued by A10 countries or the EMA. The above-mentioned documents can be replaced with the approval information on the A10 countries highest health competent authority or the EMA’s official website and approval letter of new indications issued by the of A10 countries or the EMA;
5.An original approved copy of the form with labels and package inserts attached along with the central health competent authority’s stamp on the seams. The above-mentioned documents can be exempted when the original copy was approved via the electronic submission platform;
6.Two actual packaging materials (or color photos) or drafts of package inserts, labels, outer boxes, and aluminum blister foil sheets. For imported drugs, two copies of package inserts in the original foreign language are needed;
7.For imported drugs, the notification letter of post-approval changes issued by the original manufacturer is needed.
8.The comparison table of changes of package inserts or drafts of package inserts with tracking revisions and comments.
If there is evidence from clinical trials conducted in Taiwan to justify that the drug is effective and safe for the new indication, then the first applicant applying for the addition of the new indication can be exempt from the requirement described in Item 4 in the preceding paragraph.
The first applicant of the addition of a new indication (including changes of indications and addition of indications) may decide whether or not to conduct local clinical trials. If a local clinical trial has been conducted by the first applicant to justify the drug is effective and safe for the new indication, then during the following 5 years, other applications filed by other manufacturers of drugs with the same ingredients, dosage form and dose, either for licensing the new indication or for extending an existing license, should also provide local clinical trial reports up to the standard conducted by the first successful applicant in addition to all the required documents set out in Paragraph 1 Item 1, 2 and 5-7.
If the first successful applicant of a new indication (including changes of indications and addition of indications) did not conduct local clinical trials; or the approval was issued more than 5 years ago, then any other applications of drugs with the same ingredients, dosage form and dose, either for licensing the new indication or for adding the new indication to an existing license, should provide all the required documents set out in Paragraph 1 Item 1, 2 and 5-7.
If labels and package inserts are revised according to the indications announced by the central health competent authority, the license holder should submit the application form for post-approval changes and the original copy of drug license when applying for post-approval changes of indications.

The following documents are required for the changes in drug administration and dosage:
1.Application form for post-approval changes;
2.Photocopy of drug license (front and back sides);
3.Two copies of complete clinical trial report or related references of the claimed drug administration and dosage;
4.An original approved copy of the form with labels and package inserts attached along with the central health competent authority’s stamp on the seams. The above-mentioned documents can be exempted when the original copy was approved via the electronic submission platform;
5.Two actual packaging materials (or color photos) or drafts of Chinese package inserts, labels, outer boxes, and aluminum blister foil sheets. For imported drugs, two copies of package inserts in the original foreign language are needed;
6.A photocopy of official reference books, or certificates claiming drug dosage and administration approved by the central health competent authority and authenticated by the R.O.C. foreign affairs offices is needed. If these documents are not available at the time for filing, the applicant shall provide the required documents before approval. The authentication requirement is waived for documents issued by A10 countries or the EMA. The above-mentioned documents can be replaced with the approval information on the A10 countries highest health competent authority or the EMA’s official website and approval letter of new drug administration and dosage issued by the of A10 countries or the EMA;
7.For imported drugs, a notification letter of post-approval changes issued by the original manufacturer;
8. The comparison table of changes of package inserts or drafts of package inserts with tracking revisions and comments.

The following documents are required for the change in excipients:
1.Application form for post-approval changes;
2.If the change in excipients could affect the characteristics of the drug, the applicant should follow the notice issued by the central health competent authority to perform drug testing and to provide two copies each of the testing specifications, methods, and certificate of analysis, as well as one copy each of the safety data, BE test data and stability test data;
3.Photocopy of the drug license;
4.For imported drugs, a notification letter of post-approval changes issued by the original manufacturer and the CPP from the country of origin.
The application of the above-mentioned changes has to comply with Article 46.
Whereas the active ingredients, dosage form, dose and administration route of a licensed drug remain unchanged, the appearances or shapes are altered by changing its aromatics, coloring agents or flavours without any pharmacological effects, and 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.

The following documents are required for changes of drug testing specifications, methods and product appearance:
1.Application form for post-approval changes;
2.Photocopy of drug license (front and back sides);
3.Two copies each of the testing specifications, methods and certificate of analysis of changed drugs, and an explanation of the differences in specifications before and after the changes;
4.For imported drugs, a notification letter of post-approval changes issued by the original manufacturer.
If the changes of testing specifications and methods are according to the update on pharmacopoeias, then the application form should include details of the cited pharmacopoeias, including the title, publication year and edition. The cited pharmacopoeias are restricted to Chinese Pharmacopoeia and pharmacopoeias published in the A10 countries or acknowledged by the central health competent authority and should be the latest edition from the date of application.
If the change does not involve the testing items and testing methods, the submission of documents mentioned in Item 3 of the previous paragraph can then be exempt. However, manufacturers should retain all original data and figures for future inspection.

The changes of manufacturing process and batch size of drug product as specified in the Appendix 12-1 should be applied to the central health competent authority for the applications of post-approval changes.
The documents involving the above-mentioned changes shall be submitted as specified in Appendix 12-2.

• Appendix 12-1：Matters that Should be Applied for Changes of Manufacturing Process and Batch Size of Drug Product.pdf
• Appendix 12-2：Documents for the Application of Registration Changes of Manufacturing Process and Batch Size of Drug Product.pdf

The following documents are required for changes of immediate packaging materials:
1.Application form for post-approval changes;
2.Original copy of drug license;
3.The Stability study report
4.For injections or liquid dosage forms, the testing specifications, methods and certificate of analysis of finished products. For injections packed in syringes or soft bags, the testing specifications, methods and certificate of analysis and leachables and/or extractables assessments of containers;
5.For locally manufactured injections, a photocopy of formulation basis. If the formulation basis is not available, the applicant should provide the safety data of packaging and go through the testing procedure as requested by the central health competent authority.
6.For imported drugs, a notification letter of post-approval changes issued by the original manufacturer;
7.If soft bags are added as a new packaging material of injections, Standard Manufacturing and Control Procedures and the amount of all starting materials in the batch record or the batch record of the same lot as the finished product should be submitted.

The following documents are required for changes in the filling quantity of injections (under conditions of no changes in unit strength and container materials):
1.Application form for post-approval changes;
2.Original copy of drug license;
3.For locally manufactured drugs, a photocopy of the reference of drug administration and dosage; for imported drugs, a notification letter of post-approval changes issued by the original manufacturer;
4.The stability study data in situation where the filling quantity is reduced.

The following documents are required for changes in the pharmaceutical company’s name without transfer of rights:
1.Application form for post-approval changes;
2.Original copy of drug license;
3.A list of all drug licenses;
4.A photocopy of the changed drug company licenses. No supporting documents of factory registration are required when the complete manufacturing process is commissioned to toll-manufacturers. For imported drugs, the applicant may submit a photocopy of the changed drug company licenses.
When applying for changes mentioned in the preceding paragraph, the applicant can include all drug licenses in one application. If the applicant divides the licenses in different applications, the follow-up applications should quote the document reference number of the first approval or attach a photocopy of the approval letter to the follow-up applications. A photocopy of the drug company’s license is not required.
If the merger of multinational companies causes the changes of a drug company’s name and the reorganization of different subsidiaries and agents in Taiwan, the application of changes should comply with the following regulations. If the merger involves the transfer of rights, the applications should be jointly filed by both sides.
1.Application form for post-approval changes: The application should be signed jointly by the companies involved in the merger, specifying that the change is due to the merger of multinational companies. However, if the original drug company name is no longer available after the reorganization, then the application can be filed only by the new drug company under the new name;
2.The notification letter of the company merger issued by the foreign manufacturer, its headquarters or the foreign license holder, or officially certified by responsible competent authorities;
3.An original copy of the authorization letter issued by the foreign manufacturer or its headquarters after the merger, or by the foreign license holder. The authorization letter should be authenticated by the R.O.C. foreign affairs offices;
4.Photocopy of the drug company license after the merger;
5.Assurance statement signed by the person in charge of the drug company after the merger. By signing the statement, the drug company assures that all drugs are imported and sold in compliance with related regulations and the company will take full responsibilities. The company should also make a statement to certify that the manufacturer does not have other products of the same formulation.
6.If prior to the merger, the drug company already held some drug licenses, then the original copies of all drug licenses and a list of all licenses of imported drugs should be attached to the application of changes. In principle, the transfer for all licenses is done in a single application. After the application is approved, the applicant should, of their own accord, change the company’s name on all labels, package inserts, outer boxes, aluminium blister foil, etc. Those materials should be submitted upon request for inspection;
7.If prior to the merger the drug company has some drug application cases still in progress, the applicant should fill in another application form (both original and duplicate copies), therein stating the new drug company name.

The following documents are required for the application of changes in the drug company name while the address remains the same:
1.Application form for post-approval changes;
2.Original copy of drug license;
3.A list of all drug licenses;
4.For local manufacturers, a photocopy of each changed license;
5.For manufacturers of imported drugs, a notification letter of post-approval changes issued by the original manufacturer and documents certifying the change in the manufacturer’s name issued by the highest health competent authority of the country of origin, and authenticated by the R.O.C. foreign affairs offices. The authentication requirement is waived for documents issued by A10 countries.
If the only change is the name of the manufacturer or foreign license holders, while the address remains the same and there is no transfer of rights, the following documents should be submitted for the application of post-approval changes:
1.Application form for post-approval changes;
2.Original copy of drug license;
3.A list of all drug licenses;
4.Notification letter of post-approval changes issued by the original manufacturer.

For post-approval change, the following documents are required for the changes of the drug manufacturer’s address:
1.If the change is due to building-numbering adjustment, then the following documents shall be submitted:
(1) Application form of post-approval changes;
(2) Original drug licenses;
(3) A list of all drug licenses;
(4) For local drug manufacturers, a photocopy of each changed license, and the documents issued by the household registration authorities to prove the implementation of building-numbering adjustment;
(5) For foreign manufacturers of imported drugs, a notification letter of post-approval changes issued by the original manufacturers and documentation issued by the relevant household registration authorities. The documents should be authenticated by the R.O.C. Foreign affairs offices. The authentication requirement is waived for documents issued by A10 countries.
2.The following documents are required for site relocation or changes in the place of production:
(1) Application form of post-approval changes;
(2) Original drug licenses;
(3) For local drug manufacturers, a list of all drug licenses, a photocopy of each changed license, and a photocopy of the GMP certificate for the new site after relocation;
(4) For foreign manufacturers of imported drugs, a letter of proxy, the original notification letter of post-approval changes issued by the original manufacturer, CPP from the manufacturing country, a photocopy of the GMP compliance certificate, the Standard Manufacturing and Control Procedures and the amount of all components in the batch record or the manufacturing records of the same lot for the final products, the testing specifications, the testing methods and certificate of analysis for the final products and the raw materials of the same lot, and data of stability tests. If the holder the GMP compliance certificate is not the applicant, then this documentation can be replaced by a letter of authorization issued by the original manufacturer or the local drug company holding the certificate, therein specifying the approval number of the original certificate.
(5) For foreign manufacturers of imported drug substances, a letter of proxy, the original notification letter of post-approval changes issued by the original manufacturer, the GMP compliance certificate of the active pharmaceutical ingredients, and the relevant technical documents as specified in Appendix 12.
(6) Article 46 should be followed for documentation submission.
(7) If renewal of license is required, the original application form shall be submitted.
For imported drugs, if the foreign manufacturing site’s address remains the same, but the address of the drug company or the foreign license holder is changed, and there is no transfer of rights, then the following documents shall be submitted.
1.Application form for post-approval changes;
2.Original drug license;
3.A list of all drug licenses;
4.Notification letter of post-approval changes issued by the original manufacturer.

The following documents are required for changes in package inserts, labels, outer boxes and aluminum blister foil or for the reissuance of the originally approved copy that was lost:
1.Application form of post-approval changes;
2.Photocopy of the drug license (front and back sides);
3.Originally approved copy of the form for sticking label and package insert with the central health competent authority’s stamp on the seams. The above-mentioned documents can be exempted when the original copy was approved via the electronic submission platform. Applications of reissuance of the approved copy can be exempt from this submission;
4.Two actual packaging materials (or color photos) or drafts of package inserts, labels, outer boxes, and aluminum blister foil sheets. If there is any change in the package insert, the changes should be highlighted in the draft package inserts, both in Chinese and in foreign language and the comparison table of changes of package inserts or drafts of package inserts with tracking revisions and comments. For imported drugs, the original package inserts and the draft of Chinese translation should be provided. The Chinese version should be precisely translated from the original version. If the changes only occurred in package inserts, then the applicant can just submit package inserts without other packaging materials;
5.For applications of the reissuance of lost original license, an assurance statement should be submitted to certify that the document is missing;
6.A notification letter of post-approval changes issued by original manufacture is required for imported drugs, except for applications of the reissuance of lost license.

Applications for registration of pharmaceutical toll-manufacturing shall comply with the Regulations on Pharmaceutical Toll-Manufacturing and Contract Analysis and shall submit the following documents:
1. Application form for toll-manufacturing;
2. A photocopy of toll-manufacturing contracts, therein stating the details about the management of toll-manufacturing;
3. Application form for post-approval changes;
4. Original drug license;
5. A list of all drug licenses categorized by dosage forms, but it is exempted for toll-manufacturing only one drug license;
6. A description of each toll-manufacturing process. This requirement can be exempted, if a complete manufacturing process is commissioned to the toll-manufacturers;
7. Standard Manufacturing and Control Procedures and the amount of all components in the batch record or the batch record of the same lot as the finished product. This document can be exempted if the local manufacturers have no intention to start the manufacture yet. The certificates should be noted with the phrase: “Manufacturing is not allowed”. Manufacturers are required to submit the Standard Manufacturing and Control Procedures and obtain approval from the central competent health authority prior to production;
8. A photocopy of the contract giver’s company license;
9. A photocopy of each of the contract acceptor’s factory registration license and drug manufacturing permit. For imported drugs, those documents can be replaced with a photocopy of the acceptor’s GMP compliance certificate. If the holder of the GMP compliance certificate is not the applicant, then this document can be replaced by a letter of authorization issued by the original manufacturer or the local drug company who holds the certificate, therein specifying the approval number of the original certificate.
10. The testing specifications and methods of the finished products issued by the contract acceptor;
11. Documents of rescission with previous acceptors. Those entering into a toll-manufacturing contract for the first time can be exempted from this requirement;
12. If the imported drugs were toll-manufactured, a notification letter of post-approval changes issued by the original manufacturer and the CPP from the country of origin shall be submitted. For the imported drug substances, the CPP can be exempt. However, the relevant technical documents for changing toll-manufacture, specified in Appendix 12, are required.
Drug license holder should comply with Article 46 when applying for pharmaceutical toll-manufacturing or changing the original pharmaceutical toll-manufacturing.
The change of the licenses mentioned in Paragraph 1 will be processed by noting the original license rather than issuing another one. However, in situations where the assessment results show that an import permit is required to change into a manufacturing permit, a new license has to be issued.
Under such circumstances, the applicant shall complete the checklist for toll-manufacturing dossiers, and provide all relevant documents, as well as the application form for drug registration and the Declaration (A).
After the application is approved, the applicant shall, of their own accord, modify the labels, package inserts, outer boxes, aluminum blister foil, etc. Those materials should be submitted upon request for inspection.

The following documents are required, if the manufacturer intends to manufacture a drug which used to be toll-manufactured.
1.Application letter for the shift from toll-manufacturing to self-manufacturing;
2.Application form for post-approval changes;
3.Original copy of drug license;
4.Original copy of the application form of drug registration;
5.Assurance Statement (A);
6.A photocopy each of the changed certificates and licenses;
7.Manufacturing and Control Standard and the amount of all components in the batch record or batch records of the tentative production batch;
8.The testing specifications, methods and certificate of analysis of the finished products;
9.If the applicant was originally not a GMP manufacturer, then certificate for the GMP compliance should be submitted.

Applications for contract analysis should follow the Regulations on Pharmaceutical Toll-Manufacturing and Contract Analysis and provide the following documents:
1.Application letter for contract analysis;
2.Application form for contract analysis;
3.Photocopy of the contract, therein specifying the scope of contract analysis and related issues;
4.The standard operation plan for contract analysis (including sampling method, sample storage method, sample delivery and transfer conditions, etc.) co-established by the appointer and the appointee;
5.Testing specifications and methods of the contracted items.
The central health competent authority may carry out site inspection if it is necessary.

Concerning locally manufactured drugs for exportation, the following documents are required for the applications for changes or additions in immediate packaging materials, maximum package size, labels, package inserts, outer boxes, drug names, indications, excipients, testing specifications, methods and appearance:
1.Application form for post-approval changes;
2.Original copy of drug license for the application of changes in drug name, indications, immediate packaging materials and maximum package size;
3.Photocopy of the front and back of drug license for the application of changes or addition of labels, package inserts, outer boxes, excipients, testing specifications, methods, and product appearance ;
4.Assurance statement for drug exportation;
5.Two copies of the drafts of package inserts, labels, outer boxes and aluminium blister foil for changes of in package inserts, labels, outer boxes and aluminium blister foil;
6.For changes of testing specifications and methods, a description of the differences in specifications before and after the changes. The new testing specifications, methods and certificate of analysis should be retained by the manufacturer for future inspection.

The following documents are required for changes in drug storage conditions:
1.Application form for post-approval changes;
2.Photocopy of drug license;
3.The stability study report;
4.For imported drugs, a notification letter of post-approval changes issued by the original manufacturer.

The following documents are required for changes in virus strain for a flu vaccine:
1.Application form for post-approval changes;
2.Original copy of the drug license;
3.Two copies of post-change testing specifications, methods and certificate of analysis of the ingredients, manufacturing processes, raw materials and finished products;
4.Drug stability study report. If the stability study report for drugs of the new virus strain is not yet available at the time of application, the applicant can submit the stability study report of the old strain, then submit the report of the new strain when the test is finished;
5.Clinical reference in relation to the new virus strain
6.The originally approved copy of the form for sticking label and package insert. The above-mentioned documents can be exempted when the original copy was approved via the electronic submission platform;
7.Two copies of the draft of labels, package inserts and outer boxes after the changes, and the comparison table of changes of package inserts or drafts of package inserts with tracking revisions and comments.;
8.For imported drugs, the notification letter of post-approval changes issued by the original manufacturer and the CPP from the country of origin. The above-mentioned documents can be replaced with the approval letter of new virus strain issued by the of A10 countries or the approval information on the official website of A10 countries highest health competent authority or the EMA and approval letter of new virus strain issued by the A10 countries or the country of origin. If the above mention documents are not available at the time of filing, the applicant shall provide it before approval.