CBPE

Promoting science based, medically appropriate policies for biologic medicines

Taiwan
Number of Biosimilars Available

Not publicly available

Country Spotlight: Taiwan

The Taiwan FDA (TFDA) is the department of the government of Taiwan with responsibility for assuring the safety and effectiveness of human and veterinary drugs. The Division of Drugs and new Biotechnology Products within TFDA is responsible for the scientific evaluation of biologics and biosimilars for use in Taiwan.

 

Biosimilars Available

Not publicly available.

Score Overview

Taiwan is Partially Compliant.

The WHO guidance was compared to the relevant sections across the TFDA guidelines resulting in an overall score for Taiwan is 3.1/5. This means the TFDA guidelines are partially or fully compliant with the WHO in many areas, in a few instances exceed the WHO, and in some areas are minimally or non-compliant with the WHO standards.

The graph below shows individual scores by each of the 28 components of biosimilar policy

There are eleven areas where TFDA is not as specific as the WHO, being either non-compliant, minimally compliant, or partially compliant with the WHO biosimilar policy.

Scores by measured component
Gaps
Gap 1

Reference Product:

When comparing the biosimilar to the original medicine, the TFDA guidelines do not specify that the same host cell should be used to produce the medicine.

Gap 2

Dosage Form and Strength:

The topic of container system is not addressed by the TFDA guidelines.

Gap 3

Quality/Analytical, Isolation of Drug Substance:

The guidelines from TFDA, do not specify that studies should be carried out to ensure that the characteristics of the drug substance (the active ingredient of a biologic medicine) are not affected by the isolation process.

Gap 4

Quality/Analytical, Immunological Analysis:

This topic is not addressed by the TFDA guidelines.

Gap 5

Nonclinical, General:

The guidelines do not specify that the final formulation should be used for the nonclinical studies, nor do they provide information on the range of studies required, or the factors that will determine how much nonclinical data is needed.

Gap 6

Nonclinical, Pharmacokinetics:

This topic is not addressed by the TFDA guidelines.

Gap 7

Clinical, General Considerations:

The guidelines do not address the fact that if relevant differences between the biologic and biosimilar are identified, the new product may not qualify as a biosimilar and a full licensing application should be considered.

Gap 8

Indication Extrapolation:

The guidelines do not provide the same degree of detail as the WHO in describing when it is appropriate for the biosimilar to be approved for all the indications held by original biologic, regardless of whether those indications have been studied.

Gap 9

Pharmacovigilance and Risk Management Plans:

The regulations and guidelines for pharmacovigilance are not as specific or details as those described by the WHO.

Gap 10

Naming:

This topic is not addressed by the TFDA guidelines.

Gap 11

Labeling:

This topic is not addressed by the TFDA guidelines.

Overall country score as compared to peers

History of Policy

TFDA finalized their Guideanc for Review and Approval of Biosimilar Products in 2008, and published two additional guidelines subsequently: Points to Consider for Review and Approval of Biosimilar Products in 2010, and Guideline for Review and Approval of Biosimilar Monoclonal Antibodies in 2013.[1][2]

Policy Guidelines

Guidance for Review and Approval of Biosimilar Products

  • The objective of this document is to provide guidance to those making biosimilar medicines to enable them to satisfy the requirements for the authorization of biosimilars in Tawian.
  • First issued 2008; Most recent update 2008

Points to Consider for Review and Approval of Biosimilar Products

  • Highlights key issues of importance when submitting a marketing application for a biosimilar
  • First issued 2010; Most recent update 2010

Guideline for Review and Approval of Biosimilar Monoclonal Antibodies

  • Provides specific detail on the requirements for demonstrating biosimilarity, safety and efficacy of biosimilar monoclonal antibodies.
  • First issued 2013; Most recent update 2013

Side by side comparison of each of the score components

For each of the 28 components of biosimilar policy evaluated, the specific wording in the FDA's biosimilar policy is listed, alongside the accompanying wording in the WHO policy (shown in the blue box).

Scope

[§ 3.0] Well-established and well-characterized biotherapeutic products such as DNA-derived therapeutic proteins. A well-established biotherapeutic is one that has been marketed for a suitable period of time with proven quality, safety, and efficacy.

Excludes vaccines, plasma-derived products, and their recombinant analogues.

[Ch. 1.IV] Applies to biotechnology-derived products containing recombinant proteins or recombinant peptides.

Excludes vaccines, allergenic products, and blood/plasma derived products and their recombinant substitutes, and any products not included the above definition of scope (such as products for gene/ cell therapy).

[Ch. 1.III] Excludes products that are difficult to characterize (such as natural substances extracted from biological sources) or products with little clinical or regulatory experience (such as products for gene/cell therapy).

Annex 1 of the Guideline provides guidance on four types of biosimilar products (somatropin, recombinant human soluble insulin, recombinant granulocyte-colony stimulating factor, and recombinant erythropoietins). This chart does not reflect this product-specific guidance.

Concept of Biosimilarity

[§ 4] A biosimilar is a biotherapeutic product that is similar in terms of quality, safety, and efficacy to an already licensed RP.

[Ch. 1.I] Biosimilars and Reference Products have similar nature in terms of quality, safety, and efficacy.

[Ch. 1.III] The biosimilar’s active ingredient must be similar, in molecular and biological terms, to that of the Reference Product.

[Ch. 2.V] The quality attributes of a biosimilar may not be identical to those of the Reference Product. Variability in post-translational modifications may be acceptable but should be justified.

[Ch. 3.II] Comparability studies must demonstrate the similarity of the biosimilar and the Reference Product in terms of efficacy and safety.

Reference Product

[§ 7.0] The same RP should be used throughout the entire comparability exercise and it must be approved in the country/region in question (or, where the licensing country lacks an approved RP, approved and widely marketed in another jurisdiction with a well-established regulatory framework for, and experience in evaluation and post-market surveillance of, biotherapeutics).

[§ 8.1] As a general rule, the biosimilar product should be expressed and produced in the same host cell type as the RP. The applicant should determine the potential impact of changing the host cell on product quality, safety, and efficacy based on available evidence from public information and experience with previous use of the RP. The rationale for accepting a difference in host cell must be justified based upon sound science and clinical experience with the biosimilar or the RP.

[Ch. 2.III] The chosen reference product should be used throughout the comparability studies evaluating quality, safety, and efficacy.

[Ch. 1.1, 2.VI] An reference product must have been approved for marketing in Taiwan. Applicants should justify the selection of the reference product, with specific attention paid to critical parameters and quality attributes.

The brand name, dosage form, formulation, and strength of the reference product should be clearly identified.

Reference standards listed in a public pharmacopoeia may not be appropriate reference products for comparability studies.

Formulation

[§ 8.1] The biosimilar manufacturer should assemble all available knowledge of the RP concerning the formulation used. The applicant should determine the potential impact of changing the formulation on product quality, safety, and efficacy based on available evidence from public information and experience with previous use of the RP. The rationale for accepting differences must be justified based upon sound science and clinical experience with the biosimilar or the RP.

[Ch. 2.IV] Formulation studies are necessary to justify the chosen dosage form, even if the biosimilar’s excipients are the same as those of the Reference Product. Formulation studies include studies examining the stability of the formulation, the compatibility of the active substance with excipients, diluents, and packaging material, etc., and the integrity (both biologically and physicochemically) of the active substance.

Route of Administration

[§ 5.0 ] Same as that of the RP.

[Ch. 1.III] Should be the same as that of the Reference Product.

If the route of administration is not the same, the applicant should provide nonclinical and clinical data to substantiate safety and efficacy.

Dosage Form And Strength

[§ 5.0] Dosage form should be the same as that of the RP. Strength is not addressed.

[§ 8.1] The biosimilar manufacturer should assemble all available knowledge of the RP concerning the type of container closure system used. The applicant should determine the potential impact of changing the container closure on product quality, safety, and efficacy based on available evidence from public information and experience with previous use of the RP. The rationale for accepting a difference in container closure must be justified based upon sound science and clinical experience with the biosimilar or the RP.

[Ch. 1.III] Dosage form and strength should be the same as that of the Reference Product.

If the dosage form or strength are not the same, the applicant should provide nonclinical and clinical data to substantiate safety and efficacy.

General Considerations

[§ 8] The application must contain a full quality dossier for both the drug substance and the drug product.

To evaluate comparability, the manufacturer should carry out a comprehensive physicochemical and biological characterization of the biosimilar in head-to-head comparisons with the RP. All aspects of product quality and heterogeneity should be assessed.

[§ 5] Development of the biosimilar involves a stepwise approach starting with characterization and evaluation of quality attributes. Differences should always be explained and justified and may require additional data.

[§ 8.2] Investigation of differences between the biosimilar and the RP should be based on knowledge of the relationship between quality attributes and clinical activity of the RP and related products, the clinical history of the RP, and lot-to-lot differences of commercial lots of the RP.

[Ch. 3.V] Clinical study requirements will depend on the type of biosimilar and its claimed indications. The clinical comparability program should begin with PK and PD studies and be followed by clinical efficacy and safety trials.

If the biosimilar produced using the final manufacturing process is not evaluated clinically, additional data should be provided to justify reliance on data involving product produced using a different manufacturing process.

Isolation of Drug Substance

[§ 8] Methods used to isolate RP drug substance for characterization must be justified and demonstrated to be appropriate. Studies must be carried out to demonstrate that product heterogeneity and relevant attributes of the active moiety are not affected by the isolation process.

[Ch. 2.VI] If analyses of the quality attributes of the Reference Product’s active substance can be made at the finished product stage, testing of the isolated active substance may not be needed.

The applicant should adopt a suitable and validated approach to derive representative active substance from the Reference Product.

Physicochemical Analysis

[§ 8.2.1] The comparative physicochemical characterization should include the determination of primary and higher order structure and other biophysical properties using appropriate analytical methods (e.g. mass spectrometry, NMR).

The RP and the biosimilar are likely to contain a mixture of post-translationally modified forms, and appropriate efforts should be made to investigate, identify, and quantify these forms.

[Ch. 2.VIII] The physicochemical comparison consists of evaluating physicochemical parameters and the structural identification of product-related substances and impurities, including testing degradation by performing stress and accelerated stability studies.

A physicochemical characterization program should include tests of the composition, physical properties, and higher order structures of the active substance.

If the biosimilar contains post-translationally modified forms, these differences should be analyzed and addressed.

Biological and Immunological Analysis

Biological

[§ 8.2.2] Comparative evaluation with a biological assay complements the physicochemical analyses by confirming the correct higher order structure of the molecule.

Ideally, the biological assay will reflect the understood MoA of the protein and will thus serve as a link to clinical activity.

The use of a relevant biological assay(s) with appropriate precision and accuracy provides an important means of confirming that a significant functional difference does not exist between the biosimilar and the RP.

Immunological

[§ 8.2.3] When immunochemical properties are part of the characterization (e.g., for antibody-based products), the manufacturer should confirm that the biosimilar is comparable to the RP in terms of specificity, affinity, binding kinetics, and Fc functional activity, where relevant.

Biological

[Ch. 2.IX] Comparability studies should include an assessment of the biological properties of the biosimilar and the Reference Product. Different methods should be applied to compare these properties.

The results of biological assays should be expressed in units of activity calibrated against an international or national reference standard. These assays should comply with requirements for biological assays as stated in a pharmacopoeia approved by the Department of Health.

Immunological

Not addressed.

Impurities

[§ 8.2.4] It is recognized that the comparison of the impurity profiles between the biosimilar and the RP will be generally difficult. Nevertheless, process- and product-related impurities should be identified, quantified by state-of-the-art technology, and compared between the biosimilar and the RP. If significant differences are observed in the impurity profiles, their potential impact on efficacy and safety, including immunogenicity, should be evaluated.

[Ch. 2.V] Differences in the impurity profiles of the biosimilar and the Reference Product should be explained on a case-by-case basis. Data from comparability studies should “justify the quality attributes of safety and efficacy.” Because impurity profile differences may affect a biosimilar’s safety and efficacy, the required amount of nonclinical and clinical data may vary accordingly.

[Ch. 2.X] Product-related substances and impurities should be identified and compared, using state-of-the-art technologies.

Process-related impurities may cause differences in product attributes and should be confirmed by appropriate studies, including nonclinical and clinical studies.

Stability Studies

[§ 8.5] Head-to-head accelerated stability studies will be of value in determining the similarity of the products because they can reveal otherwise-hidden properties of a product that warrant additional evaluation. They are also important for identifying the degradation pathways of a protein product.

[Ch. 2.VI] The applicant should address whether the Reference Product’s shelf-life affects the quality profile.

[Ch. 2.VIII] The applicant should test degradation by performing stress and accelerated stability studies.

Specifications

[§ 8.3] Specifications should capture and control important quality attributes known for the RP. Their setting should be based on the experience with the biosimilar and the results of the comparability evaluation, but should not be wider than the range of variability of the RP unless justified.

Specifications should be set as described in established guidelines and monographs, where these exist. Pharmacopoeial monographs may only provide a minimum set of requirements for a particular product, and additional test parameters may be necessary

[Ch. 2.XI] If “the test item of tests to be included in the specifications is product-specific,” the rationale used to establish the proposed range of acceptance criteria should be described.

The acceptance criteria should be established and supported by data from: (1) lots used in nonclinical and clinical studies; (2) lots demonstrating manufacturing consistency; (3) stability studies; (4) product development; and (5) comparability studies evaluating quality, safety, and efficacy.

The test margins should not be wider than the range of variability of that of the Reference Product, unless justified.

General

[§§ 9.1, 9.2] Nonclinical studies should use the final formulation intended for clinical use unless otherwise justified; the nonclinical evaluation encompasses a broad spectrum of PD, PK, and toxicity studies (per ICH S6); the amount of additional nonclinical data for safety and efficacy is dependent on product-specific factors (for example, quality, unknown or poorly understand MoA, significant toxicity, and/or narrow therapeutic index).

[Ch. 3.IV] Nonclinical studies should be designed to detect differences in response, rather than just detecting the response.

Pharmacology

[§ 9.2] In vitro studies: Assays like receptor-binding studies or cell-based assays should normally be conducted to establish comparability of PD activity.

In vivo studies: Animal studies should be designed to maximize information obtained; be conducted in relevant species (shown to possess PD and/or toxicological activity); and employ state-of-the-art technology. In vivo studies may not be needed if highly reliable in vitro assays that reflect clinically relevant PD activity of the RP are available.

[Ch. 3.IV] In vitro studies: Receptor-binding studies or cell-based assays should normally be performed to establish comparability in reactivity and, when comparability cannot be established, the likely causative factors.

In vivo studies: Animal studies should be designed to maximize the information obtained and should be performed in a known species using state-of-the-art technology.

Pharmacokinetics

[§ 9.2] Nonclinical evaluation normally encompasses a broad spectrum of studies, including PK studies. The amount of data is highly dependent on the product and class-related factors.

Not addressed.

Toxicology

[§ 9.2] Comparative repeat-dose toxicity in relevant species (including TK measurements and antibody responses); local tolerance may need to be evaluated depending on the route of administration.

Safety pharmacology, reproductive toxicology, genotoxicity, and carcinogenicity studies are generally not needed unless cause for concern (based on repeat dose toxicity study or local tolerance study, for example).

[Ch. 3.IV] The applicant should conduct at least one repeat dose toxicity study that includes TK measurements (including antibody titres, cross reactivity, and neutralizing capacity). If there are special safety concerns, relevant observations should be included in the study.

The duration of the nonclinical toxicity study should be justified. The study should be long enough to detect differences in toxicity and/or immune responses.

Other routine toxicological studies (e.g., safety pharmacology, reproduction toxicology, mutagenicity, and carcinogenicity) are normally not required, unless the results of the repeat dose studies suggest they should be conducted.

PK and PD

[§ 10] Clinical studies should be designed to demonstrate comparable safety and efficacy of the biosimilar to the RP and therefore need to employ strategies that are sensitive enough to detect relevant differences. The comparability exercise is a stepwise procedure that should begin with PK and PD studies followed by the pivotal clinical trials.

If any relevant differences between the biosimilar and the RP are detected, the reasons need to be explored and justified. If this is not possible, the new product may not qualify as a biosimilar and a full licensing application should be considered.

[Ch. 3.V] Comparative PK studies should be able to detect critical PK parameters to demonstrate clinical comparability between the biosimilar and the Reference Product. Studies should explore the differences in the elimination characteristics of the two products, e.g., clearance rate and elimination half-life.

The cross-over design is not appropriate for therapeutics with a long half-life or for proteins for which formation of anti-drug antibodies is likely.

The acceptance range should be defined and justified prior to conducting the study.

A population where possible differences can best be observed should be tested and PD endpoints should be selected based on their relevance to the biosimilar’s efficacy.

Combined PK/PD studies may be conducted. The dose should be in the steep part of the dose-response curve. Studying more than one dose may help detect PD differences between the products.

Comparative PK/PD studies are sufficient to justify clinical comparability (and clinical efficacy trials are not needed) if the following conditions are met: (1) the Reference Product’s PK data are clearly analyzed; (2) knowledge of the Reference Product’s PD properties is well-developed; (3) descriptions of the therapeutic concentration-response curve are sufficient; and (4) at least one PD marker can be justified as a surrogate marker for efficacy.

A reasonable dose range must be established to demonstrate assay sensitivity. The margins defining comparability of PK/PD parameters must be justified and “have the top priority.”

Efficacy Assessment

[§ 10.1] The PK profile should always be investigated. This is best achieved with single-dose, cross-over studies in a homogenous study population using a dose where the sensitivity to detect differences is largest. Where there are dose and time-dependent pharmacokinetics, it may be necessary to perform a comparative multi-dose study.

The traditional equivalence range is often used. If this range is not met, the biosimilar may still be considered similar with sufficient evidence from other comparisons.

[§ 10.2] PD studies may be advisable prior to efficacy and safety trials if differences of unknown relevance have been detected in PK studies. In many cases, PD parameters are investigated in the context of combined PK/PD studies.

[Ch. 3.V] Comparative clinical trials should be conducted to demonstrate clinical comparability of the two products unless comparative PK/PD studies are sufficient to justify clinical comparability.

Assay sensitivity should be ensured and clinical comparability margins should be pre-specified and justified.

Safety

[§ 10.3] Usually, clinical trials are required to demonstrate similar efficacy. Confirmatory PK/PD may be used in lieu of efficacy trials provided there is sufficient knowledge of the PK/PD profile of the RP, at least one PD marker has a well-established relationship to efficacy, and the relationship between dose/exposure, the relevant PD marker, and response/efficacy of the RP is established.

[§ 10.4] Similar efficacy means similar treatment effects are achieved at the same dosages.

Similar efficacy will usually have to be shown in a controlled, adequately powered, study that is, preferably, double blind. Potential differences between the products should be investigated in a sensitive and well-established clinical model.

[Ch. 3.VI] A license can be issued only after comparing the type, severity, and frequency of common adverse reactions of the biosimilar and the Reference Product.

The application should include a detailed statement about risks.

Immunogenicity

[§ 10.5] Safety data should be obtained in a sufficient number of patients to provide a comparison of type, frequency, and severity of adverse events. Safety data from the efficacy trials may be sufficient for this purpose (or may need to be extended), but in any case additional monitoring is usually necessary after approval.

[Ch. 3.VII] The assessment of immunogenicity requires an appropriate antibody testing strategy, an analysis of the characteristics of immune response, and an evaluation of the correlation between antibodies and PK or PD and of the effect on clinical safety and efficacy. A sufficient amount of data involving a sufficient number of should be obtained to statistically characterize the variability in antibody response. The risk of immunogenicity in different indications should be considered separately.

The applicant should describe the rationale for its proposed antibody-testing strategy, which should involve state-of-the-art methods with appropriate specificity and sensitivity. The screening method should be validated and sensitive enough to detect low titre and low affinity antibodies.

Long-term monitoring of antibodies at pre-determined intervals should be planned. In the case of long-term medication, at least one year of follow-up data is required.

If the biosimilar produces a different immune response than that of the Reference Product, the applicant must conduct further analysis of the characteristics of the antibodies, and also evaluate the possible impact on clinical safety, efficacy, and PK parameters.

Antibody tests should be included in all clinical trials.

Extrapolation of Indications

[§ 10.6] Immunogenicity should always be investigated in humans prior to authorization, because animal data are usually not predictive and because it could affect PK, PD, or safety. Generally, the data from a comparative efficacy trial will be sufficient prior to market authorization, subject to appropriate post-market pharmacovigilance for rare adverse events or where clinically meaningful or serious antibody development has been encountered in the RP or substance class.

In the case of chronic administration, one year of data prior to market authorization is usually appropriate.

[§ 10.6] Antibody assays need to be validated for their purpose. Detected antibodies need to be characterized for their clinical implications with special attention to the possibility of interaction with endogenous protein.

[Ch. 3.I] In certain situations, it is possible to extrapolate a biosimilar’s therapeutic similarity in one indication to other indications of the Reference Product. Extrapolation could be justified by clinical trials, available literature, and the actions and receptors involved in all indications (whether or not the MoA is the same in all indications).

Possible safety concerns for different ethnic groups also should be addressed.

Risk Management Plans

[§ 10.7] Extrapolation to other approved indications of the RP may be possible if all of the following conditions are met: (1) a sensitive clinical test model has been used that is able to detect potential differences between the products; (2) the clinically relevant MoA and/or receptors are the same (or, if the MoA is different or not known, a strong scientific rationale and additional data will be needed); (3) safety and immunogenicity of the biosimilar have been characterized and there are no special safety issues expected with the extrapolated indication; and (4) if the efficacy trial used a non-inferiority study design and demonstrated acceptable safety and efficacy of the biosimilar compared to the RP, the applicant should provide convincing arguments that this finding can be applied to the extrapolated indications.

If these prerequisites for extrapolation of efficacy and safety data of the biosimilar to other indication(s) of the RP are not fulfilled, the manufacturer will need to submit its own clinical data to support the desired indication(s).

[Ch. 3.VI] The applicant should present an RMP in accordance with current regulations and PV guidelines. The RMP should respond to safety warnings identified in nonclinical and clinical trials, as well as address safety issues associated with other products of the same type.

The PV system and procedures should be in place when a marketing approval is granted.

License holders must include “the tolerability report and other relevant information” in their dossiers.

Interchangeability

[§ 11] Data from pre-authorization clinical studies are usually too limited to identify all potential unwanted effects of a biosimilar, and in particular, rare adverse events.

Therefore, further close monitoring of the clinical safety of these products in all approved indications and continued benefit-risk assessment is necessary in the post-market phase.

A safety specification and PV plan are required at the time of submission, describing safety issues for the RP, the class, and/or the biosimilar.

Any special safety monitoring imposed on the RP or product class should be incorporated into the PV plan for the biosimilar, unless there is a compelling justification not to do so.

The regional authority should provide a framework establishing the ability to ensure specific identification of the biosimilar (i.e., traceability). There should be a legal framework adequate to identify any biotherapeutic marketed in its territory that is the subject of adverse event reports.

Not addressed specifically.

[Ch. 1.III] The specific product given to the patient should be clearly identified and subject to PV.

Naming
Not addressed specifically. To be determined by national authorities.

[§ 6, bullet e] Biosimilars “are not generic medicines; and many characteristics associated with [that] authorization process generally do not apply.”

[§ 12] The biosimilar should be clearly identifiable by a unique brand name, and the prescribing information should be as similar as possible to that of the RP except for product-specific aspects such as different excipients.

Note: Naming and interchangeability should be treated as separate issues. WHO has recommended a generic name plus numbering system. Naming, per se, is not about the basic science of interchangeability.

Not addressed.

Labeling

[§ 12.0] A biosimilar should be clearly identifiable by a unique brand name. Where an international non-proprietary name (INN) is defined, it should be stated. The WHO’s policy on INNs should be followed. The provision of a lot number is essential and critical for traceability.

[Note: In July 2014, the WHO issued a proposal for unique biologic identifiers (BQs) that could be added to the INNs of biologics, whether innovative or biosimilar. See INN Working Doc. 14.342 (July 2014).]

Not addressed.

Considerations for Quality by Design

[§ 12] The prescribing information for the biosimilar should be as similar as possible to that of the RP, except for product-specific aspects, such as different excipient(s). This is particularly important for posology and safety-related information, including contraindications, warnings, and adverse events.

If the biosimilar has fewer indications than the RP, the related text in various sections may be omitted unless it is considered important to inform doctors and patients about certain risks (e.g. because of potential off-label use). In such cases it should be clearly stated in the prescribing information that the biosimilar is not indicated for use in the specific indication(s) and the reasons why.

The national regulatory authority may choose to mention the biosimilar nature of the product and the studies that have been performed with the biosimilar, including the specific RP, in the product information.

The national regulatory authority may choose to include instructions for the prescribing physician on how to use biosimilar products.

[Ch. 2.I] The manufacturing and control of biosimilars should take into consideration the biosimilar’s development and relevant up-to-date information about the product and its manufacturing process.

[Ch. 2.IV] The latest information should be taken into account to develop and optimize the manufacturing process and the consequences on product characteristics.

[Ch. 2.VI] The applicant should demonstrate, using state-of-the-art analytical methods, that the biosimilar’s active ingredient is representative of the active ingredient in the Reference Product.

[Ch. 2.VII] The analytical techniques should be state-of-the art. Applicants should demonstrate that the selected analytical methods are able to detect slight differences in quality.

[Ch. 2.X] The product-related substances and impurities should be identified and compared to those of the Reference Product using state-of-the-art technologies.

Footnotes

[1] Source: Biosimilar Regulation and Review System in Taiwan, Chao-Yi (Joyce) Wang Senior Specialist Taiwan FDA, DOH. Regulation and Development Strategy of Biosimilar Products Conference, September 5, 2011. http://www.tgpa.org.tw/EDM/Epaper/%E7%8E%8B%E5%85%86%E5%84%80.pdf

[2] Recent Trend of Pharmaceutical Regulations in Taiwan, Meir-Chyun, Tzou, PhD Director, Division of Medicinal Products, Taiwan Food & Drug Administration, Ministry of Health and Welfare. 10th Annual DIA Meeting, Nov 6-8, 2013.

http://www.fda.gov.tw/upload/133/Content/2014033109035995639.pdf