CBPE

Promoting science based, medically appropriate policies for biologic medicines

Number of Biosimilars Available

6

Country Spotlight: South Korea

The Biopharmaceuticals and Herbal Medicines Bureau of the Ministry of Food and Drug Safety (MFDS) is responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the South Korea.

Biosimilars Available

As of April 2016, there are 6 biosimilars available in South Korea[1][2]

A growth hormone used to treat patients with growth deficiencies (somatropin)
Two medicines used to treat Rheumatoid Arthritis, Psoriatic Arthritis, Psoriasis, and Ankylosing Spondylitis (entanercept)
Two medicines used to treat Rheumatoid Arthritis, Psoriatic Arthritis, Psoriasis, and Ankylosing Spondylitis, Ulcerative colitis and Crohn’s disease (infliximab)
A medicine used to treat patients with HER2+ breast cancer and Advanced (metastatic) stomach cancer

Score Overview

South Korea is Partially Compliant.

The overall score for South Korea is 3.13/5. This means the South Korean guidance is partially or fully compliant with WHO in many areas, exceeds in a few areas, and in some areas is not compliant with the WHO standards.

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

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

Gaps

Gap 1

Reference Product:

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

Gap 2

Formulation:

This topic is not addressed by the MFDS guidelines.

Gap 3

Dosage Form and Strength:

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

Gap 4

Nonclinical, pharmacokinetics:

This topic is not addressed by the MFDS guidelines.

Gap 5

Clinical, General Considerations:

The MFDS guidelines imply that clinical evaluations are not always required. Additionally, 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 6

Pharmacovigilance and Risk Management Plans:

This topic is not addressed by the MFDS guidelines.

Gap 7

Naming:

This topic is not addressed by the MFDS guidelines.

Gap 8

Labeling:

This topic is not addressed by the MFDS guidelines.

Overall country score as compared to peers

History of Policy

The MFDS issued a Guideline on Evaluation of Biosimilar Products regarding the regulation of biosimilar products in July 2009, which became effective in 2010. This was updated in 2014. The Korean biosimilar guideline is based on the European, Japanese and WHO guidelines.

Policy Guidelines

Overarching Guidelines

Guideline on evaluation of biosimilar products

This guideline outlines general principles and the non-clinical and clinical requirements for demonstrating biosimilarity
First issued 2009 (effective 2010); Most recent update 2014

Questions & answers regarding biosimilar guideline

Provides answers to frequently asked questions for those developing biosimilars
First issued 2009; Most recent update: unknown

Medicine Specific Guidances

These guidelines describe the non-clinical and clinical requirements for demonstrating biosimilarity for specific medicines

Analytical methods for characterization of biosimilars (erythropoietin)

Date of issuance not publicly available

Guideline on non-clinical and clinical evaluation of erythropoietin and somatropin biosimilar products

First issued 2011; Most recent update 2011

Guideline on non-clinical and clinical evaluation of G-CSF biosimilar products

First issued 2012; Most recent update 2012

Guideline on non-clinical and clinical evaluation of monoclonal antibody biosimilar products

First issued 2013; Most recent update 2013

Guideline on non-clinical and clinical evaluation of erythropoietin and somatropin biosimilar products

First issued 2011; Most recent update 2011

Guideline on non-clinical and clinical evaluation of G-CSF biosimilar products

First issued 2012; Most recent update 2012

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.

[§ 2] Biological products containing well-characterized proteins and for which comparability can be demonstrated through characterization, nonclinical studies, and clinical studies.

Applies only to approval of products that are comparable to Reference Products in terms of quality, safety, and efficacy. Excludes the authorization of a product on the basis of clinical equivalence.

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.

"[§ 4] A biosimilar is a biological product that is comparable to an already marketed Reference Product in terms of quality, safety, and efficacy.

“Comparability” is a scientific comparison of a biosimilar with an Reference Product with the goal of establishing that no detectable differences exist in terms of quality, safety, and efficacy.

[6.2] Comparability should be determined by considering comprehensively the quality, nonclinical, and clinical data.

The biosimilar’s quality attributes are not expected to be identical to those of the Reference Product. Information demonstrating that differences will not affect safety and efficacy should be provided.

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.

[§ 3] The reference product is a drug already authorized by a regulatory authority on the basis of a full dossier.

[§ 5] The reference product should be authorized in Korea. If an reference product authorized in Korea is not commercially available or there is another justifiable reason, a product authorized abroad that is the same as the product authorized in Korea (including the products use the same manufacturing site and process) may serve as the reference product. There should be sufficient data concerning the safety and efficacy of the reference product.

[§§ 5, 7] The same reference product should be used throughout the comparability exercise to test quality, safety, and efficacy.

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.

Not addressed.

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.

[§ 5] Dosage form and dose must be the same as that of the Reference Product.

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.

[§ 7] Clinical evaluations are usually required to establish the safety and efficacy of a biosimilar,

[§ 8] Pivotal clinical data should be generated using product derived from the final manufacturing process. If the product studied clinically was manufactured using a non-final manufacturing process, the differences should be justified and additional data may be required.

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.

[§ 6.2] If the applicant isolates the Reference Product’s active ingredient, the applicant should provide information demonstrating that: (1) the sample preparation is suitable; and (2) the isolated active ingredient’s characteristics are not changed.

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.

[§ 6.2.1] The physicochemical characterization should include the determination of the composition, physicochemical properties, and primary and higher order structures of the active ingredient. If process-related and product-related impurities are generated, or if degradation is identified through stress and accelerated stability studies, the impurities and/or degradation should be evaluated.

The biosimilar may contain a mixture of post-translationally modified forms. Appropriate efforts should be made to investigate and identify such forms.

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

[§ 6.2.1] A set of relevant functional assays designed to evaluate the range of activities of a product with multiple biological activities should be developed and employed.

Biological assays can: (1) determine the protein’s MoA and, in some cases, be linked to clinical activity; (2) verify whether changes to quality are caused by a product-related substance with biological activity or an impurity without biological activity; and (3) verify the protein’s higher order structure.

A biological assay may not be able to detect differences between the biosimilar and Reference Product due to considerable variability in the assay.

Immunological

If immunological properties are part of the characterization studies (e.g., for antibodies or antibody-based products), the applicant should compare the biosimilar’s specificity, affinity, binding activity, and Fc function with that of the Reference Product. Results from immunogenicity studies in animals should also be considered.

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.

[§ 6.2.1] The drug substance’s and drug product’s purity and impurity profiles should be assessed qualitatively and quantitatively using a combination of analytical procedures. Accelerated conditions, conditions that may cause degradation, and potential post-translational modifications should be considered in evaluating the impurity profiles.

Product-related impurities should be identified and compared to those of the Reference Product using state-of-the-art technology and more than one analytical technology (if possible).

State-of-the-art technology should verify the effect of the biosimilar’s process-related impurities (which may be quantitatively and qualitatively different from that of the Reference Product).

In-process acceptance and action limits should be established to assure the quality of the drug substance and drug product.

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.

[§ 6.5] A long-term stability study should establish the drug product’s shelf-life and storage conditions.

A comparative stability study with the Reference Product is not necessarily required, but accelerated and stress stability studies to establish impurity profiles at the drug substance and drug products levels are often useful in determining comparability.

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

[§ 6.3] Specifications should be established for routine quality controls. Product-specific tests should be selected to ensure quality.

Acceptance criteria should be based on data obtained from representative lots. Justifications for the methods used and the proposed range should be provided.

[§ 6.4] Analytical procedures included in the specifications should be appropriately validated in accordance with the “Regulation on Review and Authorization of Biological Products” and the “Guidelines on Specifications of Biotechnological/Biological Products.”

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).

[§ 7] Nonclinical evaluations are usually required to establish the safety and efficacy of a biosimilar,

Nonclinical studies should be conducted with the final formulation intended for clinical use. If this is not possible, minimal modifications to the formulation may be made within a justifiable range. Any differences in dosage form, dose, and route of administration between the Reference Product and biosimilar studied nonclinically should be justified.

Nonclinical studies should be designed to demonstrate the comparability of the two products.

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.

[§ 7] In vivo and in vitro studies should be tailored to the specific product, on a case-by-case basis.

In vitro studies: Assays such as receptor-binding studies or cell-based assays should normally be undertaken to establish the comparability of the biosimilar’s biological/PD activity with that of the Reference Product.

In vivo studies: Animal studies should be performed in species known to be relevant to maximize the information obtained (e.g., a species in which the Reference Product has shown to possess PD and/or toxicological activity) and should employ state-of-the-art technology.

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).

[§ 7] The applicant should consider conducting a nonclinical toxicity study (at least one repeat dose toxicity study in a relevant species, including TK measurements), a local tolerance study, and other toxicological studies.

The TK measurements for a repeat dose toxicity study in the relevant species should include determination and characterization of antibody responses. The duration of the studies should be long enough to allow detection of potential differences between the products in terms of toxicity and antibody responses.

A comparative repeat dose toxicity study is useful in predicting any unexpected toxicity during clinical use of the biosimilar.

Depending on the biosimilar’s route of administration, a local tolerance study may be performed. It can be performed as part of the repeat dose toxicity study, if appropriate.

If the biosimilar’s comparability to the Reference Product is verified through the quality evaluation, toxicological studies (e.g., safety pharmacology, reproductive toxicology, genotoxicity, and carcinogenicity studies) are generally not required, unless they are triggered by the results of the repeat dose toxicity study and/or by other known toxicological properties of the Reference Product.

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.

[§ 8.1] The biosimilar’s PK profile should always be investigated. PK testing should generally be performed for all proposed routes of administration using doses within the dosing range recommended for the Reference Product.

Ideally, single-dose PK studies should be performed in a sensitive and homogenous population using a dose most sensitive to detecting differences between the two products.

The study design should be justified. A cross-over design may not be appropriate for products with long half-lives or for proteins for which formation of anti-drug antibodies is likely. If a cross-over design is adopted, the applicant must demonstrate that half-life, antibody formation, and other characteristics do not affect the PK profile.

The PK comparison should include absorption/bioavailability as well as elimination characteristics.

Acceptance criteria for the demonstration of similar PK between the two products should be pre-defined and appropriately justified.

If a biosimilar’s active ingredient is an endogenous protein with measurable concentration, its concentration-time profile may be substantially affected. The approach to minimize the endogenous protein’s influence on the results should be described and justified.

[§ 8.2] PD studies may be performed in combination with PK studies. PD parameters should be selected on the basis of their relevance to demonstrating clinical efficacy.

In comparative PD studies, PD effects should be investigated in a suitable patient population using one dose within the steep part of the dose-response curve.

[§ 8.4] Confirmatory PK/PD studies may be appropriate (and clinical efficacy studies may not be needed) in the following cases: (1) if the Reference Product’s PK and PD properties are well-characterized; (2) if at least one PD marker is an accepted surrogate marker for efficacy; or (3) if the relationship between dose/exposure, the relevant PD marker(s), and the Reference Product’s response/efficacy is well-established.

The study population and dosage should be sensitive to detecting potential differences between the two products. The acceptance ranges for demonstrating comparability should be predefined and appropriately justified.

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.

[§ 8] An efficacy equivalence trial (adequately powered, randomized, and parallel group) should be conducted. If confirmatory PK/PD data demonstrate comparability, however, the applicant may omit a clinical efficacy study.

Ideally, clinical studies should be double-blinded or at least observer-blinded. The equivalence margin should be predefined and appropriately justified. Potential efficacy differences between the biosimilar and the Reference Product should be investigated in a sensitive and well-established model.

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.

[§ 8.5] The type, frequency, and severity of adverse reactions observed clinically with the biosimilar should be compared with safety data for the Reference Product.

Safety data obtained from clinical trials are usually sufficient for product authorization, but further close monitoring of the biosimilar’s safety is usually necessary post-market.

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.

[§ 8.6] The biosimilar’s immunogenicity always should be investigated in humans because animal data usually are not predictive. All patients in the clinical studies should be evaluated for immunogenicity.

The two products should be compared with respect to the frequency and type of antibodies induced as well as the possible clinical consequences of an immune response.

The antibody-testing strategy should be described in detail. A screening assay with sufficient sensitivity should be used for antibody detection and a neutralization assay should be available for further characterization of antibodies. Possible interference of the circulating antigen with the antibody assay(s) should be taken into account.

Potential clinical implications regarding safety, efficacy, and PK should be evaluated if the amount of antibodies induced by the biosimilar is greater than that of the Reference Product.

The applicant should study immunogenicity for a period of time sufficient to evaluate antibody incidence, antibody persistence, the development of antibody titers over time, potential changes in the character of the antibody response, and possible clinical implications.

Further characterization of the biosimilar’s immunogenicity profile may be necessary post-market, particularly if rare antibody-related serious adverse events may occur that are not likely to be detected premarket.

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.

[§ 3] If the applicant demonstrates that efficacy and safety of the biosimilar is similar to that of the Reference Product, extrapolation of these data to the Reference Product’s other indications “for which a postmarketing survey was completed” may be possible if all of the following are satisfied: (1) a sensitive clinical test model was used that is able to detect potential differences between the two products; (2) the clinically relevant MoA and/or involved receptor(s) are the same; and (3) safety and immunogenicity have been sufficiently characterized.

[§ 8] If an applicant intends to extrapolate efficacy data to support approval of other indications of the Reference Product, an equivalence clinical study design is more desirable than a noninferiority design.

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).

Not addressed.

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.

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.

[§ 6.1] The manufacturing process should be reasonable and justifiable, taking into account modern science, technology, and the product’s nature.

[§§ 6.2.1, 6.4] Extensive, state-of-the-art characterization studies should be performed to show that the biosimilar’s quality is comparable to that of the Reference Product.

[§ 6.4] Analytical procedures used in characterization studies should be scientifically sound and capable of producing reliable results. The procedures do not necessarily need to be validated.

Footnotes

[1] Source: http://www.biosimilarz.com/?page_id=242

[2] Source: http://www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-South-Korea

[3] Source: http://www.gabionline.net/Guidelines/South-Korean-guidelines-for-biosimilars

[4] Biosimilar regulation in Republic of Korea and Asia-Pacific Economic Cooperation (APEC) developments, Ministry of Food and Drug Safety, Jeewon Joung. April 2014 http://www.gpaconferences.com/presentations/bios14/5_Jeewon_Young.pdf