Tag Archives: similar biological medicinal products

DMA publishes concept paper on bio similars containing proteins

Posted on November 14, 2011 by damienbove| Leave a comment

In the current EMA guideline on similar biological medicinal products containing biotechnology derived proteins as active substances, nonclinical and clinical issues lays down the requirements of such products to determine its similarity to one another. This guidance came into effect in June 2006, however since then several by a similar products have come to the market and the number of guidance is in this area has increased significantly and the regulatory framework is becoming wider.

The EMA considers it necessary to update these guidance and bring together a number of issues into a single document. In order to tackle the complex issues that are arising. And to allow for the WHO guidelines on evaluation of similar biotherapeutic products. And also to be compliant with the Three R principals (replacement, reduction and refinement) with regard to the use of animal experiments.

excerpt from concept paper

full text here

The Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues (EMEA/CHMP/BMWP/42832/2005) lays down the  nonclinical and clinical requirements for a biological medicinal product  claiming to be similar to another one already marketed. This guideline came into effect in June 2006. Since then several biosimilar products
have come into the EU market, the number of scientific advices given by the CHMP on the development of biosimilar products has increased significantly and the regulatory framework is becoming wider, e.g. the draft guideline of the biosimilar monoclonal antibodies is being finalised. .An increasing number of biosimilar products are under development, especially biosimilar monoclonal antibodies. The development of more complex biosimilar medicinal products is challenging, and several issues in the development are under re-evaluation. These include the selection of relevant species for
non-clinical studies, need for clinical equivalence studies and other issues of the design of the pivotal clinical studies, role of biomarkers, amount of immunogenicity data needed, and the possibility to
extrapolate to other indications. The WHO Guidelines on Evaluation of Similar Biotherapeutic Products with detailed recommendations on clinical development were published in October 2009. In addition,
the EMA is emphasizing the need to follow the 3 R principles (replacement, reduction and refinement) with regard to the use of animal experiments. All these factors suggest revising the current guideline.

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EMA Publish Concept Paper on Bio-Similar products containing Active Proteins: Clinical and Non-Clinical

Posted on October 24, 2011 by admin| Leave a comment

EMA Publish Concept Paper on Bio-Similar products containing Active Proteins: Clinical and Non-Clinical

Full Text Here

The Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues (EMEA/CHMP/BMWP/42832/2005) lays down the  nonclinical and clinical requirements for a biological medicinal product claiming to be similar to another one already marketed. This guideline came into effect in June 2006. Since then several biosimilar  products have come into the EU market, the number of scientific advices given by the CHMP on the development of biosimilar products has increased significantly and the regulatory framework is becoming wider, e.g. the draft guideline of the biosimilar monoclonal antibodies is being finalised.

An increasing number of biosimilar products are under development, especially biosimilar monoclonal antibodies. The development of more complex biosimilar medicinal products is challenging, and several issues in the development are under re-evaluation. These include the selection of relevant species for non-clinical studies, need for clinical equivalence studies and other issues of the design of the pivotal clinical studies, role of biomarkers, amount of immunogenicity data needed, and the possibility to extrapolate to other indications. The WHO Guidelines on Evaluation of Similar Biotherapeutic Products with detailed recommendations on clinical development were published in October 2009. In addition, the EMA is emphasizing the need to follow the 3 R principles (replacement, reduction and refinement) with regard to the use of animal experiments. All these factors suggest revising the current guideline.



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Damien Bové is THE Drug Development and Regulatory Consultant (pharmaceutical or biotechnology), I work with my clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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EMA Publish Paper on Revision of Non-Clinical and Clinical Development of Similar Biologicals – Human Insulin

Posted on September 25, 2011 by admin| Leave a comment

EMA Publish Paper on Revision of Non-Clinical and Clinical Development of Similar Biologicals – Human Insulin

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The current Guidance on Similar Medicinal Products containing Recombinant Human Insulin provides recommendations for the development of recombinant soluble (short-acting) human insulin claimed to be similar to a reference product already authorised in the EU. This guideline came into effect in June 2006 but, so far, no biosimilar insulin has been licensed in the EU. Three products applied for by the same Applicant were withdrawn prior to Opinion.

More recently, several EMA scientific advices on the development of biosimilar insulins, particularly insulin analogues, have been requested. Insulin analogues and long-acting human insulin preparations are currently not covered by the above guideline. In addition, different study populations, study designs and insulin doses have been proposed for the pivotal PD study (clamp study). Moreover, the guideline does not appear to be clear on whether the PK study can be combined with the PD study. Questions were raised regarding the most suitable patient population and size of the clinical safety study. It has also been questioned whether non-clinical studies would always be needed in the development of biosimilar insulins.

Although similar considerations and scientific principles may apply to biosimilar insulin analogues and long-acting human insulin preparations as to soluble insulins, some thoughts may need to be given to the sensitivity of the clamp study for detection of potential differences in the duration of action or other summary measures between long-acting insulin formulations due to the flat PK profile of these insulins and high variability in the tail part of the clamp study. In addition, further considerations regarding the study population (patients with type 1 diabetes versus healthy volunteers), study design (e.g. with
versus without basal insulin infusion) and insulin dose in the clamp study could be included. It may be clarified that the comparative PK evaluation is usually expected to be part of the clamp (PD) study. It
could also be clarified that no formal non-inferiority testing for antibody frequency is expected in the safety study and that inclusion of patients with type 1 and type 2 diabetes may be appropriate. Regarding non-clinical requirements, a risk-based approach may be introduced.



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Damien Bové is THE Drug Development and Regulatory Consultant (pharmaceutical or biotechnology), I work with my clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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EMA Publishes Concept Paper on Clinical and Non-Clinical Development of Similar Biological Medicinal Products Containing Heparins

Posted on September 14, 2011 by admin| Leave a comment

EMA Publishes Concept Paper on Clinical and Non-Clinical Development of Similar Biological Medicinal Products Containing Heparins

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The Guideline on Similar Medicinal Products containing Low-Molecular-Weight Heparins (LMWH) lays down the non-clinical and clinical requirements for the development of LMWH claimed to be similar to a
reference product already authorised in the EU. This guideline came into effect in October 2009. So far, no biosimilar LMWH has been licensed in the EU.

LMWHs are complex sugar molecules and difficult to characterise. Structure-activity relationship is not fully elucidated and other mechanisms of action beyond Anti-Xa and Anti-IIa activity may be important for the pharmacological activity. The current CHMP guidance requires a comparative clinical trial demonstrating similar efficacy and safety of the biosimilar versus the reference LMWH in the prevention of venous thromboembolism (VTE) in patients undergoing major orthopaedic surgery. Based on scientific and analytical progress, e.g. in the field of physicochemical characterisation, it can
be discussed if in exceptional cases convincing analytical data can substitute for clinical data, at least for clinical efficacy.

The BMWP suggests discussing the inclusion of considerations about the possibility to modify clinical data requirements in the guideline taking into account the extent and quality of characterisation and the possibility to convincingly ensure similar efficacy and safety (including immunogenicity) of the biosimilar and the reference LMWH by other means. It should be discussed if a reduction in clinical data requirements could, in exceptional cases, be possible.



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Damien Bové is THE Drug Development and Regulatory Consultant (pharmaceutical or biotechnology), I work with my clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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EMA Publish Concept Paper on BioSimilars for Recombinant Human Insulin

Posted on September 8, 2011 by admin| Leave a comment

EMA Publish Concept Paper on BioSimilars for Recombinant Human Insulin

Full Text Here

The current Guidance on Similar Medicinal Products containing Recombinant Human Insulin provides recommendations for the development of recombinant soluble (short-acting) human insulin claimed to
be similar to a reference product already authorised in the EU. This guideline came into effect in June 2006 but, so far, no biosimilar insulin has been licensed in the EU. Three products applied for by the same Applicant were withdrawn prior to Opinion.

More recently, several EMA scientific advices on the development of biosimilar insulins, particularly insulin analogues, have been requested. Insulin analogues and long-acting human insulin preparations are currently not covered by the above guideline. In addition, different study populations, study designs and insulin doses have been proposed for the pivotal PD study (clamp study). Moreover, the guideline does not appear to be clear on whether the PK study can be combined with the PD study. Questions were raised regarding the most suitable patient population and size of the clinical safety study. It has also been questioned whether non-clinical studies would always be needed in the development of biosimilar insulins.

Although similar considerations and scientific principles may apply to biosimilar insulin analogues and long-acting human insulin preparations as to soluble insulins, some thoughts may need to be given to the sensitivity of the clamp study for detection of potential differences in the duration of action or other summary measures between long-acting insulin formulations due to the flat PK profile of these insulins
and high variability in the tail part of the clamp study. In addition, further considerations regarding the study population (patients with type 1 diabetes versus healthy volunteers), study design (e.g. with
versus without basal insulin infusion) and insulin dose in the clamp study could be included. It may be clarified that the comparative PK evaluation is usually expected to be part of the clamp (PD) study. It could also be clarified that no formal non-inferiority testing for antibody frequency is expected in the safety study and that inclusion of patients with type 1 and type 2 diabetes may be appropriate. Regarding non-clinical requirements, a risk-based approach may be introduced.



For Assistance with Development of Bio-Similars Click Here

Damien Bové is THE Drug Development and Regulatory Consultant (pharmaceutical or biotechnology), I work with my clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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EMA Publish Guideline on Bio Similar Monoclonals

Posted on January 31, 2011 by admin| Leave a comment

EMA Publish Guideline on Bio Similar Monoclonals.

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This guideline lays down the non-clinical and clinical requirements for monoclonal antibody (mAb) containing medicinal products claiming to be similar to another one already marketed. The non-clinical section addresses the pharmaco-toxicological requirements and the clinical section the requirements for pharmacokinetic, pharmacodynamic, efficacy and safety studies as well as pharmacovigilance aspects.
As regards non-clinical development, a risk-based approach to evaluate mAb on a case-by-case basis is recommended to decide on the choice and extent of in vitro and in vivo studies. In vitro studies should be conducted first, and a decision then made as to the extent of what, if any, in vivo work will be required. If an in vivo study is deemed necessary, the focus of the study (pharmacokinetics, pharmacodynamics, and/or safety; normally comparative in nature) depends on the need for additional information, and the availability of a relevant animal model. The conduct of large comparative toxicological studies in non-human primates is not recommended. As regards clinical development, a comparative pharmacokinetic study in a sufficiently sensitive and homogeneous study population (healthy volunteers or patients) normally forms an integral part of biosimilar mAb development, usually in a parallel group design due to the long half-life of mAbs and potential interference of immunogenicity. The design of a pharmacokinetic study will depend on various factors, including
55 clinical context, linear versus non-linear pharmacokinetics etc. Pharmacokinetic data can be helpful to extrapolate data on efficacy and safety between different clinical indications of the reference mAb. It may, on a case-by-case basis, be necessary to undertake multidose pharmacokinetic studies in patients, or even to perform pharmacokinetic assessment as part of the clinical study designed to establish similar efficacy and safety. Pharmacokinetic studies can be combined with pharmacodynamic (PD) endpoints, where available. Sponsors should always explore possibilities to study dose concentration-response relationships since this approach, if successful, may provide strong evidence of biosimilarity. Normally, similar clinical efficacy should be demonstrated in adequately powered, randomised, parallel group comparative clinical trial(s), preferably double-blind, normally equivalence trials. To establish biosimilarity, deviations from disease-specific guidelines issued by the CHMP (for example, choice of endpoint, timepoint of analysis of endpoint, nature or dose of concomitant therapy, etc) may be warranted. The focus of the biosimilarity exercise is to demonstrate similar efficacy and safety compared to the reference product, not patient benefit per se, which has already been shown for the reference product. In principle, the most sensitive model and study conditions (pharmacodynamic or clinical) should be used in a homogeneous patient population, since this reduces variability and thus the sample size needed to prove similarity, and can simplify interpretation. In cases where comparative pharmacodynamic studies are claimed to be most suitable to provide the pivotal evidence for similar efficacy, Applicants will have to choose clinically relevant markers and also provide sufficient reassurance of clinical safety, particularly immunogenicity. It may be difficult to define an appropriate equivalence margin for pharmacodynamic equivalence based on clinical relevance, and to provide reassurance that all relevant aspects of a biosimilar mAb as regards similar clinical efficacy are covered. Comparable safety with respect to pharmacologically mediated adverse reactions could also be considered as a measure of biosimilarity. Extrapolation of clinical efficacy and safety data to other indications of the reference mAb, not specifically studied during the clinical development of the biosimilar mAb, is possible based on the results of the overall evidence provided from the biosimilarity exercise and with adequate justification. As regards post-authorisation follow-up, the concept to be proposed by Applicants may have to exceed routine pharmacovigilance, and may have to involve more standardized environments.

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Damien Bové is THE Drug Development and Regulatory Consultant (pharmaceutical or biotechnology), I work with my clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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EMA Publish Guideline on Immunogenicity assessment of Monoclonals for Clinical Use

Posted on January 30, 2011 by admin| Leave a comment

EMA Publish Guideline on Immunogenicity assessment of Monoclonals for Clinical Use

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This guideline addresses issues relating to the unwanted immunogenicity of monoclonal antibodies intended for clinical use. These include the variability of immunogenicity of mAbs and its consequences, prediction and minimizing immunogenicity, the clinical consequences of immunogenicity, assay related problems, assessing neutralizing antibodies induced by monoclonal antibodies and consideration of a risk-based approach for the evaluation of immunogenicity of monoclonal antibodies.

Unwanted immunogenicity can be a significant problem in the treatment of patients with therapeutic biologicals. The importance of the unwanted immunogenicity problem has led to the preparation and adoption of the ‘Guideline on Immunogenicity Assessment of Biotechnology-Derived Therapeutic Proteins’ by the CHMP (adopted April 2008, referred to henceforth as ‘the general guideline’), which in principle is applicable to monoclonal antibodies (mAbs). However, some specific aspects of immunogenicity are exclusively or primarily relevant for mAbs, novel mAb derivatives (eg Fab fragments, scfv, nanobodies, minibodies) or biosimilar mAbs and these are addressed in this guideline. Monoclonal Antibodies (mAbs) comprise a large important class of therapeutic biologicals. The range of clinical indications with potential for treatment with mAbs is very wide. Many mAb products are known to be associated with unwanted immunogenicity and in some cases the immunogenicity causes impaired clinical responses or rarely serious adverse reactions which require clinical intervention. The wide range of mAbs in development, and approved for different clinical indications precludes specific guidelines that are pertinent to all situations. This guideline addresses the major quality and clinical aspects that are important to consider in order to adequately address the problems with detection of and risk related to the development of an immune response to the particular mAb in the particular clinical indication sought.

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Damien Bové is THE Drug Development and Regulatory Consultant (pharmaceutical or biotechnology), I work with my clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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EMA Publish Guideline on Biological Similar Monoclonal Antibodies

Posted on December 8, 2010 by admin| Leave a comment

EMA Publish Guideline on Biological Similar Monoclonal Antibodies.

Full Text Here

This guideline lays down the non-clinical and clinical requirements for monoclonal antibody (mAb) containing medicinal products claiming to be similar to another one already marketed. The non-clinical section addresses the pharmaco-toxicological requirements and the clinical section the requirements for pharmacokinetic, pharmacodynamic, efficacy and safety studies as well as pharmacovigilance aspects.

As regards non-clinical development, a risk-based approach to evaluate mAb on a case-by-case basis is recommended to decide on the choice and extent of in vitro and in vivo studies. In vitro studies should be conducted first, and a decision then made as to the extent of what, if any, in vivo work will be required. If an in vivo study is deemed necessary, the focus of the study (pharmacokinetics, pharmacodynamics, and/or safety; normally comparative in nature) depends on the need for additional information, and the availability of a relevant animal model. The conduct of large comparative toxicological studies in non-human primates is not recommended. As regards clinical development, a comparative pharmacokinetic study in a sufficiently sensitive and homogeneous study population (healthy volunteers or patients) normally forms an integral part of biosimilar mAb development, usually in a parallel group design due to the long half-life of mAbs and potential interference of immunogenicity. The design of a pharmacokinetic study will depend on various factors, including clinical context, linear versus non-linear pharmacokinetics etc. Pharmacokinetic data can be helpful to extrapolate data on efficacy and safety between different clinical indications of the reference mAb. It may, on a case-by-case basis, be necessary to undertake multidose pharmacokinetic studies in patients, or even to perform pharmacokinetic assessment as part of the clinical study designed to establish similar efficacy and safety. Pharmacokinetic studies can be combined with pharmacodynamic (PD) endpoints, where available. Sponsors should always explore possibilities to study dose concentration-response relationships since this approach, if successful, may provide strong evidence of biosimilarity. Normally, similar clinical efficacy should be demonstrated in adequately powered, randomised, parallel group comparative clinical trial(s), preferably double-blind, normally equivalence trials. To establish biosimilarity, deviations from disease-specific guidelines issued by the CHMP (for example, choice of endpoint, timepoint of analysis of endpoint, nature or dose of concomitant therapy, etc) may be warranted. The focus of the biosimilarity exercise is to demonstrate similar efficacy and safety compared to the reference product, not patient benefit per se, which has already been shown for the reference product. In principle, the most sensitive model and study conditions (pharmacodynamic or clinical) should be used in a homogeneous patient population, since this reduces variability and thus the sample size needed to prove similarity, and can simplify interpretation. In cases where comparative pharmacodynamic studies are claimed to be most suitable to provide the pivotal evidence for similar efficacy, Applicants will have to choose clinically relevant markers and also provide sufficient reassurance of clinical safety, particularly immunogenicity. It may be difficult to define an appropriate equivalence margin for pharmacodynamic equivalence based on clinical relevance, and to provide reassurance that all relevant aspects of a biosimilar mAb as regards similar clinical efficacy are covered. Comparable safety with respect to pharmacologically mediated adverse reactions could also be considered as a measure of biosimilarity. Extrapolation of clinical efficacy and safety data to other indications of the reference mAb, not specifically studied during the clinical development of the biosimilar mAb, is possible based on the results of the overall evidence provided from the biosimilarity exercise and with adequate justification. As regards post-authorisation follow-up, the concept to be proposed by Applicants may have to exceed routine pharmacovigilance, and may have to involve more standardized environments.

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Damien Bové is THE Drug Development and Regulatory Consultant (pharmaceutical or biotechnology), I work with my clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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EMA Publish Guideline on Immunogenicity Assessment of Monoclonals

Posted on December 7, 2010 by admin| Leave a comment

EMA Publish Guideline on Immunogenicity Assessment of Monoclonals

Full Text Here

This guideline addresses issues relating to the unwanted immunogenicity of monoclonal antibodies intended for clinical use. These include the variability of immunogenicity of mAbs and its consequences, prediction and minimizing immunogenicity, the clinical consequences of immunogenicity, assay related problems, assessing neutralizing antibodies induced by monoclonal antibodies and consideration of a risk-based approach for the evaluation of immunogenicity of monoclonal antibodies.

Unwanted immunogenicity can be a significant problem in the treatment of patients with therapeutic biologicals. The importance of the unwanted immunogenicity problem has led to the preparation and adoption of the ‘Guideline on Immunogenicity Assessment of Biotechnology-Derived Therapeutic Proteins’ by the CHMP (adopted April 2008, referred to henceforth as ‘the general guideline’), which in principle is applicable to monoclonal antibodies (mAbs). However, some specific aspects of immunogenicity are exclusively or primarily relevant for mAbs, novel mAb derivatives (eg Fab fragments, scfv, nanobodies, minibodies) or biosimilar mAbs and these are addressed in this guideline. Monoclonal Antibodies (mAbs) comprise a large important class of therapeutic biologicals. The range of clinical indications with potential for treatment with mAbs is very wide. Many mAb products are known to be associated with unwanted immunogenicity and in some cases the immunogenicity causes impaired clinical responses or rarely serious adverse reactions which require clinical intervention. The wide range of mAbs in development, and approved for different clinical indications precludes specific guidelines that are pertinent to all situations. This guideline addresses the major quality and clinical aspects that are important to consider in order to adequately address the problems with detection of and risk related to the development of an immune response to the particular mAb in the particular clinical indication sought.

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Damien Bové is THE Drug Development and Regulatory Consultant (pharmaceutical or biotechnology), I work with my clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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Drug Regulators, EMA (EMEA), Publish Draft Concept Paper on Similar Biological Medicinal Products Containing Recombinant Follicle Stimulating Hormone

Posted on May 10, 2010 by admin| Leave a comment

Drug Regulators, EMA (EMEA), Publish Draft Concept Paper on Similar Biological Medicinal Products Containing Recombinant Follicle Stimulating Hormone.

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Follicle stimulating hormone (FSH) is a pituitary glycoprotein hormone that plays a key role in regulating reproductive function in both males and females. FSH is a heterodimeric hormone composed of two linked subunits. The alpha subunit (92 amino acids) is common to other glycoprotein hormones whereas the beta subunit (111 amino acids) is specific. Recombinant human FSH (rhFSH) is used in fertilization medicine for women, and for men to induce and maintain spermatogenesis. The guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues (EMEA/CPMP/42832/05) lays down the general requirements for demonstration of the similar nature of two biological products with respect to safety and efficacy. A product class-specific guidance will lay down specific requirements for the demonstration of comparability of rhFSH-containing medicinal products with respect to safety and efficacy.
This guideline should be read in conjunction with the requirements laid down in the EU Pharmaceutical legislation and other relevant CHMP guidelines.

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Damien Bové is THE Drug Development and Regulatory Consultant (pharmaceutical or biotechnology), I work with my clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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ida consultants freestrategyconsultation 515x64 Drug Regulators, EMA (EMEA), Publish Draft Concept Paper on Similar Biological Medicinal Products Containing Recombinant Follicle Stimulating Hormone

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“Please note that the pages on this website are designed to provide you with general information only. We make no warranties, representations or undertakings about any of its content. This includes the completeness, accuracy and fitness for any particular purpose, or the content of any third party site referred to or accessed through it. You are personally responsible for ensuring that the information is correct and we will not be held liable or accountable for any mistakes that occur.”

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Drug Regulators, EMEA, Publish Concept Paper on the Development of a Guidance on Similar Biological Medicinal Products Containing Monoclonal Antibodies

Posted on December 27, 2009 by admin| Leave a comment

Drug Regulators, EMEA, Publish Concept Paper on the Development of a Guidance on Similar Biological Medicinal Products Containing Monoclonal Antibodies

Full Text Here

Monoclonal Antibodies (mAbs) comprise a large important class of therapeutic biologicals. Different mAb products share some properties, e.g. on a functional level, but differ in aspects like the mechanism of action. The complexity of mAbs is a challenge for the development of new mAb products that are claimed to be similar to marketed mAbs. Nevertheless, such mAbs are being developed, and CHMP has given scientific advice for the development of some individual products. This guideline lays down the non-clinical and clinical requirements for monoclonal antibody-containing medicinal products claiming to be similar to another one already marketed, i.e. similar biological medicinal products (biosimilars). It may also include a chapter on quality aspects more pertinent to biosimilar monoclonal antibodies, should BWP/BMWP consider it necessary. The non-clinical section addresses the pharmaco-toxicological assessment. The clinical section addresses the requirements for pharmacokinetic, pharmacodynamic, efficacy and safety studies as well as the risk management plan.

Guidance for development of biosimilars is already available, including class-specific guidance. With monoclonal antibodies, a next step is taken towards more complex and large molecules. Whilst available guidances (Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Quality Issues, CHMP/49348/05; Production and Quality Control of Monoclonal Antibodies and Related Substances, CHMP/BWP/157653/07) appear to provide sufficient guidance on quality of biosimilar mAbs, there are several issues pertinent to non-clinical and clinical development that are not sufficiently covered by current guidances. There are several areas of increased complexity as regards design of a biosimilar development programme in these fields, which require careful consideration and exploration of further science-based approaches.
The guideline has in its main focus monoclonal antibodies, but principles may also be applicable to related proteins like, for example, fusion proteins.

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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ida consultants freestrategyconsultation 515x64 Drug Regulators, EMEA, Publish Concept Paper on the Development of a Guidance on Similar Biological Medicinal Products Containing Monoclonal Antibodies

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“Please note that the pages on this website are designed to provide you with general information only. We make no warranties, representations or undertakings about any of its content. This includes the completeness, accuracy and fitness for any particular purpose, or the content of any third party site referred to or accessed through it. You are personally responsible for ensuring that the information is correct and we will not be held liable or accountable for any mistakes that occur.”

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Drug Regulators Publish Draft Guidance on Biosimilars for Recombinant Erthropoietins

Posted on October 27, 2009 by admin| Leave a comment

Drug Regulators, EMEA, Publish Draft Guidance on the Development of Biosimilars for Recombinant Erthropoietins

Full Text Here

This guideline lays down the non-clinical and clinical requirements for erythropoietin containing medicinal products claiming to be similar to another one already marketed. The non-clinical section addresses the pharmaco-toxicological assessment and the clinical section the requirements for pharmacokinetic, pharmacodynamic, efficacy and safety studies as well as the risk management plan. Criteria for extrapolation of clinical data to other indications approved for the reference medicinal product are discussed.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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ida consultants freestrategyconsultation 515x64 Drug Regulators Publish Draft Guidance on Biosimilars for Recombinant Erthropoietins

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Drug Regulators Publish Draft Guidance on Development of Similar Recombinant Erythroproetins Containing Prodcuts

Posted on October 20, 2009 by admin| Leave a comment

Drug Regulators EMEA publish Guidance on the Development of Similar Biological Products Containing Erythropoietins.

Full Guidance Here.

This guideline lays down the non-clinical and clinical requirements for erythropoietin containing medicinal products claiming to be similar to another one already marketed. The non-clinical section addresses the pharmaco-toxicological assessment and the clinical section the requirements for pharmacokinetic, pharmacodynamic, efficacy and safety studies as well as the risk management plan. Criteria for extrapolation of clinical data to other indications approved for the reference medicinal product are discussed.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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ida consultants freestrategyconsultation 515x64 Drug Regulators Publish Draft Guidance on Development of Similar Recombinant Erythroproetins Containing Prodcuts

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Drug Regulators Publish Reflection Paper – Development of Similar Interferon Alfa

Posted on July 17, 2009 by admin| Leave a comment

The Drug Regulator, EMEA, has published Guidance on developing Generic Interferon Alfa

The EMEA, published a reflection paper on the Non-Clinical and Clinical Development of Similar Medicinal Products Containing Recombinant Interferon Alfa.  in 2007, and has re-published the document on their website again.

This reflection paper lays down considerations on the non-clinical and clinical development of recombinant Interferon alfa-containing medicinal products claiming to be similar to another such product already authorised. Human interferon-alfa 2a or 2b are well-known and characterized proteins consisting of 165 amino acids. The non-glycosylated protein has a molecular weight of approx. 19,240 D. It contains two disulfide bonds, one between the cysteine residues 1 and 98, and the other between the cysteine residues 29 and 138. The sequence contains potential O-glycosylation sites. Physico-chemical and biological methods are available for characterisation of the proteins.

Recombinant Interferon Alfa 2a or 2b is approved in a wide variety of conditions such as viral hepatitis B and C, leukaemia, lymphoma, renal cell carcinoma and multiple myeloma. The sub-types Interferons alfa 2a and 2b have different clinical uses. IFN-alfa is used alone or in combination. Interferon alfa may have several pharmacodynamic effects. The relative importance of these effects in the different therapeutic indications is unknown. In general, interferon-alfa 2a or 2b use in oncology indications has reduced considerably and been superseded by other treatments.

Scope

This product specific reflection paper presents the current view of the CHMP on the non-clinical and clinical data for demonstration of comparability of two recombinant, on-pegylated, Interferon alfa containing medicinal products and should be read in conjunction with the requirements laid down in the EU Pharmaceutical legislation and other relevant CHMP guidelines (see References).

Non-Clinical Studies

Before initiating clinical development, non-clinical studies should be performed. These studies would be comparative in nature and designed to detect differences in the pharmaco-toxicological response between the similar Interferon alfa and the reference Interferon alfa and not just assess the response per se. The approach taken will need to be fully justified in the non-clinical overview.

Pharmacodynamics Studies

In order to compare differences in biological activity between the similar and the reference medicinal product, data from a number of comparative bioassays could be provided.

To support the comparability exercise for the sought clinical indications, the pharmacodynamic activity of the similar and the reference medicinal product could be quantitatively compared in an appropriate pharmacodynamic animal model, a suitable animal tumour model OR a suitable animal antiviral model.

Toxicological Studies

Data from at least one repeat dose toxicity study in a relevant species should be considered (for example, human Interferon alfa may show activity in the Syrian golden hamster). The study duration should be at least 4 weeks. Data on local tolerance in at least one species should be provided in accordance with the “Note for guidance on non-clinical local tolerance testing of medicinal products” (CPMP/SWP/2145/00).

Clinical Studies

Pharmacokinetic Studies

The pharmacokinetic properties of the similar and the reference medicinal product could be compared in single dose crossover studies using subcutaneous and intravenous administration in healthy volunteers. The recommended primary pharmacokinetic parameter is AUC and the secondary parameters are Cmax and T1/2 or CL/F.

Pharmacodynamic Studies

There are a number of PD markers, such as β2 microglobulin, neopterin and serum 2´, 5´-oligoadenylate synthetase activity, which are relevant to the interaction between Interferon -alfa and the immune system. The selected doses should be in the linear ascending part of the dose-response curve. Whereas the relative importance of these effects in the different therapeutic indications is unknown a comprehensive comparative evaluation of such markers following administration of test and reference products could provide useful supporting data.

Efficacy

Patient Population

The mechanism of action of interferon comprises of several different unrelated effects. Demonstration of similar efficacy between test and reference products is required. This could be performed in treatment-naïve patients with chronic hepatitis C (HCV) as delineated by the indication for the reference product. Other patient population(s) might be studied depending on the indications desired.

Study Design and Duration

A randomised, parallel group comparison against the reference product over at least 48 weeks is recommended. If possible, the study should be double-blind at least until data to complete the primary analysis have been generated. If this is not feasible, justification should be provided and efforts to reduce/eliminate bias should be clearly identified in the protocol.

Endpoints

Primary: Virologic response as measured by the proportion of patients with undetectable levels of HCV RNA by quantitative PCR at week 12. The assay used to measure HCV RNA and the cut-off applied should be justified. A 2-log decrease in viral load may be a co-primary endpoint. Secondary: virologic response at week 4 and end-of-treatment; sustained virologic response (24 weeks after completion of treatment); change in liver biochemistry including transaminase levels and morbidity.

Safety

Safety data should be collected from patients after repeated dosing in a comparative clinical trial over the treatment period plus 24 weeks of follow-up. The number of patients should be sufficient for the comparative evaluation of the adverse effect profile. Laboratory abnormalities for immune mediated disorders should be included. The safety profile should be similar to the reference products for the common adverse events (such as flu-like illness, alopecia, myalgia, leucopenia, anaemia and thrombocytopenia).

Immunogenicity

Comparative immunogenicity data (antibody levels) should be presented during the treatment period plus 24 weeks of follow-up according to the principles described in the “Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: nonclinical and clinical issues” (EMEA/CPMP/42832/05/) and the “Guideline on immunogenicity assessment of biotechnology-derived therapeutic proteins” (EMEA/CHMP/BMWP/14327/2006).

Extrapolation of Evidence

In principle extrapolation from one therapeutic indication to another is appropriate where the mechanism of action and/or the receptor are known to be the same as the condition(s) for which similarity in efficacy has been established. If indication(s) are sought, where the mechanism of action is not known to be the same, such extrapolation
should be adequately justified.

Pharamcovigilance Plans

Within the authorisation procedure the applicant should present a risk management programme/pharmacovigilance plan in accordance with current EU legislation and pharmacovigilance guidelines. Attention should be paid to immunogenicity and potentially rare and/or delayed serious adverse events, especially in patients undergoing chronic administration. Safety should be collected from patients representing all approved indications.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

ida consultants freestrategyconsultation 515x64 Drug Regulators Publish Reflection Paper Development of Similar Interferon Alfa

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This guideline ap
recombinant vaccines for the prevention and treatment of infectious disease, and provides guidance on quality, non-clinical and clinical aspects.

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