Quality and safety considerations for recombinant biological medicines: A regulatory perspective

Barnes, Henry J.; Ragnarsson, Gert; Alván, Gunnar

doi:10.3233/jrs-2009-0454

Cited by 8 publications

(8 citation statements)

References 32 publications

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“…Manufacturers of originator products use proprietary growth and purification conditions and specially adapted cell lines for their processes; therefore, knowledge of the protein sequence or cells used by the originator is not sufficient for a biosimilar sponsor to produce the same biologic product. Differences in structure between proposed biosimilar and reference product need to be minimized because even subtle differences can potentially affect PK, efficacy, safety, and immunogenicity [ 16 – 18 ].…”

Section: Development Of Biosimilarsmentioning

confidence: 99%

Developing the Totality of Evidence for Biosimilars: Regulatory Considerations and Building Confidence for the Healthcare Community

et al. 2017

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Biosimilars are highly similar versions of approved branded biologics. Unlike generics, they are not exact replicas of reference products. Minor differences between biosimilars and reference products in some aspects are expected; likewise, biosimilar products will differ from each other. The objective of this review is to discuss the challenges associated with the development and approval of biosimilar products that are unique because of their complex structure and specialized manufacturing processes, which can impact not only efficacy but also immunogenicity and safety. Regulatory guidelines recommend a totality-of-evidence approach focused on stepwise development that involves demonstration of structural similarity and functional equivalence. Structural and functional characteristics of the proposed biosimilar are compared with the reference product; similarity of these functions forms the foundation of the biosimilar development program, including potential animal studies, a human pharmacokinetics/pharmacodynamics equivalence study, and a clinical study to confirm similar efficacy, safety, and immunogenicity. The clinical study should be performed in a sensitive population using appropriate endpoints to allow detection of any clinically meaningful differences between the biosimilar and the reference product if such differences exist. In conclusion, development of biosimilars is focused on the minimization of potential differences between the proposed biosimilar and reference product and the establishment of a robust manufacturing process to consistently produce a high-quality biosimilar product.

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Section: Development Of Biosimilarsmentioning

confidence: 99%

Developing the Totality of Evidence for Biosimilars: Regulatory Considerations and Building Confidence for the Healthcare Community

et al. 2017

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“…These minor differences between a proposed biosimilar and the reference product can influence the pharmacologic profile, efficacy, safety and immunogenicity and therefore must be carefully identified and quantified at the outset. [11][12][13] Another important consideration in developing biosimilars is to understand the difference between comparability and biosimilarity. Comparability refers specifically to the assessment of characteristics of the biologic product after a specific change is made to the manufacturing process by the manufacturer of the product.…”

Section: Development Of Biosimilars: Analytical Preclinical and Clinmentioning

confidence: 99%

“…Mutations in the cell line also may contribute to minor sequence variants. These minor differences between a proposed biosimilar and the reference product can influence the pharmacologic profile, efficacy, safety and immunogenicity and therefore must be carefully identified and quantified at the outset …”

Section: Development Of Biosimilars: Analytical Preclinical and Clinmentioning

confidence: 99%

Biosimilars: what the dermatologist should know

Yamauchi¹,

Crowley

Kaur

et al. 2018

Acad Dermatol Venereol

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Biosimilars are highly similar versions of approved branded biologics. In contrast to generics, which are identical copies of the originator medicines, biosimilars are considered unique but related molecules that differ from the originator reference product as well as from each other. Owing to the complexity of biologic medicines, such as therapeutic monoclonal antibodies, minor differences between biosimilars and the reference products are acceptable provided these differences do not result in any clinically meaningful differences in safety or efficacy. In addition, minor changes in structure and function may occur over time in originator biologic products as a result of alterations in production materials (e.g. cell lines), processes or conditions. The developmental process for biosimilars focuses on a 'totality of evidence' approach that emphasizes a stepwise investigational process, including comprehensive structural, functional, pharmacologic and clinical assessment for similarity. The goal of the phase 3 clinical development programme for a biosimilar is not to establish efficacy, per se, but to demonstrate that there are no clinically meaningful differences between the proposed biosimilar and the reference product. The requirement to show clinical similarity informs biosimilar study design, including the selection of the patient population, disease state (indication), study endpoints and statistical methods. Based on the clinical trial results in a representative patient population, results may be extrapolated to other indications provided scientific justification is demonstrated based on, among other things, similar mechanism of action in the extrapolated indications. This review presents the current state of knowledge with respect to biosimilars. We aim to provide the practising clinician with a working knowledge of biosimilars as well as provide some practical guidance on their use and potential benefits in treating dermatologic diseases.

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“…It was found that 3 years after their marketing approval, 14% of medicines are subject to interventions, a figure that increases to 29% after 10 years [57]. Moreover, the first medicines belonging to a new therapeutic class are associated with an increased prevalence of adverse events [60].…”

Section: Risk and Traceabilitymentioning

confidence: 99%

Biologicals and biosimilars: safety issues in Europe

Portela

Sinogas

Almeida

et al. 2017

Expert Opinion on Biological Therapy

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Medicinal products of a biological origin are approved by the EMA at a centralized level. However, there is no harmonization about their use in Europe. The current regulation referring to the safety of biological medicinal products and biosimilars in Europe has been identified. The safety associated with medicinal products of a biological origin is assured by the pharmacovigilance system, which has evolved, but doesn't yet incorporate all of the specific information from this market segment, namely that related to the identification of drugs, and its use - including the prescription and dispensing, given the possibility of interchangeability and substitution. The terminology, information systems and traceability systems aren't entirely appropriate to ensure the safety requirements for therapy with medicinal products of a biological origin. Areas covered: This article aims to identify the prescription and dispensing profiles of reference biological medicines and biosimilars in the EU, and the determinants that support their safe use. Expert opinion: The European pharmacovigilance system must evolve to ensure the safety along all of the biologicals' therapeutic cycle. It must consider the safety for each of the medicines in addition to their safety pattern related to the eventual switching procedure.

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Quality and safety considerations for recombinant biological medicines: A regulatory perspective

Cited by 8 publications

References 32 publications

Developing the Totality of Evidence for Biosimilars: Regulatory Considerations and Building Confidence for the Healthcare Community

Developing the Totality of Evidence for Biosimilars: Regulatory Considerations and Building Confidence for the Healthcare Community

Biosimilars: what the dermatologist should know

Biologicals and biosimilars: safety issues in Europe

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