ENGLISH ONLY
FINAL
EXPERT COMMITTEE ON BIOLOGICAL STANDARDIZATION
吵架英文
options是什么意思Geneva, 19 to 23 October 2009
GUIDELINES ON EVALUATION OF SIMILAR
BIOTHERAPEUTIC PRODUCTS (SBPs)
© World Health Organization 2009
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The mention of specific companies or of certain manufacturers’ products does not imply that they are endord or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expresd or implied. The responsibility for the interpretation and u of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its u. The named authors [editors] alone are responsible for the views expresd in this publication.
Adopted by the 60th meeting of the WHO Expert Committee on Biological Standardization, 19-23 October 2009. A definitive version of this document, which will differ from this version in editorial but not scientific details, will be
published in the WHO Technical Report Series.
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Table of contents
1. Introduction (3)
2. Aim (4)
3. Scope (4)
4. Glossary (5)
5. Scientific considerations and concept for licensing SBPs (7)
6. Key principles for the licensing of SBPs (8)
creating a green campus7. Reference biotherapeutic product (9)
8. Quality (10)
9. Non-clinical evaluation (16)
10. Clinical evaluation (19)
11. Pharmacovigilance (28)
12. Prescribing information and label (29)
13. Roles and responsibilities of NRAs (29)
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Authors and Acknowledgements (31)
References (33)
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Page 3 1 Introduction
Biotherapeutic products (biotherapeutics) have a successful record in treating many life-threatening and chronic dias. However, their cost has often been high, thereby limiting their access to patients, particularly in developing countries. Recently, the expiration of patents and/or data protection for the first major group of originator’s biotherapeutics has ushered in an era of products that are designed to be ‘similar’ to a licend originator product. The products rely, in part, for their licensing on prior information regarding safety and efficacy obtained with the originator products. The clinical experience and established safety profile of the originator products should contribute to the development of similar biotherapeutic products (SBPs). A variety of terms, such as 'biosimilar products', 'follow-on protein products' and 'subquent-entry biologics' have been coined by different jurisdictions to describe the products.
The term 'generic' medicine is ud to describe chemical, small molecule medicinal products that are structurally and therapeutically equivalent to an originator product who patent and/or data protecti
on period has expired. The demonstration of bioequivalence of the generic medicine with a reference product is usually appropriate and sufficient to infer therapeutic equivalence between the generic medicine and the reference product. However, the approach established for generic medicines is not suitable for development, evaluation and licensing of SBPs since biotherapeutics consist of relatively large, and complex proteins that are difficult to characterize. The clinical performance of biotherapeutics can also be much influenced by the manufacturing process and some clinical studies will also be required to support the safety and efficacy of a SBP.
As part of its mandate for assuring global quality, safety and efficacy of biotherapeutics, the World Health Organization (WHO) provides globally accepted norms and standards for the evaluation of the products1,2. Written standards established through the Expert Committee on Biological Standardization (ECBS) rve as a basis for tting national requirements for production, quality control and overall regulation of biological medicines. In addition, International Standards for measurement are esntial tools for the establishment of potency for biological medicines worldwide3. Often they are ud as primary standards for calibration of the condary standards that are directly ud in the biological assays.
An increasingly wide range of ‘SBPs1’ are under development or are already licend in many count
ries and a need for guidelines for their evaluation and overall regulation was formally recognized by the WHO in 20074. This document is intended to provide guidance for the development and evaluation of such biotherapeutics. However, the guidelines will rve as a living document that will be developed further in the line with the progress in scientific knowledge and experience.
托福与雅思哪个好考It is esntial that the standard of evidence supporting the decisions to licen SBPs be sufficient to ensure that the product meets acceptable levels of quality, safety and efficacy to ensure public health. Also, it is expected that the elaboration of the data requirements and considerations for 1 Not all products deemed to be ‘SBPs’ will be consistent with the definition and/or process for evaluation of SBPs as described in this guideline
一套英文Page 4
the licensing of the products will facilitate development of and worldwide access to biotherapeutics of assured quality, safety and efficacy at more affordable prices. In most cas, their authorization will be evaluated on a ca-by-ca basis, and the amount of data required by a National Regulatory Authority (NRA) may vary. However, it is expected that a guideline on the scientific principles for evaluation of SBPs will help harmonize the requirements worldwide and will lead to greater ea and
spring是什么意思speed of approval and assurance of the quality, safety and efficacy of the products. It is important to note that biotherapeutics which are not shown to be similar to a RBP as indicated in this guideline should not be described as 'similar', nor called a 'SBP'. Such products could be licend through the usually process using a more extensive non-clinical and clinical data t or full licensing application.
It was recognized that a number of important issues associated with the u of SBPs need to be defined by the national authorities. They include but are not limited to the following: •intellectual property issues;ckeditor
•interchangeability and substitution of SBP with RBP; and
•labelling and prescribing information.
Therefore, the above mentioned issues are not elaborated in this document.
2 Aim
The intention of this document is to provide globally acceptable principles for licensing biotherapeutic products that are claimed to be similar to biotherapeutic products of assured quality, safety, and effic
acy that have been licend bad on a full licensing dossier. On the basis of proven similarity, the licensing of a SBP will rely, in part, on non-clinical and clinical data generated with an already licend reference biotherapeutic product (RBP). This guideline can be adopted as a whole, or partially, by NRAs worldwide or ud as a basis for establishing national regulatory frameworks for licensure of the products.
3 Scope
This guideline applies to well-established and well-characterized biotherapeutic products such as recombinant DNA-derived therapeutic proteins.
Vaccines, plasma derived products, and their recombinant analogues are excluded from the scope of this document. WHO recommendations and regulatory guidance for the products are available elwhere (www.who.int/biologicals/areas/en/).
Page 5 4 Glossary
The definitions given below apply to the terms ud in this guideline. They may have different meanings in other contexts.
Comparability exerci
Head-to-head comparison of a biotherapeutic product with a licend originator product with the goal to establish similarity in quality, safety, and efficacy. Products should be compared in the same study using the same procedures.
Drug product
A pharmaceutical product type that contains a drug substance, generally in association with excipients.
Drug substance
The active pharmaceutical ingredient and associated molecules that may be subquently formulated, with excipients, to produce the drug product. It may be compod of the desired product, product-related substances, and product- and process-related impurities. It may also contain other components such as buffers.
Equivalent
Equal or virtually identical in the parameter of interest. Equivalent efficacy of two medicinal products means they have similar (no better and no wor) efficacy and any obrved differences are of no clinical relevance.
Generic medicine
A generic medicine contains the same active pharmaceutical ingredient as and is bioequivalent to an originator (comparator) medicine. Since generic medicines are identical in the active pharmaceutical substance, do, strength, route of administration, safety, efficacy, and intended u, they can be substituted for the originator product.
Head-to-head comparison
Direct comparison of the properties of the SBP with the RBP in the same study. Immunogenicity
哈尔滨英语培训The ability of a substance to trigger an immune respon or reaction (e.g. development of specific antibodies, T cell respon, allergic or anaphylactic reaction).
