BIO Comments on EMA Guideline on Biosimilar Quality Issues


The Biotechnology Industry Organization (BIO) thanks the European Medicines Agency (EMA or Agency) for the opportunity to submit comments on the “Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (revision 1)” (the Guideline).

BIO represents more than 1,100 biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 nations.  BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products, thereby expanding the boundaries of science to benefit humanity by providing better healthcare, enhanced agriculture, and a cleaner and safer environment.

BIO commends EMA for the issuance of this science-based revision on quality requirements for a biological medicinal product claiming to be similar to one already marketed.  The document addresses many relevant issues associated with the topic, and we believe it will assist manufacturers that are developing biosimilar products and help ensure that patients will receive high quality biosimilar products, especially since the Guideline facilitates a global development approach for biosimilars, including embracing the concept of Quality Target Product Profile (QTPP). 

BIO welcomes the inclusion of Quality Target Product Profile (QTPP), and we request greater clarity on its intended use.  BIO believes that the QTPP has a recognized place in the development of biosimilar products, as it is acknowledged that the first step in developing a biosimilar molecule is to characterise, as fully as possible, the reference product to allow for a meaningful comparability program and process.  Accordingly, we agree that the QTPP should be “detailed at an early stage of development” and “form the basis for the development of the biosimilar product and its manufacturing process.” 

BIO continues to welcome EMA’s distinction between comparability exercises for process changes introduced during development and exercises intended to demonstrate biosimilarity (see line 77 stating that “This guideline does not address the comparability exercise for changes introduced in the manufacturing process of a given product (i.e., changes during development and post-authorisation), as outlined by ICH Q5E;” and line 123 stating “That for the purpose of clarity, any comparability exercise(s) for process changes introduced during development should be clearly indentified in the dossier and addressed separately from the comparability exercise versus the reference medicinal product.”).  Accordingly, in the past, BIO has requested EMA ensure that it uses the term “comparability” to apply to intramanufacturer situations only, as consistent with other regulatory documents including the International Conference on Harmonization’s (ICH) Q5E – Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process.  (See BIO Comments Draft Guideline on Similar Biological Medicinal Products (CHMP/437/04) available at;  and on Draft Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Quality Issues (EMEA/CHMP/BWP/49348/2005) available at

However, because the draft Guideline continues to use the terms “comparability” and “similarity” interchangeably, we urge EMA to formally make a statement explicitly recognizing the difference between conducting a comparability assessment of an innovator product before and after a manufacturing change versus assessments required to establish biosimilarity.  This recognition would serve to clarify the extremely important point that information contained in documents concerning changes within a company’s own process are not to be considered and adopted as adequate scientific guidance for the development of similar biological medicinal products by a second company. 

Specific, detailed comments on the text are included below. We would be pleased to provide further input or clarification of our comments, as needed.