Are You Ready for the Challenges of
Developing a Biosimilar Product?

With over 16 years of experience, we can help you gain approval for your biosimilar product

HW is at the forefront of biosimilar development.

Since 2002, we have provided regulatory affairs expertise and support, including to the first biosimilar G-CSF (Filgrastim) approved in the EU in 2008.

Since 2009, we’ve advanced the development of over 20 biosimilars , from relatively simple recombinant proteins to complex monoclonal antibodies and fusion proteins.

Table of Contents

  • What you need to know about the high regulatory expectations for biosimilars
  • Why analytical development is a critical step in the development of a biosimilar product
  • What is the relationship between biosimilar risk level and analytical similarity?
  • What is a QTPP and why do I need one?
  • When do I approach FDA?
  • What questions do we ask the FDA during our meeting?
  • Why immunogenicity must be addressed for a biosimilar
  • What an uncommon interdisciplinary approach can do for you

High regulatory expectations for biosimilars

We understand the FDA requirements to demonstrate analytical and functional similarity that serve as the foundation for the biosimilarity exercise. We can assist you in selecting the right assays, conducting a risk assessment to assign tier ranking and determining the statistical analyses to best evaluate your proposed biosimilar against the reference product.

Don’t lose time to FDA approval by conducting a biosimilarity exercise that the FDA will not accept.

Analytical development is a critical step in the development of a biosimilar product

We understand the challenges that you face:

  • How many lots of reference product do I need?
  • How many lots of the proposed biosimilar product do I need?
  • What assays do I need to demonstrate that my proposed biosimilar is highly similar to the reference product?
  • Do my results demonstrate that my proposed biosimilar is highly similar to the reference product?
  • Can I use reference product that was purchased outside of the US?
  • What if analytical and functional similarity are not established? What do I do now?
  • How do I address reference product variability?
  • What is a Critical Quality Attribute (CQA)? How is it established?

We’ve addressed these challenges many times and can help you. A comprehensive analytical similarity exercise is crucial for reducing uncertainty.

What is the relationship between biosimilar risk level and analytical similarity?

The risk level of the individual biosimilar product indicates which statistical methods you should use for that product:

  • Tier 1 – highest risk rankings; equivalence testing
  • Tier 2 – lower risk rankings; quality ranges
  • Tier 3 – lowest risk rankings; visual comparisons

Tier ranking is based on critical quality attributes. It is essential that the correct tier risk and associated statistical method be used for your biosimilar product.

What is a QTPP and why do I need one?

A Quality Target Product Profile (QTPP) guides the development of a biosimilar. It will allow you to take a step-by-step approach to development as expected by the FDA. Each step that you take evaluates uncertainty and must use science to justify the differences between the proposed biosimilar and the reference product.

Let us draft a QTPP for you!

When do I approach FDA?

Your analytical and functional biosimilarity program should be discussed with FDA once you have generated data, conducted your risk assessment, established your tiers, and conducted preliminary analyses. A Biosimilar Product Development Meeting or a Biosimilar Initial Advisory Meeting should be held. We have these meetings on a regular basis. We can write your meeting requests and packages for you and obtain your meeting with the FDA.

Just remember that your Biosimilar User Fee Act (BsUFA) fee must be paid upfront prior to your Biosimilar Product Development Meeting. There is no fee for the Biosimilar Initial Advisory Meeting. As the goals of these FDA meetings are different and they take place at different points in development, timing is important.

You don’t want to risk FDA rejecting your meeting request or moving you from your requested free Biosimilar Initial Advisory Meeting to a fee-based Biosimilar Product Development Meeting.

What questions do we ask the FDA during our meeting?

  • Is the analytical and functional similarity strategy acceptable? Are the number of reference product and biosimilar lots acceptable? Is the statistical analysis approach acceptable?
  • Are the planned non-clinical comparative studies appropriate and adequate for IND and/or BLA filing?
  • Is a reference product bridge necessary?
  • Is the PK dose acceptable? Is it possible to see a difference at this dose?
  • Is the comparative safety and efficacy study designed to show evidence of similarity in safety, efficacy, and immunogenicity to support a BLA? Is it sufficient to demonstrate that no clinically meaningful differences exist between the reference product and biosimilar?

Immunogenicity must be addressed for a biosimilar

The consequences of an immune reaction can range from minor and temporary to less-common severe, life-threatening conditions. Patient-, disease- and product-related factors influence the development of antibodies, and assessment of immunogenicity is always required for approval of a biosimilar.

First, you must develop an assay to measure the level of antibodies that have developed against your product. This screening assay must have suitable sensitivity, precision, recovery and reproducibility. The type of product, potential interference in the assay from co-medications, dosing regimen, disease-specific issues and/or appropriate epitope exposure will all affect decisions made in developing your assay.

For the positive tests, confirmatory assays then eliminate false positives. Neutralizing antibody assays then assess the antibodies with a clinical response.

Inadequate immunogenicity assays are one of the most common analytical issues that delay approval. Don’t let this happen to you.

The clinical effect of antibodies can only really be determined in a clinical study of appropriate duration. This study should be designed to measure comparative safety and efficacy as it relates to immunogenicity.

Let us conduct an immunogenicity risk assessment for you. This assessment should be conducted early on and the regulators expect it.

What an uncommon interdisciplinary approach can do for you

Our biosimilars regulatory consulting approach has always been interdisciplinary with a strong emphasis on the science underlying the product and FDA regulations.

Accordingly, our backgrounds are relevant and important for our FDA biosimilars consulting work.

Our backgrounds include:

  • Molecular and cell biology
  • Protein biochemistry
  • Immunology
  • Aseptic processing
  • Manufacturing
  • GCP, GLP, & GMP

An advantage for you is that we require a minimum introduction and education in biosimilars – we’ve been working with these products for over 16 years!

Your biosimilar regulatory affairs and development team

Regulatory and Product Development for Biosimilars

With our FDA and industry experience, we provide you with advice on regulatory and product development for biosimilars. We are well positioned to assist you in gaining FDA biosimilars approval.

We have assisted clients from:

  • United States
  • Europe
  • Australia
  • Japan
  • India
  • China
  • And other regions to achieve successful outcomes with the FDA.

As with all biologics, biosimilars are regulated by the Center for Biologics Evaluation and Research (CBER) and the Center for Drugs Evaluation and Research (CDER) under the Public Health Service (PHS) Act and the Federal Food, Drug and Cosmetic (FD&C) Act.

More information about the FDA guidelines for biosimilars can be found on their website.

Are you in the process of
developing a biosimilar product?

Do you need help in preparing your IND or BLA? We can help. Contact us today to learn more about how we can help you gain approval from the FDA.