Discovery

Biosimilar development:
biologics and biosimilars 101

Inside drug development

Amgen’s development process is customized for each biosimilar. To begin, it is imperative that we understand the reference product. To do so, we:

  • Review the literature on both the disease and the reference product.
  • Use the same scientists and state-of-the-art facilities that manufacture our novel medicines to produce our biosimilar medicines, as their creation requires the same high level of precision.
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Biologics vs biosimilars

What are biologic medicines?

Biologics are produced through the metabolic activity of living cells and are often isolated using a process called “biotechnology.” Biologics are generally larger and more complex than chemically synthesized drugs.1,6

What are biosimilar medicines?

Biosimilars are medicines that are demonstrated to be highly similar to a biologic that has already been authorized for sale (also known as a reference biologic).6

Due to the size, complexity, and natural variability of biologic drugs, and because biologic drugs are made in living cells rather than with chemically synthesized drugs, a biosimilar and its reference biologic can be shown to be similar, but not identical.6

Amgen’s development process is customized for each biosimilar. To begin, it is imperative that we understand the reference product. To do so, we:

  • Review the literature on both the disease and the reference product.
  • Use the same scientists and state-of-the-art facilities that manufacture our novel medicines to produce our biosimilar medicines, as their creation requires the same high level of precision.

Quality attributes

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Biosimilars are not generics

Differences between generics and biosimilars:

  • A generic drug, by definition, is a copy of its reference medicine.4
  • A generic must have identical active ingredients as its reference product.4-5 Each biosimilar requires additional evidence beyond that needed for a generic to prove similarity.5
  • Unlike a generic, the active ingredient in a biosimilar will not be identical to its reference product.6
  • Biosimilars are “similar” to but not identical copies of the reference biologic.6

Unlike chemically synthesized drugs, biologics tend to be labile and sensitive to changes in manufacturing processes. Even slight differences in the manufacturing process may cause differences in product characteristics such as stability, which in turn can have an impact on the safety and efficacy of the drug product.1

Key manufacturing process considerations1,2

To support the creation of high-quality products, biologic manufacturers should have the following:

  • A well-defined manufacturing process that contains process controls and safeguards
  • To ensure that a quality product is produced on a consistent basis
  • Significant understanding of the interplay between structure and function

Reference biologic manufacturing information is proprietary. Therefore, a biosimilar manufacturer must develop an entirely new customized process. The process begins by characterizing the reference biologic to quantify its quality attributes, which evaluate relevant physicochemical properties, biological activity, immunochemical properties, purities and impurities. This allows for an acceptable range of acceptance criteria to be established. Critical control points are also established in the manufacturing process. They will be used to verify a biosimilar's quality attributes’ similarity with respect to the reference product.

Learn more
Biosimilars are not generics

Differences between generics and biosimilars:

  • A generic drug, by definition, is a copy of its reference medicine4
  • A generic must have identical active ingredients as its reference product.4-5 Each biosimilar requires additional evidence beyond that needed for a generic to prove similarity. 5
  • Unlike a generic, the active ingredient in a biosimilar will not be identical to its reference product.6
  • Biosimilars are “similar” to but not identical copies of the reference biologic.6

Unlike chemically synthesized drugs, biologics tend to be labile and sensitive to changes in manufacturing processes. Even slight differences in the manufacturing process may cause differences in product characteristics such as stability, which in turn can have an impact on the safety and efficacy of the drug product.1

Key manufacturing process considerations1,2

To support the creation of high-quality products, biologic manufacturers should have the following:

  • A well-defined manufacturing process that contains process controls and safeguards
    • To ensure that a quality product is produced on a consistent basis
    • Significant understanding of the interplay between structure and function

Reference biologic manufacturing information is proprietary. Therefore, a biosimilar manufacturer must develop an entirely new customized process. The process begins by characterizing the reference biologic to quantify its quality attributes which evaluate relevant physicochemical properties, biological activity, immunochemical properties, purities and impurities. This allows for an acceptable range of acceptance criteria to be established. Critical control points are also established in the manufacturing process. They will be used to verify a biosimilars quality attributes’ similarity with respect to the reference product.

Critical Quality attributes (CQAs) are physical, chemical, biological, or immunochemical properties or characteristics that should be within an acceptable range to ensure the desired product quality.1,2

Next, we acquire the product and use sophisticated analytical tests to determine its critical quality attributes (CQAs), which are characteristics that affect the identity, purity, biological activity and stability of a drug. CQAs should be within an appropriate limit, range, or distribution to ensure the desired product quality.3

The reference product characteristics, or CQAs, form the basis for the development of the biosimilar product. Characteristic considerations could include:3

  • intended use in clinical setting, route of administration, dosage form and delivery systems;
  • dosage strength(s);
  • container closure system;
  • release or delivery and attributes that affect pharmacokinetic characteristics; and
  • drug product quality criteria (sterility, purity, stability and drug release).

Various reference product samples are tested in order to establish equivalence margins, or “goal posts,” for each CQA, against which the potential biosimilar will be evaluated. Each manufacturer determines the extent of testing and provides information on their plan to health authorities.1,2

  • Physicochemical properties
    • Composition
    • Primary structure
    • Higher order structure
  • Biological activity
  • Immunochemical properties
    • Binding assays
  • Purity, impurities and contaminants

Scientists evaluate attributes of the biosimilar in comparison to the reference product, determining which are most important for producing a high-quality biosimilar.1 Only the gene sequence of the reference product is known, so it is impossible to exactly replicate the manufacturing process. The attributes of the biosimilar medicine are highly unlikely to ever be identical to those of the reference product. However, the biosimilar is close enough to the reference product to demonstrate that any identified differences have no impact on the clinical attributes of the final product.1,2

References: 1. Health Canada Guidance Document: Information and Submission Requirements for Biosimilar Biologic Drugs. Accessed May 24, 2018. Available at: https://www.canada.ca/content/dam/hc-sc/migration/hc-sc/dhp-mps/alt_formats/pdf/brgtherap/applic-demande/guides/seb-pbu/seb-pbu-2016-eng.pdf. 2. ICH. ICH Harmonised tripartite guideline. Specifications: Test procedures and acceptance criteria for biotechnological /biological products Q6B. 1999. Accessed May 24, 2018. Available at: http://www.ich.org/fileadmin /Public_Web_Site/ICH_Products/Guidelines/Quality/Q6B/Step4/Q6B_Guideline.pdf. 3. ICH. ICH Harmonised tripartite guideline. Pharmaceutical Development Q8R (R2). 2009. Accessed May 24, 2018. Available at: https://www.canada.ca/content/dam/hc-sc/migration/hc-sc/dhp-mps/alt_formats/pdf/prodpharma/applic-demande/guide-ld/ich/qual/q8r2-step4etape-eng.pdf. 4. Health Canada. The safety and effectiveness of generic drugs. Accessed August 23, 2018. Available at: https://www.canada.ca/en/health-canada/services/healthy-living/your-health/medical-information/safety-effectiveness-generic-drugs.html. 5. CADTH. Similarities and differences between brand name and generic drugs, Accessed August 28, 2018. Available at: https://www.cadth.ca/sites/default/files/pdf/similarities_differences_brandname_generic_drugs_e.pdf. 6. Health Canada. Fact Sheet: Biosimilars. Accessed May 24, 2018.

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