Biologics and Biosimilars
Biologics
Biologics are very specific, highly effective medicines made in
living cells. They improve health in many complex conditions, Biologics have continued to
including Crohn’s disease, ulcerative colitis, diabetes, evolve throughout the years
rheumatoid arthritis, cancer, osteoporosis, psoriasis, human into powerful medicines
immunodeficiency virus (HIV), multiple sclerosis, growth that have revolutionized
deficiencies, and more. treatment for debilitating
Some examples of biologics include hormones, blood diseases, giving patients a
products, cytokines, growth factors, vaccines, gene and cellular new chance for a life.
therapies, fusion proteins, insulin, interferon, and monoclonal
antibody (mAb) products. Patients receive biologics mainly by
injection under the skin (subcutaneously) or by intravenous
infusion. You cannot take these medicines orally, since the What are Biosimilars?
process of digestion (e.g., acidic stomach pH, digestive enzymes, Biosimilars are brand name products that are highly similar
and limited permeation through the gastrointestinal (GI) to an already approved brand name innovator or originator
tract) breaks down the biologic, making it ineffective. Ongoing biologic but, unlike a generic drug, are not identical. To
research into developing less-invasive or non-invasive routes understand why biologics cannot be identical to each other, we
for the systemic delivery of biologics that bypasses the GI need to look at how biologics are different from other medicines.
tract includes via the inner cheek (buccal), through the nose Small Molecule: Most medicines, such as acetylsalicylic
(nasal), under the tongue (sublingual), inhalation into the lung acid or ASA (Aspirin®), are small molecule products. This
(pulmonary), and through the skin (transdermal). While all means that they have simple molecular structures with low
these routes avoid transit through the gastrointestinal tract, molecular weight. These small structures are easy to produce
each has its own strengths and weaknesses that may be optimal or copy. Once a patent expires, other manufacturers can make
for specific classes of compounds. You can take some biologic copies of small molecule drugs by reproducing the exact same
vaccines currently available intra-nasally. active ingredient (typically a chemical) as the original product.
After Health Canada approval, they can then sell this copy as a
generic version. The original product and the identical generic
We have been using biologic copies are considered bioequivalent because the active part
medicines since 1796, when of the medicines behave the same way in the body producing
equivalent levels of drug in the body. A generic manufacturer is
scientists created the first
not typically required to conduct studies in patients with specific
rudimentary vaccines for
illnesses (clinical trials) for Health Canada to approve a generic
smallpox.
drug to treat the same conditions for which the original patented
medicine has approval. However, they do require bioequivalence
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studies with healthy volunteers measuring the amount of drug more are on the way, as the patents for originator biologics
in the body. continue to expire.
Biologics: By comparison, biologics are very large and Health Canada makes decisions to approve some biosimilars
have complex molecular structures, created by living cells, to treat conditions that the originator biologic has approval
from specialized ingredients, using an intricate biotechnology for, through educated assumptions by extrapolating scientific
process. It is impossible to produce an exact copy without evidence. Therefore, a biosimilar might have an indication to
using the exact same ingredients, the same living cell lines, and treat a specific disease without testing in that disease. The array
identical manufacturing conditions. In fact, it is not possible of indications for some biosimilars might be fewer than the
to demonstrate that a batch of any biologic – originator or array of indications for the reference product. This may be due
biosimilar – is identical to its previous batches, but it must be to patent protection for specific indications, that the process of
within a tight range set by Health Canada. All companies gathering the data necessary for Health Canada is ongoing, or
must report to Health Canada any significant changes in the due to a manufacturer not requesting regulatory approval for a
manufacturing process. specific indication. Different biosimilars of the same reference
As with other medicines, once a patent expires for a biologic, product might not have all of the same approved uses (known as
it is legal for other manufacturers to copy the drug. However, indications).
the innovator company doesn’t have to share its patented
manufacturing processes (which may include the room Substitution, Interchangeability, and Non-
temperature, the type of cells that produce the biologic, and the Medical Switching
food the cells use to grow), and since there is always variability Typically, if a person has a prescription for a small molecule
in a live biological system, it is impossible to create an identical medication, a pharmacist may substitute a generic version
biosimilar. Since biosimilars are not identical, they are not without consulting or informing the patient’s physician. This is
generic versions of the biologic they are mimicking. interchangeability. However, biosimilars are not interchangeable
Differences: With small molecule drugs, there are often with their reference biologic in Canada. A physician may
many generic versions. They all work the same and you can choose to switch their patient from an originator biologic to
interchange or substitute them with each another. For example, the biosimilar product if they think it will be beneficial, but a
whether you buy name brand Aspirin® or one of the many generic pharmacist may not change the prescription for an originator
versions, they are the same chemical and – for the most part – biologic to a biosimilar.
perform in the same way in the body. However, with biologics, Physicians, in consultation with their patients, should make a
there could be many different biosimilars all referencing one decision about the right medication to prescribe in each unique
drug, each with a different manufacturing process, resulting in a situation, using the available clinical evidence and any relevant
similar molecule to the innovator, but there are no requirements provincial or territorial policies.
for studies or comparisons among biosimilars. A non-medical switch occurs when someone other than your
physician says you have to change your medicine for no medical
Biologic and Biosimilar Regulations in Canada reason, typically when a government or private insurance
Health Canada approves biosimilars as new drugs by payer will not cover your original medication and only pay
comparison with an innovator reference product previously for an alternative, for a number of different reasons, discussed
authorized and marketed in Canada. As the federal authority, below (Benefits of Biosimilars). Non-medical switching from
Health Canada states that biosimilars are not generic biologics. originator biologics to biosimilars is arising in Canada, without
Health Canada only approves biosimilars for marketing in the support of the Canadian Association of Gastroenterology.
Canada when the manufacturer demonstrates that their product To assess whether switching is a good thing, professional
is of similar quality, safety, and efficacy to the original reference physician associations should develop disease-specific exclusion
drug. Health Canada describes a biosimilar as a drug that has criteria for vulnerable patients, and governments need to
been demonstrated to be highly similar to a reference biologic monitor patients for whom they have mandated a switch policy
drug and that there are no clinically meaningful differences in closely, e.g., thorough data analysis and impacts on patients in
safety and efficacy between them. Clinical trials in patients conjunction with patient groups and patient registries.
(not just healthy volunteers) with at least one of the conditions
the reference biologic treats are required for Health Canada to Immunogenicity
approve a biosimilar. Because biologics are proteins, the body can develop
There are many biosimilars on the market (with more than antibodies to them over time, which might affect how they work.
one biosimilar version for each reference product), and many This immune response, called immunogenicity, can also occur
2 © GI Society www.badgut.org
with biosimilar products, and you should discuss this with your government and private drug plans are refusing to allow this,
physician before initiating therapy or switching among biologic even though they could have the same, or greater, savings.
products. Although initially there were theoretical concerns These issues may be due to some manufacturers being unable
that a switch to a biosimilar may enhance the development of to publicly disclose the lower prices. The gastrointestinal
immunogenicity, studies have not demonstrated this to be community is concerned about some governments’ refusal to
occurring. More concern arises when a patient takes a medicine allow patients to stay on their original medication when finances
holiday and then tries to resume the same medication, as this is are no longer an issue.
more likely to cause antibodies to form, so be sure you follow
your prescribed medicine regime. Conclusion
Biosimilars are not generic versions of originator biologics,
Naming Biosimilars but they can be affordable alternatives that work similarly to
The naming of biosimilars has been a complicated issue. achieve similar outcomes. For patients who have not begun
Typically, each version of the same small molecule medication an originator biologic, biosimilars may be a useful lower cost
uses the same international non-proprietary name (INN) alternative for physicians to prescribe. However, if the costs of
because they are the same molecule. However, biologics aren’t biosimilars are close to the cost or the originator biologic, then
identical, yet we still use the same INN for originator biologics the Canadian Association of Gastroenterology recommends that
as well as biosimilars. For example, Remicade® is the originator gastroenterologists prescribe the originator, because these have
brand name of the INN infliximab, for which there are currently been in use for a longer period. Only a physician, in consultation
three brand name biosimilars, Inflectra®, Renfexis®, and Avsola™. with the patient, should switch a patient from an originator
Because of this, Health Canada and other similar groups biologic to a biosimilar, and only if it does not adversely affect
internationally have looked into options for distinguishing patients’ health.
between reference biologics and biosimilars. As of 2019, Health
Canada has settled on a biosimilars naming convention that Questions to ask your healthcare provider
involves identifying the products by their INN in combination about biosimilars
with their unique brand name, without the addition of a Are you considering talking to your healthcare provider
product-specific suffix. The World Health Organization is still about biosimilars or has your healthcare provider talked to you
deliberating on a global position. already about biosimilars? As patient organizations, we have
put together some questions that might be helpful to be part of
Benefits of Biosimilars a conversation with your healthcare provider about biosimilars
Treatment options are very important for patients who have and originator biologics.
serious health conditions. With appropriate regulations in place
around approval, advertising, and post-market monitoring, Will the biosimilar provide me with similar benefits
as well as private and public insurance coverage, products that and risks as my current biologic (if you are currently
demonstrate effective and safe treatment of conditions should be on one)? If not, what might be different? How would
available for physicians and their patients to choose from. I know if I have an adverse reaction (to a biosimilar or
The cost of pharmaceuticals, particularly biologics, is an biologic)?
important consideration as experts look at ways to make
pharmaceutical care sustainable. Due to their complexity, Can I go back to the original medication I was on if
biologics are costly and consume a large portion of public and the biosimilar does not work as well for me, or if I
private drug spending. In most cases, biosimilars are less costly experience different side effects?
than the originator biologic, given that biosimilar manufactures
only need to demonstrate that their product is safe, effective, and What is the name of the biosimilar(s) that could be
of quality, but do not need to conduct extensive clinical trials, as taken instead of the originator biologic? (Note that
the innovative manufacturer had to do, to be granted approval medications have two names – one the manufacturer
in one or more indications. However, at the end of a product’s gives it, which is also called the brand name, and
patent life, most manufacturers are willing to lower their prices one that is its non-proprietary or chemical/molecule
to compete in the biosimilar market space. name.)
Controversy exists because some originator biologic
companies have offered to match the price of the biosimilars How will I take the biosimilar? If I take it by infusion,
so a patient can remain on the reference product but some will I need to go to a different infusion centre from
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About the Gastrointestinal Society
where I go now? (You should note if the The GI (Gastrointestinal) Society is a registered Canadian charity
infusion centre is easier to get to or more committed to improving the lives of people with gastrointestinal and
liver conditions, supporting research, advocating for appropriate patient
difficult to get to than your current centre,
access to healthcare, and promoting gastrointestinal and liver health.
and if its hours of operation align with your
schedule.) Want to learn more on this subject? The Inside Tract®, the GI Society’s
quarterly newsletter, provides the latest on digestive and liver research,
disease and disorder treatments (e.g., medications, nutrition), and a
What is the dosing schedule – will it be the whole lot more. If you have any kind of digestive problem, then you will
same as my current biologic? want this timely, informative publication. Subscribe today!
This pamphlet was produced in partnership with the Canadian Society
If I administer the biosimilar myself, are there of Intestinal Research under the guidance of affiliated healthcare
any different special storage requirements? professionals. This document is not intended to replace the knowledge,
Will I receive everything I need to administer diagnosis, or care of your physician. © Gl Society 2020. All rights reserved.
the biosimilar?
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originator biologic and its biosimilar(s)?
What will the biosimilar cost me? What does
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annual or lifetime maximum drug coverage?
Does my physician need to complete any City, Province, Postal Code
forms for me to receive the originator
biologic if it is covered? Daytime Phone Email
Patient Friend/Family Member Professional
When your healthcare provider starts a conversation
with you about biosimilars, you may also choose to ask
these additional questions along with those listed above: Diagnosis/Area of Interest (This optional information helps us to
determine which topics might be of interest to you and is kept strictly
confidential. We never sell our lists.)
Why are you recommending this biosimilar
for me?
Would you like more information? Please list your topics.
What if I don’t want to change my medication
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