have gained experience developing and taking biosimilars through regulatory procedures. This combined with a greater understanding of the biosimilar business model has meant that biosimilars are now being developed earlier and with greater competition than was the case previously. Moving forward, the lag time between biologic loss of patent protection and biosimilar launch will decrease.22
2.7.3 Interchangeability and Substitution
Another factor that may affect uptake of biosimilars is that a biosimilar generally cannot be automatically substituted for the reference product (i.e. brand‐name or innovator biologic) at the pharmacy level unless it is determined to be interchangeable with the reference product. An interchangeable product “can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product. Interchangeable products may be substituted for the reference product by a pharmacist without the intervention of the prescribing health care provider.” In January 2017, FDA released draft guidance on interchangeability, and final guidance on 10 May 2019. FDA has not yet approved an interchangeable biologic product.23
2.8 Biosimilars in Emerging Markets
The emerging markets typically have relatively low access to biologic medicines when compared with developed markets. Patients in these markets stand to gain the greatest increase in access as a result of biosimilar competition. This has caused emerging market health authorities to put significant effort into encouraging use of non‐original biologics (NOBs). NOBs are copy‐biologics that have not gone through a biosimilar pathway with strict regulatory scrutiny such as the EMA, FDA, or WHO biosimilar guidelines. They have been preferred in the emerging markets due to their early access and lower price relative to true biosimilars. NOB uptake has been significant, the market was worth US$2.1 billion in 2015 relative to US$1.1 billion globally for true biosimilars (IMS MIDAS, 2016). They equate to 18% of all biologic sales in Pharmerging markets (countries having low positions in the pharmaceutical market but having rapid pace of growth) and are growing at almost twice the speed. However, the biosimilar regulatory environment in the emerging markets is changing rapidly. There has been a marked push for increasing quality of copy biologic medicines but increasing access and affordability will continue be the top priorities for policy makers.24
2.9 Top 10 Biologic Drugs in the United States
The 10 drugs on the list all have exceeded the monetary definition of a “blockbuster,” which designates a drug as having generated more than US$1 billion in annual sales.25 Figures are based on 2018 sales data reported by the respective manufacturers for revenues generated in 2017.
2.9.1 Humira ®
The anti‐inflammatory drug Humira® is not only the best‐selling biologic; it is one of the best‐selling drugs worldwide, regardless of class.
Indications: Rheumatoid arthritis, plaque psoriasis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, polyarticular juvenile idiopathic arthritis
Manufacturer: AbbVie, an Abbott Laboratories spinoff
Global Sales in 2017: $18.4 billion
Generic name: Adalimumab
Launch date: 2002
2.9.2 Rituxan ®
Rituxan® (rituximab) was developed by IDEC Pharmaceuticals under the name IDEC‐C2B8. Rituxan® is currently co‐marketed in the United States by Biogen Idec and Roche subsidiary Genentech.
Indication: Non‐Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis
Manufacturer: Roche
Global Sales in 2017: $9.2 billion
Generic name: Rituximab
Launch date: 1997
2.9.3 Enbrel ®
Enbrel® was developed by researchers at Immunex. Today the drug is co‐marketed in North America by Amgen and Pfizer, by Takeda Pharmaceuticals in Japan, and by Wyeth in the rest of the world.
Indication: Rheumatoid arthritis, plaque psoriasis, psoriatic arthritis
Manufacturer: Pfizer/Amgen
Global Sales in 2017: $7.9 billion
Generic name: Etanercept
Launch date: 1998
2.9.4 Herceptin ®
Herceptin® was developed by Genentech, now a Roche subsidiary, and UCLA's Jonsson Comprehensive Cancer Center.
Indication: HER2+ breast cancer
Manufacturer: Roche
Global Sales in 2017: $7.4 billion
Generic name: Trastuzumab
Launch date: 1998
2.9.5 Avastin ®
When launched in 2004, Genentech's Avastin® was one of the most expensive drugs on the market, with a US$4400 monthly price tag.
Indication: Breast, colorectal, kidney, non‐small‐cell lung, glioblastoma, ovarian cancers
Manufacturer: Roche
Global Sales in 2017: US$7.1 billion
Generic name: Bevacizumab
Launch date: 2004
2.9.6 Remicade ®
Remicade® was originally developed by Centocor Ortho Biotech, which is now Janssen Biotech, a Johnson & Johnson subsidiary.
Indications: Rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, ulcerative colitis
Manufacturer: Johnson & Johnson/Merck & Co.
Global Sales in 2017: US$7.1 billion
Generic name: Infliximab
Launch date: 1998
2.9.7 Lantus ®
Lantus® was developed at Sanofi‐Aventis's biotechnology research center in Frankfurt‐Höchst, Germany.
Indication: Diabetes
Manufacturer: Sanofi
Global Sales in 2017: US$5.7 billion
Generic name: Insulin glargine [rDNA origin] injection
Launch date: 2000
2.9.8 Neulasta ®
Neulasta® is