Safe Biologics

ASBM, in conjunction with the Long Island University College of Pharmacy (LIU-Pharmacy), is now offering a comprehensive continuing education course on biosimilars entitled “Biosimilars: What Pharmacists Need to Know”. The course is accredited by the American Council on Pharmaceutical Education (ACPE), meaning course credit is available to pharmacists nationwide.

The first entry in the series is entitled “Biologic and Biosimilar Medicines: Their Purpose, Development, Structure, and Effects”, and is presented by ASBM Advisory Board Chair, Philip J. Schneider, MS, FASHP.

In the presentation, Dr. Schneider provides a basic overview of biologic medicines and biosimilars, covering topics such as:

• defining biologic medicines and biosimilars
• development and approval
• treatment applications (e.g. rheumatoid arthritis, cancer, etc.)
• Immunogenicity concerns
• safety, storage and handling considerations
• differences between biosimilars and generics
• pharmacovigilance implications
• interchangeability and pharmacy substitution
• recent Federal legislation

The course is offered as a 1 hour CE/homestudy for $10.00, but ASBM is offering the course for FREE when you use the code “BioJune1”.

The user has to visit pharmce.liu.edu and create an account, and then select the course from the catalog. When checking out, the user enters the code.

ASBM and LIU-Pharmacy will be adding additional courses throughout the summer on a wide range of topics including biosimilar substitution practices, non-medical switching, patient and physician perspectives, and biologic pharmacovigilance.

View the first entry in the series here. 

The first interchangeable biosimilars- a long-acting insulin biosimilar and a short-acting insulin biosimilar- should be available this summer, according to Sonia T. Oskouei, PharmD, BCMAS, DPLA; in an interview published May 26th in the American Journal of Managed Care at the Center for Biosimilars. Dr. Oskouei is Vice President of Biosimilars at Cardinal Health.
“We are eagerly awaiting this significant milestone in US biosimilar history- to finally experience an interchangeable biosimilar in the market and, additionally, our first true retail biosimilar as well.” observed Dr. Oskouei.

“Current guidance by the FDA says these biosimilars have to conduct switching studies, whereby you switch back and forth 3 times to show no differences in outcome, Dr. Oskouei explains. “So, it’s through the submission of that data; that is what is used for the designation.”

See the interview with Dr. Oskouei here.

On May 18th, Quebec announced its intention to become the fourth province to require patients to switch to biosimilars. British Columbia and Alberta have already implemented similar policies, and in April, New Brunswick announced it will follow them.

Starting April 12, 2022, Quebec will cover, “with exceptions,” only the biosimilar version of drugs. “Despite the inclusion of several biosimilar drugs on the drug lists for many years… they remain underused,” Health Minister Chrisitan Dubé said in a release.

The province will require all patients, even those stable on their physician-chosen biologics, to switch to the government-preferred products.

Quebec’s National Institute of Excellence in Health and Social Services (INESS) had previously released a report “Safety of switching biologics and their interchangeability”. The report found:

There is very little clinician opposition to the use of biosimilars in treatment-naive patients…the picture is different and much more nuanced regarding the use of biosimilars in individuals who are already being treated with a reference biologic drug, in particular because of the risks of immunogenicity posed by the use of biologic drugs and the possible loss of efficacy.

In this respect, all the learned societies are clearly opposed to non-medical switching of a biologic drug, and instead favour medical switching, by which the decision to switch a patient’s treatment rests with the individual and his or her doctor. This position is shared by all the clinicians consulted for this project, who stress that the physician is the best person to assess the risk of treatment switching in a given patient.

The INESSS report also contrasts BC- and Alberta- style forced-substitution policies with those of Western Europe, likening it more to those in Eastern Europe:

“Most of the jurisdictions examined are in favour of switching patients being treated with a reference biologic drug to a biosimilar, but do not impose this on all patients (via financial penalties or incentives, quotas, etc.)… Only a few European countries (Denmark, Bulgaria, Poland and Serbia) and two Canadian provinces have adopted policies for mandatory non-medical switching for the vast majority of patients (national tendering processes or reimbursement of biosimilars only).”

The pro-competition, pro-physician choice policies found in most European biosimilar markets were the subject of a recent whitepaper by ASBM’s Michael Reilly and Philip Schneider; read that paper here. 

Read more about Quebec’s announcement here. 

The Global Colon Cancer Association is conducting a brief survey on biosimilars among the global patient and caregiver community. The goal of this survey is to gather information directly from patients and caregivers so that we can develop educational materials and campaigns that best meet the needs of various communities across the globe.

You do not need to be a colorectal cancer patient to take this survey. We are seeking input from individuals who are patients being treated for all disease types as well as caregivers.

By completing this survey, you have the option to be entered into a drawing where 2 survey respondents will have a $500 donation made to the charity of their choice, in their name (or a loved one’s name).

Your contact information will NOT be shared with anyone outside of the GCCA. You can opt out of communications from GCCA at any time.

Note: In this survey, we refer to your country’s regulatory agency. A regulatory agency oversees the approval and monitors the safety of many products including drugs and medical devices. Here are a few examples of the names of the regulatory agencies in various countries:

• Brazil: National Heath Surveillance Agency (ANVISA)
• Canada: Health Canada’s Health Products and Food Branch (HPFB)
• India: The Central Drugs Standard Control Organization (CDSCO)Europe: European Medicines Agency (EMA)
• Nigeria: National Agency for Food and Drug Administration and Control (NAFDAC)
• US: The U.S. Food and Drug Administration’s (FDA)
• Vietnam: Drug Administration of Vietnam (DAV)

Take the GCCA Biosimilars survey here. 

Bowel Cancer Australia has issued a Patient Alert for Australia’s metastatic cancer patients: beginning on June 1st, 2021, the popular drug Avastin will be withdrawn from Australia’s Pharmaceutical Benefit Scheme (PBS) meaning it will no longer be available to metastatic bowel cancer patients as a subsidized treatment. Avastin is designed to block a protein called vascular endothelial growth factor, or VEGF. Normal cells make VEGF, but some cancer cells make too much VEGF.
The delisting of Avastin coincides with the anticipated listing on the PBS of a biosimilar competitor, removing any real choice for many patients and unfairly penalizing those who are unable to privately fund Avastin.
“The introduction of biosimilars was intended to increase treatment options, but reality suggests the impact will be the opposite” as Bowel Cancer Australia explains on their website:
If metastatic bowel cancer patients remain on Avastin after 1 June, they will have to pay for it. If they cannot afford it, they will be forced to switch to the biosimilar. There is currently no publicly available evidence to support the safety of nonmedical switching in patients with metastatic bowel cancer.

Policies that directly impact patients need to consider patient circumstances and preferences.

A 2016 ASBM survey of Australian physicians revealed that 90% considered it “very important” or “critical” that physicians and patients retain sole authority to choose which biologic the patient receives.

81% believed that “statistically robust comparative clinical trial data that show no increase in risk to safety and efficacy” should be required before a biosimilar could be substituted in place of its reference product.

Australian patients have organized an e-petition to Parliament, urging reversal of the decision. The petition reads, in part:

This drug is used by thousands of people diagnosed with stage 4 metastatic colorectal cancer and is instrumental to their treatment regime. June is Bowel Cancer Awareness month. Bowel cancer is fast becoming one of this countries biggest killers. Let’s not celebrate the month by taking away people’s medication!

View and sign the petition here.

Read Bowel Cancer Australia’s Patient Alert here.

Missed last month’s ASBM Newsletter? Read it Here.

15th Biosimilars Congregation 2021

Virtual – June 23 – June 24, 2021

DIA Global 2021 Annual Meeting

Virtual – June 27 – July 1, 2021 

WHO 73rd INN Consultation

Geneva, Switzerland – October 19, 2021

World Drug Safety Congress

Boston, Massachusetts – October 20-21, 2021

World Biosimilar Congress Europe 2021

Basel, Switzerland – November 9-11, 2021

On April 22nd, Oklahoma Governor Kevin Stitt signed SB 4, making Oklahoma the 50th and final state to enact a law permitting biosimilar substitution.

SB 4, like similar legislation in other states, permits interchangeable biosimilars to be substituted at the pharmacy level once approved by the FDA. Patients and physicians must be informed of a substitution, and one may be prevented by the physician if deemed medically necessary.

The substitution of medicines is governed at the state level, but state pharmacy acts were written before the advent of biosimilars and did not reflect their differences from generics of small-molecule drugs. Updating these acts nationwide has been a 10-year endeavor involving the collaborative efforts of many patient advocacy organizations, physician and pharmacist societies, manufacturers of originator products and biosimilars, and many other stakeholders.

ASBM has worked since 2011 to educate policymakers nationwide by sharing with them the perspectives of the physicians that prescribe biologics, the pharmacists who dispense them, and the patients who receive them.

ASBM’s efforts in this decade-long campaign consisted of three nationwide physician surveys, the gathering dozens of patient testimonials, physician and pharmacist interviews, innumerable letters and legislator briefings, meetings with state medical and pharmacy societies, in-person expert testimony before state legislatures, educational videos, and holding countless educational forums at colleges of medicine and pharmacy.

As ASBM Executive Director Michael Reilly observed:

“This 10-year educational campaign spanned the terms of three ASBM Chairmen and touched every single U.S. state and territory. Today marks the end of a long journey- and a fully-realized victory for patients, as the protections of this legislation now reach nationwide.”

Read about Oklahoma’s SB4 here.

Read about biosimilar substitution laws nationwide here.

On April 13th, ASBM presented to the World Health Organization’s (WHO’s) 72nd Consultation on International Nonproprietary Names (INN) for Pharmaceutical Substances, held in Geneva, Switzerland. This was the sixteenth INN Consultation at which ASBM has presented.

ASBM was represented by Executive Director Michael Reilly, Esq., and Advisory Board Chair Philip Schneider, MS, FASHP. Due to coronavirus-related travel restrictions in place at the time of the consultation, the presentation was made online.

Since 2013, ASBM has worked extensively on the issue of international harmonization of biologic nomenclature, most recently by hosting a series of meetings with FDA, Health Canada, and the WHO.

In 2014, the WHO proposed that all biologics sharing an INN be assigned a unique four-letter suffix called a “biological qualifier” or BQ. While initially supported by many national regulatory authorities including the FDA, Health Canada, and Australia’s Therapeutic Goods Administration (TGA), the BQ proposal has not yet been implemented. In 2015 the FDA adopted its own BQ-like suffix system, and until recently was in conversations with Canada about harmonizing nomenclature systems regionally.
While the discussions in the Open Session at which ASBM presented are bound by confidentiality agreements pending the publication of an Executive Summary by the INN Programme, the Executive Summary from the 71st INN Consultation – held on October 20, 2020 and in which ASBM also participated – may be viewed here. From the Executive Summary:

One argument against distinguishable names was that biosimilars may be seen as inferior and that this would hamper their use. But that has not happened in the USA, and in 5 years of use, two biosimilars of filgrastim have achieved a 72% share of the market; good uptake has also been seen bevacizumab, trastuzumab and pegfilgrastim biosimilars. So, distinguishable names are not an impediment to uptake.

Another argument against the BQ is the presence of existing ways of distinguishing biologics, particularly in pharmacovigilance (PV) programmes. Efforts have been made to improve PV programmes through regulation but in a study of the UK adverse drug reaction (ADR) reporting program, no one reporting system is consistently used. Ideally, all methods of identification should be used but in the UK study, only 38% of reports included an identifiable brand name and only 15% had batch numbers. These findings prompted the authors to conclude that the system needs to be improved. These data are consistent with ASBM’s survey findings that show inconsistent information being included in ADR reports with brand name, batch number and the name of the manufacturer not always being specified.

As biologics and biosimilars continue to increase, with distinguishable non-proprietary names not having a negative impact on the update of biosimilars, and with PV programmes needing to be improved, the lack of a consistent approach points to a need for WHO leadership, just like is happening for the pandemic.

Several early supporters of the BQ have reversed their views, explicitly citing lack of WHO action on naming. Yet they remain willing to harmonise with a global standard should one be made available by the WHO. At the April INN Consultation, the ASBM offered to draft a letter to gauge the level of support for BQ among regulators, and the ASBM repeated this offer

ASBM surveys have consistently shown strong support for distinct naming among physicians worldwide. 66% percent of U.S. physicians surveyed support distinct naming for all biologics, including biosimilars, as do 68% of Canadian and 79% of Australian physicians. Among physicians in Latin America, 94% believe the WHO’s BQ proposal would be helpful in ensuring their patients receive the correct medicine.

Read more about ASBM’s work with the WHO’s INN Group here. 

From June 27-July 1, 2021, ASBM will virtually present a poster the DIA Global Annual Meeting 2021 entitled “A Review of Problems with Pharmacovigilance Programs and Biologics”. The poster is authored by ASBM Executive Director Michael Reilly and Advisory Board Chair Philip Schneider. Dr. Schneider will present the poster in video recording available to conference attendees for the duration of the four-day event.

The poster will examine a variety of published literature on global pharmacovigilance of biologic medicines, with a focus on difficulties in accurately identifying biologics at the product level in Adverse Drug Reaction (ADR) reports and self reporting surveys (SRS). For example, in a 2019 analysis of European ADR reports for infliximab in 2018, 35% did not provide a brand name, despite this being required by EU law since 2012.

Lack of a consistent international standard for biologic naming was identified as a barrier to biosimilar adoption in a recent WHO-sponsored 20-country study. “There is still no consensus among countries on the naming and labeling of biosimilars,” its authors observed, “and the WHO does not provide specific nomenclature for biosimilars.”

In 2014 the WHO’s INN Expert Group proposed a voluntary naming standardto promote accurate biologic identification. But despite early support for the standard from many countries including the US, Canada, Australia, and Japan, it has not yet been made available to national regulatory authorities.

DIA 2021 runs from June 27-July 1, 2021. EPosters will be featured in an online gallery within the virtual meeting platform that is hosting DIA 2021.

Learn more about DIA 2021 and see the draft Program Agenda here. 

On April 23rd, President Biden signed into law S. 164, the “Advancing Education on Biosimilars Act of 2021,” which authorizes the Food and Drug Administration (FDA) to educate consumers and health care providers on biologic products, including biosimilars.

In March, the US Senate unanimously passed the bill, which directs the FDA to improve education on biosimilars with the goal of increasing uptake. Under the law, the FDA will create a biosimilars education website targeted at health care providers. Educational materials offered on the website may include:

• Explanations of key statutory and regulatory terms, including “biosimilar” and “interchangeable”, and clarification regarding the use of interchangeable biosimilars
• Information related to development programs for biological products, including biosimilars and interchangeable biosimilars, and relevant clinical considerations for prescribers
• An explanation of the process for reporting adverse events for biological products, including biosimilars and interchangeable biosimilars
• An explanation of the relationship between biosimilars and interchangeable biosimilars licensed under section 351(k) and reference products (as defined in section 351(i)), including the standards for review and licensing of each such type of biological product

Comparative data for originator biologics and biosimilars will also be made available; and, on an ongoing basis, the FDA will maintain continuing education programs to inform health care providers, including nurses, about biosimilars.

Read more about the Advancing Education on Biosimilars Act (S. 164) here.

Missed last month’s ASBM Newsletter? Read it Here.

DIA Global 2021 Annual Meeting

Virtual – June 27- July 1, 2020 

WHO 73rd INN Consultation

Geneva, Switzerland – October 19, 2021

World Drug Safety Congress

Boston, Massachusetts – October 20-21, 2021

World Biosimilar Congress Europe 2021

Basel, Switzerland – November 9-11, 2021

From March 29th-31st ASBM representatives led three panel discussions at the World Biosimilar Congress USA 2021, part of the annual Festival of Biologics USA. Typically held in San Diego, CA, the event was conducted virtually this year due the COVID-19 pandemic.

On March 29th, ASBM Steering Committee Member Andrew Spiegel moderated a keynote panel discussion entitled “Biosimilar Regulatory Reform”.  Panelists included Eva Temkin, Acting Director for Policy at the U.S. Food and Drug Administration’s Office of Therapeutic Biologics and Biosimilars from 2019-2021 and Leah Christl, former director of the Therapeutic Biologics and Biosimilars Staff (TBBS) in the Office of New Drugs (OND).

Panelists shared their thoughts on how clinical biosimilar development may evolve in the future, both in the US and in Europe. Also discussed were challenges in developing orphan biosimilar medicines including what is being done at regulatory level to encourage their development.

On March 31st, Spiegel moderated a second panel, entitled “Biosimilar Uptake and Progress from the Healthcare Perspective”. Panelists  included representatives from Hematology/Oncology departments at Boston Medical Center and Highland Hospital, and a representative from the pharmacy contracting company Vizient.

The speed of biosimilar uptake was a key topic of the discussion. Recently approved rituximab, trastuzumab, and bevacizumab oncology biosimilars, experienced much faster uptake than earlier biosimilars (filgrastim, peg-filgrastim, erythropoietin alpha and infliximab). Mr. Spiegel asked panelists whether they thought the adalimumab and etanercept biosimilars due in 2023 were likely to experience similarly speedy uptake. The Vizient panelist suggested uptake might be slower.  Gastroenterologists and rheumatologists have been less supportive of biosimilars than oncologists in his view, citing slower uptake among infliximab biosimilars.

On March 31st, ASBM Advisory Board Chair Philip Schneider moderated the Closing Keynote Panel that concluded the conference. The topic of the panel was “Harnessing influence  to change biosimilar policies: current programs and ideas for the future.”  Panelists included representatives from the ERISA Industry Committee (ERIC); Boston Medical Center; Ponchartrain Cancer Center; Employers Health; and Biocon.

Key points raised during the panel were the importance of transparency in the payment process- particularly among payers and the insurance companies; the role of competition and biosimilars in the marketplace to control the costs of expensive biologics, the need to align incentives among employers and providers, and the need for curricula on biologic in the education of health care professionals.

Learn more about the Festival of Biologics USA 2021 and view the full program agenda here. 
 

On March 12th, the Program Committee for the DIA Global Annual Meeting 2021 informed ASBM that our poster abstract “A Review of Problems with Pharmacovigilance Programs and Biologics” has been accepted for an ePoster presentation. The abstract was authored by ASBM Executive Director Michael Reilly and Advisory Board Chair Philip Schneider.

The poster will examine a variety of published literature on global pharmacovigilance of biologic medicines, with a focus on difficulties in accurately identifying biologics at the product level in Adverse Drug Reaction (ADR) reports and self reporting surveys (SRS). For example, in a 2019 analysis of European ADR reports for infliximab in 2018, 35% did not provide a brand name, despite this being required by EU law since 2012.

Lack of a consistent international standard for biologic naming was idenitifed as a barrier to biosimilar adoption in a recent WHO-sponsored 20-country study. “There is still no consensus among countries on the naming and labeling of biosimilars,” its authors observed, “and the WHO does not provide specific nomenclature for biosimilars.”

In 2014 the WHO’s INN Expert Group proposed a voluntary naming standard to promote accurate biologic identification. But despite early support for the standard from many countries including the US, Canada, Australia, and Japan, it has not yet been made available to national regulatory authorities.

DIA 2021 runs from June 27-July 1, 2021. EPosters will be featured in an online gallery within the virtual meeting platform that is hosting DIA 2021.

Learn more about DIA 2021 and see the draft Program Agenda here. 

A new study in the journal Regulatory Toxicology and Clinical Pharmacology suggests in vivo animal studies of biosimilars “have added little evidence to provide clinically relevant information for biosimilar development.” The authors reviewed animal study findings from development of eight biosimilars candidates. Among their findings:

• In vivo assessments show no unexpected safety or toxicity findings.
• These animal studies have added little clinically relevant information.
• The value of conducting in vivo studies for some biosimilars may be questionable.
• Comparative clinical studies are the best way to confirm clinical similarity.

The study will be published in the print edition of the journal Regulatory Toxicology and Pharmacology Volume 122, June 2021.

Read it online here.

On March 3rd, the US Senate unanimously passed the Advancing Education on Biosimilars Act (S 1681). The bill directs the FDA to improve education on biosimilars with the goal of increasing uptake.

The bill would require FDA to create a biosimilars education website explaining key statutory and regulatory terms associated with biosimilars, such as “interchangeability”. The website would be targeted at health care providers/
The bill would also require that comparative data for originator biologics and biosimilars is made available; and, on an ongoing basis, continuing education programs would be maintained to inform health care providers, including nurses, about biosimilars.

The Senate version of the bill was introduced in May 2019 and was voted on successfully in December 2020, but required a new vote this year. A House version of the bill (HR 4400) was introduced in September 2019 and referred to the Subcommittee on Health.

Read more about the Advancing Education on Biosimilars Act (S 1681) here.

Missed last month’s ASBM Newsletter? Read it Here.

Biologics Europe Online 

Virtual – April 26-27, 2021

DIA Global 2021 Annual Meeting

Virtual – June 27- July 1, 2020 

World Biosimilar Congress Europe 2021

Basel, Switzerland – November 9-11, 2021