Allison Inserro

Amneal Pharmaceuticals Wednesday said the FDA approved the company’s Biologics License Application (BLA) for bevacizumab-maly, a biosimilar referencing the originator product (Avastin).

Amneal said the product will be sold under the name Alymsys. It is the third bevacizumab biosimilar approved in the United States, and the second of 3 US biosimilars the company expects to see approved this year. 

Earlier this year, Amneal received approval of filgrastim-ayow (Releuko) which references Neupogen. The firm’s pegfilgrastim biosimilar referencing Neulasta is currently under FDA review.

Bevacizumab-maly was developed by mAbxience. The vascular endothelial growth factor inhibitor is indicated for the treatment of:

Metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy for first or second-line treatment

Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab product-containing regimen

First-line non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel

Metastatic renal cell carcinoma in combination with interferon alfa

Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan

Epithelial ovarian, fallopian tube, or primary peritoneal cancer, in combination with paclitaxel

Articles

Amneal said the product, to be sold under the name Alymsys, is the second of 3 US biosimilars the company expects to see approved this year.  

FDA Approves Amneal Pharmaceuticals’ Avastin Biosimilar, Bevacizumab-maly

A recent opinion piece highlighted the considerations that US stakeholders should include in any discussion about the necessary balance to finance new drug innovation, ensure incentives exist, and create a predictable framework for decision making, all while ensuring patient access, especially for new curative treatments.

Currently, the pharmaceutical system in the United States relies on companies having set periods of marketing exclusivity through intellectual property rights and the ability to command reimbursement to ensure a return on investment while awaiting future competition from biosimilars and generic drugs, explained the authors in the journal 

The provision for the entry of biosimilars, through the Biologics Price Competition and Innovation Act of 2009 (BPCIA) is new, they noted, and its impact is unknown, given the continued lagging introduction and uptake of biosimilars in the United States. With the exception of what they called “incremental provisions addressing specific gaps and priorities,” the current US drug system has been in place since the passage of the Hatch-Waxman act in 1984, the Bayh-Dole act of 1980, and the Stevenson-Wydler act of 1980.

However, there are multiple objectives that should be balanced when thinking about how to address future challenges, they wrote: effective incentives in order to create new therapies, encouraging competition, and making the treatment affordable.

Systems to finance drug innovation must balance multiple objectives, they said. Those objectives include “predictable frameworks” for payers and developers as they make long-range decisions, but these frameworks should also be flexible enough to adapt to new scientific advances.

However, they cautioned, the lack of what they call a “sustainable insurance coverage and payment model” could not only harm patient access but also deter future development.

For instance, they cited one estimate that says that by 2030, it is possible that 50,000 individuals might be treated with cell and gene therapies, mostly in oncology, at a hypothetical cost of $1 million per patient, or $50 billion for that area alone.

The authors cited prior research that says the research and development timeline, from inception to approval, is about a decade. Including the cost of failed candidates, average direct costs per approved new compound were $1.4 billion (in 2013 dollars). Fewer than 1 in 8 candidates entering phase 1 trials makes it to an approval.

Given these challenges, some have advocated other ways to provide for innovation and access, but there are pros and cons to those approaches, the researchers said.

Those methods include alternatives such as direct government purchasing, limits on certain patents and orphan drug designations, or conversely, targeted incentives for certain conditions. Other methods look to stimulate generic competition, such as barring “pay-to-delay” agreements.

Other ideas include outcome-based contracts and government prizes and backing of research and development activities. One example is Louisiana’s subscription-based model for unlimited hepatitis C drug access to its Medicaid and prison population.

Some of the concerns with these approaches include whether future innovation would be constrained, and in the case of more direct government involvement with research and development and purchasing, whether the government currently has the infrastructure to support an increased role.

Uncertainty about potentially curative, 1-time treatments could hinder investment if developers do not know who will pay the bill, but payers might be willing to consider alternative payment models for revolutionary therapies, depending on how they are constructed, the authors said.

A number of logistical and financial obstacles exist: if a treatment has a high-upfront cost and the patient may switch from 1 payer to another over a period of time, which party should bear the cost and which should reap the later benefits, in terms of having a healthier patient in their enrollee mix?

Alternatives to a single payment at the start of therapy could include breaking it up into smaller, multiple payments over time, much like a mortgage.

“However, given uncertainty about the magnitude and duration of the clinical effects of the new therapies, payers likely would require performance guarantees as part of the payment model,” the authors note.

But the idea of patients moving from one insurance plan to the next gives may payers pause, they said. To ensure patient accessibility and continued development of game changing therapies, experimentation and stakeholder input will be needed, the authors concluded.

Cutler D, Kirson N, Long G. Financing drug innovation in the US: Current framework and emerging challenges. 

. Published online May 26, 2020. doi:10.1007/s40273-020-00926-2

A recent opinion column outlines some principles to consider when thinking about changing the current US system of financing drug innovation, especially potentially curative therapies.

 

How to Pay for Future Drug Innovation? Paper Examines a Few Ideas

The next stop in a long-running court battle between Sandoz and Amgen over a biosimilar etanercept could be the Supreme Court of the United States, after a federal court upheld 2 patents held by Amgen for its originator drug Enbrel. In 

 Wednesday, the US Court of Appeals for the Federal Circuit ruled against Sandoz, which won FDA approval for Erelzi in August 2016.

In a statement, Sandoz said it was reviewing all options, including a possible appeal to the high court, and said it “cannot speculate on next steps or timing."

“Sandoz will continue its efforts to make Erelzi available to US patients with autoimmune and inflammatory diseases,” said Carol Lynch, president of Sandoz US and head of North America, 

. "Our company respects valid intellectual property, however Sandoz continues to believe the patents asserted by Amgen are not valid, and that it should not be able to use them to extend the drug’s exclusivity."

The win solidifies Amgen’s biggest moneymaker and best seller; Enbrel generated $1.15 billion in first-quarter sales for this year and is the biotech company’s best-selling drug.

, which covers the fusion protein etanercept, and US Patent 

, which covers a method of manufacturing. The 2 patents expire in 2028 and 2029, respectively. Roche was the first to file applications for these patents, and Amgen and its subsidiary Immunex obtained rights to the patents from Roche.

Prior to a 2-week bench trial in September 2018, Sandoz did not contest infringement of the patents, but asked the court to find the patents invalid because of a lack of written description and enablement, obviousness, and obviousness-type double patenting.

US District Judge Claire C. Cecchi, JD, found that Sandoz failed to show by clear and convincing evidence that the patents are invalid. Two judges Wednesday affirmed her decision, saying it founded the biosimilar manufacturer’s arguments unpersuasive.

Elrezi, like another eteanercept biosimilar, Eticovo from Samsung Bioepis, is sold in the European Union. Eticovo is also FDA-approved but has yet to launch.

 found that 72% of Enbrel's total patent applications were filed after it had already received FDA approval.

Sandoz said it was reviewing all options, including a possible appeal to the Supreme Court. The case concerns Amgen's originator drug Enbrel and the biosimilar Erelzi.

Federal Panel Upholds Decision Against Sandoz 2-1 in Enbrel Battle With Amgen

A series of reports from a subsidiary of drug distributor McKesson says patients are having trouble getting the medications they need—particularly specialty medications&mdash;due to prior authorization requirements and cost, among other things.

, CoverMyMeds said electronic prior authorization (ePA) can help speed up the process to get approval for specialty medications. ePA can cut approval time from 17 days using phone and fax to as little as 1.5 days, the report said.

According to one survey conducted by the company, 60% of patients have reported some difficulty in getting their first dose of a specialty medication. A survey of providers said that 91% of them said that prior authorizations have delayed care, and 75% reported that the prior authorization process caused their patients to abandon treatment.

Providers are using outdated technology such as phone and fax to complete prior authorization requests, and this is part of the problem, the report said. On the approval side, nearly 100% of payers and pharmacies accept ePAs.

Other reasons have to do with physicians not acting soon enough. Only 17% of providers say they initiate the prior authorization request at the time the prescription is written, with the majority of the requests, 60%, happening retrospectively. Another 20% complete the request after a patient tells them authorization it is needed.

At the same time, a majority of providers report a heavy administrative burden completing the authorization request—an average of 2 business days a week. That burden has increased over the past 5 years, 88% of providers said.

The administrative process cuts into time with patients, said 26% of providers; and 16% said they have less time to interpret lab and scan results.

The use of costly specialty meds, often for rare and chronic conditions, is increasing at more than twice the rate of other medications. They account for 45.4% of total pharmacy spending, this week's report said; 

 predicts that specialty drugs will soon account for 55% of US drug spending, as more expensive, although potentially curative, therapies are in the pipeline.

To facilitate access to specialty medications, vendors, or so-called hubs, that provide patient support have sprung up, the report notes. Specialty pharmacies can also provide assistance. But only 40% of providers and 80% of patients are aware of the services, the report said.

The use of specialty medications has also created affordability issues for patients, the report notes. Some 29% said they have quit their therapies. With the rise of high-deductible health plans, which force patients to pay more out of pocket (OOP), patient abandonment of treatment has become more common. For each dollar increase in average OOP costs, the report said, prescription therapy abandonment rises 0.6%, the report said.

AARP noted last year that the average annual price for a single specialty drug used for a chronic condition for a Medicare beneficiary is $79,000. The CoverMyMeds report said 69% of patients surveyed have made “personal sacrifices” when the deductible is in effect.

Although the cost of specialty drugs is an increasing concern for patients as well as payers and employers, 

 said that few US health plans select biosimilars as a cost-savings option. Just 14% of US health plans selected a biosimilar as the preferred drug in the time period covered by the report.

Patients have problems getting timely authorizations for specialty meds and physicians face time burdens in getting them approved, a new report from CoverMyMeds says.

Authorization for Specialty Drugs Still a Patient Hurdle, Report Says

What do UK patients think about the process and communication used to switch to adalimumab biosimilars by the National Health Service (NHS) and the local home care trusts?

 at the European Hematology Association (EHA)’s 25th Annual Congress, EHA25 Virtual, not very much.

, even before the results of the tender for adalimumab (reference product Humira) had taken place. The United Kingdom has made no secret of its hopes of significant cost savings on a switch to biosimilar adalimumab, aspiring to save £300 million (approximately US $386 million) of its £400 million (approximately US $514 million) annual spending on adalimumab as a result of using biosimilars.

In the UK setting, self-administered biologics are delivered to patients in their homes by commercial companies that are paid for by pooled funds from the pharmaceutical industry. Once a prescription is initiated by a hospital prescriber, nurses deliver the products and teach patients how to inject their therapy at home.

Nearly 2 years in, researchers sought patient feedback on the switch process with the intent of reporting findings to NHS England. In addition, they sought to give organizations representing rheumatology, dermatology, and gastroenterology patients information to develop any future resources to help improve shared decision making (SDM).

These organizations had worked with National Health Service (NHS) to produce the materials for disseminating information to prescribers and patients, and they now wanted to know how the process was implemented and if SDM was practiced.

A working group of 4 organizations created an online survey asking questions about:

How the individual was communicated with regarding their treatment being switched to a biosimilar

Was there any choice or perceived input into the decision making process

Overall satisfaction on how the individual felt their personal preferences/needs were met

The results demonstrate how challenging the switch process turned out to be.

899 useable responses, with patients identifying as 52% rheumatology, 42% gastroenterology, and 5% dermatology patients; the remaining 1% were “more complex specialties,” the researchers said.

More than half of patients were not asked for their consent before their treatment was switched to a biosimilar adalimumab, while 40% said they gave consent. A minority (7%) couldn’t remember or were unsure if consent was given.

Three-fourths were not at all satisfied or not satisfied with the ability to decline being switched. Just 12% felt that they had been given an option to refuse the switch.

SDM “needs to be put into action not just words,” concluded the authors, who represented the National Rheumatoid Arthritis Society, 1 of the 4 organizations that created the survey. The other organizations were the National Axial Spondyloarthritis Society UK; Crohns’ & Colitis UK; and the Psorarsis Association, UK.

They said they will continue to work with NHS and other stakeholders to make SDM “a reality not just rhetoric.”

The UK results show how challenging switching to a biosimilar can be, according to patient groups.  

Looking Back, UK Patients Unhappy With Adalimumab Biosimilar Switch

Plaintiffs in a novel class-action lawsuit against AbbVie have until the end of June to try again to pursue their claims that the maker of the blockbuster originator adalimumab (Humira) had created a patent thicket of invalid and unenforceable patents as well as conspired in so-called “pay-for-delay” schemes with competitors to delay market entry.

The judge in the case, while noting that the patents have made it nearly impossible for rivals to gain a foothold, said the suit did not constitute a valid antitrust claim.

, filed last fall, AbbVie said that the suit seeks to “upend the well-settled balance between the patent and antitrust laws,” that the complaint would end international early-entry patent settlements that do not have the same global market entry date, and that it would “chill medical and therapeutic innovation.”

, US Northern District Court Judge Manish Shah dismissed the consolidated class action suit filed by unions and local governments without prejudice and gave the plaintiffs until June 29 to file a statement as to whether they wish to file an amended complaint or ask that the dismissal convert to a dismissal with prejudice so they can seek appellate review.

AbbVie has more than 100 patents on Humira, which the plaintiffs tried to assert was anticompetitive. In addition, the plaintiffs alleged that the agreements AbbVie reached with 

 to prevent competition in the United States, while allowing entry in Europe, constituted illegal market allocation based on geography.

The judge wrote that AbbVie may have acted aggressively to protect the Humira patents, but wrote that the suit does not meet the standard for competitive harm that falls under antitrust law.

In his dismissal, the judge said the company is immunized from antitrust liability by the 

 doctrine, which holds that there is immunity for defendants’ efforts to petition the government for relief that allegedly has anticompetitive effects.

Shah would have had to find that the firm’s petitions (patent applications, patent dance exchanges, and resulting lawsuits) are “objectively baseless.” With a success rate of 53.4% of AbbVie’s patent applications resulting in patents, “it compels the conclusion” that they are not objectively baseless, the court wrote. As well, the company had a high rate of success during 

The judge did find that not all of AbbVie’s conduct was protected by 

 during the patent dance, but said that the “plaintiffs’ theory depends on all the components of AbbVie’s conduct as the means to suppress competition.”

He also did not find a basis for the assertion that the “European entry dates are the quid pro quo for the U.S. market entry dates, and for the period that falls between the two, AbbVie effectively allocated to itself the U.S. market while allocating to the other defendants the European market.”

These arrangements were not illegal and did not meet the Supreme Court’s standard to be considered an anticompetitive “reverse payment.” Furthermore, the court found that plaintiffs failed to plead antitrust injury, as the existence of even “one valid and infringed patent” would have precluded biosimilar manufacturers from entering the US market prior to 2023.

In addition, the judge said the plaintiffs were not successful in pleading antitrust injury because they did not allege that all of AbbVie’s asserted patents were invalid or unenforceable.   

 think the case is not yet over, calling it an area of unsettled law, but for now, it appears to give an advantage to originator firms looking to defend themselves against aggressive patent portfolios and to settle cases with rivals under the Biologics Price Competition and Innovation Act.

A request for comment from the plaintiffs' attorneys was not immediately returned. 

The judge in the Humira case, while noting that the patents have made it nearly impossible for rivals to gain a foothold, said the suit did not constitute a valid antitrust claim.

Plaintiffs Suing AbbVie Have Until June 29 to Decide Whether to Continue Class Action

Patient safety might be compromised because of home infusion regulatory changes brought about by the coronavirus disease 2019 (COVID-10) pandemic, according to the Community Oncology Alliance (COA), although other groups support the changes, which affect Medicare Part B beneficiaries.  

The virus has altered healthcare not just for those with the novel virus, but also for patients with cancer or rare diseases. Providers are working overtime to accommodate the sudden need.

 to increase the capabilities and ranks of frontline healthcare workers during this emergency. In an additional change, added Thursday, CMS allowed doctors to work across state lines and nurse practitioners to perform medical exams in nursing homes.

Many providers are pleased with these new flexibilities, which include the use of telehealth.

 standards for home infusion therapy, physician contracts, remote monitoring, and coverage determinations  

Last week, COA said of the health of patients with cancer could be jeopardized by some of these changes. COA said it 

 home infusion of chemotherapy, cancer immunotherapy, and supportive drugs related to cancer.

Home infusion “by a provider who may not be a trained oncology nurse and may not recognize or be prepared to treat any of the serious adverse reactions that frequently occur is of significant concern,” COA said, adding that many of the adverse events related to cancer treatment cannot be adequately monitored if patients are self-administering at home.

Cancer treatments can lead to unpredictable adverse events, so a COVID-19–related measure allowing home infusion jeopardizes patient health and safety, according to the Community Oncology Alliance (COA).

COA Says COVID-19 Policy Changes Put Patients at Risk

question-and-answer guidance document for industry

 about the upcoming transition for how certain products will now be approved under a biological pathway, including exceptions to the transition and how companies will receive notifications about their applications.

The nonbinding final industry guidance, “The ‘Deemed to be a License’ Provision of the BPCI Act: Questions and Answers” represents the FDA’s current thinking as it implements the “transition” provision of the of the Biologics Price Competition and Innovation Act of 2009 (BPCIA).

The document aims to facilitate transition planning and describes FDA’s compliance policy for the labeling of biological products that are the subject of deemed biologics license applications (BLAs). Besides insulin, other biological products affected by the transition include human growth hormone (somatropin), pancrelipase, chorionic gonadotropin, follitropin alfa, and menotropins.

An application for a biological product previously approved under section 505 of the Federal Food, Drug, and Cosmetic Act will change on March 23 and will be deemed to be a license for the biological product under section 351 of the Public Health Service (PHS) Act. Last month, the FDA 

 on the definition of the term “biological product.” The FDA said it was no longer necessary to include the interpretation of the term “chemically synthesized polypeptide” as first proposed in December 2018.

The document lays out certain exceptions to the transition period and also how such products will be identified.

The BPCIA is “silent regarding the process for accomplishing the transition of approved NDAs to deemed BLAs,” the document noted. The FDA intends to send a letter to those application holders on March 23 advising that the approved NDA was deemed to be a BLA at 12:00 am Eastern Daylight Time on March 23 and no longer exists as an NDA.

If the NDA is approved on March 23, the approved NDA will be deemed to be a BLA immediately after approval.

Three questions address situations of particular interest to developers:

One discusses where an applicant might, or might not, be able to use the FDA’s finding of safety, purity, and potency for another licensed biological product. For the most part, an applicant cannot rely on data from another product.

Another discusses if a biological product approved in an NDA that is deemed to be a 351(a) BLA on the transition date can later be a “reference product” for a proposed biosimilar or interchangeable product.

And another discusses when the application holder for a biological product that is the subject of a deemed 351(a) BLA can seek a determination of biosimilarity or interchangeability under section 351(k) of the PHS Act to another biological product licensed under section 351(a) of the PHS Act.

The document addresses things like application numbers, license numbers, program fees, withdrawals of applications, and labeling requirements. It also discusses supplements to applications, including changes to manufacturing sites, comparability data, batch analysis data, appropriate stability data, and facility inspections.

It also includes information about the transition from the Orange Book to the Purple Book and about the designation of proper names.

Looking to March 23, the FDA released a question-and-answer guidance document for industry about the upcoming transition for how certain products will now be approved under a biological pathway, including exceptions to the transition and how companies will receive notifications about their applications.

FDA Releases Q&A for Industry With Details About Insulin Transition

Pregnancy in women with rheumatic and musculoskeletal disease (RMD) may lead to serious maternal or fetal adverse outcomes, but the majority of women with RMD can have successful pregnancies with adequate planning, treatment, and monitoring, the American College of Rheumatology (ACR) said Monday as it released the first clinical practice guideline regarding the management of reproductive health in this population.

2020 Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

 includes 12 ungraded good practice statements and 131 graded recommendations that are intended to guide care, except where indicated as being aimed at patients with specific conditions or antibodies present, such as systemic lupus erythematosus (SLE); antiphospholipid antibody, or APL (persistent moderate-to-high—titer anticardiolipin or anti–β2-glycoprotein I antibody or persistent positive lupus anticoagulant); or antiphospholipid syndrome (APS), either obstetric and/or thrombotic.

Taking into consideration patients’ values, preferences, and comorbidities, the guidelines, based on clinical evidence, are a pathway to a shared decision-making process between patients and their physicians, the ACR said.

The ACR said that “good practice statements are those in which indirect evidence is compelling enough that a formal vote was considered unnecessary.” They are presented as suggestions rather than formal recommendations.

While some of the recommendations are strong, many of the recommendations presented are conditional due to a lack of data. Pregnant women are not generally enrolled in clinical studies, and few maternal health studies focus on patients with these diseases, the ACR noted.

The recommendations are divided into 6 categories: medication use, contraception, assisted reproductive technology, fertility preservation with gonadotoxic therapy, menopausal hormone replacement therapy, and pregnancy assessment and management.

The guidelines make a strong recommendation against use of cyclophosphamide (CYC) and thalidomide in men prior to attempting conception, and a strong recommendation against the use of nonsteroidal anti-inflammatory drugs in the third trimester.

For biologic medications, the guidelines conditionally recommend continuing anti—tumor necrosis factor inhibitor therapy with infliximab, etanercept, adalimumab, or golimumab prior to and during pregnancy. In addition, the guidelines strongly recommend continuation of certolizumab therapy prior to and during pregnancy; certolizumab does not contain an Fc chain and thus has minimal placental transfer.

The guidelines conditionally recommend continuing treatment with anakinra, belimumab, abatacept, tocilizumab, secukinumab, and ustekinumab while a woman is trying to conceive, but discontinuing once she is found to be pregnant.

In addition, the guidelines conditionally recommend continuing treatment with rituximab while a woman is trying to conceive, and conditionally recommend continuing rituximab during pregnancy if severe life- or organ-threatening maternal disease warrants.

Patients with RMD typically underutilize effective contraception, the guidelines say, even though the risks of unplanned pregnancy include worsening or life-threatening disease activity as well as adverse pregnancy outcomes such as pregnancy loss, severe prematurity, and growth restriction. Congenital birth defects are another risk.

The guidelines specify a strong recommendation for women with rheumatic disease who do not have lupus or APS to use effective contraceptives. In addition, the guidelines provide a conditional recommendation to preferentially use highly effective intrauterine devices or a subdermal progestin implant.

In women who test positive for APL or APS, there is a strong recommendation against using combined estrogen-progestin contraceptives.

Fertility is typically normal in women with RMD, assuming they have not received treatment with CYC, the authors said.

The authors strongly recommend proceeding with assisted reproductive technology if needed in women with uncomplicated RMD who are receiving pregnancy-compatible medications, whose disease is stable, and who are negative for APL.

They make more specific recommendations for patients who test positive for APL and suggest an anti—blood clotting procedure. However, the guidelines provide a conditional recommendation against increasing prednisone dosage during fertility therapy procedures in patients with lupus.

For men, the guidelines state a good practice suggestion to cryopreserve sperm before CYC treatment in men, if they wish, and a conditional recommendation against testosterone co-therapy in men with rheumatic disease receiving CYC.

For women, the guidelines state a conditional recommendation for monthly gonadotropin-releasing hormone agonist co-therapy for premenopausal women with rheumatic disease who are receiving monthly CYC injections/infusions to prevent premature ovarian insufficiency.

The guidelines make a strong good practice suggestion to advise women who are considering pregnancy about the improved maternal and fetal outcomes associated with starting pregnancy during low disease activity.

The guidelines also make a conditional recommendation to treat patients lupus with low-dose aspirin daily (81-100 mg) starting in the first trimester. For women testing positive for APL who do not meet the criteria for obstetric or thrombotic APS, it is conditionally recommended to preventatively treat with a daily aspirin (81-100 mg) starting early in pregnancy and continuing through delivery.

Menopause and Hormone Replacement Therapy

The guidelines make a good practice suggestion to use hormone replacement therapy (HRT) in postmenopausal women with rheumatic disease who do not have lupus or have a positive APL test and who have severe vasomotor symptoms, have no contraindications, and desire treatment.

The guidelines make a conditional recommendation for HRT in women with lupus and without APL. They conditionally recommend against treating with HRT for women with asymptomatic APL and strongly recommend against hormone replacement therapy for women with any form of APS.

The guidelines, based on clinical evidence, are a pathway to a shared decision-making process between patients and their physicians, said the American College of Rheumatology (ACR).

ACR Releases Guideline to Managing Reproductive Health With Comorbid Rheumatic Disease

 about the long-awaited shift that begins March 23, when insulin and certain other biological products transition to a new regulatory pathway, as it amended the definition of “biological product” to match recent statutory changes regarding use of the word “protein.”

In addition, FDA published information for 

 about the changes, stressing that the changes won’t have an impact on access, prescribing practices, or product appearance.

Besides insulin, other biological products include human growth hormone (somatropin), pancrelipase, chorionic gonadotropin, follitropin alfa, and menotropins.

The changes reduce “regulatory uncertainty,” the FDA said, and “will allow both FDA and private industry to avoid spending time and resources on case-by-case determinations for each product.”

The final rule, “Definition of the Term ‘Biological Product,’” incorporates changes made by the Biologics Price Competition and Innovation Act (BPCIA) of 2009 and language relating to the FDA in the end-of-year spending bill signed into law by the president in December 2019.

The bill, the Further Consolidated Appropriations (FCA) Act, removed the parenthetical “(except any chemically synthesized polypeptide)” from the category of “protein” in the statutory definition of “biological product.” The parenthetical phrase was included in the BPCIA Act definition of  biological product in section 351(i) of the Public Health Service (PHS) Act.

Thus, FDA said Thursday, it was no longer necessary to include the interpretation of the term “chemically synthesized polypeptide” 

The definition of “protein” would encompass any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size.

Starting March 23, an application for a biological product approved under the Federal Food, Drug, and Cosmetic Act (FD&C Act), including applications for insulins and other biological products, will be deemed to be a license for the product under the PHS Act.

Insulin biosimilars approved under the PHS Act will be able to seek interchangeable designations for the first time, and interchangeable insulins will be, pursuant to state laws, eligible for substitution at the pharmacy level.

“This transition will open new pathways for manufacturers to bring biosimilar and interchangeable versions of insulin and other transitioning products to market, facilitating greater competition in the marketplace,” FDA Commissioner Stephen M. Hahn, MD, 

So far, only Boehringer lngelheim Pharmaceuticals has announced its intention to seek interchangeability status, for its adalimumab biosimilar, Cyltezo, which cannot launch until at least July 1, 2023, due to a patent settlement with AbbVie, the manufacturer of the originator product, Humira.

Also on March 23, the FDA will remove biologic products approved through New Drug Applications from the Orange Book and into the Purple Book.

The FDA said it was no longer necessary to include the interpretation of the term “chemically synthesized polypeptide” as first proposed in December 2018.