Skylar Jeremias

Boehringer Ingelheim (BI) said that it has filed a citizen petition asking the FDA to change its interpretation of a portion of the Biologics Price Competition and Innovation Act (BPCIA).

Citizen petitions are an avenue for companies and other interested parties to ask the FDA commissioner to change agency regulations or take administrative action.

The company requested that the FDA alter its interpretation of the term “strength” as used in section 351(k) of the Public Health Services Act, in regard to parenteral solutions, to mean “total drug content” without taking into account the concentration.

According to BI, the FDA’s current interpretation does not allow a biological product to receive licensing as a biosimilar or an interchangeable biosimilar if there are any variations in the volume of inactive drug content, even if the amount of active drug content is consistent with the reference product.

“By working closely with industry peers, payors, healthcare providers, and patient advocates, and engaging in a transparent and public discussion of the issues we have raised, Boehringer Ingelheim believes that correction of the interpretation by the FDA may increase access to more affordable biosimilar and interchangeable biological products approved via the 351(k) pathway,” said the company in a statement.

BI Identifies 4 Issues With FDA’s Current Interpretation

, BI gave 4 specific reasons that the interpretation should be changed. The first was that it conflicts with the clear meaning of “strength” that Congress adopted in 2009 when it passed the BPCIA.

Second, the company argued that the current interpretation permits reference drug sponsors to use minor concentration changes to prevent competition from biosimilar and interchangeable biological products.

“We believe the actions requested in this petition will benefit patients and the healthcare system, potentially leading to more robust biosimilar development and use, and reduce anti-competitive behavior within the biosimilars industry,” said BI.

Third, BI noted that the interpretation allows for parenteral solutions to be treated differently than other parenteral products, such as lyophilized powder used in treating pediatric patients who have a growth failure, without appropriate justification.

Lastly, BI contended that its suggestion for “strength” to mean “total drug content” without regard to concentration better promotes the goals of the BPCIA and that there are no opposing regulatory interests that outweigh the benefits that the change could bring.

In the past, reference product manufacturers have 

 of citizen petitions to stall competition, using them to call on the agency to refrain from approving a generic or biosimilar product unless certain conditions are met.

In 2019, the FDA finalized industry guidance to prevent companies from using citizen petitions to delay market entry of competitive products.

In April 2019, HR 2387, a bipartisan bill intended to stop sham citizen petitions from disrupting the FDA’s approval process for generic drugs, was introduced into the House of Representatives. In November 2019, the House Energy and Commerce Subcommittee on Health voted to 

 the bill to the full Energy and Commerce Committee.

Articles

To spur more biosimilar development and reduce anticompetitive practices, the company argued the FDA could improve its interpretation of the term “strength” in the Biologics Price Competition and Innovation Act (BPCIA).

Boehringer Ingelheim Files Citizen Petition to Change FDA's BPCIA Interpretation

 a new draft guidance document to clarify submission procedures for applicants looking to gain licensing for a product seeking to be designated as an interchangeable biosimilar.

The question-and-answer document provides guidance for applicants as they formulate their submission documents  in order to streamline the approval process.

Interchangeability designations are important to ensure patients have access to biosimilars as they allow for biosimilars to be administered in place of a reference product without a pharmacist needing to request approval from a physician first.

 accepting comments on the draft guidance

 until January 19, 2021. Guidance documents represent the agency's most current thinking about a subject, but are not legally binding.  

 to clarify what data requirements are needed for a drug candidate to be licensed as an interchangeable biosimilar.

Gaining interchangeability status may require developers to conduct expensive and lengthy switching trials in additional to standard clinical trials, leading some 

 to call for the FDA to further revise their requirements. Currently, there are no biosimilars that have received this designation, however, a number of companies have 

Information for New Biosimilar Applicants

For applicants who are submitting a biologics license application (BLA) under the 351(k) of the Public Health Services Act for a new biosimilar but also want to have an interchangeable designation, they should indicate that in an affirmative statement in the cover letter for the application.

“This approach provides for a more efficient and predictable review of BLAs,” wrote the FDA.

However, if an application contains sufficient information for a candidate to be licensed as a biosimilar but does not contain enough information to receive an interchangeability designation, the agency said that it would split the application, review the BLA as if it was only for biosimilar licensing, and update the applicant in a complete response letter of what supplement information is needed to obtain interchangeability.

The FDA also said that applicants can specifically request that the agency only license a drug candidate as a biosimilar if it is also deemed an interchangeable product by including the phrase “INTERCHANGEABLE-ONLY REVIEW” in the cover letter accompanying the BLA.

If the FDA needs to send a complete response letter to the applicant because of missing information, it will include deficiencies pertaining to licensing as a biosimilar and as an interchangeable biosimilar because a demonstration of biosimilarity is a required to receiving interchangeability approval.

Once an applicant receives a complete response letter, they “may then choose to amend and resubmit their application to address the deficiencies and support a demonstration of interchangeability or to amend and resubmit their BLA seeking licensure as a biosimilar product,” wrote the FDA.

Under the guidance, applicants that already hold a BLA for a biosimilar should submit an original application to obtain interchangeability status under section 351(k). Applicants will still be able to market and distribute their biosimilar while their application is under review.

The FDA also included information on formatting labeling statements on interchangeability for BLA holders of an approved interchangeable biosimilar.

The FDA clarified a number of concerns surrounding the appropriate procedures for industry to apply for interchangeability status.

FDA Issues Draft Guidance Q&A on Biosimilar Interchangeability Submission Requirements

As the fate of the US biosimilar pathway was deliberated by the Supreme Court, experts weighed in throughout the month on what could be done to improve biosimilar access and uptake.

On November 10, the Supreme Court heard arguments on whether the individual mandate is severable from the Affordable Care Act (ACA). Caught in the middle of this argument is the Biologics Price Competition and Innovation Act (BPCIA), which outlines the regulatory pathway for biosimilars and is part of the ACA. The individual mandate, which was found to be unconstitutional, dictates that individuals must have health insurance or pay a penalty.

Chief Justice John Roberts, along with several associate justices, hinted that the 

 if the mandate is deemed severable, saying, “It’s hard for you to argue that Congress intended the entire act to fall if the mandate was struck down,” and that “there seems to be compelling evidence” that the intent of Congress was for the “rest of the law to survive if an unconstitutional provision were severed.”

In an expert column for The Center for Biosimilars

, 2 intellectual property attorneys offered their 

, stating that although a ruling for severability is likely, “It is not unheard of” for justices to do something unexpected.

Molly Burich, MS, associate director for Public Policy at Boehringer Ingelheim Pharmaceuticals, takes a cautious view of the potential for robust improvements in biosimilar access in the near future, but she 

 at the Association for Accessible Medicines GRx+Biosims 2020 conference, saying that current legislative efforts to boost biosimilar adoption have strong bipartisan support.

Burich examined 6 bills that have been introduced in the House of Representatives. These include bills that would eliminate patient cost sharing for biosimilars under Medicare Part B, increase incentives for providers to prescribe biosimilars, make patent information more accessible to developers, and increase biosimilar education efforts.

In November, the Supreme Court heard arguments on the Affordable Care Act, Europe fired up its efforts to create a more biosimilar-friendly environment, and Genentech fought to protect its bevacizumab franchise.

Biosimilar Legal Roundup: November 2020

Minute differences between biosimilars and reference products are not considered “clinically meaningful,” but these differences are exploitable when it comes to addressing allergies related to originator products, said a panelist at the National Policy and Advocacy Summit on Biologics.

In the United States, some physicians and patients remain wary of using biosimilars, even though the FDA certifies them as equivalent to originators on safety and clinical efficacy. Because they are made from living organisms, biologics—whether reference drugs or biosimilars—may differ slightly from one manufactured batch to another, but strict process controls keep these differences within tight margins of allowed variation.

Panelist Jeffrey VanDeusen, MD, PhD, explained that these subtle differences can actually be an asset in treating certain patients. “Instead of perhaps 1 therapy that is able to target a pathway, we've got multiple medications that are different enough that if a patient may be allergic to that medicine, now we have different options to offer that patient.”

VanDeusen, medical director of the James Cancer Network and an assistant professor of medicine at the Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, gave an example of one of his current patients with cancer who developed an allergy to originator trastuzumab (Herceptin) and was able to continue treatment using a biosimilar.

“Ten years ago, I would have had to stop the medication for her. Now, I can continue that medicine….I can effectively continue to control her disease without relying on new or different medicines,” he said.

VanDeusen discussed other ways biologics have improved treatment options in the oncology space. He said that biologics, especially growth factors, have extended the lives of patients much longer than before.

“We are able to target specific proteins in cancer cells or pathways in cancer cells, and this has allowed us to either control or even completely eliminate cancers, whereas before, we would just have drugs that would perhaps delay the growth for a while. Now, instead of weeks to months, we can change that to years or even a normal lifespan,” said VanDeusen.

Further, “as we get more and more sophisticated in our understanding of the immune system and how to help it defeat cancer, we are going to see biologics play a larger role as these agents are used in that in that type of fight.”

During the panel, VanDeusen mentioned that delays in diagnostic testing, with genomic sequencing or proteomics, could prevent patients from receiving a biologic treatment in a timely fashion. Without diagnostic testing, which can be expensive, physicians are not able to prescribe biologic treatments.

“For oncologists, when a procedure is done as a diagnostic test—for example, a liver biopsy—often there is a 2-week cool-off period, where we have to wait before additional testing can be ordered on the specimen. And in that time, the patient’s disease can grow. And that is hard for both the oncologist and the patient,” said VanDeusen.

Additionally, VanDeusen said that a lack of health coverage can delay diagnostic sequencing even further to where the patient’s symptoms may worsen, allowing the cancer to spread. In some cases, he said, delays may allow a patient’s disease to worsen to the point that therapy is no longer an option.

The National Policy and Advocacy Summit on Biologics was a virtual conference on November 18, 2020, hosted by Biologics Prescribers Collaborative, the Institute for Patient Access, and the Alliance for Patient Access.

Minute differences between biosimilars and reference products are not considered “clinically meaningful,” but these differences are exploitable when it comes to addressing allergies related to originator products.

Skylar Jeremias

Boehringer Ingelheim Files Citizen Petition to Change FDA's BPCIA Interpretation

FDA Issues Draft Guidance Q&A on Biosimilar Interchangeability Submission Requirements

Biosimilar Legal Roundup: November 2020

Providers Exploit Minor Differences Between Innovator Drugs and Biosimilars