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Biosimilars Law Blog

Posted in News & Events

EMA takes steps toward facilitating global clinical trials for biosimilars

Applicants for marketing authorisation for biosimilars in the European Union (“EU”), under certain conditions, will be able in the near future to use batches of reference biological medicinal products sourced from outside the European Economic Area (“EEA”) in pre-clinical and clinical studies that are part of the comparability exercise preceding authorisation of biosimilars. On 28 September 2012, the European Medicines Agency (“EMA”) announced that it has updated its procedural advice document for applicants for marketing authorisation for biosimilars to reflect this change.

As a result, pharmaceutical companies developing biosimilars in multiple jurisdictions both within and outside the EU would be permitted to conduct related comparability studies with batches of the reference medicinal product sourced from outside the EEA without the need to repeat the studies with EU-sourced reference product batches. This would simplify the global development of biosimilars and would avoid the duplication of studies. The requirement that the reference biological medicinal product is authorised to be placed on the market in the EU is, however, maintained. Applications for marketing authorisation in the EU for biosimilars relying on a reference medicinal product which is not authorised in the EU would not be permitted.

The new regime will apply after the adoption of the revised EMA Guideline on similar biological medicinal products (CHMP/437/04) (“EMA Biosimilars Guideline”). The draft of the revised Guideline is expected to be published and released for public consultation in the beginning of 2013. The expected date for the adoption of the revised EMA Biosimilars Guideline is not yet announced. Continue Reading

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FDA has announced rates for biosimilar user fees for FY 2013

The biosimilar biological product development (BPD) fee has been set at $195,880 (10% of the full application fee).  This is the amount due when a sponsor submits an investigational new drug (IND) application for a biosimilar (or within 5 days of FDA granting a BDP meeting request – whichever occurs first).

When a sponsor is ready to submit a fully-developed biosimilar marketing application, the application fee for FY 2013 is $1,958,800 ($979,400 if the application does not include clinical data).

Notably, President Obama’s budget for FY 2013 projected approximately $20 million to be collected by the federal government in biosimilar user fees.  Based on the just-announced user-fee rates, therefore, a maximum of 10 biosimilar marketing applications have been anticipated, and probably somewhat fewer depending on whether (and how many) INDs are anticipated.  However, even if we see half that many applications in FY 2013, it will still be enough to trigger a host of novel issues, including the sharing of each application with the corresponding pioneer and the initiation of the biosimilar patent exchange procedures.

FDA published details of the user fees in an August 1, 2012 federal register notice.

Posted in Uncategorized

President signs The Food and Drug Administration Safety and Innovation Act: Summary of certain key provisions

President Obama recently signed into law The Food and Drug Administration Safety and Innovation Act (FDASIA). FDASIA will reauthorize for another five years the Prescription Drug User Fee Act (PDUFA V) and the various related user fee agreements between the drug and device industries and FDA. FDASIA includes provisions related to drugs, devices, generic drugs, and biosimilar biological products.

Below is a summary of certain key provisions pertaining to innovator and, where specified, generic drugs and biosimilar biological products. Continue Reading

Posted in News & Events

Biosimilars Marching Forward as Planned

With the 5-4 decision from the U. S. Supreme Court upholding almost the entire Patient Protection and Affordable Care Act, for those who were hoping for a fresh opportunity to re-debate the biosimilars statute, and perhaps plug some holes or make some basic changes to the law, those hopes have been dashed for now.

While the merits of the Biologics and Price Competition Act were not in play during the Supreme Court’s evaluation of the constitutionality of PPACA, few changes to the approval and regulations of medicines in this country have had the potential for such a large effect on what medicines will be available to patients.  Prior to enactment, there was no abbreviated pathway for approval of biologic medicines under the Public Health Service Act. BPCIA, buried within PPACA, created that pathway in the U.S.

With Thursday’s (June 28, 2012) Supreme Court decision, any remaining legal debris has been cleared from the path and it looks like biosimilars in the U.S. will march ahead.

Posted in News & Events

Breaking decisions from the Supreme Court: Term in review

On Tuesday afternoon, three of Hogan Lovells’ Appellate practice partners will provide an analysis of some of the key decisions that will impact businesses as the Supreme Court concludes its current term.

Neal Katyal, former Acting Solicitor General of the United States and Appellate practice Co-Director, Cate Stetson, Co-Director of our Appellate practice; and Chris Handman, a seasoned Appellate partner, will conduct a 30-minute webcast on the ramifications of decisions handed down by the high court this term, which may include the Affordable Care Act, and how the three key cases challenging aspects of President Obama’s healthcare plan will be resolved.  As previously posted, the outcome of the decisions on the Affordable Care Act could have direct implications for the U. S. biosimilars pathway.

The half-hour program, which begins at 1 p.m. on June 26, will also provide essential background on the Supreme Court, including the composition, recent personnel changes, and background on the Justices, and explain the impact of these structures on the decisions.

Register online for the free webcast.

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Making U.S. Biosimilars a Reality – Everyone Seeks Clarity and Direction from FDA

The usual suspects from regulated industry, patient and physician groups turned out for the U.S. Food and Drug Administration’s public meeting on the biosimilars guidances.  Now that the draft guidances have been out for several months and the FDA has a stack of comments to consider, the dialogue has moved from the theoretical to the practical:  How is this really all going to work?

Stakeholders lined up for their turns at the podium at the Public Hearing held on May 11, 2012.  To be sure, there were the predictable disagreements among stakeholders on issues such as naming and interchangeability, in addition to the now-familiar (and sometimes conflicting) views on the need to protect patient safety, encourage product innovation, and create meaningful cost-savings.  However, the strong consensus that FDA should implement an education and communication plan about biosimilars was noteworthy.  For example, a speaker from the American Pharmacists Association said pharmacists don’t know what to expect or do when they start seeing prescriptions for biosimilar products. Patient advocates and physician groups also said their constituents will need additional educational materials and are interested in interactive presentations from FDA on the appropriate use of these new products. 

It’s not clear what steps FDA will take to articulate clear policy and provide guidance in these areas.  At the hearing, however, the agency asked speakers for details and supporting data, and encouraged everyone to submit these and other concrete suggestions on implementation to the docket (FDA-2011-D-0618), which is open until May 25th.

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SCOTUS review of the Patient Protection and Affordable Care Act and “the biosimilar thing”

While a Supreme Court ruling on the constitutionality of the healthcare reform law is not expected until June, sponsors and regulators continue to lay the groundwork for biosimilars in the U.S. An unintended consequence of embedding the Biologics Price Competition and Innovation Act within PPACA without a severability clause leaves the biosimilars law vulnerable to the fate of constitutional challenges to more controversial parts of the Affordable Care Act. 

The Supreme Court recently concluded three days of oral argument challenging the constitutionality of several provisions of PPACA. There was general agreement amongst the petitioners, defendants and the Justices that the biosimilars provisions are “peripheral” to the challenges under review by the Court.  Nevertheless, it remains possible that if the Court decides any one provision (such as the so-called “individual mandate”) is unconstitutional, rather than parsing out the constitutional bits, even those recognized to be peripheral to the provisions at issue, the Court could strike down the entire Act to let Congress sort it out.  So even though “the biosimilar thing,” as described by Justice Breyer, would seem to stand on its own without the other parts of the Act, the BPCIA could be swept into a sweeping decision that would invalidate the biosimilars pathway along with the rest of the Act.

The BPCIA was the result of significant bipartisan effort and support in both the House and Senate.  FDA reports (PDF) at least 35 requests for biosimilar pre-IND meetings as of February 15 and is holding a public meeting on the three issued draft biosimilar guidances in May.  If the Supreme Court throws out the BPCIA with the bath water, it is reasonable to expect that the law would be re-enacted as a stand-alone.  However, as we head into the presidential election season, the ability or will of Congress to enact any laws may come to a halt.  There is little profit here in speculation, but in terms of setting expectations, it is possible that the BPCIA would come off the books temporarily, leaving many interesting questions about the legal significance of the gap period if the law were re-enacted in, say, early 2013. 

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Awaiting FDA Guidance on Interchangeability for Biosimilars

The three draft Guidances recently released by the U.S. Food and Drug Administration on implementation of the Biologics Price Competition and Innovation Act of 2009 focus on how to demonstrate biosimilarity but don’t say much about demonstrating interchangeability.  FDA has asked for stakeholder input on biosimilar interchangeability at the agency’s upcoming one-day public hearing on the biosimilar draft Guidances to be held on May 11, 2012. Docket No. FDA-2011-D-0618. However, there are a few tidbits on interchangeability in the draft Guidances.


By statute, to be found interchangeable, a biological product must:

  • Be biosimilar to the reference product;
  • Be expected to produce the same clinical result as the reference product in any given patient; and
  • If the product will be administered more than once to a patient, the risk (in terms of safety or diminished efficacy) associated with switching between the product and the reference product cannot be greater than the risk of repeated use of the reference product.

There are two potentially significant implications of FDA determining that a product is interchangeable with a reference product.  First, an FDA finding of interchangeability means the product “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.”  An important unanswered question is how this federal statutory definition will intersect with state laws governing pharmacy substitution of prescribed drugs.  Second, the first biological product found to be interchangeable with a given reference product receives a period of exclusivity during which no other product can be approved as interchangeable to the same reference product.

Statements on Interchangeability in the Draft Guidances

For those awaiting guidance on interchangeability, the draft Guidances released in February provide remarkably little, but there are a few statements of interest.

FDA is not sure what data will be needed to demonstrate interchangeability

The Q&A Guidance (PDF) affirms the ability to file for and achieve an interchangeability determination in an initial 351(k) application, as well as in a supplement, and in the same paragraph states:

“At this time, it would be difficult as a scientific matter for a prospective biosimilar applicant to establish interchangeability in an original 351(k) application given the statutory standard for interchangeability and the sequential nature of that assessment. FDA is continuing to consider the type of information sufficient to enable FDA to determine that a biological product is interchangeable with the reference product.” (Q&A I.14.)

Interchangeability applies to delivery device

Differences in products’ delivery devices or container closures may be relevant to interchangeability.

“(D)esign differences in the delivery device or container closure system used with the proposed biosimilar product may be acceptable. . . . Additional considerations apply for a proposed interchangeable product. For example, in reviewing an application for a proposed interchangeable product, FDA may consider whether the differences from the reference product significantly alter critical design attributes, product performance, or operating principles, or would require additional instruction to healthcare providers or patients, for patients to be safely alternated or switched between the reference product and one or more interchangeable products without the intervention of the prescribing healthcare provider. Additional performance data about the delivery device may also be necessary.” (Q&A I.4.)

Interchangeability (or not) should be stated in the label

In the section on labeling of the Scientific Considerations Guidance (PDF), mention is made that labeling should clearly indicate “This product (has or has not) been determined to be interchangeable with the reference product.” (Scientific Considerations at 21)

Foreign-reference product data not likely to support interchangeability

While elaborating on the considerations for sponsors in the use of comparative non-clinical and clinical data with a non-U.S.-licensed product, FDA notes that such data are unlikely to fulfill the additional requirements to support interchangeability.

“At this time, as a scientific matter, it is unlikely that clinical comparisons with a non-U.S.-licensed product would be an adequate basis to support the additional criteria required for a determination of interchangeability with the U.S.-licensed reference product.” (Q&A I.8)

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So, although the Guidances provide significant information and direction regarding biosimilarity and biosimilar applications, FDA’s thinking on interchangeability – or at least what the agency is willing to say publicly about its thinking – is not as advanced.  The May 11 public hearing may be an opportunity to learn more, identify to FDA issues that need to be addressed, and perhaps propose how they should be addressed.

Posted in News & Events

Biosimilars: Who’s Who at FDA?

According to several recent presentations by U.S. Food and Drug Administration (FDA) officials, the agency has established three committees charged with discussing and coordinating issues related to biosimilars to ensure consistency in the regulatory approach and guidance to sponsors.  While FDA set up this infrastructure some time ago, with the issuance of the Draft Guidances and the upcoming Stakeholder Meeting, it is important to understand where the key policy and precedent-setting decisions will be made. 

Essentially, CDER and CBER have established a joint implementation committee, and CDER and CBER have each established their own review committees.   CDER, however, appears to be playing a lead role in managing the process, as sponsors are directed under the Biosimilars Q&A Document to contact CDER’s Office of Medical Policy to initiate any questions or dialogue with the joint implementation committee.

We also note that there will be one or more representatives from the Office of the Commissioner – which may include the Office of the Chief Counsel – on the joint implementation committee.  The Office of the Commissioner typically refrains from being directly involved in individual product development programs and reviews.  However, the Office of the Commissioner is now well positioned to play a role on cross-cutting decisions impacting biosimilars, particularly as issues arise at the Center level.  Whether the role of the Office of the Commissioner will be active or will be more that of an observer remains to be seen.

The FDA biosimilars committees are:

  • The Biosimilar Implementation Committee;
  • The CDER Biosimilar Review Committee; and
  • The CBER Biosimilar Review Committee

The CDER/CBER joint Biosimilar Implementation Committee is the agency’s forum for discussing overarching policy issues, while the review committees focus on product-specific and scientific issues related to biosimilars development programs. 

CDER/CBER Biosimilar Implementation Committee (BIC):

Janet Woodcock, M.D., and Karen Midthun, M.D, are the co-Chairs for the BIC (Dr. Woodcock is CDER’s Director, and Dr. Midthun is CBER’s Director).  The lead for the committee is Rachel Sherman, M.D., who leads CDER’s Office of Medical Policy.  This cross-center committee consists of staff from CDER, CBER, CDRH, and the Office of the Commissioner.

The BIC has been tasked with focusing on cross-center policy issues regarding implementation of the Biologics Price Competition and Innovation Act of 2009 (BPCIA), including developing initial interpretations of the statute, policy development, and agency resource needs. 

CDER Biosimilar Review Committee & CBER Biosimilar Review Committee (BRC):

John Jenkins, M.D., Director of Office of New Drugs, is Chair of CDER’s BRC, and Robert Yetter, Ph.D, Associate Director for Review Management, is the Chair of CBER’s BRC, and both groups have members from both centers.  These committees have been tasked with product-specific issues related to biosimilars within CDER.

Compiled with assistance from Anne R. Mutashi.

Posted in News & Events

Public Comment on FDA Draft Biosimilars Guidances

Thoughts on the U.S. Food and Drug Administration’s recently issued biosimilar guidance documents?  The time to act is now.  As described in our earlier post , FDA must provide the public an opportunity to comment on the three recently issued biosimilars draft guidances.  42 USC 262(k)(8)(B)(i).  As described in the announcement notices in the Federal Register, FDA has opened a dedicated docket for each guidance:

FDA will accept comments to these dockets until April 16, 2012.

As the agency acknowledges in the Federal Register notices, FDA regulations allow the public to comment at any time on any guidance.  21 CFR 10.115(g)(5).  Nevertheless, we expect that all three of the guidance dockets will see a significant amount of input from industry stakeholders and all other interested persons.

With regard to the Q & A Guidance, FDA has also announced that:

“FDA intends to update this guidance to include additional Q&As as appropriate and intends to post information by Q&A number on FDA’s Web site regarding the publication date of draft guidance Q&As for comment, the comment period, and the publication date of final guidance Q&As.”

77 Fed. Reg. 8885, 8886 (February 15, 2012).  We will update you as soon as FDA issues any further draft Q&As for comment or finalizes any of the recently proposed ones.