Biosimilar Substitution: Battles are Brewing at the State Level

from FDA Law Blog by FDABlog HPM

By Kurt R. Karst –

Although FDA has yet to accept an application for a biosimilar version of a biological product licensed under the Public Health Service Act (“PHS Act”) pursuant to the provisions of the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) – let alone consider whether a biosimilar product is also interchangeable with the reference product – the groundwork is already being laid in various states for the consideration and passage of legislation governing the substitution of interchangeable biosimilar biological products. In some respects, the battle is a continuation of what happened way back in the 1970s when state antisubstitution laws were changed to drug product selection (or substitution) laws permitting (or directing) pharmacists to substitute therapeutically equivalent generic drug products for their brand-name counterparts. After many of the state drug substitution laws were put in place, FDA prepared the Orange Book to assist state health agencies in administering those laws with respect to generic drug substitution. (Here’s a copy of the first edition of the Orange Book from 1980.)

State legislation concerning the substitution of an interchangeable biosimilar biological product for the brand-name reference product counterpart has already started cropping up, and 2013 may be the year when legislation takes off and is enacted. For example, in 2012, House Bill 5581 (here and here) was introduced in the Illinois General Assembly to amend the state Pharmacy Practice Act to permit interchangeable biosimilar product substitution provided certain conditions are met by both the prescribing physician and pharmacy. Among other things, House Bill 5581 would permit a pharmacy to substitute a prescription biosimilar product for a prescribed product only if:

(1) the biosimilar product has been determined by the FDA to be interchangeable with the prescribed product for the specified indicated use;
(2) the prescribing physician does not designate in writing on the prescription that substitution is prohibited;
(3) the patient (or patient’s authorized representative) provides written consent for the substitution;
(4) the pharmacist notifies the prescriber in writing within 24 hours after the substitution; and
(5) the pharmacy and the prescribing physician retain a written record of the biosimilar substitution for a period of no less than 5 years.

To continue:
Biosimilar Substitution: Battles are Brewing at the State Level 

FDA Considering Alternative Approval Pathway

from FDA Law Blog
By Alexander J. Varond 

FDA announced earlier this week that it will hold a public hearing to obtain input on a potential new pathway to expedite the development of drugs and biological products for serious or life-threatening conditions that would address an unmet medical need. The new pathway would be used to approve drugs studied in well-defined subpopulations of patients with more serious manifestations of a condition. By focusing on patients with more serious manifestations of a condition, the pathway opens the door to the use of smaller and faster clinical trials. This approach was recently outlined in FDA’s draft guidance entitled “Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products.” We wrote about that draft guidance here. FDA notes that by focusing on obtaining approval in well-defined, sicker subpopulations, the risk-benefit considerations may favor approval compared with trials that aim for approval in broader groups of patients with wide ranges of clinical manifestations. The potential new approval pathway could also help reduce the development of resistance to antibacterial drugs by limiting their use to certain patients.

http://www.fdalawblog.net/fda_law_blog_hyman_phelps/2013/01/fda-considering-alternative-approval-pathway.html

The Other Shoe Drops: ViroPharma Sues FDA – Challenges Denial of 3-Year Exclusivity and ANDA Approvals, from FDA Law Blog

By Kurt R. Karst –     

Last Friday, ViroPharma Incorporated (“ViroPharma”) filed a Complaint and a Motion for Temporary Restraining Order And/Or Preliminary Injunction in the U.S. District Court for the District of Columbia challenging FDA’s approval of three ANDAs for generic versions of ViroPharma’s VANCOCIN (vancomycin HCl) Capsules (Case No. 1:12-cv-00584-ESH).  The lawsuit follows FDA’s April 9, 2012 response to a March 2006 petition for stay of action submitted by ViroPharma (and supplemented on several occasions since).  FDA largely denied ViroPharma’s requests and approved ANDAs for generic VANCOCIN (see our previous post here).  FDA determined that the Agency “has clear legal authority to recommend in vitro dissolution data to demonstrate generic vancomycin bioequivalence,” and that a December 2011 supplemental NDA FDA approved for VANCOCIN is not eligible for 3-year exclusivity because of the limitation on such exclusivity for a so-called “old antibiotic” like vancomycin set forth in FDC Act § 505(v) as added by Section 4 of the 2008 QI Act.

According to ViroPharma, FDA violated the Administrative Procedure act (“APA”) “by adopting and applying in vitro dissolution testing as the bioequivalence testing method for vancomycin, in direct conflict with the FDA’s own regulations, and by basing its approval of the three generic vancomycin ANDAs on this improper in vitro testing.”  In approving ANDAs for generic VANCOCIN, says ViroPharma, “FDA did not follow its own rules, the plain text of which require that bioequivalence be established through in vivo testing absent a waiver unavailable under the circumstances at issue here.  Accordingly, the agency’s ‘deviant action’ must be invalidated.”   FDA’s regulations at 21 C.F.R. Part 320 discuss the various requirements for bioequivalence testing, including the various types of tests available to meet in vivo or in vitro requirements. “Nowhere in § 320.22, or anywhere else in the regulations, does it state that FDA has discretion to approve ANDAs based solely on in vitro testing whenever it chooses and regardless of whether any of the circumstances in § 320.22 are satisfied,” says ViroPharma.

With respect to FDA’s denial of 3-year marketing exclusivity, ViroPharma alleges that FDA violated the APA and the FDC Act (§ 505(c)(3)(E)(iv) & § 505(j)(5)(F)(iv)).  According to ViroPharma:

FDA erred in concluding that every one of the recent fundamental and extensive changes to Vancocin’s labeling constitutes a “condition of use for which” Vancocin “was [previously] approved.”  To the contrary, virtually all of those changes, including in particular the new renal monitoring and dosing requirements, constitute new conditions of use not previously approved, and ViroPharma is therefore entitled to three-year exclusivity (running from December 14, 2011, to December 15, 2014) for its new label.  Critically, even if just one of Vancocin’s labeling changes qualifies for exclusivity, then the entire basis for the FDA’s rejection of exclusivity and hence for approving the generic vancomycin ANDAs is undermined.

more... http://www.fdalawblog.net/fda_law_blog_hyman_phelps/2012/04/the-other-shoe-drops-viropharma-sues-fda-challenges-denial-of-3-year-exclusivity-and-anda-approvals.html

GAO Says Device Reviews Are Taking Longer…and FDA Says It Is Because Your Submission had Quality Issues

In a report released last week, the U.S. Government Accountability Office (“GAO”) provides the results from a study it conducted to determine whether FDA has met timeframe performance goals related to the completion of reviews for premarket notification (510(k)) submissions and premarket approval (“PMA”) applications.

The study found that while FDA met performance goals for 510(k)s and the average number of submissions per year remained generally steady during fiscal year (“FY”) 2003 through FY 2010, the review times for 510(k)s increased.  Likewise, review times for PMAs also increased despite FDA meeting most performance goals for PMA applications.  There has also been a decrease in the number of 510(k) clearance determinations and PMA approvals.  In sum, FDA is taking longer to complete the reviews of 510(k)s and PMAs when the purpose of the user fee program was to streamline the regulatory process.

And who is responsible for this unintended effect?  While assuming some responsibility, FDA points a heavy finger at industry stakeholders.  We will explain this further below, after first providing a brief overview of the device user fee program and discussing the noteworthy GAO study results.

http://www.fdalawblog.net/fda_law_blog_hyman_phelps/2012/04/gao-says-device-reviews-are-taking-longerand-fda-says-it-is-because-your-submission-had-quality-issu.html

FDA Extends Deadline for Reporting Samples Under ACA

FDA Extends Deadline for Reporting Samples Under ACA

By Alan M. Kirschenbaum –
Two days ago, during argument before the Supreme Court on the Affordable Care Act ("ACA"), Justice Breyer referred to “loads” of miscellaneous provisions of the Act outside the core insurance provisions.  One of these is section 6004, which requires manufacturers and authorized distributors of record to submit information on drug samples to FDA annually beginning April 1, 2012 (this Sunday).  Today, FDA issued a brief draft guidance announcing that FDA will exercise its enforcement discretion to extend the deadline for reporting until at least October 1, 2012.  The guidance states that FDA will provide notice before revising this policy, indicating the possibly of a further extension.  By then, we will know whether this and “loads” of other ACA provisions will survive the Supreme Court’s decision, expected in June.  If and when required, the sample information will be submitted electronically through FDA’s Electronic Submissions Gateway.

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