how recent fda guidelines impact generic pharma companiesall views expressed are paul braier’s,...
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How Recent FDA Guidelines
Impact Generic Pharma
Companies
Paul A. Braier, Ph.D., Esq. Greenblum & Bernstein, P.L.C.
[email protected] Pharma IPR India 2017
1 March 2017
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Background
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What are Rules and Guidances?
• What is a Rule (or Regulation)?
– Prepared and implemented by an agency (FDA) in order to clarify and enforce its statute
– Notice & Comment
– Binding
• What is a Guidance?
– Reflects an Agency’s thinking
– Not binding
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The Final Rule
• “Abbreviated New Drug Applications and 505(b)(2) Applications”
• Published October 6, 2016
• Two Main Purposes
– To implement the MMA (enacted Dec. 2003)
– To reflect court decisions
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When in Effect, and What They
Affect
• Effective Date December 5, 2016
• All new NDAs, 505(b)(2)s, and ANDAs submitted after that date
• Prior Applications
– Patent amendments
– Listing of new patents
– Challenges to patent listing
– Reporting court decisions
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New Definitions
21 C.F.R. § 314.3
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New Definitions
• “505(b)(2) Application”
– Defined as a subset of 505(b)(1) applications (NDAs)
– Rules that apply to NDAs apply to 505(b)(2)s
• “Reference Standard”
– The drug product selected by FDA for which an ANDA applicant must perform BE studies
– (as opposed to RLD, which encompasses all brand dosage strengths)
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New Definitions
• “Acknowledgement Letter”
– Written communication from FDA that an ANDA is sufficiently complete for substantive review
• “Paragraph IV Acknowledgement
Letter”
– Written communication from FDA that a 505(b)(2) or ANDA with P-IV is sufficiently complete for substantive review
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New Definitions
• “Commercial Marketing”
– Introduction into interstate commerce of an ANDA drug or an AG, outside control of the ANDA holder
– Implications:
• Marketing an AG by an FTF can trigger the 180-day exclusivity
• Exports from Indian parent to its US subsidiary? – Both should be identified in ANDA
• Settlements w/brand
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Marketing Notice
21 C.F.R. § 314.107(c)(2)
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FTF Marketing Notice
• New ANDAs (submitted after Dec. 5, 2016)
• A first-filer must inform FDA within 30 days of beginning marketing
• Penalty: 180-days deemed to begin upon final approval
• Unforeseen Issue?
– Multiple first filers
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FDA Stay of Approval
(a/k/a 30-Month Stay of Approval)
21 C.F.R. § 314.107(b)(3)
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FDA Stay of Approval
• New regulations codify FDA’s previous policies
• Entry of a Preliminary Injunction (PI) during original stay period extends the stay
– PI: likelihood of both validity and infringement PI
• Stay ends upon
– Win by ANDA
– Court order to end stay
– Lawsuit dismissal without finding on infringement 13
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New NDA Orange Book
Requirements
21 C.F.R. §§ 314.53 (b) and (f)
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Heightened Use Code
Requirements
• Applies to
– New NDAs and 505(b)(2)s – New patent listings in old NDAs and 505(b)(2)s
• Use Code Must Be Specific to the Approved
Indication of Use
– Broad claim: narrower UC, only to specific approved MOU – Coextensive claim: UC only to the specific approved MOU – Narrower claim: UC only to the specific approved MOU
claimed in the patent (not the broader product insert) • MOU
– Use Code limit increased to 250 characters – Must specifically identify sections of package insert
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Updating OB info
• NDA holder must update w/in 14 days if:
– Patent no longer meets requirements for listing
• E.g., non-appealable finding of invalidity
– A court orders NDA holder to amend or withdraw patent from OB
– Patent term is extended by PTO
• FDA won’t remove from OB if implicates
180-days
• Generic’s remedy: delisting counterclaim
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Challenging OB Information
21 C.F.R. § 314.53(f)(1)
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Challenging OB Information
21 C.F.R. § 314.53(f)(1)
• Anyone can challenge listing of any
patent listed for any NDA
– Anyone: • Does not need to be a generic company or an
ANDA/505(b)(2) applicant
– Any Patent: • Does not need to be a P-IV or section viii patent
• Regardless of date listed
– Any NDA • Regardless of approval date
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Challenge Procedure
Drug Substance or
Product
• Challenger Submits Statement of Dispute – Specific grounds for
disagreement with accuracy or relevance
• FDA Forwards (unreviewed) to NDA Holder
Method of Use
• Challenger Submits Statement of Dispute – Specific grounds for
disagreement with accuracy or relevance
– Limited to narrative description of scope of patent claim, up to 250 characters
• FDA Forwards (unreviewed) to NDA Holder
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Challenge Procedure (cont.)
Drug Substance or
Product
• NDA Holder Must Respond w/in 30 Days (Form 3542) to: – Confirm correctness of listing,
or
– Amend or withdraw listing
Method of Use
• NDA Holder Must Respond w/in 30 Days (Form 3542) to: – Confirm correctness of Use
Code, or
– Amend patent information (e.g., UC of up to 250 characters)
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Challenge Procedure (cont.)
Drug Substance or
Product
• FDA will not change OB listing unless NDA holder amends or withdraws
Method of Use
• Rule Does Not Address Any “Default” FDA Action
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Remedy?
• Court order in a validity action • Counterclaim for delisting or
correction • Standing: not just “Anyone”
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Revised Notice Letter
Requirements
21 C.F.R. § 314.95
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Notice Letter Timing & Content
• Notice Letter is Invalid if Sent:
– Before receipt of Paragraph IV acknowledgment letter, or
– After P-IV letter, but before 1st working day after new patent is listed in OB (for newly-listed patent)
• Contents:
– Slightly revises or adds some required statements
– E.g., that the applicant has received the P-IV acknowledgment letter for the ANDA
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Sending the Notice Letter
• Method of Sending
– Old: USPS registered mail, or advance permission
– New: registered or certified mail OR any “designated delivery service”
– Designated Delivery Service:
• Generally available to the public
• Maintains electronic records
• Overnight or 2-day delivery services
• E.g., FedEx, UPS
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Questions? [email protected]
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All views expressed are Paul Braier’s, and are not necessarily the views of Greenblum & Bernstein, P.L.C.