1. Afternoon Breakout Session: FDA and Regulatory Environment As We Enter the User Fee Reauthorization Period
Mike Druckman, Partner, Hogan Lovells

2. FDA Update: Regulatory Environment and PDUFA Reauthorization
Mike Druckman
November 2016

3. Topics
PDUFA VI highlights, including innovative trial design, MIDD, and RWE initiatives
Impact of Sorrell, Caronia, and Amarin on ability of sponsors to make claims beyond approved labeling
CBER Reorganization
FDA’s orphan drug policy and strategies to consider
Other issues of interest to the audience

4. Topic 1
PDUFA VI Highlights

5. PDUFA VI Reauthorization Timeline

6. Topic 2
Impact of Sorrell, Caronia, and Amarin on ability of sponsors to make claims beyond approved labeling

7. Topic 3
CBER Reorganization

8. Topic 4
FDA’s orphan drug policy and strategies to consider

9. Scope of Exclusivity Blocks Approval of the “Same Drug”
Same Drug analysis has two components
Chemical comparison
Clinical comparison
316.3(b)(14): Same drug means:
(i) small molecule drug: the “same active moiety as a previously approved drug … for the same use … except that if the subsequent drug can be shown to be clinically superior to the first drug…”
(ii) If it is a drug composed of large molecules (macromolecules), a drug that “contains the same principal molecular structural features (but not necessarily all of the same structural features)…”
Proteins, polysaccharides, polynucleotides, “closely related, complex partly definable drugs…”

10. Scope of Exclusivity Clinical Superiority
316.3(b)(3): Clinically superior means “shown to provide a significant therapeutic advantage over and above that provided by an approved orphan drug (that is otherwise the same drug)” in one of three ways:
Greater effectiveness as assessed by effect on a clinically meaningful endpoint in adequate and well-controlled trials;
Greater safety in a substantial portion of the target population; or
In unusual cases, a demonstration that the drug makes a major contribution to patient care

11. Clinical Superiority as Prerequisite for Exclusivity
OOPD has long taken the position, now codified in the regulations, that a clinical superiority showing is required whenever there is a previously approved “same drug”
Where first drug has ongoing exclusivity: needed to “break” exclusivity and gain approval
This is the basic operation of the clinical superiority regime as originally conceived
Where first drug has expired exclusivity: needed to obtain exclusivity
Where first drug never had orphan exclusivity: needed to obtain exclusivity

12. Clinical Superiority as Prerequisite for Exclusivity
Depomed and Eagle cases
Depomed case
Depomed’s Gralise (gabapentin) for PHN; Pfizer’s Neurontin never had orphan exclusivity
OOPD designated Gralise on a plausible hypothesis of clinical superiority under old regulations
DDC held that Orphan Drug Act unambiguously prohibited FDA from imposing additional requirements for exclusivity beyond designation and approval; Chevron Step 1
FDA announced that it will not apply the Depomed holding. Policy on Orphan-Drug Exclusivity; Clarification, 79 FR (Dec. 23, 2014)
Eagle v. Burwell: pending in DDC
Eagle’s Bendeka (bendamustine HCl) for CLL/iNHL; Cephalon’s Treanda has expired orphan exclusivity = second scenario

13. Fixed Combination Drug Products
OOPD considers fixed-combination drug products to be “different drugs” than single ingredients
We are aware of a handful of examples where OOPD has designated the combination as well as the single ingredients as orphan drugs for the same disease
Separate designation requests
Scope of exclusivity is similarly limited
For recombinant plasma therapeutics, FDA has considered addition of fusion protein a factor in rendering a product to be not the “same drug”
What about co-administration use?

14. Strategies to consider in being first to approval
FDA’s Expedited Programs:
Priority review (shortens FDA PDUFA deadline to 6 months from acceptance for filing)
Fast Track
Breakthrough therapy designation
Accelerated approval (surrogate endpoints)
Priority Review Vouchers (Tropical Disease; Rare Pediatric Disease)
Entitles holder to priority review (can be purchased)
Adaptive and innovative trial designs

15. Topic 5
Other issues of interest to the audience

16. Other potential issues of interest
FDA’s increasingly aggressive position on international inspections –
Including citations based on processes used to manufacture products outside the U.S. and shipped wholly outside the U.S., based on U.S. standards, when the manufacturer makes identical or similar products that are imported into the U.S.
Priority review vouchers – for tropical diseases and rare pediatric diseases
Sold for as high as $350 million
Resurgence of gene therapy clinical trials
Challenges of genetic indications and genotyping programs
Human tissue draft guidance documents and recent public hearings
Final rule on clinicaltrials.gov results submission – now results must be posted even if the drug has not been, and never will be, approved

17.
"Hogan Lovells" or the "firm" is an international legal practice that includes Hogan Lovells International LLP, Hogan Lovells US LLP and their affiliated businesses. The word “partner” is used to describe a partner or member of Hogan Lovells International LLP, Hogan Lovells US LLP or any of their affiliated entities or any employee or consultant with equivalent standing.. Certain individuals, who are designated as partners, but who are not members of Hogan Lovells International LLP, do not hold qualifications equivalent to members. For more information about Hogan Lovells, the partners and their qualifications, see Where case studies are included, results achieved do not guarantee similar outcomes for other clients. Attorney advertising. Images of people may feature current or former lawyers and employees at Hogan Lovells or models not connected with the firm. © Hogan Lovells All rights reserved