1. Joan Bergstrom Henkel Consumer Goods, Inc.
Fundamentals of Regulatory Affairs, 8th edition Ch. 14 Patents and Exclusivity
Joan Bergstrom
Henkel Consumer Goods, Inc.

2. Introduction
Hatch-Waxman Act of 1984 gave brand-name drug companies incentives to do new drug research including:
Patent term extension for time lost during Regulatory review
Listing patent in Orange Book
Eligibility for a period of non-patent exclusivity
Additional incentives created by other laws including:
Orphan Drug Act – drug development for rare diseases
Best Pharmaceuticals for Children Act – developing medicine for kids

3. Patents and Exclusivity
Affords right to prevent competitor from making same
Granted by the Patent and Trademark office
Awarded anytime during development of a drug
Usual duration is years
Affords manufacturer exclusive marketing rights
Granted by the FDA
Awarded upon approval of a drug (NDA)
A statutory provision, if requirements are met
Duration varies

4. Patents and Exclusivity
Patents can be expired before drug approval, issued after drug approval, and anywhere in between
Exclusivity is granted upon approval of a drug product if the statutory requirements are met
Some drugs have both patent and exclusivity protection while others have just one or none
Patents and exclusivity may or may not run concurrently and may or may not encompass the same claims
Exclusivity is not added to the patent life

5. Patent-Related Market Exclusivity
Patent generally keeps other companies from making same product for a period of time, protecting the $ investments by patent holder
Time is lost during regulatory review of a product is an issue
Regulatory Review Time = Testing Phase Time + Review Phase Time
Period from submission to approval of NDA
Hatch-Waxman Act of 1984 says patent term may be extended
Extension = ½ Testing Phase time + Review Phase time
Assuming due diligence is maintained!
Not to exceed 14 years after date of approval of marketing application

6. Patent Term Extension Law
Definition: “Drug Product” is active ingredient (AI) of a new drug, and salts or esters, as a single entity or in combination with other AI
Law provides that patent for drug may be extended from original issue date IF:
Term of patent has not expired
Patent not previously been extended
Extension application submitted by owner w/in 60 days of NAD approval
Product in Reg. Review before it is commercially available
NDA is first permitted commercial use of drug product

7. Orange Book
Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book)
Lists drug products approved on the basis of safety and effectiveness by the FDA under the Federal Food, Drug, and Cosmetic Act
First published in 1980, now electronic database
Orange Book Data updated Monthly
Generic Drug Product Information updated Daily
Patent Information updated Daily

8. Orange Book Patent Listing
Patent information is required to be submitted with all new drug applications at the time of NDA submission
Patent information is published in the Orange Book after approval of NDA, upon receipt of FDA form 3542
For patents issued after approval of the NDA, the applicant holder has 30 days in which to file the patent to have it considered as a timely filed patent. Patents may still be submitted beyond the 30 day timeframe, but the patent is not considered a timely filed patent.
Expired patents and exclusivity are not included in the published list

9. Non-Patent Statutory Market Exclusivity
Five Year Exclusivity
5-year exclusivity granted to sponsor of a drug not previously approved under NDA, referring to a New Chemical Entity
Sometimes called “NCE Exclusivity”, prevents approval of a generic equivalent for 5 years
Three Year Exclusivity
3-year exclusivity granted to sponsor of a drug previously approved under NDA, but reports New Clinical Investigations (studies)
Must be studies essential to approval
Must be studies conducted by same sponsor
Called the “NCI Exclusivity” or “New Use Exclusivity”

10. Non-Patent Statutory Market Exclusivity (cont.)
Pediatric Exclusivity
Provides an additional 6 months exclusivity to sponsor that conducts acceptable and beneficial Pediatric Studies
Submit Pediatric Written Request (PWR) to FDA
Applies to ALL indications of the drug or formulation, not just pediatric
Orphan Drug Exclusivity
Grants 7 year exclusivity to sponsor of a drug for a “rare disease or condition”
Affects fewer than 200,000 people or sponsor shows inability to recover development or marketing costs
Other or subsequent drugs must be “different” or “clinically superior” to be approved within the 7 years

11. Duration of Drug Exclusivity
How long is exclusivity granted for?
It depends on what type of exclusivity is granted: New Chemical (NCE) - 5 years Orphan Drug (ODE) - 7 years New Clinical Investigation (NCI) - 3 years, if criteria are met Pediatric (PED) - 6 months added to existing Patents/Exclusivity Patent Challenge (PC) – 180 days (this exclusivity is for ANDAs only)
See 21 C.F.R New Drug Product Exclusivity

12. Patent Filing
Leahy-Smith America Invents Act (AIA) of 2011 significantly modified the patent filing process
AIA went into effect March 2013
Grants the patent to the entity “first to file” the application regardless of any previous publications
Caused defensive publication planning by many companies
Requires greater diligence of competitive landscape

13. Joan Bergstrom Henkel Consumer Goods, Inc.
Fundamentals of Regulatory Affairs, 8th edition Ch. 15 Over-the-Counter Drug Products
Joan Bergstrom
Henkel Consumer Goods, Inc.

14. Introduction
Over-the-counter (OTC) drugs play increasingly important role
Durham-Humphrey Amendment to the FD&C Act in 1951 established three criteria for Prescription status drugs
Habit forming drugs
Not safe for use unless supervised by healthcare professional
Limited to prescription use under NDA
All drugs that did not meet these criteria = OTC drugs

15. Regulation of OTC Drugs
Regulations applicable to Rx drugs also apply to OTC drugs
All aspects of drug manufacture and testing (GMP’s)
Facility listing and inspections
Drug registrations
Clinical trials and safety oversight
Both review and approval of OTC drugs done by FDA Center for Drug Evaluation and Research’s (CDER) office
Two main avenues to receive approval for an OTC drug
OTC Monograph route – Safety and efficacy data known, using approved active ingredients and labeling
NDA / ANDA route – submit safety and efficacy data

16. OTC Monograph Route In 1972, FDA initiated OTC Drug Review Process
Encompassed review of safety and efficacy of products on the market
Started by grouping products into therapeutic categories and evaluating the active ingredients rather than each product
FDA now reviews active ingredients and labeling for more than 80 therapeutic classes of drugs (monographs, not all finalized)
OTC Monograph is developed and published in the Federal Register

17. OTC Monograph Review Process
Review of safety and efficacy data done by therapeutic category specific Advisory Panels, subject matter experts
Advisory Panel recommended active ingredients be classified as
Category I – generally regarded as safe and effective, not misbranded
Category II – not generally regarded as safe and effective, or is misbranded
Category III – insufficient data to permit classification
After comment periods, FDA published conclusions as
Tentative Final Monographs (Proposed Rule)
Final Monograph (Final Rule)
No defined timelines to move from TFM to FM, can be lengthy process
Can market products under TFMs
FDA can amend FMs as new information is available

18. NDA Route
Products not covered by OTC monographs are subject to NDA process prior to marketing
Four NDA Routes
Direct-to-OTC NDA – same requirements as Rx NDA, PLUS demonstration product can be safely used without healthcare professional supervision
Rx-to-OTC Switch – used when Rx shows it can be safely used without healthcare professional supervision
NDA Monograph Deviation – used when a drug product deviates in any aspect from the OTC Monograph, like dosage form. NDA submitted with S&E data.
Generic (ANDA) - same requirements as Rx NDA, with bioequivalence data

19. OTC NDA Products and Specific Studies
Manufacturers must conduct Safety, Efficacy, and Preclinical studies
Additional studies for OTC products:
Label comprehension – evaluate extent to which a consumer can understand and apply information on OTC label when making drug product use decisions
Open label and uncontrolled
No drug product is used
Self-selection – evaluate whether consumer makes correct decision on use/no use based on label information and knowledge of personal medical history
No drug product used
Suitable label based on comprehension should be created before test
Actual use test (AUT) or Simulation Trial – evaluate consumer behavior
Conducted under an IND
“all comers” study with actual product

20. Labeling of OTC Drugs
Primary responsibility over OTC drug labeling belongs to FDA
In 1999, “Drug Facts” labeling rule became effective
Standardized format, content, headings, graphics, and min. type size
Ensure product information is easy to find and understand when used by ordinary people

21. Drug Facts Label Regulation 21 CFR 201.66
Specific information on OTC label:
Active ingredient
Uses
Warnings
Inactive ingredients
Purpose
Directions

22. OTC Drug Packaging Requirements
Tamper evident packaging has become standard
Regulation 21 CFR
Statement on both inner and outer pack show tamper-evident features
Must comply with child-resistant package requirements
Requirements as defined in the Poison Prevention Packaging Act (PPPA) of 1970
Consumer Product Safety Commission (CPSC) enforces child-resistant package requirements

23. FDA Oversight
All OTC drug manufacturing activities must comply with 21 CFR 210 and 211
Drug manufacturing sites are required to register with the FDA
Subject to prior approval inspections for NDA products and other routine inspections
All OTC drug products must be drug listed, though NDC number not required on OTC drug product label
Mandated safety reporting per the Dietary Supplement and Nonprescription Drug Consumer Protection Act of 2006

24. Assigning a Product Class
Classified based on intended use as defined by FD&C Act
Intended use determined by:
Product claims ex. Cleans
Consumer perception
Drug ingredients ex. Fluoride
Products can be both cosmetics and drugs – if two intended uses
Examples: Antidandruf shampoo, antibacterial hand soap
Must comply with requirements for either/both drugs and cosmetics

25. Advertising
Since 1971, Regulated by the Federal Trade Commission (FTC)
No requirement to submit advertising to FTC before use
FTC has policy guides on advertising that must be consulted
National Advertising Division (NAD) of the Better Business Bureau is the investigative arm of the voluntary self-regulation program
NAD casework includes
competitive challenges from other advertisers
self-monitoring traditional and new media
Ensure all claim support data is available before advertising