When filing an Abbreviated New Drug Application (ANDA) with the USFDA, applicants must certify how their generic product relates to patents listed in the Orange Book for the reference listed drug (RLD). This certification falls under one of four categories: Paragraph I, II, III, or IV.
A Paragraph III (Para III) Certification means that the ANDA applicant acknowledges an existing patent but will wait until its expiration before launching the generic. In contrast, a Paragraph IV (Para IV) Certification challenges the validity or enforceability of the patent, potentially allowing early market entry.
This decision significantly impacts market entry timing, exclusivity, risk, and financial costs. Below is a detailed comparison to help determine the best approach.
Paragraph III (Para III) Certification
Key Features
- Acknowledges Existing Patents – The applicant does not dispute the patent.
- Market Entry After Patent Expiry – The generic can launch only after the patent expires.
- No Risk of Patent Litigation – Since the applicant does not challenge the patent, the NDA holder (innovator) has no reason to sue.
- Lower Regulatory & Legal Costs – The ANDA follows a straightforward approval process.
- No 180-Day Exclusivity – Unlike a first-to-file Paragraph IV, a Para III filing does not offer market exclusivity.
When to Choose Para III?
- The patent is strong, making a Para IV challenge unlikely to succeed.
- The company prefers a predictable and lower-risk approach.
- The goal is cost-efficient entry post-patent expiry.
- There’s no urgency to enter the market early.
Paragraph IV (Para IV) Certification
Key Features
- Patent Challenge Strategy – The applicant claims that the listed patent is either invalid, unenforceable, or will not be infringed by the generic.
- Potential for Early Market Entry – If successful, the generic can launch before patent expiry.
- 180-Day Market Exclusivity – If the applicant is the first-to-file and wins, they get six months of exclusivity.
- Risk of Patent Litigation – The NDA holder will likely sue the ANDA filer, delaying approval by up to 30 months unless the case is won or settled.
- Higher Legal & Regulatory Costs – Patent lawsuits are expensive and time-consuming.
When to Choose Para IV?
- The patent has weaknesses or can be designed around.
- The company wants early market entry and is willing to handle litigation.
- Exclusivity benefits (180 days) are achievable for maximum profits.
- The company has legal and financial resources to manage the risk.
Strategic Comparison: Para III vs. Para IV
- For high-value drugs, companies often attempt Para IV first and, if unsuccessful, revert to Para III.
- For less competitive molecules or highly protected patents, Para III is often the better business decision due to its low-risk, low-cost nature.
- If exclusivity is lost, even a Para IV challenge may not be worth the legal cost.
- Paragraph IV (Para IV) Filing | Overview & Strategies
- Bypassing Patents for Para IV Filing
- Understanding Patent Length and Generic Competition in Pharmaceuticals
