Continuing on with our magical mystery tour of the Proposed Rule (see previous posts here, here, here, and here), we are now concentrating on some additional codifications of past Agency practice.

Commercial Marketing Trigger for 180-day exclusivity for ANDAs

There used to be two ways to trigger the 180-day market exclusivity provision for ANDA – a final court decision finding a patent not valid or not infringed or unenforceable and, of course, first commercial marketing of an ANDA product for which a PIV certification has been made after the 30-month stay.  Now it is just commercial marketing.  A twist to the commercial marketing of a product first came into play with the generic for Procardia XL.  A generic firm made a patent settlement with the innovator and, as part of the settlement, the generic firm was permitted to sell the authorized generic (AG) (in other words, the brand name product as a generic).  Because there was no court finding against the patent, the only trigger at the time was commercial marketing.  Another generic firm argued that the first commercial marketing of the AG actually should be a trigger of the 180-day exclusivity period even though the product being marketed was not the product subject of the approved ANDA.  The FDA agreed and, from that time on, FDA has considered the marketing of an AG as a trigger to 180-day exclusivity.  FDA is now proposing to codifying this provision.

Bioequivalence Issue

FDA is proposing to codify in 21 CFR 320 the long standing practice of permitting bioequivalence determinations for drug products that are not systemically absorbed to be evaluated through “scientifically valid” methods.  This regulatory revision mirrors the statutory language of section 505(j)(8)(A) of the Federal Food, Drug and Cosmetic Act to align the new regulation with the textual content of the law.

“Lawfully Maintain Paragraph IV Certification” 

For the longest time, most people thought that there was a mistake in the congressional history and law where the phrase “continue to lawfully maintain a paragraph IV certification” appeared.   However, time has demonstrated that Congress actually knew what it was doing.  Readers thought that the word maintain should have been contain.  But  to be eligible  to maintain first-to-file status and be eligible for 180-day exclusivity the Proposed Rule clarifies that it will require that a first filer must “lawfully maintain” a PIV certification to one or more patents for which it was first-to-file in order to continue to retain that eligibility.  Meaning that if it ever withdraws the certification or changes it to a paragraph III certification, then the application will lose its eligibility for the exclusivity period.

Further Definition of Listed Drug to be Codified

FDA is proposing to clarify that the definition of Listed Drug includes a drug product in the discontinued section of the Orange Book, which was suspended, withdrawn or otherwise discontinued from sale for other than safety or efficacy reasons.  This clarification is consistent with longstanding Agency practice, policy and precedent.

There is so much to absorb from the Proposed Rule and I am certain we will see lots of comments from industry on many of the provisions.  In addition, as we have learned over the last 30 years, whenever a regulation is tweaked, revised or clarified, there is always someone who interprets the change in a manner other then what FDA intended.  This is what keeps us all on our toes and provided the real excitement of being involved in the regulatory process.