FDA “Orange Book

Insulin lispro protamine [FDA Orange Book for Humalog mix... 

Electronic Orange Book, Approved Drug Products with Therapeutic Equivalence Evaluations, [Internet]. URL http //www.fda.gov/cder/ob/default.htm, accessed 7-29-2000. 

The FDA maintains a database of approved excipients Drug Information Electronic Orange Book, http //www.fda.gov/cder/ob/default.htm). Standards and tests for regulatory acceptable excipients are included in the US Pharmacopoeia and National Formulary. Two such tests, dissolution and stability, are included in Exhibit 5.12 for reference. For new excipients to be included in a drug formulation, they have to satisfy one of the following criteria ... 

Yes. If a brand-name company lists an additional patent in the Orange Book after the generic applicant has filed its AND A, more than one 30-month stay may be generated. The generic applicant is required to re-certify to this later-listed patent, and if, upon notice of the generic s re-certification, the brand-name company sues within 45 days, then FDA approval of the generic s previously filed ANDAis stayed for an additional 30-months from the notice date or until a court decision in the newly instituted patent litigation. 

From 1992 through 2000, brand-name companies have listed patents in the Orange Book after an ANDA has been filed for the drug product in 8 instances 6 of these 8 instances occurred since 1998. For the 8 drug products, the additional delay of FDA approval caused by the additional 30-month stay (beyond the first 30-month stay) ranged from 4 to 40 months. In all 4 of the... 

There have been various suggestions to address this situation, each with its own pros and cons. One proposal has been to establish an administrative procedure through which generic applicants could obtain substantive FDA review of listability. The FDA, however, has taken the position that it lacks the expertise and resources necessary to perform such a review, and its solely ministerial review of Orange Book listings has been upheld by the courts. At a minimum, it appears useful for the FDA to clarify its listing requirements see Appendix H). 

Moreover, most of the later-issued patents in the Orange Book raise questions about whether the FDA s patent listing... 

Many brand-name companies noted that they could only provide information about when they had submitted the patent to the FDA for Orange Book listing rather than the date on which the patent was actually listed. 

The FDA has adopted regulations governing the types of patents that can be listed in the Orange Book. The listing regulation is separated into 6 subsections below for ease of reading. Specifically, the brand-name company must list in the Orange Book each patent which ... 

Several generic applicants have attempted to obtain court orders requiring the FDA or brand-name companies to delist certain patents from the Orange Book. 

The FDA has stated that it laeks the resources and the expertise to review patents submitted with NDAs. The ageney does not ensure that a submitted patent elaims the approved drug before listing it in the Orange Book. Moreover, the FDA has deelined to enaet any administrative proeedures for resolving listing disputes. If a party disputes the accuracy of a listed patent, it may notify... 

The FDA approved Paxil in December 1992. Patent No. 4,007,196 (the 196 patent) covering the active ingredient paroxetine hydrochloride had expired prior to this date and, therefore, was not listed in the Orange Book. However, GSK listed Patent No. 4,721,723 (the 723 patent) whieh elaims paroxetine hydrochloride hemihydrate. (A hemihydrate is a form of the active ingredient that has one water molecule for every two paroxetine molecules incorporated into its crystalline structure.)... 

Orange Book means the FDA s publication entitled Approved Drug Products with Therapeutic Equivalence, in which the patents claiming a drug product approved through an NDA are listed. 

Paragraph 1 certification means a certification that a generic applicant seeks FDA approval of its ANDA for a relevant NDA for which no patent information has been filed in the Orange Book. 

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