Ravicti是Buphenyl散剂与片剂的活性成分苯丁酸钠的一种新盐/酯。作为一种新盐或酯，按照Hatch-Waxman法案此变更将享有三年的专营期。此外，由于服务于罕见病群体并作为一种新（化学）实体，它享有长达七年的罕见病用药专营期（Orphan Drug Exclusivity，ODE），直至2020年2月1日才将到期。Ravicti仅有一种用法，因此看来在罕见病用药专营期到期前，将不会有ANDA获批。同样有多项专利覆盖该NDA产品。一项药物专利将于2015年2月7日到期，该专利也声称对一种用途具有专有权；然而，两项分别于2030年9月以及2032年3月过期的专利也收录了看起来在失效之前都会阻止仿制药进入的一项用途。如果存在小八条排除可能（排除专利或专营期所保护的用途或信息，如果有其它已获批不受保护的用途），那么有关产品获批用途标签信息以及使用说明还不够明确方面尚有机可乘。这一方面，要么ANDA申请者另有锦囊妙计，要么只是顾虑ANDA获批的中位时间；即便有关专利看起来无效，ANDA能够获批的最早时间,从现在算起，也要等到6年以后了。
Lachman CONSULTANTS - Bob Pollock先生 2014-03-11
校译：识林-Kapok 2014-03-18
OGD's Paragraph IV Database and Two Interesting Listings
Written by Bob Pollock • March 11, 2014
The Office of Generic Drugs (OGD) updated its Paragraph IV Database (PIVDB) yesterday and two new entries caught my eye. For those of you not familiar with the PIVDB, it was developed to give prospective ANDA applicants information on when the first ANDA for a patent-protected product was submitted to OGD. This had two purposes: 1) It gave prospective ANDA applicants an indication that someone else had already submitted an ANDA for a particular product which may dissuade subsequent applicants from seeking to file an ANDA to challenge a patent if their sole goal was to be first to file.; 2) It gave the date of submission of the first applicant, and thus, the date of the first to file application(s), and firms would know from that date if they were eligible for award of 180-day exclusivity. The FDA does not provide the name of the applicant, only the date of submission, and thus, there could be either single or multiple applications submitted on that day.
Anyway, now back to the interesting listings. An ANDA for glycerol phenylbutyrate oral solution (a copy of the NDA for Ravicti held by Hyperion Therapeutics) was listed as submitted on November 19, 2013 and posted on 3/10/14 or about 4 months after the original submission. In this case, it is not the length of time the ANDA has been at OGD, but rather the exclusivity and patent issues associated with the product and the jump on first-to-file status that at least one generic firm has decided to seek, especially since the original NDA was approved on February 1, 2013, only 9 months prior to ANDA submission.
Ravicti is a new salt/ester of sodium phenylbuterate, the active ingredient in Buphenyl powder and tablets. Because it was a new salt or ester, it was awarded a period of 3-year Hatch-Waxmanexclusivity for this change. In addition, because it serves an orphan population and it is a new entity, it was also awarded 7-year Orphan Drug Exclusivity (ODE) that expires February 1, 2020. Ravicti appears to have a single indication, and thus, it would seem that no ANDA can be approved until that ODE expires. There are also patents that cover the NDA product. A drug substance patent expires on February 7, 2015 and that patent also claims a use; however, there are two additional patents expiring in September 2030 and March 2032 that also include a use that would appear to block generic entry unless invalidated. If there is a little viii carve out potential (excluding a patent or exclusivity protected indication or information if there are other non-protected indications already approved) , it is not obvious from the use codes and the labeling related to the approved use of the product. In that regard, the ANDA applicant must either have something up its sleeve or is just worried about the median time to approval of an ANDA, since it would seem that the earliest that an ANDA could be approved, even if the patents are invalidated, with be about 6 years from now.
The second listing that got my blood flowing was for Memantine Hydrochloride extended-release capsules, a generic form of Namenda XR Capsules. There was an approximate 10-month period from submission to acceptance of the ANDA. While that is not the longest review time for completeness and acceptability we have seen, it certainly indicates that either OGD had a difficult time evaluating the ANDA for receipt (maybe bioequivalence issues?) or their backlog could be a factor.
OGD publishes new additions to the list frequently, and often times, there are more there than meets the eye. You may want to zero in on one of the updates if this sort of thing interests you and your firm.
Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Act)
Mandatory Reading:
Regulatory Affairs (Reg)
Intellectual Property (IP)
Quality Assurance (QA)
Legal Department
Work Suggestions:
Reg: Ensure the company's drug applications comply with the new drug application procedures and bioequivalence standards.
IP: Monitor patent term extensions and the impact on the company's patent strategy.
QA: Verify that manufacturing processes meet the identity, strength, quality, and purity requirements.
Legal Department: Advise on patent infringement issues and the legal implications of abbreviated new drug applications.
Scope of Application: The Drug Price Competition and Patent Term Restoration Act of 1984 applies to chemical drugs, including new molecular entities and generic drugs, in the United States. It is intended for regulatory bodies, pharmaceutical companies, and legal entities involved in drug development and approval processes.
Key Points Summary:
Abbreviated New Drug Applications (ANDAs): The Act allows for the streamlined approval of generic drugs by submitting abbreviated applications showing bioequivalence to the listed drug, without repeating costly and time-consuming clinical trials.
Patent Term Restoration: Offers a mechanism to extend the effective patent life of a drug to partially compensate for the time lost during the regulatory review process, up to a maximum of five years.
Data Exclusivity: Provides a period of data exclusivity, during which the FDA cannot approve ANDAs for other companies that rely on the innovator's safety and efficacy data.
Patent Certification: Requires ANDA applicants to certify about the listed drug's patents or periods of exclusivity, which can trigger a patent infringement lawsuit.
Regulatory Review Period: Defines the regulatory review period for calculating patent term extensions and sets rules for due diligence during the application process.
Conclusion: The Drug Price Competition and Patent Term Restoration Act of 1984 is a landmark legislation that balances the need for accessible, affordable medications with the incentive for innovation. It has significantly impacted the pharmaceutical industry by fostering competition and ensuring that both innovator and generic drug companies have clear pathways to market. The above points are not exhaustive; for comprehensive understanding, the full text of the Act should be consulted.
