On November 19, 2018, the FDA submitted a proposal to the White House Office of Management and Budget (OMB) to approve a review that will assess current communication practices between FDA review staff and Investigational New Drug (IND) sponsors.  The FDA has contracted with Eastern Research Group (ERG) to determine whether the current mode of communication between these parties needs to be adapted moving forward.  Depending on the results of this review, communication practices and requirements could be altered, which might have an effect on the IND application process. Possible modifications might occur that could assist in removing communication bottlenecks hindering approval timelines.

By filing an IND, a drug developer seeks approval to conduct human trials of investigational new drugs.  After an organization submits an IND application to the FDA for approval, the FDA review team must review the submission within a 30 day period and determine whether to approve or deny the application.  During this period, the FDA review staff and IND sponsors communicate regarding IND status, concerns, and questions, and the clock stops on the 30-day period any time the FDA requests additional information from the sponsor. Overall, this process is designed to minimize the risk of harm to clinical trial volunteers and confirm that the clinical trial protocols are appropriate. Further, the FDA reviews the proposed study protocol to confirm sponsors’ plans support compliance with good clinical practice requirements.  The FDA released guidance last December on best practices for communication between IND sponsors and FDA review staff in order to assist in improving the effectiveness, timeliness, and transparency in communications between the parties.  Additionally, the FDA believes that improved communication may assist in facilitating the availability of effective and safe drugs to consumers.

The FDA expects that the upcoming review, pending OMB approval, will shed more light on how commercial IND sponsors perceive their communications with FDA staff.  During this review, ERG will collect data from sponsors of “a sample of up to 150 active commercial INDs that have activity during a one-year period.”  The surveys (which can be found here) and interviews with IND sponsors are intended to assess sponsors’ experiences when communicating with the FDA review staff, and will examine “what is working well, ongoing challenges and pain points, lessons learned, and opportunities for improvement.” After this data is analyzed and reported by ERG, the FDA will “publish the report on the Agency’s public website and hold a public meeting about the assessment.”

The study findings may be useful in assisting the FDA in meeting its PDUFA commitment to promote transparency between sponsors and review personnel.  The PDUFA plan emphasizes its goal to promote effectiveness and efficiency of the first cycle review process while minimizing the number of review cycles necessary for approval. Sponsor recommendations through the surveys may very well shed light on current communication issues as well as other factors that might hinder the approval process.  An understanding of such hindrances may assist FDA in improving communication and transparency between parties and, thus, the IND approval process itself.

EBG will continue to monitor all developments in FDA’s regulation of the IND approval process as well as the forthcoming results from ERG’s review of IND sponsor communication with FDA review staff.

On November 13, 2014, the Health Resources and Services Administration (“HRSA”) announced its plans to abandon the much anticipated “mega-reg” amid questions concerning HRSA’s rule-making authority.  The “mega-reg” was expected to provide much needed clarity to the 340B drug discount program (the “340B Program”) by addressing, among other things, the definition of an eligible patient, compliance requirements for contract pharmacy arrangements, hospital eligibility, and criteria for hospital off-site facilities.

HRSA submitted draft regulations to OMB in April 2014, and the proposed “mega-reg” was expected to be released in June 2014.  However, several legal challenges to other 340B Program regulations undermined HRSA’s legal posture to proceed.  A federal district court ruling in May 2014 determined that HRSA did not have the statutory authority to issue regulations concerning the Orphan Drug provision of the 340B Program.[1] This decision called into question HRSA’s authority for promulgating regulations for the 340B Program, except for limited rulemaking authority granted to it under the Affordable Care Act.[2]  In response to the May 2014 decision, on July 23, 2014, HRSA released a nonbinding Interpretive Rule that set forth the same Orphan Drug policies as the challenged regulation.[3]  EBG has previously posted more in-depth detail as to the court’s decision on the PhRMA lawsuit and the Interpretative Rule here.

After release of the Interpretative Rule, PhRMA filed a motion for miscellaneous relief arguing that the challenged regulation was outside of HRSA’s rulemaking authority and incapable of surviving as an Interpretive Rule.[4]  The court decided to limit its initial decision to whether HRSA had the authority to issue the Orphan Drug rule as a legislative rule, and PhRMA filed a second lawsuit on October 9, 2014, challenging HRSA’s Interpretive Rule as violative of the plain language of the statutory Orphan Drug exclusion.[5]  Despite questions concerning its rulemaking authority, HRSA has updated its frequently asked questions asserting that the failure to comply with statutory requirements as interpreted by HRSA could be considered a violation of the Orphan Drug statute and subjects the drug manufacturer to enforcement action.[6]

Despite the withdrawal of the “mega-reg,” HRSA has stated that it will pursue proposed rules where it has clear legislative rulemaking authority.  To this end, the HRSA Office of Pharmacy Affairs website includes a statement that HRSA will issue proposed rules pertaining to civil monetary penalties for manufacturers, calculation of the 340B ceiling price, and administrative dispute resolution in 2015.[7]  In addition, the website states that HRSA will issue proposed guidance to address “key policy issues,” which are surmised to include the areas that would have been addressed by the “mega-reg.”  Historically, HRSA has not issued regulations, but has issued program guidance through a series of Notices issued through the Federal Register, as well as other sub-regulatory guidance, including FAQs on its website.

HRSA’s ability to issue and enforce guidance will likely be impacted by ongoing litigation and challenges brought forth by the drug industry.  In addition, calls from the drug industry, and a new conservative majority in the Senate, may cause the Senate to reopen the original 340B statute to address the policy debates, lack of clarity regarding the permissible interpretation of 340B Program requirements and standards and HRSA’s rulemaking authority.  Thus, even in the absence of the “mega-reg,” significant changes to the 340B Program should be expected by stakeholders in 2015.

 


[1]Pharm. Research & Mfrs. of Am. v. United States HHS, No. 13-1501, 2014 U.S. Dist. LEXIS 70894 (D.D.C. May 23, 2014).

[2]As codified in the Public Health Service Act 42 U.S.C.§ 256b(d) (administrative dispute resolution), § 256b(d)(1)(B)(i)‒(ii) (calculation of 340B ceiling price), and § 256b(d)(1)(B)(vi)(I) (civil monetary penalties).

[3] HRSA, Notice Regarding Availability of Interpretive Rule: Implementation of the Exclusion of Orphan Drugs for Certain Covered Entities Under the 340B Program, 79 Fed. Reg. 42801 (July 23, 2014).  See also HRSA Freqeuntly Asked Questions, available at http://www.hrsa.gov/opa/faqs/index.html.

[4] PhRMA Supplemental Memorandum in Support of PhRMA’s Mot. for Misc. Relief, PhRMA v. HHS, No. 13-1501, ECF No. 52.

[5] PhRMA Complaint PhRMA v. HHS, Case No. 14-1685, ECF No. 1.

[6] HRSA, Office of Pharmacy Affairs website, Freqeuntly Asked Questions, available at http://www.hrsa.gov/opa/faqs/index.html (last visited Nov. 20, 2014) (follow link to”Orphan Drugs”).

[7]HRSA Office of Pharmacy Affairs website, available at http://www.hrsa.gov/opa/index.html (last visited Nov. 20, 2014).