FDA Sets New Goal For Biosimilar, Drug Promotion Guidances

Agency plans to issue 102 new and revised draft guidances this year, including those on use of multiple endpoints in clinical trials, 180-day exclusivity, and ANDA refuse-to-receive standards.

Last year, stakeholders eagerly awaited FDA guidance documents on such hot topics as biosimilar interchangeability and use of links in social media advertising. But the agency didn't meet its self-imposed deadline and has rolled over these and several other planned guidances to its to-do list for this year.

FDA's guidance agenda includes 102 new and revised draft guidances that the Center for Drug Evaluation and Research plans to publish during calendar year 2016. They include two guidances on biosimilarilty: labeling for biosimilar products, and statistical approaches to evaluation of analytical similarity data to support a demonstration of biosimilarity.

The agency also plans to issue several guidances on advertising, including one that addresses use of health care economic information in promotional labeling and advertising for prescription drugs and another on manufacturer communications regarding unapproved uses of drugs and biologics.

The latter is a critical topic for the agency as it has fought numerous suits over its policies on drug promotion. Last year a court ruled against FDA in a First Amendment suit brought by Amarin Pharmaceuticals Inc., allowing the company to tell physicians about the unapproved uses of its fish oil pill Vascepa (icosapent). And the agency reached a settlement with Pacira Pharmaceuticals Inc. in a dispute over FDA's interpretation of Exparel (bupivacaine liposome injectable suspension) labeling.

FDA also plans to issue several guidances related to generics, including guidance on 180-day exclusivity and another on three-year exclusivity determinations for drug products. FDA is routinely sued over its exclusivity decisions and has issued policies on a case-by-case basis.

Other planned guidances will focus on multiple endpoints in clinical trials; implementation of the Drug Supply Chain Security Act; and public disclosure of FDA-sponsored studies, which has been in the works since 2013. Below is a chart of some of the key guidances on FDA's agenda.

FDA Guidance Agenda For 2016
Title	Background
Advertising/Promotion
Health Care Economic Information In Promotional Labeling and Advertising for Rx Drugs	FDA originally said it would issue a draft guidance on industry's interactions with formulary committees in 2014 and then moved the goal to the first part of 2015 (Also see "FDA Guidance On Health Care Economic Data Is Coming In 2015" - Pink Sheet, 2 Jan, 2015.). Claims that manufacturers are interested in making to payers mostly fall within a "gray zone" of legality (Also see "Potential Rx Economic Claims To Health Plans Presented In Tufts Analysis" - Pink Sheet, 4 Jun, 2015.).
Internet/Social Media Advertising and Promotional Labeling of Rx Drugs and Medical Devices – Use of Links to Third Party Sites	FDA had planned to issue this in 2014, after issuing three social media guidances, on character space limitations, correcting third party misinformation and reporting requirements for websites that firms control for the content on third party sites (Also see "Social Media Marketing: FDA’s Old-Time Approach May Turn Industry Away" - Pink Sheet, 23 Jun, 2014.).
Manufacturer Communications Regarding Unapproved, Unlicensed, or Uncleared Uses of Drugs, Biologics and Medical Devices	FDA planned to issue guidance in 2014 in response to two citizen petitions by the Medical Information Working Group asking the agency to clarify its policies on truthful, non-misleading communication about off-label use of products (Also see "FDA Promises More Off-label Guidances As Part Of First Amendment Harmonization" - Pink Sheet, 10 Jun, 2014.).
Biosimilarity
Considerations in Demonstrating Interchangeability With a Reference Product	FDA had targeted 2015 for release of the document. AbbVie Inc. filed citizen petition requesting that biosimilar sponsors show interchangeability for every indication on the reference product's label to get the designation (Also see "AbbVie Seeks Strict Interchangeability Standards For Biosimilars" - Pink Sheet, 31 Dec, 2015.).
Labeling for Biosimilar Products	Agency planned to issue the document last year. BIO and PhRMA submitted a citizen petition asking FDA to include certain information in biosimilar product labeling (Also see "Biosimilar Labeling Needs Greater Transparency, BIO And PhRMA Say" - Pink Sheet, 7 Jan, 2016.).
Statistical Approaches to Evaluation of Analytical Similarity Data to Support a Demonstration of Biosimilarity	Document is expected to address issues such as variability limits between the biosimilar and reference product (Also see "Biosimilar Statistical Guidance Will Stress Flexibility, Woodcock Says" - Pink Sheet, 28 Sep, 2015.).
Clinical/Statistical
Measuring Treatment Benefit in Pediatric Populations: Use of Clinical Outcome Assessments	FDA recently launched a pilot compendium of clinical outcome assessments (Also see "FDA Launches Compendium Of Clinical Outcome Assessments With Eye On Patients" - Pink Sheet, 13 Jan, 2016.).
Adaptive Design Clinical Trials for Drugs and Biologicals (revised draft)	FDA draft guidance issued in 2010 expressed caution about use of these trials (Also see "Adaptive Trials Could Have A Steep Regulatory Learning Curve" - Pink Sheet, 8 Mar, 2010.).
Meta-Analysis of Randomized Controlled Clinical Trials to Evaluate the Safety of Human Drugs or Biological Products	FDA held a workshop on the issue in 2013 in preparation for drafting the guidance (Also see "FDA’s Temple: Better Meta-Analyses Needed Ahead Of Agency Guidance" - Pink Sheet, 27 Nov, 2013.).
Multiple Endpoints in Clinical Trials	Entire clinical trial system may get review upon Robert Califf's expected confirmation as FDA commissioner (Also see "Clinical Trial System Needs Radical Change, FDA’s Califf Says" - Pink Sheet, 14 May, 2015.).
Generics
180-Day Exclusivity: Guidance for Industry	FDA is frequently sued over its exclusivity decisions and has relied on court rulings to help shape its policy (Also see "FDA Wrangles With Generic Exclusivity, Looks To Courts For Direction" - Pink Sheet, 18 Oct, 2010.).
ANDA Submissions Refuse to Receive Standards: Questions and Answers	FDA issued draft guidance on refuse-to-receive standards in 2013 (Also see "FDA Will Allow ANDA Corrections … Until 10 Minor Deficiencies Found" - Pink Sheet, 1 Oct, 2013.). Generic Pharmaceutical Association wants a mechanism to challenge refuse-to-receive letters (Also see "FDA ‘Monster’ Patent Reg: Brands, Generics Each Want More Options To Pick Fights" - Pink Sheet, 6 Jul, 2015.).
Issuance of ANDA Complete Response Letters Before Completion of Review By One or More Disciplines	FDA has said it wants to inform ANDA sponsors of major deficiencies before complete response letters are issued (Also see "FDA/Generic Communications Plan Restoring Best Of Past Practices" - Pink Sheet, 18 Dec, 2014.).
Three-Year Exclusivity Determinations for Drug Products	FDA exclusivity determinations have been challenged in court. In one case, Otsuka Pharmaceutical Co. Ltd. sued FDA seeking to block generic versions of Abilify (aripiprazole) (Also see "Otsuka’s Battle To Block Abilify Generics Heats Up As Patent Expires" - Pink Sheet, 23 Apr, 2015.).
Updating ANDA Labeling After the Marketing Application for the Reference Listed Drug Has Been Withdrawn	FDA plans to finalize a proposed regulation that would allow ANDA holders to unilaterally make safety labeling changes by July 2016 (Also see "Generic Labeling Rule: Will Delay Spell Doom?" - Pink Sheet, 3 Dec, 2015.).
Procedural
Drug Supply Chain Security Act Implementation: Waivers, Exceptions and Exemptions for Product Tracing Requirements	Last year FDA issued guidance on product tracing requirements for dispensers (Also see "Track & Trace – And Delay: Pharmacies Get Enforcement Discretion From FDA" - Pink Sheet, 30 Jun, 2015.). In 2014 it issued guidance on vigilance standards (Also see "FDA Setting “Vigilance” Standards For Track And Track Process" - Pink Sheet, 10 Jun, 2014.).
Public Disclosure of FDA-Sponsored Studies	FDA announced in June 2013 that it plans to allow experts outside the agency to analyze clinical trial data that is masked and excludes information that could identify patients (Also see "FDA’s Trial Data Disclosure Policy Diverges From EMA’s By Masking Products" - Pink Sheet, 4 Jun, 2013.).
Use of Electronic Health Records Data in Clinical Investigations	In March 2015 FDA issued draft guidance on electronic informed consent in clinical investigations .