Pediatric OTC Cough/Cold Rulemaking Absent From FDA Regulatory Agenda

The Spring 2015 unified agenda lists June for a final rule on deeming electronic cigarettes and other alternatives to traditional cigarettes and smokeless tobacco products subject to FDA regulation. FDA adds an item to create a single set of regulations on fixed-combination Rx and OTC drugs.

The latest semi-annual unified agenda indicates FDA could be changing course on some regulatory initiatives, such as pediatric OTC cough/cold labeling, while staying the course in others, with a final rule revising nutrition and supplement facts labels forecast for March 2016.

The Spring 2015 UA published May 27 also lists June 2015 as the target date for a final rule on deeming electronic cigarettes, cigars, pipe tobacco and other alternatives to traditional cigarettes and smokeless tobacco products subject to FDA regulation under the Family Smoking Prevention and Tobacco Control Act (Also see "Electronic Cigarettes Granted Two-Year Grace Period Under Proposed FDA Rule" - Pink Sheet, 24 Apr, 2014.).

New to the UA (see table below) is an item on amending regulations on fixed-combination Rx and OTC drugs to create a single set of regulations and codify existing policy on studies needed to show combination drug requirements are met.

However, the UA does not include an update on a proposed rule for pediatric OTC cough/cold labeling, an item that has been a fixture of FDA’s regulatory initiatives since 2008. The Fall 2014 UA, published in December, listed it with October 2015 as a target date for a notice of proposed rulemaking.

FDA initially noted work on an NPRM for proposed changes to a final OTC monograph to address safety and efficacy concerns associated with pediatric cough/cold products after a joint advisory committee in 2007 recommended restricting OTC cough/cold medicines to children 6 years and older, and institute a “no use” rule for the products in children younger than 2 years.

The American Academy of Pediatrics suggests FDA move ahead with the NPRM changes.

Kathleen Neville, a physician and chairwoman of the AAP Committee on Drugs said the academy “expresses profound disappointment with the Food and Drug Administration’s failure to act on safety and efficacy problems associated with cough and cold medicines for children.”

“Pediatricians are quite concerned that FDA’s decision to remove the monograph revision from its regulatory agenda signifies that this issue is not a high priority for the agency. It has already been seven years since FDA pledged to re-evaluate the dosing and labeling of these products to ensure that they are consistent with existing data on safety and efficacy in children, and no action has yet been taken,” Neville added in a statement.

The Department of Health and Human Services, in its fiscal 2015 regulatory priorities statement attached to the UA, noted nutrition and supplement facts labels have not been updated since 1993, when mandatory nutrition labeling of food was first required. “The aim of the proposed revision is to provide updated and easier to read nutrition information on the label to help consumers maintain healthy dietary practices,” according to the statement.

Also absent from the latest UA after inclusion in numerous iterations is an NPRM to amend the OTC monograph to account for a reassessment of acetaminophen’s safety amendments. The Fall 2014 UA set target dates for publishing an NPRM in October 2014 for an amendment to require age- and weight-based dosing for acetaminophen products for children under 2 years, and December 2014 to lower the individual or daily doses, prohibit the ingredient in combination products, limit the quantity of doses in a pack and other changes – some of which industry has made already voluntarily (Also see "Lower Acetaminophen Doses Recommended Despite Cost Impact, Lack Of Data" - Pink Sheet, 6 Jul, 2009.).

FDA in October published a draft guidance with label clarifications, packaging and delivery device recommendations and product concentration standardization for liquid acetaminophen pediatric products; in November the agency published a draft guidance to formalize a request it made in a 2013 Drug Safety Communication for firms marketing OTCs containing acetaminophen to add label warnings about serious, but rare, skin reactions, Stevens-Johnson Syndrome and toxic epidermal necrolysis ( (Also see "Draft Guidance Drills Down With Details To Cut Pediatric Acetaminophen Overdose Risk" - Pink Sheet, 8 Oct, 2014.) and (Also see "Industry News Roundup" - Pink Sheet, 25 Nov, 2014.)).

Other pending OTC drug regulatory items noted in the previous UA but absent from the latest are:

• Combinations of Bronchodilators With Nasal Decongestants or Expectorants; Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for OTC Human Use: remove from the monograph and reclassify as not generally recognized as safe and effective the combination of the bronchodilators epinephrine and its salts and an expectorant, such as guaifenesin, or oral nasal decongestants based partly on concern that secretions loosened by the medication could dry in and narrow the airways of asthmatics.
• OTC Drug Review – Laxative Drug Products: finalize professional labeling for sodium phosphate products; the agency in 2008 warned the products should not be used for bowel cleansing because of a risk of acute phosphate nephropathy and said it wanted to remove professional labeling for the ingredient as a bowel cleanser. More recently, FDA warned the ingredient is associated with serious adverse events following overdose (Also see "In Brief: laxatives warning, FTC settlement, ChromaDex inks 5LINX deal" - Pink Sheet, 13 Jan, 2014.).
• OTC Drug Review – Oral Health Care Products: labeling changes to address the safety of oral health care products with the painkiller benzocaine. Public Citizen in July 2014 asked FDA to remove teething for children 2 years and older as an indication for benzocaine OTC oral health care products and require a contraindication on labels advising against using gel and liquid products containing the ingredient for teething pain. The agency in 2011 published a consumer warning that products with benzocaine are linked to rare but serious and potentially fatal adverse events (Also see "OTC Benzocaine Needs Label Warning, Indication Change – Public Citizen" - Pink Sheet, 30 Jul, 2014.).

Department of Health and Human Services agencies and divisions of other federal departments publish semi-annual updates to their ongoing regulatory initiatives with estimated deadlines, which are not binding and often missed.

FDA Spring 2015 Unified Agenda: Consumer Health Care Products
Regulation	Description Of FDA Action
Status
Over-the-Counter Drug Review – Cough/Cold (antihistamine) Products	Add the common cold indication to certain OTC antihistamine active ingredients. This proposal is the result of collaboration under the U.S.-Canada Regulatory Cooperation Council as part of efforts to reduce unnecessary duplication and differences. This pilot exercise will help determine the feasibility of developing an ongoing mechanism for alignment in review and adoption of OTC drug monograph elements.
NPRM: expected September 2015 (Also see "Cold Indication For Antihistamines Targeted In Regulatory Agenda" - Pink Sheet, 7 Jan, 2013.).
OTC Drug Review – Topical Antimicrobial Drug Products	Does not affect health care antiseptics approved through NDAs or consumer antibacterial soaps or hand sanitizers. Health care antiseptics – hand washes and rubs, surgical hand scrubs and rubs and patient preoperative skin preparations, including pre-injection preparations – primarily are used by professionals in hospitals, clinics, doctors’ offices, outpatient settings and nursing homes.
Comments period ends Oct. 28 on proposed rule requiring additional safety and effectiveness data to demonstrate triclosan and other ingredients in the OTC health care antiseptics monograph are GRASE (Also see "Industry Roundup: Colgate, GNC, Sanofi, Pfizer Earnings" - Pink Sheet, 4 May, 2015.).
Regulations on Fixed-Dose Combination and Co-Packaged Drug and/or Biological Products	Amend regulations on fixed-combination Rx and OTC drugs, for which current regulations require sponsors to demonstrate each of the components makes a contribution to the drug's claimed effects. Proposed rule would create a single set of regulations for Rx and OTC combination drugs and codify existing policy on studies needed to show the combination drug requirements are met; also would apply to combinations of biological drug products and to drug-biological product combinations; clarify application of FDA's requirements regarding fixed-dose combinations to certain natural source drugs and certain synthetic drugs; establish circumstances under which FDA might waive the combination requirements for a particular drug or biological product; and address co-packaging.
NPRM: August 2015
Additional tobacco products subject to FDA regulation	Finalize FDA’s proposed rule to give the agency oversight of cigars, pipe tobacco, e-cigarettes and other tobacco or nicotine products not covered in the 2009 Family Smoking Prevention and Tobacco Control Act (Also see "Electronic Cigarettes Granted Two-Year Grace Period Under Proposed FDA Rule" - Pink Sheet, 24 Apr, 2014.).
Proposed rule published April 2014; publication of final rule expected June 2015.
Clarification of When Products Made or Derived From Tobacco Are Regulated as Drugs or Devices	Describe circumstances in which a product made or derived from tobacco intended for human consumption will be subject to regulation as a drug, device or a combination product.
NPRM: June 2015.
Foreign Supplier Verification Program	Explain responsibilities of importers of food products, including dietary supplements, for demonstrating food produced abroad is as safe as food made in the U.S.
Supplemental NPRM comment period ended in December 2014; final rule targeted October 2015 (Also see "In Brief: FSMA deadlines, adulteration bill, pharma supply chain pilot" - Pink Sheet, 24 Feb, 2014.).
Amendments to Food Facility Registration Requirements	Require food facilities submit registrations in an electronic format beginning in 2016 and codify the requirement that facilities renew registrations every two years; also amend the definition of "retail food establishment," and require certain additional information be submitted as part of food facility registration (Also see "Industry News Roundup" - Pink Sheet, 24 Sep, 2014.).
NPRM published in April 2015; comment period ends June 8.
Food Labeling; Gluten-Free Labeling of Fermented, Hydrolyzed, or Distilled Foods	Establish requirements concerning compliance for using "gluten-free" labeling claim for foods for which there is no scientifically valid analytical method available that can reliably detect and accurately quantify the presence of 20 parts per million gluten in the food.
NPRM: May 2015.
User Fees for FDA’s Third-Party Accreditation Program for Food and Feed	Establish a reimbursement program to assess user fees and require reimbursement for the work performed to establish and administer the Accreditation of Third-Party Auditors system under Food Safety Modernization Act.
NPRM: May 2015.
Food Labeling; Revision of the Nutrition and Supplement Facts Labels	Amend labeling regulations for conventional foods and dietary supplements to provide updated nutrition information to assist consumers in maintaining healthy dietary practices; modernize the nutrition information on the Nutrition Facts label, as well as its format and appearance.
Final rule: March 2016 (Also see "In Brief: FTC, FDA Enforcement; Insider Trading On NBTY Sale; Comment Period On Label Changes" - Pink Sheet, 26 May, 2014.).