Supplement, Drug Co-Packaging Potential Could Be Clipped In FDA Proposed Rule

Innovus Pharmaceuticals is among the firms offering supplements and OTC drugs sold together, an option CRN encourages FDA to allow. FDA will determine on a case-by-case basis whether co-packaged OTCs and supplements already available are in violation of a proposed rule on drug co-packaging.

Dietary supplements sold in tandem with pharmaceuticals, including some currently available, are considered unapproved drugs under a proposed rule on co-packaging drug products that FDA anticipates finalizing in a year.

Innovus Pharmaceuticals Inc. is among the firms offering a supplement and OTC drug sold in tandem. Innovus in July launched tandem sales of its Apeaz OTC pain relief topical and its ArthriVarx joint health supplement, with both products sold together though not in a single package, or co-packaged.

Innovus CEO Bassam Damaj said the San Diego firm, which commercializes OTC drugs and other consumer products for men's and women's health, vitality and respiratory diseases, is testing the market for supplements and OTCs sold together. “We’re looking to see how it’s going to perform,” Damaj said in an interview.

FDA’s Center for Drug Evaluation and Research says it would determine on a case-by-case basis whether co-packaged nonprescription drugs and vitamin, mineral or supplement products already available in the US are in violation of a proposed rule on drug co-packaging. The agency published the proposed rule in December 2015, and its latest regulatory agenda update, which is non-binding. estimates October 2018 publication of a final rule.

“It is difficult to respond to questions about hypothetical scenarios, particularly where the outcome is rather fact-dependent/fact specific. Depending on the specific facts and circumstances, a dietary supplement co-packaged with an OTC drug could suggest or imply that the dietary supplement is intended for a drug use and would, therefore, be considered a drug under” FDA regulations, said Tralisa Colby, a public affairs specialist in CDER’s Office of Communications.

Innovus Pharmaceuticals offers its Apeaz topical analgesic OTC only in tandem sales with its ArthriVarx joint health supplement.

However, the proposed rule – Fixed-Combination and Co-Packaged Drugs: Applications for Approval and Combinations of Active Ingredients Under Consideration for Inclusion in an Over-the-Counter Monograph – doesn’t allow exemptions for supplements that are sold as part of a single package with a drug.

“When used as part of a fixed-combination or co-packaged drug, dietary supplements are considered to be an active ingredient in that product and subject to the requirements of this proposed rule,” CDER said in the proposed rule.

In a footnote clarifying its thinking in the proposal rule, CDER said it considers “dietary supplements that are combined into a single dosage form with, or co-packaged with, a drug to meet the definition of ‘drug’ under” FDA regulations. The center also stated in the footnote that the “proposed rule does not otherwise address nor affect FDA policy on dietary supplements.”

However, the proposed rule would affect the supplement industry. Moreover, defining dietary supplements as drugs in a proposed rule on drug co-packaging appears to the industry as a short-sighted and unfair regulatory statement.

A Drug Regulation For Supplement Marketing?

The Council for Responsible Nutrition let FDA know about its concerns in May 2016 comments on the proposed rule.

“FDA was ostensibly putting out a proposed rule around drugs and we saw them referencing supplements. We dropped [comments] into the agency just to remind them that that, ‘Hey this is not supposed to be a conversation about supplements. If you want to have that, you should have that separately, but not in the context of this drug rule,’” said CRN President and CEO Steve Mister.

FDA previously has compelled firms that were combining drug and dietary supplements in a single formulation to cease making and marketing the products, enforcement that met little pushback. (Also see "Bayer Warning Letters Reinforce FDA Ban On Supplement/Drug Combinations" - Pink Sheet, 3 Nov, 2008.)

But offering separate supplement and drug products in a single package is unlike combining supplement and drug ingredients in a single formulation.

FDA seems to be on thin regulatory ice, Mister says, to include vitamins, minerals and supplements in the proposed drug co-packaging rule. “It says that a dietary supplement becomes a drug by virtue of being packaged with a drug.”

“Now we are moving from just not putting the ingredients in the same pill to where FDA seems to be saying, ‘Well, you can’t even co-package them together.’ We don’t see anything in [FDA regulations] that prohibits that,” he said in an interview.

“We’re saying, ‘This is not the place to have that conversation, FDA. If you want to have it then you should have a conversation separately about the co-packaging of supplements with a drug.’”

FDA is not estimating when the final rule will be published beyond the regulatory agenda statement as it considers CRN’s and other comments on the proposed rule. “We have received several comments including some concerning co-packaging OTC drugs with dietary supplements and are still reviewing those comments as we develop the final rule,” CDER’s Colby said.

Distinguishing Supplement From Medicine?

Part of FDA’s concerns about co-packaging a supplement and a drug is that consumers would confuse the products’ doses and directions, perhaps using the drug product indefinitely as most supplements are used, or using a supplement at the dosage indicated for the co-packaged drug.

That isn’t a potential problem with Innovus’ Apeaz OTC and ArthriVarx supplement, Damaj said. “The topical product is completely different and it is not in the same box as Apeaz,” he said.

Although dissimilar in delivery format, the topical drug and the oral supplement provide complementary benefits, which is why Innovus is offering them together only. “When somebody orders Apeaz, they get it with the supplement,” Damaj said.

Apeaz is an OTC topical analgesic monograph compliant drug for arthritis pain relief containing– camphor 4%, menthol 10% and methyl salicylate 30% – that also contains excipient ingredients that are common as active ingredients in joint health supplements, methyl-sulfonyl methane (MSM) and glucosamine sulfate.

“There are no other products that contain those five ingredients at those concentrations and tested in the collagen arthritis model showing efficacy,” Damaj said.

According to its label, Apeaz is indicated for temporary relief of minor aches and pains of muscles and joints associated with simple backache, arthritis, strains, bruises and sprains.

Innovus says ArthriVarx’s “two main ingredients” are the herb andrographolide paniculate and hyaluronic acid in a formulation “designed to maximize joint health.”

Sales Driver For Firms …

Including a vitamin, mineral or supplement product that complements the indicated effect of a nonprescription drug available in a single package, as Innovus is doing with Apeaz and ArthriVarx, could have appeal as a sales driver.

That is an option CRN wants FDA to allow the industry. “We could foresee that somebody might want to have supplements and an OTC medicine that are shrink-wrapped together,” Mister said.

While a tandem offering with a topical drug and an oral supplement might appear as easier for users to distinguish between the two products, CRN expects it is not asking too much of consumers to correctly follow dose and usage directions for co-packaged oral delivery drugs and supplements.

“What I think consumers are smart enough to know is that if it has a Supplement Facts box on it, it’s a supplement, and if it has a Drug Facts box on it, it’s a drug,” Mister said.

“If you have two products that are co-packaged and they each have their own labeling consumer can figure out that one is a supplement and one is a drug.”

… Convenience For Consumers

In addition to consumers correctly distinguishing packages of nutritionals from drugs, trends in nonprescription drug use support allowing co-packaging the products.

“What’s happening at the same time is you’re seeing more and more OTC medicines that are meant for either a chronic condition or you’re taking them every single day,” Mister said.

For instance, consumers using daily OTC allergy remedies and omega-3s or herbals daily would appreciate the convenience of the drug and supplements being available together.

“Why couldn’t the manufacturer whose making both of those products co-package them for consumer convenience?” Mister said, adding, “Even if it’s not on the condition [indicated for the OTC], it’s just convenient to have them all packaged together.”

Innovus’ Apeaz and ArthriVarx offering is gauging consumer regard for the convenience of supplements and drugs sold together. “So far the response has been great. We’ve been shipping a lot of orders,” Damaj said.

Innovus markets a total of 25 consumer health products, including OTC topicals for premature ejaculation prevention and hemorrhoid treatment and supplements for prostate health, bladder control and sexual health. It also expects FDA approval this year for its abbreviated new drug application filed in 2015 for a fluticasone proportionate spray intranasal corticosteroid, a generic of GlaxoSmithKline Consumer Healthcare LP’s Flonase Allergy Relief. (Also see "Fluticasone Spray Competition Grows With Perrigo Launch Of West-Ward Product" - Pink Sheet, 6 Jun, 2016.)

In 2016, Innovus closed its $630,000 acquisition of brands from Beyond Human LLC, a firm known for its testosterone booster supplement Beyond T Human and its natural human growth agent HGA. (Also see "Industry Roundup: Supplement Labeling Guide Corrected, Nu Skin Settles" - HBW Insight, 7 Mar, 2016.)

More recently, Innovus in June licensed exclusive rights to the University of Iowa Research Foundation’s US patent application on use of thymol and carvacrol (monoterpene phenols) for induction of increased skeletal muscle endurance, lean muscle mass and reduced adiposity. The monoterpene phenols are considered generally recognized as safe by FDA for use in dietary supplements and conventional foods and beverages. (Also see "Tech Transfer Roundup: Janssen, Eisai, Apexian, Innovus And More" - Scrip, 11 Jul, 2017.)