Combo Product Firms Lose Patience As Regs, Guidance Are Delayed Again

Industry firms especially eager to see proposed GMP and adverse event reporting rules.

Combination product companies want the next FDA commissioner to raise the profile of combo product issues within the agency.

"Our concern is that FDA - through inadvertence, not through intention - is not paying a whole lot of attention to combination products," says attorney Brad Thompson, head of the Combination Products Coalition trade group.

Thompson says combination product companies are growing frustrated with FDA's slowness in issuing key rules and guidance documents.

"Our number one concern is that the agency focus more on combination products, that they give that subject matter a higher priority, and that they start moving the freight on these important policy issues," he said.

Of several projects in the works at FDA's Office of Combination Products, the most critical to the coalition are proposed rules on good manufacturing practices and adverse event reporting for combo products, and draft guidance on auto-injectors, Thompson said.

The office, established in 2002, has been headed by CDRH veteran Thinh Nguyen for about a year. When Nguyen took over from former director Mark Kramer and temporary fill-in Joanne Less, the coalition hoped the office's work would speed up (¹ (Also see "Industry Looks To FDA’s New Combo Products Chief For Answers" - Medtech Insight, 18 Feb, 2008.), p. 3).

The office currently has seven staffers; an eighth, Janice Soreth, recently left to join the FDA Office of International Programs.

"We move as quickly as we can inside the agency to get these rules out," Nguyen said in an interview. "Unfortunately for us, we got caught right in the middle of a change in administration."

The office had hoped to issue the GMP and adverse event reporting proposed rules last year. President Obama's temporary freeze on regulations from all federal departments and agencies may delay the releases further (² (Also see "President Obama Freezes Pending Bush Regulations For Review" - Medtech Insight, 26 Jan, 2009.), p. 5).

"Those are important rules," Thompson emphasized. "When you're developing a combination product and you have to make investment decisions about what kind of a plant will be necessary and what kind of systems and so forth will be necessary in order to produce it, there are a number of gray areas."

"The industry has been anxiously awaiting these rules for four years - and nothing."

On tap: GMP case studies, auto-injector guidance

Nguyen explains that the proposed rules are done, but are still undergoing the usual higher-level clearances.

Meanwhile, an Office of Combination Products workgroup is looking at some specific GMP case studies provided by industry with questions about how to proceed in particular situations. The office will try to answer those questions and "put the proposed rule to the test," says Nguyen.

In 2008, the office issued one draft guidance - guidelines outlining the regulatory pathway for imaging equipment makers seeking to add new contrast agent indication labeling - but the imaging industry says the document needs an overhaul ³ (Also see "Imaging Industry Wants A Rewrite On FDA Contrast Indication Guidance" - Medtech Insight, 19 Jan, 2009.), p. 11).

The contrast agent draft guidance was due last fall under 2007 user fee legislation, and must be finalized by the end of this year.

"We need to take a close look, and if we need to, we'll have a public meeting to hear their comments [and] concerns," Nguyen said.

The technical guidance on auto-injectors should be out within the next six months, Nguyen said.

Other key projects for 2009 include a long-awaited concept paper on drug-device cross-labeling issues and a draft guidance defining the term "chemical action," which helps determine whether a product's primary mode of action is as a drug or a device.

FDA conducted a public workshop and received industry feedback on cross-labeling in 2005, but Thompson says the coalition would prefer FDA to direct its efforts toward "some of these other policy areas, rather than spend more time now with cross-labeling."

The coalition is now drafting a proposed guidance on clinical trial issues for combination products, which it hopes to present to FDA within a month.

-Jessica Bylander ([email protected])

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