FDA's Readiness Questioned In Electronic AER Comments

FDA's planned move to mandatory electronic filing of adverse event reports is raising concerns about costs for small businesses and the agency's ability to fully integrate its growing number of electronic filing requirements.

The proposed ¹ rule would require manufacturers of all prescription drugs, OTCs approved through applications, vaccines and medical products to electronically report to FDA any adverse events from use of their products within 15 days of receiving them from consumers, patients or physicians.

The proposal, published in August 2009, does not apply to monograph OTCs, but the Center for Drug Evaluation and Research asked for comment on whether to require electronic submission for AERs concerning all nonprescription drugs.

The Consumer Healthcare Products Association strongly endorses electronic filing, even though manufacturers of OTCs that do not require new drug applications were not required to file adverse events reports until January 2008 under the Dietary Supplement and Nonprescription Drug Consumer Protection Act passed in December 2006 (² 'The Tan Sheet' Nov. 16, 2009, In Brief, and ³ (Also see "Final Guidance For Reporting Adverse Events Gets Serious On Definitions" - Pink Sheet, 20 Jul, 2009.)).

"We supported the law and it certainly makes sense to get it done electronically," David Spangler, CHPA's senior VP for policy, said in an interview. "We want to make sure the FDA has what it needs to ensure the public's trust in the safety of OTC medications."

Johnson & Johnson also favors including OTCs in the electronic filing requirement. Pointing out that it markets Rx and nonprescription drugs as well as medical devices, the firm says "it would be optimal" to apply the electronic standard to all AER filings.

Flexibility Needed On Effective Date

However, like other firms, J&J recommended in November 2009 comments that FDA remain flexible on the effective date for the requirement, which is proposed at a year after publication of a final rule.

In the event of changes in the "technical details" of the Electronic Systems Gateway FDA currently operates, firms should be allowed more time for compliance, Carrie Corboy, Benefits Risk Management senior director for J&J Pharmaceutical Research & Development, said in the comments.

Corboy also recommended FDA clarify the rule's provision concerning submitting product labels with AER filings. The rule's reference to the "content of labeling" should be explained so firms know what label information is required, she wrote.

FDA Wants To Expedite Identification

Firms' quarterly reports on AERs will also be filed electronically under the proposed rule, which aims "to expedite the identification of emerging safety problems."

Companies that still file paper reports force FDA staff or contractors to transcribe their data into the FDA's electronic adverse events database, which can delay the process anywhere from two weeks to two months and cost the agency up to $2.4 million a year.

However, not everyone is pleased at the prospect of moving the adverse events reporting system into the 21st century.

One unnamed nonprescription drug firm, represented by Chicago-area attorney John Lemker, complained about FDA's recent move to electronic registration of products, which it claimed took the company more than 350 hours and $10,000 to implement.

Software systems frequently were changed, Lemker wrote. The system left users wondering if products were successfully registered, and proved unnecessarily complicated.

The company's attempt to reach the designated FDA staffer was met with a full in-box message by the automated answering system, claimed Lemker, who submitted the comments while with the K&L/Gates firm but has since moved to the Wood Burditt Group.

"Their history with the other requirements for electronic reporting doesn't bode well," said Lemker, who did not disclose his client's name. "If we can't list, how are they [FDA] going to do anything electronically?"

He recommended that for the purposes of the electronic AER rule, FDA define small businesses as those with fewer than 100 employees and less than $10 million in sales.

"Small business entities should be categorically exempted from mandatory electronic submissions until the agency gains experience with any electronic reporting requirements that are imposed regarding reporting safety information," according to Lemker's comments.

Safe Products Elicit Few AERs

CHPA also has considered the possible impact on small businesses, Spangler noted, adding firms that market a small number of safe and effective products receive few AERs.

"If you're a small company and it's a product without many adverse events, the reporting is tiny," he said.

He compared two CHPA members making similar products: multinational Pfizer markets the Chapstick line, and family-owned Blistex Inc. markets the Blistex lip care line with the same name. "Both are supporting the law," Spangler said.

Setting Criteria For Waivers

The proposed rule allows FDA to issue temporary waivers to companies that cannot meet the electronic filing requirements. While the agency anticipates such waivers would be "rare," the rule does not state the criteria waiver applicants must satisfy.

San Diego-based Amylin Pharmaceuticals proposed waivers be allowed "for companies that are bringing their first commercially available product to market." Amylin already markets injectable Byetta (exenatide) for diabetes, and has an application pending for a longer-lasting version of the drug.

The proposed rule anticipates that manufacturers of vaccines will be able to file their adverse event reports using the same electronic gateway as the one for drugs. But the system still isn't up and running.

"Developments are under way to implement this submission capability" to the Vaccine Adverse Events Reporting System, the proposed rule noted.

"We are concerned that it will not be fully operational when the effective date is implemented," said Brian Mayhew, director of global medical and regulatory policy for Merck.

Merck also wants FDA to encourage the International Conference on Harmonisation, the global group that includes European, Japanese and U.S. regulators, to include medical devices and all vaccines under its electronic reporting rules.

Currently, devices are not covered and vaccines have only limited reporting requirements.

"We believe FDA should collaborate with other regional and country regulatory health authorities to ensure a comprehensive approach to this matter," Mayhew said.

The Merck official also pointed out what could be a loophole in the proposed final rule, which has been more than 10 years in the making. While it covers combination drug products, it does not specifically list drug devices such as drug-eluting stents or biologic-device combination products.

The Biotechnology Industry Organization supported the new rule, but also raised cost concerns. It asked that the system eliminate all fees to remove barriers for small companies.

"About 80 percent of companies are already reporting electronically," said Andrew Emmett, director of science and regulatory affairs at BIO. "We want to ensure there aren't any barriers for the remaining 20 percent."

Like J&J, BIO expressed concern about the robustness of the software interface, fearing computer glitches might lead a company to believe it had successfully filed an adverse event report when in fact FDA had not received it.

No consumer groups reacted to the proposed final rule, for which comments were due in November. FDA still has no timeline for publishing the final rule, according to Roger Goetsch, senior regulatory officer in CDER's Office of Surveillance and Epidemiology.

[Editor's note: This story was contributed by ⁴ 'The Pink Sheet,' your weekly source for prescription pharmaceutical news. For more information call 1-800-332-2181.]

- Merrill Goozner ( ⁵ [email protected] )