New drug GMPs, tobacco rules, Part 11 emphasis and return to old warning letter policy seen possible under Obama's FDA.

Drug, device and biologics manufacturers can expect a reversal of several Bush administration policies as they relate to FDA enforcement as soon as President Obama names an FDA Commissioner, which could come sooner than later now that it appears Kansas Gov. Kathleen Sebelius (D) will become his Secretary of Health and Human Services (HHS).

Within the past week, word has surfaced that the Obama administration will revive the issue of having the agency firmly regulate tobacco and not support preemption for state product liability suits against drug firms.

FDA tobacco regulation was tried in earnest under President Clinton from 1994 until 1998 when the U.S. Supreme Court ruled--on a narrow 5-4 vote--that Congress had not delegated such authority to the agency. Whether President Obama seeks legislation in Congress to give FDA such powers is unclear, but changes in the composition of the Supreme Court since the 1990s might lead his administration to seek redress through the courts, potentially by reviving the 1996 regulation the agency issued on tobacco.

Under that rule, which FDA rendered final, cigarettes would have been regulated as "drug delivery devices" and be subject to GMPs, inspections, record-keeping and agency control over advertising and marketing. FDA used the little-known "restricted devices" provision of the 1976 medical device amendments, which is intended to regulate device advertising and marketing, effectively wresting its control from the Federal Trade Commission. The agency also reasoned nicotine was a drug because tobacco companies "intended" to deliver it to users to addict them. They also said nicotine was a component of smoking cessation patches, which are regulated as drugs.

Pre-emption could come under the knife, too. In a setback for drug firms, the U.S. Supreme Court March 4 ruled 6-3 that Wyeth's Phenergan, which had been the subject of product liability suits, should not be preempted from state liability just because it was NDA-cleared under the Food, Drug & Cosmetic Act. The Bush administration had sided with Wyeth and had led the effort to allow pre-emption for Rx drugs, in the same way that the 1976 device law pre-empts PMA'd devices from state liability action in so far as FDA approval standards.

However, in the opinion, written by Justice John Paul Stevens, the court rejected Wyeth's argument that it should be pre-empted. Wyeth said it was unable to change warnings on the I.V.-delivered anti-nausea drug because FDA's "Changes Being Effected" regulations blocked firms from adding warnings to products without agency clearance.

In addition to ramping up inspections, particularly of API plants in China and India, the Obama administration might be tempted to rewrite the 1978 drug GMP rules. The Clinton administration issued a proposed rule in 1996, but it was shelved, largely because of the success of the medical device Quality Systems regulation and industry opposition. A few years later, the Center for Drugs opted to launch "systems-based inspections," which emulated the medical device inspection approach and design controls without having to redo the 1978 regulation.

For many years, several FDAers have maintained they do not need new rules to deal with modern drug manufacturing. However, according to those in the drug chemistry area, the industry has been slow to embrace process analytical technology and Quality by Design. As a result, some believe it may be necessary to demand such changes in regulation, and a new commissioner may be more inclined to issue such a rewrite, and thus codify QbD and PAT by regulation. A new GMP rule also could provide better guidance on how many retests are acceptable in out-of-specification (OOS) cases.

In addition, the new FDA can be expected to reverse the Bush administration 2002 policy on warning letters.

Prior to 2002, field offices and headquarters could issue warning letters once a 483 was issued, without top-level clearance. But due to complaints from industry, then HHS Secretary Tommy Thompson issued a policy barring warning letters from being issued unless they were pre-cleared by the Office of Chief Counsel at FDA. The purpose was to ensure consistency of such letters. In addition, drug advertising "untitled" letters required pre-clearance.

The net result was a precipitous drop in warning letters since 2002 since it became difficult for compliance personnel to get them cleared. In fiscal 2001, 1,032 warning letters were issued by various centers, according to the 2001 "Enforcement Story," which is issued by FDA's Office of Regulatory Affairs. By fiscal 2007, this had dropped to 471, according to that year's edition.

Another policy that could be reversed is the electronic signature/records regulation (21 CFR Part 11). In late 2002, FDA revoked all of its guidance documents and compliance policies for the regulation, and in recent years was considering yanking the regulation altogether, largely because of an industry petition. A new commissioner may decide to re-enact Part 11 regulation and enforcement, or at least update the rules for a modern era of instant communications.

No decisions are likely to be made until Obama appoints a new commissioner, and Sebelius (if she is confirmed by the Senate) will likely have say in the matter. So will House Commerce Chairman Henry Waxman (D-CA), who is among those eager to ramp up FDA enforcement and reignite the agency's regulations over tobacco. By Ken Reid, Editor