MEMORANDUM

Stengel, District Judge.

This case is part of a Multidistrict Litigation (MDL) involving claims of liver damage from the use of Tylenol at or just above the recommended dosage.1 This is the first "bellwether" scheduled for trial.2 The plaintiff claims that her sister died of acute liver failure after taking Extra Strength Tylenol "as directed" by its label.3 She asserts that defendants Johnson & Johnson and McNeil — the makers of Tylenol — knew or should have known that consumers may develop acute liver failure after taking Extra Strength Tylenol at or just above the recommended dose, yet failed to warn users of this risk.

The defendants moved for summary judgment on the plaintiff's failure-to-warn claim, arguing that the plaintiff has not offered sufficient evidence of this claim and/or the claim is preempted by federal law. For the reasons explained below, I will deny the defendants' motion.

I. A HISTORICAL OVERVIEW OF TYLENOL4

The plaintiff's claims are different from those previously asserted against the defendants about the safety of Tylenol. While previous cases have questioned whether Tylenol can cause liver damage, this case and others in this MDL question the extent of such damage and the quickness with which it can occur. A historical overview of the regulation and science of Tylenol is helpful in explaining the plaintiff's claims.

a. TYLENOL, ACETAMINOPHEN, AND LIVER DAMAGE5

Extra Strength Tylenol is an over-the-counter (OTC) pain reliever; consumers do not need a prescription to buy it. The active ingredient in Extra Strength Tylenol is acetaminophen, which is an analgesic and antipyretic or pain reliever and fever reducer.6 Defendant McNeil manufactures and markets many different Tylenol products, including Extra Strength Tylenol and Regular Strength Tylenol. The two products differ in that one tablet of Extra Strength Tylenol contains 500 mg of acetaminophen while a tablet of Regular Strength Tylenol contains only 325 mg of acetaminophen per tablet. Johnson & Johnson is the parent company of McNeil and is involved in managing its operations.

Acetaminophen was first synthesized as a pain reliever in the 1890s and has been available OTC since the 1960s.7 Tylenol is one of more than 600 acetaminophen-containing products on the market in the United States in OTC and prescription formulations.8 Acetaminophen is one of the most widely used OTC drugs.9 Twenty percent of Americans — 60 million people — ingest an acetaminophen-containing product each week.10 The Food and Drug Administration (FDA), which regulates OTC drugs, has found acetaminophen to be a "safe and effective OTC analgesic" when taken in recommended doses and used according to the label.11 However, acetaminophen has been known to cause severe liver damage.12

i. Acetaminophen's Link to Acute Liver Failure

Acetaminophen is different from other OTC pain relievers in two ways: 1) it is the only one to have an antidote, and 2) its maximum total daily limit is the same for both OTC and prescription products.13 Acetaminophen is a "dose-related toxin," meaning it can be safely used at certain doses but harmful at higher doses.14 As a result, there is evidence that it has a "narrow therapeutic margin" — i.e., there is little difference between the current maximum recommended dose of acetaminophen and the doses that could cause liver injury.15 The parties debate how narrow this margin is.

A simplistic explanation of how the body metabolizes acetaminophen helps frame the issues in this case. Typically, glutathione — an antioxidant found in the liver — will bind to the toxic parts of acetaminophen, to neutralize them and prevent them from harming the body.16 These neutralized toxins are then excreted.17 However, if the body does not have enough glutathione, those toxins can build up in the liver, causing acute liver failure (ALF). Glutathione stores may be low when a person is malnourished or when the liver has been neutralizing a lot of toxins at once.18

"Acute liver failure (ALF) is a rapid deterioration of the organ's ability to function."19 Patients who experience ALF can fall into a coma or die.20 They may require a liver transplant.21 A person who has recovered from ALF may still be at risk of redeveloping it, if the person again consumes too much acetaminophen.22

If acetaminophen-induced ALF is recognized quickly, acetaminophen's antidote (N-acetylcysteine or NAC) can be given to a patient to supply glutathione and prevent or decrease liver injury.23 However, persons who have developed ALF from an unintentional acetaminophen overdose may not realize their liver injury because symptoms of ALF are not readily apparent or may look like the symptoms the acetaminophen is being used to treat (i.e., flu symptoms).24

ii. FDA Actions to Address Acetaminophen-Induced Acute Liver Failure

The majority of acute liver failure cases in the United States are related to the use of acetaminophen.25 Each year, acetaminophen is responsible for hundreds of deaths and liver transplants, in addition to tens of thousands of hospitalizations.26 These acetaminophen-induced liver injury patients include both people who are intentionally trying to harm themselves (i.e., attempting suicide) and those who take acetaminophen for therapeutic reasons (i.e., to treat physical pain).27 There is evidence that patients taking acetaminophen at 4 g per day — the recommended maximum daily dose until recently — may be at risk of developing acute liver failure.28

Medical literature began questioning the safety of acetaminophen at or just above therapeutic levels as far back as the 1980s.29 During the 1990s, members of the medical community continued to raise concerns about acute liver failure occurring in patients at or even lower than the maximum daily dose of 4 grams.30 Throughout this same time period, McNeil was also actively engaged in research and development of a drug or combination of ingredients that would reduce or eliminate acetaminophen's potentially toxic effects on the liver.31

In 2002, the FDA convened an Advisory Committee to discuss ways to prevent liver injury caused by unintentional acetaminophen overdose.32 During the Committee Meeting, the FDA presented findings from medical literature: 1) that hepatotoxicity may occur "at recommended doses of APAP," 2) that such cases were linked to risk factors such as alcohol use and/or fasting, and 3) that some cases of unintentional overdose led to death.33 The FDA also presented its own findings from a review of its own internal Adverse Event Reporting (AER) database. The FDA found hepatotoxicity (i.e., liver damage) in persons who have ingested less than 4 grams/day and who had risk factors like alcohol and "poor nutritional status."34 As a result, the American Association of the Study of Liver Disease (AASLD) and the FDA offered specific recommendations for enhancing safety warnings and instructions for acetaminophen-based products.35

In 2006, the FDA proposed a rule to strengthen warnings regarding the risk of liver damage from taking acetaminophen. After receiving and reviewing public comments, the FDA promulgated a final rule outlining the liver warnings it found to be necessary.36 This final rule, issued in 2009, is explained further below.

In February 2008, the Acetaminophen Hepatotoxicity Working Group for the Center for Drug Evaluation and Research of the FDA met to discuss ways to address unintentional acetaminophen overdose.37 The Group outlined several recommendations, including a reduction in the maximum tablet strength from 500 mg to 325 mg.38 The reduction in tablet strength was intended to reduce the overall recommended daily dose of Tylenol from 4,000 mg to 3,250 mg.39 This recommendation was made over the objection of an unnamed acetaminophen manufacturer which asserted the data did not support a need for the change; the Group looked at Adverse Events Reports (AERs) showing that daily doses of 4 g presented a risk for some individuals.40 Survey data also showed that "people routinely and knowingly take more than the recommended dose of OTC pain relievers."41

In June 2009, a joint meeting of several FDA Advisory Committees was held to discuss the issue of liver injury related to acetaminophen use.42 The joint committee recommended that the warning on acetaminophen products be further strengthened and the recommended dose reduced.43

b. THE REGULATORY FRAMEWORK FOR TYLENOL

OTC drugs are approved by the FDA through two separate routes: the New Drug Application (NDA) process and the monograph system.44 During the forty or so years Extra Strength Tylenol has been available OTC, it has been regulated under both FDA regulatory processes.

i. New Drug Application v. Monograph Process

The NDA process requires specific products be approved for sale with specific labeling.45 The monograph system allows for the marketing of OTC drugs containing particular ingredients, which were already on the market before the FDA established the monograph system in 1972.46 These active ingredients, which include acetaminophen, were ones which had been found to be generally safe and effective through general usage.47 Therefore, they were allowed to remain on the market OTC.

Because Extra Strength Tylenol's active ingredient is acetaminophen, it was automatically regulated by the monograph system as of 1972. In 1975, the FDA approved Extra Strength Tylenol as "safe and effective for use as recommended in the submitted labeling," pursuant to a New Drug Application (NDA 17-552).48 In the FDA's letter approving Extra Strength Tylenol for OTC sale and use under the NDA, the FDA also noted that "upon publication in the FEDERAL REGISTER of the OTC Monograph for acetaminophen, revision of the labeling or other action affecting the marketing of [Extra Strength Tylenol] may be required."49 In 1998, McNeil voluntarily withdrew the NDA for Extra Strength Tylenol.50 Since that time, Extra Strength Tylenol has been marketed pursuant to the monograph system only.51

The monograph system is essentially an expanded version of administrative notice-and-comment rulemaking, which required two rounds of proposals and comments as opposed to just one. The monograph process includes four main steps: 1) a review by panels of qualified experts which then recommend the conditions under which the drug can be used, 2) publication of a the expert panel's recommendations as a proposed rule in the Federal Register for public comment on safety and effectiveness, 3) FDA review of the comments on the experts' proposed rule and publication of a tentative final monograph (TFM) with a second opportunity for comments on the TFM, and 4) publication of the final monograph which includes the FDA's findings on when a drug is considered to be generally safe and effective for use.52 See 21 C.F.R. § 330.10. A drug is considered "safe" under the monograph system when it has "a low incidence of adverse reactions or significant side effects under adequate directions for use and warnings against unsafe use as well as low potential for harm which may result from abuse under conditions of widespread availability." 21 C.F.R. § 330.10(a)(4).

ii. Regulation of Acetaminophen Under the Monograph System

In 1972, acetaminophen was listed as "an effective analgesic" under the Drug Efficacy Study Implementation program implemented by the FDA, which was the first phase of what would become the monograph process.53 In 1977, the FDA published a Proposed Rule for Internal Analgesic, Antipyretic, and Antirheumatic (IAAA) Products reflecting the Advisory Panel's report on this category of ingredients.54 This Rule categorized acetaminophen as a Category I active ingredient, meaning that it was "generally recognized as safe and effective" or GRASE. That proposed rule made clear that warnings on products containing those ingredients were still important: "[b]ecause OTC products can be purchased by anyone [and] the public generally does not regard those products as medicines which, if used improperly, can result in injurious or potentially serious consequences."55 The rule explained: "The consumer should be informed of any possible signs of known toxicity or any indication requiring discontinuation of the use of the drug so that appropriate steps may be taken before more severe symptoms become apparent."56 Specifically, the Proposed Rule noted: "acetaminophen has no [ ] sign of toxicity or `safety valve' to alert the consumer [to the development of ALF]."57 For this reason, the Proposed Rule recommended that all products containing acetaminophen contain the warning, "Do not exceed recommended dosage because severe liver damage may occur."58 The Proposed Rule also stated that a single dose of acetaminophen (2 tablets) containing 500 mg — i.e., Extra Strength Tylenol — should be taken every 6 hours while a single dose of 325 mg tablets could be taken every 4 hours.59

On November 16, 1988, the FDA issued a Tentative Final Monograph (TFM) for Internal Analgesic, Antipyretic, and Antirheumatic (IAAA) products, including acetaminophen.60 In the TFM, the FDA reviewed comments on the 1977 Proposed Rule and determined which parts remained valid and which it declined to adopt. Though the FDA made its recommendations for regulating IAAA products, the TFM was still considered a proposed regulation subject to additional comments.61 In the TFM, the FDA continued to categorize acetaminophen under Category I: GRASE.62 It adopted the Panel's recommended dosing as well.63 Specifically, products containing acetaminophen were expected to have the following dosing instructions for adults: "325 to 650 milligrams every 4 hours or 325 to 650 milligrams every 3 hours or 650 to 1,000 milligrams every 6 hours, while symptoms persist, not to exceed 4,000 milligrams in 24 hours or as directed by a doctor."64 It also "tentatively decided not to adopt the liver warning recommended by the Panel" though the FDA was "aware that liver damage can occur from acetaminophen overdosage."65

The FDA has not yet issued a Final Monograph for IAAA products. These products, including those containing acetaminophen, continue to operate under the Tentative Final Monograph (TFM). During the relevant timeframe of this case, Extra Strength Tylenol was only regulated by the TFM.66 The FDA has explained: "Under a TFM, manufacturers market products at their own risk and are able to make voluntary adjustments [to their product's label] taking into account the information presented in the proposed TFM."67 Until that final regulatory determination is made — if it ever is — the defendants remain responsible for all aspects of the Tylenol label.68

c. EXTRA STRENGTH TYLENOL LABELING FROM 1977 TO 2010

From 1977 until 1994, the label on Extra Strength Tylenol bottles remained virtually unchanged. Over the next ten years, McNeil petitioned the FDA three times to allow them to add additional warnings to the Extra Strength Tylenol label. In 1994, McNeil sought approval from the FDA to add a warning that taking Extra Strength Tylenol with alcohol or other products containing acetaminophen could cause liver damage.69 The FDA approved this request.70 During the approval process, the FDA informed McNeil that the Extra Strength Tylenol label was not in conformity with the TFM because it instructed consumers to take 2 caplets "every 4-6 hours" as opposed to every 6 hours.71 In 1998, the FDA promulgated a final rule requiring that an alcohol warning be included on all acetaminophen products.72

In 2001, McNeil again petitioned the FDA to add a warning stating: "[t]aking more than the recommended dose (overdose) could cause serious health problems."73 After an advisory committee meeting with the FDA about acetaminophen labeling and safety, McNeil submitted a second request to further strengthen its proposed warning change by replacing "serious health problems" language with specific language warning of overdose and liver damage.74 The FDA approved that change in 2003.75 In 2004, McNeil introduced a Tylenol warning that contained the following overdose/organ-specific liver damage language:

In 2006, the FDA proposed new organ-specific warnings for all OTC internal analgesic, antipyretic, and antirheumatic (IAAA) drug products — including acetaminophen.77 Using the notice and comment procedure found in the Administrative Procedures Act, the FDA put forth a proposed rule about the warnings, allowed for public comment, and then issued a "Final Rule" on April 29, 2009.78 This "Final Rule" set the minimum requirements for acetaminophen labeling regarding liver damage warnings.79 The 2009 Final Rule was designed "to inform consumers about the risk of liver injury when using acetaminophen."80 The 2009 Final Rule is codified at 21 C.F.R. § 201.326.81

The 2009 Final Rule requires that all OTC products containing acetaminophen must include the following language on their label:

The rule requires that the liver warning be the first warning under the "Warnings" heading for the label.83

During the notice and comment period for the 2009 Final Rule, the FDA considered whether to add a warning about the adverse effects acetaminophen may have on persons who are fasting or malnourished. The FDA declined to adopt a "fasting" warning because it did not find sufficient evidence was presented to support such a requirement.84

The new liver warnings were required to be on all products by April 29, 2010. 74 Fed. Reg. 19385 (Apr. 29, 2009). Following the implementation of the 2009 Final Rule, McNeil changed the Extra Strength Tylenol label to include the following warnings:

The previous label included the following warnings: "Acetaminophen may cause liver damage," "Do not use with any other product containing acetaminophen," "Overdose warning: taking more than the recommended dose (overdose) may cause liver damage," and "do not take more than directed (see overdose warning)."86

II. OVERVIEW OF PLAINTIFF'S CLAIMS

a. FACTS REGARDING DENICE HAYES'S DEATH

Plaintiff Rana Terry brings this wrongful death and products liability action on behalf of her deceased sister's estate.87 Her sister Denice Hayes died on August 31, 2010.88 Denice was a single woman living with another sister Rebecca Hayes; the two had lived together for most of her life, up until the time of Denice's death.89 Denice was not working at the time of her death due to health problems. Prior to leaving the workforce in 2008 for health reasons, she was employed as a teacher for several years.90

Denice's medical history included weight issues, back and leg pain, high blood pressure, and type II diabetes.91 Denice had taken Extra Strength Tylenol periodically for years to treat some of these health conditions with no adverse effects.92 She allegedly preferred Extra Strength Tylenol to Regular Strength Tylenol.93 Rebecca typically did the shopping for both she and her sister. Rebecca was unaware of the difference between Extra Strength Tylenol's dosage and that of Regular Strength Tylenol.94 However, she purchased Tylenol over its generic version because she and her sister thought Tylenol was a better, safer product.95 The two sisters often watched television together and viewed ads for Tylenol.96 According to Rebecca, Denice believed Tylenol was easier on the stomach based on advertising about the product.97

In August 2009, Denice underwent gastric bypass surgery to rectify her ongoing health problems.98 After the surgery, she lost 180 pounds; she was able to stop taking her medications for high blood pressure and diabetes.99 She used painkillers less than before because her back and leg pain had lessened.100 In June 2010, she then had a fall which exacerbated her back pain.101

In mid-August 2010, Denice underwent lumbar laminectomy surgery.102 She was instructed by her doctor to take Regular Strength Tylenol in conjunction with Lorcet, a prescription drug containing acetaminophen, and was not to exceed four grams of acetaminophen in a 24-hour period.103 Denice took Extra Strength Tylenol from August 12, 2010 to August 29, 2010 at "appropriate times and in appropriate amounts."104 She allegedly took tablets from a medium-sized bottle Rebecca had purchased the previous August to treat Denice's gastric bypass surgery pain.105 That bottle was shared by the two sisters during that year.106 Denice allegedly used that bottle until it ran out. Rebecca purchased another bottle of Extra Strength Tylenol for her sister on August 28, 2010.107

After her surgery, Ms. Hayes also began taking Lorcet as instructed by her doctor. However, she allegedly stopped taking Lorcet at some point before her death because she didn't like its side effects.108 She continued to only take Extra Strength Tylenol because she thought it was gentler on her stomach.109

Between August 12, 2010 and August 31, 2010, Denice was in and out of the hospital.110 She was admitted to the hospital overnight on August 20, 2010 for "nausea, vomiting, and impending dehydration."111 She was experiencing back and rectal pain.112 She was released on August 23, 2010.113 During the week of August 23, 2010, Denice continued to experience symptoms of nausea and vomiting.114 She was having trouble eating solid foods.115 She allegedly took three to four doses of Extra Strength Tylenol each day during that week.116 During this timeframe, Denice was cared for by several members of her family.117

Denice was again admitted to the hospital on August 29, 2010.118 The doctor diagnosed her with acute liver failure "most likely [from] accidental Tylenol overuse" and treated her with the acetaminophen antidote.119 Denice died in the hospital two days later. Her cause of death is listed as "liver failure" caused by "acetaminophen intoxication."120

b. PLAINTIFF'S CLAIMS

In January 2012, Ms. Terry filed suit against Johnson & Johnson and McNeil asserting, inter alia, a negligent failure-to-warn claim. According to the plaintiff, the defendants knew that Tylenol could cause liver damage at or just above the recommended dose, especially when a person has been fasting or malnourished. The plaintiff claims the defendants are liable for Denice's death because they failed to warn consumers about the risk of injury and/or death Tylenol could cause.

The defendants move for summary judgment, arguing that the plaintiff cannot offer sufficient evidence at trial to support her failure-to-warn claim. The defendants also argue that the plaintiff's failure-to-warn claim is impliedly preempted.121

III. SUMMARY JUDGMENT STANDARD

Summary judgment is appropriate "if the movant shows that there is no genuine dispute as to any material fact and that the movant is entitled to judgment as a matter of law." FED. R. CIV. P. 56(a). A dispute is "genuine" when "a reasonable jury could return a verdict for the nonmoving party" based on the evidence in the record. Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 248, 106 S.Ct. 2505, 91 L.Ed.2d 202 (1986). A factual dispute is "material" when it "might affect the outcome of the suit under the governing law." Id.

A party seeking summary judgment initially bears responsibility for informing the court of the basis for its motion and identifying those portions of the record that "it believes demonstrate the absence of a genuine issue of material fact." Celotex Corp. v. Catrett, 477 U.S. 317, 323, 106 S.Ct. 2548, 91 L.Ed.2d 265 (1986). Where the non-moving party bears the burden of proof on a particular issue at trial, the moving party's initial Celotex burden can be met simply by demonstrating to the district court that "there is an absence of evidence to support the non-moving party's case." Id. at 325, 106 S.Ct. 2548. After the moving party has met its initial burden, the adverse party's response must cite "particular parts of materials in the record, including depositions, documents, electronically stored information, affidavits or declarations, stipulations (including those made for purposes of the motion only), admissions, interrogatory answers, or other materials." FED. R. CIV. P. 56(c)(1). Summary judgment is therefore appropriate when the non-moving party fails to rebut by making a factual showing that is "sufficient to establish the existence of an element essential to that party's case, and on which that party will bear the burden of proof at trial." Celotex, 477 U.S. at 322, 106 S.Ct. 2548.122

Under Rule 56 of the Federal Rules of Civil Procedure, the court must draw "all justifiable inferences" in favor of the non-moving party. Anderson, 477 U.S. at 255, 106 S.Ct. 2505. The court must decide "not whether ... the evidence unmistakably favors one side or the other but whether a fair-minded jury could return a verdict for the plaintiff on the evidence presented." Id. at 252, 106 S.Ct. 2505. If the non-moving party has produced more than a "mere scintilla of evidence" demonstrating a genuine issue of material fact, then the court may not credit the moving party's "version of events against the opponent, even if the quantity of the [moving party's] evidence far outweighs that of its opponent." Big Apple BMW, Inc. v. BMW of N. Am., Inc., 974 F.2d 1358, 1363 (3d Cir. 1992).

IV. Plaintiff Has Offered Sufficient Evidence for Her Failure-To-Warn Claim

I previously determined that Alabama law governs all of the plaintiff's claims. See Choice of Law Decision, May 20, 2015 (Doc. No. 41, 42).

a. Alabama Products Liability Law (AEMLD)

Product liability cases in Alabama are governed by the Alabama Extended Manufacturer's Liability Doctrine (AEMLD). The AEMLD is a hybrid liability doctrine which follows the tenets of Restatement 402A but allows defendants to pursue traditional tort defenses like assumption of the risk, lack of causation, or contributory negligence. See Casrell v. Altec Indus., Inc., 335 So.2d 128, 131-34 (Ala.1976); Atkins v. Am. Motors Corp., 335 So.2d 134, 137-43 (Ala.1976).123 The AEMLD may be applied to wrongful death cases. Casrell, 335 So.2d at 134; Atkins, 335 So.2d at 144. To establish liability under the AEMLD, a plaintiff must show:

Casrell, 335 So.2d at 132-33.

"Under the AEMLD, a manufacturer has the duty to design and manufacture a product that is reasonably safe for its intended purpose and use." Townsend v. Gen. Motors Corp., 642 So.2d 411, 415 (Ala.1994). This does not mean that the manufacturer is expected to insure against all harm or "to produce an accident-proof or injury-proof product." Id. "Proof of an accident and injury is not in itself sufficient to establish liability under the AEMLD; a defect in the product must be affirmatively shown." Id. (citing Casrell, 335 So.2d 128; Atkins, 335 So.2d 134). See also Sears, Roebuck & Co. v. Haven Hills Farm, Inc., 395 So.2d 991, 994-95 (Ala. 1981); Thompson v. Lee, 439 So.2d 113, 115 (Ala.1983); Brooks v. Colonial Chevrolet-Buick, Inc., 579 So.2d 1328, 1332 (Ala. 1991); Verchot v. Gen. Motors Corp., 812 So.2d 296, 301 (Ala.2001).

Under the AEMLD, "the important factor is whether [the product] is safe or dangerous when the product is used as it was intended to be used. However, danger may be obviated by adequate warning." Yarbrough v. Sears, Roebuck and Co., 628 So.2d 478, 481 (Ala.1993)(quoting Casrell, 335 So.2d at 133 (Ala.1976); Atkins, 335 So.2d 134 (quotation marks omitted)). When a drug manufacturer "has reason to anticipate that danger may result from a particular use, as where a drug is sold which is safe only in limited doses, [the manufacturer] may be required to give adequate warning of the danger... and a product sold without such warning is in a defective condition." Atkins, 335 So.2d at 147 (quoting Restatement 402A Comment as an appendix to its decision to adopt AEMLD); see id. at 143, n. 5 ("Although our holding modifies the Restatement's theory of strict liability, the Comment, in large measure, retains its utility; therefore, we attach the official Comment to s 402A as an appendix hereto."). "[A] seller is not required to warn with respect to products, or ingredients in them, which are only dangerous, or potentially so, when consumed in excessive quantity, or over a long period of time, when the danger, or potentiality of danger, is generally known and recognized." Id. at 148.

b. The Elements of a Failure-to-Warn Claim

To establish liability under the AEMLD, the plaintiff must show that her sister was injured by the defendants' product sold to her "in a defective condition unreasonably dangerous ... as the ultimate user or consumer." Casrell, 335 So.2d at 132-33. "Showing these elements, the plaintiff has proved a prima facie case although [the defendants have] exercised all possible care in the preparation and sale of [their] product, and [the decedent had] not bought the product from, or entered into any contractual relation with, the seller." Id. Under the AEMLD, "[a] manufacturer is under a duty to warn users of the dangerous propensities of a product only when such products are dangerous when put to their intended use." Gurley By and Through Gurley v. Am. Honda Motor Co., Inc., 505 So.2d 358, 361 (Ala.1987). Specifically, the plaintiff must show that the warning provided was defective or inadequate in order to establish this breach of duty. See Deere & Co. v. Grose, 586 So.2d 196, 198 (Ala.1991).

i. Adequacy of Warning

The defendants argue that the plaintiff has not offered sufficient evidence to show that a different, more adequate warning would have prevented the decedent's death. To be adequate, a warning "need not be the best possible warning" nor "warn of every potential danger." Gurley, 505 So.2d at 361. But, the manufacturer does have a duty to warn of potential hazards of foreseeable misuse if the dangers of misuse are ones of which the general public is unaware. See Yarbrough, 628 So.2d at 481; Gurley, 505 So.2d at 361 ("The objective of placing a duty to warn on the manufacturer of a product is to acquaint the user with a danger of which he is not aware, and there is no duty to warn when the danger is obvious." (citation omitted)).

The plaintiff offers evidence that the label was inadequate.124 The plaintiff offers several reasons why a jury could find the label was inadequate. First, the plaintiff points out that the Extra Strength Tylenol label, at the time of the decedent's death, recommended that consumers take two tablets every 4 to 6 hours. The TFM offered dosing instructions of two tablets every 6 hours. Under the defendants' dosing instructions, a consumer could potentially take more acetaminophen over a 24-hour period than was recommended by the TFM. The TFM is not a final rule; therefore, the defendants' dosing instruction would not be per se negligent. However, the defendants' decision to instruct consumers to take more acetaminophen than recommended by the TFM, without also warning of the potential risk of taking too much, could lead a reasonable jury to find that Extra Strength Tylenol's label was inadequate.125

Second, the plaintiff argues that the Extra Strength Tylenol label was deficient because it did not disclose the risk of severe liver damage or death from taking Extra Strength Tylenol at or just above the recommended dose.126 The plaintiff has offered evidence from her own experts that Tylenol may be unsafe at recommended dosage levels.127 She also has offered testimony from the defendant's own experts that they recommend their patients take below the recommended daily dose of Tylenol and emphasize to patients to take no more than the maximum daily dose, though Tylenol is advertised as "safe and effective."128

Lastly, the plaintiff argues that the label did not warn consumers about the risk of liver damage to those who were fasting or malnourished. To support this argument, the plaintiff offers scientific evidence, as far back as the 1990s, to suggest that fasting may put a consumer of Tylenol more at risk of hepatotoxicity.129 The 2009 Final Rule itself also indicated that those who are fasting or malnourished may have lower glutathione stores, putting them at possible risk of liver damage. See 2009 Final Rule, 74 Fed. Reg. 19385, 19397 (Apr. 29, 2009)("Malnourished individuals have been shown to have reduced glutathione levels (Refs. 37, 38, and 39). Therefore, it is possible that low glutathione levels may increase the risk for liver injury because there would be less available to bind to NAQPI. Low glutathione levels may [be] a surrogate for identifying a population at increased risk of liver injury with acetaminophen, but it was unclear how much of the deficiency is necessary."). Drawing all inferences in the light most favorable to the plaintiff, a reasonable jury could find that the defendants did not adequately warn of this risk as well.

Even if Denice did take more than the recommended dose, this error would not necessarily defeat the plaintiff's claim. "[P]roof that a product was used as intended is not an element of a prima facie case under the AEMLD." Sears, Roebuck and Co. v. Harris, 630 So.2d 1018, 1028 (Ala.1993). Instead, "a user's misuse of an allegedly defective product is an affirmative defense to liability under the AEMLD, which the defendant must plead and prove." Id. (citing Kelly v. M. Trigg Enters., Inc., 605 So.2d 1185, 1192 (Ala.1992)). "Where a warning has been provided, a question arises as to whether the warning was adequate, and adequacy of the warning is a question of fact for the jury." Brasher v. Sandoz Pharm. Corp., Nos. CV-98-TMP-2648-S, CV-98-TMP-2650-S, 2001 WL 36403362, at *13 (N.D.Ala. Sept. 21, 2001)(citing Toole v. McClintock, 999 F.2d 1430, 1433 (11th Cir.1993)).130

The plaintiff offers evidence that even if Denice took more than the recommended dose, this error was foreseeable. There is evidence that the defendants were well aware that consumers often unintentionally took too much Tylenol, leading to liver damage. See, e.g, Summary of Studies Examining Consumer Use of Acetaminophen at 2 (Pl. Ex. 34)(offering evidence from 2000s, including survey conducted by McNeil itself, that upwards of half of acetaminophen users misuse or take more than the recommended dose). This was a topic of concern in the medical community for several years before Denice died. In addition, the plaintiff argues that the information presented by the defendants about the risks of Tylenol — both on the label and in advertisements — would lead a reasonable consumer to be unaware that acute liver failure or death was a possible result of taking too much Tylenol over a short period of time.131 From what has been provided, a reasonable jury could find that the Tylenol label did not adequately warn consumers of the risk of taking Tylenol at or just above the recommended dose.132

The plaintiff also offers evidence that an adequate label would have prevented Denice's death. The plaintiff's cause of death is listed as acetaminophen-induced liver failure.133 She was treated in the hospital before she died for this condition. The plaintiff offers an expert report from Timothy Davern, II, M.D. who has studied ALF for many years. See Expert Report of T. Davern M.D. (Pl. Ex. 20). Dr. Davern points to parts of Denice's medical record which show she was not experiencing liver or renal problems prior to June 2010. See Expert Report of T. Davern M.D. (Pl. Ex. 20)(discussing how Ms. Hayes' liver was "normal in size" at the time of her gastric bypass surgery in August 2009 and how a colonoscopy in June 2010 produced benign results). After reviewing her medical history, he concluded that Denice's ALF "was caused by acetaminophen poisoning related to Tylenol ingestion for therapeutic purposes." Expert Report of T. Davern M.D. (Pl. Ex. 20).

In addition, Rebecca testified she would not have purchased Extra Strength Tylenol if she were aware of the risks of liver failure and death.134 The plaintiff offers evidence that Denice, who was not a risk taker, stopped taking Lorcet because she was concerned about its side effects.135 Drawing all inferences in the light most favorable to the plaintiff, a reasonable jury could find that the defendants breached their duty to warn of known risks of Extra Strength Tylenol, making the label inadequate. Furthermore, a jury could find that an adequate label would have prevented Denice's death.

ii. Proof for Causation: Read and Heeded

To prove causation, the plaintiff will also have to show at trial that Denice would have read and heeded an adequate warning and that an adequate warning would have prevented the decedent's death.136 See Yarbrough v. Sears, Roebuck and Co., 628 So.2d 478, 482 (Ala.1993)("A negligent-failure-to-adequately warn case cannot be submitted to a jury unless there is some evidence that the allegedly inadequate warning would have been read and heeded and would have kept the accident from occurring." (quoting Gurley v. Am. Honda Motor Co., 505 So.2d 358, 361 (Ala. 1987)); Deere & Co. v. Grose, 586 So.2d 196, 198 (Ala.1991)(same); Sears, Roebuck and Co. v. Harris, 630 So.2d 1018, 1030 (Ala.1993). See also Brasher v. Sandoz Pharm. Corp., Nos. CV-98-TMP-2648-S, CV-98-TMP-2650-S, 2001 WL 36403362, at *13 (N.D.Ala. Sept. 21, 2001)("Under Alabama law, to prevail in a warnings claim, the plaintiffs also must demonstrate a causal link between the allegedly inadequate warning and the injury. In cases such as these, that means that the plaintiffs must demonstrate that, had the defendant given an adequate warning, it would have been read and heeded by the prescribing physicians."); Garrison v. Novartis Pharms. Corp., 30 F.Supp.3d 1325, 1335-1337 (M.D.Ala. 2014); Barnhill v. Teva Pharms. USA, Inc., 819 F.Supp.2d 1254, 1262 (S.D.Ala.2011)(explaining that Alabama law does not presume that the plaintiff would have read and heeded an adequate warning).

The defendants argue that the plaintiff cannot offer evidence that Denice would have read and heeded the label's warnings. In response, the plaintiff has offered evidence that Denice followed warnings on labels. Her sisters testified in their depositions that Denice would read labels, not take medication which would harm her, and would follow doctor's instructions.137 There is evidence in her medical record that Denice was generally compliant with her doctor's instructions.138 Doctor's notes indicate Denice told her doctor she had taken her last dose of Tylenol the night before she was admitted to the hospital on August 29, 2010.139 There is also no evidence to show that Denice was intentionally trying to commit suicide or overdose to harm herself.140

The defendants argue that there is no evidence that anyone actually saw Denice take the recommended dose of Tylenol or that she actually read and heeded the warnings on the label.141 Denice was being cared for by several family members so no one person can verify the dosage she took.142 However, the plaintiff plans to offer testimony by the decedent's sisters and doctors that she was compliant with her doctor's medical directions.143 Denice's sister Rebecca lived with her for most of her life; she can speak to her sister's habits. This information is admissible under Federal Rule of Evidence 406. Whether this information about habit is credible is for a jury to decide.

Drawing all inferences in the light most favorable to the plaintiff, a reasonable jury could find that Denice would have read and heeded adequate warnings. Viewing the facts in the light most favorable to the plaintiff, a reasonable jury could find that the Extra Strength Tylenol label did not adequately warn of acute liver failure and possible death. It is for a jury to decide if the Tylenol label adequately advised users of known risks of Tylenol.

V. Genuine Disputes of Material Fact Exist

The parties agree on all material facts except two. These two disputes are genuine and require this case to proceed before a jury.

a. Regarding the Label

First, the parties dispute which label was on the bottle of Extra Strength Tylenol used by Denice before she died. The plaintiff contends the bottle was purchased in August 2009. The defendants claim the bottle was purchased in August 2010.144 This dispute is material because the label on Extra Strength Tylenol changed in early 2010. The new label added one word but that word is important. While the old label warned that an overdose of Extra Strength Tylenol could cause liver damage, the new label warned that an overdose could cause "severe" liver damage. If Denice relied on the warnings in the 2009 label, a reasonable jury could find that the lack of the warning of "severe" liver damage could have made that label inadequate.

While cleaning out Denice's belongings after her death, Denice's sisters discarded both the bottle of Extra Strength Tylenol and the bottle of Lorcet.145 According to Rebecca, she had purchased a medium-sized bottle of about 100 to 120 caplets of Extra Strength Tylenol in August 2009.146 That bottle was shared by the two sisters during the following year.147 Denice allegedly used that bottle in August 2010 until it ran out. Rebecca purchased another bottle of Extra Strength Tylenol for her sister on August 28, 2010.148 Denice may have taken doses from this bottle before going to bed. She then was taken to the hospital the next morning.

Which warning Denice viewed is a question for the jury to answer. A jury will need to make credibility determinations about the family members' rendering of Denice's final days to answer this question. For this reason, this dispute is genuine and must be decided by a jury.

b. Regarding the Cause of Death

The parties also dispute Denice's cause of death. The plaintiff, relying on Denice's medical records from doctors treating her before her death and on expert opinions, cite acetaminophen-induced acute liver failure as the cause of death.149 The defendants, relying on experts who reviewed Denice's medical records, claim that Denice died from multi-system organ failure likely caused by sepsis. What caused the decedent's death is a genuine dispute of material fact. This alone defeats summary judgment.

VI. The Plaintiff's Claims are Not Impliedly Preempted

The defendants also argue that the plaintiff's claims are preempted "under implied conflict principles."150

a. Implied Preemption

Preemption is a concept based on the Supremacy Clause of the U.S. Constitution that provides a conflicting state law will be trumped by its federal counterpart. See Mut. Pharm. Co. v. Bartlett, ___ U.S. ___, 133 S.Ct. 2466, 2472-73, 186 L.Ed.2d 607 (2013)(citing U.S. Const., Art. VI, cl. 2). Even if a federal statute does not expressly preempt a state law, the state law may be impliedly preempted where it is "impossible for a private party to comply with both state and federal requirements." Id. at 2473 (quoting English v. Gen. Elec. Co., 496 U.S. 72, 79, 110 S.Ct. 2270, 110 L.Ed.2d 65 (1990)(quotation marks omitted)).151 There is a general presumption against preemption. See, e.g., Deweese v. Nat'l R.R. Passenger Corp. (Amtrak), 590 F.3d 239, 246 (3d Cir.2009)(citing Cipollone v. Liggett Group, Inc., 505 U.S. 504, 516, 112 S.Ct. 2608, 120 L.Ed.2d 407 (1992)).

"Impossibility pre-emption is a demanding defense." Wyeth v. Levine, 555 U.S. 555, 573, 129 S.Ct. 1187, 173 L.Ed.2d 51 (2009). The Third Circuit has cautioned against "lightly infer[ring]" preemption where "state compensatory regimes have traditionally played an important role." Fellner v. Tri-Union Seafoods, L.L.C., 539 F.3d 237, 249 (3d Cir.2008). Whenever possible, preemption analysis should attempt to reconcile the state law and federal law with one another. See Deweese, 590 F.3d at 248. "[S]tate tort law and other similar state remedial actions are often deemed complementary to federal regulatory regimes" and fall "squarely within the realm of traditional state regulation." Fellner, 539 F.3d at 248-49.

b. The 2009 Final Rule and Wyeth v. Levine

The defendants argue that they were preempted from adding a "fasting" or "malnourishment" warning because the 2009 Final Rule did not include such a warning. McNeil argues that it "cannot unilaterally supplement or change its label with language inconsistent with the 2009 Final Rule." Defendants' Statement of Material Facts, Doc. No. 49-31 at ¶ 43. See also Jones Decl. at ¶¶ 58-59. This argument assumes that Ms. Hayes read the 2010 label — which included the 2009 Final Rule warnings — and not the 2009 pre-Final Rule label. Which label Ms. Hayes viewed is a question for the jury to answer.

Even assuming that Ms. Hayes viewed the post-Final Rule label warnings, the defendants' preemption argument fails. The Supreme Court rejected a similar argument in Wyeth v. Levine, 555 U.S. 555, 129 S.Ct. 1187, 173 L.Ed.2d 51 (2009). Wyeth argued that it could not comply with both state and federal law because the FDA's approval process required it to use the exact text on a proposed drug label. Id. at 567, 129 S.Ct. 1187. The Supreme Court explained that reliance on this approved text was not enough for Wyeth to escape liability for a deficient label. Id. "[I]t has remained a central premise of federal drug regulation that the manufacturer bears responsibility for the content of its label at all times." Id. at 570-71, 129 S.Ct. 1187. Brand-name drug manufacturers are "charged both with crafting an adequate label and with ensuring that its warnings remain adequate as long as the drug is on the market." Id. at 571, 129 S.Ct. 1187 (citing 21 CFR § 201.80(e), § 314.80(b); 73 Fed. Reg. 49605).

Specifically, the Supreme Court found that FDA regulations offer drug manufacturers a process by which to change their drug labels without using the formal administrative rulemaking process. Id. at 566, 129 S.Ct. 1187. "[T]his `changes being effected' (CBE) regulation provides that if a manufacturer is changing a label to `add or strengthen a contraindication, warning, precaution, or adverse reaction' or to `add or strengthen an instruction about dosage and administration that is intended to increase the safe use of the drug product,' it may make the labeling change upon filing its supplemental application with the FDA; it need not wait for FDA approval. §§ 314.70(c)(6)(iii) (A), (C)." Id. at 568, 129 S.Ct. 1187. "[A]bsent clear evidence that the FDA would not have approved a change to [the drug's] label, we will not conclude that it was impossible for Wyeth to comply with both federal and state requirements." Id. at 571, 129 S.Ct. 1187.

The Supreme Court opined in dicta that a failure-to-warn claim may be preempted if a drug manufacturer submitted a CBE change and the FDA rejected it. Id. at 571, 129 S.Ct. 1187. The defendants focus on this language, claiming that the FDA's exclusion of a "fasting" or "malnourishment" warning in the 2009 Final Rule indicates a rejection of such a warning and is analogous to the Court's hypothetical. I do not interpret the FDA's actions as the defendants do.

The 2009 Final Rule explained that the FDA only received three submissions regarding the fasting warning. See 74 Fed. Reg. 19397 (Apr. 29, 2009). The FDA could not "make a conclusion about the risk of liver injury due to acetaminophen in malnourished individuals." Id. The 2009 Rule did not require a fasting warning but stated the FDA would reconsider that position if new data became available. Id.152 To decline to add a warning because public comments did not offer sufficient scientific evidence is a vastly different proposition than the FDA rejecting a warning because it is scientifically inaccurate, flawed, or confusing.153 The FDA's decision is far from "clear evidence" in itself that the FDA would not approve a label change if McNeil offered evidence that it was warranted.154 See Wolfe v. McNeil, 773 F.Supp.2d 561, 568-69 (E.D.Pa.2011)(finding that FDA's decision not to adopt a citizen's request for a warning was not clear evidence of preemption because the FDA indicated stronger warnings were needed but disapproved of the proposed language), compared with, Robinson v. McNeil Consumer Healthcare, 615 F.3d 861, 873 (7th Cir.2010)(finding clear evidence that the FDA would not have approved a label change because the "FDA decided not to require such a warning because it would confuse rather than inform"); Dobbs v. Wyeth Pharms., 797 F.Supp.2d 1264, 1276-80 (W.D.Okla.2011)(finding implied preemption when the FDA had repeatedly rejected a proposed label alteration submitted by the drug manufacturer).155

c. No Clear Evidence That McNeil Was Prevented from Changing the Label

Furthermore McNeil's own actions show that it was not impossible for McNeil to change the Extra Strength label.156 As Wyeth made clear, the onus has always been on McNeil to ensure its label accurately reflects the risks of Extra Strength Tylenol.157 If McNeil had knowledge and notice that a "fasting" or "malnourishment" warning was needed to supplement or strengthen Extra Strength Tylenol's existing warnings, it could have made a CBE application.158 See Wyeth, 555 U.S. at 573, 129 S.Ct. 1187.

Nonetheless, the defendants argue that they could not have voluntarily changed the label on Extra Strength Tylenol because the CBE procedure is only available for drugs regulated by the NDA process. This argument is logical given that Extra Strength Tylenol was only governed by the monograph process, not the NDA process, at the time of the decedent's injury and death. The CBE procedure is affiliated with the NDA process, not the monograph process. See 21 C.F.R. § 314.70 ("Supplements and other changes to an approved application"); Wyeth, 555 U.S. at 578-79 (explaining the CBE process).

A close look at the history of Extra Strength Tylenol's label changes contradicts McNeil's argument. In 1994, McNeil petitioned the FDA to add an alcohol warning and a concomitant use warning (i.e., "Do not use with other products containing acetaminophen") to the Extra Strength Tylenol label; it used the CBE process in accordance with 21 C.F.R. § 314.70 for NDA 17-552.159 In its request for this label revision, McNeil indicated that the label change would be incorporated in the labeling "for all of [its] acetaminophen containing products for adults distributed under the OTC drug monographs."160

In 1998, McNeil withdrew the NDA for Extra Strength Tylenol (NDA 17-552). When it made this withdrawal, McNeil indicated that it would "continue to submit acetaminophen Adverse Drug Experience reports under NDA 19-872."161 NDA 19-872 is the application for Tylenol Extended Relief Caplets.162

In 2001, after petitioning the FDA, McNeil added a warning stating: "[t]aking more than the recommended dose (overdose) could cause serious health problems."163 This CBE petition was made under NDA 19-872 for Tylenol Extended Relief formula. McNeil indicated it would include the new warning on Tylenol Arthritis Pain Extended Relief "as well as other Tylenol acetaminophen products that are distributed under the OTC drug monographs."164 It reiterated this point again in its petition saying: "These same changes will be made to all other Tylenol products distributed under the OTC monographs."165

In 2002, at an advisory committee meeting with the FDA discussing acetaminophen labeling and safety, McNeil sought to further strengthen its Tylenol labels by replacing "serious health problems" language with specific language warning of overdose and liver damage.166 The FDA approved that change in 2003.167 In 2004, McNeil introduced the stronger warning regarding overdose/organ-specific liver damage on all Tylenol products.168 Despite the defendants' insistence that changing the Extra Strength Tylenol label would be impossible, they already have done it.169

Furthermore, Extra Strength Tylenol was and still is regulated by the Tentative Final Monograph (TFM) which is only a proposed rule. See 21 C.F.R. §§ 310, 343, 369 at 42604 (TFM)(Pl. Ex. 48); FDA letter to McNeil, 11/17/11 (Pl. Ex. 4). As explained by the FDA itself: "Under a TFM, manufacturers market products at their own risk and are able to make voluntary adjustments taking into context the information presented in the proposed TFM."170 See FDA letter to McNeil, 11/17/11 (Pl. Ex. 4).171 If the defendants became aware of information that fasting and malnourishment posed a serious health risk to Tylenol consumers, the onus was on them to seek a label revision.172 McNeil's own former Vice President and Chief Medical Officer Anthony Temple, M.D. admitted as much during his deposition.173

There is no clear evidence that the defendants could not comply with both state law tort principles and FDA regulations.174 The plaintiff's claims are not impliedly preempted.

VII. CONCLUSION

For the foregoing reasons, I will deny the defendants' motion for summary judgment on the plaintiff's failure-to-warn claim.

An appropriate Order follows.