Kyle Sampson, Hunton & Williams LLP 09.05.13
In April, the Food and Drug Administration (FDA) determined that OxyContin (oxycodone hydrochloride) extended-release tablets approved under New Drug Application (NDA) 20-533 (Original OxyContin) were withdrawn from sale for safety reasons. FDA concluded that Original OxyContin was withdrawn from sale because it was not as safe as a reformulated version of OxyContin approved under NDA 22-272 (Reformulated OxyContin) that was “developed with physicochemical properties that are intended to make the tablet more difficult to manipulate for purposes of abuse or misuse.” As a result, FDA removed Original OxyContin from the Agency’s publication entitled Approved Drug Products with Therapeutic Equivalence Evaluations (the “Orange Book”), and stated that it would not approve any abbreviated new drug applications (“ANDAs”) that refer to Original OxyContin.1
Less than a month later, in May, FDA determined that another opioid analgesic, Opana® ER (oxymorphone hydrochloride) extended-release tablets approved under NDA 02-1610 (Original Opana), was not withdrawn from sale for safety reasons — notwithstanding the availability of a reformulated version of Opana approved under NDA 20-1655 (Reformulated Opana). FDA concluded that Reformulated Opana — although designed to be safer than Original Opana — was not, in fact, any safer. As a result, FDA stated that the agency would continue to list Original Opana in the Orange Book, would approve ANDAs that reference Original Opana, and would not suspend and withdraw its approval of generic versions of Original Opana already on the market.2
FDA’s determination that Original OxyContin was withdrawn from sale for safety reasons is diametrically opposed to its determination that Original Opana was not withdrawn from sale for safety reasons. Both OxyContin and Opana are opioid analgesics that, in their original formulations, have been subject to significant abuse and misuse resulting in what FDA has called “a major public health crisis of addiction, misuse, abuse, overdose and death.”3 Both are subject to the same Risk Evaluation and Mitigation Strategy (REMS) implementing safety measures that are intended “to reduce risks and improve safe use of [extended-release and long-acting] opioids while continuing to provide access to these medications for patients in pain.”4 Both OxyContin and Opana are manufactured by companies, Purdue Pharma LP (Purdue) and Endo Pharmaceuticals Inc. (Endo), that invested millions of dollars to develop reformulated versions of the drug products designed to deter abuse, and both reformulated versions were approved by FDA. And after FDA approved both reformulated versions, both original versions of the drug products were withdrawn from sale. Despite these numerous similarities, FDA treated OxyContin and Opana differently when it determined that Original OxyContin was withdrawn from sale for reasons of safety, but that Original Opana was not. Why? How does FDA determine whether a drug was withdrawn from sale for safety reasons?
Background
FDA publishes a list of all approved drugs in the Orange Book. The Orange Book lists the official and proprietary name of each approved drug product, the date the drug was approved, and patents protecting the drug from competition. The Hatch-Waxman amendments to the Federal Food, Drug, and Cosmetic Act (FD&C Act) provide that generic drug manufacturers can submit an ANDA for FDA approval of a generic version of any approved drug that is listed in the Orange Book.5
If the manufacturer of an approved drug listed in the Orange Book withdraws the drug from sale, then FDA usually must determine the reason for the withdrawal.6 If FDA “determines that a drug has been withdrawn from sale for safety or effectiveness reasons,” then the drug “shall be immediately removed” from the Orange Book.7 If an approved drug is removed from the Orange Book, then the agency will refuse to approve any ANDA that references the no-longer-listed drug. In addition, the agency will suspend and withdraw its approval of any approved ANDA that refers to the drug that has been removed from the Orange Book.8
Legal Standard
FDA’s decisions regarding OxyContin and Opana reveal that, when evaluating whether a drug product was withdrawn from sale for safety reasons, the agency will consider the drug’s abuse potential, as well as the availability of an alternative safer product. In addition, the OxyContin and Opana decisions reveal that FDA will make such determinations on a case-by-case basis.
Abuse Potential
In evaluating whether a drug product was withdrawn from sale for safety reasons, FDA considers the abuse potential of the drug. Usually, the evaluation of a drug’s safety is linked to the conditions of use set forth in its approved labeling. FDA’s approval of an NDA, for example, is contingent on the agency finding that the proposed “drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof.”9 Similarly, FDA may withdraw its approval of a drug for safety reasons if evidence shows that the drug either is “unsafe” or “not shown to be safe” “for use under the conditions of use upon the basis of which the application was approved.”10 Evaluating a drug’s safety under the conditions of use set forth in its labeling makes sense; after all, all drugs can be unsafe if they are not used as directed in their labeling.
In assessing the safety of Original OxyContin, however, FDA did not evaluate whether the drug was safe for use under the conditions set forth in its labeling. To the contrary, FDA evaluated whether Original OxyContin was safe when not used as directed. Unsurprisingly, the agency concluded that the drug was not safe when not used as directed. FDA emphasized, “Original OxyContin was often abused by manipulating the product to defeat its extended-release mechanism, causing the oxycodone to be released more rapidly. Original OxyContin also was manipulated for therapeutic purposes, for example, by crushing the product to sprinkle it onto food or to administer it through a gastric tube.”11 The agency noted that Original OxyContin’s labeling warned against “disruption of the tablet and controlled-release mechanism for abuse or misuse,”12 but only as an aside, to illustrate the consequences of abuse and misuse of the drug.
In the notice of its OxyContin determination, FDA argues that it is not bound to evaluate a drug product’s safety under the conditions of use set forth in the drug’s labeling. According to FDA, it has long considered the abuse potential of a drug in numerous regulatory contexts. Where appropriate, FDA may take into account abuse potential as part of the safety profile of a drug when weighing its benefits and risks. In this case, FDA has considered the abuse potential as part of the Agency’s determination of whether the original formulation of OxyContin was withdrawn from sale for reasons of safety or effectiveness. This approach is particularly appropriate here in light of the extensive and well-documented history of OxyContin abuse.13
Interestingly, the agency cites no authority for this proposition,14 nor does it explain how it can escape the FD&C Act’s mandate that it evaluate a drug product’s safety in the context of the drug’s approved uses.
Comparative Safety
In addition to considering the abuse potential of a drug, FDA also considers whether an alternative product that is safer is available. This, too, is not FDA’s standard practice. In determining whether an NDA should be approved, the FD&C Act provides that FDA’s evaluation of a drug product’s safety is to be based on “full reports of investigations which have been made to show whether or not such drug is safe for use,” and that such investigations must “include adequate tests by all methods reasonably applicable to show whether or not such drug is safe for use.”15 Likewise, in determining whether approval of an NDA should be withdrawn, FDA’s safety evaluation is to be based on “clinical or other experience, tests, or other scientific data [that] show that such drug is unsafe for use.”16 The statute does not state that FDA is to evaluate the safety of a drug product in comparison to other alternative drug products.
In its evaluation of safety of Original OxyContin and Original Opana, however, FDA compared the safety of the original formulations of those drugs to their reformulated versions. FDA observed, “when compared to original OxyContin, reformulated OxyContin has an increased ability to resist crushing, breaking, and dissolution using a variety of tools and solvents.”17 Similarly, FDA observed, “insufflation of finely crushed reformulated OxyContin was associated with lower ‘liking’ compared to finely crushed original OxyContin in recreational opioid users with a history of intranasal drug abuse.”18 As a result, FDA concluded that Original OxyContin “poses an increased potential for abuse . . . when compared to reformulated OxyContin.”19 Accordingly, FDA determined that Original OxyContin was withdrawn from sale for safety reasons.
Similarly, with regard to Original Opana, FDA compared the relative safety of Original Opana and Reformulated Opana and concluded that the “alleged safety advantages” of Reform-ulated Opana were illusory. FDA observed that, [w]hile there is an increased ability of [Reformulated Opana] to resist crushing relative to [Original Opana], data from in vitro and pharmacokinetic studies show that [Reformulated Opana’s] extended-release features can be compromised, causing the product to “dose dump,” when subjected to other forms of manipulation such as cutting, grinding, or chewing, followed by swallowing.20
FDA further observed that Reformulated Opana “can more easily be prepared for injection” as compared to Original Opana.21 Because FDA concluded that Reformulated Opana is no safer than Original Opana, the agency determined that Original Opana was not withdrawn from sale for safety reasons.
“In its denial of Endo’s Citizen Petition, FDA asserts that, in evaluating the safety of a drug product, the agency has the authority to recognize “that a drug’s benefit/risk profile can change due to the availability of alternative products.”22 As support for this assertion, FDA cited to its then month-old OxyContin Determination: “Recently, the agency considered the increased potential for abuse of original OxyContin . . . relative to reformulated OxyContin . . . in determining that original OxyContin was withdrawn for safety or effectiveness reasons.”23
Case-by-Case
FDA’s decisions regarding OxyContin and Opana reveal that the agency will determine whether a drug has been withdrawn from sale for safety reasons on a case-by-case basis. According to FDA, the agency’s “decisions take into account the totality of the evidence for the particular drug at issue, and must be made on a case-by-case basis.”24 FDA reviewed “in vitro, pharmacokinetic, clinical abuse potential, and postmarketing study data” related to Original OxyContin and Reformulated OxyContin, and determined that there were sufficient data to conclude that “Original OxyContin . . . poses an increased potential for abuse by certain routes of administration . . . when compared to reformulated OxyContin.”25 By contrast, FDA reviewed “preliminary postmarketing data and analysis concerning abuse” of Original Opana, generic versions of Original Opana, and Reformulated Opana, and determined that “there currently are not sufficient data to conclude that [Original Opana] poses an increased potential for abuse compared to [Reformulated Opana].”26
Where it can, FDA generally seeks to promote generic competition. FDA’s Opana determination is pro-competitive, in that it allows new generic versions of Original Opana to be approved and enter the market (and existing generic versions to remain on the market). A contrary determination would have cleared the market of all but the reformulated version of Opana. In contrast, FDA’s OxyContin determination effectively blocks entry of a generic version of OxyContin onto the market, since elements of the Reformulated OxyContin dosage form and labeling enjoy patent protection for years to come.27
FDA frequently touts its public health mission. To that end, FDA’s OxyContin determination squarely addressed the “large and growing problem” of abuse and misuse of opioid analgesics, including OxyContin, which the agency has called “a public health epidemic.” Indeed, the actions taken by FDA may incentivize drug manufacturers to develop “opioid analgesics that can deter abuse and misuse,” which the agency considers “to be a public health priority.”28 With regard to the public health, however, FDA’s Opana determination did nothing to address the abuse of prescription opioid analgesics, including Opana, that Endo acknowledges “is at the center of a major public health crisis of addiction, misuse, abuse, overdose and death.”29 Indeed, FDA’s Opana determination could cause drug manufacturers to think twice before investing in the development of abuse-deterrent formulations.
References
Kyle Sampson is a partner in the Washington, D.C. office of Hunton & Williams LLP (www.hunton.com) and a member of the Firm’s Food and Drug Practice. He can be reached at ksampson@hunton.com.
Less than a month later, in May, FDA determined that another opioid analgesic, Opana® ER (oxymorphone hydrochloride) extended-release tablets approved under NDA 02-1610 (Original Opana), was not withdrawn from sale for safety reasons — notwithstanding the availability of a reformulated version of Opana approved under NDA 20-1655 (Reformulated Opana). FDA concluded that Reformulated Opana — although designed to be safer than Original Opana — was not, in fact, any safer. As a result, FDA stated that the agency would continue to list Original Opana in the Orange Book, would approve ANDAs that reference Original Opana, and would not suspend and withdraw its approval of generic versions of Original Opana already on the market.2
FDA’s determination that Original OxyContin was withdrawn from sale for safety reasons is diametrically opposed to its determination that Original Opana was not withdrawn from sale for safety reasons. Both OxyContin and Opana are opioid analgesics that, in their original formulations, have been subject to significant abuse and misuse resulting in what FDA has called “a major public health crisis of addiction, misuse, abuse, overdose and death.”3 Both are subject to the same Risk Evaluation and Mitigation Strategy (REMS) implementing safety measures that are intended “to reduce risks and improve safe use of [extended-release and long-acting] opioids while continuing to provide access to these medications for patients in pain.”4 Both OxyContin and Opana are manufactured by companies, Purdue Pharma LP (Purdue) and Endo Pharmaceuticals Inc. (Endo), that invested millions of dollars to develop reformulated versions of the drug products designed to deter abuse, and both reformulated versions were approved by FDA. And after FDA approved both reformulated versions, both original versions of the drug products were withdrawn from sale. Despite these numerous similarities, FDA treated OxyContin and Opana differently when it determined that Original OxyContin was withdrawn from sale for reasons of safety, but that Original Opana was not. Why? How does FDA determine whether a drug was withdrawn from sale for safety reasons?
Background
FDA publishes a list of all approved drugs in the Orange Book. The Orange Book lists the official and proprietary name of each approved drug product, the date the drug was approved, and patents protecting the drug from competition. The Hatch-Waxman amendments to the Federal Food, Drug, and Cosmetic Act (FD&C Act) provide that generic drug manufacturers can submit an ANDA for FDA approval of a generic version of any approved drug that is listed in the Orange Book.5
If the manufacturer of an approved drug listed in the Orange Book withdraws the drug from sale, then FDA usually must determine the reason for the withdrawal.6 If FDA “determines that a drug has been withdrawn from sale for safety or effectiveness reasons,” then the drug “shall be immediately removed” from the Orange Book.7 If an approved drug is removed from the Orange Book, then the agency will refuse to approve any ANDA that references the no-longer-listed drug. In addition, the agency will suspend and withdraw its approval of any approved ANDA that refers to the drug that has been removed from the Orange Book.8
Legal Standard
FDA’s decisions regarding OxyContin and Opana reveal that, when evaluating whether a drug product was withdrawn from sale for safety reasons, the agency will consider the drug’s abuse potential, as well as the availability of an alternative safer product. In addition, the OxyContin and Opana decisions reveal that FDA will make such determinations on a case-by-case basis.
Abuse Potential
In evaluating whether a drug product was withdrawn from sale for safety reasons, FDA considers the abuse potential of the drug. Usually, the evaluation of a drug’s safety is linked to the conditions of use set forth in its approved labeling. FDA’s approval of an NDA, for example, is contingent on the agency finding that the proposed “drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof.”9 Similarly, FDA may withdraw its approval of a drug for safety reasons if evidence shows that the drug either is “unsafe” or “not shown to be safe” “for use under the conditions of use upon the basis of which the application was approved.”10 Evaluating a drug’s safety under the conditions of use set forth in its labeling makes sense; after all, all drugs can be unsafe if they are not used as directed in their labeling.
In assessing the safety of Original OxyContin, however, FDA did not evaluate whether the drug was safe for use under the conditions set forth in its labeling. To the contrary, FDA evaluated whether Original OxyContin was safe when not used as directed. Unsurprisingly, the agency concluded that the drug was not safe when not used as directed. FDA emphasized, “Original OxyContin was often abused by manipulating the product to defeat its extended-release mechanism, causing the oxycodone to be released more rapidly. Original OxyContin also was manipulated for therapeutic purposes, for example, by crushing the product to sprinkle it onto food or to administer it through a gastric tube.”11 The agency noted that Original OxyContin’s labeling warned against “disruption of the tablet and controlled-release mechanism for abuse or misuse,”12 but only as an aside, to illustrate the consequences of abuse and misuse of the drug.
In the notice of its OxyContin determination, FDA argues that it is not bound to evaluate a drug product’s safety under the conditions of use set forth in the drug’s labeling. According to FDA, it has long considered the abuse potential of a drug in numerous regulatory contexts. Where appropriate, FDA may take into account abuse potential as part of the safety profile of a drug when weighing its benefits and risks. In this case, FDA has considered the abuse potential as part of the Agency’s determination of whether the original formulation of OxyContin was withdrawn from sale for reasons of safety or effectiveness. This approach is particularly appropriate here in light of the extensive and well-documented history of OxyContin abuse.13
Interestingly, the agency cites no authority for this proposition,14 nor does it explain how it can escape the FD&C Act’s mandate that it evaluate a drug product’s safety in the context of the drug’s approved uses.
Comparative Safety
In addition to considering the abuse potential of a drug, FDA also considers whether an alternative product that is safer is available. This, too, is not FDA’s standard practice. In determining whether an NDA should be approved, the FD&C Act provides that FDA’s evaluation of a drug product’s safety is to be based on “full reports of investigations which have been made to show whether or not such drug is safe for use,” and that such investigations must “include adequate tests by all methods reasonably applicable to show whether or not such drug is safe for use.”15 Likewise, in determining whether approval of an NDA should be withdrawn, FDA’s safety evaluation is to be based on “clinical or other experience, tests, or other scientific data [that] show that such drug is unsafe for use.”16 The statute does not state that FDA is to evaluate the safety of a drug product in comparison to other alternative drug products.
In its evaluation of safety of Original OxyContin and Original Opana, however, FDA compared the safety of the original formulations of those drugs to their reformulated versions. FDA observed, “when compared to original OxyContin, reformulated OxyContin has an increased ability to resist crushing, breaking, and dissolution using a variety of tools and solvents.”17 Similarly, FDA observed, “insufflation of finely crushed reformulated OxyContin was associated with lower ‘liking’ compared to finely crushed original OxyContin in recreational opioid users with a history of intranasal drug abuse.”18 As a result, FDA concluded that Original OxyContin “poses an increased potential for abuse . . . when compared to reformulated OxyContin.”19 Accordingly, FDA determined that Original OxyContin was withdrawn from sale for safety reasons.
Similarly, with regard to Original Opana, FDA compared the relative safety of Original Opana and Reformulated Opana and concluded that the “alleged safety advantages” of Reform-ulated Opana were illusory. FDA observed that, [w]hile there is an increased ability of [Reformulated Opana] to resist crushing relative to [Original Opana], data from in vitro and pharmacokinetic studies show that [Reformulated Opana’s] extended-release features can be compromised, causing the product to “dose dump,” when subjected to other forms of manipulation such as cutting, grinding, or chewing, followed by swallowing.20
FDA further observed that Reformulated Opana “can more easily be prepared for injection” as compared to Original Opana.21 Because FDA concluded that Reformulated Opana is no safer than Original Opana, the agency determined that Original Opana was not withdrawn from sale for safety reasons.
“In its denial of Endo’s Citizen Petition, FDA asserts that, in evaluating the safety of a drug product, the agency has the authority to recognize “that a drug’s benefit/risk profile can change due to the availability of alternative products.”22 As support for this assertion, FDA cited to its then month-old OxyContin Determination: “Recently, the agency considered the increased potential for abuse of original OxyContin . . . relative to reformulated OxyContin . . . in determining that original OxyContin was withdrawn for safety or effectiveness reasons.”23
Case-by-Case
FDA’s decisions regarding OxyContin and Opana reveal that the agency will determine whether a drug has been withdrawn from sale for safety reasons on a case-by-case basis. According to FDA, the agency’s “decisions take into account the totality of the evidence for the particular drug at issue, and must be made on a case-by-case basis.”24 FDA reviewed “in vitro, pharmacokinetic, clinical abuse potential, and postmarketing study data” related to Original OxyContin and Reformulated OxyContin, and determined that there were sufficient data to conclude that “Original OxyContin . . . poses an increased potential for abuse by certain routes of administration . . . when compared to reformulated OxyContin.”25 By contrast, FDA reviewed “preliminary postmarketing data and analysis concerning abuse” of Original Opana, generic versions of Original Opana, and Reformulated Opana, and determined that “there currently are not sufficient data to conclude that [Original Opana] poses an increased potential for abuse compared to [Reformulated Opana].”26
Where it can, FDA generally seeks to promote generic competition. FDA’s Opana determination is pro-competitive, in that it allows new generic versions of Original Opana to be approved and enter the market (and existing generic versions to remain on the market). A contrary determination would have cleared the market of all but the reformulated version of Opana. In contrast, FDA’s OxyContin determination effectively blocks entry of a generic version of OxyContin onto the market, since elements of the Reformulated OxyContin dosage form and labeling enjoy patent protection for years to come.27
FDA frequently touts its public health mission. To that end, FDA’s OxyContin determination squarely addressed the “large and growing problem” of abuse and misuse of opioid analgesics, including OxyContin, which the agency has called “a public health epidemic.” Indeed, the actions taken by FDA may incentivize drug manufacturers to develop “opioid analgesics that can deter abuse and misuse,” which the agency considers “to be a public health priority.”28 With regard to the public health, however, FDA’s Opana determination did nothing to address the abuse of prescription opioid analgesics, including Opana, that Endo acknowledges “is at the center of a major public health crisis of addiction, misuse, abuse, overdose and death.”29 Indeed, FDA’s Opana determination could cause drug manufacturers to think twice before investing in the development of abuse-deterrent formulations.
References
- See FDA, Notice, Determination that the OXYCONTIN (Oxycodone Hydrochloride) Drug Products Covered by New Drug Application 20-553 Were Withdrawn From Sale for Reasons of Safety or Effectiveness, 78 Fed. Reg. 23,273, 23,273-75 (Apr. 18, 2013) [hereinafter “OxyContin Notice”]. FDA also approved a supplemental NDA for Reformulated OxyContin that made changes to the product labeling that describe certain abuse-deterrent properties of the reformulated product. See id. at 23,273.
- See Letter from Janet Woodcock, M.D., Director, Center for Drug Evaluation and Research, FDA, to Robert Barto, Vice President, Regulatory Affairs, Endo Pharmaceuticals Inc., re: Petition Denial, Docket No. FDA-2012-P-0895 (May 10, 2013), at 1, 5-9 [hereinafter “Opana Petition Denial”].
- FDA, Risk Evaluation and Mitigation Strategy (REMS) for Extended-Release and Long-Acting Opioids (Apr. 25, 2013), available at http://www.fda.gov/Drugs/DrugSafety/ InformationbyDrugClass/ucm163647.htm.
- Id.
- See generally FD&C Act § 505(j).
- See 21 C.F.R. § 314.161(a) (providing that FDA is required to make a determination regarding the reason an approved drug was withdrawn from sale (1) before approving an ANDA that references the drug, (2) if an already approved ANDA references the drug, and (3) when a person submits a Citizen Petition asking FDA to make a determination).
- Id. § 505(j)(7)(C); see also 21 C.F.R. § 314.162(a).
- See FD&C Act § 505(j)(6); see also 21 C.F.R. §§ 314.153(b) & 314.161(a)(1).
- FD&C Act § 505(d)(1).
- Id. § 505(e)(1) & (2).
- OxyContin Notice, 78 Fed. Reg. at 23,274.
- Id.
- Id.
- See also Opana Petition Denial at 4 (repeating contention that “FDA may take abuse potential into account when weighing a drug’s benefits and risks,” but citing no authority).
- FD&C Act §§ 505(b)(1) & 505(d)(1)-(2); see also 21 C.F.R. § 314.125(b)(2)-(4).
- FD&C Act § 505(e) (1)-(2); see also 21 C.F.R. § 314.150(a)(2)(i)-(ii).
- OxyContin Notice, 78 Fed. Reg. at 23,274 (emphasis added).
- Id. (emphasis added).
- Id. (emphasis added).
- Opana Petition Denial at 5; see also id. at 5 n.14 (stating that “[i]nclusion of language regarding reduced crushability in the labeling could be misleading and result in health care practitioners or patients thinking that [Reformulated Opana] is safer than [Original Opana]”).
- Id. at 6.
- Id. at 4.
- Id. In a footnote, FDA also cited to its Determination That Halflytely and Bisacodyl Tablets Bowel Prep Kit (Containing Two Bisacodyl Delayed Release Tablets, 5 Milligrams) Was Withdrawn From Sale for Reasons of Safety or Effectiveness, 76 Fed. Reg. 51037 (Aug. 17, 2011) (“FDA determined that the 10mg presentation of Halflytely and Bisacodyl Tablets Bowel Prep Kit was withdrawn for safety reasons because the 5mg presentation had ‘comparable effectiveness to the 10mg product and . . . a safety advantage over the 10mg product.’”).
- Id. at 7.
- OxyContin Notice at 23,274.
- Opana Petition Denial at 3, 8.
- See Bloomberg BNA, “FDA Announces Abuse-Deterrent Labeling for Reformulated OxyContin,” Pharmaceutical Law & Industry Report (Apr. 19, 2013) (noting that patents for Reformulated OxyContin “have expiration dates ranging from April 16, 2013, to March 30, 2025”).
- OxyContin Notice, 78 Fed. Reg. at 23,274.
- Endo Pharmaceuticals Inc., Citizen Petition, Docket No. FDA-2012-P-0895 (Aug. 13, 2012) (internal quotation omitted).
Kyle Sampson is a partner in the Washington, D.C. office of Hunton & Williams LLP (www.hunton.com) and a member of the Firm’s Food and Drug Practice. He can be reached at ksampson@hunton.com.