| Pharmaceutical manufacturers are starting to | | | | make decisions on matters of medical science. |
| worry that the recent trend in court decisions | | | | The Supreme Court decided in favor of the |
| may leave them open to civil liability lawsuits. To | | | | manufacturer in Riegel v. Medtronic, a case |
| guard against this, companies need to consider | | | | involving a product that was still on the market. |
| how to mitigate risk in their choice of pipeline | | | | However, in Warner-Lambert v. Kent, the Court |
| projects and in the way in which they conduct | | | | did not block litigation on a product that had been |
| those projects. Tailoring therapies to smaller | | | | removed from the market due to numerous and |
| patient populations, prioritizing projects in which | | | | severe adverse events. This suggests that |
| the underlying science is better understood and | | | | products removed from the market due to |
| for which well-vetted biomarkers have been | | | | significant adverse events may be targets for |
| developed, and choosing compounds for which | | | | litigation in the future. |
| toxicity is predictable will help to mitigate risk. | | | | As state courts continue to challenge the |
| Designing studies to answer specific questions in | | | | authority of FDA scientists to decide, as Justice |
| an unambiguous manner, supporting continuing | | | | Breyer puts it, whether a drug is "on balance, |
| research into the development of better models | | | | going to save people or, on balance, going to hurt |
| of metabolism and toxicity, and working closely | | | | people," and instead assert the findings of a |
| with the FDA to explore compound safety and | | | | 12-person jury with no particular expertise, they |
| efficacy will argue convincingly against fraud. | | | | may well open the door to class-action lawsuits |
| This is particularly important because of recent | | | | involving FDA-approved products. |
| events taking place in federal courts. In March, the | | | | How to Mitigate Risk |
| U.S. Supreme Court's 4-4 vote allowed 27 | | | | Regardless of how the courts ultimately decide, |
| Michigan residents to bring suit against | | | | here are some steps that pharmaceutical |
| Warner-Lambert for damages incurred by its | | | | companies can take now to mitigate risk in the |
| diabetes drug Rezulin, which the company | | | | future:o Forget the concept of blockbuster drugs. |
| removed from the market in 2000 after reports | | | | Although only a decade ago, blockbusters were |
| of liver damage. [Warner-Lambert Co. v. Kent, | | | | the holy grail of the pharmaceutical industry, it is |
| 128 S.Ct. 1168 (2008) (per curium) in which Chief | | | | increasingly obvious that drugs should be tailored |
| Justice John Roberts recused himself because of | | | | to smaller, more specific patient populations to |
| his investment in Pfizer, Warner-Lambert's parent | | | | avoid the widespread, devastating adverse |
| company.] | | | | events that have been under public scrutiny |
| Although Michigan law generally prohibits product | | | | lately.o Choose indications for which more of the |
| liability lawsuits against manufacturers of | | | | biology of the mechanism of action and the |
| FDA-approved drugs, people can sue if they can | | | | repercussions of modulating it is really understood. |
| show that FDA approval was obtained | | | | If licensing a candidate from another company, |
| fraudulently. The Supreme Court was asked | | | | look beyond that company's discovery research |
| whether the FDA's approval of the drug in 1997 | | | | efforts to verify and supplement their findings. |
| pre-empted Michigan law and blocked the plaintiffs | | | | For in-house discovery efforts, resist the urge to |
| from bringing suit against the manufacturer. Their | | | | move candidates forward until detailed knowledge |
| tie vote left standing an earlier opinion by the U.S. | | | | of the pertinent biology has been documented |
| Court of Appeals for the 2nd Circuit that the | | | | and validated by the findings of other |
| Supreme Court's 2001 decision in Buckman v. | | | | researchers.o Choose compounds for which |
| Plaintiffs' Legal Committee, which concerned | | | | metabolism and toxicity can be predicted from |
| medical device law and is unrelated to Michigan's | | | | structure. Consider metabolic stability, the |
| immunity statute, did not apply in this case, | | | | possibility of active metabolites, and whether |
| allowing the suit to go forward. | | | | these metabolites are likely to cause |
| Riegel Could Set the Stage | | | | development-limiting toxicity or side-effects.o |
| A recent ruling in Riegel v. Medtronic asserted that | | | | Choose disease states/indications for which |
| the FDA's pre-market approval of a balloon | | | | well-vetted biomarkers have been developed, or |
| catheter pre-empted states from hearing cases | | | | plan to co-develop biomarkers with your therapy. |
| alleging fraud on the FDA. However, charges of | | | | The trend away from "one-size-fits-all" |
| manufacturing defects were not necessarily | | | | blockbuster drugs to more individualized therapies |
| pre-empted. In other words, Medtronic's catheter | | | | requires patient diagnosis and disease state |
| had passed the rigorous testing required by the | | | | monitoring. As a result, biomarker test kits will |
| FDA, and the company had complied with all | | | | become part of the pharmaceutical product.o |
| regulatory requirements for approval. A state | | | | Support research into the development of more |
| court hearing liability claims would not be allowed | | | | predictive in vitro and in silico models of toxicity. If |
| to second-guess what the FDA had already | | | | this is not something your company can do in |
| approved. However, if there was evidence that | | | | house, consider joining consortia or supporting |
| manufacturing specifications were not met in the | | | | academic research in this direction. Make it clear |
| particular medical device in question, restitution | | | | to the FDA and to the public that you |
| could probably be sought. | | | | acknowledge the lack of adequately predictive |
| In October of this year, the Supreme Court will | | | | models of toxicity, and that you are actively |
| hear the case of Levine v. Wyeth, which will not | | | | involved in remedying the situation.o Ensure the |
| be complicated by state laws such as Michigan's. | | | | careful planning of preclinical and clinical studies. |
| In this case, Vermont state law failure-to-warn | | | | Each should be designed to answer a specific |
| claims challenge the FDA's prior approval of a drug | | | | question in such a way that results are not |
| label. | | | | ambiguous. Complex studies designed to answer |
| Ethics and FDA Funding under Scrutiny | | | | multiple questions are not recommended. All too |
| These important cases come at a time when the | | | | often the complexity obscures and confuses the |
| ethics of drug makers and the capabilities of the | | | | results.o Look for (and suspect) toxicological |
| under-funded FDA are being publicly questioned. | | | | responses. If there is any question, look further. |
| The argument of pre-emption assumes that the | | | | Compounds "killed" early in the development |
| FDA, as a federal agency, is solely responsible for | | | | process are far less expensive than those that fail |
| evaluating a potential product's efficacy and | | | | in Phase III or are removed from the market due |
| safety according to the regulations it has devised, | | | | to patient injury.o Be diligent about reporting all |
| and that it can and will deal with issues of fraud | | | | study results to the FDA; be clear that you are |
| should they arise. Allowing plaintiffs to argue | | | | interested in developing safe and effective |
| fraud-on-the-FDA claims, some argue, would only | | | | medicines for patients in need and that you have |
| hamper the agency's ability to do its job. More | | | | a strong interest in moving the science forward |
| serious considerations have been voiced by | | | | both in the disease area of your project and in |
| Justice Stephen Breyer concerning the | | | | understanding any underlying toxicity issues. |
| appropriateness of allowing the lay-person to | | | | |