12 Post-A t ppr A oval Requirements Following approval of a new product, the manufact f ur t er and the approved product are subj u ect to continuing regulation by the FDA, including, among other things, monitoring and record-keeping requirements, requirements to report adverse experiences, and comply with promotion and advertising requirements, which include restrictions on promoting drugs r for unappr a oved uses or patient populations (known as “off-label use”) and limitations on industry- r sponsored scientific f and educ d ational activities. Although physicians may prescribe legally availabl a e drugs r for off-l f abel uses, manufact f ur t ers may not market or promote such uses. Prescription drug r promotional materials must be subm u itted to the FDA in conjunction with their first use. Further, if there are any modifications to the drug r or biologic, including changes in indications, labe a ling or manufac f turing processes or facilities, the applicant may be required to subm u it and obtain FDA approval of a new NDA/BLA or NDA/BLA suppl u ement, which may require the development of additional data or preclinical studi t es and clinical trials. The FDA may also place other conditions on approvals including the requirement for a Risk Evaluation and Mitigation Strategy, or REMS, to assure the safe use of the product. A REMS could include medication guides, physician communication plans or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products. Product approvals may be withdrawn for non-compliance with regulatory r standards or if problems occur following initial marketing. The FDA may withdraw appr a oval if compliance with regulatory r requirements and standards is not maintained or if problems occur afte f r the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufact f ur t ing processes, or failure to comply with regulatory r requirements, may result in revisions to the approved labe a ling to add new safety information; imposition of post- market studi t es or clinical studi t es to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things: • the restrictions on the marketing or manufac f turing of the product, complete withdrawal of the product from the market or product recalls; • fines, warning letters or holds on post-approval clinical studi t es; • refusal of the FDA to approve pending applications or suppl u ements to approved applications; • applications, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; or • inju n nctions or the imposition of civil or criminal penalties. The FDA strictly regulates marketing, labe a ling, advertising, and promotion of products that are placed on the market. Drugs r and biologics may be promoted only for the approved indications and in accordance with the provisions of the approved labe a l. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-l f abel uses, and a company that is found to have improperly promoted off-l f abel uses may be subj u ect to significant liabi a lity. Othe t r U.S. Regu e latory Laws Manufact f ur t ing, sales, promotion and other activities following product approval are also subj u ect to regulation by numerous regulatory r authorities in the United States in addition to the FDA, including the Centers for Medicare & Medicaid Services, or CMS, other divisions of the Department of Health and Human Services, or HHS, the Department of Justice, the Drug r Enforcement Administration, the Consumer Produc d t Safety Commission, the Federal Trade Commission, the Occupa u tional Safety & Health Administration, the Environmental Protection Agency and state and local governments. For example, in the United States, our business operations, including any sales, marketing and scientific f and educ d ational programs, also must comply with state and federal fraud and abuse laws, including the federal Anti-Kickback Statue t and false claims laws; federal data privacy and security laws; and federal transparency laws related to payments and/or other transfer f s of value made to physicians and other healthcare profes f sionals and teaching hospitals. The federal Anti-Kickback Statut t e makes it illegal for any person, including a prescription drug r manufac f turer (or a party acting on its behalf), f to knowingly and willfully solicit, receive, offe f r or pay any remuneration that is intended to induce or reward referrals, including the purchase, recommendation, order or prescription of a particular drug, r for which payment may be made under a federal healthcare program, such as Medicare or Medicaid. Moreover, the ACA provides that the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statut t e constitutes a false or fraudulent claim for purpos r es of the False Claims Act. Federal false claims laws, including the False Claims Act, prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, false or fraudulent claims for payment of federal funds, and knowingly making, or causing to be made, a false record or statement material to a false or fraudulent claim to avoid, decrease or conceal an obligation to pay money to the federal government.