By Kurt R. Karst –
Last week, Representative William Keating (D-MA) announced the introduction of new legislation – the Stop Tampering of Prescription Pills Act of 2012, or STOPP Act (H.R. 6160) – that is intended to direct companies “to invest in research and production to formulate tamper resistant drugs in order to compete with drugs of a similar nature that already employ tamper resistant technologies.” Although Congress has, over the years, encouraged companies to develop drug products with tamper- or abuse-resistant characteristics and has issued certain directives to FDA with respect to such products (see here, page 142; here, page 102; and here, page 81), including directing FDA to issue guidance on the development of abuse-deterrent drug products as part of the recently enacted FDA Safety and Innovation Act (§ 1122), the STOPP Act goes much further.
The STOPP Act would amend the FDC Act to, among other things, establish new requirements for the approval of brand-name and generic drugs that are otherwise available in a tamper-resistant formulation. Specifically, under the STOPP Act:
• If a pharmaceutical manufacturer submits an [ANDA] to [FDA] that refers to a listed drug that utilizes a tamper resistant formulation, the application must include data demonstrating that the new drug is tamper resistant to a degree comparable to the listed drug. If the ANDA does not make such a showing, FDA must refuse approval of the application.
• FDA must refuse approval of a [NDA] for a new drug, which is an oral dosage form, that contains a controlled substance as an active ingredient and does not utilize a tamper resistant or abuse deterrent formulation, where FDA has previously approved a drug that: (1) is an oral dosage form, (2) contains the same controlled substance as an active ingredient, (3) utilizes a tamper resistant or abuse deterrent formulation, and (4) has not been discontinued from marketing.
• If a listed drug begins to utilize a tamper resistant formulation, any drug previously approved under an ANDA that refers to such listed drug must be deemed not therapeutically equivalent – and thus not substitutable – to the listed drug, unless and until the generic also begins to utilize a tamper resistant formulation.
• If approval of a listed drug has been withdrawn, or if such drug is withdrawn from sale, after a tamper resistant version of that drug has been approved under another NDA, then such drug shall be considered withdrawn from sale for a safety reason.
• FDA must refuse a suitability petition where the petition references a listed drug that utilizes an abuse deterrent formulation, and the new drug contains any active ingredient(s) that differ in any respect from those contained in the listed drug. As a result, any such new drug must be approved under an NDA rather than an ANDA.
One example cited by Rep. Keating as a basis for the STOPP Act is the tamper-resistant version of Purdue Pharma L.P.’s OxyContin (oxycodone hydrochloride) Controlled-Release Tablets that FDA approved in April 2010 under NDA No. 022272 and that replaced the original and now discontinued non-tamper-resistant version of the drug FDA approved in December 1995 under NDA No. 020553. FDA has already received several citizen petitions (Docket Nos. FDA-2011-P-0473, FDA-2010-P-0540, and FDA-2010-P-0526) requesting that the Agency determine whether the discontinued version of OxyContin was voluntarily withdrawn for safety or effectiveness reasons. FDA’s decision on the issue will determine whether the agency can approve any pending ANDAs for the discontinued formulation.
More recenty, and just a week prior to the introduction of the STOPP Act, Purdue submitted a 75-page citizen petition to FDA (Docket No. FDA-2012-P-0760) requesting that the Agency, among other things, issue guidance detailing the in vitro and in vivo tests that must be performed by the sponsor of an ANDA for a generic version of the tamper-resistant version of OxyContin “to characterize the physicochemical properties of the proposed generic product and to assess the release of oxycodone when the product is manipulated in order to simulate attempts to tamper with the product for purposes of abuse or misuse,” and to refuse to approve any ANDA that does not meet such standards. In July 2010, FDA issued draft guidance specifying the types of bioequivalence studies the Agency recommends for generic versions of the tamper-resistant version of OxyContin; however, the draft guidance makes no mention of studies taking into account tamper resistance. More recently, FDA issued draft bioequivalence guidance with respect to generic versions of EMBEDA (morphine sulfate and naltrexone hydrochloride) Extended-Release Capsules that includes a crush study that “allows for the assessment of Naltrexone bioequivalence in a potential abuse situation.”