Regulatory Focus™ > News Articles > FDA Says Abuse-Deterrence Equivalence Guidance is Under Development

FDA Says Abuse-Deterrence Equivalence Guidance is Under Development

Posted 25 March 2014 | By Alexander Gaffney, RAC

The US Food and Drug Administration (FDA) has announced it intends to issue a guidance document regarding the equivalence of abuse-deterrent qualities between generic and branded versions of Purdue Pharma's Oxycontin, laying a pathway to approval for future generic market entrants-and perhaps other types of drugs as well.


In April 2013, FDA announced that it had determined that an original, non-abuse-deterrent version of Oxycontin (oxycodone hydrochloride) had been removed from the market for reasons of safety or efficacy.

Because the patent on that original drug had expired, Purdue had been facing competition from generic entrants who would have been able to market the drug without its current abuse-deterrent qualities.

"[B]ecause original Oxycontin provides the same therapeutic benefits as reformulated Oxycontin, but poses an increased potential for certain types of abuse, the FDA has determined that the benefits of original Oxycontin no longer outweigh its risks and that original Oxycontin was withdrawn from sale for reasons of safety or effectiveness," FDA wrote.

Citizen Petition: Give us Guidance

Then, in October 2013, Purdue filed a Citizen Petition with FDA requesting that FDA "adopt and announce" a new guidance document regarding which in vivo and in vitro tests would be necessary to show that a generic drug's abuse-deterrent qualities were equivalent to the abuse-deterrent qualities used by Purdue's reformulated, FDA-approved version of Oxycontin.

In particular, Purdue requested the following elements be included in a future FDA guidance document:

(a) Tablet manipulation studies to determine the resistance of the proposed generic formulation to methods of reducing tablets to particles using a variety of commonly available tools, and to establish the time and effort required to reduce the proposed generic tablets to fine particles;

(b) In vitro small and large volume extraction and dissolution studies on intact tablets and on standardized particle sizes of manipulated tablets, using an appropriate range of solvents, conditions, and pretreatments;

(c) In vitro studies measuring the syringability and injectability of tablet contents, extracted by standardized procedures;

(d) In vitro studies measuring the ability to create and extract free oxycodone base from the tablets;

(e) In vitro smoking simulation studies measuring the ability to vaporize oxycodone from fine particles prepared from the tablets;

(f) An in vivo bioequivalence/non-inferiority study with clinical endpoints evaluating the abuse potential of orally ingested manipulated tablets (ingested after chewing, or after reducing the tablets to fine or coarse particles), providing measures of T max, Cmax, and AUC, and liking; and

(g) An in vivo bioequivalence/non-inferiority study with clinical endpoints evaluating the abuse potential of insufflated fine particles, providing measures of (PK measures ofT max, Cmax, and AUC, and liking; and

(h) Additional in vitro and/or in vivo tests necessary to evaluate any potential formulation-specific vulnerabilities associated with physical and chemical features of the generic product, using reformulated Oxycontin as a control.

FDA: Guidance Still in the Works

Now, five months later, FDA has a response for Purdue: That requested guidance is on its way, but it's not ready yet.

"The agency intends to issue guidance regarding Abbreviated New Drug Applications (ANDAs) and abuse-deterrent properties," FDA wrote in its response to Purdue, posted on 21 March 2014.

The agency has reportedly formed an "internal working group" on the guidance, and is already working internally to test "both approved products and internally-developed formulations to evaluate the robustness and reproducibility of in vitro test and to develop optimal test conditions." Externally, FDA has awarded a contract to test the performance of abuse-deterrent drugs, FDA noted in its Citizen Petition response.

FDA did not provide any details about when the guidance would be published.


FDA Response to Purdue

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