the key learnings of the adderall xr® suspension and re-instatement of noc in 2005

8/6/2019 The key learnings of the Adderall XR suspension and re-instatement of NOC in 2005

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Our purpose

We enable people with life-altering conditions to lead better lives

ADDERALL XR

Suspension and Re-instatement of NOC

in 2005


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To be as brave as the people we help

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Presentation Outline

The facts

Background

Outcome


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Summary

After being marketed for one year, the Notice ofCompliance (NOC) forAdderall XR was suspended by

Health Canada on Feb 9, 2005

After a review involving independent experts following aprocess vaguely described in the Food and Drug

Regulations, Adderall XRs NOC was re-instated 6

months later


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Impact on operations

The product was primary focus of one sales force

Impact on the US operations

Immediate stop of promotion

Impact on patients and physicians

Redeployment to second product

Other actions


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Background

Adderall XR was first approved for the treatment ofADHD inchildren 6 and over in Canada in January 2004.

The immediate-release formulation ofAdderall, available in the US,was never marketed in Canada

US Package Insert forAdderall XR was revised in Aug 2004 Based on post-marketing adverse reaction reports of sudden death,

serious cardiovascular and cerebro-vascular events with immediate-release Adderall and Adderall XR

Warnings regarding sudden death in relation to drug misuse/abuse andpre-existing structural cardiac abnormalities were added

On review of the same proposed labeling changes and supportingdocumentation, Health Canada suspended the Adderall XR NOC onFeb 9, 2005


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Health Canadas Reasons for Suspension

20 cases of sudden/cardiac death & 12 cases of

cerebro-vascular accident reported globally forAdderall IR and Adderall XR over 9-year period

Adderall XR is associated with risk of sudden/cardiac

death and cerebro-vascular accident

Preliminary Health Canada analysis suggested that

signal for sudden/cardiac death appears to be higher for

Adderall IR/XR compared to other stimulants

Reporting rates at or above background rate forsudden/cardiac death

Risks cannot be adequately managed through labeling


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NDC process

Shire appealed Health Canadas decision immediately,

under C.08.009 of the Food and Drug Regulations

Old regulation, not implemented in last 30 years

according to Health Canada Involves appointing a New Drug Committee to consider

Health Canadas decision and make recommendations

to the Minister

Independent 3-member New Drug Committee (NDC) appointed

by Shire and Health Canada

No guidelines, process or timelines available other than what is

in C.08.009


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NDC Review

Month 1: Request and receipt of Health Canadas reasons for the

suspension

Establishment of process / timelines:

Meeting with Health Canada to agree on NDC process

Submission of Shires NDC nominee, Health Canadanominated a member, and a third member (the Chairman of

the NDC) was selected

NDC consisted of:

pediatric cardiologist

specialist in pediatric development and behavioral problems, and pharmacoepidemiologist


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NDC Review

Month 2: Preparation of Shires NDC Briefing Package:

Creation / finalization of five expert reports (cardiology, neurology,

pharmacoepidemiology, clinical data summary, benefit/risk)

Health Canada also prepared an extensive Briefing Package for

submission to the NDC


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Materials reviewed by NDC

In addition to complete background clinical and post-marketing information:

Comprehensive review of background rate and profile of

sudden/cardiac death in general age-matched population

Comprehensive review of background rate of stroke in general

age-matched population

Additional, more comparable, analyses of relative estimated

reporting rates of sudden/cardiac death and stroke forAdderall

versus otherADHD drugs.


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NDC Review

Months 4-5: Preparation and submission to NDC of rebuttal to Health

Canadas Briefing Package

Health Canada also prepared and submitted a rebuttal to ShiresBriefing Package

Questions from, and answers to, NDC members

Meeting with NDC:

Presentations by experts representing Health Canada and Shire

Month 6: NDC recommendation with suggested reinstatement conditions

Health Canada final decision / NOC re-instatement

Reintroduction communication:

Press release

DHPL


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Conclusions of Health Canada and NDC

Re-assessment

The reporting rate for sudden death and stroke in patients takingAdderall (IR and XR) is not greater than the general unexposed

population, even when accounting for underreporting of adverse

events.

There is insufficient evidence to support Health Canadas concern

that there is an increased risk of sudden/cardiac death or stroke withAdderall XR compared to otherADHD treatments.

Theoretically, there exists a pharmacological potential for all ADHD

drugs (stimulant and non-stimulant) to increase the risk of

sudden/cardiac death.

Adderall XR NOC should be reinstated immediately concurrent withlabeling changes previously proposed by Shire


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Recommendation of the NDC & Health Canada

The NDC recommended ; immediate reinstatement of NOC with labeling changes previously

proposed by Shire

Re-instatement conditions proposed: Dear Healthcare Professional Letter be distributed by Shire

Continuing Medical Education be sponsored by Shire regarding the

profile and predictors of sudden/cardiac death in the general population

Health Canada adopted the NDC recommendations, and NOC wasre-instated on August 26, 2005


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C.08.009

(1) Where the Minister has decided

(a) to notify the manufacturer of a new drug for veterinary use that the sale ofthat drug to qualified investigators is prohibited, or

(b) to suspend a notice of compliance issued in respect of a new drugsubmission or an abbreviated new drug submission or a supplement to eithersubmission,

the manufacturer, if dissatisfied with that decision, may require the Minister toprovide him with the reasons for the decision.

(2) Where the manufacturer has received the reasons for a decision of theMinister pursuant to subsection (1), he may require the Minister to refer thatdecision to a New Drug Committee and thereupon shall provide the Ministerwith a statement of the reasons for his dissatisfaction and any information andmaterial upon which he relies in support of those reasons.


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C.08.009 (contd)

(3) Where the Minister has been required to refer a decision to a New Drug

Committee pursuant to subsection (2), he shall appoint a member of the NewDrug Committee, the dissatisfied manufacturer shall appoint a member of theNew Drug Committee and the two members so appointed shall appoint a thirdmember of the New Drug Committee who shall be chairman, or, if they areunable to do so within a reasonable time, the Minister shall appoint a thirdmember of the New Drug Committee who shall be chairman.

(4) Any person who is in the full-time employment of the Department or in the

full-time employment of the dissatisfied manufacturer shall not be appointed amember of a New Drug Committee.

(4.1) A member of a New Drug Committee shall, on appointment, sign anundertaking not to disclose or use any information, material, data, evidence orrepresentations considered pursuant to subsection (6).

(5) The Minister shall pay the reasonable fees and costs incurred by themember of the New Drug Committee appointed by the Minister, and the

dissatisfied manufacturer shall pay the reasonable fees and costs incurred bythe member appointed by the dissatisfied manufacturer, and the Minister andthe dissatisfied manufacturer shall each pay half of the reasonable fees andcosts incurred by the chairman.


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C.08.009 (contd)

(6) The New Drug Committee formed pursuant to subsection (3) shall consider

the reasons for the decision of the Minister, the reasons for the dissatisfactionof the dissatisfied manufacturer and any information or material in support ofthe reasons of the Minister or the dissatisfied manufacturer and may considerother evidence, material, information or representations.

(7) The New Drug Committee formed pursuant to subsection (3) shall report itsfindings and recommendations to the Minister.

(7.1) No member of a New Drug Committee shall disclose or use any

information, material, data, evidence or representations considered pursuant tosubsection (6).

(8) Where the Minister has received the findings and recommendations of aNew Drug Committee, he may reconsider the decision to which those findingsand recommendations relate.

the key learnings of the adderall xr® suspension and re-instatement of noc in 2005

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