Notice of Compliance with Conditions-qualifying Notice

Date: 2007-03-16

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Contact
BCANS Enquiries

Therapeutic Products Directorate
Holland Cross, Tower "B"
6th Floor, 1600 Scott Street
Address Locator #3106B
OTTAWA, Ontario
K1A 0K9

9427-S1354\4-28

[employee name removed]
Vice-President
Medical & Regulatory Affairs
Solvay Pharma Inc.
60 Columbia Way, Suite 102
MARKHAM, Ontario
L3R 0C9

[employee name removed]:

This Notice of Compliance with Conditions Qualifying Notice (NOC/c-QN), issued in accordance with the Health Canada NOC/c Policy, is to advise you that information submitted in support of the New Drug Submission for DUODOPA (levodopa/carbidopa intestinal gel, 20 mg/ml levodopa and 5 mg/ml carbidopa), Control Number 102539, for the treatment of advanced levodopa-responsive Parkinson's disease in which satisfactory control of severe, disabling motor fluctuations and hyper-/dyskinesia cannot be achieved with available combinations of Parkinson medicinal products, qualifies to be considered for authorization under the NOC/c Policy. In keeping with the provisions outlined in the NOC/c Policy, the following additional information is required to complete the assessment:

1. A letter, signed by the Chief Executive Officer or designated signing authority of Solvay Pharma Inc. indicating that you agree to have this submission considered under the NOC/c Policy. Please be reminded that in agreeing to accept an NOC under the NOC/c Policy, Solvay Pharma Inc. consents to the posting of the NOC/c-QN on Health Canada's website.
   
   
2. A draft Letter of Undertaking signed by the Chief Executive Officer, or designated signing authority of Solvay Pharma Inc., having a form and content satisfactory to Health Canada, as indicated in the Guidance for Industry: Notice of Compliance with Conditions, including commitments to supply the following:
   
   
   1. A protocol for a well designed and controlled study of at least 12 weeks duration in patients with advanced idiopathic Parkinson's disease, documented levodopa-responsiveness and persistent, severe motor fluctuations, dyskinesia and hyperkinesia despite optimized therapy with various combinations of antiparkinsonian medications. The proposed study should confirm promising efficacy results of preliminary studies in which DUODOPA treatment was associated with a decrease in the variation of plasma levodopa levels, improvements in motor and decreases in OFF time, in patients with advanced Parkinson's disease. The confirmatory study is expected to evaluate the safety and efficacy of DUODOPA under the proposed conditions of use as an infusion delivered to the upper intestine through a catheter inserted via percutaneous endoscopic gastrostomy (PEG) or percutaneous fluoroscopic gastrostomy (PFG); and as monotherapy or in combination with other (non-levodopa-containing) antiparkinsonian medications. This study should also employ established, clinically meaningful and validated efficacy outcome measures; and should be of sufficient power to provide clinically and statistically significant efficacy results.
      
      Safety data from this study should include the evaluation of routine safety outcomes related to the drug treatment. The safety data should also include the evaluation of all safety outcomes specific to the use of the device required for administration of the drug. This includes assessment of adverse events related to PEG surgery and stoma healing during treatment, all adverse events associated with intestinal tubing used for intraduodenal infusion, all complications associated with mechanical device and its operation.
      
      The confirmatory study should be initiated within a timeframe that is agreed upon between Health Canada and Solvay Pharma.
      
      
   2. Additional long-term data from ongoing open extension studies or studies completed after filing the NDS, which demonstrate the duration/extent of maintenance of treatment benefit and safety of long-term treatment should be submitted as they become available.
      
      
   3. A synopsis of the DUODOPA Education Program, as outlined in the Product Monograph, to be implemented by Solvay Pharma Inc. for training/educating healthcare professionals and patients/caregivers about the proper use of DUODOPA.
      
      
   4. Periodic Safety Update (PSUR-Cs) on a semi-annual basis. PSURs should be prepared in accordance with ICH Guidelines and should include events reported for levodopa/carbidopa intestinal gel (manufactured and marketed by Solvay Pharma) administered by intraduodenal infusion. PSURs should be submitted in paper and electronic (bookmarked and searchable) formats.
      
      
   5. Report of all serious Adverse Reactions (AR) that occurred in Canada and all serious unexpected ARs that occurred outside of Canada should be forwarded within 15 days to Health Canada. One copy is provided to the Marketed Health Products Directorate and another copy to the Bureau of Cardiology, Allergy and Neurological Sciences in the Therapeutic Products Directorate in accordance with current regulations and guidelines.
      
      
   6. Notification and reporting on specific issues of concern as outlined in Section 6.2.4 of the Notice of Compliance with Conditions Guidance.
      
      
   7. Additional information to be provided in the Letter of Undertaking includes an outline of agreed-upon advertising, labeling or distribution requirements; a complete listing of ongoing additional clinical trials (append to Letter of Undertaking); copies of any marketing approvals for the drug under review from any other drug regulatory authority; and a commitment to provide a revised Product Monograph as new information is made available.
      
      
3. A draft of the "Dear Healthcare Professional Letter" detailing the issuance of a Notice of Compliance under the NOC/c Policy for DUODOPA for the indication of treatment of patients with advanced idiopathic Parkinson's disease. This indication includes patients with levodopa-responsive symptoms and documented, persistent, severe motor fluctuations, hyperkinesia and dyskinesia when treated with various combinations of antiparkinsonian medications and for whom other therapies are not appropriate options.
   
   
4. A draft of the "Fact Sheet" outlining in lay language the potential risks, benefits and side effects of DUODOPA for the indication of treatment of patients with advanced idiopathic Parkinson's disease. This indication includes patients with who have levodopa-responsive symptoms and documented, persistent, severe motor fluctuations, hyperkinesia and dyskinesia when treated with available combinations of antiparkinsonian medications and for whom other therapies are not appropriate options.
   
   
5. A draft of the Product Monograph which is consistent with the requirements outlined in Section 5.2.1 of the Notice of Compliance with Conditions Guidance. Please note that, if applicable, a boxed text must appear on the cover page, at the beginning of each major section of the Product Monograph (Parts I, II and III), the first page, and the start of the Consumer Information section, disclosing the nature of the authorization granted for DUODOPA and the need to conduct confirmatory studies.
   
   

I wish to advise you that this Qualifying Notice is being issued in accordance with Health Canada's guidance and policy on the Management of Drug Submissions and Notice of Compliance with Conditions, respectively. Sponsors are instructed to submit a complete response (refer to "Guidance for Industry: Notice of Compliance with Conditions") to the outstanding information within 30 calendar days of the date of this letter.

In order to facilitate and to ensure proper processing, please include a revised Submission Certificate with your response, quote the product name and control number, and address all correspondence to:

Submission and Information Policy Division
Therapeutic Products Directorate
Health Canada
Finance Building Address Locator 0201A1
101 Tunney's Pasture Driveway
Ottawa, Ontario
K1A 0K9

Yours sincerely,

Original signed by

Supriya Sharma, MD MPH FRCPC
Associate Director General