PRA700Regulatory Affairs II

1
PRA700Regulatory Affairs II

• New Drug Submissions

2
NEW DRUG SUBMISSIONS

• INTRODUCTION
• What is a New Drug Submission?
• Presentation of complete information to obtain
  approval for marketing
• Information must comply with Sections C.08.002,
  C.08.003 and C.08.005 of the Food and Drug Act

3
NEW DRUG SUBMISSIONS

• FOOD DRUG ACT
• C.08.002 (1) No person shall sell or advertise a
  new drug unless
• a) the manufacturer of the new drug has filed
  with the minister a new drug submission or an
  abbreviated new drug submission relating to the
  new drug that is satisfactory to the Minister
• b) the Minister has issued a notice of compliance
  to the manufacturer of the new drug in respect of
  the new drug submission or an abbreviated new
  drug submission

4
NEW DRUG SUBMISSIONS

• FOOD DRUG ACT contd
• c) the notice of compliance in respect of the
  submission has not been suspended pursuant to
  section C.08.006 and
• d) the manufacturer of the new drug has submitted
  to the Minister specimens of the final version of
  any labels, including package inserts, product
  brochures and file cards, intended for use in
  connection with that new drug, and a statement
  setting out the proposed date on which those
  labels will first be used.

5
NEW DRUG SUBMISSIONS

• FOOD DRUG ACT contd
• (2) A new drug submission shall contain
  sufficient information and material to enable the
  Minister to assess the safety and effectiveness
  of the new drug, including the following
• a) a description of the new drug and a statement
  of its proper name or its common name if there is
  no proper name
• b) a statement of the brand name of the drug or
  the identifying name or code proposed for the new
  drug

6
NEW DRUG SUBMISSIONS

• FOOD DRUG ACT contd
• c) a list of the ingredients of the new drug,
  stated quantitatively, and the specifications for
  each of those ingredients
• d) a description of the plant and equipment to
  be used in the manufacture, preparation and
  packaging of the new drug
• e) details of the method of manufacture and the
  controls to be used in the manufacture,
  preparation, and packaging of the new drug

7
NEW DRUG SUBMISSIONS

• FOOD DRUG ACT contd
• f) details of the tests to be applied to control
  the potency, purity, stability and safety of the
  new drug
• g) detailed reports of the tests made to
  establish the safety of the new drug for the
  purpose and under the conditions of use
  recommended
• h) substantial evidence of the clinical
  effectiveness of the new drug for the purpose and
  under the condition of use recommended
• i) a statement of the names and qualifications of
  all investigators to whom the new drug has been
  sold

8
NEW DRUG SUBMISSIONS

• FOOD DRUG ACT contd
• j) a draft of every label to be used in
  conjunction with the new drug
• k) a statement of all representations to be made
  for the promotion of the new drug respecting
• (i) the recommended route of administration of
  the new drug
• (ii) the proposed dosage of the new drug
• (iii) the claims to be made for the new drug,
  and
• (iv) the contraindications and side-effects of
  the new drug

9
NEW DRUG SUBMISSIONS

• FOOD DRUG ACT contd
• l) a description of the dosage form in which it
  is proposed that the new drug be sold
• m) evidence that all test batches of the new
  drug used in any studies conducted in connection
  with the submission were manufactured and
  controlled in a manner that is representative of
  market production.

10
NEW DRUG SUBMISSIONS

• What is a New Drug Submission? Contd
• Format must comply with requirements as per
  Guideline (Preparation of New Drug Submissions in
  the CTD Format, 2203/06/25)
• All available information must be presented

11
NEW DRUG SUBMISSIONS

• WHEN TO FILE AN NDS
• When sufficient information available
• Corporate decision
• Coordinate between head-office and Canadian
  office
• Coordinate between marketing, clinical and
  regulatory affairs

12
NEW DRUG SUBMISSIONS

• WHEN TO FILE AN NDS
• RA helps to determine if sufficient data
• Must have reasonable certainty of success
• Charges apply to all submissions

13
NEW DRUG SUBMISSIONS

• WHEN TO FILE AN NDS
• Innovative companies
• New chemical entity
• New dosage
• New formulation

14
NEW DRUG SUBMISSIONS

• WHEN TO FILE AN NDS contd
• Generic companies
• Generic copy of a marketed drug

15
NEW DRUG SUBMISSIONS

• WHEN IS AN NDS NOT NECESSARY
• Administrative changes
• Change in product name (DIN)
• Change in manufacturers name (DIN)
• Change in manufacturing site
• Change of supplier(s)

16
NEW DRUG SUBMISSIONS

• WHEN IS AN NDS NOT NECESSARY
• Notifiable changes (usually manufacturing or
  minor Product Monograph changes)
• Additional information (e.g.... Safety)

17
NEW DRUG SUBMISSIONS

• TYPES OF NDS
• NDS
• Supplemental NDS
• Abbreviated NDS
• Supplemental Abbreviated NDS

18
NEW DRUG SUBMISSIONS

• SUBMISSION FEES
• Cost recovery since 1994
• Introduced to reduce review backlog and to
  increase efficiency in the review process
• Specific fees for each type of submission
  depending on content

19
NEW DRUG SUBMISSIONS

• SUBMISSION FEES contd
• Fee form must accompany the submission
• Applicable only to submissions filed after
  October 1994

20
NEW DRUG SUBMISSIONS

• SUBMISSION FEES contd
• Preclinical Clinical 117,000
• Clinical only 52,000
• Comparative 17,200
• Comparative for each added strength 2,700
• Removal from Schedule F new indication 52,900
• Removal from Schedule F same indication 17,200
• Chemistry Manufacturing -drug substance 11,500
• Chemistry Manufacturing -drug product 15,300
• Medical literature 2,200

21
NEW DRUG SUBMISSIONS

• SUBMISSION FEES -examples
• Single condition/ dosage form/ route
• 117,000 11,500 15,300 143,800
• Two conditions of use
• 117,000 11,500 15,300 52,900 196,700
• Two dosage forms (clinical data)
• 117,000 11,500 15,300 52,900 15,300
  212,000
• Two dosage forms (comparative data)
• 117,000 11,500 15,300 17,200 15,300
  176,300

22
NEW DRUG SUBMISSIONS

• SUBMISSION FEES contd
• Refiled submissions
• Following withdrawal by Sponsor or NON or NOD
• Fees as per submission fee guideline in effect on
  the date of refiling

23
NEW DRUG SUBMISSIONS

• SUBMISSION FEES contd
• When payable
• upon notification that application has been
  screened 10
• upon notification that application has been
  accepted for examination 65
• Billed together 75

24
NEW DRUG SUBMISSIONS

• SUBMISSION FEES contd (3)
• upon notification that examination has been
  completed 25
• (i.e.. NOC or NON withdrawal letter)
• Fees for withdrawn submissions based on when
  submission withdrawn
• Fees less than 10,000 payable when submission
  filed

25
NEW DRUG SUBMISSIONS

• REVIEW PROCESS
• Filing to Submission and Information Policy
  Division
• A control number is assigned
• Screening within appropriate Bureau
• PreClinical/Clinical Review
• PreClinical/Clinical Negotiation Period
• Sponsors response

26
NEW DRUG SUBMISSIONS

• REVIEW PROCESS contd
• CMC review
• CMC Negotiation Period
• Sponsors response
• Product monograph/ label finalization
• NOC
• Duration 345 days NDS, 225 days ANDS

27
NEW DRUG SUBMISSIONS

• RESPONSIBILITIES of SCREENING DIVISION
• Content
• for every part of the submission
• proper conclusions for each section
• cross-referencing

28
NEW DRUG SUBMISSIONS

• TYPES OF REVIEW RESPONSES
• Clarifax
• No limit on the number of Clarifaxes issued for a
  submission, but the same deficiency will only be
  addressed once
• Sponsor has 15 calendar days to respond
• If not satisfactory, a NOD or NON will be issued.

29
NEW DRUG SUBMISSIONS

• PRE-NDS MEETING
• Purpose
• meet with the reviewing team
• introduce the data
• outline the content of the submission
• discuss any special issues - e.g.... electronic
  submissions, different formats, fast-tracking,
  etc............

30
NEW DRUG SUBMISSIONS

• PRE-NDS MEETING contd
• Who should attend
• Reviewers (TPP)
• RA professional
• Sponsors clinician
• Independent Canadian expert

31
NEW DRUG SUBMISSIONS

• PRE-NDS MEETING contd
• When
• Prior to submitting
• Make sure strategy is in place
• Give yourself enough time to make adjustments as
  per discussions with reviewers

32
NEW DRUG SUBMISSIONS

• THE NDS SUBMISSION
• Bound in 3-ring binders
• Each volume identified (on both the spine and the
  front cover) with the name of the drug, name of
  manufacturer and section/module number
• All pages must be paginated - sequentially for
  the entire submission or by volume

33
NEW DRUG SUBMISSIONS

• Each volume must be numbered sequentially,
  starting at 1 and colour-coded
• French or English
• Ensure submission complies with Sections
  C.08.002, C.08.003 C.08.0051
• Deviations from the formatting guidelines are
  acceptable with prior agreement

34
NEW DRUG SUBMISSIONS

• SUBMISSION VOLUME LABEL
• New Drug Submission
• ABRA (abracadabra) in the treatment of rheumatoid
  arthritis
• Module 3, Vol. 4
• Magic Pharma Canada Inc.
• October 27, 2003