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Prescription medicine BPR update newsletter, November 2011

10 November 2011

Introduction

The BPR update was created to provide sponsors with information during the transition period on the streamlined submission process. As sponsors will be aware, the transition period ended on 31 October 2011.

The key implication of this milestone for sponsors is the end of the 48-hour grace period to rectify deficiencies in pre-submission planning forms and submission dossiers.

In this edition:

  • end of the transition period - what this means for sponsors
  • streamlined submission process
    • progress to date
    • PPF and submission regulatory requirements
  • Christmas-new year arrangements.

Transition period ends: no 48-hour grace period

The streamlined submission process for prescription medicines was introduced on 1 November 2010. To assist sponsors with changes under the new process, the TGA agreed to a twelve-month transition period. This period ended on 31 October 2011.

During the transition period, the TGA assisted sponsors to correct deficiencies in pre-submission planning forms (PPFs) and submission dossiers by providing a transitional 48-hour''grace period' for sponsors to correct deficiencies identified by the TGA. A deficiency occurs when the sponsor does not comply with regulatory requirements. During the transition period, each sponsor with a submission containing one or more deficiencies was given a 48-hour grace period in which to resolve the deficiencies; this translated to between an extra 2 and 7 days of work for the TGA, placing significant stress upon the TGA's ability to meet the streamlined submission process milestones for all applications, not only the PPFs and submissions that required such corrective action.

As detailed in the September 2011 BPR update, the TGA committed considerable resources to assist sponsors who lodged deficient PPFs and submission dossiers. From the beginning of the streamlined submission process on 1 November 2010 until August 2011, the TGA received more than 56 deficient PPFs (approximately 20% of all PPFs), and more than 110 deficient submission dossiers (approximately 45% of all submission dossiers). If deficiencies in the physical dossier quality requirements are added, this proportion is significantly higher. However, as a direct result of significant TGA assistance, only 12 PPFs were considered not complete, and only 5 submission dossiers were considered not effective.1

Although the grace period has now ended, the TGA will continue to provide assistance to sponsors in the planning letter. The TGA will advise sponsors in the planning letter (issued when a PPF is considered complete and acceptable) of any issues that must be addressed in the submission dossier to ensure legislative compliance. In accordance with regulatory requirements set out in CTD Module 1, at Module 1.8.3: Declaration of compliance with pre-submission planning form and planning letter, sponsors must:

  • review any issues identified in the planning letter and for each issue, confirm it has been addressed and provide detail on how it has been addressed
  • declare the submission is consistent with the PPF or if not, list any inconsistencies with an appropriate justification for each inconsistency.

During the transition period, the TGA has provided information for sponsor attention in the planning letters in the expectation this information would assist sponsors to prepare effective submission dossiers. However, a significant number of sponsors are not addressing issues that have been identified in the planning letter and are not providing module 1.8.3 in the submission dossier. This represents a significant proportion of the number of deficiencies reported in the 'Summary of progress to date' section of this newsletter.

As sponsors will be aware, section 23 of the Therapeutic Goods Act 1989 (the Act) requires the TGA to reject any applications that do not meet the regulatory requirements. From 1 November 2011 any PPFs or submission dossiers that do not meet the regulatory requirements will immediately be considered not complete and not acceptable (in the case of PPFs), or not effective and not accepted for evaluation (in the case of submission dossiers). Sponsors, should they wish to continue with their application, will need to re-start the process at the beginning by lodging a new PPF in the next available batch. Sponsors will no longer be given an opportunity after lodgement to correct any deficiencies with their PPF or submission dossier.

Sponsors are strongly encouraged to read the information in the September 2011 edition of the BPR update and this newsletter, and refamiliarise themselves with regulatory requirements. Sponsors are also urged to read the physical and packing requirements for submission dossiers in part A of CTD Module 1.

In addition to the documents specified by the section 23 instruments, the TGA has produced other documents which provide further assistance for sponsors who are lodging a PPF or submission dossier. These include:

id="references"References

  1. These statistics are calculated from the November 2010 to August 2011 batches, inclusive.

Streamlined submission process

Summary of progress to date

The following is a summary of key statistics from applications lodged under the streamlined submission process. The TGA is working to finalise the full record of progress to date under the streamlined submission process that would normally be published as an attachment at the end of this newsletter; this will be released in the next edition.

  • October 2011 batch
    • 32 PPFs lodged
    • 69% nominated 60-day response period to s. 31 request
    • new entity - 5; new fixed combination - 0; generic - 14; minor variation - 8; major variation - 1
Streamlined submission process - summary statistics
Item Nov-10 Dec-10 Jan-11 Feb-11 Mar-11 Apr-11 May-11 Jun-11 Jul-11 Aug-11 Sep-11 Oct-11
Pre-submission planning forms
PPFs lodged 28 34 24 25 27 33 28 29 35 26 33 32
Deficiencies - 12% 12% 24% 30% 24% 7% 28% 25% 31% 30% TBA
Not complete 5 3 2 1 0 0 1 0 0 1 TBA TBA
Submission dossiers
Lodged 23 >30 >21 21 27 33 27 34 TBA TBA TBA
Deficiencies 65% 40% 43% 29% 48% 52% 67% 69% 56% TBA TBA TBA
Not effective 1 0 1 0 0 1 2 1 TBA TBA TBA TBA

During the transition period, rather than immediately considering a PPF not complete or a submission dossier not effective, the TGA gave sponsors a 48-hour grace period to address any deficiencies identified by the TGA. From 1 November 2011 any PPFs or submission dossiers that do not meet the regulatory requirements will immediately be considered not complete and not acceptable (in the case of PPFs), or not effective and not accepted for evaluation (in the case of submission dossiers). Sponsors, should they wish to continue with the application, will need to re-start the process at the beginning by lodging a new PPF in the next available batch. Sponsors will no longer be given an opportunity after lodgement to correct any deficiencies with their PPF or submission dossier.

Pre-submission planning form - common issues

The following information draws on common issues identified with pre-submission planning forms (PPF) lodged to date under the streamlined submission process. This information applies to all applications lodged under the streamlined submission process.

Pre-submission planning form - regulatory requirements
Deficiency TGA requirement TGA workflow impact
Section 1.3 - Product details table

Sponsors must complete the product details table in section 1.3 of the PPF.

See-

  • Information for sponsors completing a pre-submission planning form
This information allows the TGA to understand the number and types of products that will require evaluation. Without this information the TGA is unable to assess or arrange the evaluation resources required.
Inaccurate information provided in PPF

The TGA continues to receive PPFs which do not accurately represent the submission dossier that is subsequently lodged.

When completing the PPF, sponsors declare they understand the Therapeutic Goods Act 1989 provides for offences and penalties for making statements that are false or misleading in a material particular in or in connection with an application for registration of therapeutic goods.

Should the submission dossier differ in scope and scale from that indicated in the PPF, sponsors are reminded this is grounds for the TGA to consider the submission not effective and not accepted for evaluation.

See-

The information provided by sponsors in the PPF allows the TGA to assess and arrange processing and evaluation resources. Should the submission dossier differ in scope and scale, the TGA will not have arranged appropriate resourcing for the evaluation to proceed. In such cases, the submission dossier will be considered not effective and not accepted for evaluation.
Module 2 or equivalent requirements for new generic medicines

The following CTD documents must be provided for submissions to support an application to register a generic medicine:

  • Module 2.5 - must be provided for all generic submissions
  • Module 2.7 - must be provided where new additional clinical or biopharmaceutic studies are to be included in the submission dossier.

These documents, or equivalent information, must be provided with the PPF for generic medicine applications.

See -

The module 2 or equivalent information allows the TGA to determine the scope and scale of the submission and to ensure appropriate processing and evaluation resources are allocated. Without this information, the PPF will be considered not complete and not acceptable.

Guidance for an effective submission

Submissions that do not meet regulatory requirements will be considered by the TGA to be not effective and not accepted for evaluation.

Guidance for sponsors - submission dossiers
Deficiency TGA requirement TGA workflow impact
Module 1.8.3

A common deficiency in submission dossiers is the failure to provide Module 1.8.3 or to provide a Module 1.8.3 that is compliant with regulatory requirements.

Module 1.8.3 must:

  • be included for all submissions for which a PPF has been lodged
  • contain a declaration that either:
    • states that the submission is consistent with the PPF lodged
    • lists any inconsistencies with an appropriate explanation
  • identify how the sponsor has addressed any issues requiring sponsor action raised by the TGA in the planning letter.

See -

If a submission dossier is required to include module 1.8.3 but this is not provided in the submission dossier at lodgement, the TGA must consider the submission not effective and not accepted for evaluation.
Packaging

Sponsors are reminded to use bubble wrap to protect binders in transit. Foam beads or peanuts are not to be used.

See -

If a submission dossier arrives at the TGA in a damaged state, this is grounds for the TGA to consider the submission not effective and not accepted for evaluation.
Submission lodgement date

Sponsors are responsible for ensuring the courier they engage delivers the submission dossier to the TGA by the date notified in the planning letter.

When completing the PPF, sponsors declare they will lodge the submission dossier on the date specified and its contents will comply with the information provided in the PPF.

If the TGA does not receive the submission dossier by the date identified in the planning letter, it is considered not effective and not accepted for evaluation.

See -

The TGA arranges in advance the processing and evaluation resources for the entire evaluation process based on the submission lodgement date specified in the planning letter. If the submission is not lodged by this date, evaluation and processing resources are immediately reallocated.

Product information documentation - new products

Subsection 23(2)(ba) of the Therapeutic Goods Act 1989 (the Act) requires that applications for the registration of a restricted medicine are accompanied by product information in the form approved under s. 7D of the Act.

The form approved by the Secretary under s. 7D of the Act changed in May 2011. Changes include (but are not limited to) the following:

  • sub-heading Interactions with other medicines is now a heading
  • preferred format for information under the heading Adverse effects is now described
  • Date of approval replaced by two dates: Date of first inclusion in the ARTG and Date of most recent amendment.

Sponsors are advised to consider the new form carefully to ensure full compliance.

See -

The application cannot be considered effective under s. 23 of the Act. The TGA cannot proceed to evaluate the submission.
Product information documentation - altering a PI already lodged/approved

A product information document lodged in the submission dossier must meet the following requirements:

  • proposed changes to a PI document must be clearly highlighted - track changes mode is preferred
  • all PI documents must be annotated to include sufficient information to direct evaluators to the evidence base in modules 2, 3, 4, and/or 5 that support any changes or new information being proposed.

See -

Information in the PI must be linked to the evidence base in modules 2, 3, 4, and/or 5 or the PI cannot be evaluated.
GMP requirements

For all medicines, irrespective of the country of origin, it is expected that key manufacturing and/or processing steps in the production of active ingredients and finished pharmaceutical products are performed in plants of acceptable standards (see section 4.1.9 of the ARGPM).

GMP clearances must be valid for at least 6 months, and preferably 24 months, at the time of submission lodgement. For category 1 and category 2 submissions where it is anticipated that a manufacturing licence or GMP clearance will expire during the evaluation period, a renewal application must be lodged with OMQ and the details provided in module 1.7.3 of the submission dossier.

See -

The TGA uses manufacturing licences (for Australian manufacturing sites) and good manufacturing practice (GMP) clearances (for overseas sites) to establish whether the manufacturing/processing standards are acceptable.

Without manufacturing licences or GMP clearances, the TGA cannot evaluate the submission.

Application forms

Sponsors must lodge a separate application form for each separate and distinct good in their submission. Section 16 of the Therapeutic Goods Act 1989 provides a definition for 'separate and distinct good'.

If sponsors have any questions, they should contact streamlinedsubmission@tga.gov.au.

See -

If the submission dossier does not comply with the regulatory requirements and contain all information required for evaluation, it will be considered not effective and not accepted for evaluation.
Electronic copy requirements

Sponsors must provide electronic copies of the submission dossier at submission lodgement.

Electronic copies of the submission dossier are to be in NeeS format or eCTD format. Each table of contents in the submission dossier must have active links to the documents it lists.

Failure to provide electronic copies of the submission dossier, or failure to comply with the regulatory requirements established in the documents below is grounds for the TGA to consider the submission not effective and not accepted for evaluation.

See -

The timeframes for phase 2 of the streamlined submission process and the achievement of milestone 2: outcome of submission consideration sent, are dependent on sponsors lodging complete and effective electronic copies of the submission dossier.

Christmas-new year arrangements

TGA shutdown

The TGA will close at 3.00 pm on Friday 23 December 2011 and will re-open on Tuesday 3 January 2012. During this period, no TGA personnel will be answering phone calls or monitoring the BPR or streamlined submission process email inboxes. To accommodate this Commonwealth public service shutdown period, the following arrangements will be made.

Arrangements for December/January batches

As a consequence of the TGA shutdown, PPFs lodged in the December batch (before 1 December 2011) will be processed in accordance with January 2012 batch milestone dates. This means, the planning letter for PPFs lodged in the December batch will not be issued until 15 February 2011.

Arrangements for other milestone dates

The TGA has made the following arrangements for other milestone dates falling over the Christmas-new year period. The TGA has considered these arrangements carefully so as to not impact on eligibility for planned ACPM meetings.

The TGA estimates that approximately 100 submissions currently in the streamlined submission process that will be impacted by these arrangements. Sponsors should ensure they are familiar with these arrangements as the TGA may not be able to issue revised dates on a submission-by-submission basis until the next milestone.

Streamlined submission process Christmas-new year arrangements
Milestone/phase Affected batch/es* Original due date Revised due date Comments
MS1
PPF (December batch)
Dec 2011 15 Jan 15 Feb

Milestones for all December PPFs will be aligned with those of the January batch of PPFs. The default dates for both December and January batches will therefore be:

  • submission dossier lodged by COB 14 March
  • milestone 2 - 31 March 2012
  • milestone 3 - 31 July 2012 (assuming default evaluation period)
M2
Outcome of submission consideration sent
Oct 2011 31 Dec 2011 16 Jan 2012 The milestone 3 for these submissions will be extended to align with the end of the month. This means the timeframe for milestone 3 for this batch will be 4½ or 5½ months (depending on response timeframe to s. 31 request nominated) rather than 4/5 months.
M3
Outcome of 1st round assessment sent
May 2011
June 2011
31 Dec 2011 21 Dec 2011 Due dates for relevant responses will be remain as specified in the planning letter to ensure statutory timeframes are met.
M4
End of s.31 response period
March 2011
April 2011
May 2011
31 Dec 2011 3 Jan 2012 As the TGA will not be open to accept deliveries or post during the shutdown period, the due date for sponsors to deliver their responses is extended to the first working day of the new year.
M5
Outcome of assessments sent
Feb 2011
March 2011
April 2011
31 Dec 2011 16 Jan 2012 The sponsor's response period to advise the TGA of any errors of fact or omission in the evaluation report/s will be maintained at two weeks.
M7
Decision made by delegate
Nov 2010
Dec 2010
31 Dec 2011 case-by-case The TGA will, wherever possible, complete the decision phase before the Christmas shutdown.
M8
Administrative and regulatory activities complete
Nov 2010
Jan 2011
31 Dec 2011 case-by-case The TGA will, wherever possible, complete the post-decision phase before the Christmas shutdown. Note, however, that there are sponsor dependencies.

* This information is provided as a guide only and sponsors should check the most recent milestone letter from the TGA for each submission to determine if it is affected by these arrangements.

© Commonwealth of Australia 2011
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