Published: 27 June 2019

Consultations

Outcome of consultation on the revision of CMN Form B

About the consultation
Submissions received
Consultation feedback and Medsafe’s response
Implementation
Enquiries

About the consultation

In May 2018 Medsafe sought comments on a proposed revision of CMN Form B. A number of updates were proposed for CMN Form B that included, but were not limited to, the following:

• revised category names to create consistency in category headings
• introduction of additional criteria to some categories to ensure correct categories are selected for CMN submissions
• introduction of additional categories to address changes that are currently notified without suitable categories to select
• removal of some unused/redundant categories
• introduction of additional Self-Assessable Change Notification categories
• editorial changes to improve clarity of the category descriptions and criteria.

Medsafe would like to thank all those who took the time to respond to the consultation.

Submissions received

Medsafe received six submissions in response to this consultation. Five of the submission were made by sponsors on behalf of their respective organisations, and one submission was from an industry organisation.

The six submissions are published below. Personal information that can identify submitters has been removed where requested.

Note: No requests to withhold submissions from publication were received.

1. Abbvie (PDF 30 KB, 1 page)
2. Amgen (PDF 78 KB, 1 page)
3. GSK (PDF 131 KB, 4 pages)
4. MSD (PDF 126 KB, 2 pages)
5. Mylan (PDF 129 KB, 2 pages)
6. New Zealand Self Medication Industry (PDF 152 KB, 5 pages)

Consultation Feedback and Medsafe’s response

All submissions received have been reviewed by Medsafe. Feedback from this consultation has been used to amend the revised CMN Form B.

Submitters were generally supportive of the revised CMN Form B. Several submitters suggested wording and/or formatting changes to improve clarity and noted minor errors for correction. Where appropriate, changes have been incorporated into the final document to address these editorial suggestions.

A number of submitters suggested that CMN Form A and CMN Form B could be either be combined to create a single form, or aligned with each other to streamline the forms. These suggestions are acknowledged by Medsafe, but are outside the scope of this consultation. These suggestions may be considered in the future.

Aside from editorial suggestions and alignment of CMN Form A and CMN Form B, a summary of the issues raised by submitters that were within the scope of the consultation and Medsafe’s responses to each of these issues is discussed below.

Addition of the new category ‘Active ingredient method of manufacture – Grade 2’

1. One submitter sought clarity on whether the criteria ‘‘change in room for cell substrate preparation activities’, requires only changes in rooms for cell substrate preparation activities to be notified, or if room changes more broadly should be notified to Medsafe.

Response

1. This category should be used for changes to rooms concerned with cell substrate preparation activities only, as changes to rooms at other steps in the manufacturing process will be captured under other categories in CMN Form B. Medsafe should be notified of room changes at any step in the manufacturing process if they are accompanied by a reduction in the environmental classification from that currently approved.

Introduction of the new category ‘Finished product testing site’

1. Clarity was sought by some submitters regarding the criteria ‘implementation of additional (previously approved) test methods at a current finished product testing site’.

Response

1. Medsafe included this criteria to create a notification category for situations where a registered testing site is increasing its testing repertoire by taking on a previously approved finished product test that is already performed at another finished product testing site. Based on this feedback Medsafe has amended the criteria description to improve clarity.

Introduction of new criteria for ‘Finished product manufacturing process – Grade 3

Clarity was sought by a submitter regarding the criteria ‘change from a single product to a multi‐product manufacturing facility’. Specifically the following questions were raised;

1. Do sponsors only notify Medsafe if the manufacturing process of a product changes as a result of a change in manufacturing facility?
2. If there is a change from a single to multi‐product manufacturing facility, but no change to the manufacturing process, is a submission to Medsafe required?

Response

1. and ii. Sponsors should notify Medsafe if a manufacturing facility that is registered as a single product manufacturing facility changes to a multi-product manufacturing facility, regardless of whether the manufacturing process of a product changes or not. It would be expected that a change from a single product to a multi-product manufacturing facility would result in an update to Section 3.2.A of the dossier. If there are changes to the manufacturing process as a result of a single product manufacturing facility changing to a multi-product facility, then these changes should be notified using either the category ‘Finished product manufacturing process – Grade 1’ or Finished product manufacturing process – Grade 2’.

Finished product secondary packing site

1. A submitter suggested that the category ‘Finished product secondary packing site’ should be a self-assessable change notification, or at least a self-assessable change notification where the packing site is in NZ and has a Medsafe issued packing licence.

Response

1. For the addition of any secondary packing site, regardless of whether it is overseas or in New Zealand, Medsafe checks that the GMP certification for that site is current and includes authorisation for secondary packing activities. The Medsafe database for the affected product(s) must also be updated to include the new secondary packing site. Consequently, these activities preclude a self-assessable category option.

Introduction of criteria under ‘Test methods and specifications – Grade 5’ and ‘Test methods and specifications – Grade 6’ to include extension of reference standard expiry or retest period.

1. Two submitters correctly highlighted that Medsafe not only had introduced additional criteria under the ‘Test methods and specifications’ categories for extension of reference standard expiry or retest periods, but had also introduced an additional category ‘Shelf life/storage conditions – Reference standard used for potency/assay’ for the same change. This had potential to create confusion about which was the appropriate category to select.

Response

1. Medsafe has removed the additional criteria for extension of reference standard expiry or retest periods from the category section ‘Test methods and specifications’. Suitable categories for extension of reference standard expiry or retest periods are now only included under ‘Stability and Packaging’.

Introduction of categories for ‘Excipient specifications/test methods’

1. One submitter requested clarification on whether a CMN submission is required if there are changes to excipient specifications/testing methods resulting from an update to the latest version of a pharmacopoeia.
2. One submitter requested that where an excipient is not controlled according to a pharmacopoeial monograph, tightening of specification limits should be a notification only.

Response

1. Medsafe confirms that no CMN submission is required if there are changes to excipient specifications/test methods that are a result from an update to the latest version of a pharmacopoeia, where the excipient is already controlled to that pharmacopoeia. This scenario is currently described in Section 4.9 in Part 2 of the Guidelines on the Regulation of Therapeutic Products in New Zealand.
2. Medsafe has amended the criteria of ‘Excipient specifications/test methods – Grade 1’ to allow for this type of change to be a self-assessable change notification.

Shelf life/storage conditions categories

1. Two submitters correctly highlighted that Medsafe not only had introduced additional criteria under the ‘Test methods and specifications’ categories for extension of reference standard expiry or retest periods, but had also introduced the additional category ‘Shelf life/storage conditions – Reference standard used for potency/assay’ for the same change. This had potential to create confusion about which was the appropriate category to select.
2. One submitter requested that a self-assessable change notification category be introduced for a reduction in shelf life, where the shelf life was being reduced for commercial reasons, e.g. to harmonise product with other markets.

Response

1. Refer to the above response for ‘Introduction of criteria under ‘Test methods and specifications – Grade 5’ and ‘Test methods and specifications – Grade 6’ to include extension of reference standard expiry or retest period’.
2. Medsafe considers that any reduction in shelf life would require a review to determine the reason(s) for the reduction in shelf life. The Medsafe database would also need to be updated to amend the registered shelf life. Consequently, these activities preclude a self-assessable category option.

Container/closure/packaging categories

1. One submitter commented that there was no suitable category for minor changes to the packaging components that do not contact the product.
2. One submitter highlighted that the fee for the new category “Container/closure/packaging – Grade 3” did not align with other similar categories.

Response

1. Minor changes to the container, closure, or packaging can be submitted under the self-assessable change notification category “Container/closure/packaging – Grade 4”, if appropriate. If a sponsor or company is uncertain about whether minor changes to the container, closure, or packaging can be submitted using this self-assessable change notification category, then they should contact Medsafe to determine the appropriate notification category.
2. Medsafe has changed the fee for ‘Container/closure/packaging – Grade 3’ to align with similar categories.

Implementation

The revised CMN Form B will be effective from 1 July 2019. All CMN Form B submissions received after this date should use the revised CMN Form B.

Enquiries

Please send any questions relating to this consultation or CMN Form B to medsafeapplications@health.govt.nz