GUIDANCE ON MEDICINAL PRODUCT REGISTRATION IN SINGAPORE CHECKLIST FOR MINOR VARIATION APPLICATIONS (MIV-2) FOR BIOLOGICS

JANUARY 2009

APPENDIX 15B CHECKLIST FOR MINOR VARIATION APPLICATIONS (MIV-2) FOR BIOLOGICS
Applicants should be familiar with the documentary requirements for MIV submissions refer to Table A in Appendix 15 for the list.
NOTE: When submitting the Checklist, please delete the MIV-2 checklist category(ies) that do not relate to the MIV application.

The following documents must be submitted with each MIV submission, as given in Table A below:
Hard Copy PRISM application form Table of Contents Checklist for MIV applications Table of Amendment Details MIV-specific Supporting documents Administrative (Module 1/Part 1) Other supporting documents Relevant CTD section(s) of the currently registered version with the proposed change(s) clearly annotated Current and proposed product labelling (annotated and pristine copies), where applicable * E-copies may be submitted via PRISM or CD-ROM. Yes Yes Yes Yes Yes Optional Optional Yes E-Copy N/A Optional* Optional* PRISM PRISM PRISM/CD PRISM/CD PRISM

When submitting the Checklist for Minor Variation Applications for Biologic Drugs , applicants must make the following declaration: Declaration of the applicant for MIV-2 I hereby submit an application for the concerned product to be varied in accordance with the proposals given above. I declare that There are no other changes than those identified in Section 0.4 Amendment Summary; The change(s) will not adversely affect the quality, efficacy and safety of the product; All Conditions for the notification(s) concerned are fulfilled; and, The required documents as specified for the notification(s) have been submitted.

HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP

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GUIDANCE ON MEDICINAL PRODUCT REGISTRATION IN SINGAPORE CHECKLIST FOR MINOR VARIATION APPLICATIONS (MIV-2) FOR BIOLOGICS

JANUARY 2009

DOSSIER REQUIREMENTS FOR BIOLOGICS MIV-2 Declaration of the applicant for MIV-2 I hereby submit an application for the concerned product to be varied in accordance with the proposals given above. I declare that (please tick the appropriate declarations) There are no other changes than those identified in Section 0.4 Amendment Summary; The change(s) will not adversely affect the quality, efficacy and safety of the product; All Conditions for the notification(s) concerned are fulfilled; and, The required documents as specified for the notification(s) have been submitted.

____________________ Applicants Name

______________________ Applicants Signature

_______________ Date

C1

Change of Contact Person Condition The product licence holder remains the same. Supporting Documents Particulars of the contact person updated in the on-line PRISM application 1) form.

C2

Change of Product Name Conditions There is no change to the product (formulation, specifications, manufacturing source and process) except the product name; No perceived conflict, confusion, or similarity to name(s) of existing medicinal products; New name does not imply (a) greater safety or efficacy than supported by clinical data, (b) superiority over a similar product in Singapore, (c) imply a therapeutic use for the product, or (d) the presence of substance(s) not present in the product. Supporting Documents 1) 2) 3) 4) Official letter authorising change of product name; A declaration from the applicant that there is no change to the product except name; Official letter of commitment to inform users of the relevant changes, and that the current product stocks will be exhausted before the product labelled with the new name is marketed; CPP.

C3

Change of Product Owner Condition The product licence holder remains the same. Supporting Documents

HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP

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GUIDANCE ON MEDICINAL PRODUCT REGISTRATION IN SINGAPORE CHECKLIST FOR MINOR VARIATION APPLICATIONS (MIV-2) FOR BIOLOGICS

JANUARY 2009

1) 2)

Official letter by the new product owner declaring the change, and authorising the local licence holder to be responsible for the product licence in Singapore; If the new product owner is not the manufacturer of the drug product, an official letter by the new product owner authorising the manufacturer to produce the drug product on its behalf.

C4

Change of Batch Numbering System Supporting Documents 1) 2) Official letter stating the commencement date of the change; Description of batch number system.

C5

Renaming (e.g. street name, postal code) of Manufacturing Site Condition The current manufacturing site(s) of drug substance, drug product, process intermediates, packaging, and/or batch release remains unchanged and at the same physical location. Supporting Documents Official letter authorising the site to perform the related activity (not required if 1) the manufacturer is the product owner); A declaration from the applicant that the manufacturing site remains the same, 2) and that the renaming does not involve changes of the manufacturing process and/or quality of the product; 3) Official letter stating the commencement date of the change; 4) GMP certificate with new name or address.

C6

Change of Batch Release Site Condition 1) 2) Batch release procedure is equivalent between the current and new site. Official letter authorising the site for batch release; GMP certificate of the new site. Supporting Documents

C7

Addition or Replacement of Secondary Packaging Site Supporting Documents Official letter authorising the new manufacturer to perform secondary 1) packaging; Evidence (i.e. GMP certificate) demonstrating that the proposed site is 2) appropriately authorised for the packaging activity concerned.

C8

Withdrawal of Manufacturer or Manufacturing Site Supporting Documents Official letter stating the withdrawal or deletion of the manufacturer or 1) manufacturing site to perform the related activity.

C9

Deletion of Pack Size for Drug Product Supporting Documents 1) No additional documents required.

C10

Change of Secondary Packaging

HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP

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GUIDANCE ON MEDICINAL PRODUCT REGISTRATION IN SINGAPORE CHECKLIST FOR MINOR VARIATION APPLICATIONS (MIV-2) FOR BIOLOGICS

JANUARY 2009

Conditions Conformance to current drug product release and shelf life specifications; The change is consistent with the dosage regimen and duration of use as approved in the PI. Supporting Documents Official letter stating that release and shelf life specifications, the container and 1) closure system compositions have not been changed; Justification that the change is consistent with the dosage regimen and duration 2) of use as approved in the PI. Change of Imprints, Bossing or Other Markings (except Score/Break Line) on Tablet or Printing on Capsule Including Addition or Change of Inks Used for Product Marking Conditions New markings do not cause confusion with other tablets or capsules; The inks are acceptable for pharmaceutical use; Conformance to current drug product release and shelf life specifications except for appearance. Supporting Documents A declaration from the applicant that that the release and shelf life 1) specifications (except appearance) of the drug product have not been changed; Official letter of commitment to inform users of the relevant changes, and that 2) the current product stocks will be exhausted before the new product is marketed; Detailed drawings and/or written descriptions of the current AND new imprint/ 3) bossing/ markings/ink/etc; 4) Drug product release and shelf life specifications. Change of Dimensions of Tablet, Capsule, Suppository or Pessary Without Change in Qualitative and Quantitative Composition and Mean Mass C12.1 Conventional dosage form, suppository and pessary C12.2 Critical dosage form and scored tablet Conditions No change in dissolution profile; Release and shelf life specifications of the drug product have not changed (except for dimensions). Supporting Documents C12.1 Conventional dosage form, suppository and pessary Detailed drawing or written description of the current and proposed 1) appearance; 2) Release and shelf life specifications of the drug product; Revised drafts of the package insert and labelling incorporating the proposed 3) variation (where applicable). C12.2 Critical dosage form and scored tablet 4) 5) 6) In addition to C12.1 Documents 1 to 3; Comparative dissolution data on at least one pilot/production batch of the current and proposed dimensions in accordance with HSAs drug registration guidelines; Justification for not submitting a new bioequivalence study according to the current Bioavailability and Bioequivalence guidelines; -

C11

C12

HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP

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GUIDANCE ON MEDICINAL PRODUCT REGISTRATION IN SINGAPORE CHECKLIST FOR MINOR VARIATION APPLICATIONS (MIV-2) FOR BIOLOGICS

JANUARY 2009

7)

Where applicable, data on the test for uniformity of content of the subdivided parts of tablets at release should be submitted and commitment to conduct the test at the end of shelf life, data should be provided only if outside the release and shelf life specifications (with proposed action).

C13

Change in the Colouring or Flavouring System of the Product Including Addition, Deletion or Replacement of Colourant(s) or Flavourant(s) Conditions Same functional characteristics, no change in dissolution profile for solid dosage forms; The colouring system must not have been rejected for pharmaceutical use; Conformance to current drug product release and shelf life specifications except for colour/flavour. Supporting Documents A declaration from the applicant that that the release and shelf life 1) specifications (except colour and/or flavour) of the drug product have not been changed; Official letter of commitment to inform users of the relevant changes, and that 2) the current product stocks will be exhausted before the new product is marketed; Official letter of commitment to conduct the appropriate stability studies of at 3) least three batches produced with the revised formulation in accordance with the relevant stability guidelines; 4) Detailed information of the colouring or flavouring agent; 5) 6) Revised product formulation; Drug product release and shelf life specifications.

C14

Quantitative Change in Coating Weight of Tablet or Weight of Capsule Shell Conditions No change in dissolution profile; Conformance to current drug product release and shelf life specifications except for weight. Supporting Documents A declaration from the applicant that that the release and shelf life 1) specifications (except weight) of the drug product have not been changed; Comparative dissolution data of at least one pilot or production batch of the current version versus the proposed version in accordance with HSAs drug 2) registration guidelines; for modified release products, also provide correlative data comparing in vitro and in vivo data; Justification for waiving requirements for a new bioequivalence study according 3) to the relevant guidelines; 4) Drug product release specification. -

C15

Change of Product Labelling due to Safety Updates: Note: Changes to safety information on product labels and package insert may be allowed without prior approval from HSA provided the changes fulfil the conditions stipulated below. Companies that need to disseminate safety information urgently can continue to do so through Dear Healthcare Professionals Letters, in consultation with HSA. Thereafter, product labelling should be updated in accordance with the labelling safety-related update notification system. Conditions

HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP

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GUIDANCE ON MEDICINAL PRODUCT REGISTRATION IN SINGAPORE CHECKLIST FOR MINOR VARIATION APPLICATIONS (MIV-2) FOR BIOLOGICS

JANUARY 2009

Addition of warnings, precautions, contraindications or adverse events/effects to the current product labelling, or Tightening of the target-patient population.

Supporting Documents A declaration from the applicant that no other changes have been made to the 1) labelling and that the change is supported by data. Change of Product Labelling Relating to: Addition/Deletion of Bar Code Replacement of Distributor Details Layout without Altering Text or Meaning Deletion of Indication (Note: Re-inclusion of the deleted indication in the future should be submitted as MAV-1 according to the prevailing requirement.) Addition/Deletion/Replacement of Pictures or Diagrams that do not Imply an Unapproved Indication Conditions No change to the text or meaning of the wordings; No unapproved indications, usages, dosage regimens or promotional information. Supporting Documents A declaration from the applicant that no other changes have been made to the 1) labelling. C17 Change of Product Labelling of Language(s) other than English Conditions No change to the text or meaning of the English wordings; No unapproved indications, usages, dosage regimens or promotional information. Supporting Documents A declaration from the applicant that the information in other language(s) 1) provides complete, accurate and unbiased information on the product and is consistent with the English version. -

C16

HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP

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