GUIDELINE ON THE SUBMISSION OF RISK MANAGEMENT PLAN DOCUMENTS

Transcription

1 APPENDIX GUIDELINE ON THE SUBMISSION OF RISK MANAGEMENT PLAN DOCUMENTS This document is intended to provide guidance on the submission of risk management plan (RMP) documents in support of NDA, GDA and MAV applications. 1 SUBMISSION REQUIREMENTS FOR DIFFERENT APPLICATION TYPES The submission of RMP documents in support of all NDA-1 and biosimilar applications is mandatory. For other product application types, such as NDA-2/3, MAV or GDA, HSA may also request for the submission of RMP documents on a case-by-case basis following the evaluation of the application dossier. 2 DOCUMENTARY REQUIREMENTS The required RMP documents should be attached in PRISM, Section 7 (Supporting Attachments) under Other Supporting Documents. The submission of the documents in hardcopy is not required. 2.1 NDA-1 and Biosimilar Applications RMP documents required in support of NDA-1 and biosimilar applications should be provided as part of the application dossier at the point of application submission. The RMP documents should include the following: a) Singapore-Specific Annex (SSA); b) Latest version of the approved EU-RMP and/or US REMS (where available); and c) Proposed local RMP materials (e.g. draft educational materials, if any). Please refer to Annex I for further details on the vigilance requirements for biosimilar applications Singapore-Specific Annex (SSA) The SSA serves as documentation of the RMP to be implemented for the medicinal product in Singapore. A SSA template has been provided as Annex II of this appendix, to guide companies in the drafting of the SSA. The SSA template should include the following sections: Product information (product name and active ingredients); Safety concerns (important identified and important potential risks); Description of the proposed local pharmacovigilance activities; Description of the proposed local risk minimisation activities; and Additional information (if applicable). HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP Appendix - Page 1 of 8

2 2.1.2 Proposed local RMP materials If a medicinal product has been identified to be associated with safety issues that could be prevented or minimised with close monitoring, additional risk management plans in the form of the following local RMP materials may be proposed. Examples include: Provision of physician educational material(s); Provision of patient medication guide(s); and/or Issuance of Dear Healthcare Professional Letter. For more details on the content of the SSA, supporting RMPs, and local RMP materials, please refer to the Guidance for Industry Post-marketing Vigilance Requirements for Medicinal Products. 2.2 Other Application Types (NDA-2/3, GDA, MAV) For other application types, routine submission of RMP documents at the point of application submission is not required. However, if deemed necessary, the company will be informed about the RMP documents that are required in support of the application during the evaluation process. 3 TIMELINES FOR SUBMISSION 3.1 NDA-1 and Biosimilar Applications RMP documents required in support of NDA-1 and biosimilar applications should be provided as part of the application dossier at the point of application submission. For applications submitted via the full or abridged route, if the applicant is unable to submit the complete RMP documents before the acceptance of the application, a letter of commitment to provide these documents within 40 working days from the date of application acceptance will be required. If the documents are not received within the 40 working days, an Input Request (with corresponding stop-clock imposed) will be sent to the applicant for the submission of the RMP documents. For applications submitted via the verification route, the complete set of RMP documents has to be submitted prior to the acceptance of the application. 3.2 Other Application Types (NDA-2/3, GDA, MAV) RMP documents requested by HSA in support of NDA-2/3, GDA, or MAV applications should be submitted within the timeline specified in the Input Request. HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP Appendix - Page 2 of 8

3 4 UPDATES DURING EVALUATION STAGE During HSA s product application evaluation, if a new version of the EU-RMP and/or US REMS that was provided to HSA as part of the application dossier becomes available, it should be submitted to HSA upon receipt of the updated information to facilitate the timely review of the application. The relevant updates should be highlighted to HSA in a cover letter. 5 FINALISATION OF RMP DOCUMENTS RMP documents will be reviewed together with the application dossier and the final local risk management activities to be implemented in Singapore will be discussed during the evaluation process. All local RMP materials to be implemented in Singapore will have to be finalised before approval of the product application. 6 POST-APPROVAL UPDATES/AMENDMENTS Post-approval revisions to the approved local RMP materials (e.g. educational materials) should be submitted for review and approval by HSA should be obtained prior to distribution to the physicians and/or healthcare professionals. However, for revisions that do not affect the safety content of the local RMP materials (e.g. editorial changes, administrative changes, corrections of typographical errors, and changes in address), a notification to HSA with the soft copy of the revised materials will be sufficient (i.e. approval from HSA is not needed). All revised local RMP materials should be submitted via to [email protected]. HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP Appendix - Page 3 of 8

4 ANNEX I The post-marketing vigilance requirements outlined below are required for biosimilar products seeking product approval in Singapore. 1 ADVERSE REACTION (AR) REPORTING All fatal or life-threatening spontaneous ARs occurring in Singapore that arise from the use of the biosimilar product should be reported to the Vigilance and Compliance Branch as soon as possible but no later than 7 calendar days after first knowledge by the product licence holder, followed by as complete a report as possible within 8 additional calendar days. All other serious spontaneous ARs occurring in Singapore that arise from the use of the biosimilar product should be reported as soon as possible and no later than 15 calendar days after first knowledge by the product licence holder. The clock for reporting starts as soon as any personnel of the product licence holder, including sales representatives, is aware of the ARs. When submitting the AR report, the brand name and batch and/or lot number of the biosimilar product should also be provided. The product licence holder should follow up on the information if they are not available in the initial report. 2 SUBMISSION OF PRODUCT BENEFIT-RISK EVALUATION REPORT (PBRERs) Routine submission of PBRERs may be requested for biosimilar products. Where requested, the frequency for submission of PBRERs to HSA should be at intervals of six months commencing from either the international birthdate or date of registration of the biosimilar product locally, for a period of two years; and thereafter, annually, for the next 3 years unless otherwise specified. 3 RISK MANAGEMENT PLANS (RMPs) Submission of RMP documents in support of all biosimilar applications is mandatory. RMP documents should be provided as part of the submission dossier at the point of product application. The RMP documents should include the following: a) Singapore-Specific Annex (SSA); b) Latest version of the approved EU-RMP and/or US REMS (where available); and c) Proposed local RMP materials (e.g. draft educational materials, if any) HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP Appendix - Page 4 of 8

5 4 EDUCATIONAL MATERIALS AND DISTRIBUTION RECORDS 4.1 EDUCATIONAL MATERIALS FOR PHYSICIANS AND/OR PATIENTS Educational materials for physicians and/or patients (e.g. physician educational material, patient medication guide) may be requested as part of risk management plan for biosimilar products. The objective of such materials is to inform physicians and/or patients of the identified and potential risks associated with the use of these products and to educate them on the early detection of ARs. For physician educational materials, there should also be a paragraph to remind physicians of the following: Information regarding interchangeability; The importance of keeping good records of patients who are prescribed the biosimilar product (including the batch number) for traceability purposes in the event of safety/ quality concerns; and To report ARs (including brand name and batch and/or lot number) associated with the biosimilar product to the product licence holder and HSA. The educational materials (for physicians and/or patients) should be submitted to HSA for approval prior to their dissemination to healthcare professionals. Subsequent revisions to the materials (e.g. new safety information) are to be submitted to HSA for approval prior to dissemination. However, for revisions that do not affect the safety content of the educational materials (e.g. editorial changes, administrative changes, corrections of typographical errors, and changes in address), a notification to HSA with the soft copy of the revised materials will be sufficient (i.e. approval from HSA is not needed). All revised educational materials should be submitted via to [email protected]. Please refer to the Guidance for Industry Post-marketing Vigilance Requirements for Medicinal Products for further details on the requirements for educational materials. 4.2 DISTRIBUTION RECORDS The product licence holder should ensure that all healthcare professionals who will be prescribing the biosimilar product are provided with a copy of the latest approved physician educational materials (where applicable). Copies of the latest approved patient educational materials and medication guides, where applicable, should also be made available to healthcare professionals for distribution to all patients who will be supplied with the biosimilar product. The product licence holder should keep records of the distribution of the educational materials to healthcare professionals. The distribution records should include: Names of the healthcare institutions//clinics/pharmacies receiving the educational material(s); and Date of distribution of the educational material(s) When requested by HSA, the product licence holder will be required to provide the distribution records for compliance check purposes. HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP Appendix - Page 5 of 8

6 5 PRODUCT SALES DATA The product licence holder is required to provide sales data of the biosimilar product, in terms of number of units of product sold and the buyer categories (e.g. restructured hospitals, private hospitals, specialist clinics, general practitioner clinics) on a quarterly basis to HSA. These data will be used to estimate the local exposure to the product. When requested by HSA, the product licence holder will be required to provide the list of buyers for their biosimilar product for compliance check purposes. Please refer to the Guidance for Industry Post-marketing Vigilance Requirements for Medicinal Products for further details regarding the above PV requirements. HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP Appendix - Page 6 of 8

7 Singapore-Specific Annex (SSA) Template ANNEX II I Product Information Product name: Active ingredient(s): e.g. ABC123 e.g. safetyzumab II Safety Concerns To list the important safety concerns relevant in the Singapore context. Important identified risks (an untoward occurrence for which there is adequate evidence of an association with the medicinal product) e.g. Drug-induced liver injury (DILI) Severe cutaneous adverse reactions (SCAR) Heart failure Myopathy Rhabdomyolysis Elevated liver enzymes (ALT and AST) Important potential risks (an untoward occurrence for which there is some basis for suspicion of an association with the medicinal product) e.g. Malignant cell growth (haematological malignancy) QT prolongation Peripheral neuropathy Potential medication error/ dispensing error Unknown safety in special populations (e.g. elderly, immunocompromised patients, patients who are renally impaired or with hepatic dysfunction) III Description of the Proposed Local Pharmacovigilance (PV) Activities To describe the PV activities (routine and/or additional), relevant to the local context, that are planned to address the safety concerns. (A) Routine PV Activities [required for all products] Please refer to the Guidance for Industry Post-marketing Vigilance Requirements for Medicinal Products on the respective timelines for the following routine PV activities. Reporting of local serious adverse reactions to HSA in accordance with stipulated timeline Timely update on significant safety issues that may influence the overall benefit-risk profile of the product Timely update on safety-related regulatory actions taken by other agencies, particularly HSA s reference agencies (i.e., Australia TGA, EMA, Health Canada, UK MHRA and US FDA) HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP Appendix - Page 7 of 8

8 (B) Additional PV Activities Where applicable, to include planned date for such activities. If no additional PV activities are considered to be required, it should be indicated as such (i.e. Nil ). Examples: Active soliciting of local serious adverse reaction reports, post-authorisation safety studies (applicable to local context), drug event monitoring, exposure registries e.g. To conduct active soliciting of local serious adverse reaction reports associated with the use of ABC123 from physicians who prescribe the product. Solicited local serious adverse reaction reports will be complied on a quarterly basis and submitted to HSA. (e.g. end of March, June, September, December) IV Description of the Proposed Local Risk Minimisation Activities (RMAs) To describe RMAs (routine and/or additional), relevant to the local context, that are planned to address the safety concerns. (A) Routine RMAs [required for all products] Provision of warnings and precautions in the package insert Timely safety updates to labelling and packaging of products (B) Additional RMAs If no additional RMAs are considered to be required, it should be indicated as such (i.e. Nil ). Examples: Provision of physician educational materials and patient medication guides, provision of sales data, issuance of Dear Healthcare Professional Letter, restricted access programme, controlled distribution, pregnancy prevention programme e.g. Physician educational material is developed to highlight the identified safety concerns, signs and symptoms to look out for and to highlight on the potential risk of medication error/dispensing errors A patient medication guide is developed to highlight the identified safety concerns, signs and symptoms to look out for and when to seek medical attention A Dear Healthcare Professional Letter will be issued to reinforce the significant safety concerns at product launch. V Additional Information To list the RMP documents enclosed in this application and to provide other comments (if any) e.g. The following RMP documents are enclosed in this application for your perusal: Latest version of the approved EU-RMP (i.e. version 2.1) Draft physician educational materials and patient medication guide Draft Dear Healthcare Professional Letter Last updated: Apr 2015 HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP Appendix - Page 8 of 8