Amgen Australia Pty Ltd A B N 31 051 057 428

 Head Office: Level 7, 123 Epping Rd NORTH RYDE NSW 2113 (PO Box 410 NORTH RYDE NSW 1670) Tel + 61 2 9870 1333 Fax +61 2 9870 1344

 Medical Information: 1800 803 638

          

Submission in Response to the Consultation: Strengthening monitoring

of medicines in Australia  

         

01 May 2017 

       

Amgen Australia Pty Limited    

Level 7, 123 Epping Road NORTH RYDE NSW 2113

              

Execytjve summary

Amgen acknowledges that the Therapeutic Goods Administration's (TGA) consultation document on Strengthening Monitoring of medicines in Australia meets the some of the recommendations of the MMDR review. The proposals concerning the Black Triangle Scheme, the Improved Collection of Data and International Information Sharing appear intended to meet specific recommendations made by the MMDR panel. Whilst not a conclusion from the MMDR review, reformat of the Australian Product Information has been the subject of consultation in previous years. Amgen notes that the TGA is proposing to strengthen Compliance monitoring for pharmacovigilance obligations in addition, with the introduction of a Pharmacovigilance Inspection Program and Risk Management Plan Compliance Monitoring.

Amgen is concerned about lack of detail for many of the proposed activities in light of the proposed implementation time frame for the next steps. Significant consultation on the detail behind the proposed concepts is required for these initiatives to be effectively introduced. Further, there is extensive global governance of sponsor pharmacovigilance activities due to the international nature of good pharmacovigilance practices, which will require adequate time for revision of sponsor procedural documentation once the details are confirmed by the TGA.

In addition, it is important that changes being made to the post-market monitoring of medicines align with changes also occurring to the pre-market phases. Amgen encourages collaboration across the branches of the TGA to achieve this.

Introduction

About Amgen:

Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's largest independent biotechnology companies and is developing a pipeline of medicines with breakaway potential.

Amgen Australia contributes disproportionately to the global clinical trial effort by being in the top ten countries for active clinical studies and in the top five for interventional studies. At any one time, Amgen Australia is involved in approximately 25% of interventional studies in the global clinical trial program.

Through its significant clinical presence, Amgen Austral ia conducts on average two First in Human (FIH) studies every year and almost half of its clinical trial activity is in early phase research (PI­PII ). In 2016, we conducted 52 different studies at 96 sites across Australia and New Zealand, involving 1,108 patients trialing Amgen's innovative medicines.

Amgen is committed to taking an active role in contributing to future public policy that is relevant to biologic medicines and industry development in Australia.

Response to the specjfic jssyes rajseg io the consultati0 o Pocuroeot Amgen supports the response to the consultation document made by Medicines Australia. In addition we wish to make comment on the specific questions raised in the document. For ease of reference, our comments are provided below in tabulated form with reference to the section of the consultation document in the left hand column.

Comments on the Consultation Document: Strengthening monitoring of medicines in Australia

Enhancements

• Do the proposed criteria for inclusion in the Black Triangle Scheme appropriately target new medicines for which adverse event reports should be sought?

• What information, communication and education activities would assist health professionals and consumers to understand the Black Triangle Scheme and the importance of reporting adverse events for these medicines?

Comments

Amgen agrees that the proposed criteria for inclusion in the Black Triangle Scheme appropriately target new medicines for which adverse event reports should be sought. There should be a duration or other endpoint applied for inclusion of new chemical or biological entities in this scheme, otherwise it will simply become a default scheme for all products approved after the implementation date and dilute the message that the medicine is newly available. Amgen suggests that such an end point could be related to evaluation over time of adverse event reports received and consequent risk assessment.

Amgen encourages the TGA to be transparent about its criteria for determining the requirement for prioritised monitoring that is described in the consultation document.

No implementation time period for the Black Triangle Scheme is proposed in the consultation document. The requirement to implement newly applied Black Triangle warnings for existing products will need to take into account the lead time for generation of revised materials. As mentioned below, where the Product Information or Consumer Medicine Information are included in the pack of products there is an extensive lead time to implement changes to such materials. Amgen recommends that the TGA consults with sponsors and other providers of information materials to ensure that any proposed implementation time frames can be achieved. Further, as mentioned below, Amgen also considers it important that TGA tests its communication messages with healthcare professionals and consumers, and considers this should be done prior to implementation of the Black Triangle Scheme.

Amgen considers that messages concerning the role of the Black Triangle Scheme should be consistent and managed centrally. The TGA is ideally placed to develop and manage these messages. Amgen encourages the TGA to undertake user acceptance testing of any standard messaging wording to convey such information before its adoption to ensure it is appropriately understood by the intended audience.

 

It will be important that the messages about the Black Triangle Scheme do not create undue alarm about the role of the Black Triangle in encouraging adverse event reporting for medicines with a demonstrated positive benefit/risk balance. Additional messages may also be required for products approved through the expedited pathways. The messages should be consistent with Quality Use of Medicines principles.

• Are the proposed changes to the Product Information (PI) leaflet useful for health professionals?

Amgen supports changes that improve the utility of the Product Information format to healthcare professionals, and notes that the current format of the PI is inconsistent with the approach taken in many other regulatory jurisdictions that have revised prescribing information format to include clinically relevant information at the beginning of the document. Amgen recommends that TGA establish a baseline measure of utility of the current format PI in order to assess the impact of the proposed changes once they are implemented.

In the digital technology era Amgen is concerned at the description of the Product Information as a leaflet. It is important that healthcare professionals have timely access to current Product Information. In particular, the current TGA requirement that a PI be physically included in the packs of injectable medicines is incompatible with providing current information in a timely manner, as the lead time for producing revised leaflets and having them flow through the supply chain to be available to the end user is extensive and partially outside the sponsor’s control. The optimal method of ensuring timely update of PI content is to do this in an electronic format. Further, the requirement for self injectable medicines to include the PI rather than the CMI does not reflect the user of the package. Amgen encourages the TGA to explore the appropriateness of novel mechanisms of provision of PI/CMI at the point of product use, such as inclusion of quick reference codes on product packaging or reference to information provided in patient support programs, and to ensure that the revised regulatory practices are forward looking in being able to adapt to future technology changes.

• What support will sponsors need to comply with the new format and what are achievable timelines for implementation of the new format?

The consultation paper provides no detail on the new format, but it is expected that the proposal for the new format will align with that currently in place in the European Union. Amgen encourages the TGA to align the content of the PI with globally accepted norms and not to require specific Australian content unless

Comoliance

• What activities could TGA undertake to assist sponsors in complying with their pharmacovigilance requirements?

there is a strong, evidence based rationale. For example, the adverse reaction section of the Pl should align with the globally accepted CIOMS format rather than the current requirement for specific AE tables that are often uniquely prepared for Australia. Amgen also notes that the format of the New Zealand data sheet was recently changed, and encourages the TGA to work with Medsafe on harmonised requirements for the Pl and data sheet in order to support regional supply chain efficiencies.

Consistent with good pharmacovigilance principles, companies have robust governance procedures in place for changing country prescribing or patient information content. These procedures can involve significant multi layer reviews of changes and will require a lengthy transition period. In addition, transitions need to take account of reformatting vs content change and whether the TGA will be reviewing any new content. Although more detail is required in order to provide an accurate estimate of achievable timelines for implementation of the new format, it would not be less time than is required to implement new product labelling formats, for which a four year transition time was adopted.

Comments

It is important the TGA is absolutely transparent in detail about pharmacovigilance requirements. Availability of specific details with respect to pharmacovigilance inspection guidance and advice on the TGA's website or as an additional section to the Australian requirements and recommendations for pharmacovigilance responsibilities of sponsors of medicines version 1.3, June 2014 would be of benefit to prepare companies regarding inspection conduct and expectations. For example, the TGA expectation that a variation will be submitted within 6 months from identification of any safety related issue is not documented in any public domain information, but the TGA presentation of results from the pilot PV Inspection Program at the May 2016 ARCS Scientific Congress noted that this was considered an audit finding 1. Published de­identified outcomes of inspections could be used as an additional source of information for companies to evaluate compliance impact, and can be used for benchmarking purposes to improve and streamline current existing process with what is considered industry best practice.

1 Presentation available at http://www.tga.gov.au/presentation-tga-pharmacovigilance-inspection-pilot-program-2015-2016, accessed 26 April 2017

 

Further to routine pharmacovigilance inspections, a suggested approach could be for the TGA to propose for compliant companies to self-regulate, once compliance has been intensely demonstrated following a pre-determined number of inspections and periodic satisfaction of a standard list of key compliance indicators. As a potential deterrent for sponsors, an additional activity the TGA could consider could include increased visibility of extent of fines imposed for non-compliance.

The consultation document is silent about any costs associated with the proposed inspection program. Given that the TGA is fully cost recovered, Amgen encourages the TGA to be transparent about the mechanism for funding the enhanced compliance activities. In the event that there will be direct costs of an inspection, which has not occurred in the past, this will have budgetary impact for sponsors and should be communicated in sufficient time to allow for industry financial planning cycles.

Amgen notes that RMP evaluations within Category 1 applications are already protracted, and miss evaluation milestone due dates. We encourage the TGA to ensure that the proposed changes to its approach for pharmacovigilance compliance are adequately resourced, without adverse impact to other activities within the Pharmacovigilance and Special Access Branch, or other branches, of the TGA.

• Is the information regarding RMP requirements included in the AusPARs sufficient to inform you of the risk minimisation and pharmacovigilance commitments that have been made by the sponsor?

Amgen agrees that the information currently published in AusPARs provides sufficient information regarding RMP requirements for medicines. As outlined in our response to the consultation on the Provisional Approval pathway, Amgen does not agree with publication of progress against confirmatory efficacy studies through the RMP Compliance Monitoring Process.

• What activities could we undertake to assist sponsors in complying with their RMP requirements?

Amgen encourages the TGA to develop an integrated approach to reviewing and approving RMPs that aligns with the prescription medicines evaluation processes (including new or revised processes associated with the expedited pathways to be introduced), as currently RMP evaluations are protracted and regularly miss review times. Whilst Amgen supports the proposal to proactively monitor RMP compliance, we consider it equally important that TGA adopt an efficient process for managing RMP content both within major evaluations but also for updates outside evaluation processes, so that both the sponsor and TGA have a clear and agreed understanding of the approved content of RMPs.

Amgen recommends that the TGA provide additional clarification regarding the precise trigger points for RMP updates and submissions, in order to avoid misinterpretation.

The current TGA guidance materials indicate that an updated RMP should be submitted to the TGA when there is a significant (material) change to the RMP. Amgen seeks clarification on the requirement that sponsors seek agreement with the TGA to make any changes to the RMP - does this mean proactive agreement in every case or in certain circumstances to be further elaborated?

Additional comments Comments

Amgen welcomes the introduction of a new system that will streamline the reporting of adverse events and commends the approach of aligning with global reporting standards. Will the change from the Adverse Drugs Reporting System to the Adverse Events Management System have any impact on current reporting mechanisms for sponsors, and will this require any transmission methodoloav changes (E2B, XML, etc)?

Amgen notes the TGA's intention is to use the feedback from the current consultation, which closes on 1 May 2017, to inform implementation of the Medicines Vigilance Framework during the period between September 2017 and January 2018. The consultation document provides very little detail for activities that have significant global compliance impacts. Amgen encourages the TGA to rapidly consider feedback from the current consultation and to consult with sponsors on the detail of changes over the coming four months in order to allow adeauate time for sponsors to revise their processes.

As a point of principle, Amgen encourages the TGA to effectively measure the impact of changes proposed to be introduced as a result of this consultation document and use the results to drive continuous improvement of practices by all stakeholders in the collaborative activity of post-market monitorina.