ensuring compliance with regulatory requirements in a

Ensuring Compliance with Regulatory Requirements in a Global OrganisationAndrew DeavinDirector, Global Regulatory Affairs

18 September 2015, International Good Submission Practice Workshop, Taiwan

Challenges and opportunities

Challenges:Rapidly evolving regulatory requirements worldwideLarge global organisation with many stakeholdersStrategies still largely driven out of EU and/or USA

Large organisations with 1000’s of licences worldwide

Opportunities:Large global organisations have capacity to obtain

information and meet requirements in many markets simultaneously

But this needs to coordinated

218 September 2015Compliance in Global Organisations

Development, registration, life cycle and cancellation

1. Gather Intelligence and information on new requirements1. Build strong intelligence networks2. Build close connections between local RA and central RA3. Inform the organisation about changes to legislation and implement

2. Submit high quality dossiers and measure success1. Build high quality dossiers that meet the requirements2. Establish clear and robust processes that are updated/reviewed regularly3. Measure and monitor through Key Performance Indicators

3. Ensure changes to dossier in life cycle are reported1. Effective change control process

4. Reduce the regulatory footprint1. Cancel unwanted licences

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How does industry meet the challenges and opportunites



1.0

Gather Intelligence and Information on New Requirements

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Build Strong Intelligence Networks

Strong intelligence networks

Gather intelligence

RA Structure

Central Coordination

Internal Databases


Local teams in place in country with detailed knowledge of local requirements; Central teams with detailed product knowledge

Through Trade Associations, electronic databases (external and internal, see below) and web searches

LOC* informs central repository through notification system that automatically informs all key stakeholders for regulatory intelligence

To assess intelligence and decide on actions to take – inform and implement

*LOC = Local Operating Company

Helpful if Authorities issue bulletin to share with

Industry planned changes in regulations and a

structured system to collect comments

How a global organisation can link together

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And seek to maximise expertise across the organisation


Central GRA*

Regional Hub 1

Regional Hub 3

LOCs in region 1

LOCs in region 3

Detailed product knowledge;

understanding of global impact

Strong coordination and

linkage

Local registration expertise e.g.

regulatory intelligence of local legislation

changes

*GRA = Global Regulatory Affairs

Approach of GSK and Other Organisations

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Methods to inform the organisation


• Systematic updates to regulatory organisation and other stakeholders (verbal)

• Regular newsletters

• Specific targeted email/communications

• Poster presentations

• Update or create new relevant procedures and conduct appropriate training amongst stakeholders

Processes

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Well written, clear processes are critical to an organisation


• Process built around critical legislation and policy principles

• Written in clear and simple language with clear accountabilities

• Critical requirements in high level control document e.g. Standard Operating Procedure (SOP)

• More details in lower lever control document e.g. guideline or working instruction

• Training– Plan training in advance– Ensure that the right people are being trained– Ensure that the person has the right level of training as some may need more in depth

training than others given the role they play

• Important – Ensure training records are updated/recorded – auditable evidence of right skill set for each Regulatory Professional


2.0

Submit high quality documents and measure success

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Three parts to a dossier


• Technical Regulatory File – Submitting same dossier everywhere – Important for

• Maintenance (makes knowing what you have submitted easier to manage)

• Authorities know reviewing same level of detail as in all countries– ICH CTD is widely accepted format but other formats exist e.g. ASEAN CTD

• Packaging/label– Variable requirements

• Country specific items and product samples for testing– Variable requirements– GMP cert, declarations, CPP etc….

Ensuring high quality submissions that meet requirements

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Dossier writing


• Develop templates for CTD modules and templates that detail the information needed in each section and the supporting international requirements (i.e. ICH)

– Ensures that the right information is included and that this is consistent from product to product even if different writers

• Ensure writers are trained in the templates and know what is expected

• Ensure accuracy of source documents

• Provide the right network and opportunities to consult during the writing process

Ensuring high quality submissions that meet requirements

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Dossier Review


• Review is critical – describe in process

• Data generators to review dossier to ensure the that information given is correct (data generator and dossier writer may be different especially in large global companies)

• Senior level sign off to ensure consistency across products

• Checks and sign-off before publication– Content structure determined in advance and agreed before writing starts

Consult Regulatory Authorities

• Consult Regulatory Authorities in pre-submission meetings

• And Regulatory Authorities to provide opportunities for companies to consult in advance


Samples and Country Specific Requirements


• Variable requirements worldwide

• Difficult to manage and often incur delays and complexities for submission of new applications and variations

• Electronic tools to record and track requests of country specific requirements very useful for management

• Convergence of requirements is important to reduce complexity

LOC inputs request electronically for country specific requirements

Central team confirms request and each item tracked

Tracking visible to both LOC and central team which allows a more effective follow up

Central team gathers information and inputs into tracker


3.0

Ensure changes to dossier are identified and reported

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Assessing changes to regulatory information

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A robust change control system


• Change control system involves many different players– Site Conformance, Quality, Quality in Research and Development as well as

Regulatory

• Robust processes, with all stakeholders and roles clearly identified and appropriately trained

• Different companies approach in different ways– Some send to all markets for an initial assessment– Others do a general assessment first

• e.g. assessed against most comprehensive dossier and most comprehensive variation requirements e.g. Europe, USA, Canada

• But ultimately all changes need to be sent to all registered markets and assessed for regulatory action

– Experts in market need to decide if regulatory action needed based on dossier content and local legislation/requirements


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Recording the change in a regulatory database


• Need a comprehensive regulatory product data base – Which tracks and records submissions and approvals of all variations (or if

no submission necessary)– Should indicate if the change can be implemented before, at submission, at

approval

• Aim to have the same change authorised across all registered markets

– Sometimes a specification is not approved or modification made that is unique to one market

– In which case need a database to record the registered details in each market – often core registered details (not necessarily all parts of the dossier)

– Unique differences then need to be communicated to manufacturing and incorporated into market specific requirements


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Lot release


• Each time a lot is released to market, quality need access to comprehensive database to decide if the lot being release conforms

– i.e. confirm that all changes impacting the lot have been approved

• Challenge!

• Timelines for changes worldwide are highly variable – Can take 3m to 12-24m depending on market – Leads to overall time for approval of one change ~3yrs. – Makes management of changes and supply very complex

• And can have significant impact on a company’s ability to supply product in conformance with its licence



• Process and timelines for NCE important

• BUT equally and perhaps more important is life cycle management impacting timelines for supply

•e.g. Labeling/safety; new indication; process modifications/new sites

• Regulators need to speak with one voice

•consistent interpretation of requirements

• Variable interpretations, unclear regulations and guidancesare challenging to manage


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Regulators have a role in this….


• That its why it is important that regulators….– Look at ways of reducing timelines for assessing changes and

making assessments more efficient– Look to utilise other regulators’s expertise and decisions to maximise

review resource– Seek to align timelines for changes – better for all– Seek convergence of requirements and decisions across

regulators/across regions (leading to same product registered details across regions and for all customers)

• Global guidance is important for convergence, such as:• WHO (TRS 993, Annex 4) ‘Guidelines on changes to approved vaccines’ [final] • and ICH Q12 ‘Technical and Regulatory Considerations for Pharmaceutical

Product Lifecycle Management’ [draft stage, adoption 2017]

“One product for all”


4.0

Reduce the regulatory footprint

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Reduce the regulatory footprint


• Companies should periodically assess the need to maintain licences

– e.g. for presentations that are no longer marketed– Need to ensure that not patient need, no impact on clinical trials, etc.– Cannot cancel whilst product still on market

• Important– Cancellation does not mean an issue with product – if no sales and no

patient need, why maintain?– Reduce maintenance needs and complexity – Allows the regulatory team to focus on what is important for public health– Reduce compliance risks associated with old licences


5.0

Measuring Performance and Addressing Issues

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How can performance and compliance be measured?


• Key Performance Indicators (KPIs) can be established

• For example, monthly reports on:– Measure of Output - Number of RA activities dispatched per month (by

Central team)– Measure of Workload - Number of RA activities forecasted per month– Measurement of approval time

• Trends can then be generated based on KPI reports e.g.:– Number of activities past their due date– Number of activities that are unplanned– % of activities with upcoming planning dates

When issues occur….

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Learn from them!


• We need to learn from them – e.g. requirement not followed by part of the organisation, new requirement

not identified

• Need to perform reviews of what went wrong

• May require revisions to existing processes or development of new processes or re-training programmes

• Perform internal audits and checks on quality of data – Internally in regulatory department as well as at a corporate level. – Findings addressed as Corrective and Preventive Action (CAPAs) that

require follow up resolution within a defined timeframe

Conclusion


• Large organisations are complex but have capacity to assess significant amounts of information and supply many high quality registrations

• Consistent quality and communication can be issues but is addressed through

– Robust processes in line with latest requirements (regular review)– Measurement of performance (and correction when issues identified)– Connected Regulatory organisations– Communication mechanisms to inform the organisation of changes

• Convergence of requirements is very important

• Regulatory Authorities and Industry must work together, using converged regulatory mechanisms, to deliver safe and efficacious products for the benefit of patients worldwide

Thank you

ensuring compliance with regulatory requirements in a

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