PowerPoint Presentation© Copyright 2019 Covance Inc.
Best Practices and Points To Consider for Small-Medium Bio-Pharma Companies June 3, 2019
Speaker: David Balderson, Head of Global Safety Operations
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Agenda
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Process documentation • Internal vs external
Safety database • Need for a single source • Single vs multi tenancy
Coordinating submissions • Regulators, sites and IRBs/ECs
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What do I need to think about?
RSI management and IB updates • Managed through IB or separate DCSI?
Annual reports • DSUR, IND Annual Report • Coordination with the RSI!
Review of all safety data • Access to data, process and documentation
Meeting the 2012 IND Rule & Guidance • Safety Assessment Committee
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Where are we going?
Commercialization strategy is key • Going it alone or through partnerships? • Will I try to control the partner …?
Country & region specific considerations • Europe, Japan & China all need local presence and expertise • LATAM, ME&A becoming more complex
Increasing adoption of many EU requirements • QPPV, PSMF, RMP
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Qualified Person(s) for Pharmacovigilance & PV System Master File Both originally EU requirements
• QPPV: single person accountable for global activities • PSMF: documents the global PV system
Now expanded to many countries/regions • Even EU countries require a local QP
Practical implementation • For QPPV can’t have everyone ‘influencing the PV system’
MHRA interpretation post-Brexit? • For PSMF, use of regional/local annexes
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Management of Expectedness in Clinical Trials
Key driver behind critical findings from MHRA over past 2 years
RSI is tied to the protocol and conduct of the study • needs to be identified in the CTA • can be Section 4.8 of SmPC for approved products • needs an amendment if changed
Can’t just change expectedness based on a new IB • prior association with DSUR no longer applies • must submit an amendment for a change in what you consider expected
and wait for it to be approved …!
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IND Safety Reporting Guidance & The Safety Assessment Committee Intent of 2012 Rule update was to reduce the volume of INDSRs
primarily by using the sponsor’s causality assessment as driver for reporting
• Differential reporting between US and elsewhere
In 2015 draft guidance introduced concept of a Safety Assessment Committee to identify need to report INDSRs based on aggregate data
• Need to look at aggregate data in an unblinded/semi-blinded manner • Similar to DSMB/IDMC but not study specific
Adoption of SACs has been limited due to process and resourcing concerns
• Unblinding is a challenge to trial integrity • For smaller organizations in particular, assessment independent from
product teams is difficult to resource
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Key drivers for decision making Global footprint
• I can build in the US, but elsewhere? • Commercialization strategy is key
Investment in talent • Cost of PV subject matter experts and physicians • How do I scale?
Core vs non-core activities • Few organizations currently perform PV Ops work in-house • Database hosting and management • Retain key decision-making in-house, e.g. signal detection?
Although the SAC model for data review lends itself to external management … • Many have adopted a hybrid ‘delivery out / review and decision-making in’ model
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Key drivers for decision making
If outsourcing, consider the following • Does their footprint match your strategy? • Do they have the necessary niche capabilities?
e.g. QPPV, PSMF, RMP • What about capabilities to support higher-level tasks?
SAC support, signal detection • Do I get a single global safety database that I can access? • Are call center capabilities a factor? If so, which geographies? • If work is done offshore, can they provide onshore support? • How do they support inspections?
15CONFIDENTIAL
Bill Haddock, MD, MPH
B Haddock MD, MPH
The presenter is an employee of Ovid Therapeutics Inc and owns stock in the company.
The opinions expressed in this presentation are those of the presenter and not those of Ovid Therapeutics Inc.
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Topics
• Small vs Large Biotech engage vendors differently • Scope of Work • Request for Proposals • Checklist for engaging PV services • SOPs & Safety Management Plan • Safety IT • Oversight of CRO
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Small/Medium/Large Biotech retain internal safety decision making, analysis and risk management
Rationale - Gain efficiencies and capacity by leveraging external expertise/resources
Difference is Small Biotech = Limited staff (< 100)
• Multiple people covering multiple responsibilities • Outsource MOST safety services including safety database (SDB)
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• Creation and implementation of Safety Management Plan (SMP) • SUSAR processing including medical review • SAE reconciliation • Signal Detection Plan • Creation of aggregate safety reports (eg, DSUR) • Regulatory intelligence to assess evolving regulations
• Out of Scope • Medical review of legacy cases • Regulatory reporting
• ICSR and Aggregate report submission • *Submission of SAEs to CECs/IRBs, investigators
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B Haddock MD, MPH
Worldwide reporting ex Japan, China, etc.
Case processing for Clinical trials (eg, SAEs)
Aggregate Report Writing
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B Haddock MD, MPH
expertise &
experience
Greater reliance on CRO experts More efficient to leverage multiple experts using a single CRO
Sponsors oversees
PV Processes
Oversee CRO process for case narratives Sponsor reviews CRO drafts of SAEs/SUSARs Sponsor reviews CRO Signal Detection Plan
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*GAMP® 5 – A Risk-Based Approach to Compliant GxP Computerized Systems. Tampa, FL: 964 GAMP Forum, International Society for Pharmaceutical Engineering (ISPE); 2008.
CRO IT expertise essential for Small Biotech
B Haddock MD, MPH
Integrity • IT Service Availability and
Business Continuity
• Leverage Pharmaceutical And IT Industry Standards and Good Practices
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• PV Startup with CRO • Project management • Safety Database implementation
• Data Migration to safety database • Safety and Quality Management Plans
• Bridging Sponsor SOPs/processes with CRO SOPs/policies
• CRO PV support for Clinical Trials & Post market drugs
• Project Management • Safety Database Cloud (Hosting)
Services • SAE Case Processing; • Assistance with SUSAR/SADR reporting • SAE Reconciliation • Aggregate Reporting • Signal Detection • Business continuity • Quality and Compliance Management
B Haddock MD, MPH
• Scope of Work • Request for Proposals (RFP)
• Duration of collaboration (eg, 3 year contract)
• Verify CRO expertise • Check their references • Technical expertise (ex CVs) of assigned staff • Tenure of vendor's senior managers and technical staff
B Haddock MD, MPH
At BID defense
• Negotiate Quality metrics for milestone payments • monthly, quarterly, etc.
• Specify Audit Plan • Validation of processes prior to initiation • Audit 1 year after system initiation • For Cause audits • UAT testing
B Haddock MD, MPH
B Haddock MD, MPH
SAE Report Form receipt
SAE/SUSAR Submission by CRO/Sponsor
Aggregate Reporting by CRO/Sponsor
B Haddock MD, MPH
Select best provider and establish clear scope of work •Engage vendor at bid defense •Ask about small biotech experience
(eg, % small companies) •Check small biotech references
1 Engage CRO across broad range of services – Do not just delegate •Integrate CRO into internal processes,
participate in CRO processes
2 Fully engage CRO as partner to keep each party accountable •Audit vendor processes regularly (may
need to outsource audit) •Define contingency plans in case one
party does not comply •Identify and address company-vendor
relationship inefficiencies
3 Map processes involving CRO and Sponsor •Flowchart details of information
exchange is key •Weekly dashboard essential to
monitor key processes •Updated Reporting instructions
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Flowcharts key to implementing and correcting processes for CRO interactions – DO NOT SKIMP ON THIS
Not shown- Timelines for reporting SAEs and SUSARs
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• Recommend weekly Dashboard process to monitor • Site list with investigators, Study coordinators, and CRAs for EACH
study • Signal Detection
• AE listings • SAE reconciliation with Clinical CROs and Corporate Partners • Version control of key documents
• Investigator Brochure • Protocol • ICF
• Check Email Distribution list for SAEs and SUSARs at least monthly • Mock SUSARs to test system if low volume of SAEs and SUSARs
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Continuously update your organization • Drug safety requires cross functional collaboration
• Inform your organization on a regular basis… • Continuously update them on safety processes • Listen and respond to feedback internally at every opportunity • Seek to understand how safety and other processes interact • Inform team of key compliance issues and Safety Regulatory guidance
• Set up an Open House to showcase what you are doing… • DO NOT WAIT until something goes wrong…
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Summary: CROs services for Small vs Large Biotech • Small Biotechs have
• Fewer staff who oversee multiple functions • Fewer processes, less structure
• CRO services for Small Biotech broad in scope • Greater reliance upon Safety CRO expertise • Oversight is essential for Sponsor
• Vendor selection • Audit and validation of processes • Map and Monitor key processes with flowcharts and
dashboards • Accountabilities detailed in SMP • Continuous engagement with Safety CRO is key
B Haddock MD, MPH
• Contractual agreement: well-defined accountabilities • Communication & escalation paths • Flowchart to map processes • Dashboards for tracking key processes
• Facilitate Cooperation with CRO at each opportunity • Strategic direction and oversight of business relationships, quality and compliance
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© Copyright 2019 Covance Inc.
Covance Inc., headquartered in Princeton, NJ, USA, is the drug development business of Laboratory Corporation of America Holdings (LabCorp). COVANCE is a registered trademark and the marketing name for Covance Inc. and its subsidiaries around the world. The Americas +1.888.COVANCE (+1.888.268.2623) +1.609.452.4440
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Best Practices and Points To Consider for Small-Medium Bio-Pharma Companies
Agenda
What do I need to think about?
What do I need to think about?
Global Expansion
Management of Expectedness in Clinical Trials
IND Safety Reporting Guidance & The Safety Assessment Committee
Build or Buy?

Request for Proposals (RFP):Small Biotech
Support Requirements for Small Biotech
CRO IT expertise essential for Small Biotech
PV Startup to Up and Running with CRO
Checklist for Engaging CRO services
Checklist for Engaging CRO services
Safety Management Plan (SMP)
Sponsor Oversight is essential fromCRO selection & throughout engagement
Flowcharts key to implementing and correcting processes for CRO interactions – DO NOT SKIMP ON THIS
Dashboard essential for managing key processes
Continuously update your organization
Conclusion: Navigating with CROs