Slide 1 © PharmOut 2018
Sponsor – Contract Manufacturer Relationship in Clinical Supplies
Presented by Yaara Dromi,
August 2018
Slide 2 © PharmOut 2018
Sponsor – Contract Manufacturer Relationship
Sponsor/Contract Giver Responsibilities
Sponsor/Contract Giver Requirements
Contract Acceptor Requirements
Challenges of Clinical Supplies
How to Execute the Ultimate Responsibility by Sponsor/Contract Giver?
Slide 3 © PharmOut 2018
Guidelines
Please contribute
Please stop me to ask a question
Please relax and enjoy yourself
Please place your phone on silent mode
Slide 4 © PharmOut 2018
Sponsor Responsibility (Clinical Supplies)
• PE009-13, the PIC/S, Annex 13, Manufacture Of Investigational
Medicinal Products
Co-operation is required with trial sponsors who undertake the ultimate
responsibility for all aspects of the clinical trial including the quality of
investigational medicinal products.
Slide 5 © PharmOut 2018
Contract Giver/Owner Responsibility (Commercial)
• PE009-13, the PIC/S guide to GMP for medicinal products, Chapter 7:
Outsourced Activities
“The Contract Giver is ultimately responsible to ensure processes are in place to assure
the control of outsourced activities.“
• FDA – Contract Manufacturing Arrangements for Drugs: Quality Agreements
Guidance for Industry
“When an owner uses a contract facility, the owner’s quality unit is legally responsible for
approving or rejecting drug products manufactured by the contract facility, including for
final release.”
Slide 6 © PharmOut 2018
Contract Giver/Owner Responsibility (Commercial)
• ICH guidance for industry Q10 Pharmaceutical Quality System
The pharmaceutical company is ultimately responsible to ensure processes are in place to
assure the control of outsourced activities and quality of purchased materials.”
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Contract Giver (PIC/S, Chapter 7)
• Assessing the legality, suitability and the competence of the Contract Acceptor to
carry out successfully the outsourced activities.
• The Contract Giver is also responsible for ensuring by means of the contract that
the principles and guidelines of GMP
• Provide the Contract Acceptor with all the information and knowledge necessary
to carry out the contracted operations correctly in accordance with regulations in
force, and the Marketing Authorisation for the product concerned.
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Contract Giver (PIC/S, Chapter 7)
• Monitor and review the performance of the Contract Acceptor and the
identification and implementation of any needed improvement.
• Responsible for reviewing and assessing the records and the results related to
the outsourced activities.
• Ensure that all products and materials delivered to him/her by the Contract
Acceptor have been processed in accordance with GMP and the Marketing
Authorisation.
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Contract Acceptor Requirements
• Must have adequate resources to perform the work ordered (premises,
equipment, knowledge, personnel)
• Ensure suitability of products, materials and information received
• Should not subcontract without formal approval by Contract Giver
• Should not make unauthorised changes that may adversely affect the outsourced
activity.
• Should understand that the activities may be subject to audit
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Challenges in Clinical Supplies
Data Integrity
Blinding of packaging material
Blinding investigational product Vs. Comparator/
Placebo
Maintaining randomisation
Products/ processes are in different
development stages
Slide 11 © PharmOut 2018
Imagine….
Yaara50 (A) Placebo to match Yaara50 (P)
Pharmout100 (A)A, A A, P
Placebo to match Pharmout100 (P)P, A P, P
1. Product Yaara50 is a 50mg tablet to be tested in comparison to comparator/ placebo
2. Product Yaara50 is a 50mg tablet to be tested for dose and therefore we will need the following doses:• 0mg• 50mg• 100mg• 150mg
3. Product Yaara50 is a 50mg tablet to be tested in combination with Pharmout100 (100mg) for the interaction. What are the options of combinations including placebo to both products?
Slide 12 © PharmOut 2018
Imagine
4. Combination of 2 pathways to achieve the requested effect.
• Pathway A: Product A1, A2 (Comparator to A1), PlaceboA
• Pathway B: Product B1, B2 (Comparator to B1), PlaceboB
A1 A2 PlaceboA
B1 A1, B1 A2, B1 PlaceboA ,B1
B2 A1, B2 A2, B2 PlaceboA, B2
PlaceboB A1, PlaceboB A2, PlaceboB PlaceboA, PlaceboB
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How to Execute the Ultimate Responsibility?
Evaluate
Contract
Information Transfer
Controls
Communication
Continuous Review
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Evaluate the Contract Acceptor
Evaluation is performed in a few steps:
1. Questionnaire
2. Certificates (GMP, ISO, Lab testing)
3. Audit
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Audit
• When auditing a potential contract manufacturer ask the hard questions
• Examine the performance of the quality system
• Look at registers! (an empty register should raise an alarm)
• Basic GMP requirements: Line clearance, reconciliation, product segregation and
disposition, cleaning, MBR generation
Finally
It is OK to identify that a potential contractor is not suitable to be
contracted and continue to search for a more suitable one.
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Contract
• Determined the standard to follow
• Identify who is responsible for each activities
Activity Contract Giver Contract Acceptor
Write MBR X V
Approves MBR V V
Review executed BR V V
Release batches V X
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Information Transfer
• Transfer all applicable information/knowledge to contract acceptor to allow the
contractor to plan prepare, implement changes and controls for the purpose of
execution of the contract
Contract acceptor
Product information
Study protocol and design
Process requirements
Quantities Time lines
Distribution
Randomisation
Contact details
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Controls
• Testing of product
• Sampling method
• Review final product before release (physical product or photographic evidence)
• Review of Batch Records
• Designed release process
• Control of distribution
Strategy for all the above should be risked based and on the basis of experience
with the contractor and build of trust. This will be specified in the contract.
Slide 19 © PharmOut 2018
Communication
• Continuous communication and report of issues in real time
• Communication must go both ways
• Communication must be clear and unambiguous
• Information should be delivered in appropriate time frame to allow parties to
respond:
• Due dates and required quantities
• Issues raised during processing
• Changes in processes/expectations/timelines
Slide 20 © PharmOut 2018
Continuous Review
• Review of performance and KPIs
• General discussion and planning
• Continuous improvement activity and monitoring
The review allows the Sponsor/Contract Giver to evaluate the performance of
contractors and continue to select the best performing contractors.
Sponsor may chose to reduce/stop engagement with unsatisfactory contractors or
enhance work volume with best performing contractors.
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Recap?
Clinical supplies are more complicated and therefore susceptible to error than commercial.
Sponsors holds the ultimate responsibility to the patients safety and trial integrity.
Sponsors must apply control strategy to assure their responsibility
Slide 22 © PharmOut 2018
Keep safe and manage ethical trials!
Yaara Dromi
Consultant
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