Transcript Slide 1

Case Studies in Change
Management
IFF February 2009
Analytical Methods – ACN
• Scope of Change
Very comprehensive – many products: stability and release,
development:
Notification:
Regulators /Markets: US, EU (member states), Japan etc.
Partners: (API manufacture – all clients) (Contract
Manufacture / Contract testing – all clients)
• Major change
• Risk: High / Medium / Low
could affect impurity profile
product is still the same – might not detect an impurity that
you previously did
methods validation /verification: spiking
Packaging – Securitainer - Blister
• Scope of Change
One product : packaging line (new
qualification) and stability
• Risk: High / Medium / Low
Key Excipient – Chinese Source
• Scope of Change
Change a key excipient affects 5 different
products – specification, finished product
stability, impurities, release profile etc. etc.
• Risk: High / Medium / Low
High
Possible control measures
• Quality Agreement
• Copy of batch manufacturing record
Chinese and English versions
• Copy of QC test procedures
Chinese and English versions
• Samples: to be taken by their personnel
during on-site audit
• On site audit: see production and QC
operations taking place
Possible control measures
• Additional QC testing at my company particularly –
sample every container for full monograph testing
• Develop identity tests that can identify potential
contaminants
• Yield controls: reconciliation of materials in vs
materials out – even on a batch by batch basis
• Where do they purchase their raw materials
• Supply chain – actual site(s) of manufacture – agents
and brokers identified and you audit them as well
• Functionality testing: small scale manufacture and pilot
runs using the new supply of excipient and generate
some “process validation data” on small scale batches
Packaging change: Securitainer - Blister
• Title: introduction of an existing product to new market
• Description of the Change: Introducing an additional packaging
form of a blister for a (name of product and item number, pack size,
dosage form)product already sold in a securitainer in the USA
• Description of the Current Situation: Product manufactured in
securitainers and sold in USA. We have a blister packaging line used
for other products therefore we might be able to use existing films /
al etc.
• Reason for the change:
The new presentation is for the European Market (!!!!)
• Signature and date of originator of the change
(Marketing department)
(Could add at the end of the change management process a “lessons
learned” section and “cost assessment for the change”
Packaging change: Securitainer - Blister
• Risk Assessment / consequences of the
change:
– Impacts packaging specifications and packaging
instructions – sampling instructions
– (Re) Qualification of packaging line
– Process Validation
– Stability studies
– Transportation studies
– Cleaning procedures / validation
– Training
Packaging change: Securitainer - Blister
• Controls to be put in place
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Revise packaging specifications
Revise packaging instructions
Revise sampling instructions
(Re) Qualification of packaging line
Partial Process Validation
Stability studies
Transportation studies
Cleaning procedures - revised / validation – review
Matrix
– Training of concerned persons
Packaging Change
• Deadline of 14 days for input from concerned
parties – Initiation meeting – outcome defined
upfront: do you agree that we can proceed
with planning the change
• 30 days deadline for change plan approval
(meeting recommended)
• Senior Management budget or resources
approval if needed
Packaging Change
• Costs associated with the change
• Communication plan
• Implementation dates / notification
Replacing Tableting Machine with
same Principle different manufacturer
• Description of change: same as above
• Current situation: manufacturing x 1000
tablets per hour on the existing machine. The
machine is old and we are worried that soon it
won’t be able to produce any more because
we are calling maintenance 6 times a day.
Did we do process validation back in those
days and how good was it and is it still
relevant
Replacing Machine
• Process qualification / validation
(comparability) – base on validation on
existing machine and data trending in
particular SPC and Product Quality Review and
Risk Assessment
• Product hold for first batch or more
depending on Risk Assessment and Regulatory
requirements / expectations
Packaging change: Securitainer - Blister
Responsibilities:
Overall – Project Leader: Mr X
RA – notification of authorities and classification of change: type of variation
R&D – information regarding product stability: RH, temp, exposure to light, reaction
with Al etc.
Stability lab
Logistics: Warehouse, shipping
Packaging materials sampling and testing
QC
QA
Technical Operations
Production and Packaging
Purchasing: suppliers
Marketing
Target Date for Successful completion: 01/01/2011
Review team:
Packaging change: Securitainer - Blister
Review team:
Change Management Plan
1. Description of the (proposed) Change:
2. Description of Current Situation:
3. Reason for the change:
4. Risk Assessment
Change Management Plan
5.
Change Review Team:
6.
Change Plan:
Controls
Monitoring
Acceptance criteria
7.
Change Implementation Timetable:
8.
Responsibilities
9.
Review and approval of change plan
10. Communication
Change Management Plan
11. Implementation
12. Follow-up
13. Close-out and product release
Case Studies – Day 2
• Analytical Methods – ACN needs to be
replaced
• Change a key excipient from EU source to
Chinese source (EU stopping manufacture)
• Define Scope and Complexity of change
• Define Risk associated with change
ACN
• Scope of change:
Replace ACN with a different mobile phase
• Complexity:
Compare old method with new – method validation
and qualify impurities – maybe new additional or
different impurities might show up – ID them and
quantify
Ongoing stability would be affected?
Risk: (Low / Medium / High)
Key Excipient – Chinese Supplier
• Scope of change: affects 5 products
• Complexity:
Straightforward change – we know what to do
– the problem is the Chinese Supplier
• Risk: (Low / Medium / High – because of the
Chinese element)
When do we fill out a Change Request
Form?
Do we have sufficient information?
• WHY? Is the change being made
• WHO? Initiated the change
• WHEN? Time table for implementation – is it
urgent e.g. Regulatory requirement (e.g.
change to pharmacopoeial method for
Heparin)
• WHICH? Products / department / people are
involved
• WHAT? Samples / tests need to be performed
Packaging Change – from Securitainer
to Blister Pack
Description of change:
Addition of a new presentation / Change of primary
packaging material for one product
Current Situation:
Have an approved packaging line for securitainers and
we have an existing blister packaging line which we can
use for the additional product.
The securitainer includes silica gel – so product has
some sensitivity to humidity
Reason for Change:
Marketing believes that it will boost sales by 200%
Packaging Change – from Securitainer
to Blister Pack
Change Review / Analysis:
Reg Affairs:
New stability will be required
Variation: Type II
Process validation ? Increased in-process / packaging sampling
Package Integrity
Cleaning
Quality:
Artwork will need preparation, review, approval, control of printers,
specifications, testing
Packaging materials specifications
Leachables and Extractables (compatability)
Standard Operating Procedures updated
Master Packaging Instructions revised
Supplier qualification for packaging materials
Sampling instructions
Packaging Change – from Securitainer
to Blister Pack
Responsibilities:
Project Manager – Marketing Manager
- Production and planning: evaluate capacity of
current blister line and validation
- documentation dept to update relevant docs
- engineering dept for new tooling if needed
- R&D for packaging materials and stability and
compatibility
- Purchasing for primary and printed pack
materials, supplier evaluation
- Reg Affairs
Replace Tableting Machine – same
operating principle different manufacturer
Description of the Change:
Replacement of tableting machine with a new
one that operates on same principle but different
manufacturer – new machine has three times the
capacity of the old
Current situation:
existing machine is 35 years old with frequent
breakdowns, lack of capacity
Reason for the Change:
increase capacity and save operational resources
Replace Tableting Machine – same
operating principle different manufacturer
Change Review:
• Back to development to understand what the
change will do the product(s) and processes
before deciding on regulatory strategy
• URS
• Involve technical department, maintenance
and validation for qualification of the machine
• Make a project team with Manufacturing
Manager at helm