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 / Lowcould affect impurity profileproduct is still the same – might not detect an impurity that you previously didmethods 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 ChangeChange a key excipient affects 5 different products – specification, finished product stability, impurities, release profile etc. etc.

• Risk: High / Medium / LowHigh

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– 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 XRA – notification of authorities and classification of change: type of variationR&D – information regarding product stability: RH, temp, exposure to light, reaction

with Al etc.Stability labLogistics: Warehouse, shippingPackaging materials sampling and testingQCQATechnical OperationsProduction and PackagingPurchasing: suppliersMarketing Target Date for Successful completion: 01/01/2011Review 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 Plan5. Change Review Team:

6. Change Plan:ControlsMonitoringAcceptance 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

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 requiredVariation: Type IIProcess validation ? Increased in-process / packaging samplingPackage IntegrityCleaning

Quality:Artwork will need preparation, review, approval, control of printers, specifications, testingPackaging materials specificationsLeachables and Extractables (compatability)Standard Operating Procedures updatedMaster Packaging Instructions revisedSupplier qualification for packaging materialsSampling 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 manufacturerDescription 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 manufacturerChange 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