technology transfers & quality kenan kösoğlu novartis Ürünleri eskişehir, 25th may., 2012

Technology Transfers & Quality

Kenan KösoğluNovartis Ürünleri

Eskişehir, 25th May., 2012

Quality not only concerned with the drug product What is QC ?

Quality also needs to be considered & comprehend all activities around

the production / tech transfers What is QA ? Documentation

Communication

Project management

Change management

Rules & Regulations (GMP, corporate, Health Authorities, legal requirements, etc...)

Production process

Quality control process, standard operation procedures, manuals

All other activities related production process

We need to assure fast “time to market “ and continuous supply with Quality at competitive

cost while leading tech transfers with minimized one time cost. 2 | Tech Transfer & Quality / Novartis / May.2012

Technology Transfer & QualityQualityTechnology Transfer & QualityQuality

Technology Transfer & Quality Objectives & Reasons of Technology TransfersTechnology Transfer & Quality Objectives & Reasons of Technology Transfers

Technology Transfer from R&D to regular (large-scale) production

from site to site (regular productions) why tech transfers needed?

Objectives / Reasons : Strategy of production site / corporation

• Capacity optimization & harmonization

• Technology of Granulation, Tabletting, Coating

• Site area changes

• Productivity & financial effectiveness of the site/company

• Life cycle of the products & site product portfolio management

• Dosage forms (TAB, FCT, SCT, Capsules, EFT, LOZ, ...)

Pharmaceutical Sector

• Legal requirements of products, production process & regulations

• Product base changes & competition3 | Tech Transfer & Quality / Novartis / May.2012

Technology Transfer & Quality Life Cycle of productsTechnology Transfer & Quality Life Cycle of products

Development Growth Maintenance Decline

Orphan indications

New indications

FDCs

Sec. patents

New formulations

New doses

Phase IIIB / IV

IITs

New indications

FDCs

Sec. patents

New formulations

Pediatric formulation

New doses

New dosage regimens

Regulatory exclusivities

Data protection

New chemistry

New processes

Publication strategy

Geographical expansion

New indication/newdose in newformulation

Pediatric formulation

Drug delivery

New salt

OTC switch

Defend patents

Re-purposing

Successor molecules (research or BD&L)

Raise purity / BEQ standards

Packaging innovation

Lean manufacturing

Loyaltyprogrammes

Volume purchasingcontracts

White papers

Authorised generics

Focus on self-paymarkets

Local LCM

Milk

Foster

Divest

Prune

Time

Sale

s

Good LCM means optimising lifetime brand performance, every

time, within the context of the overall product and project portfolio

When to start for Tech Transfer Projects ?

4 | Tech Transfer & Quality / Novartis / May.2012

Technology Transfer & QualityProject Management Tool in Technology TransfersTechnology Transfer & QualityProject Management Tool in Technology Transfers

Scope Complexity of the project Local vs. multi market , # of SKU, # of countries, dosages, etc

Cost : Project budget, cash flow, investment management

Time management :

Launch the products within planned time

Resource Management : Human, Technical Know-how, Machine & Equipment Stakeholder management Project sponsor, manager & team with roles & responsibilities

Who will be in project team ? 5 | Tech Transfer & Quality / Novartis / May.2012

Technology Transfer & QualityEnvironment Technology Transfer & QualityEnvironment

We are living in global environment which effect directly decisions

and plans on tech transfers. Requirements need to be followed and

applied properly during tech transfer projects :

Patients Doctors, universities, ... Diseases Health Authorities (all countries) , government & legal requirements Corporate requirements Pharmaceutical Sector & GMP Rules World technology trends

Samples of environment effects on tech transfers?


Technology Transfer & QualityFunctions in Organization during the TransferTechnology Transfer & QualityFunctions in Organization during the Transfer

Quality do not focus only the production . It is must that all activities within the organization (cross-functional) needs to be managed considering Quality.

Project management Health, Safety & Environment Supply chain management / logistics Regulatory & Medical Marketing Engineering Quality Assurance & Quality Control IT Systems Legal requirements

• Finance

• Personal Why Quality needed for those activities too ?


Technology Transfer & QualityPhases in Tech TransferTechnology Transfer & QualityPhases in Tech Transfer

Evaluation & Approval Phase Financial & Technical Ffeasibility of the tech transfer, capability & resource mang.

Planning Phase : Tech Transfer Project plan : Who, What, When, How,..

Technical Phase : Validation productions as per Planning Phase

Regulatory & Registration Phase : Regulatory documentation & submissions to Health Authorities

Logistics & Execution Phase : To ensure the first supplies properly as per planned at the previous phases

How much time needed for each phase ?


Technology Transfer & QualityEvaluation & Approval PhaseTechnology Transfer & QualityEvaluation & Approval Phase

Corporate & Site strategy Current & long term site capacity Investment need, tooling , equipment (technical feasibility) Incremental human resources need Available technology, infrastructure, layout , know-how New countries, audit requests Product basis requirements Project volume figures Brand life cycle status & long term forecasts Competition & generics Regulatory requirements by Health Authorities Financial figures & costs (financial feasibility)

Cost per pack

Cost per worker

Which risks available & how to eliminate them?


Technology Transfer & Quality Planning Phase (Transfer Master Plan-1) Technology Transfer & Quality Planning Phase (Transfer Master Plan-1)

Validation Strategy Process Validation Protocol

Packaging Validation Protocol

Cleaning Validation studies

On-site technical visit & good communication practice between GS vs. RS

Qualification, calibration & comparison of equipments, infrastructure

Product annual review data , previous trends (stability, OOS, etc..)

Update, review current process before the tech transfer, check lessons

learned from previous tech transfers, review GS documentation & knowledge

Site production area conditions (temperature, humidity, light, ..)

Evaluate all IPC (test methods & specifications) & plan all parameters

Planning of manufacturing lines, equipment & infrastructure :

• Decide which lines will be used for the related tech transfer

Check microorganism requirements

Prepare master batch records/production documents before the validation production.

Why planning phase is most cruical ?


Technology Transfer & Quality Planning Phase (Transfer Master Plan-2)Technology Transfer & Quality Planning Phase (Transfer Master Plan-2)

Registration Strategy Stability Protocol, conditions, shelf life decision

Method Transfer (lab to lab) : Lab capacity & capability

TM Testing Monograph update if needed (raw mat., drug product,..)

Dissolution profile requirements (medias, conditions, time points, ..)

Raw Material & Drug substance specs, comparison & supplies

Pack material specs, comparison & supplies

Change management (trace & document all changes)

Document transfer , know-how & information from R&D & giving sites

Plan GMP audits / inspections in case needed

Country approvals ( 1-24 months)

Submission strategy & groupings

• EU Countries with 3 months stability data

• RoW Rest of the World countries with 6 month stability data

Evaluate Health Authority requirements during planning phase and take

into consideration properly not to face conflict at registration phase


Importance of Stability studies ? Importance of Dissolution profile test studies ?

Technology Transfer & Quality Planning Phase (Transfer Master Plan-3) Technology Transfer & Quality Planning Phase (Transfer Master Plan-3)

Logistics Strategy HSE requirements of the transferred product

• Transport conditions, storage conditions

• Product status (hazardous, flammable, ..)

Technical requirements of pack materials and availability

Data management, system definitions

Transfer check list

Site Storage & warehouse conditions (temperature, humidity, light, ..)

Train all staff concern with the transferred product & process

Get ready in terms of purchasing, supply chain, logistics

If needed perform investment plans

Bridging inventory calculations

Plan the budget & resource management

Plan communication management tools

• Regular informative & decision meetings

• Committee meetings, status reports


Importance of planning logistics strategy at planning phase ?

Technology Transfer & QualityTechnical PhaseTechnology Transfer & QualityTechnical Phase

Perform the validations as per Transfer Master Plan

and Documents & information decided at Planning Phase

Validation Report Stability tests & studies

Stability report Perform dissolution profile comparison tests within both sites

Dissolution profile comparison report Executed Batch Records / production QC release & test results All changes & deviations needs to be classified & documented (planned

protocols vs. actual reports)

Which difficulties could be in technical phase ?


Technology Transfer & Quality Regulatory & Registration PhaseTechnology Transfer & Quality Regulatory & Registration Phase

Collection of the documentation created from technical phase CMC document writing Communication with all stakeholders to perform the documentation

properly considering Quality. Submissions to Health Authorities (HA)

“right at first time” not to cause variations Reply questions from HAs Document the changes properly as planned at registration strategy Follow approvals & reply HA questions Requests from HAs ;

Samples, Reference materials Certificates (GMP, CPP, ...) Previous Audit reports

Why “right at first time” is important ?


Technology Transfer & Quality Logistics & Execution PhaseTechnology Transfer & Quality Logistics & Execution Phase

Logistics activities : Define production lead-time, minimum order quantities, system Definition of the products, raw materials, BOM, Routing, etc... Complete the artwork studies as per registered designs Start communication & activities with suppliers & customers Complete financial activities such as costing & pricing Check short, mid & long term plans, capacity Last supplies to giving site First supplies from receiving sites

Handover from Transfer Project team to regular functions : Correct & on-time handover Full handover might be within 1-3 years Alignment of regular productions according to registered process

during the tech transfer 15 | Tech Transfer & Quality / Novartis / May.2012

How to handover ?

Technology Transfer & Quality Best Practices & lessons learnedTechnology Transfer & Quality Best Practices & lessons learned

Good project planning at Technology Transfers are crucial and this

ensures the volumes at the site as estimated and cause positive effect

on corporate strategy & competitiveness at long term.

Weak project plans & wrong bridging inventory quantities could cause ; Stock-out Write-off cost One time cost Less income Risk to loose the brand Less reliability of brand / corporation


Eliminate all risks with good team working .....

Project Planing - Quality

Thank You !

Questions & Answers

Thank You !

Questions & Answers