biopharmaceutical method transfer: how to marry … · to perform an analytical method ... •...

Biopharmaceutical Method Transfer: How to marry quality & compliance with productivity & speed

Camille Dycke, MMTech Bioassay, Global Biologics QCGenentech, a member of the Roche group

Acknowledgements

• Micah Thompson, QC Sr manager, Global method transfers

• Glenn Smith, Head, Method Transfers, Monitoring & External QC

• QC biologics network, and partners from the Development organization

• Emma Ramnarine, Head, Global Biologics QC

Presentation outline

• Introduction– What is the purpose of an analytical tech transfer?– What are the drivers?– What are the challenges?

• Element of solution 1: Analytical tech transfer team and clear business process

• Element of solution 2: Method transfer document templates and standard guidance

• Element of solution 3: Alternative approaches to tech transfer designs

Analytical method transfers life cycle

Development phase

- Method development

- Used for clinical release

1 lab

2-5 analysts

Co-validation

initial transfer

Commercial phase

Transfer to new manufacturing site, partners, CMO…

Transfer for in-country testing

- Method life cycle mgt

- Used for global release

2-5 labs across the globe4-15 analysts

Method history…

Roche/Genentech Biologics QC Network

VV

OCN

SSFGRZ

PZKAU

RSTO

Dev. DevGlobal

QC

MH

6

VV

OCN

SSFGRZ

PZKAU

RSTO

Dev DevGlobal

QC

• Transfers from Development to Commercial QC

• Transfers to new Commercial sites

MH

7

VV

OCN

SSFGRZ

PZKAU

RSTO

PTD PTDMMTech

• Transfers to CMO, partners, in country testing

MH

8

• Transfers from Development to Commercial QC

• Transfers to new Commercial sites

Method Transfer at a GlanceWhat are we trying to achieve with a method transfer?

• Qualify a new laboratory to perform an analytical method

• Qualification ensures the Receiving Lab has the procedural knowledge and ability to perform the transferred analytical procedure as intended (USP<1224>)

• Ability to perform the method should confirm that the Receiving Lab:

– is able to get results comparable to other qualified sites

– hasn’t introduced undesirable variability in execution of the method

Elements of Receiving Lab Qualification

• Provides procedural knowledge– Knowledge transfer– Hands on training

• Ensures result comparability:– Equipment, reagent procedure gap

assessment– Assessment of results between Receiving

and Donor labs

Standard Elements of an Analytical Method Transfer

1. Planning and definition of

transfer strategy


2. Site Preparation


3. Define Transfer Experiments and

Acceptance Criteria


4. Execution and Data Evaluation


5. Document Results

Drivers for Executing Rapid, Efficient Method Transfers

• Accelerated product development timelines (BTD, accelerated review)

– How to stay off of overall tech transfer critical path

• Additions to tech transfer portfolio (launches, new commercial manufacturing sites, control system lifecycle)

• New experimental design and statistical data assessment strategies

• Global donor and receiving labs, internal and external labs, transfers to emerging market countries

Timeline and resource

pressures

Changes in method transfer best practices

Complex QC networks

Challenges to Rapid, Efficient Method Transfers

• Lack of clarity around roles and responsibilities

• Insufficient connection and knowledge exchange between Donor and Receiving labs

• Absence of detail guidance on meeting compliance requirements

• Wide range of instrument utilization

Sub-optimal Team Structure, Unclear Business Process,

Insufficiently Standardized Work

• Non-collaborative document authoring and review

• Use of paper documents

Inefficient Systems

Analytical Tech Transfer Team (ATTT)

The cross-functional Analytical Tech Transfer Team (ATTT) is responsible for the successful implementation of the analytical control system at the commercial testing site(s).

The team structure establishes clear ownership of method transfer activities and ensures direct engagement between Donor and Receiving Labs

ATTT reviews team’s RACI at the start of each project

ATTT initiates collaborative work with face to face Kick off meeting

ATTT Structure and Responsibilities

Analytical Tech

Transfer Lead

Analytical Donor SPOC

Addtl. Analytical

SMEs

Commercial Quality

Lead

Analytical Receiving SPOC(s)

Commercial

Control System Owner (ATL)

Identify method transfer strategy, interdependencies, and risks. Implement all methods at the receiving site. Implement method training at the receiving site. Coordinate the Reference Standard

Characterization. Implement a commercial stability program at

the testing site. Implement control strategy (specification

documents, sampling plan, IPC, and additional monitoring) Ensure that any potential impact to control

systems for existing products (due to the new product) is adequately addressed through the relevant product ATLs. Perform method troubleshooting. Implement assays for adventitious agent.

Participate in scientific review of methods and control system.

Orange – Donor site functions

Green – Receiver site functions

Gray– Global functions

Analytical Receiving SPOC and Analytical Donor SPOC

The Analytical Receiving SPOC is a partner to the Analytical Donor SPOC; this partnership enables direct SME-to-SME communication and knowledge transfer. Together they are responsible for site visits, protocols, reports, execution of the transfer and co-validation activities, and any required method troubleshooting.

The Analytical Receiving SPOC is responsible for the implementation of the control system at the receiving site including site testing documents, change records, and the Laboratory Information Management System (LIMS) build.

Document TemplatesUse of document templates provide numerous benefits to any method transfer:

General Benefits CommentsImproved quality compliance

Required process elements can be pre-populated to ensure better compliance with governing Quality System requirements

Incorporate current best practices

Templates can serve as device for knowledge management enabling inclusion of best practices in method transfer documents/activities

Detailed work instructions

Templates can incorporate detailed instructions for document planning/creation within the context of the document

Rapid documentauthoring, review and archival

Standardized document format and content facilitates rapid document preparation (no reinventing a wheel) as well as review (reviewers familiar with content/align with quality requirements).

Extent of Document/Process Templating

• Gap Assessment Reports

• Method Transfer Master Plans (Transfer Strategy Summary)

• Method Transfer Protocol

• Method Transfer Reports

• Data reporting sheets– Data tables and calculations– Statistical reports

Use of Alternate Method Transfer Strategies

Transfer Strategy

Description

ComparativeTesting

Donor and Receiving laboratories analyze the same sample set, selected as representative of the product/storage condition.

Co-validation Donor and Receiving laboratories participate in the execution of the method validation

Revalidation Method is fully or partially validated at Receiving labTransfer Waiver Omission of method transfer via comparative testing, co-

validation or method validation under well-justified circumstances. Receiving lab is considered to be qualified to use the test procedures without generation and comparison of inter-laboratory data.

USP <1224> outlines four common method transfer strategies

Considerations should be made for use of all method transfer strategies to minimize transfer timeline/resources, while still maintaining visibility to advantages/risks present with each strategy

Assessment of Alternate Method Transfer StrategiesTransfer Strategy Advantages Risks/Challenges

ComparativeTesting

• Classical approach to method transfer

• Potentially longest timeline due to sequential execution

Co-validation • Potentially shortened method transfer timeline/reduced overallresources due to parallel execution at multiple sites

• Number of reviewers/approvers increases with number of sites (document complexity)

• Need to ensure that comparability is sufficiently addressed (e.g., satisfactory design of reproducibility)

Revalidation • Can be utilized if Receiving lab method has been sufficiently changed

• Little/no donor lab resources required

• Site-to-site comparability may not be fully addressed

• Longer timeline needed to assess attributes not required when able to use comparative testing

Transfer Waiver • Site experience with specific methods can be leveraged to eliminate execution of method transfer experiments

• Unacceptable method execution at specific sites due to insufficient site qualification

• Inadequate gap assessment or assessment of site experience utilized to justify waiver

Current expectations for transfer designsCurrent regulations on method transfer designs

“[transfer] Acceptance criteria should bebased upon current validation study ofthe methodology and with respect to ICHrequirements”

“The transfer acceptance criteria, which arebased on method performance andhistorical data from stability and releaseresults, if available, should include thecomparability criteria for results from allstudy sites”

“The comparative studies areperformed to evaluateaccuracy and precision,especially with regard toassessment of inter-laboratory variability. Incases where the transferredanalytical procedure is also astability indicating method,forced degradationsamples or samplescontaining pertinent product-related impurities should beanalyzed at both sites”

Design for assessment of lab to lab comparability

• Traditional method transfer: – 1 donor site (development) + 1 recipient site (QC site)Side by side (1:1) comparison of method performance

• With product globalization:– N (>1) testing sites across the globe + 1 recipient siteWho is the donor site? Who is the training site?What data to use to assess comparable method performance?How to set up comparability acceptance criteria?

Camille Dycke, CASSS Bioassays, March 2015

How to select donor data for transfer comparability test?

Method history Validation – Development lab

Site CSite BSite A

Site D

Site E

Historical successful

transfers

How to transfer to site F?Site F

How to select donor data for transfer comparability test?

Method history Validation – From development lab

Site CSite BSite A

Site D

Site E

Historical successful

transfers

Site FHow to transfer to site F?

Global method performance

Product control trending from each site

Conclusion

Analytical transfers are key elements needed in the overall process transfer strategy to qualify a new site to reliably and timely release the product and ensure product quality….BUT…analytical transfers are

time-consuming

resource-intensive

cannot be in the critical pathway of process transfers…

Key aspects to put in place to overcome these challenges:

Analytical tech transfer team and clear business process

Method transfer document templates and standard guidance

Alternative approaches to tech transfer designs

Doing now what patients need next

biopharmaceutical method transfer: how to marry … · to perform an analytical method ... •...

Documents