From Traditional Approach to Verification Approach · Traditional Approach - Basic Concepts •...

www.telstar-lifesciences.com

Commissioning and Qualification:

From Traditional Approachto

Verification Approach(Science & Risk Based)

Ricardo GirãoTiago Pires

Reunião Anual do Colégio de Indústria Farmacêutica da Ordem dos Farmacêuticos

Batalha 06 Abril 2019


▪ Basic Concepts

▪ Traditional Approach (Commissioning and Qualification)

▪ Guidelines for a more efficient approach

▪ The Verification Approach – Science & Risk Based

▪ New concepts and fundamentals

▪ (Examples)

▪ Final considerations

Contents


OBJECTIVE

Traditional Approach

(IQ;OQ;…)

Verification Approach (Science & Risk

Based)

You may stay here …just stop here …or here ..and want to get here…

What is the most appropriate approach?

Demonstration of fitness for intended use


Traditional Approach - Basic Concepts

• Qualification

As per FDA’s January 2011 Process Validation Guideline: “…qualification refersto activities undertaken to demonstrate that utilities and equipment are suitablefor their intended use and perform properly”

As per ISPE Good Practice Guide: Applied Risk Management for Commissioningand Qualification: “Qualification: is the demonstration of suitability forintended use which has been formally documented and approved”

Qualification of a system shall be understood as set of activities that will provide documental evidence that its design, construction, installation and operational mode are in accordance with predefined specifications.


Traditional Approach - Basic Concepts

• Commissioning

As per ISPE Baseline Guide Volume 4, Commissioning and Qualification:

“A well planned, documented, and managed engineering approach to the start-upand turnover of facilities, systems, and equipment to the End-User that results in asafe and function environment that meets established design requirements andstakeholder expectations.”

Commissioning has historically been viewed as an engineering activity that was early in the process where Q-Unit involvement was not necessary.

Physical Completion

and Inspection

Setting to Work

Regulation and Adjustment

Testing and Performance

Testing

Planning and preparation associated with managing the above activities


Qualification Traditional Approach

TRADITIONAL APPROACH: QUALIFICATION

▪ Quality Assurance/Quality Unit approves each and every protocol test

▪ Organization refused to leverage commissioning

▪ Automated systems and controlled equipment were qualified separately and inefficiently

▪ Deviations from trivial items diluted Q-Unit attention

▪ Disqualifying verification documentation made by suppliers because they occurred prior to

Quality unit pre-approval protocol

▪ Separate Commissioning from Qualification and establishing not added value thresholds

between different qualification



Qualification consists of a series of IQ, OQ and PQ Protocols (followingcompetition of construction and start-up).

- Diluting efforts and resources across documental formalities.

- Focus on all system features instead of on quality-critical aspects related tothe product.

- Inefficiency practices.

- The goal is mostly concentrated on the release of the system for use

- Undervalues a life cycle approach.

Issuing of IQ/OQ

IQ TestingApproval of

IQOQ Testing

Approval of OQ

Release for PQ/PV

Qualification Activities Finished

TRADITIONAL QUALIFICATIONRIGID PROCESS

TRADITIONAL QUALIFICATION

RIGID PROCESS



Example 1:

The deviation is evaluated and approved by the Q-Unit.

The Q-Unit designee who handles the deviation might not have the properprocess equipment knowledge to evaluate it.

Is this the most efficiency approach?

Reactor / Tank Qualification

Verification to open a certain valve

It is verified that it is another one that opens



Example 2:

Vendor:

Q-Unit:

Repeat that verification (already knowing the “answer”).

Opportunity for minor deviations due to erroneous test description.

Are we properly using our resources?

Implements a HVAC AHU motor

Verifies the motor rotation direction

Reports under Commissioning

Approves Protocol and Acceptance

Criteria


Reports on Qualif. Protocol



Example 3:

It is verified during the IQ that one instrument is not calibrated.

Option 1:

- Open a deviation to be evaluated and approved by the Q-Unit.

Option 2:

- Stop the Qualification / Project and wait for the instrument to be calibrated.

Shall we concentrate our efforts merely formal issues?


• What is the added value of:

- Discrepancies without product-quality impact being approved by the Q-unit.

- Repetition during Qualification of verifications performed during commissioning.

- Interrupt a project due to documental formal issues.


Efficiency (cost)

Product Quality

(Risk Control)

Patient Safety

NO ADDED VALUE

A more efficient approach is needed!


GUIDELINES FOR A MORE EFFICIENT APPROACH

ASTM E2500 - Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment

https://www.astm.org/Standards/E2500.htm

Key Concepts

▪ Describes a risk-based and science-based approach to specification, design, and verification of manufacturing systems

▪ Intended to ensure that systems are fit for intended use, and to satisfy requirements for design, installation, operation, and performance

▪ Encompasses all types of approaches - commissioning and qualification, verification, system validation, or other.

▪ Applies concepts and principles introduced in the FDA initiative, Pharmaceutical cGMPsfor the 21st Century—A Risk-Based Approach

▪ Supports, and is consistent with, the framework described in ICH Q8, ICH Q9, ICH Q10, and ICH Q11.

https://www.astm.org/Standards/E2500.htm


Fundamentals of S&RB Approach

▪ Risk-based - applied to specification, design, and verification – QRM principles aligned with ICH Q9

▪ Science-based – use of product and process information, such as Critical Quality Attributes (CQA) and Critical Process Parameters (CPP) – in line with ICH Q8

▪ Identify Critical Aspects of the systems - functions, features, abilities, and performance or characteristics to ensure consistent product quality and patient safety.

▪ Verification documentation shall be sufficiently flexible to be synchronized with the project progress rather than to rigidly dictate the project execution

▪ Use Good Engineering Practices (GEP) to verify installation and operation, including vendor documentation, and to address discrepancies not related with Critical Aspects

▪ Identify Subject Matter Experts (SME) and emphasize their role as key through all phases

▪ Re-focus the role of the Q-Unit to the approval of requirements, specs, test plans and deviations related only with Critical Aspects for product quality and patient safety

▪ Design Reviews and Change Management to assure fitness for use through the system life-cycle

▪ All activities must bring value

Science & Risk Based Verification Approach


Science & Risk Based Verification

Approach(as defined in ASTM E2500)



QA

EngineeringOperations

SMECQA; CPP GEP

QRM

SUBJECT MATTER EXPERT

▪ Defines or oversees:

– The verification strategy

– The verification deliverables

– The verification activities

– The acceptance criteria

– The evaluation of deviations

– The release for use


HOW TO GET THERE

Provides a roadmap for the transition of traditional IQ/OQ approach to science and risk-based approaches, including

practices and terminology.

▪ Adopting practices which are lean and efficient is optional

▪ Ensuring that practices provide verification of aspects related with product quality and patient safety is compulsory

▪ Recommends elimination of wasteful practices for development of IQ and OQ documentation.

▪ There is a business case as well as a quality case for implementing these approaches.

https://ispe.org/publications/guidance-documents/good-practice-

guide-applied-risk-management-cq

https://ispe.org/publications/guidance-documents/good-practice-guide-applied-risk-management-cq


• Verification Process Flow Chart


List of Critical Aspects

Approved by Quality Unit

Verification Plan


Verification Testing (Design to Performance) to confirm Critical Aspects and meet

Acceptance Criteria


Review all completed verification test by a

second, independent SME

Acceptance and Release

Operation, Continuous

Improvement

Subje

ct

Matt

er

Expert

s

CQACPP


• Verification Process Application

All testing methodology procedures development and protocol issuance, as well as their execution and revision are performed by the proper SMEs.


Verification PlanDefines the Tests and Acceptance Criteria

Developed by SME and Approved by Q-Unit


Example 1:

The deviations is treated by equipment and process SMEs.

The corrective actions can be controlled through an Engineering ChangeManagement System.

Addressed prior to Q-Unit Acceptance & Release.


Reactor / Tank Qualification

Verification to open a certain valve

It is verified that it is another one that opens


Example 2:

Vendor:

Evaluated as non critical aspect for product-quality or patient safety.

The verification can be documented on commissioning activities.


Implements a HVAC AHU motor


Reports under Commissioning


Example 3:

It is verified during the IQ that one instrument is notcalibrated.

There is no definition of which activity is includedduring “IQ,” or which should only be included during“OQ.” The logical sequence of testing is moreimportant than which activity is included during “IQ,”or which should only be included during “OQ,” e.g., thecalibration of measuring loops needs to be performedsuccessfully before functional tests are executedutilizing the measured results.



Suggested Tools:

Use of Red-Lined documentation

Ex:

- Applicable to P&ID drawing or SOPs.

- Changes document by hand, initialed, dated

and controlled.

- At an appropriate point these red lineddocuments can be transferred to the nextupdated version of the document and re-approved.

- Available for use by SMEs for review andapproval or in the execution of C&Q testingplans.

Testing: Verification of P&ID

Missing a non-critical instrument on an P&ID

Use of Red-Lined documentation

Open Deviation (Usage of Quality Unit Resources)

Traditional

Verification



• Quality Risk Management Trends

These trends are already being considered in reference practices.

EU GMP Annex 1 - Manufacture of Sterile Medicinal Products (Under Consultation / Revision)

Example – For room classification (Maximum permitted Non-viable Airborne Particles)

▪ Initial Qualification – The particles equal to or greater than 0.5 μm should be measured.

▪ For Monitoring – The particles equal to or greater than 0.5 μm and 5 μm should be measured.


Verification Approach



• Quality Risk Management Trends

These trends are already being considered in reference practices.

EU GMP Annex 15 – Qualification and Validation – In force since October 2015

▪ The QRM principles were introduced.

Curiosity – Did you know how many times does the word “Risk” appears?


Verification Approach

Version from July 2001 Version from October 2015

3 23



Why change our work cultures, & regulatory framework to move from the traditional qualification approach to a value added model?

QRM and Science

Base Approach

Significantlyreduce

costs/time

Adopting practices which are lean and

efficient

Alignment with post-ICH Q8, Q9 and Q10 regulatory

expectations

Decrease projects

complexity and “bureaucracy”

Ensure focus is on quality-

critical system features

Improve process

knowledge as basis for

subsequent operations and

life cycle maintenance

Provideclarification of

roles and responsibilities,

with more efficient use of

SMEs

More consistent and reliable

achievement of URS



FINAL CONSIDERATIONS

You may stay here

…just stop here

…or here

...or may want to get there!

Risk Assessment

Departmental Approach

Functional Roles

Predefined Steps

Conservative

Being In Conformity

Risk Management (QRM)

Process Approach

Expertise and Knowledge

Added Value Activities

Flexible and Efficient

Being In Control


REFERENCES

▪ ASTM E2500-07 “ Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Systems and Equipment” (2007)

▪ ISPE Guide: Science and Risk-Based Approach for the Delivery of Facilities, Systems and Equipment (ISPE FSE Guide) (2011)

▪ ISPE Baseline® Guide: Volume 5 –Commissioning and Qualification (2001)

▪ European Good Manufacturing Practice (EU GMP) Part I - Basic Requirements for Medicinal Products

▪ EU GMP Annex 1 – Manufacture of Sterile Medicinal Products

▪ EU GMP Annex 15 – Qualification and Validation

▪ EU GMP Annex 20 – Quality Risk Management

▪ FDA 21 CFR Part 210 – Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs; general.

▪ FDA 21 CFR Part 211 – Current good manufacturing practice for finished pharmaceuticals.

▪ ICH Q9 – Quality Risk Management

▪ ICH Q10 – Pharmaceutical Quality System


Questions?

Thank you for your [email protected]

[email protected]

mailto:[email protected]

mailto:[email protected]

From Traditional Approach to Verification Approach · Traditional Approach - Basic Concepts •...

Documents

Transcript of From Traditional Approach to Verification Approach · Traditional Approach - Basic Concepts •...