Day-2, Session - 8.2Day-2, Session - 8.2

““Water System Water System Commissioning & QualificationCommissioning & Qualification””

(30 m)(30 m)

Speaker -Speaker - Sumant Baukhandi, PhDSumant Baukhandi, PhD

Commissioning & Qualification

IntroductionQuality By DesignRisk Based ApproachSystem Qualification DocumentationSystem Qualification Sampling ProgramAcceptance CriteriaQualification ReportsChange Control, andRe-qualification

Commissioning & Qualification

Established science & engineering methods to deliver cost effective

• Design and installation considering:• cGMP

• Health

• Safety

• Environmental

• Ergonomic

• Maintenance

• Operation

• Statutory requirements

• Recognized industry guidance

QBDQBD

QRMQRM

EQSEQS

Commissioning & Qualification

Commissioning and qualification comprise the

validation process by which a system is put into

service and demonstrated to consistently produce

water of a specified quality under various

conditions, while operated under set procedures

Although both are typically separated within a

project schedule, they are in essence, one

continuous process

Purified Water System Skid

Commissioning & Qualification

۩ Summary of key concepts during Commissioning and qualification: ¤ Due to the interdependence between activities and those

involved, excellent communication, planning and coordination between operations, engineering, commissioning, and validation personnel will enable timely and cost-effective project completion

¤ Each component of the system should be built in accordance with plans and specifications and should be inspected, tested and documented by qualified individuals.

¤ These activities, and production of supporting documentation, are defined as Good Engineering Practice (GEP)

Commissioning & Qualification

۩ Summary of key concepts during Commissioning and qualification: GEP recommends a minimum level of documentation

for all systems and equipment.

This encompasses design, fabrication, vendor testing,

construction, field inspection and commissioning.

If these documents are appropriately planned,

organized and authorized, they may become an

integral part of qualification support documentation,

thus avoiding redundancy and saving time and money

Commissioning & Qualification

۩ Summary of key concepts during Commissioning and qualification:

ФDesign criteria and documentation requirements

should be clearly defined early in the design phase, to

ensure clear expectations and appropriate planning

ФThe firms, vendors and contractors should be required,

per the system specifications:

Ф to provide the necessary documentation,

Ф to avoid unnecessary costs and delays associated with

obtaining or creating them

Ф these facilitate timely commissioning and validation

Commissioning & Qualification

۩ Summary of key concepts during Commissioning and qualification:

ФDuring construction, timely review of documentation

and periodic “walk-throughs” can ensure that

Installation Qualification requirements are met

ФCommissioning takes the system from a state of

substantial completion to a state of operation. It is the

phase of a project that includes mechanical

completion, start-up and turnover

Commissioning & Qualification

۩ Summary of key concepts during Commissioning and qualification: Ф Commissioning incorporates a systematic method of testing

and documenting the system at the conclusion of

construction and prior to the completion of validation

activities

ФCommissioning documents should not be created and

executed just for the purpose of regulatory compliance

ФHowever, commissioning tests and documentation will

typically satisfy many installation and operational

qualification requirements

System Qualification & Documentation

۩ This documentation encompasses engineering, installation & testing:

ФA system description stating design intent

ФA Schematic drawing (P & ID)

ФWritten system specifications

ФDetailed design drawings

ФVendor manuals and drawings

ФField inspection & test reports

ФSystem qualification test results

System Qualification & Documentation

۩ When compiling documentation, particular attention should be paid to the following:Ф Schematic documentation may be enhanced by the inclusion of a

system isometric diagram(s), indicating location and numbering

of welds, relative elevations, slope of lines and points of drainage

Schematic of Water System & Splg.xls

Ф The system specification should indicate performance criteria &

design parameters

Ф Field inspection & test reports should include cleaning and

passivation procedure and record weld parameter documentation

and inspection reports, slope verification and verification of the

absence of “dead-legs”

System Qualification & Documentation

System Qualification & Documentation

۩ When compiling documentation particular attention should be paid to the following:Ф System qualification tests may or may not be a subject to a

pre-approved protocol addressing qualification test

requirements.

Ф In either case, test results should be reported in direct

comparison to acceptance criteria derived from system

design and operating specifications

Ф System qualification tests should include verification of all

automated functions, specified temperature control,

distribution system velocity and initial water quality

determination

System Qualification Sampling Program

۩ The qualification of water systems is unique in that performance must be proven over an extended period of time, and is subject to variations in use rate and initial feed water quality.

۩ Therefore, the sampling program associated with pharmaceutical water systems validation is unique & specialized

System Qualification Sampling Program

۩ Extensive sampling is required to establish and confirm that the entire system will operate within specified operating ranges: Ω to develop and evaluate the system

operation and maintenance procedures, and

Ω to verify that the water produced and delivered to the point-of-use consistently meets the

required quality specifications and acceptance criteria

۩ This portion of the program is sometimes termed PQ

System Qualification Sampling Program

۩ Because of the critical impact that water has upon pharmaceutical quality, the sampling program and evaluation of results is usually subject to a pre-approved plan or protocol, with clearly defined acceptance criteria

۩ Also included should be procedures to deal with deviations from specified parameters and analytical results

System Qualification Sampling Program

۩ The sampling program consists of three successive phases, each with a specific purpose and sampling scheme, as outlined later

۩ The initial phase of the sampling program typically begins after the water system is shown to be fully operational, as demonstrated through integrated system testing in OQ

System Qualification Sampling Program

PHASEPRIMARY OBJECTIVES

* Develop appropriate operating ranges

* Develop & finalize operating, cleaning, & maintenance

procedures

* Demonstrate production and delivery of water of the

required quality

* Demonstrate consistent operation within established ranges

* Demonstrate consistent production and delivery of water of

the required quality

* Demonstrate extended performance

* Ensure that potential seasonal variations are evaluated &

treated

Weekly 1 year

2

3

Chemical Thrice

a day & Micro

once a day

Daily

DURATION

1Daily for

2-4 weeks

2-4 weeks

System Qualification Sampling Program

۩ Phase I¤ Purpose of this phase is to establish appropriate

operating ranges and provide data for the development of cleaning & sanitization procedures & frequencies

• Sampling should be performed after each step in treatment process & from each POU

Sampling Plan for Water System.xls

• Incoming feed water tested as per relevant drinking water regulations

• The FDA Guide to Inspections of HPWS and WHO Guidelines suggest daily sampling for two to four weeks, but recognizes that other sampling programs may be acceptable

System Qualification Sampling Program

۩ Phase I¤ In devising the sampling scheme,

consideration should be given to: the system configuration, maintenance cycles, how the water is drawn for use, and the expected or potential variation in Chemistry &

microbiological attributes, at each potential sampling point In treatment, chemistry testing is specific for each

processing step and microbiological testing between each components is important to determine the microbial load and the component’s ability to manage the load (Component qualification)

RO Modules

System Qualification Sampling Program

۩ Phase I¤ At the end of this phase, SOPs for system operation &

maintenance should be developed and approved for continued interim use during next phase

System logs, documentation for critical parameters (e.g., conductivity, TOC data, sanitization data etc) and responses to critical alarms or action levels should be reviewed, to verify the appropriate procedures are in place

In addition, the process that will be followed to investigate a confirmed test failure should be developed at this time. The intent of this process is to assess whether a failure is localized (i.e., isolated to a specific port) or systematic and to define how different types of failures will be handled

System Qualification Sampling Program

۩ Phase II¤ Purpose of this phase is to demonstrate that the system

consistently operates within the predetermined operating ranges and delivers water of the required quality when operated in accordance with the SOPsIf water is used through an attached hose, then the

sample should be taken from the hose

Phase II allows the gathering of sufficient data to establish microbial alert and action limits

Here the SOPs and the Specifications are firmed up.

System Qualification Sampling Program

۩ Phase III¤ Purpose of this phase is to demonstrate that, when

operated for an extended time period (typically one year) the system produces and delivers water of the required quality despite possible seasonal variations of the feed water Sample locations, frequencies and test requirements are

based on the established procedures

At the end of this phase the validation is considered completed

Ongoing monitoring & trending, then will establish a continuing record of water quality

Acceptance Criteria

۩ Acceptance criteria for water are dependent upon its use:

For Purified water & WFI, chemical acceptance criteria can be as per USP

It is expected that a well designed water system, operating within specified design parameters will consistently be able to meet these criteria

Therefore, failures in chemical analysis during Phase 1 & 2 must be investigated, the reason for failure corrected, and (except where errors in sampling or laboratory error are clearly indicated) the sampling phase extended to re-establish consistency of performance

Acceptance Criteria

۩ Acceptance criteria for water are dependent upon its use:

Microbial quality although described by the USP, is in fact, established by the user based upon the water use.

• The USP does recommend action levels for the different waters in its General Information chapter. These are 10 CFU/100mL for WFI and 100 CFU/mL for Purified water

• These may be employed as initial acceptance criteria for system qualification, although some flexibility is allowable, depending upon system design and use

• It is permissible that a single excursion followed by acceptable re-sampling would not constitute a failure

Acceptance Criteria

۩ Acceptance criteria for water are dependent upon its use:

In addition, because of the inherently bacteriostatic nature of WFI production and distribution systems, it should be expected that the large majority of samples should be well below the initial acceptance criterion

• Therefore, for WFI it is prudent to establish a sample average acceptance criterion, which will be below the limit for a single sample

• Failure investigation would be handled similarly to chemical analysis failure

Acceptance Criteria

۩ Acceptance criteria for water are dependent upon its use:

During Phase 1 and 2, normal system microbial limits may be established

Acceptance criteria may be then converted to alert and action levels for use during Phase 3 and beyond

This would take into account repeated excursions from the norm as well as step increases in micro count

Qualification Reports

۩ Qualification data should be compiled and conclusions written into summary report:

• Reviewed and approved by those responsible for operation and quality assurance of the water system

• An interim report should be written and approved at such time during the qualification sampling program, as it is desired to use water in production activities

• A summary report should be prepared at the conclusion of Phase 2, periodic updates provided throughout Phase 3 and a major update issued at the conclusion of Phase 3

Change Control & Re-qualification

۩ Changes to the system must be assessed with regard to potential impact of the change on the entire system

۩ Required action would be determined based on that assessment

۩ It may involve extensive re-qualification, localized increased in sampling frequency, or inclusion in the routine monitoring program

THANKS!

For inquiries please contact –Sumant Baukhandi, PhD 

Director – Pharma Institute of GMPs,

Director – pharmaACCESS

7, Phase-1, Vasant Vihar,

Dehradun-246 006

Uttaranchal State, INDIA

 

Landphone: 91-135 276 3092

Cellphone: 91- 99970 10901

Email ID: pigmpinstt@gmail.com ; sumant091154@rediffmail.com

Website: www.pigmp.com