PREPURCHASE PHASE

9.2 PREPURCHASE PHASE

9.2.1 Identification of Needs

The rationale for bringing a new instrument into the laboratories should be well founded. The benefits of acquiring the instrument, such as increasing productivity, meeting a specific need or regulatory compliance requirements, or enhancing the capability of the laboratories, should justify the expenditure of valuable resources required to bring the instrument in house and to support its operation.

9.2.2 Planning

Instruments to be used in a GMP environment have to be validated prior to regular use. It is useful to develop the instrument implementation plan as a plan to outline the steps necessary to validate the instrument and to support the use of the instrument through its functional life in the laboratories. The implementation plan should highlight the activities in the validation of the system and will be the guiding document of the project. Typically, the validation plan includes:

ž The objectives and scope of the project

A description of the system to be implemented ž The location of the instrument to be installed

A validation approach ž The roles and responsibilities of the implementation team

A project time line and milestones ž Constraints: physical (space, facility), financial, and project deadline ž References of relevant information

Note: The instruments used in the laboratories vary significantly in the design and operation complexity. The validation requirements should reflect the level of complexity of the instrument. It is obvious that the amount of effort required to validate a simple pH meter will be different from that required for a fully auto- mated dissolution system. The Good Automated Manufacturing Practice (GAMP)

PROCUREMENT, QUALIFICATION, CALIBRATION

Table 9.1. GAMP Classification for Laboratory Instruments

GAMP Classification Examples A. Simple COTS instrument (commercial

Balance, pH meter, digital thermometer off-the-shelf) B. Complex COTS instrument

HPLC firmware, GC firmware C. Simple SCADA (supervisory control and HPLC, GC, FTIR, UV data acquisition) system

D. Complex configurable SCADA system Automated workstations for tablet assay and dissolution E. Bespoke (custom) SCADA system

Custom-designed automation systems

Table 9.2. Validation Activities for Instruments in Each GAMP Class

Class Activity

A B C D E Planning

Yes Yes Yes Requirements

Yes

Yes

Yes Yes Yes Supplier audit

Yes

Yes

Evaluate Yes Yes Evaluation

No

Evaluate

Yes Yes Yes Design qualification

Yes

Yes

Evaluate Yes Yes Qualification: IQ, OQ, PQ

No

Evaluate

Yes Yes Yes Validation report

[4] developed by the International Society of Pharmaceutical Engineers (ISPE) provides a useful reference for classification for laboratory instruments according to their complexity (Table 9.1) and the related activities required to validate the instruments (Table 9.2).

9.2.3 Budgeting and Justification for Acquiring New Instruments

It is necessary to capture all the costs required in implementing an instrument in

a facility to avoid serious budget shortfalls. The cost should include at least:

ž The purchasing cost of the instrument and accessories. ž Applicable taxes associated with the purchase. ž Site preparation. It can be a significant percentage of the total cost, depend-

ing on the scope of the building modification that is required. ž System qualification. Qualification protocols and the service to execute the

qualification protocol may not be included in the cost of the instrument and have to be purchased separately from the instrument vendor.

PREPURCHASE PHASE

ž Training. There may be a need to send users to the instrument supplier to take operation and maintenance training. The traveling and tuition should

be included in the budget. ž Contingency funding. This is included to cover any unforeseeable expenses. which is typically 10% of the sum of the cost of the foregoing items. Building modification changes during site preparation can lead to significant cost overruns.

Different emphasis may be used when justifying a new piece of instrument for use in a quality control laboratory as compared to an R&D laboratory. In a quality control environment, the justification is based primarily on the need and also on the return on investment. For R&D laboratories, the capability enhancement potential of the new instrument is also a major consideration. The investment in new R&D instruments may not have an immediate return.

9.2.4 Requirements

User Requirements. The users first need to decide on the major tasks the instru- ment should be able to accomplish. For example, if users need an HPLC for routine product release testing, an HPLC system with a variable-wavelength UV detector, isocratic pump, and an autoinjector is likely to be sufficient for routine assay of main active ingredient(s) in a pharmaceutical dosage form. However, if the HPLC system is intended to be used for stability-indicating assay or impuri- ties assay, a system with a gradient pump that provides a wider choice of solvent strength for better separation and a more sensitive detector may be required. These high-level requirements, such as a HPLC system for routine product test- ing or stability studies, are captured in the user requirements. The ability of the system to perform tasks outlined in the user requirements has to be demonstrated in the performance qualification phase of the qualification process.

Caution should be used when putting together the user requirements since it will have a major impact on the amount of work required for the system qualifications. The more tasks that are specified in the user requirements, the more work has to be done during the qualification process to demonstrate that the instrument is capable of fulfilling the requirements. If the system is capable of performing additional tasks that are not required by the user requirements, there is no need to validate those tasks.

Functional Requirements. Based on the user requirements, more detailed func- tional requirements can then be defined. Take as an example a gradient HPLC system with UV–Vis detection required to run a stability-indicating method. The functions of each of the hardware and software components required to perform the tasks in the user requirements should be specified. The functional specifications typically include:

Hardware Components

ž Functions of each component and operation range:

PROCUREMENT, QUALIFICATION, CALIBRATION

ž Pump: flow rate range, gradient mixing mechanism, gradient accuracy, and solvent-delivering capability

ž Detector: wavelength range, wavelength switching, sensitivity, and reso- lution (slid width) ž Autoinjector: injection volume range, sample capacity, level of carryover, precision, and temperature range if refrigeration of samples is required

ž Column temperature control: temperature range ž Operation environment of the system: building temperature and humidity

range ž Site requirements to support the operation of the instrument: power supply (voltage and current) and ventilation ž Health and safety requirements: electrical and mechanical safety ž Uninterrupted power supply (UPS): the length of the support during power

failure and the power rating of the UPS

Software

ž Computer operation system and network requirements if required ž User interface: operation modes and setup ž System interface with hardware: supervisory control and data acquisition

(SCADA) program ž Data type and memory capacity

21 CFR Part 11 Electronic Records and Electronic Signatures (ERES): sys- tem security, data integrity and tracibilty, audit trail, and archive

ž System recovery Design Qualification. For a commercial system, users generally have very little

or no input into the design of the instrument. The design qualification in this case outlines the user and functional requirements and the selection rationale of a particular supplier. For a custom-designed system, the design qualification outlines the key features of the system designed to address the user and functional requirements.

9.2.5 System Evaluation

In addition to the factors already discussed, there are several others that need to

be considered: ž It is obvious that the instrument has to be able to perform the tasks detailed

in the user requirements. ž Cost. It is best to strike a balance between the cost and the performance of an instrument. The least expensive instrument may not be the best invest- ment; the most expensive instrument may not be the best instrument for a particular operation.

POSTPURCHASE PHASE

ž Ease of use. Simplicity is beauty. Purchasers should think about the gen- eral background of potential users. Not all users are ready to tackle very complicated operations, due to time constraints and training.

ž Vendor’s reliability. The vendor that supplies the instrument should have a track record of providing high-quality instruments and after-sale support. A

vendor audit should be conducted for a new instrument supplier to eval- uate the company’s ability to build high-quality products. Purchasing an instrument from a financially unstable vendor is risky.

Most modern instruments are controlled by computer. It is important to have assurance from the vendor that the software and hardware were developed accord- ing to industrial standards such as the IEEE software development guide or the Good Automated Manufacturing Practice (GAMP) guide developed by the International Society of Pharmaceutical Engineers (ISPE). The software develop- ment life-cycle approach should have been used during development. Key quality assurance procedures, such as change control, security, management involvement, and off-site storage should be in place [5–10]. Computer system validation is discussed in Chapter 17.