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Design Qualification of TruScan Raman Handheld Spectrophotometer

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1 2 3

OBJECTIVE .................................................................................................................................................... 1 REFERENCE MATERIAL ............................................................................................................................... 2 ROLES & RESPONSIBILITIES ...................................................................................................................... 2

4 PRODUCT FUNCTIONAL REQUIREMENTS FOR TRUSCAN RAMAN HANDHELD SPECTROPHOTOMETER ...................................................................................................................................... 2 4.1 Introduction .............................................................................................................................................. 2 4.2 System Description Overview .................................................................................................................. 2 4.3 Basic Theory ............................................................................................................................................ 2 4.4 Instrument Overview ................................................................................................................................ 3 5 GMP AND ER/ES ............................................................................................................................................ 4 6 TECHNICAL REQUIREMENTS ...................................................................................................................... 4 6.1 Instrument/Basic Operational Design ...................................................................................................... 5 6.2 IT Infra structure (computer hardware, operating system) ...................................................................... 9 6.3 Application software................................................................................................................................. 9 6.4 Methods and parameters ....................................................................................................................... 10 6.5 Data collection / data entry .................................................................................................................... 11 6.6 Report .................................................................................................................................................... 12 6.7 User properties and access ................................................................................................................... 13 6.8 User account and password management ............................................................................................ 14 6.9 Data integrity / audit trail ........................................................................................................................ 15 6.10 Data backup and restore ....................................................................................................................... 18 6.11 Data transfer (export/import) ................................................................................................................. 18 6.12 Safety ..................................................................................................................................................... 18 6.13 Suppliers quality system ....................................................................................................................... 19 6.14 Documentation requirements ................................................................................................................ 20 6.15 Service and support ............................................................................................................................... 20 6.16 Training .................................................................................................................................................. 21 6.17 Delivery and installation ......................................................................................................................... 22 6.18 Qualification services ............................................................................................................................. 23 7 DEFINITIONS ................................................................................................................................................ 24 8 9 MODIFICATION / CHANGE CONTROL ....................................................................................................... 25 APPROVALS ................................................................................................................................................ 25

OBJECTIVE

The objective of the document is to provide the owner of this document with the critical design qualification criteria for TruScan Raman Handheld Spectrophotometer for design, reliability, performance and compliance. Specifications are listed in terms of the design specification requirement, a brief summary justification for the need for the requirement and a summary explanation of how the design specification was implemented in the product.

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REFERENCE MATERIAL

The reference materials used to develop the critical design qualification criteria are Ahura Scientifics internal documents developed during the initial design of the TruScan such as the User Requirement Document, the System Requirement Document. These documents are archived under electronic format at an off-site secure location and area available on demand provided that a non disclosure agreement is signed between Ahura Scientific and the demander.

ROLES & RESPONSIBILITIES

Its the responsibility of QC management to insure that all the validation steps have been executed properly and that all the documentation pertinent to the validation of the TruScan Raman Handheld Spectrophotometer are available for subsequent inspection.

PRODUCT FUNCTIONAL REQUIREMENTS FOR TRUSCAN RAMAN HANDHELD SPECTROPHOTOMETER

Introduction

4.1

The TruScan instrument is intended to simplify and secure the receiving goods control of raw materials and packaging material at pharmaceuticals manufacturing facilities. The raw materials above are used to produce pharmaceutical products and therefore the instrument must fulfill the requirements of a pharmaceutical industry. The various physical forms of raw materials to be analyzed consist of: - Solids (fine powder, micronized powder and granules) - Liquids (high viscosity and low viscosity) - Capsule gels (semi-finished product; oil base filled into capsule) The Ahura Scientific TruScan Raman analyzer is designed for the non-contact analysis of active pharmaceutical ingredients and excipients for identification purposes. The Raman analyzer is completely self-contained, operating on battery power (small lithium ion rechargeable cell), and housed within a rugged and sealed enclosure. The unit is constructed with a stabilized 785-nm solid-state laser source, an integrated imaging module, and a 2048-pixel diode-array-based spectrograph. All electronics, including a single-board processor, also are fully integrated. The user interface is a simple set of pushbutton controls linked to a menu-driven color liquid crystal display. A chemometrics-based spectral search package is included that provides conclusive identification. 4.2 System Description Overview

The Raman analyzer system is designed to support process development and production of pharmaceutical products. The system is a hand-held device and operated through a set a push buttons and configurable to operate through a PC. The output is through the color liquid crystal display and may be communicated over a network. The Raman analyzer operates by illuminating the materials in a container with a laser and collecting and analyzing the scattered light. 4.3 Basic Theory

Raman spectroscopy is a form of vibrational spectroscopy and as such is related to near- and mid-IR absorption spectroscopy. Similar to the IR absorption techniques, Raman spectroscopy measures the vibrational frequencies of various parts of a molecule. These frequencies depend on both the bond strength and mass of the bound atoms as well as other factors such as intermolecular interactions. The 'pattern' of vibrational frequencies from a molecule is, therefore, highly

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Design Qualification of TruScan Raman Handheld Spectrophotometer

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characteristic of a given molecular species and, for solid samples, of the crystalline arrangement of those molecules. Raman spectra may be readily recorded from gasses, liquids and solids. While IR spectroscopy is essentially based on illuminating the sample with a broad range of wavelengths of IR light and measuring which are absorbed, a Raman spectrum is obtained by illuminating the sample with a single wavelength of light from a laser and collecting and analyzing the resulting scattered light. Briefly, the basic experimental arrangement to perform Raman spectroscopy includes the following steps: 4.4 4.4.1 To obtain a Raman spectrum the sample is illuminated with light from a laser. The molecules in the sample 'scatter' the incident laser light. Some of this scattered light contains detailed information about the molecular properties of the sample. The scattered light is collected and analyzed using a Raman spectrometer to produce a Raman spectrum. Raman spectra are generally clear, well resolved and rich in features facilitating detailed and unambiguous interpretation. The spectra contain large amounts of information about chemical composition, intra- and intermolecular phenomena, and the longer range structure of a sample. Instrument Overview System overview

The figure below shows the TruScan instrument. The shaded box in figure 2.1 highlights the parts covered by the Product Functional Requirement Specifications in this document (the TruScan instrument and its Syncserver application). The user access levels Admin and Developer need access to a web browser (Internet Explorer IE). Detailed system component requirements are stated this Chapter.

TruScan Instrument

Sync application on server/PC

Network Printer
Figure 4.1 Overview of the TruScan instrument.

Archive

PC/IE

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4.4.2

Operational process

The proposed use of the instrument is: 1. User creates and validates methods. Methods are stored in the instrument. 2. To perform ID verification, user chooses Identification method. 3. User performs ID verification of incoming goods with TruScan. 4. User connects TruScan to network for transfer of result files and reports. 5. Electronic data (result files) are stored on a network data drive for archiving and further processing (such as signature, second review)

Data and document created during system use: Instrument test data (yearly test and daily test performed by Users) Raw data (spectral data and calculated data in the report files) Reports (printed report files)

GMP AND ER/ES

The TruScan instrument will be used at manufacturing facilities within pharmaceutical organizations, in an area controlled by Good Manufacturing Practice (GMP) for pharmaceutical production. The TruScan instrument collects electronic data in GMP environment. The electronic data collected in such environment must closely follow 21 CFR part 11 Electronic Records & Electronic Signatures (ER/ES) guidance. TruScan complies with all the 21 CFR part 11 Electronic Records & Electronic Signatures (ER/ES) rules. Detailed requirements on system and data security are stated in chapter 6 Technical requirements section System and computer security.

TECHNICAL REQUIREMENTS

(Requirements marked with * are GMP requirements) Operational Performance and Basic Design Continued next page

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6.1 ID

Instrument/Basic Operational Design Requirement description 6.1.1 Device must Identifies the solids and liquids raw materials with PASS/FAIL decision and Raman Spectroscopy Device must be identifying materials without sample preparation

6.1.2 6.1.3

The device must be fitted to use a variety of power sources.

6.1.4 6.1.5

Power Indicator. Visual indication of the battery power must be present on the device Power-Power Savings. Device must have an inactive power mode to minimize power consumption when not in use. Power Low Power Warning. Device must warn user when battery is running low. Subsequently, device must be able to soft shut down automatically Power hard off. Device must be able to successfully handle a recovery from a brutal power interruption

6.1.6

6.1.7

6.1.8 Device must be equipped with a permanently mounted sign or equivalent that contains: supplier name, model and serial no and technical data (voltage, frequency etc). 6.1.9 If the instrument contains firmware, its identity and version must be clear either from a label or readable on the instrument (display or in the system). Environmental noise such as Environmental Light and Stray Light: Environmental light/Stray Light must not be interferencing with measurement. Detector Device must have a Raman excitation laser wavelength between 700 and 800 nm.

Implementation in TruScan TruScan can identify solid and liquids with PASS/FAIL decision by Raman spectroscopy. The TruScan can return some other possibilities and their probabilities of match if the result was a FAIL. The TruScan can identify materials without sample preparation The system is battery powered or mains powered via a supplied universal voltage transformer unit. The transformer unit can use 100 240 V, 50 or 60 HZ power when mains powered or for battery recharging. Battery operating life is no less than 5 hours of continuous use. Battery can be swapped very easily without tool. TruScan displays the battery power level (bars) on its screen. TruScan can be put to sleep during inactivity period. The sleep mode can also be triggered automatically if the unit is not in use for a defined period of time. TruScan battery indicator turns read when the TruScan device is running out of battery. TruScan will soft shut down automatically if battery is running low. TruScan was tested to recover from a power hard off. However, soft shutdowns are recommended by the manufacturer. Windows CE and the TruScan internal software architecture have been designed to withstand a hard off . Instrument is fitted with a permanently mounted label stating supplier name, model, and serial number. Power technical data details are moldedin to the case next to the power input connector (9 VDC, 1.5 A) (power at instrument coming from universal voltage transformer). Instrument Firmware Version is available on instrument screen for administrator access under Tools>Settings>Support>Ver Environment conditions such as neon light or sun light are considered incertitude and are measured automatically. TruScan adjust stray light and dark current automatically. In-house manufactured 2048 element silicon CCD TE cooled detector TruScans excitation laser wavelength is 785 +/0.5mm, 2 cm-1linewidth.

6.1.10

6.1.11 6.1.12

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6.1.13 6.1.14

Laser output must be less than 500 mW Source life must be adequate so as to not require frequent changes. Device must acquire Raman Spectra in the range of at least 260cm-1 to 2800cm-1. Device must have a spectral bandwidth of 15cm-1. The supplier must give suggestions for tolerance limits for instrument test procedures.

6.1.15 6.1.16 6.1.17

6.1.18 The system must have performance characteristics for spectrometer noise, LOD, LOQ and spectral bandwidth that meet the acceptance criteria for USP 1120 Raman qualification protocol and USP 1220 for validation of analytical methods.

Laser is a class3B laser. Laser output is approximately 350mW or lower. >10,000 hrs MTBF corresponding to about 2,000,000 runs or 1and year of continuous laser operation MBTF TruScans spectral range is at least 250cm-1to 2875 cm-1. Spectral bandwidth or spectral resolution is 7-10 cm-1. Instrument self-test procedures are built-in to instrument, and tolerance limits are embedded in test procedures. These are not user-modifiable. TruScan is designed to perform category IV assays (identity tests) as detailed in USP <1225>. USP <1225> indicates that the only data element required for category IV assay method validation is specificity. As such, LOD and LOQ are not relevant. Additionally, spectral bandwidth and spectrometer noise are not settable/alterable on TruScan, so it is Ahura Scientifics interpretation that the DQ and method validation will be sufficient to demonstrate sufficiency for the intended use. TruScan is fully handheld and fully portable. It weighs less than 3 pounds. The TruScan enclosure form factor measures 12.5 x 5.88 x 3.14 in. It can be used in any orientation and moved around to be used at the point of need. The instrument has been designed for field usage and is not susceptible to vibration, temperature and shocks. Code 39, code 93, code 128, EAN-13, UPC-A, interleaved 2 of 5 are supported by TruScan TruScan is CE rated TruScan is supplied with a nose cone shield that assists in positioning materials for point and shoot analysis. TruScan can be used with this accessory to test solids, liquids and powders. The separate purchase of a vial holder and tablet holder facilitate the testing of chemicals in these forms. TruScan can analyze materials through clear vial, amber vials, plastic double bags and other transparent containers. Ethanol, 5% bleach and detergent are perfectly acceptable cleaning agents for the TruScan unit. Plastic sleeves for TruScan are available to prevent cross-contamination

6.1.19

6.1.20

6.1.21 6.1.22

Device must be supplied with a statement referring to the capability of being moved about to make measurements in various localities without detrimental effects to performance. Device must withstand shock and vibration caused during mobilization and analyzing activity to maintain accuracy and reproducibility of results Device must read material bar codes used at pharmaceuticals facilities and insert that information into the data file and the result report. Device must be CE Rating

Device must be supplied with suitable accessories for measuring solids, powders and liquids

6.1.23

6.1.24

The device must be able to be cleaned with no detectable damage with the following cleaning agents: Ethanol; 1% detergent, 5% bleach aqueous solution The device must minimize the risk of crosscontamination

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6.1.25

Device must meet USP, NIST and ASTM requirements for compliance and be supplied with: Primary wavelength accuracy (x axis) calibration check and standards traceable to a national standards. Raman laser wavelength accuracy calibration check and standards Signal level(y axis) calibration checks and standards traceable to national standard.

TruScan complies with the requirements of USP<1120> Raman spectroscopy and its reference to NIST and ASTM as they pertain to identity testing (qualitative analysis; note that significant portions of <1120> only apply to a quantitative analysis). Pursuant to the guidance in the ISPE/AAPS/FDA document Qualification of analytical instruments for the use in pharmaceutical industry: A Scientific Approach(AAPS PharmSciTech Vol 5, art 22(2004)) and the new USP general chapter <1058> Analytical instrument qualification (USP 31-NF 26First supplement) the TruScan uses the preferred holistic evaluation in its test function which tests all TruScan subsystems in concert to assure that the instrument is operating in a manner consistent with its intended use for material identity testing. This holistic evaluation encompasses 12.1,12.2 and 12.3. This test is conducted using a polystyrene rod (or acetaminophen, benzonitrile, acetaminophen, cyclohexane: ASTME1840 materials) provided by Ahura as part of its standard offering. All references come with a certificate of analysis. If desired, the user can set up additional methods using ASTM E1840 materials and/or their own site materials for the purposes of PQ and/or system suitability testing. Detailed statements of compliance with US<1120>, EP 2.2.48 and 21 CFR part 11 are available as supporting documentation.

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6.1.26

User must be able to perform calibration of the device

6.1.27

Device must prompt for preliminary System Suitability checks before use. Device must be able to be used by non-scientific operators such that the operator is taken through a device controlled measurement sequence Software applications must be configurable in regard to acceptance limits for Pass/Fail recognition

6.1.28

TruScan does not need to be recalibrated on a regular basis. TruScan is calibrated at the factory directly in accordance with ASTM E1840-96 (2002). Cyclohexane, acetonitrile, and toluene bands are used to define the x-axis calibration of the system, and this calibration is subsequently verified with cyclohexane, acetonitrile, toluene, acetaminophen (4-acetomidophenol), and polystyrene. (All five (5) of these materials are recommended in ASTM E1840-96 (2002)). The laser is also directly calibrated to zero (0) wavenumbers at this time, and continuously monitored thereafter with automated compensation in software. The procedure using atomic emission lamps is common for laboratory spectrometers with tunable gratings and lasers (for convenient field realignment and calibration). TruScans spectrometer components are fixed-in-place and hermetically sealed and can not be field adjusted. A neon atomic lamp internal to TruScan is simply used to monitor the calibration in the context of intended use for ID testing. This function is performed as part of the Test system suitability function on TruScan. A performance test can be executed to verify and certify the performance of the TruScan. Protocols and Standards kit are available. TruScan is not designed for quantitative analysis. To enable method transfer between instruments TruScan is calibrated at the factory using an externally-placed white light source in full accordance with method A in <1120>. Furthermore, TruScan is not a laboratory instrument. TruScan includes a Test function that employs an external polystyrene sample to evaluate system suitability at the standard point of sampling. Performance qualification (PQ) regimes may, at the customers discretion, use additional samples. There is no prompt. Before each run, a system check is automatically performed to insure reliable data. TruScans embedded workflow software ensures the correct standard operating procedure or method is followed for each sample. The software is not configurable in regard to acceptance limits Pass/Fail recognition.

6.1.29

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6.2 ID

IT Infra structure (computer hardware, operating system) Requirement description 6.2.1 Handheld device must allow secured communication with PC/server directly or through a LAN 6.2.2 The Transfer application must work on computers with operating systems Windows 2000, Windows Vista or Windows XP. It must be possible to use Antivirus program on the PC/server where the Transfer application is installed.

6.2.3

6.2.4 Device must permit the upgrade and update of the antivirus program.

Implementation in TruScan TruScan can be networked to a computer through a cross0ver cable or through a LAN using TCP/IP protocol. TCP/IP protocol ensures the integrity of the data and a fail-proof connection. Data generated on TruScan can be transferred to a PC or a server. Sync application has been tested on computers with Windows XP Professional installed and Windows 2000 as well as Vista. It is anticipated that it will also work on windows 7. Ahura Scientific has run the Sync server software on computers with Symantec (Norton) Antivirus Version 10 installed and no problems have been encountered. It is anticipated that Sync will remain compatible with future Symantec (Norton) Antivirus products, or that Ahura will issue a new version of Sync that is compatible with new releases of Symantec Antivirus products, but without knowledge of future functionality an absolute guarantee cannot be given.

6.3 ID

Application software Requirement description 6.3.1 Optional. User properties within the application software should be connected to the global user groups in the Corporate network.

Implementation in TruScan TruScan software is self contained, and does not have a facility to interrogate corporate user group database, therefore it cannot access details of individual users or user groups, and cannot use those details to configure TruScan user identities and access privileges.

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6.4 ID

Methods and parameters Requirement description 6.4.1 Device must have a storage capacity to store identification methods 6.4.2 * It must be possible to protect / lock methods.

Implementation in TruScan TruScan has a 1GB storage capacity to store methods and scans. Access to methods is permitted only to users with Developer and Administrator access privileges, under password protection. There is no separate password-controlled lock for each method. All modifications of methods are recorded, together with identification of modifying user, in the audit trail. Not possible at present. Note that a method history can be stored as an html file in the method folder. The audit log records that the method has changed, but not what was changed in the method. Method information is captured elsewhere: Every time a method or self-test is run, a full electronic record is created with a snapshot of all of the relevant information, including the complete method information. Method summary is available at the Method Management page in the WebAdmin program. Instrument connection icon on TruScan screen turns red when attempting to sync but failing to connect to SyncServer. Sync Error screen reports connection failure and type (e.g. no host detected). Sync filenames are configurable (by Administrator) to include fields: SampleID Barcode Method Name User Unit Serial No. (always included) Pass/Fail Administrator can also specify which field will form the first part of the filename.

6.4.3

6.4.4

* Optional. It should be possible to enter a comment when changing methods or parameters. * The system must create a new version of the method (parameter set) when it is changed; alternatively log the change in an audit trail (event log).

6.4.5 6.4.6

* It must be possible to print a summary of the method elements and parameters. * The device must give a warning for and report of communication problems identified during sync process. Optional. Naming of files should be configurable to contain information on: Sample ID Barcode Method name User to facilitate searching and sorting of result files.

6.4.7

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6.5 ID

Data collection / data entry Requirement description 6.5.1 * The system must insure that data generated by the device can be traced to its source (identity of user, instrument, and software).

Implementation in TruScan Identity of user, instrument serial number, and software version are embedded in all run and test data files.

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6.6 ID

Report 6.6.1 Requirement description * Reports must be printable. The following must be clearly indicated on every printed page: Instrument identity, Page number and total no of pages, Date and time of measurement User identity. * The report must contain identifier, for example Sample ID; to ensure that report can be traced to its sample. Implementation in TruScan Reports are stored in .pdf and .jpg file formats, both of which are printable. Reports include Device serial number, date of measurement, time of measurement, user identity. All reports are single page reports, and do not have a page number. All reports include Sample ID Reports include: Method name Raw data (spectrum and reference spectrum as overlaid figures Result (PASS or FAIL). Audit trail data in report includes: User name User login date and time Instrument serial number Instrument software version Instrument last self-test date and time Instrument last self-test result (PASS or FAIL) Instrument warnings in force Method name Run label Run calibration test result Run CCD check result Run laser power check result Run date and time Sample ID P value Result (PASS or FAIL) User note 6.6.4 * The instrumented must log data (time, event, and user) automatically for every step in a measurement. Optional. An administrator should be able to create, change or remove report templates. 6.6.6 * Users must not be allowed to change report templates. Data is logged (to report and audit log) on completion of the measurement. Administrator cannot modify report templates. Administrator can specify which file formats will be stored on Sync (Ahura binary format (.ASO) compulsory; .pdf, .jpg, .txt. .spc are optional). User access privilege level cannot modify report templates.

6.6.2

6.6.3

Reports must contain: Method name Raw data (spectrum as a figure) Results Audit Trail (AT) for the above data.

6.6.5

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System and computer security (Requirements marked with * are GMP requirements) 6.7 ID User properties and access Requirement description 6.7.1 * Tiered User access with password must ensure that only duly authorized user can have access to the device. The different access levels must insure that method development/modification and device settings are restricted to select groups. 6.7.2 *

Optional. It should be possible to show access levels and their configurations (what permissions are connected to each access level) in the system and on a printout.

6.7.3

6.7.4

* User authorization must be checked both when logging directly in the instrument and when using the web interface. * Screen saver on computer must be password protected. * Computer screen saver must be activated after 10 minutes of user inactivity. The instrument must have a configurable inactivation setting. The computer screen saver must have a function for manual activation.

6.7.5

6.7.6

6.7.7

Implementation in TruScan 3 user access levels exist: Administrator Developer User All authorized users must be allocated to one of these levels. Administrator has access to all the functionalities of TruScan, Developer has access to method development functionalities and user has access to run functionalities. The administrator can view and print a summary of unit users and their access levels from the Web Administration (WebAdmin) interface. Access levels and their configurations are detailed in the User Manual, section 4 Menus. User name and password checks control direct access to the instrument and access via the WebAdmin interface. Standard setting for computer shall fulfill the requirement. Computer setting should be set up by IT personnel of the purchasing organization Standard setting for computer shall fulfill the requirement. Computer setting should be set up by IT personnel of the purchasing organization An Administrator can configure the unit to require a new login after a settable inactivity time of 5 to 30 minutes. Standard setting for computer shall fulfill the requirement. Computer setting should be set up by IT personnel of the purchasing organization

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6.8 ID

User account and password management Requirement description 6.8.1 * Users must be configured in the application with unique names. 6.8.2 * It must not be possible to delete users, only to inactivate them. 6.8.3 * The system security function should give possibility to configure security principles for users. The following settings should be configurable: Password validity time (recommended is 3 months). Minimum password length (recommended is 6 characters). Number of passwords remembered in password history per user (recommended is 5). Number of failed password entries until locking (recommended is 3). 6.8.4 6.8.5 * Users must be permitted to change their own passwords. * It must be possible to print a list of current users.

Implementation in TruScan Identical names cannot be simultaneously active on the instrument. An Administrator can Inactivate or Delete a user from the system (an action which is audited in the system logs). TruScan does not impose a limitation on user password validity time. The establishment of and adherence to such controls should be assured by external measures. TruScan does not impose a minimum password length. The establishment of and adherence to such controls should be assured by external measures. TruScan does not record previously used passwords. The establishment of and adherence to such controls should be assured by external measures. Administrator can set the number of failed password attempts permitted before locking access to the instrument. Administrator can specify that, once locked, unlocking is by manual action of the administrator, or by automatic release of lock after a period of time configured by an Administrator. Users can change their own passwords on the instrument without Administrator intervention. Administrator can print a User Summary report from the WebAdmin interface.

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6.9 ID

Data integrity / audit trail Requirement description 6.9.1 * The system must secure that data cannot be overwritten. 6.9.2 *

Implementation in TruScan Data cannot be overwritten. If data storage capacity is full, instrument will refuse to make further measurements. TruScan automatically generates audit trails. Electronic records cannot be changed once created. TruScan also maintains a system configuration audit trail that documents changes made to the system configuration by developers and administrators. Audit trails are delivered to a secure location (identified by the system administrator in the device configuration) for permanent storage. System administrator cannot change raw data or reports on the system. All changes to configuration (users, methods, settings, etc) are recorded in audit log with user, date-time details. Administrator can change system clock function. The unit uses the following date format: mm/dd/yyyy hh:mm pm or dd-mmm-yyyy hh:mm

The device must ensure that data is securely stored to prevent any tempering deleting or overwriting attempt. Every change to methods should be managed through version handling or an audit trail.

6.9.3

The system administrator must not be able to change or delete electronic records (raw data, reports etc) without this being automatically traced to the individual.

6.9.4

* The system clock function of the instrument that registers time in event logs (for example access log, audit trail) must not be changeable by any user. The system clock function must use Windows standard format for date and time.

6.9.5

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6.9.6

The unit records in an audit log that the following events occurred, when they occurred (date and time) and who initiated the event: USER EVENTS: User lock-out Successful unit login Failed unit login Unit logoff successful web login failed web login web log off user password change user modified (any modification) user added user delete The system must automatically register/log events in an audit trail, when the user creates, changes or deletes Electronic Records (raw data, reports etc). SIGNATURE EVENTS active signatures import active signatures export active signature add active signature rename active signature delete active signature rename METHOD EVENTS method added method modified (any modification) method run method delete OTHER: configuration import configuration modified note list modified self-test run It is not possible to delete raw data, reports, or audit logs on the system. Not applicable. Raw data, reports and audit logs cannot be changed or deleted by users on the system. They can be transferred to a location specified by the administrator during the synchronization process.

6.9.7

* The system should make possible for the user to enter a reason for change/delete of ER.

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6.9.8

* Audit trail should have at least the following contents: Identity of user who performed activity to create, change or delete information. Date and time when this happened. The event that created changed or deleted the information. The reason for the change. *

6.9.9

New events must not overwrite previously registered events in the audit trail.

Audit trail includes: Identity of user who performed activity to create, change, or delete information. Date and time of creation, change or deletion of information. The category of the information created, changed or deleted (e.g., Method, User, Configuration setting). It is not currently possible to record a reason for the change. Between Syncs, new events are appended at the end of the audit log file, and do not overwrite previously registered events. During Sync, after confirmation of successful transfer of the existing audit log file to the secure archive, the existing Sync file is erased and a new audit log file is created which will be used until the next Sync. Audit trail function cannot be switched off. The audit log file cannot be amended or deleted in the system. The audit log file is not accessible to users on the system. Once transferred to the secure archive, the audit log file is a text file that can be searched using a text editor. The audit log file is an electronic file that can be printed once accessed from the secure archive.

6.9.10 6.9.11 6.9.12

* No shutoff of audit trail function must be possible when the system in use. * It must not be possible for a user to change or delete audit trail or parts thereof. Audit trail should be searchable for records, users, date, time and for type of event.

6.9.13

* Audit trail must be retrievable in electronic form as well as in paper printout.

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6.10 ID

Data backup and restore Requirement description 6.10.1 * Electronic data and reports must be copied to another physical storage unit with X equaling number of days interval. 6.10.2 * Electronic data and reports must be restorable with full integrity from another physical storage unit.

Implementation in TruScan Users organization must have plan for backing up data and this plan must be followed the drives and servers containing the data related to TruScan. Users organization must restore data to network drives when necessary using the backup plan in place.

6.11 ID

Data transfer (export/import) Requirement description 6.11.1 The system must be able to create and store electronic data and reports in the following formats: JPEG, PDF, TXT and SPC. 6.11.2 PDF files should be readable with Adobe Acrobat Reader version 7.01. 6.11.3 The system should allow further integration of the data file into a LIMS system

Implementation in TruScan Electronic data and reports can be stored in Ahura proprietary binary format (.ASO), and in JPEG, PDF, TXT, and SPC formats. PDF files are readable with Adobe Acrobat Reader version 7.01 The TruScan creates electronic records in TXT and PDF formats. These formats can be exploited by a LIMS system.

SHE (Requirements marked with * are GMP requirements) 6.12 ID Safety Requirement description 6.12.1 All instrument components must be CE marked and UL certified Implementation in TruScan The TruScan instrument, mains power and battery charging transformers, and the battery charging holder are all CE marked. The instrument is also UL913 certified. It is also UL61010-1 and CSA C22.2 No. 61020-2, EN 616010-1:03/93 +A2:07/95, FDA CDRH 1040.1 certified. The instrument has a warning label stating that it is a CLASS 3B LASER PRODUCT. It also has generic laser warning labels near the aperture.

6.12.2

The instrument must have a suitable warning label for laser radiation.

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Requirements for supplier and delivery (Requirements marked with * are GMP requirements) 6.13 ID Suppliers quality system Requirement description 6.13.1 *

The supplier must upon request be able to show certification and/or documents to describe which quality system that is used for development of the system (instrument, hardware and software).

6.13.2

The supplier must have a system for version handling of documents supporting the system.

6.13.3

* The supplier must have documented statements that the application software source code is available for review by the purchasing organization or by Purchasing organizations inspecting authority (for example FDA, MPA).

6.13.4

The supplier should have documented records of training and experience for its software developers.

Implementation in TruScan Certification and documents describing the quality system used for development of the system are available for inspection at the Wilmington, Massachusetts, USA headquarters of Ahura Scientific. Completion of appropriate confidentiality and non-disclosure agreements may be necessary for access to these documents. Ahura Scientific is also ISO certified. Registrar for the ISO certification is NSAI. ISO certificate has a date of June 17 2009. Ahura Scientific has a version control system in place for control of documents supporting the system. Ahura Scientific can supply statements that the software source code is available for review by the purchasing organization or inspecting authorities (for example FDA, MPA) at the Wilmington, Massachusetts, USA headquarters of Ahura Scientific. Completion of appropriate confidentiality and non-disclosure agreements may be necessary for access to these documents. Training for all personnel is documented in training records. Education and experience are documented in resumes (CV) for all employees, including software developers. All training records for Ahura Scientific personnel are on file in the human resources department of Ahura Scientific.

6.13.5

* The supplier should have documented records (for example copy of certificate) of training and experience for any service personnel performing work at Purchasing Organization.

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6.14 ID

Documentation requirements Requirement description 6.14.1 * Technical documentation must be delivered with the system. It should give foundation for procedures regarding: Calibration/instrument tests and maintenance System configuration and administration. 6.14.2 * The supplier must have a description of electronic records (ER) that the system creates, handles and stores. * Manuals for the use and maintenance of the instrument must be a part of the delivery. One manual per instrument. Documentation must be delivered in both paper and electronic format. One set of documents in paper format per instrument. Documents in electronic format must be delivered as PDF files alternatively in Word (DOC) format.

Implementation in TruScan A User Manual is supplied with the system which describes how to carry out: Instrument tests Maintenance System configuration and administration. A onetime calibration is carried out at the factory. No further calibration of the device is needed during its useful life. The User Manual describes the run reports and other records that TruScan creates, handles and stores. A User Manual is supplied with the system which describes the use and maintenance of the system. The User Manual is delivered in electronic format and paper format. Documents in electronic format are delivered as PDF files.

6.14.3

6.14.4

6.14.5

6.15 ID

Service and support Requirement description 6.15.1 * Documentation on which parts of the instrument needs service and how often must be delivered with the system. 6.15.2 The supplier must present a service agreement where checkpoints and service frequency are specified. The supplier must have a support function. The supplier should have telephone support during purchasing organizations office hours. 6.15.5 Optional. The supplier should have telephone support 24 hours a day, 7 days a week.

Implementation in TruScan There are no routine service or maintenance requirements for the instrument. An annual system evaluation and recertification of performance is available. A Service Contract is available on request, at additional cost. Tiered level services are available. Ahura Scientific provides an internet and telephone based support function. Ahura Scientific provides 24 hour, 365 days per year telephone support, free for the first 12 months, and as part of the service contract beyond 12 months. See above.

6.15.3 6.15.4

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6.15.6

The supplier must have a procedure in place to address problems reported by the purchasing organization.

6.15.7

The supplier should guarantee that service and support is available, even if the agency is transferred to another supplier, for at least 5 years from delivery. There will be at least one year warranty that covers the function of delivered goods. The instrument must be supported for an extended period of time

Issues are captured, updated and resolved via a web based issue tracking tool. Customer profiles are maintained in a database associated with the issue tracking tool. Customers support manager call customers on ALL reported issues to determine the level of support provided, timeliness of issue resolution, etc Software Patches and upgrades will be announced to the purchasing organization by email and/or regular mail. Ahura Scientific will guarantee that service and support packages purchased by the purchasing organization will remain available for the entire coverage duration even if the agency is transferred to another supplier. TruScan is supplied with 12 months warranty. The TruScan will be supported for a minimum of 5 years after the last sale. Parts will be available during this time period.

6.15.8 6.15.9

6.16 ID

Training 6.16.1 6.16.2 Requirement description * A basic training on the instrument and the application must be a part of the delivery. * Instructions in setting up and administration of user groups for access control in the system must be a part of the delivery. Training must be performed at the latest one month after approved delivery or at an agreed time. All training must take place on-site at The purchasing organization manufacturing sites. * The supplier should give a certificate or equivalent of accomplished training to each participant. Implementation in TruScan Instrument training on-site is available upon purchase of the instrument. Instructions and training in setting up an administering user access control is included in the IQOQ purchase and is performed during the visit. Training will be provided within one month of approved delivery date or at a mutually agreed time. Training will take place at on site. A Certificate of Completed Training will be provided to each trained person.

6.16.3

6.16.4 6.16.5

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6.17 ID

Delivery and installation Requirement description 6.17.1 The instrument must have suitable packaging or in other ways be protected from damage and moisture during transport. 6.17.2 The supplier is responsible for delivery of instrument and application with associated software licenses. Necessary communication cards and cables for access and control of the instrument must be part of the delivery. The supplier is responsible for performing the installation. Installation should be performed at an agreed time and date. The supplier should give time and date for the delivery in an advance notice. Installation should be started at the latest 30 days after delivery or at an agreed time and date. * The installation must be performed according to a documented installations procedure that has been approved by the purchasing organization in advance.

Implementation in TruScan The instrument will be delivered in suitable packaging to avoid damage and moisture during transport. The instrument is delivered in a Storm Case. Ahura Scientific is responsible for delivery of the instrument and associated software licenses. All communication cards and cables necessary for access to and control of the instrument will be supplied as part of the delivery. Ahura Scientific will perform the installation at a mutually agreed date and time. Ahura Scientific will notify the purchasing organization of the date of delivery in an advance notice. Installation will be started within 30 days of delivery or at a mutually agreed time and date. The installation will be performed according to a documented installation procedure that will be approved in advance by the purchasing organization.

6.17.3

6.17.4

6.17.5

6.17.6

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6.18 ID

Qualification services Requirement description 6.18.1 The supplier should offer services for installation qualification (IQ) and operational qualification (OQ) according to documented procedures. 6.18.2

It should be possible for the purchasing organization to require changes or additions to the suppliers qualification documents (IQ/OQ).

6.18.3 6.18.4 *

The qualification procedure (IQ/OQ) should be adapted to the system configuration. It must be possible for the purchasing organization to approve the Suppliers final qualification documents (IQ/OQ) before qualification of the system is started. The acceptance criteria of the supplier for qualification (IQ/OQ) of the system should be fulfilled before approval of the delivery.

6.18.5

Implementation in TruScan Ahura Scientific offers services for Installation Qualification and Operational Qualification (IQ/OQ), according to documented procedures. At the purchasing organizations request, Ahura Scientific will supply a copy of the documented procedures for IQ/OQ in advance. The purchasing organization can propose changes or additions to the procedures for consideration by Ahura Scientific but we request that the requested changes be submitted 5 business days prior to scheduled on-site execution so that we have adequate time to review the changes, file internal documentation, and plan accordingly. Significant changes to the TruScan IQ/OQ protocol may necessitate incremental charges. The IQ/OQ procedures will be appropriate for the particular configuration supplied. At the purchasing organizations request, Ahura Scientific will supply a copy of the documented procedures for IQ/OQ for approval by the purchasing organizations before qualification of the system is started. The system will pass Ahura Scientifics IQ/OQ qualification procedure before installation will be deemed to be complete.

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DEFINITIONS

User/analyst User is a person using the system. Examples of users are analysts, service and maintenance personnel and administrators. Audit Trail A secure, date and time stamped record, which enables reconstruction of course of events for who has created, changed or deleted an ER and when that has happened. When required, by GxP and/or current SOP, the reason for change should also be clear. Electronic Record (ER) All combinations of text, graphics, data, sound, image or other digitally represented information that has been created changed, managed, archived, reproduced or distributed in a computerized system. Hotfix Something that corrects or fixes an error or a defect in a software or hardware, for example a patch. Instrument TruScan. IT Infrastructure Hardware and software components that the application is dependent upon to function. Infrastructure includes computer hardware, servers, network, operating system or other embedded software that the specific application uses or builds on. Template A file used to create reports from the measurements performed by the instrument. Mandatory requirements Requirements by GMP or requirements critical for operation, which directly or indirectly influence the system function or fulfillment of regulatory requirements. Report Printout of an analysis can be for example: text, an image, a spectrum. Record Information created, received and managed by an organization. Records are used as evidence and information for the organization's business and/or to fulfill legal obligations.

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Raw data/Data All original records (or verified exact copies of these) that are the result of original observations, measurements and activities. Data collection of spectra and calculated data and result files that are created. Sync application The application installed on a PC or server. The application transfers data from the instrument and places them on a network drive. System The system consists of the TruScan instrument and the sync application. The PC/server is not part of the system but is used both for installation of the sync application and for administrative tasks such as for example user access administration. The administrative tasks are managed using a web browser.

MODIFICATION / CHANGE CONTROL

Any changes or modification to this document must be documented and approved. The likely impact of the change of the status of the protocol should be evaluated, reviewed, approved and training of those responsible for its execution prior to implementation.

APPROVALS
Written/Revised By: Date:

Name / Department Frederic Prulliere/Product Management

Reviewed By: Date:

DD-MMM-YYYY

Name / Department
Reviewed By: Date:

DD-MMM-YYYY

Name / Department
Approved By: Date:

DD-MMM-YYYY

Name / Department

DD-MMM-YYYY