Process Control Systems GAMP 5 Software Categories

In the article Validation Determination the use of categorising software was discussed and how this can support the approach to the validation. In this post we are looking at types of software which fall in to these categories for Process Control Systems / Automation Systems.

Categorising software is used to support the approach to the validation based on complexity and novelty of the computerised system.

The categories detailed within this post are based on GAMP 5 Software Categories.

Validation Determination

In the article Computer System Impact / Risk Assessment from May 2010 I discussed the use of the Impact Assessment for a Computerised system to determine the validation requirements. This article continues with that theme to provide guidance on performing and documenting the assessment within a Validation Determination Statement (VDS) for a computerised system.

FDA Warning Letter - Microsoft Excel Spreadsheet

Date: 13 June 2012
Link FDA 483 (New Window)

Observation

5. Your firm has not established and documented the accuracy, reliability and performance of your computer systems employed in the release of drug products [21 C.F.R. 211.68 (a)]

For example, your firm did not verify the accuracy of Excel spreadsheets used to calculate product assay analytical results, for all products manufactured for the US market, in order to verify the accuracy of the results obtained.

This is very similar to a observation from 2010 in the use of Microsoft Excel Spreadsheets which stated

6. Your firm has failed to exercise appropriate controls over computer or related systems to assure that changes in master production and control records, or other records, are instituted only by authorized personnel [21 C.F.R § 211.68(b)].


a) Your firm's laboratory analysts have the ability to access and delete raw chromatographic data located on the (b)(4) of (b)(4) used to conduct HPLC testing. Due to this unrestrictive access, there is no assurance that laboratory records and raw data are accurate and valid.

b) Your firm's laboratory analysts have the ability to access and modify the formulas in the Excel spreadsheets used to calculate assay results for Guaifenesin and (b)(4) drug products. Due to this unrestricted access, there is no assurance that the formulas in the Excel spreadsheets are accurate and valid.

Comment

Microsoft Excel Spreadsheets are used throughout the pharmaceutical industry, generally installed on every desktop computer. However when using spreadsheets to make calculations that are used to support product release and quality based decisions then the spreadsheet must be controlled and verified to ensure that the spreadsheet is secure and that the calculations are accurate across the range.

The security of the spreadsheet should ensure that users of the spreadsheet can only enter data in to specific cells and that the calculations cannot be modified. Basic Excel security can be used to ensure this.

Calculations should be verified across the data range against manually calculated results. Care should be taken relating to rounding errors and resolution..

The spreadsheets should be maintained within a document management system or other secure location to ensure that the files can be access but cannot be modified or overwritten. Changes to the spreadsheets should be managed by Change Control.

FDA Warning Letter - Raw Data

Date: 23 February 2012
Link FDA 483 (New Window)

Observation

4. Your firm has not established appropriate controls over computer or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel. Your firm also fails to maintain a backup file of data entered into the computer or related system [21 CFR § 211.68(b)].

FDA Warning Letter - Automated System Validation

Date: 03 February 2012
Link FDA 483 (New Window)

Observation

Although this observation does not directly relate to 21CFR211.68 for computerised systems it still has an impact on the validation requirements of an automated system within a tablet manufacturing and packing line.

4. Equipment used in the manufacture, processing, packing or holding of drug products is not of appropriate design to facilitate operations for its intended use. [21 C.F.R. § 211.63) For example,

a. Our review of the equipment qualifications for multiple automated Tablet Testing System (TTS) machines, used to conduct in-process tablet testing (weight, hardness and thickness) revealed that performance qualification was not conducted to ensure the accuracy of the machine at the various available speed settings. A February 2010 investigation of OOS tablet weights for Digoxin tablets revealed that the TTSs were giving incorrect tablet weights for lighter weight ( < 200 mg) tablets when run at the default speed of (b)(4) and concluded it would give accurate results only when run at a speed of (b)(4) However, your firm failed to make a further assessment of the overall reliability of the TTS machines, including evaluating their accuracy with other products and other tablet weights at other speeds.

b. Your firm has not adequately qualified the in-line Pressure Control Device (PCD)-2 Automatic Tablet Weight Control System on the (b)(4) and (b)(4) tablet press machines. Your firm did not Qualifications (PQ) that are representative of all of the products run on the tablet presses to assure proper functioning, including evaluating the reject station timing in relation to tablet press rpm. There is no assurance that the PCD-2 system is accurately rejecting the "marked" OOS tablets throughout the compression run.