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GPC/SEC  Validation 

Paving the road to GPC/SEC validation

By Daniela Held, PhD, PSS GmbH and Clara Trimmer, PSS USA

Validation tools and tips for GPC/SEC systems are discussed here to help users understand the validation process and decision-making issues that yield cost-effective and faster validation. PSS offers services and off-the-shelf products that fulfill the validation and qualification directives that have for over 30 years, aimed to protect citizens and environment from hazardous materials and to ensure product safety.

The validation of analytical systems is not an easy task. Validation is an ongoing complex process that evaluates the entire, sample specific process, products, and analytical methods. Validation consists of several qualification phases that verify pre-defined performance specifications (design (DQ), installation (IQ), operation (OQ), and performance (PQ)). Therefore, a one-time qualification event for each component of the analytical system is not sufficient to operate a valid system. System Validation is a frequent requirement: after installation, prior to routine use, after maintenance or repair and at regular time intervals.

Many lab managers associate validation with increased workloads and paper work, because it requires extensive documentation of all testing experiments. However, if the validation process is carefully and thoroughly planned, with method know-how, it indeed decreases documentation effort and ensures data integrity, traceability and security. A validated system does not mean that there will never be a problem with a product or an application. In many cases the validation process helps identify potential problems early enough to provide proactive solutions. Ultimately the validation responsibility lies on the user.

GPC/SEC System Validation

Validation of Analytical GPC/SEC systems is complete after the instrument hardware, software, data, analytical method and operators (Table 1) are factored in the process. In addition to performance tests for each component of the system, it is essential to confirm that all parts combined, work according to the performance specifications of the analysis method.
 
Table 1.  Analytical GPC/SEC System 
Components Example PSS Product
InstrumentExample PSS product hardware Pump, injection system, detectors, data acquisition hardware, PC

SECcurity GPC1200

Universal Data Center (UDC)
Software GPC/SEC data acquisition and evaluation software

WinGPC UniChrom Macromolecular Chromatography Data System (MCDS)

Compliance Pack
Analytical Method Stationary and mobile phase, conditions, method GPC/SEC in THF on SDV columns, GPC/SEC in water on SUPREMA columns, GPC/SEC coupled with on-line light scattering detection in DMAc on GRAM columns
  Operator
Data
Reference standards
GPC/SEC training 
WinGPC Unity project files

PSS PS ReadyCal, Certified reference materials

The validation process for the components always requires the four phases of qualification:

1. Design Qualification

Often underestimated, this is the most important step in the validation process. Users need to set and document their specific requirements, as well as factor in the DQ evaluation, the extent of validation effort supported by the vendors of the analytical equipment.
Consider the following questions/issues prior to the analytical equipment selection:

  • Is the analytical equipment robust and can withstand GPC/SEC solvents? Some low cost instruments corrode easily when exposed to GPC/SEC solvents, which are different from HPLC solvents.
  • The choice of a suitable column material is crucial when validating the own application/method; the heart of a GPC/SEC system is the column set. Robust GPC/SEC, with or without specialty detectors, requires interaction free size exclusion chromatography. The PSS Magic Triangle tool will assist you to choose column materials that balance the polarity of sample, mobile and stationary phases to achieve a robust GPC/SEC system.

Organic GPCAqueous GPC
  • Choose columns of consistent quality with matching particle size and porosity, avoid artifacts and to guarantee the best resolution for your application.
  • Does column vendor support the method validation?
  •  Is it possible to reserve a dedicated batch of column material for future use (over the next years)? Occasionally, it is wise to reserve the production batch of a column material, to guarantee long-term test quality of a given application and to prevent the need of re-validation of the complete application upon columns renewal.
  • Which detectors are needed now and might be useful in future? Can the validated system be easily expanded?
  • How much (re-) validation effort is needed to integrate future additional components into the system, in order to increase versatility?
    • Detectors?
    • Full GPC/SEC systems?
    • Software modules?
  • Is the software validated and how it is verified?
  • Does it follow national and international (ISO, DIN, ASTM) rules and guidelines?
  • Is it compliant with the requirements of 21 CFR Part 11, which refer to all data acquisition and evaluation software packages?
  • Does the vendor support the user during validation? How much of the validation process can and/or should be outsourced?
  • Does the evaluation software really track all the relevant data and metadata associated with GPC/SEC? 

 

2. Installation Qualification (IQ)

The IQ should document that the system is received as designed and that it is installed properly in the selected environment. It is important to obtain documents that assert such conformity for the entire system (hardware components and software). In addition, the conformity with international GPC/SEC rules and guidelines should be documented separately:

  • ISO 13885,
  • ISO 16014
  • ASTM D 5296-05
  • DIN 55672

Of critical importance is the recording of conditions, raw data and metadata, which influence the evaluation and results. See Table 2. The modular software, WinGPC Unity, automatically tracks all metadata information in a sample audit trail and manages the samples through a comprehensive database. Not every GPC software maker can second this claim. 

 

Table 2    Data & meta data for GPC/SEC and coupling techniques
GPC/SEC GPC/SECViscometry GPC/SEC Triple (plus) GPC/SEC Light Scattering

General Data: Document with IQ and/or PQ
Components manufacturer(s), type and model number, serial numbers, firmware version
Acquisition and evaluation software, version
PC configuration and operating system
Column material, column manufacturer, serial numbers, and actual column parameters (plate count, asymmetry, resolution)

GPC/SEC GPC/SECViscometry GPC/SEC Triple (plus) GPC/SEC Light Scattering
meta data: Document with sample in audit trail
Solvent, flow rate, temperature, sample concentration (approx.), injection volume (approx.)
Baseline and integration limits left and right
Baseline type,  internal standard/flow correction used, internal standard calibration, internal standard measurement
GPC/SEC GPC/SECViscometry  
meta data: Document with sample in audit trail

Calibration method, calibration standards calibration fit used, calibration coefficients

 
  GPC/SECViscometry GPC/SEC Triple (plus) GPC/SEC Light Scattering
  meta data: Document with sample in audit trail

Precise sample concentration, precise injection volume, method to determine slice concentration and related parameters

    GPC/SEC Triple (plus) GPC/SEC Light Scattering
    meta data: Document with sample in audit trail

Sample refractive index increment, solvent refractive index, scattering angle(s), method (LALLS, MALLS, RALLS), instrument constant LS detector/Rayleigh ratio measured for toluene, laser wavelength, fit function for molar mass over elution volume for MALLS: normalization coefficients, plot type (Zimm, Debye, Berry..), fit function for plot type

  GPC/SECViscometry GPC/SEC Triple 
 
  meta data: Document with sample in audit trail

Instrument constant viscometer/DPT sensitivity, fit function for intrinsic viscosity over elution volume

 


3. Operational Qualification (OQ)

The OQ step relies on GPC/SEC know-how, to verify that the entire system will function according to the operational specifications.

The following steps may result on considerable time and effort savings:

a) Perform a system suitability test. Check the integral GPC/SEC system for its ability to measure GPC/SEC results (Mn, Mw, Mp and molecular weight distribution). PSS EasyValid Validation Kit has everything you need to complete this verification.

The EasyValid Validation procedure is straightforward and works for all GPC/SEC brands, provided their system evaluation software supports independent baseline & integration limits as well as polynomial 5th order functions for calibration curve fitting. Round robin Certified Reference Polymers are tested according to the prescribed SOP. A validation report is created with WinGPC Unity MCDS. The report and pass/fail flags are automatically generated.

b) Check additional molar mass sensitive detectors for their ability to measure the appropriate primary information such as (light scattering) Mw or (viscometer) intrinsic viscosity. PSS manufactures dedicated validation kits for the testing of light scattering detectors: viscometers, Triple, and Triple plus detection systems, once the functionality of the overall system, GPC/SEC is corroborated.

c) Validate your separation column/column set (plate count, asymmetry and resolution), to ensure conformity with international guidelines. PSS Columns come with a sufficient documentation to facilitate this step.

d) Validate your own application method for precision, robustness and reproducibility; run a checkout (quality assurance) sample that allows a quick and traceable system check prior to each analysis. The sample may come from commercial standards or from your stock.

4. Performance Qualification PQ

PQ demonstrates that the instrument performs consistently, on a day-to-day basis, according to the specifications under given analysis conditions for the application. The validation responsibility for this qualification step is solely the users. However, vendors ease the burden by offering preventive maintenance checklists, qualified maintenance and periodic training. Software SOPs and change control documents also reduce the user's workload.

Routine use of adequate software tools also eases the workload. PSS supports software users with added functionality such as the automatic generation of quality charts from the overlay mode. The WinGPC Unity Report Designer empowers the user to perform this function with just one mouse click, freeing precious time resources for other tasks. Finally, the WinGPC Unity with Compliance Pack addresses all the record-keeping desired for valid GPC/SEC systems, tracking metadata information in a sample audit trail and managing the samples through a comprehensive database. It does work! Call PSS (1888-477-7872) to talk about your validation needs or contact us. 

 References

United States Food & Drug Administration, Code of Federal Regulations, Title 21, Food and Drugs, Part 11; Electronic records, Electronic Signatures; Final Rule; Federal Register 62 (54), 13430/13466, 1997

United States Food & Drug Administration, Guidance for Industry Part 11; Electronic Records, Electronic Signatures - Scope and Application, 2003

Ludwig Huber, A primer: Good laboratory practice and current good manufacturing practice, Agilent Technologies, publication number 5968-6193E

R. D. McDowall, Quo Vadis 21 CFR 11, LC-GC Europe, February edition, 2-7, 2004SS

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