Vista can help support your drug discovery with cGMP manufacturing, testing and documentation services.

cGMP Support

The U.S. Food and Drug Administration (FDA) maintains a set of guidelines for current Good Manufacturing Practices (cGMP). Vista Biologicals offers the following services to support compliance with these guidelines:

  • Cell Line Characterization
  • Cell Banking
  • Cell Storage
  • Preparation of Batch Records
  • Pre-IND Support
  • Reference / Stability lots
  • Formulation / Stability studies
cGMP Topics

To learn more about various aspects of the cGMP guidelines and how Vista Biologicals can help you meet these requirements, select a topic below. :

Characterization of Cell Lines

As described in the FDA/CBER “Points to Consider in the testing of Monoclonal Antibody Products for Human Use (1994)” and “Points to Consider in the Characterization of Cell Lines used to Produce Biologicals (1993)”, each cell line for the product of biological therapeutics, as follows:

Master Cell Bank Characterization (MCB)

The following tests should be performed on a representative inoculum from the MCB:

  • Sterility
  • Reverse Transcriptase
  • Cultivable and Non-cultivable Mycoplasma
  • Adventitious Virus Contamination (with three indicator cell lines)
  • Mouse Antibody Production (MAP)
  • Sterility
  • HIV 1 and 2 Co-Cultivation (for human derived cell lines only)
  • Epstein-Barr virus Southern Blot (for human cell lines only)
  • Cytomegalovirus (for human derived cell lines only)
  • Hepatitis ~B and C (for human derived cell lines only)
  • Human Herpes virus 6 PCR (for human derived cell lines only)
  • Retroviral Contamination (Transmission Electron Microscopy)
  • Isoenzyme
Master Working Cell Bank (MWCB)

The following tests should be performed on a representative inoculum from the MWCB:

  • Sterility
  • Cultivable and Non-cultivable Mycoplasma
  • Adventitious Virus Contamination (with three indicator cell lines)
  • Isoenzyme
End of Process Cell Harvest (EOPC)

The following tests should be performed on a representative sample from the EOPC:

  • Sterility
  • Reverse Transcriptase
  • Cultivable and Non-cultivable Mycoplasma
  • Adventitious Virus Contamination (with three indicator cell lines)
  • Mouse Antibody Production (MAP)
  • HIV Co-cultivation (for human derived cell lines only)
  • Cytomegalovirus PCR (for human derived cell lines only)
  • Retroviral Contamination (Transmission Electron Microscopy)
  • Isoenzyme)

CHARACTERIZATION OF A MONOCLONAL ANTIBODY BULK REFERENCE LOT

Vista Biologicals recommends that one lot of bulk drug product be created to serve as a standard reference lot prior to assay development and validation (Since this material may be required prior to full or any purification development, it may have to be purified by affinity chromatography). This material should be thoroughly characterized and will be used as a comparison standard in each subsequent step of the drug development.

It is necessary, however, to determine the reasonable stability of the monoclonal antibody early in the process. We recommend the following course for the initial characterization:

SDS-PAGE (Reduced/Non-Reduced)Purity / Identity
HPLC-SECIdentify Initial Aggregates and Fragments / Purity
Isoelectric Focusing (IEF)Purity / Heterogeneity (Highly Recommended by the FDA/CBER)
Western BlotIdentifies Bands as Product Related

Once the purity and initial characterization of the bulk reference lot has been determined, it will be necessary to determine the extinction coefficient of the antibody (usually 1.4±0.2 OD/mg). This can be done by absorbance determination of serial dilutions coupled with amino acid analysis. Once the extinction coefficient is determined, the absorbance data can be used to determine the concentration of unknown samples, as well as validate the Bicinchronic Acid test (BCA).

CHARACTERIZATION OF A RECOMBINANT PROTEIN BULK REFERENCE LOT

Vista Biologicals recommends that one lot of bulk drug product be created to serve as a standard reference lot prior to assay development and validation (Since this material may be required prior to full or any purification development, it may have to be purified by affinity chromatography). This material should be thoroughly characterized and will be used as a comparison standard in each subsequent step of the drug development.

It is necessary, however, to determine the reasonable stability of the monoclonal antibody early in the process. We recommend the following course for the initial characterization:

SDS-PAGE (Reduced/Non-Reduced)Purity / Identity
HPLC-SECIdentify Initial Aggregates and Fragments / Purity
Isoelectric Focusing (IEF)Purity / Heterogeneity (Highly Recommended by the FDA/CBER)
Western BlotIdentifies Bands as Product Related

Once the purity and initial characterization of the bulk reference lot has been determined, it will be necessary to determine the extinction coefficient of the antibody (usually 0.8 to 1.6 OD/mg). This can be done by absorbance determination of serial dilutions coupled with amino acid analysis. Once the extinction coefficient is determined, the absorbance data can be used to determine the concentration of unknown samples, as well as validate the Bicinchronic Acid test (BCA).