Documentation is the key to a consistent, controlled process according to Vasilevsky.12 The documentation system is integrated with different documents approved by the Quality Assurance (QA) department following
GMP requirements. These include: Standard Operation Procedures (SOP), quality specifications, batch production records, the
legal license to produce, as well as other documents such as flowcharts, cleaning standards, calibration and equipment maintenance
Figure 4. Standard Operating Procedures. List of the SOPs that describe the main operations of the production of anti-HBsAg
monoclonal antibody and the immunoaffinity matrix.
In addition, organization and personnel-related detail is included, such as: organization charts of the production department,
descriptions of all the positions and responsibilities, as well as control lines and subordination. Behavior, hygiene, manners,
and the training of personnel are described in detail in the organization and personnel data.
Results and Discussion
Guidelines for the development of MAbs are published and periodically updated. (See Figure 5.) These guidelines serve as blueprints
for the manufacture, safety, and efficacy testing of MAbs. Because biotechnology and the development of MAbs are rapidly evolving
fields, the information contained in these guidelines may become obsolete or be subject to rapid change as new and more significant
information becomes available.
Figure 5. The Main Guides, Codes, and Regulations for the Production of MAbs Antibodies
The enclosed table, keeping in mind the guidelines issued by the World Health Organization (WHO) and FDA, enables us to see
the guidelines for MAbs used as reagents and parenteral therapeutics. The regulations on the use of monoclonal antibodies
are the same in both cases; its demanding features are the same. (See Figure 5)
WHO Technical Report Series 822
This document applies to murine and human monoclonal antibodies for use in humans, including in
vivo diagnosis and ex vivo (extra corporeal) treatment. It is recommended that monoclonal antibodies intended for use in the preparation of biological
products in humans should also meet these requirements, except those relating to the final product. (This document is not
concerned with the production of monoclonal antibodies by recombinant DNA techniques, such as "humanized" antibodies, nor
with monoclonal antibodies to be used for in vitro diagnostic purposes.)
Food and Drug Adminis-tration (FDA) 1997
The FDA documents apply to MAb used as therapeutic or in vivo diagnostic agents, as well as to ancillary products, i.e., MAb used in the manufacture of other products for in vivo use. The latter include MAb that are used alone or in conjunction with devices, for example, for ex vivo purging of cells to remove immune or tumor cells, for ex vivo collection (e.g., hematopoietic cells), or for purification of other products intended for in vivo administration. Generally, these MAb should meet the same criteria for safety and freedom from adventitious agents as MAb
intended for direct administration to patients.