Conclusion

The validation of analytical test methods, if they are not already described in an approved compendium, can present more problems in biopharmaceutical manufacturing than in chemical drug production. The high dependence of product quality on specific manufacturing processes means that even in-process tests must be accurate and reliable. However, "full" validation may not be required until fairly late in the development process; in fact, it may not be achievable until sufficient experience with the assay has been achieved and adequate data have been collected.

The use of qualified methods is acceptable at earlier development stages, but a similar level of discipline must be applied to qualification of assays as to validation. The basic difference between the two procedures lies in the extent to which critical test parameters are examined and controlled. Most people concerned with analytical procedures prefer to spend a fair amount of time at the qualification stage, so as to determine whether the method will actually be validatable. Then, final validation will depend upon analysis of sufficient test data. The secret to success in this area is "know your assay" — validation depends upon understanding the test process and its potential for variability.

REFERENCES:

1. ICH Q2A: Validation of Analytical Procedures. Guideline for Industry. US Food and Drug Administration web site. Available at: http:// http://www.fda.gov/cder/guidance/ichq2a.pdf.

2. Guidance for Industry: Analytical Procedures and Methods Validation: Chemistry, Manufacturing, and Controls Documentation; Draft Guidance. Rockville, MD: US FDA; 2000. Available at: http:// http://www.fda.gov/cber/gdlns/methval.pdf.

3. Good Manufacturing Practices (GMP): Quality System (QS) Regulation. US Food and Drug Administration web site. Available at: http:// http://www.fda.gov/cdrh/devadvice/32.html.

4. Bioresearch Monitoring, Good Laboratory Practices: GLP References and Guidance.

US Food and Drug Administration web site. Available at: http:// http://www.fda.gov/ora/compliance_ref/bimo/glp/default.htm.

5. Title 21 — Food and Drugs; Subchapter C — Drugs: General Part 211:

Current Good Manufacturing Process for Finished Pharmaceuticals. Subpart I: Laboratory Controls. US Food and Drug Administration web site. Available at: http:// http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=211&showFR=1.

6. "Laboratory Records." Code of Federal Regulations: 21 CFR 211.194(a)(2). National Archives and Records Administration web site. Available at: http://a257.g.akamaitech.net/7/257/2422/01apr20051500/edocket.access.gpo.gov/cfr_2005/aprqtr/pdf/21cfr211.194.pdf.

7. ICH Q2B: Validation of Analytical Procedures: Methodology. Guideline for Industry. US Food and Drug Administration web site. Available at: http:// http://www.fda.gov/cder/guidance/1320fnl.pdf.

8. Guidance for Industry: Analytical Procedures and Methods Validation: Chemistry, Manufacturing, and Controls Documentation. Draft Guidance. US Food and Drug Administration web site. Available at: http:// http://www.fda.gov/cder/guidance/2396dft.htm.