For the initial lot, an example requalification period may be 3, 6, and 12 months for the first year and annually thereafter.
In this scenario, it is recommended that during development, the reference standard be assessed after 3 months at the intended
storage condition and at an accelerated storage condition. Validation of the analytical method for organic impurities should
occur after the full accelerated storage condition has been evaluated. The total length of the requalification program will
depend on the intended life of the reference standard and the length of the stability and clinical programs. If the initial
lot is proven to be stable for at least one year, then subsequent lots will require annual requalification only. In all study
scenarios, a protocol is required to outline the reference-standard material, lot, storage conditions, frequency of test,
analytical procedures, acceptance criteria, and reporting criteria.
Distribution and control.
Reference-standard materials are often expensive to manufacture and are generally of limited supply. It is important, therefore,
to consider how the material will be stored, distributed, and controlled. Once the storage conditions are ascertained, the
reference-standard material should be monitored continually using a suitable environmental monitoring system. It is advisable
to store the material in at least two different locations in case there is a prolonged excursion from the storage condition.
The material should be stored in a secure environment with controlled access and distribution.
David Browne is manager of stability and pharmaceutical testing at Intertek Pharmaceutical Services, d/b/a QTI, 291 Route 22 East, Whitehouse,
NJ 08888, tel. 908.534.4445, firstname.lastname@example.org
Submitted: Mar. 20, 2008. Accepted: Sept. 22, 2008.
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1. FDA, "Reviewer Guidance, Validation of Chromatographic Methods" (Rockville, MD), 1994.
2. USP 30–NF 25 General Chapter <11>, "Reference Standards," p. 1.
3. FDA, "Guideline for Submitting Samples and Analytical Data for Methods Validation" (Rockville, MD), 1987.
4. ICH, Q3A(R2) Impurities in New Drug Substances (Geneva, Switzerland), Oct. 25, 2006.
5. USP 30 –NF 25 General Chapter <467>, "Residual Solvents."
6. ICH, Q2(R1) Validation of Analytical Procedures: Text and Methodology (Geneva, Switzerland), Oct. 1994.
7. ICH, Q1A(R2) Stability Testing of New Drug Substances and Products (Geneva, Switzerland), Feb. 6, 2003.