Every member of the quality team must be acquainted with the ICH documents as well. One or more of the team must be expert
in the statistics contained in the following ICH harmonized quality guidelines (available online at
- Q1A(R2) Stability Testing of New Drug Substances and Products
- Q1B Stability Testing: Photostability Testing of New Substances and Products
- Q1C Stability of New Drug Products
- Q1D Bracketing and Matrixing for Stability Testing of New Drug Substances and Products
- Q1E Evaluation of Stability Data
- Q1F Stability Data Package for Registration Applications in Climatic Zones III and IV
- Q2(R1) Validation of Analytical Procedures: Text and Methodology
- Q5C Stability Testing of Biotechnology/Biological Products
- Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances
- Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnology/Biological Products
- Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
- Q8(R2) Pharmaceutical Development
- Q9 Quality Risk Management.
Sampling plans are the weakest area in pharmaceutical quality. The team must be trained and competent. Not to do so is to
expose the company to great risk of material and product failures.
The team must have copies of the following documents for immediate reference when questions arise.
- American National Standard/American Society for Quality, Z1.9 Sampling Procedures and Tables for Inspection by Variables for Percent Nonconforming (ASQ, 1993)
- American National Standard/American Society for Quality, Z1.4 Sampling Procedures and Tables for Inspection by Attributes (ASQ, 2003)
- International Organization for Standardization, International Standard 2859/2 Sampling Procedures for Inspection by Attributes (Part 2: Sampling Plans Indexed by Limiting
Quality for Isolated Lot Inspection) (ISO, 1985)
- US Department of Defense, DOD Preferred Methods for Acceptance of Product, MIL-STD-1916 (DOD, 1996)
- L. D. Torbeck, "Square Root of (N) +1 Sampling Plans," Pharm. Technol. (October 2009).
There are 30 ASTM International standards for statistics; far too many to list here. Readers are encouraged to consider them
all for application. One new standard of particular note though is E2709, Standard Practice for Demonstrating Capability to Comply with a Lot Acceptance Procedure.
Other quality experts and statisticians will have additional topics they consider important but the material mentioned here
is an excellent start. Not everyone needs be an expert in everything, but the quality team must be able to defend their performance
in these complex topics with authority, competence, and confidence.
Statistics in the service of quality is not for the unqualified. All clinical trials are designed and analyzed by professional
statisticians. We can do no less in the quality department—patients' lives depend upon it.
Lynn D. Torbeck is a statistician at Torbeck and Assoc., 2000 Dempster Plaza, Evanston, IL 60202, tel. 847.424.1314, Lynn@Torbeck.org
1. Code of Federal Regulations, Title 21, Food and Drugs (Government Printing Office, Washington, DC), Part 211.25.
2. FDA, Guidance for Industry: Process Validation: General Principles and Practices (CDER, Silver Spring, MD, Jan. 2011).