The application of statistics as a major tool in assuring product quality is usually dated to May 16, 1924, when Dr. Walter
A. Shewhart of Bell Laboratories wrote his famous internal memorandum describing for the first time a control chart. It was
then used at the Western Electric Hawthorne Works manufacturing plant in Cicero, Illinois, to study fuses and heat controls.
The rest, as they say, is history.
Lynn D. Torbeck
During and since World War II, the use of statistics blossomed in American industry. By the mid-1970s, Japan had caught up
and then expanded the use of data and analysis for product quality. Following Dr. W. Edwards Deming's philosophy, great progress
was made in minimizing variability and waste.
However, statistics have not been used consistently by the pharmaceutical industry. Historically, large firms such as Abbott,
Baxter, Smith Kline and French, and others had staff formally trained in statistical quality and process control. But often,
small to mid-sized firms did not have anyone on staff with statistical training. These companies frequently received FDA 483
citations and warning letters for not meeting the statistical requirements of cGMPs.
The situation has changed little today. Many companies do not have anyone on staff who can implement a control chart correctly
or explain the concepts behind sampling plans. This is true even though cGMPs require that staff "... shall have education,
training, and experience, or any combination thereof, to enable that person to perform the assigned functions" (1).
There are indications that this may be changing in the future. FDA's guidance for industry on process validation and the International
Committee for Harmonization's (ICH) guidelines for product development and risk management have attracted the attention of
influential people in the industry as well as other departments in FDA (2). FDA has been training its staff in statistics
for some time and apparently expects to continue. Questions concerning the application of statistics to product quality may
be coming to a 483 near you soon.
In the meantime, what should personnel working in pharmaceutical quality know about applied statistics? At a minimum, the
quality department should have a team with at least one person who is a certified quality engineer (CQE), as recognized by
the American Society for Quality (ASQ), or who has a Bachelor's degree with a major in statistics. The person should also
have a background in engineering or a physical science.
In addition to the necessary training in applied statistics for quality, the team should be acquainted with the statistical
issues in the following industry documents:
- 21 CFR 210 and 211 cGMP in Manufacturing, Processing, Packing, or Holding of Drugs and Finished Pharmaceuticals
- 21 CFR 600 Biological Products: General
- 21 CFR 820 Quality Systems Regulations
Guidance for Industry: Investigating Out-of-Specification Test Results for Pharmaceutical Production (FDA, Oct. 2006)
Guidance for Industry: Process Validation: General Principles and Practices (FDA, Jan. 2011).
The quality team also should have access to the current edition of the United States Pharmacopeia (USP) and the Pharmaceutical Forum. The following chapters are the minimum that should be reviewed for their statistical content:
- General Notices and Requirements
USP, Guide to General Chapters:
• <616> Bulk Density and Tapped Density
• <701> Disintegration
• <711> Dissolution
• <788> Particulate Matter in Injections
• <905> Uniformity of Dosage Units
• <1010> Analytical Data–Interpretation and Treatment
• <1150> Pharmaceutical Stability
• <1223> Validation of Alternative Microbiological Methods
• <1225> Validation of Compendial Procedures
• <1226> Verification of Compendial Procedures
• <1227> Validation of Microbial Recovery.