OOS, OOT, OOC, and OOSC - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

OOS, OOT, OOC, and OOSC
Current GMPs demand full understandng of out-of-control concepts. This article contains bonus material.


Pharmaceutical Technology
Volume 35, Issue 10, pp. 46-47

cGMP perspective

That said, the cGMPs still call for companies to have firm control of their processes, statistical or otherwise. Being out-of-statistical-control, but within specifications is not acceptable from a cGMP perspective because there is a higher probability of manufacturing defective product. Companies are required to show continuing due diligence, provide data and analysis to prove that the process is being brought into a state of statistical control, or provide a scientific and statistical study to explain why it cannot be controlled.

To summarize, for control charts, practical significance and OOT go together, and statistical significance and statistical control go together. There are four possible combinations, the control charts for which can be viewed together at http://PharmTech.com/ controlcharts:


Figure 1: Not out-of-trend and not out-of-statistical-control.
1. Not OOT and not OOSC: the ideal situation (see Figure 1)







Figure 2: Out-of-statistical-control but not out-of-trend. Fails Western Electric rule number 2 (7 points on the same side of the center line).
2. Not OOT but OOSC: cannot yet see a practical change, but failed one or more WE8 rules (see Figure 2)







Figure 3: Not out-of-statistical-control but is out-of-trend. Passes all 8 Western Electric rules.
3. OOT but not OOSC: can see a practical change that is not yet statistically significant (see Figure 3)







Figure 4: Out-of-trend and out-of-statistical-control.
4. OOT and OOSC: can see a practical change that is statistically significant (see Figure 4).






Finally, any of these four combinations can be OOS or not OOS as the specification concept is independent of trend (practical significance) and statistical significance.

Lynn D. Torbeck is a statistician at Torbeck and Assoc., 2000 Dempster Plaza, Evanston, IL 60202, tel. 847.424.1314,
, http://www.torbeck.org/.

References

1. FDA, Guidance for Industry: Process Validation: General Principles and Practices (Rockville, MD, Nov. 2008)

2. FDA, Guidance for Industry: Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production (Rockville, MD, Oct. 2006)

3. L.D. Torbeck, Pharm. Technol. 34 (3), 21–23 (1999)

4. Matrixx Initiatives, Inc. v. Siracusano, 131 S. Ct. 1309, (2011)

5. L.D. Torbeck, Pharm. Technol. 34 (3), 76 (2010).


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
Which of the following business challenge poses the greatest threat to your company?
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
Building a sustainable pipeline of products
27%
Attracting a skilled workforce
30%
Obtaining/maintaining adequate financing
10%
Regulatory compliance
33%
View Results
Eric Langer Outsourcing Outlook Eric LangerBiopharma Outsourcing Activities Update
Cynthia Challener, PhD Ingredients Insider Cynthia Challener, PhDAppropriate Process Design Critical for Commercial Manufacture of Highly Potent APIs
Jill Wechsler Regulatory Watch Jill Wechsler FDA and Manufacturers Seek a More Secure Drug Supply Chain
Sean Milmo European Regulatory WatcchSean MilmoQuality by Design?Bridging the Gap between Concept and Implementation
Medicare Payment Data Raises Questions About Drug Costs
FDA Wants You!
A New Strategy to Tackle Antibiotic Resistance
Drug-Diagnostic Development Stymied by Payer Concerns
Obama Administration Halts Attack on Medicare Drug Plans
Source: Pharmaceutical Technology,
Click here