How to Avoid FDA Process Validation Warning Letters (21 CFR 820.75)

Overview

In this warning letter breakdown, we are going to examine how you can avoid process validation citations and also the importance of validating the equipment that is used in the manufacturing process when product cannot be verified with 100% inspection or testing.

Reference From Actual Warning Letter

2. Your firm failed to adequately validate according to established procedures a process whose results cannot be fully verified by subsequent inspection and testing, as required by 21 CFR 820.75(a). Your firm failed to adequately validate various pieces of equipment, as well as the process of adding reground material to fresh resin to manufacture plastic components.

Specifically:

a. Your firm failed to adequately validate the following pieces of equipment:

a. AG Equipment Number (b)(4), Serial Number (b)(4) Model (b)(4), installed October 2010

i. Installation Qualification (IQ) not approved by an AG Industries representative

ii. No Operation Qualification (OQ) conducted

iii. Verification Plan (Performance Qualification or PQ) consisted of only (b)(4) lot of production which is inadequate to demonstrate the reproducibility of the production line and only (b)(4) samples from the production lot. Further, the PQ documentation for the line verifications was incomplete.

b. AG Equipment Number (b)(4), Serial Number (b)(4), Model (b)(4) installed October 2010
i. Installation Qualification (IQ) not approved by an AG Industries representative

ii. No Operation Qualification (OQ) conducted

iii. Verification Plan (Performance Qualification or PQ) consisted of only (b)(4) lot of production which is inadequate to demonstrate the reproducibility of the production line and only (b)(4) samples from the production lot. Further, the PQ documentation for the line verifications was incomplete.

c. AG Equipment Number (b)(4), Serial Number (b)(4), Model (b)(4) installed September 2012
i. Installation Qualification (IQ) not approved by an AG Industries representative

ii. No Operation Qualification (OQ) conducted

iii. Verification Plan (Performance Qualification or PQ) consisted of only (b)(4) production lot, which is inadequate to demonstrate the reproducibility of the production line. Further, the sample size was set at only (b)(4) units sampled from the single (b)(4) unit production lot when the Sample Plan Standard Operating Procedure calls for (b)

(4) units to be sampled in a production lot this size.

d. (b)(4), installed September 2013
i. Installation Qualification (IQ) not approved by an AG Industries representative

ii. No Operation Qualification (OQ) conducted

iii. Verification Plan (Performance Qualification or PQ) consisted of only (b)(4) production lot, which is inadequate to demonstrate the reproducibility of the production
line. Further, the sample size was set at only (b)(4) units sampled from the single (b)(4) unit production lot when the Sample Plan Standard Operating Procedure calls for (b)

(4) units to be sampled in a production lot this size.

iv. After a complaint of (b)(4) defective filters returned on 7/29/2014, the welder on the (b)(4) was modified and subsequently validated. The validation specified (b)(4) pieces were sampled from a lot of (b)(4) units produced. Per the SOP sampling plan Wl8.76 procedure (which covers validation), the required number of samples was (b)(4). There was no documented justification for reducing the sample size for the validation. Further, 11 of (b)(4) samples from the high and low sides of weld time failed the flange thickness measurement test. Instead of the validation failing, the specification and tolerances of the part were changed to match the measurement test results.