The testing performed in this process validation stage confirms that the process design is capable of manufacturing drug product at commercial scale in accordance with the process critical control parameters and product critical quality attributes developed in Stage 1. Prerequisites to this work include completion of activities in Stage 1, qualification of the facility and critical utilities, qualification of process systems and equipment, validation of sampling and analytical methods, and performance of manufacturing operations by trained staff using approved manufacturing instructions and records.

The process qualification work is documented in a protocol that defines manufacturing conditions, operating parameters, processing limits, and raw material inputs. The protocol also defines the data to be collected and how it will be evaluated, the tests to be performed for each significant process step, acceptance criteria for those tests, a sampling plan including sampling points and numbers of samples, and the frequency of sampling based upon statistical rationale. The criteria that provide rationale to conclude that the process produces a consistent product, including statistical methods to be used in the evaluation of the data and a pre-established plan for addressing deviations and non-conformances, is also included in the protocol. The work is documented in a report summarizing the testing along with the results and their conformance with expectations that confirm consistence of the manufacturing operations. Additional in-process material and product testing beyond for-routine manufacturing operations is expected. The bases of requirements for the process qualification testing in Stage 2 with regards to process controls and in-process specifications can be found in Code of Federal Regulations (CFR) Title 21 Part 211.100(a) and 211.110(b), respectively.

This is Part II to IVT's three-part special edition series on process validation. This special edition, a collection of articles and papers from the Journal of Validation Technology and the Journal of GXP Compliance, focuses on equipment qualification, process qualification documentation, quality risk management, and compliant sampling.

Table of Contents

Case Study #2—Questionable Equipment Qualification
Timothy J. Fields

Design and Execution of a Shipping Qualification for a Vaccine Drug Substance
Jamison Tull and Brian K. Nunnally

Engineering Runs: An Insider’s Perspective
Charlie Neal, Jr.

Improving Validation Through the Use of Confidence Statements Based on Attributes Acceptance Sampling
John Haury

Original Data Supporting PQ
Paul L. Pluta

PQ Documentation-Three Simple Rules
Paul L. Pluta

Reduced Validation Effort—Approaches Used and Lessons Learned
Elaine Kelleher and Anne Greene

Responsibilities of the Validation Approval Committee
Paul L. Pluta

Risk Management for Aseptic Processing
Ed White

Sampling Errors in Validation
Patricia L. Smith

Sampling Pages
Paul L. Pluta

Should Acceptable Product Yield be a Validation Requirement? Validation Case Study #6
Paul L. Pluta and Richard Poska

Statistical Tools for Process Qualification
Eugenie Khlebnikova

Validation Answers from GXP Experts
Jerry Lanese and Alan Smith

Validation Report Conclusion–Is It Validated?
Paul L. Pluta