Guidance for Industry Process Validation: General Principles and Practices

This revised guidance of 2011 replaces the 1987 guidance. In the Federal Register of May 11, 1987 (52 FR 17638), FDA issued a notice announcing the availability of a guidance entitled Guideline on General Principles of Process Validation (the 1987 guidance). Since then, we have obtained additional experience through our regulatory oversight that allows us to update our recommendations to industry on this topic. This revised guidance conveys FDA’s current thinking on process validation and is consistent with basic principles first introduced in the 1987 guidance. The revised guidance also provides recommendations that reflect some of the goals of FDA’s initiative entitled “Pharmaceutical CGMPs for the 21st Century ― A Risk-Based Approach,” particularly with regard to the use of technological advances in pharmaceutical manufacturing, as well as implementation of modern risk management and quality system tools and concepts.

I. Introduction:

This guidance outlines the general principles and approaches that FDA considers appropriate elements of process validation for the manufacture of human and animal drug and biological products, including active pharmaceutical ingredients (APIs or drug substances), collectively referred to in this guidance as drugs or products. This guidance incorporates principles and approaches that all manufacturers can use to validate manufacturing processes. This guidance aligns process validation activities with a product lifecycle concept and with existing FDA guidance, including the FDA/ICH (International Conference on Harmonisation) guidances for industry, Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System.

Although this guidance does not repeat the concepts and principles explained in those guidances, FDA encourages the use of modern pharmaceutical development concepts, quality risk management, and quality systems at all stages of the manufacturing process lifecycle.

The lifecycle concept links product and process development, qualification of the commercial manufacturing process, and maintenance of the process in a state of control during routine commercial production. This guidance supports process improvement and innovation through sound science.

This guidance covers the following categories of drugs:

• Human drugs

• Veterinary drugs

• Biological and biotechnology products

• Finished products and active pharmaceutical ingredients (APIs or drug substances)

• The drug constituent of a combination (drug and medical device) product

This guidance does not cover the following types of products:

• Type A medicated articles and medicated feed

• Medical devices

• Dietary supplements

• Human tissues intended for transplantation regulated under section 361 of the Public Health Service Act

This guidance does not specify what information should be included as part of a regulatory submission. Interested persons can refer to the appropriate guidance or contact the appropriate Center in determining the type of information to include in a submission.

This guidance also does not specifically discuss the validation of automated process control systems (i.e., computer hardware and software interfaces), which are commonly integrated into modern drug manufacturing equipment. This guidance is relevant, however, to the validation of processes that include automated equipment in processing.

FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.

I. Introduction

Ii. Background

A. Process validation and drug quality

B. Approach to process validation

Iii. Statutory and regulatory requirements for process validation

Iv. Recommendations

A. General considerations for process validation

B. Stage 1 ― process design

1. Building and capturing process knowledge and understanding

2. Establishing a strategy for process control

C. Stage 2 ― process qualification

1. Design of a facility and qualification of utilities and equipment