GXP Talk: Questions 60 & 61 | IVT

This column is one of a continuing series in which representatives of the industry and regulatory agencies have an opportunity to express opinions on current GXP issues.

Thank you for your responses to the questions posed in the last issue of the Journal of GXP Compliance. They follow.

Question 60

It has been said that people changes fall under change control. If operator A & B are qualified, how is this change control?


The United States good manufacturing practices (GMPs) address changes in three sections: Code of Federal Regulations (CFR) Title 21 Part 211.68(b) addresses changes to computerized or automated systems, 211.100 addresses changes to procedures and processes, and 211.160(a) addresses changes to test methods, specifications, standards, and sampling plans. In 211.25, the GMPs also require that personnel be appropriately trained for the functions they perform. It is management’s responsibility to ensure that employees performing a job function are appropriately trained and qualified for the tasks they are performing before allowing them to engage in said activities.


One logical way to determine the need for a change control is a risk assessment. One would assume that if Operator A and Operator B are both trained and qualified per company standard operating procedure (SOP) to perform a function, then they should be interchangeable without need for formal change control and that risks to patient, product, or process is extremely low. 

Question 61

How are International Conference for Harmonisation (ICH) Guidances published into law in the United States? Where are ICH Guidances published? What takes precedence, FDA or ICH Guidances?


ICH Guidances are never published into law in the United States. If an observation covering a pharmaceutical drug product operation is included in an FDA 483 or a Warning Letter, it will include a reference to a paragraph of the drug GMPs (21 CFR 211). If an observation made covering an API production operation includes a reference, it will be to the Federal Food, Drug, and Cosmetic Act.

An ICH Guidance is an international guidance written by an Expert Working Group composed of representatives of the industry and the regulatory agencies of the United States, European Union, and Japan. It goes through an extensive review and approval process by the working group and regulatory agencies before it is recommended for adoption by the regulatory bodies. The progress of an ICH Guidance as it goes through the writing and approval process is generally published in the US Federal Register. The document is posted on the ICH website (1) during the various stages of development. In the United States, once an ICH Guidance is recommended for adoption, FDA reformats the guidance to meet the US government requirements for a guidance document and makes the US version of the guidance available on the FDA website (2).  The FDA version of the guidance includes the following statement:

And now, here are two more questions for comment.

Question 62

Are changes made under programs for continuous improvements or process improvements subject to validation?

Question 63

Which guidelines should be used for auditing excipient suppliers? Generally, these suppliers are International Organization for Standardization (ISO)-certified.

Let us know your opinion on these questions. Also, let us know if you have any questions to ask of the industry. Please submit your questions or responses to Jerry Lanese or Tim Fields. You may also ask your questions or respond to these, or any previous questions, via the comment section below.

“This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations.”

An ICH Guidance is not a US law or regulation. It is a statement of current FDA- thinking and has the same precedence as any FDA Guidance.


  1. International Conference for Harmonisation Website, available here.
  2. US Food and Drug Administration Website, available here.

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