Quality Overall Summary: 40 Pages That Frame Module 3

The Quality Overall Summary is section 2.3 of the CTD. It presents the quality information in Module 3 in a form a reviewer can assess quickly: the scope of the data, the control strategy, and the residual risk.

It is the first quality document a reviewer reads, and for parts of the application it may be the only one they read closely.

Page limit

The QOS should be no more than 40 pages of text, excluding tables and figures. Biotechnology products, including gene therapies, may run longer but should not exceed 80 pages.

Module 3 can run to thousands of pages. The limit makes you, rather than the reviewer, decide what matters.

Contents

It follows Module 3's structure: drug substance, then drug product, then the sections that follow.

• Drug substance: general information, manufacture, characterization, control, reference standards, container closure, stability.
• Drug product: description and composition, pharmaceutical development, manufacture, control of excipients, control of drug product, reference standards, container closure, stability.

And the control strategy: how the combination of specifications, in-process controls and process understanding assures quality, and what risk remains after all of it.

Summarizing instead of framing

The common failure is a QOS that compresses Module 3 without interpreting it. The reviewer then does the synthesis anyway, and you lose the chance to frame the data. FDA's commentary on the QOS asks for the pieces to be put together rather than shortened.

What a good QOS does that a summary does not:

• States the control strategy as an argument, rather than listing controls.
• Says where the risk is and why the controls address it. A QOS with no residual risk anywhere is not credible.
• Explains the development history that led to the current process, so the reviewer understands why it looks as it does.
• Is consistent with Module 3. Every number in the QOS appears somewhere in Module 3, and a discrepancy between them is a question, sometimes a deficiency.

Other uses, and maintenance

A QOS is required beyond a new application. It appears in the CEP procedure at EDQM, and several regions publish their own QOS templates. Health Canada has a long-standing template of its own.

A QOS also has to be maintained. A post-approval change that alters Module 3 usually alters the QOS, and an out-of-date QOS is one of the easier inconsistencies for a reviewer to find.