Clear and complete QOS yields shorter reviewer time

Validation Times, Oct, 2007 by Joseph Pickett

BETHESDA, MD -- A QOS (quality overall summary)--part of the CID format that provides a summary of CMC aspects of a drug application--that "clearly and completely addresses all the questions in the QbR [quality-based review] should result in shorter review time," a reviewer from OGD stated here Oct. 11.

Bita Mirza-Azarm told the GPhA conference that another significant benefit is that it "reduces the reviewer's time spent on fact finding and summarizing ANDA elements."

Comparing the QOS to a story, Mirza-Azarm said "there should be connection between the sections of a QOS." After completion of the QOS, the reviewer should be able to understand the choices and reasons behind those choices in the "product story."

An effective QOS provides a better understanding of the sponsor's rationale for decisions, and fewer misunderstandings and questions.

Factors affecting review times, she said, include:

* Documentation--tables, charts, chemical structures and specifications need not be reproduced in the review;

* Deficiencies generated by reviewers due to lack of product understanding; and

* Issues critical to OGD are not recognized.

Documentation and assessment time completely depends of the quality of the submission, she said. "To better understand a sponsor's rationale for decisions, reviewers want to see more formulation and process choices justified."

It also is helpful if relevant development information is submitted, which is "particularly helpful in reviewing complex dosage forms."

Submissions could be greatly improved, she added, if one thinks of QOS also as "quality of submission."

Some suggestions included:

* Submit the ANDA in CTD format, not 36-point.

* Include pertinent information as part of the QOS--avoid lengthy narratives. Tabular information is more helpful than descriptive.

* Do not repeat the same information in multiple locations.

* Do not answer a question in Module 2 by just referencing Module 3.

* QOS should be contained in one document.

The reviewer further stressed the need for consistency between Module 2 and 3. Inconsistencies she has seen include: "Unit dose formulation provided in the QOS did not correspond to the formulation specified in the BBR, EBR and main body of data."

"Tablet coating specified in QOS did not correspond to the tablet coating specified in the BBR, EBR and main body of data."

"Batch numbers and blend release data provided in QOS did not correspond to the batch numbers and blend release data appearing in the EBRs."

Other suggestions included:

* Know what information should be included in Module 2. If a question is not applicable to a specific formulation, never delete it, but answer as "N/A" with a brief justification.

* Know why OGD is asking the question. Tailor answers to demonstrate how your choices lead to your product development.

* ANDA should include physiocochemical properties, adequate drug substance specification and test methods, impurity profile, limits for impurity/residual solvent limits, method validation and reference standard.

* Provide connection between specification and product development.

* Discuss design principle, and indicate if the proposed product uses a different design/release mechanism. "This is very useful for complex dosage forms," she said.

See related data below.

Number of E-ANDAs received in 2007

* January:--49.1

* February--76.1

* March--76.2%

* April--78.1

* May--80.6%

* June--82.4%

* July--90.6%

Source: Lawrence Yu, CDER/OGD

By Joseph Pickett

Managing Editor