New FDA guidance for out-of-specification test results

By Emilie Reymond

- Last updated on GMT

Related tags Pharmacology Fda

The US Food and Drug Administration (FDA) has announced the launch
of a new guidance to help drug makers evaluate lab test results
that fall outside the specification limits.

Entitled "Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production", the new guidance is intended to provide clear communication of regulatory expectations and to promote voluntary compliance with current FDA requirements.

An OOS result is generated when a drug product undergoing release testing or stability testing fails to meet an expected result or specification.

When this happens, the FDA requires a valid reason must be determined to invalidate the OOS result and therefore an investigation into the cause of the OOS result must be conducted.

Guidance on this matter is already available for labs, yet difficulties and inconsistent approaches to out-of-specification investigations persist.

For this reason, the regulator has come up with a revised version of a draft document that was submitted for public comment back in 1998.

"FDA recognised the need for industry guidance based on our own quality control laboratory inspection findings and the number of inquiries received by the agency on this topic," an FDA spokesperson told

"The publication of the guidance document at this time is not in response to any specific event or trend but, rather, is intended to address long-standing requests from the pharmaceutical industry for clarification of FDA policy in this area."

The guidance addresses investigations of OOS results in the laboratory phase, including responsibilities of the analyst and supervisor, and when indicated, the expansion of an investigation outside of the laboratory to include production processes, and raw materials as appropriate.

One of the objectives of the new guidance, which has been in development for several years, is to tackle a practice called "testing into compliance" that is sometimes carried out by labs, and which consists in responding to an OOS result only by performing additional testing on a product until a passing result is obtained.

"This practice of retesting without proper investigation is both unscientific and objectionable under the current good manufacturing practices (cGMP) regulations," said the FDA spokesperson.

"It is unscientific because, although an OOS result can often legitimately reflect batch quality, the result is disregarded without scientific justification."

Such practices can result, for example, in the release of drug product that does not conform to an identity, strength, quality or purity specification.

In addition, according to the FDA spokesperson, testing into compliance represents a failure to perform a thorough investigation into the root causes of the OOS result, and therefore can prevent labs from detecting and correcting manufacturing issues or laboratory method problems.

The FDA said it expects this improved clarity on cGMP expectations will have major benefits for the industry.

By helping pharmaceutical firms develop sound, cGMP-compliant OOS procedures, this new guidance should provide increased efficiency for the pharma industry, it added.

Indeed, this particular document could help reduce costs due to unexplained product failures or laboratory method deviations for example.

The regulator said that it has provided this enhanced explanation of its current thinking to the pharma industry in response to industry's comments submitted in response to the draft version of the document.

Related topics Data management Ingredients QA/QC

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