Destin A. LeBlanc

Cleaning Validation Technologies

Technical Consulting Services

SEPTEMBER 1997

What cleaning and process validation do the CGMPs require for production of a bio-batch, where only a single lot has been made?

References: 21 CFR 211.67, Equipment cleaning and maintenance; 211.100, Written procedures; deviations; Guideline on The Preparation of Investigational New Drug Products, 3/91

The agency has not articulated its expectations regarding process validation or cleaning validation with respect to bio-batches, per se. The closest relevant document is our Guideline on The Preparation of Investigational New Drug Products. In that document we said:

At early clinical stages, where a single batch of drug product may be produced, and where significant formulation and processing changes may make batch replication difficult or inexact, only limited process validation may be possible. In such cases, limited validation, especially for such critical processes as sterilization, should be derived, to the extent possible, from product and process analogs. In addition, data obtained from extensive in-process controls and intensive product testing may be used to demonstrate that the instant run yielded a finished product meeting all of its specifications and quality characteristics. It is expected that more comprehensive process validation will be conducted as additional uniform batches are made under replicated conditions.

You may apply these principles to the bio-batch process and cleaning validation. We would expect adequate cleaning to have been performed and documented and that in-process and end product testing would show instant lots to meet specifications.