This article establishes the requirements for the Rework of Active Pharmaceutical Ingredients (API) and Drug Products manufactured by GMP sites including APIs, Intermediates, In-Process Material and drug products after the Site Quality Team has given the material the disposition of Acceptable for Rework/Reclaim.

This practice should apply to all GMP Sites where Pharmaceutical and Animal Health API and marketed drug products are produced.

Standard Operating Procedures (SOP) addressing reworking shall be established and maintained at each site where such operations are performed. At a minimum, such SOPs shall be reviewed and Approved by the Site Quality Team and the Site Production Team.

Rework Operations shall be performed by trained and Qualified personnel.

A Documented Evaluation of the reworking steps must be conducted, prior to initiation of the steps to assess the impact to the following requirements, as applicable to the process:

• Regulatory filing requirements for the market(s) where the reworked material will be distributed or further processed;
• Stability;
• Elapsed time between end of processing and the start of rework;
• Validation;
• For drug products, assess impact on down stream processing and the product;
• For APIs, assess impact on down stream processing and the bulk product or intermediate;
• Quality, safety, identity and purity of product;
• Equivalency to other Batches or Lots of the product;
• Potential additional analytical needs to evaluate the effectiveness of the reworking; and
• Homogeneity.

Equivalence Between Reworked Product Quality and that Produced by the Original Process shall be demonstrated and documented and shall include, but not be limited to, evaluation of the following:

• Routine In-Process Control (IPC) and release test results; and
• Formation or introduction of possible new degradants or other impurities.

A documented evaluation of the need for additional stability studies of the resultant API and/or resultant drug product shall be conducted in accordance with the site requirements.

When Routine Analytical Methods are Inadequate to Characterize the Reworked Batch or Lot, additional methods shall be used. If an additional method is not validated, the method must be shown to be applicable for use. The applicability of the method for use must be documented.

When a Rework is Initiated, a Rework Batch Record shall be used to document the activities and shall be available for review. Release of a reworked batch shall follow standard batch record review and release SOPs.

Reworked Batches and Lots shall be assigned unique and traceable Batch or Lot Numbers.