GMP Interpretation Note

Can production staff be involved in in-process QC sampling or testing?

USFDA s elucidates the roles and responsibilities of Quality Control unit as (1) assessing the suitability of incoming components, containers, closures, labeling, in-process materials, and the finished products; (2) evaluating the performance of the manufacturing process to ensure adherence to proper specifications and limits; and (3) determining the acceptability of each batch for release1. Similarly 21 CFR 211.22 states There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated2. In both the documents, the role of QC focuses on assessing, reviewing and decision making to ensure compliance to specifications and determining the acceptability of the batch for release. The documents does not explicitly indicate testing as responsibility of QC, providing an option of the test being carried out by persons other than QC staff. ICH Q7 (EU GMP Annex 2) allows in-process controls to be performed by qualified production department personnel and the process adjusted without prior quality unit(s) approval if the adjustments are made within pre-established limits approved by the quality unit(s)3. Critical Definition In-Process controls: Checks performed during production in order to monitor and, if appropriate, to adjust the process and/or to ensure that the intermediate or API conforms to its specifications. So can some QC test be performed by manufacturing staff? In order to perform intermediate release test, the production staff needs to be trained and qualified in the given analytical test as well as several QC procedures like OOS reporting etc., which will lead to additional burden on the production staff. The other major issues to address would be violation of Doer Checker concept as well as the fundamental GMP requirement of a quality unit that is independent of production4. In conclusion, it would not be advisable to employ production staff in testing and release of intermediates or quality related tests. Any analysis required for process control, example: adjusting pH of output to a target value, HPLC/OD analysis for monitoring progress of reaction etc. can be performed by manufacturing staff as long as it is predefined in procedures and batch records.

Swapnil Ballal
sballal@gmail.com

GMP Interpretation Note

Can production staff be involved in in-process QC sampling or testing?

Can sampling be performed by manufacturing staff? As far as the sampling by production staff is concerned, it is common to have sampling done by production staff 5, example: collect environmental samples, in-process samples as part of routine operation. It is expected that the production staff a. are trained to take samples according to the SOP, and the training is documented; b. there is routine monitoring of their sampling technique by QC or QA, and retraining is provided if necessary.

References: 1. Guidance for Industry : Quality Systems Approach to Pharmaceutical CGMP Regulations, USFDA 2006 2. 21 CFR 211.22 - Responsibilities of quality control unit 3. ICH Q7: 8.3 In-process Sampling and Controls 4. ICH Q7: 2.2 Responsibilities of the Quality Unit(s) 5. PharmScitech discussion forum: http://www.pharmweb.net/forum/0068/2010/msg00228.html

Last modified : July 28,2011

Swapnil Ballal
sballal@gmail.com