[Stability Testing related News – vol.64]

◆  What Errors can occur with Swab Sampling during Cleaning Validation? (01-Mar-23 ECA)

Two sampling techniques are generally used in cleaning validation: the rinse test and the swab test. The following are notes on potential issues with the swab test.

In general, the use of swabs for the detection of chemical or microbiological residues is possible. Usually, the recovery of microbiology swabs is lower compared to agar plates for microbial surface sampling, only the swab for the detection of chemical residues (product or detergent residues) is addressed in the following.

Critical steps during swab testingThe swab sampling process itself, in addition to the analysis, which will not be discussed here, has two critical steps that must be optimized considering surface materials and residues:

  • Step 1: Picking up the residues from the surface in contact with the product using the material of the “swab head”.
  • Step 2: Transfer of the residues from the material of the “swab head” into the extraction solution.

In addition to a reproducible swab technique, the material of the swab itself is crucial. Using cotton made swabs is no longer “state of the art”. These can themselves release particulates on the product contact surface, disintegrate during the swab process depending on the swab technique, or fail to release the residues into the extraction solution. Modern swabs have an abrasive material which, in addition to dissolving the residues by using a moistened swab head, also removes them mechanically from the surface. In this case, the correct pressure, which can be checked if the swab shows a slight bending, is important. In general, rectangular sampling surfaces sampled in a check pattern are preferable. To ensure a correct sampling area, it is advisable to swab in overlapping lanes and sample at least the specified surface area. More surface area swabbed means a “worst-case” and ensures that a falsely low result is generated due to a smaller surface area swabed. After swabbing, as little extraction solution, which is used for pre-moistioning the swab head, as possible should remain on the surface. In special cases it may be useful to swab the surface again with a second dry swab. In addition, it should be noted that after cleaning processes with warm or hot media or a drying step, the equipment surface needs to cool down to room temperature.

Depending on the swab technique, the transfer of the residues is carried out sequentially in step 2. Here, the swab is swirled in the extraction solution between the individual swab steps. After sampling, the swab is typically transferred into the extraction solution and left there until analysis. Prior to this, additional enhanced extraction can be achieved using a vibratory shaker or an ultrasonic bath. Sampling recovery can be improved by optimizing the extraction solution. This mainly depends on the type and condition of the residue. However, the extraction solution itself should also be easily cleanable and furthermore not interfere with the analysis.

Author: Dipl.-Ing. (FH) Robert G. Schwarz

◆  Two New PIC/S GDP Guidance Documents Published (28-Mar-23 ECA)

The Pharmaceutical Inspection Co-operation Scheme (PIC/S) has published two guidance documents for GDP inspectors, an Aide-Memoire on GDP inspections and a Q&A document.

According to a press release, these documents have been prepared by the PIC/S Expert Circle on GDP and entered into force on 01 February 2023. Both publications are available for download as a PDF file free of charge on the PIC/S website.

Aide-Memoire on GDP Inspections (PI 044-1)The first document is entitled “Aide-Memoire on the Inspection of Good Distribution Practice (GDP) for Medicinal Products in the Supply Chain”. The document contains a total of 22 pages.

According to section 3.1, “the purpose of this document is to provide guidance for GDP inspectors to assist in training and preparing for inspections.” To be precise, it is about GDP inspection of manufacturers and wholesale distributors. In section 2.5 it is pointed out that it is a “voluntary guidance document” and that it “is legally non-binding unless it has been declared a legal standard in the jurisdiction of a Participating Authority”

The main part of the PDF file consists of in total 10 tables, which contain general subjects and items to be investigated during a GDP inspection. The tables also include references to supporting documents. The following areas are covered:

  • General
  • Quality Management
  • Personnel
  • Premises and Equipment
  • Documentation
  • Operations
  • Complaints, Returns, Suspected Falsified Medicinal Products and Medicinal Product Recalls
  • Outsourced Activities
  • Self-Inspections
  • Transportation

Q&A Document (PS/INF 22/2017)The second new document bears the title “Questions & Answers document regarding the PIC/S GDP Guide (PE 011-1)” Thus, the questions and answers refer to the “PIC/S Guide to Good Distribution Practice (GDP) for Medicinal Products” from June 2014, which can also be downloaded from the PIC/S homepage.

On a total of 11 pages, various questions regarding the different chapters of the PIC/S GDP Guide are answered. This includes, for example, the following aspects:

  • “How is the effectiveness of the quality system monitored?”
  • “Is the wholesaler responsible for ensuring GDP compliance of the outsourced activity?”
  • “What is meant with “acceptable temperature limits”?”
  • “What is acceptable time limit for return to saleable stock?”
  • “Should the transportation company hold a wholesaler’s licence?”

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