Cleaning Validation and GMP reviews of those protocols are challenging. They become even more challenging at a Contract Manufacturing Organization (CMO) where compliance assessments to in-house Standard Operating Procedures (SOPs) as well as external regulatory guidelines is a requirement of in-house quality groups, clients, and of course regulators.

Assessment of compliance to procedures can be revealing as well as educational. CMOs are required to develop and qualify analytical methodology for cleaning for the many active pharmaceutical ingredients (APIs) clients contract for manufacturing and validation services. One such challenging cleaning methodology component is swab recovery.

Analytical Methods

Attention is always immediately drawn to analytical methods with low recoveries. Recently, I reviewed a swab recovery method of an API with a particularly low recovery of under 50%. At first I thought this was a single outlying event perhaps due to the inherent properties of the API. However, I decided to look at other swab recoveries of similar APIs for comparison to confirm the outlier theory or to determine if there was an underlying trend. As there was an underlying trend, I resolved to identify various factors that may be contributing to the low swab recoveries.

Related: Learn More About Cleaning Validation

Water Friendly Proteins

Review of the post-cleaning swab methodologies revealed that a large percentage of APIs had swab recoveries well under the recommended acceptance value for various materials of construction (MOC). These particular APIs are compounds that can be generally categorized as manufactured biological protein analogues and therefore inherently soluble in water. After all, these compounds are intended as therapies for the human body. To contrast, these APIs are not small molecules which can be very insoluble in water and may require the use of harsh halogenated or petroleum based solvents for proper recovery.

Intuitively, these water friendly proteins should be relatively easy to recover from various surfaces, usually in the range of 70-80% recovery. Based on the recovery data in Table 1 (below) this was not the case.

Swab recoveries less than 50% should be viewed as atypical, and require a different approach to determine what variables may be affecting swab recoveries.So what exactly are swab recoveries? Here are some terms to help clarify the issue:

• Swab Recovery: the ability of the swab to collect and retrieve API from a surface.
• Swab: a sampling tool comprised of a textile, fiber, or foam on the end of a moderately flexible handle.
• Swab technique: a procedure for sampling surfaces involving wiping the surfaces with a swab, typically saturated with water or another sampling solvent, to remove residues from a surface. The swab is then desorbed in a suitable solvent and a chemical analysis is performed on the desorbed material in solution.
• Recovery Factor: the analysis of the desorbed solvent solution for amount of residue material that is desorbed from the swab and then compared to a standard for percent API recovery.

With these terms in mind, what factors can contribute to low swab recoveries?

Let’s consider

Swab technique, the swabbing motion, direction and pressure is the physical interaction between the swab and the MOC surface, see Figure 1 (below).

The process generally comprises several manual steps, and is an inherently subjective activity that can vary widely from one person to another. It is essential to have a standardized swabbing direction and pressure to ensure that recoveries are replicable regardless of the operator performing the swabbing.

• Choice of swab is critical to the effectiveness of the sampling process. Use of two swabs, one wet with the extraction solvent and one dry swab can enhance the extraction of API from the surface of the MOC onto the swab.
• Swab material should be made of ultra low particulate and fiber releasing components, be of high absorbency, and minimal extractable interference. This is especially true for analytical assays with high sensitivity or the capability of trace levels of recovery.
• Enhancing the characteristics of the extraction solvent, such as pH, can assist in release of API from the MOC surface material and onto your swab. For residues containing different proteins, some factors to consider is the three-dimensional folding and denaturation which can have different ionic affinities that can either adhere strongly or easily extracted from MOC surface materials. By adjusting the pH of the extraction solvent, dramatic effects on the extraction of the protein or API from the MOC surface can occur. This can be especially helpful when working with surfaces such as glass, silicone, and EPDM rubber.

Conclusion

Swabbing has many different factors that can contribute to low recoveries. Taking a balanced methodical approach, which looks at data trends, swab selection, swab direction, extraction solvent, pH of extraction solvent and ionic characteristic, can lead to higher swab recoveries and overall compliance. By strengthening areas where subjectivity may contribute to low swab recoveries is a proactive approach in eliminating variation and improving your swab recovery and compliance to your own procedures and policies.