Impact of Lot-to-Lot Variability of Cation Exchange Chromatography Resin on Process Performance - A case study to understand the impact of lot-to-lot variability of a cation exchange resin on process

ADVERTISEMENT

Impact of Lot-to-Lot Variability of Cation Exchange Chromatography Resin on Process Performance
A case study to understand the impact of lot-to-lot variability of a cation exchange resin on process performance.


BioPharm International
Volume 21, Issue 5

Resin Particle Size Distribution


Table 3. Percent of particles falling within 40–90 μm
The manufacturer guarantees that at least 80% of the particles that make up any lot of the cation exchange resin it releases have diameters that fall within the range of 40–90 μm. The certificates of analysis, which accompany each lot of resin, report the percentage of particles falling within this range. Table 3 summarizes this percentage for the four lots of resin we tested.


Table 4. Percent of particles smaller than 40 μm
From the table, we can see that the percentage of particles within 40–90 μm diameter is variable from lot-to-lot, although all the lots would pass the vendor's release specification. In addition, the table shows that elution volume increases as the percentage of smaller particles, in this case those within the 40–90 μm range, decreases.6–8 On request, the manufacturer provided more detailed particle size distribution information of lots A, B, C, and D. In this information, almost all of the particles falling outside of the 40–90 μm range are smaller than 40 μm. The percentage of these small particles can be seen in Table 4.


Figure 7. Effect of resin particle size on elution volume
Figure 7 illustrates the fact that the resin lots containing a larger percentage of particles less than 40 μm in diameter produce wider elution peaks.

It is likely that smaller CEX resin particles allow for higher accessibility of the antibody to the charged sites by providing a shorter diffusional length inside the pores. This likely increases the interaction of the antibody with the charged sites, resulting in a wider elution peak and greater resolution (or higher selectivity) between the charged isoforms of the antibody.

Effect on the Product


Table 5. Product yield and removal of impurities
It is important to understand the impact of this variable elution profile on the composition of the different charged isoforms in the product. Additionally, it is important to assess if the lot-to-lot variability results in any differences in the performance attributes of this cation exchange step such as yield and clearance of process and product related impurities. Analytical results show that yield clearance of product and process related impurities were not affected by the different cation exchange chromatography profiles obtained with the four different lots. The results are summarized in Table 5.


Table 6. N- and C-terminal charged isoform distribution
The distribution of the different charged isoforms (N- and C- terminal charged isoforms) of the product was not affected either. These results, which are almost identical for each lot tested, are shown in Table 6.


blog comments powered by Disqus

ADVERTISEMENT

ADVERTISEMENT

Baxter Initiates Voluntary Recall of Potassium Chloride Injection
September 17, 2014
PDA Announces Technical Report on Drug Shortages
September 9, 2014
European Commission Approves RoACTEMRA for Treatment of RA
September 9, 2014
FDA Releases Guidance Electronic Submission of Lot Distribution Reports
September 5, 2014
Infinity and AbbVie Collaborate to Develop Oncology Drug
September 5, 2014
Author Guidelines
Source: BioPharm International,
Click here