Find Out How to Combine HRMS With ELISA to Quickly Solve HCP Challenges
The process of producing recombinant proteins — such as gene therapies, cell-based therapies, or vaccines — utilizes cells to biosynthesize the desired therapeutic molecules. The production of these therapies involves genetically altering the cells to produce the desired therapeutic protein, which is subsequently purified in anticipation of its use as a therapy in humans.
The drug purification process, although quite thorough, does not always ensure complete selectivity, leading to the extraction of not only the therapeutic protein, but also other cellular proteins produced by the host cells — aka, HCPs. These impurities are regarded as contaminants and have the potential to pose significant risks to the successful development of drug products.
HCPs Can Pose Health Risks
HCPs can pose challenges in the development and production of cell-based therapeutics, such as:
- Safety concerns — Some HCPs are inherently immunogenic and may elicit adverse reactions or immune responses in patients receiving the therapeutic product
- Efficacy problems — HCPs may reduce the efficacy of the therapeutic protein
Regulatory authorities have strict guidelines on the levels of HCPs that are acceptable in therapeutic formulations. Companies developing cell-based therapy products must demonstrate that their manufacturing process effectively removes HCPs to trace levels, as measured by highly sensitive analytical method(s).i
Drug Purification Methods Can Vary
The field of biomanufacturing is continuously evolving, and researchers are always working to develop more effective methods for minimizing HCP contamination and maximizing purity in recombinant therapeutics. Stringent quality control measures are in place to ensure the safety and efficacy of these products before they are released for clinical use.ii
The problem is that the “perfect HCP detection method” simply doesn’t exist; each available method has its own unique advantages and limitations.
Solving HCP Challenges Using a Combined Approach
Relying on any one technique to resolve HCP issues falls short, whereas harnessing the synergy of two powerful complementary techniques proves far more effective.
Success is best achieved through access to a comprehensive range of phase-appropriate methods for analyzing HCPs in biotherapeutic products, starting from early development and extending through full cGMP release testing. These methods involve the utilization of both high-resolution mass spectrometry (HRMS) and enzyme-linked immunosorbent assay (ELISA) techniques to bring you answers in the most time- and cost-effective manner.
Advantages of Using the Combined Approach
ELISA is considered to be the gold standard in biopharma, offering two main advantages:
- High throughput, enabling time and cost savings
- Straightforward outcome that can aid in monitoring purification progress
On the flip side, a significant drawback of ELISA is its lack of qualitative capabilities, leaving the specific HCP profile of a sample unknown. This level of detail is crucial when designing and developing the drug purification process.
This is where HRMS HCP analysis shines.
By adding the HRMS component to our problem-solving toolkit, we gain the profound understanding required to diagnose and resolve HCP issues. Mass spectrometry provides the process development team with precise and comprehensive information, enabling them to logically devise the drug purification method using data on HCP identity, molecular weight (MW), isoelectric point (pI), and concentration. ELISA alone cannot provide this level of detail, potentially exposing you to unknown risks.
Applicable Therapeutic Substances
At Prolytix, we excel at swiftly identifying HCP issues, allowing for their prompt and efficient resolution through the combined HRMS-ELISA approach across various therapeutic modalities, such as:
- Monoclonal antibodies
- Recombinant proteins (e.g., fusion proteins, chimeras, active enzymes, zymogens)
- Gene therapies
- Vaccines
Moreover, it is important to note that the ideal time to incorporate a combined HRMS-ELISA analysis is during process development, allowing for the proactive prevention of HCP issues, rather than dealing with them retroactively after the process has been finalized.
Over the past decade, we have refined these methods, maintaining a steadfast commitment to quality and rigorous data analysis. Contact us today for more information on how we can help you resolve your HCP challenges.
References
1 U.S. Pharmacopeia <1132> Residual host cell protein measurement in biopharmaceuticals. USP39-NF34, 2016.
2 Jones, M., Palackal, N., Wang, F., et al. “High-risk” host cell proteins (HCPs): A multi-company collaborative view. Biotechnol Bioeng. 2021 Aug;118(8):2870-2885. doi: 10.1002/bit.27808. Epub 2021 May 31.