Gene therapy quality depends on choosing the right analytical methods and technologies for each part of the production process says an expert from Biomarin.

Lyndi Rice, head of the QC viral vector analytical group at Biomarin Pharmaceutical, told delegates at the BPI East conference in September: “Analytics are really critical from the start of the manufacturing process and all the way to the end of product testing and monitoring.

“Release testing is critical for measuring product quality by assessing its identity strength, purity and safety. And stability methods measure the stability of the product under different conditions as well as over time and can help to inform shelf life for your product.”

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The key to an effective analytics strategy is ensuring the correct methods are used as each part of the development and production process, Rice said.

“It is important to ensure that the method performs as well as needed to monitor the manufacturing process at each of those steps.”

She also said information needs to be gathered at all stages of production, explaining “It’s important to collect data, especially early on in product development. These results can be leveraged during investigations to understand how product quality might have been affected, should there have been anything that maybe was a little bit off during the manufacturing process.”

Analysis “suite” spot

Incorporating analytical systems into process development – even manufacturing facility design – is the ideal approach as it ensure that the desired critical quality attributes can be monitored effectively.

However, companies also need to consider the use of alternative methods according to Rice, who urged gene therapy producers to ensure a degree of flexibility in process and facility design.

“It is very important to thoughtfully design your analytical suites to be sure that they’re measuring these attributes appropriately. And it is potential that orthogonal approaches may also be required to measure some of these attributes.”

Consistency

Gene therapies have complex mechanism of action and it is critical that developers make sure that any therapeutic impact is due to the products itself rather than variation occurring during the manufacturing processes.

Analytical technologies are key to minimizing batch to batch variation and ensuring gene therapies are consistent Rice said.

“Gene therapy products are known to be complex, heterogeneous and have complex mechanisms of action. Product characterization is therefore critical to ensure product safety as well as to demonstrate batch to batch consistency over time, and to help you interpret your clinical study outcomes.

“Robust analytical methods are therefore required for sufficient product characterization. And you can also consider during product development phase appropriate analytical method development. So by phase three pivotal trials, it is expected that you would have all of your methods validated.”

Platform process?

Again, it is critical to select the appropriate analytic method and to ensure it is providing the information needed at each stage of the process Rice said.

“You can refine your methods as product knowledge increases, and focus on method robustness, accuracy and precision early, especially for your critical methods such as dosing and potency. And this is because you’re going to be making really important decisions based on method performance and those method results.

“So you should really focus on these methods early on in product development. Platform methods can also help to save time and resources without sacrificing quality, but they do require that your manufacturing process is also somewhat platform.”

For gene therapies manufactured using more novel processes such a platform focused approach may not be as effective. In such circumstances, firms should consider a “quality by design or QBD approach for analytical method development.”