biologics drug product process development

Compatibility with manufacturing materials, such as tubing, containers and filters is important for successful drug product manufacturing. For example, the choice of aseptic filter material type is relevant for adsorption of critical excipients and active ingredients. Our DPS team will design and perform studies in order to evaluate material compatibility for manufacturing.

Hold-times during manufacturing are important to ensure physical as well as microbiological stability, and are usually under scrutiny of health authorities. Our DPS team will provide the necessary expertise to design and perform studies to provide sound justification for the hold-times.

Our DPS team have developed relevant models for each unit operation of parenteral drug product manufacturing, including mixing, filling, filtration, capping and visual inspection. Each unit operations parameters can be evaluated for their criticality based on risk assessments, and critical process parameters  are subject to studies for potential impact on relevant product-quality parameters including critical quality attributes. These process studies also serve to understand the product relevance for a given product within the typical normal operating ranges, but also to evaluate edge of failure and understanding failure modes. Related studies are often based on risk assessments, design of experiments, possibly modelling as well as lab, engineering and small scale studies.

Drug product process characterization studies are generally expected by health authority globally and are today’s standard in connection to quality-by-design thinking.

This data is also usually the basis to set up adequate process validation / process qualification studies of the drug product manufacturing process, that are required for filing a BLA or MAA.

Lyophilisation or freeze-drying may in a some cases be required to stabilize a product against degradation that would otherwise occur in liquid state to an acceptable degree. The choice and design of an adequate lyophilisation cycle is key, though may depend on stage of development. Our DPS lyophilisation experts have significant expertise in the design and evaluation of freeze-drying cycles, and can support early-stage and late-stage formulation and dosage form decisions.

Especially for late-stage development and intended commercialization, Lyophilisation cycle development and scale-up is important to ensure a cost-effective manufacturing process that guarantees the product critical quality attributes and maintains a low rejection rate. Our DPS experts are using the latest modelling techniques combined with PAT toolings to evaluate the optimal lyo cycle process and ensure a smooth up-scaling and technical transfer to manufacturing sites. With lyo robustness studies, relevant parameters of the lyophilisation cycle are studies, using bracketing approaches, in order to understand the design space and edge of failure of any lyo cycle, to ensure product robustness.

The drug product manufacturing processes require careful design, however, more important is even to ensure that the process unit operations and parameters are ensured for actual drug product batch manufacturing. This is usually a concerted effort with process development and drug product manufacturing operations and part of a process transfer. Our experts have experience in successful process transfers to ensure overall manufacturing success.

Quality is adequately assured solely by in-process and finished-product testing. Quality, safety and efficacy are designed and built into the product.

Each step of a manufacturing process is controlled to assure that the finished product meets all quality attributes, including, but not limited to, product specifications.

Process validation is the collection and evaluation of data, from the process design stage throughout actual product, establishing the scientific evidence that a process is capable of consistently delivering quality products.

Process validation be considered a stepwise approach:

• Process characterization data and process design, using small-scale models, helps to generate knowledge and understand the criticality of individual unit operations and process parameters and their impact on critical quality attributes, and support defining a design space.
• Process qualification serves to confirm the process design as being capable of reproducibly manufacturing commercial and quality product. This usually includes multiple manufacturing batches at relevant production scale, considering prior knowledge from process design and characterization in order to ensure evaluation of the whole design space for critical process parameters. Process qualification also includes qualification of the facility, utilities and equipment
• Continued process verification includes maintenance, continuous verification and process improvement, to ensure the routine production process remains in state of control. This is usually assessed and monitored as part of commercial manufacture.

Our DPS experts support process qualification and validation of the drug product manufacturing process, as required for filing a BLA or MAA by health authorities.

Deviations are not uncommon during manufacturing, and root-cause investigations (RCIs) are necessary to identify the underlying causes, followed by putting the correct corrective and preventive actions in place. Many times, such RCIs are time-critical and require wide expertise and sound scientific knowledge are often required to rapidly identify the underlying causes. Our DPS team can support with a huge variety of challenges that may be encountered during development and/or drug product manufacture. Our experts can support assessments, RCIs and generate required data to support.