Economic, competitive and healthcare pressures are driving continued change in pharmaceutical drug development as companies strive to improve returns on investment and accelerate times to market.  Taking the right active pharmaceutical ingredient (API) forward is crucial for the success of any project, making early and comprehensive characterization an absolute requirement.

Detailed physicochemical characterization of the API helps manage and mitigate the uncertainty and risks inherent in early-stage drug development. ‘Win quick, fail fast’ approaches are critical to longer-term success, enabling the rapid identification of developable APIs that meet safety, bioavailability and likely processability requirements.

Malvern Panalytical combines expertise in API development, discovery, and manufacturing, with a deep understanding of how to apply physicochemical analysis in drug development. Our systems, which are used throughout the pharmaceutical development workflow, help answer questions about API bioavailability, stability, processability and quality, to support:

  • Selection of viable candidates
  • Gaining an understanding of critical material attributes (CMAs) 
  • Implementation of scale-up for quality in API manufacturing
  • Application of Quality by Design (QbD) by helping define the physicochemical design space 

API Developers can also access uniquely tailored expert support to aid the rapid identification of suitable drug candidates through Amplify Analytics, a range of highly flexible and scalable services created as the result of the partnership between Malvern Panalytical and contract research organization Concept Life Sciences. 

API Bioavailability

The poor solubility of the majority of today’s APIs adds to the complexity of ensuring that a molecule has adequate bioavailability for effective use. Approaches such as the Developability Classification System (DCS) and Manufacturing Classification System (MCS) help identify those candidate molecules that are likely to meet bioavailability requirements and which will then also be successful in scale-up and manufacturing. These systems rely on appropriate physicochemical analyses to provide the data needed to link decisions made during lead optimization and API salt and polymorph selection to the critical material attributes (CMAs) required to meet both product and process requirements.

Common strategies employed in API design to improve solubility include particle size reduction, the identification and selection of different polymorphs, and, increasingly, the use of amorphous forms of the molecule. 

Malvern Panalytical systems help answer questions including:

  • What solid forms are available?
  • Are there multiple polymorphs?
  • What is the impact of particle size reduction on particle and polymorph stability?
  • How much amorphous content is present, and how can amorphous structures be defined and characterized?

Analysis tools that support bioavailability strategies

API Stability

Understanding the stability of the solid form API is an essential part of lead optimization, salt screening and process development. Polymorphic transitions may result in changes such as altered dissolution rates, reduced drug efficacy and possible adverse reactions, and their presence can raise patent issues. 

Polymorph selection, and confirmation of polymorphic stability over time, is therefore crucial. This becomes even more important when an amorphous form of the API is selected to improve solubility, as unexpected crystallization of an insoluble form can be fatal.

Ensuring that all polymorphic forms are known, and their behavior is understood, helps in managing API stability and reducing the risk of late breakthrough polymorphs that might jeopardize downstream development. 

Malvern Panalytical systems help answer questions including:

  • What polymorphic forms of the API are possible?
  • How will these polymorphic forms behave?

Analysis tools that enable stability studies

API Processability

Many APIs fail on scale-up, often because of issues connected with stability or processability. With the advent of continuous processing and moves towards novel manufacturing methods, it is increasingly important that the API easily fits developability, processing and scale-up requirements. 

Malvern Panalytical systems provide the insight that enables a QbD approach to API development, supporting robust design space definition, process optimization and the maintenance of process performance within that space. 

Malvern Panalytical systems help answer questions including:

  • What is the stability of the API during processing?
  • How can critical material attributes (CMAs) relating to bioavailability be controlled?
  • What is the safety profile of my product or ingredients with respect to elemental impurities?

Analytical approaches to improve processability and aid scale-up

API Quality

The handover to manufacturing requires the definition of a robust Chemical Manufacturing and Controls (CMC) package. This package must ensure that CMAs are monitored in order to maintain API product quality and safety. Microstructure and solid form analysis are often key characterizations, in line with ICH guidance (ICH Q3D, ICH Q6A and ICH Q1A).

Malvern Panalytical systems help answer requirements including:

  • Quality control of raw materials and intermediates for APIs and excipients, and stability testing for batch release
  • Root cause analysis for batch release
  • Physicochemical insight to assist process optimization
  • In vitro bioequivalence assessment to aid the transfer of processes or products between sites and/or from old to new processing methods

Supporting robust API manufacturing and quality control

API Development Services

Amplify Analytics is a new and unique range of highly flexible services designed to support developers in the rapid identification of new drug candidates that have the most appropriate bioavailability and processability requirements. 

Amplify Analytics brings together the chemistry and physicochemical analysis expertise of Malvern Panalytical and Concept Life Sciences, and their collective understanding of customer requirements with respect to assessing drug developability. The result is a range of scalable services that deliver bespoke combinations of analytics, know-how, instrumentation and expert support, tailored to fit the individual needs of each customer. 

Expert solutions in api development. Contact us to discuss your challenges.
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