The pressures associated with today’s drug development landscape has led many developers to turn to contract development and manufacturing organisations (CDMOs) to support them with their analytical requirements for both small and large-scale projects.
In some cases, CDMOs not only have the capacity to support — but also the expertise to apply — more innovative thinking to this aspect of drug development. Dr Kevin Robinson talks to Recipharm’s Senior Director of Analytical Development, Ramesh Jagadeesan, about how CDMOs are bringing innovation to analytical testing and how this may help to expedite times-to-market for many novel medicines.
KSR: What are some of the key factors that are fuelling the outsourcing of analytical services?
RJ: Analytical testing is a critical element at every stage of drug development and, like many other chemical, manufacturing and control (CMC) activities, the market for these contract services has grown rapidly. Many factors are attributed to this, including a growing preference from drug developers to redirect resources to focus on core activities, as well as increasing time pressures and in-house capacity issues.
More efficient analytical strategies are also being called for as a result of regulatory agencies’ increasingly stringent requirements for more analytical information on medicines and process development. Providers of outsourced analytical services can alleviate the burden on developers by working with them to ensure that their product meets the necessary standards.
KSR: How are technological advancements helping to bring innovation to analytical chemistry?
RJ: We are seeing the automation of analytical instrumentation becoming more simplified. Although the volume of data being generated may be increasing, the level of resource necessary to achieve this level of data is reducing, creating huge time and cost savings for pharmaceutical companies.
Analyses have traditionally been used to quantify the active ingredient and the impurities in a product. Innovation has now brought us to a point when we can also estimate any unexpected additions in a formulation, such as the elemental impurities that may be present owing to manufacturing vessels or reactants.
At the same time, the industry is realising the benefits of more modern analytical techniques, including Raman spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS), optical emission spectroscopy (OES), nuclear magnetic resonance (NMR) spectroscopy and ultra-performance liquid chromatography (UPLC).
The use of different detectors, such as refractive index, fluorescence, evaporative light scattering (ELSD) and Quadrupole Dalton (QDa) detectors during method development is also allowing for increased levels of product efficacy, safety and the provision of more substantial data for the regulatory authorities.
Furthermore, the growing use of orthogonal analytical techniques is facilitating a fuller understanding of product composition. The use of these techniques is helping to reduce timelines and, in turn, allowing medicines to be delivered to market more quickly.
KSR: How is the optimisation of analytical testing helping to reduce time-to-market?
RJ: The introduction of automation and the emergence of new analytical techniques are both helping to reduce the time needed for quality testing. Stability testing has also undergone its own transformation with simulating chambers now being used for freeze-thaw, photostability testing and the use of chambers for all temperature zones.
Ramesh Jagadeesan, Senior Director of Analytical Development,Recipharm
New developments have also seen the optimisation of packaging selection with the introduction of extractables and leachables (E&L) testing, as well as the compatibility testing of materials.
Furthermore, new technology is helping the industry to meet guidelines such as Quality by Design (QbD), elemental impurities and data integrity requirements. Together, all these innovations are making significant steps forward in reducing regulatory burden and lessening time-to-market, while also contributing to enhancements in patient safety.
From a research and development perspective, routes to market are now being optimised via an improved ability to select the most stable and effective form of drug substances. This offers both improvements in solubility and the ability to identify compatible excipients.
KSR: What are the key considerations surrounding drug development and manufacturing processes during analytical testing?
RJ: Working with a CDMO can bring a better understanding of the complete drug lifecycle, as well as the broad experience of commercial manufacturing and quality control (QC) testing. Choosing to work with a partner can also provide access to highly specialised teams that fully comprehend the varying impact that different analytical methods may have on formulation and development times within QC.
When approaching method selection, it is important to consider several factors. The method chosen must be stability indicating and sensitive enough to detect and quantitate according to with current regulations. Robustness is a further crucial consideration and any method must be transferrable from a development lab environment to a highly efficient LEAN-oriented one in a QC lab.
The development of analytical methods for genotoxic impurities should also be considered … as this will be critically reviewed by regulatory agencies.
KSR: How can appropriate method validation assist in speeding up time-to-market?
RJ: The quality of validation documents can affect the speed at which queries can be responded to, thereby influencing a product’s timelines.
By ensuring that an expert team designs the validation protocols based on current regulatory guidelines and that the execution of method validations is in line with the relevant protocols, it is possible to avoid many of the usual agency queries. For example, regulatory bodies tend to focus more on the stability indicating ability of the validated method.
By implementing a strict good manufacturing practice (GMP) environment, custom field calculation and the capability for electronic data back-ups, error-free information can be ensured. At the same time, QbD-based method validations can provide a better understanding of the critical parameters of the analytical method and can help to provide trouble-free methods throughout the product lifecycle.
KSR: Finally, how can outsourcing partnerships contribute real value to today’s drug developers?
RJ: The escalating costs of running a laboratory has become an important factor to consider by many pharmaceutical companies. CDMOs can provide a more cost-effective alternative by offering developers both the capacity and scale that today’s development programmes require.
Unlike many in-house analytical functions, most CDMOs will be equipped to run different analyses in parallel — and these providers are unquestionably leading the way in developing shorter/fewer methods, which is helping to drive down testing times.
CDMOs will have worked with many different molecules across many different pharmaceutical companies. This means that they will be applying insight to a single project that has been gained during the development of multiple formulations. This breadth of expertise is typically difficult to acquire in-house.
Further benefits can be achieved by working with a partner who can demonstrate past ability of identifying and understanding a wide range of issues related to analytical method development. By ensuring that the extensive needs of analytical testing are met to the fullest, expert CDMOs can help their customers to optimise lifecycle management and reduce time-to-market for many important medicines.
