Cambrex provides pharmaceutical products, expertise and technologies that accelerate small molecule therapeutics into markets across the world. It currently employs over 2,200 people at 13 locations across North America and Europe.

The company has a 40-year history of small molecule active pharmaceutical ingredient (API) manufacturing and a global network of development and manufacturing plants. Its team of experts offers an end-to-end partnership for the research, development and manufacture of small molecules at every stage of the lifecycle. From IND enabling through to generics, Cambrex offers classic chemistry, formulation and testing. With experts dedicated to solid state science and material characterization, the company also offers specialized technologies including enzymatic biotransformations, high potency APIs and continuous processing as well as pediatric, bi-layer and fixed dose combination formulations.

Cambrex’s site in Edinburgh, UK, is home to the company’s expert solid form development services, working with customers developing both drug substances and drug products. In 2020, the site completed a significant expansion, and Contract Pharma had the chance to talk with site director Mark Benger to discuss the services that the site offers, its growth, and the role it plays within the organization.

Contract Pharma: Why is solid state chemistry important within the industry?

Mark Benger: Every API brings its own unique development challenges, and what we do in Edinburgh is look at the molecule itself and try to determine its best version, that will offer the greatest chance of success for a drug. We provide solid state investigations such as salt, co-crystal, and polymorph screening, in addition to crystallization process development and GMP analytical services.

A drug molecule is derived from a chemical reaction, usually performed in the presence of a solvent, and possibly also involving a catalyst. Understanding the different crystal forms that a material can produce can speed up the development of an API and reduce risk in the development and manufacturing of both the drug substance and drug product, as well as adding intellectual property to the portfolio.
Reactions can create any number of impurities that can contaminate the target product, and crystallization is one of the most effective purification techniques, but developing a robust crystallization process is highly specialized, and the experience of process scientists in this field is invaluable to identify the clues that screening provides towards a robust, commercial solution.

Understanding a drug molecule is fundamental to developing robust drug development strategies such as developable and stable new solid forms which are scalable in terms of manufacturing. Having drug substances that are easy to handle, manufacture, filter, with desirable properties in terms of physical attributes are as important as a drug product’s efficacy.

CP: What does the investment and expansion undertaken at the Edinburgh site mean in terms of new capabilities that you can offer customers?

Benger: Progressing a small molecule drug through the clinical pipeline to commercialization typically requires extensive solid state analytical data, ranging from salt screening, polymorph screening, crystallization studies and process development, as well as intellectual property screens. Polymorph screening is a regulatory requirement, and our view is that you can never have enough data on a molecule to assist in its development and for future regulatory and intellectual property submissions.

The larger pharmaceutical companies will usually have access to in-house screening capabilities, but some have started to divest this capability completely, while several have expanded and even set up as service providers in their own right. For small companies, outsourcing is a must, and we work closely and collaboratively with such organizations to help guide them down the most expedient route of development.

The most important aspect of the expansion is that it gives us the ability to work on more projects simultaneously, and be able to employ more experts in this field. Our key value is not necessarily the tools we have available, but the expertise of the scientists we employ, who can interpret the data and make informed decisions based on these. The laboratory expansion has given us an increased fume cupboard capacity, allowing us to install new capabilities such as advanced process analytical technology (PAT) tools and larger scale reactors—up to 20 liters. New PAT tools increase the amount of information that can be gained from our work, and widen the scope of process understanding, while having a greater reactor scale to work with ensures that the developments we make on small scale can transfer to larger volumes, ultimately giving us more confidence that this will then translate to manufacturing scale.

CP: How does this expansion fit into the global Cambrex network and the work it does across its other sites with all its customers?

Benger: All of the work we carry out at Edinburgh is with a view to reducing the development time of programs for customers, and projects generally fall into one of two types: first, there are projects at the early stage of development where innovators are looking to gain information upfront; the other type being where a project has potentially hit a problem that needs to be solved.

We would always recommend that innovators look at the solid state aspect of drug development as early as possible. By doing this, the balance of cost efficiencies in drug development become favorable, as the cost and time implications of doing the work early are smaller than having the scenario of having to solve unforeseen issues at a later stage. That being said, it is not always possible to do this for a number of reasons.

When taking a proactive approach to finding the most suitable drug molecule form to triage compounds, it is important to understand the solid state landscape to avoid issues during manufacturing such as incorrect polymorphic form, and a product’s morphology that may hinder scale up and filtration. The group we have in Edinburgh can support phase-appropriate engineering of the right particle for the client, and this can be done as a standalone service, or as part of a wider drug substance development project. We can also look to build up a broad intellectual portfolio for clients, and this is as important for small companies looking to maximize the value of an asset to sell or license as it is for larger companies looking to protect a program from competitor fast-follower projects where data on a compound may be incomplete and can be exploited.

The expansion allows us to further solidify the link between process chemistry, drug substance manufacturing and the crystallization group here in Edinburgh and the manufacturing sites within the company’s global network. There have been a number of collaborative projects across sites, and as an organization, we continue to increase the value of customers’ programs by being able to offer allied services and offer end-to-end drug development partnerships.

CP: What is the future for the work you carry out in Edinburgh?

Benger: Cambrex is known for its expertise in small molecule drug development, and obviously with all of the implications mentioned, the work we do in terms of solid form screening is key to those. Saying that, we have undertaken a number of projects and continue to have interest in our services from developers of peptides and larger molecules.

The area of most interest for these larger molecules is looking to develop robust and efficient crystallization methods. Typically, these molecules are purified by column chromatographic techniques, which is expensive, time consuming and produces less-than-desirable yields, which, when the drug molecule is of high value, can be extremely detrimental to the economics of a program. Crystallization is obviously a more favorable option, as it can afford a streamlined process, saving time and money. As with small molecules, investing time and money at an early stage in a peptide or large molecule project to develop an efficient crystallization process can lead to savings in the long run if problems occur and need resolving at a later stage of development.