Chemical Information Services, September 2012 and Life Science Leader, July 2011

The cost of developing a new medicine continues to climb — estimates range from $800 million to $1.3 billion — and as the processes of drug development grow more complex and time-consuming, it will take strategic planning and partnering to find areas to reduce the expense of bringing a new drug to market.

Preformulation/formulation is a key stage where selecting the right outsourcing partner can address the challenges of balancing increasing complexities with developing drugs with greater speed.
Preformulation serves as the crossing point between the drug substance and the drug
product, and so the outsourcing partner selected for these projects plays a critical role in whether the compound becomes a medicine — fewer than 1% of new drug compounds
are approved by the FDA as “new molecular entities”/novel drugs.

An initial consideration in selecting an outsourcing partner for preformulation / formulation projects is whether to choose an organization with strengths that lie in discovery services or a more “full-service” organization with the ability to manufacture commercial quantities. Opting for an organization rooted in discovery for preformulation indicates your partner will be strongly attuned to the attributes of the molecule and its characteristics. However, should the need for commercial manufacturing present itself, partnering with an organization with services that end at preclinical trials presents potential risks in the technology transfer and scale-up from lab to commercial quantities, as well the costs involved in researching and selecting the right manufacturer.

If you already have a short-list or preferred provider for manufacturing, you may save on expenditure partnering with a CRO. (If you don’t, keep in mind the expense of selecting two partners, as compared to one full-service CMO.

A possible advantage of using a CMO that provides preformulation / formulation services
as well as commercial manufacturing is familiarity with end products. A business with a
keen understanding of the steps toward commercial production can help determine the final dosage form and save time, effort, and money. Yet, will organizations that are less focused on discovery rush to start clinical trials? With clear benefits and drawbacks in choosing a discovery-oriented CRO or a CMO with preformulation services, we randomly selected five of the leading businesses from each group (with respect to forecasted market share) and reviewed their quality, regulatory, cost, and productivity ratings. These drivers tie closely to the challenges the right preformulation partner can address — helping develop drugs more quickly despite development processes growing more intricate.

The CROs we selected include BASi (Bioanalytical Systems, Inc.), Bio-Synthesis, Covance, Cyanta Analytical Laboratories, and Quality Chemical Laboratories. The CMOs include
BASF, Boehringer Ingelheim, DSM Pharmaceutical Products, Johnson Matthey Pharma Services, and Lonza.

Quality scores averaged nearly even between the groups (CROs: 58%, CMOs: 59%),
although there was a wider spread in quality ratings for CROs. The CROs’ quality was just
as strong as the CMOs’, although the spread in ratings indicates extra due diligence on
this measure will be worthwhile.

The average regulatory compliance ratings for CMOs skewed lower than CROs, which
may indicate that businesses focused on discovery and research stay more aware of
changing regulatory constraints. This awareness and an understanding of risks (and
the experience to successfully manage them) are key attributes to seek out in a
discovery-focused preformulation provider.

Discovery-Focused CROs Rated Higher In Productivity And Affordability Survey respondents tended to perceive CROs as slightly more affordable than CMOs; 57% vs 51% indicated the business’ “pricing will fit my budget.” Meaning, if you already have a short-list or preferred provider for manufacturing, you may save on expenditure partnering with a CRO. (If you don’t, keep in mind the expense of selecting two partners,
as compared to one full-service CMO.) In addition, CROs were viewed as having higher productivity than CMOs (65% vs 58%). Businesses that concentrate on core competencies — providing fewer services, but in greater depth — may be able to generate a higher quantity of candidates to strengthen the pipeline.

The selected CROs outscored the leading CMOs in regulatory compliance, affordability,
and productivity (while matching quality scores), suggesting the right partner for
preformulation may be a CRO. With either option, it is essential to review the organization for a preformulation team with experts in analysis, chemical engineering, chemistry, and physical characterizations.