Xcelience, LLC

Xcelience, LLC

‘’’Xcelience, LLC’’’ is a contract research organization (CRO) based in Tampa, Florida, USA. The company provides CMC (Chemistry, Manufacturing and Control) analytical services related to [...] substance and [...] product, formulation development, and [...] product manufacturing, packaging, labeling and stability. Other services include preformulation studies which provide insight into physicochemical properties of the new chemical entity (structure, stability, solubility). Conducted during prenomination and lead optimization, preformulation studies can enable rational decisions for compound, salt or polymorph selection that maximize the probability of compound success and are essential to the establishment of a sound intellectual property position. Virtual development models in early [...] development are used by pharmaceutical companies to reduce costs, improve pharmaceutical pipeline productivity and reach critical development milestones faster.

History

The business was established in 1997 as Tricon, and acquired in 1998 by MDS Pharma Services. In 2006, MDS Pharma Services made a strategic decision to focus on their core businesses. Vice President and General Manager Derek Hennecke led a management buyout to purchase what is now called Xcelience, LLC. Xcelience expanded capacity in 2007 with the acquisition of an additional 24,000 ft2 facility. Mr. Hennecke was recognized as a finalist for the 2008 Ernst & Young Entrepreneur of the Year award. Xcelience has been a finalist for the Tampa Chamber of Commerce Small Business Award in both 2008 and 2009.

Early Phase Formulation Development

There are a number of formulation development approaches that enable speed to first-in-human studies while conserving active pharmaceutical ingredient (API) and other resources. API in Bottle, Powder in Bottle (PIB), Powder in Capsule (PIC), and traditional formulations are all approaches worthy of consideration as possible formulation options for clinical supplies for a Phase I clinical trial.

Directly weighing API into the vial or bottle eliminates the need for excipients and formulation development. Analytical methods development is minimized (API method is all that is needed) and stability is simplified. API requirements are minimal as is risk of losing API in the manufacturing process. API in Bottle supports a wide range of dosage strengths, and adding an additional strength simply requires changing the amount being weighed. Challenging physical characteristics of the API are also not a problem. Disadvantages include clinic preparation time, potential for solubility limitations, challenges associated with taste, patient inconvenience, and development of a matching placebo.

Powder in Bottle (PIB) enables rapid progression into human clinical trials, supports a wide range of dosage strengths, eliminates API characteristics, does not require cleaning verification, and is a valid option for companies facing the challenge of limited API. A minimum amount of developmental stability data are needed on both dry blend and reconstituted material, and bad taste may be masked by the addition of flavors to the powder blend. Disadvantages include longer manufacturing time, clinic preparation time, patient inconvenience if the medication is taken home, and matching placebo. Content uniformity may also be an issue depending on powder blend characteristics. Depending on how the blend is manufactured, cleaning verification might be needed.

Powder in Capsule (PIC) provides dosing flexibility without resulting loss in quality. By eliminating the need for excipients, formulation development and stability testing are reduced, which results in significantly reduced development time. Because content uniformity testing, and in some cases dissolution testing is eliminated, analytical method development and formulation requirements are also reduced. Development of a matching placebo is very straightforward, and compatibility of API with the capsule shell must be considered. Despite the advantages, PIC is a viable strategy in all cases. Depending on the chemical characteristics (BCS classification), PIC may require large amounts of API, and are not always suitable for phase II trials.

Traditional formulation development (tablets and capsules) may be initiated as early as the GLP batch, provided the chemical synthesis and physical representation of the API does not drastically change, and has two advantages over the three approaches listed earlier. In the first place, it is faster to start a Phase II trial with an acceptable dosage form that can be modified into a commercial formulation. Secondly, there is less concern about having to do a bridging study from the formula that was utilized in the Phase I study.

Disadvantages include time to develop an acceptable formulation, cost of the additional analytical support for methods development, additional requirements, such as dissolution for release and stability testing, reduced flexibility in dosage strengths, and increased API requirements. Content uniformity may be a concern, depending on strength, and physicochemical characteristics, such as particle size and shape, may present greater challenges with respect to the manufacturing process.