Material Characterization and Formulation Development

Establishing Regulatory Starting Materials & Understanding the ICH
April 1, 2021

Material Characterization and Formulation Development

CMC (chemistry, manufacturing, and control) expertise assures the proper manufacture of a pharmaceutical or biologic by coordinating material characterization, formulation development, and product testing for batch consistency, safety, and efficacy.

Materials characterization lays the foundation of understanding the makeup of a drug substance or product and its potential for efficacy or adverse biological effect when used.

CMC is involved in the entire drug development lifecycle. During preclinical stages, analytical methods are qualified for product monitoring. Stability testing is initiated, and the physicochemical properties of the drug are determined. Raw materials are selected and tested.

In the clinical-development stage, further analytical method validation characterization is performed. During clinical trials, CMC oversees a scale-up process that guarantees the product batches are the same as the drug tested in clinical trials.

CMC expertise can be invaluable throughout the high-stakes exercise of material characterization by setting New Chemical Entities (NCEs) and drug formulation quality standards from preclinical investigational new drug stages to post-approval evergreening changes—new formulations, dosages, and modes of administration.

The Role of Material Characterization and Formulation Development in Drug Manufacturing

Raw materials in pharmaceutical drug development include inactive ingredients, active pharmaceutical ingredients (APIs), and excipients. The latter strengthens the formulation to add stability, prevent reuptake, or increase/reduce drug absorption.

Material characterization refers to tests done to understand the chemical and physical properties of the raw materials and the active ingredient. In the drug manufacturing process, these properties can impact product performance, safety, visibility, and stability. Characterization is also a critical first step before in-depth impurity identification assays.

Drug formulation is a pharmaceutical manufacturing process of combining active drug substances with various chemical ingredients to create the ultimate drug product. This is an indispensable part of drug development. It helps to ascertain that the active ingredient is delivered to the right part of the body at an optimal yet balanced rate and concentration.

Formulation development can make or break the deal when it comes to a drug substance's therapeutic success, patentability, and lifecycle. Companies incorporate material characterization and formulation development processes and expertise in the product development cycle in varying ways.

For large and integrated pharmaceutical companies, internal departments may be available to deal with characterization and formulation development matters.

In small emerging biotechs, material characterization and formulation development functions may fall within the project team responsible for the entire drug development program or outsourced project managers who work with internal resources.

Materials Selection and Characterization Process

Material selection is conducted on the premises of performance, reliability, costs and manufacturing needs, and industry standards. The systematic processes entail choosing materials based on a proven understanding of drug synthesis pathways and impurity control mechanisms.

The process involves identifying and understanding how the synthetic route changes can impact the impurity profile and the source, formation, and terminus of the said impurities.

Expertise needed in the material selection process

  • Technology transfer and scaling of the original development cycle
  • Process research and development
  • Experience with difficult to manufacture and complex APIs
  • Supply chain management
  • Knowledge in design space and process validation

The material characterization process involves tests that provide critical information for establishing the chosen materials' safety, efficiency biocompatibility. The tests range from infrared analysis, physicochemical tests, plasma spectroscopy, atomic absorption spectro-analysis, and high-performance liquid/ gas chromatography.

Expertise Needed in the Material Characterization Process

  • Safe handling of controlled drug substances high potency compounds
  • Comprehensive analytical expertise from chemical to physical characterization
  • Spray drying and particle size reduction

Formulation Development Process

Formulation development activities involve pre-formulation analytical study development and active ingredient screening for assurances of the product's stability, solubility, and dosage form efficiency. The process further entails studies on delivery options and drug-device compatibility.

Expertise Needed in Formulation Development

  • Knowledge in excipient compatibility
  • NDA and NDA dosage form formulation development experience
  • Process knowledge in the development of current dosage forms and formulation troubleshooting
  • Analysis of proprietary dosage forms

Oral Solid Dose (OSD) Formulation Development

There are many drug delivery routes, but oral remains the most popular and easy route. Oral solid drug formulation focuses on process system engineering for tablet formulation, design, and manufacturing. Objectives that drive this include improving drug efficiency and quality, reducing costs, and hastening time to market.

Expertise Needed in OSD Formulation Development

  • Knowledge of current Good Manufacturing Practice regulations
  • Experience in pediatric formulations
  • Analytical and stability testing support
  • Formulation experience in dosage forms such as tablets, soft gels, capsules, powders, etc.
  • Formulation experience in abuse-deterrence, controlled release, and multicomponent capsules
  • CMC documentation and regulatory submissions

Sterile Development

All sterile products must pass a sterility test. Also, the solutions must be formulated as nonpyrogenic that is free from particulate matter. In sterile formulation development, there is a critical need for broad physicochemical characterization for the compatibility of excipients. The formulation requires careful evaluation and control of critical process parameters to guarantee a robust product that meets sterility requirements.

Expertise Needed in Sterile Development

  • Terminal sterilization and aseptic filling
  • Lyophilization process development and optimization
  • Experience in handling sensitive and precious drug substances
  • Expertise in dosage forms such as pre-filled syringes, liquid, and lyophilized vials, small-volume parenteral, etc.

Why Outsource Material Characterization and Formulation Development

Common problems that occur from material selection to characterization and formulation development include:

  • Difficulties identifying synthetic routes
  • Supply chain management issues
  • Process scalability challenges
  • Low or zero drug solubility
  • Low bioavailability
  • Incompatibilities with delivery systems

As a way to mitigate these challenges, small biotech’s often look for outside help. Contract CMC material characterization and formulation development helps to reduce timelines, augment internal expertise, and guarantee success against many challenges in drug development.

Documentation, analysis, and data form the core of FDA applications and the link in drug development processes. At DSI, we pride ourselves on solving your complex pharmaceutical drug development challenges.

Whether you are handling small APIs or biologic molecule projects, we help reduce risks and raise quality standards. We help to compress timelines and prepare you for commercial success. Call us at 855-805-8402.