Expertise in CMC (chemistry, manufacturing, and control) ensures the appropriate manufacture of a pharmaceutical or biologic by coordinating material characterization, formulation development, and product testing for batch safety, consistency, and efficacy.
Materials characterization is a cornerstone in the understanding of the composition of a drug substance or product and its potential for efficacy or adverse biological effects when consumed.
Image Credit: DSI, a PLG Company
CMC is involved during the entire drug development process. Throughout preclinical stages, analytical methods are prepared for product monitoring. Stability testing commences, and the drug’s physicochemical properties are established. Selection and testing of the raw materials also take place.
In the clinical-development stage, additional analytical method verification characterization is conducted. Throughout the course of clinical trials, CMC supervises a scale-up process that ensures the product batches are as consistent as the drug tested during clinical trials.
CMC expertise is crucial throughout the high-stakes exercise of material characterization by establishing New Chemical Entities (NCEs) and drug formulation quality standards, from preclinical investigational new drug stages to post-approval evergreening changes—new dosages, formulations, and methods of administration.
The role of material characterization and formulation development in drug manufacturing
During pharmaceutical drug development, raw materials include active pharmaceutical ingredients (APIs), inactive ingredients, and excipients. The latter strengthens the formulation to boost stability, avert reuptake, or increase/reduce drug absorption.
Material characterization refers to tests that are performed to better understand the physical and chemical properties of the raw materials and the active ingredient. During the drug manufacturing process, these properties can influence product safety, performance, visibility, and stability.
Characterization is also a vital first step prior to comprehensive impurity identification assays.
Drug formulation facilitates the creation of optimal drug products by way of a pharmaceutical manufacturing process that combines active drug substances with various chemical ingredients.
This is an essential part of drug development. It helps to determine the delivery of the active ingredient, ensuring it reaches the right part of the body at an effective yet balanced rate and concentration.
When it comes to the therapeutic success, patentability, and lifecycle of a drug substance, formulation development can make or break the deal. Companies include material characterization and formulation development processes and expertise in the product development process in numerous ways.
For larger and integrated pharmaceutical companies, internal departments may be on hand to handle any characterization and formulation development matters.
In smaller emerging biotechs, material characterization and formulation development functions be the responsibility of the project team managing the entire drug development program or outsourced project managers who work with internal resources.
Materials selection and characterization process
Material selection is carried out on the assumption of performance, industry standards, reliability, and costs and manufacturing needs. The structured processes necessitate selecting appropriate materials predicated on a given understanding of drug synthesis pathways and mechanisms of impurity control.
The process demands understanding and identifying how variances in the synthetic route can influence the impurity profile and the source, formation and terminus of such impurities.
The relevant expertise required in the material selection process includes:
- Experience with difficult to manufacture and complex APIs
- Knowledge in design space and process validation
- Process research and development
- Supply chain management
- Technology transfer and scaling of the initial development cycle
The material characterization process incorporates tests that deliver crucial information for determining the selected materials' safety, efficiency, and biocompatibility.
Tests range from physicochemical tests, infrared analysis, atomic absorption spectro-analysis, plasma spectroscopy, and high-performance liquid/gas chromatography.
Expertise needed in the material characterization process
- Comprehensive analytical expertise from chemical to physical characterization
- Safe handling of controlled drug substances high potency compounds
- Spray drying and particle size reduction
Formulation development process
Pre-formulation analytical study development and active ingredient screening are incorporated into the formulation development activities to ensure the product's stability, solubility, and dosage form efficiency. The process also necessitates studies on drug-device compatibility and drug delivery options.
Expertise needed in formulation development
- Analysis of proprietary dosage forms
- Experience in NDA and NDA dosage form formulation development
- Knowledge in excipient compatibility
- Process knowledge in the development of current dosage forms and formulation troubleshooting
Oral solid dose (OSD) formulation development
There are several drug delivery routes, but oral is still the easiest and most popular route. The focus of solid drug formulation for oral administration emphasizes process system engineering for tablet design, formulation, and manufacturing.
The objectives driving this process include enhancing drug efficiency, quality, reducing costs, and accelerating the time to market.
Expertise needed in OSD formulation development
- Analytical and stability testing support
- CMC documentation and regulatory submissions
- Experience in pediatric formulations
- Formulation experience in dosage forms such as tablets, soft gels, capsules, powders, etc.
- Formulation experience in abuse-deterrence, controlled release, and multicomponent capsules
- Knowledge of current Good Manufacturing Practice regulations
Sterile development
All sterile products must undergo and pass a sterility test. Additionally, formulating the solutions must be nonpyrogenic – not containing any particulate matter. In sterile formulation development, there is a vital need for wide-ranging physicochemical characterization for the compatibility of excipients.
The formulation demands careful evaluation and control of key process parameters to guarantee a strong product that meets sterility standards.
Expertise needed in sterile development
- 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.
- Lyophilization process development and optimization
- Terminal sterilization and aseptic filling
Why outsource material characterization and formulation development
Problems that frequently occur during material selection, characterization, and formulation development include:
- Difficulties identifying synthetic routes
- Incompatibilities with delivery systems
- Low or zero drug solubility
- Low bioavailability
- Process scalability challenges
- Supply chain management issues
in order to mitigate these challenges, smaller biotech’s tend to seek external assistance. Contracting CMC material characterization and formulation development help to scale down timelines, boost internal expertise, and assure success in the face of any number of challenges that occur during drug development.
Good documentation, analysis, and data establish both the foundations of FDA applications and the connection with drug development processes. DSI takes great pride in its ability to solve complex pharmaceutical drug development challenges.
Whether managing small APIs or biologic molecule projects, DSI can help facilitate risk reduction while raising quality standards. DSI can help to reduce timelines and prepare biotechs for commercial success: Call today on 855-805-8402.
About DSI, a PLG Company
DS InPharmatics (DSI) provides regulatory, technical, and project management consulting services to healthcare product companies that manufacture and/or market pharmaceuticals, biopharmaceuticals, and cellular and gene therapy products.
Since 2007 we have provided our clients with innovative strategies and exceptional quality work products intended to enhance product development, approval, and marketing presence. Whether advocating CMC strategy, directing CMC operations or developing CMC submission content that represent the best interests of emerging biotech, we focus on the critical CMC issues and build programs that enhance development.
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