Chemistry Manufacturing Control (CMC) directly impacts the success of your (pre)clinical studies. For fast regulatory approval of your study and with every manufactured batch, you need to ensure that the pharmaceutical product meets quality, safety, and regulatory requirements. TRACER’s CMC pharmaceutical expertise streamlines the development and manufacturing of your drug substance or (radio)labeled drug product. We set up the entire process in compliance with regulatory standards such as GMP, GLP, and ICH guidelines. We specialize in radiochemistry for radiopharmaceuticals or radiolabeling of an investigational medicinal product (IMP) to be used in imaging trials.
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Radiochemistry & CMC for (pre)clinical imaging studies
As an imaging CRO, we specialize in Chemistry Manufacturing Controls (CMC) for imaging studies. This includes labeling with:
- radionuclides (SPECT or PET radiochemistry);
- and fluorescent dyes for optical imaging studies.
Together with a network of radiopharmacies, we manage the entire process from R&D labeling strategy, regulatory approval of IMP-related documentation, to clinical patient batch production and release.
CMC workflow for labeled drug products
- Tech transfer: documentation on drug substance and previous (radio)labeling and experiments (if applicable) is shared with TRACER, and is used as a starting point for the CMC process.
- Often, the CMC process starts with R&D developing labeling strategies: choosing the radionuclide and determining the optimal radiosynthesis method. If the method is already established, we will assess reproducibility and scalability. Simultaneously, Quality Control assays (QC) are set up.
- When the radiolabeling method and QCs are established, the next step is the implementation of compound labeling in Good Manufacturing Practice (GMP) facilities. This includes qualifying and validating QC assays for the release of the radiolabelled compound.
- Before release of the compound, we conduct comprehensive in-use stability studies, assessing (radio)chemical purity, binding properties, and radionuclide dissociation to ensure the quality and reliability of your labelled drug product in vivo.
- The end product after GMP implementation is the investigational medicinal product dossier (IMPD) of the radiolabelled drug product, which we use for regulatory submission.
- Once the study has been approved, per-patient batch manufacturing will be initiated with GMP production tailored to the study’s needs.
TRACER engages with sponsors across the full CMC process or at selected stages, with the flexibility to enter at any point. Including regulatory guidance, strategy development, and troubleshooting.
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Tailored pharma CMC solutions
For each of our collaborations, we’ve delivered tailored pharma CMC across three key areas.
Quality control
- Development and validation of quality control methods
- Quality assurance and stability studies (purity, binding properties)
- Validation of assays for drug product release (HPLC, etc.)
- Stability testing of pharmaceutical products
IMP manufacturing
- Qualified Person (QP) release of (radiolabeled) drug products for clinical trials
- Fluorescence/radiolabeling method development and validation
- Radiosynthesis and GMP synthesis of precursors for labeling
Good Laboratory Practice (GLP)-grade drug substance manufacturing
- Clinical trial material and small-batch GLP/GMP manufacturing, already from 2-3 grams.
- Contract Development and Manufacturing Organization (CDMO) selection and management regarding clinical trial material
Regulatory and strategy
- CMC regulatory support for clinical development
- Preparation and review of IMPD/IND for Clinical Trial Application (CTA) submissions
- Development of protocols for method validation
- Stability study design and evaluation
CMC case studies
GMP labeling of two scFv fragments with Zirconium
- Development of labeling strategy
- Preparing two IMPDs in one Investigator’s Brochure (IB)
- All CMC work, up to QP release
- Design of clinical trial, including necessary preclinical work and determining timepoints for (dynamic) imaging
- Quantification of radioactivity concentration in vivo
- Immunofluorescence for cross-validation of the target on ex vivo samples
The sponsor was able to select a lead compound for further development based on data from the in-patient study, which was also conducted by TRACER.
Zirconium-89 and Indium-111 preclinical radiolabeling of antibody fragment
- Conjugation of antibody fragments to a chelator
- Radiolabeling of two batches, one with Zirconium-89 and one with Indium-111
- Optimizing radiolabeling, followed by quality control, purification, and in vitro stability
- In vitro binding and internalization assays to evaluate binding properties
- Assessment of biodistribution, tumor targeting, and PET/SPECT image quality in tumor-bearing mice
The sponsor was able to compare imaging methods in a preclinical study and consider antibody drug conjugate or radiopharmaceutical development of the antibody. The study, also performed by TRACER, delivered data on biodistribution and on- and off-target binding/uptake.
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CMC Project Management by TRACER
As your CMC partner, we bring structure and strategic oversight to every phase of your CMC pathway. We ensure your development program progresses efficiently from early (pre-clinical) research to GMP-compliant manufacturing.
Whether you require tailored quality control strategies, optimized IMP manufacturing, (radio)labeling, or expert regulatory support: our team is ready to guide you through every step of the CMC process.
Questions about CMC or interested in receiving a quotation for your project?
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Abbreviations
| CMC | Chemistry Manufacturing Control |
| CTM | Clinical Trial Material |
| IMP | Investigational Medicinal Product |
| GMP | Good Manufacturing Practice |
| GLP | Good Laboratory Practice |
| ICH | International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use |
| HPLC | High-Performance Liquid Chromatography |
| QP | Qualified Person |
| CDMO | Contract Development and Manufacturing Organization |
| IMPD | Investigational Medicinal Product Dossier |
| IND | Investigational New Drug |
| CTA | Clinical Trial Application (or Clinical Trial Agreement) |
| CRO | Contract Research Organisation |