14C Radiolabelling

14C RadiolabellingQC and analytical support, including method development and validation, method transfer and radiolabelling stability studies
With our extensive experience in the synthesis and analysis of stable and 14C isotope labelled compounds – from drug discovery through to launch. We can label any compound at any stage, including small molecules, peptides, and antibody drug conjugates.

14C is the radioisotope of choice in preclinical and clinical ADME studies. 14C avoids the challenges encountered with tritium labelling, including label exchange and the loss of label due to radioactive decay.

2H, 13C and 15N stable labels are routinely used to prepare stable labelled versions of APIs. Multiple labels are typically incorporated to ensure complete mass resolution from the unlabelled API.

Isotopic labelling imposes many synthetic challenges beyond those found in normal chemical synthesis. When the isotope is radioactive, this becomes even more demanding. That’s why we offer advice on the most appropriate label position for your molecule, including feasibility and metabolic stability.

We can provide a complete suite of solutions for your radiolabelling needs, including:

Non-GMP and GMP Stable Labelling

A track record in stable labelling

By working with us, you will have access to expertise in non-GMP and GMP stable labelling of your small molecule, peptide, fermentation product and ADC. We will assess the target molecule and recommend the appropriate, most cost-effective label position. We typically offer isotopic enrichments greater than 98%, and isotopic purity is determined using our state-of-the-art mass spectrometry equipment.

We Provide:

  • non-GMP synthesis of labelled API
  • GMP synthesis of labelled API including analytical tech transfer and validation
  • Storage and stability studies of your API
  • A breadth and depth of chemistry and analytical experience gained over many projects
  • Fully equipped laboratories for efficient and effective working
  • Biology and fermentation expertise were appropriate
  • Labelled metabolites
  • Access to selectAZymeTM enzymes for selective and mild transformation
  • Solida dosage form (powder in botlle and capsule formulations)

Facilities and Equipment

Our State-of-the-art facilities include:

  • Controlled access
  • Dedicated GMP areas
  • QA input into facility design
  • MHRA approved
  • Extensive analytical capability within our 14C Radiolabelling facility

Our validated quality critical equipment include:

  • Tri-Carb 2900 scintillation analyser
  • 3, 5, and 6 point analytical balances
  • Agilent HPLC with radioflow, UV and fluorescence detection
  • Agilent semi-prep HPLC
  • 2-8°C, -20°C and -80°C fridges and freezers
  • Büchi Rotavapors
  • Mini series beta and bremsstrahlung detectors
  • FlashMaster chromatography system
  • Hot plate stirrers
  • Hanna pH meter
  • Vacuum manifold
  • Vacuum oven
  • NMR / MS / LC-MS / GC

ADC Labelling

Experienced in this critical stage of modern drug development

In recent years, the interest in antibody drug conjugates for the targeted treatment of various cancer types has grown massively. Therefore, the need for the evaluation of their pharmacokinetic profile is becoming more important. We have significant experience in the manufacture of 14C-labelled Antibody Drug Conjugates (ADCs), which are typically placed on either the active drug or the linker moiety, or incorporated into both.

Our expertise in this area comes from the integration of a number of diverse disciplines within the 14C Radiolabelling group. These disciplines include biology, chemistry, peptide and purification science, and analytical and quality assurance. Our ability to prepare labelled linkers and/or payloads and to complete the bioconjugation within one team, shortens timelines and creates a cost effective solution for you.

We provide:

  • non-GMP synthesis of 14C ADC
  • GMP synthesis of 14C ADC including analytical tech transfer and validation
  • Expertise in purification and isolation of ADC
  • Storage and stability studies of your ADC
  • A breadth and depth of chemistry and analytical experience gained over many projects
  • Fully equipped laboratories including the appropriate DSP for efficient and effective working
  • Biology expertise

QC and analytical support, including method development and validation, method transfer and stability studies

Deploying a wide range of capabilities to analyse your product

At Almac, we routinely develop, tech transfer and validate methods for analysis in-house. We issue Certificates of Analysis, which specify the batch number, identity, results of analyses, GMP status and retest date. Our stability studies are fully compliant with ICH standards.

We use the following techniques:

  • Experience with a wide range of analytes
  • Experienced in analytical tech transfer, method development and validation of methods
  • Experienced in using existing analytical methods. These methods are efficiently transferred to our facility and verified for use with radiolabelled analytes
  • HPLC systems with radioflow, UV and fluorescence detection
  • Mass spectrometry for stable and radiolabelled products
  • Radio-TLC using the Cyclone Phosphor Imaging system
  • Gravimetric
  • Mass Spectrometric
  • Specific activity determination
  • NMR (400 & 500 MHz)
  • LC-MS, LC-MS-MS and GC-MS, for accurate determination of isotopic enrichment
  • X-Ray Powder Diffraction (XRPD)
  • Particle Size Analysis (microscope)
  • GC for residual solvents
  • SDS-PAGE

Stability studies:

We conduct stability studies, which range from short and informal, to detailed studies over long periods. These studies are carried out to ICH standards.

Our facilities include:

  • Validated –80°C stability storage facility for radiochemicals
  • Storage at 2-8°C, -20°C
  • 25°C/60%RH, 30°C/65%RH, 40°C/75%RH stability chambers for stable-labelled materials

To ensure an uninterrupted service, stability and storage units are continuously monitored and connected to a Building Management System.

Storage and Re-purification

Recommending storage conditions specific to your compound

Radiolabelled materials are subject to radiochemical decomposition in varying degrees. Stability can vary widely depending on the specific activity and nature of the molecule.

With that in mind, we provide the following services:

  • Stability studies – to provide an assessment of your compound’s decomposition rate and recommend storage conditions
  • ICH compliant stability chambers - these are available for radio and stable-labelled materials, covering the full range of conditions:
    • -80°C
    • -20°C
    • 5°C
    • 25°C/60%RH
    • 30°C/65%RH
    • 40°C/75%RH
    • Flash chromatography (including FlashMaster system)
    • Semi-prep HPLC, including normal and reversed phase, SEC and HIC
    • Ultra filtration and lyophilisation
    • Chemical techniques
    • Chiral chromatography
  • On-Site, validated storage of radio and stable-labelled products - keeping your compound under the most appropriate conditions, whether 2-8°C, -20°C, or –80°C
    • Purification through a range of techniques including:
      • Flash chromatography (including FlashMaster system
      • Semi-prep HPLC, including normal and reversed phase, SEC and HIC
      • Ultra filtration and lyophilisation
      • Chemical techniques
      • Chiral chromatography
  • Advice on the storage of your delivered materials

We are MHRA certified for 14C IMP and GMP compliance and we are fully equipped to deliver an industry-leading, cost-effective radiolabelling service.

 

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