Advanced Therapies Require Advanced Testing Solutions  

As short shelf-life therapies and advanced therapy medicinal products (ATMPs), such as cell and gene therapies, continue to grow in importance, so does the need for a test method as advanced as these therapies. This emerging class of advanced products create a new set of challenges for biopharmaceutical companies than those faced by traditional pharma when trying to adhere to CGMP manufacturing methods.  

Challenges of ATMP Rapid Testing

Since ATMPs are typically short shelf-life products, batches must be released at risk and administered to patients ahead of official sterility testing results, when using traditional methods. Small volumes and overall batch sizes limit the amount of total product available for short shelf-life therapy testing. Since living cells exist in an ATMP quality control sample, which may render traditional culture media inherently turbid by nature, this often requires adding sub-culture steps which may extend the test by 14-21+ days.  

Short shelf-life, cell therapy, and gene therapy manufacturing have a specific set of needs based on these challenges:

image of cells under a microscope
  • The need for faster results than traditional methods to avoid unnecessary extra days that jeopardize patient safety
  • Objective, confident tests with minimal complexity are needed due to low batch volumes to minimize the risk of human error and need for retesting
  • Non-destructive assays are needed to allow for confirmation and investigations

3 Day Sterility Results for Short Shelf Life Products 

The Celsis Adapt™ Concentrator and Celsis Adapt™ Cell Reagent Kit can overcome the unique challenges needed for cell, gene, and ATMP production and commercialization. Compatible with a wide variety of cellular sample testing from early development to final rapid release results within 3 days, this system ensures patient safety while allowing organizations to deliver critical medicines to patients quickly.

Features and Benefits of Celsis Adapt™

  • Faster Time to Results than Traditional Sterility Methods (USP <71> and Ph. Eur. 2.6.1)

    Short shelf-life products often deteriorate so quickly that the 14-day traditional final sterility release test is not an option. Medicines must be administered to the patient ahead of testing results, placing critically ill patients and the manufacturer at risk. With short shelf-life products, even the typical time-to-detection (6-7 days) provided by current rapid microbiological methods may not be fast enough. Providing a faster time to results (three days) will provide even greater patient safety benefits.  

  • Sensitive to Small Batch Sizes, Requires Minimal Sample for Testing

    Batch sizes may be for just a single patient (autologous therapy) or for many patients (allogeneic therapy) but does not have surplus product to be saved for multiple retests. 

  • Aligned with Emerging Industry Guidance for QC Testing ATMP, Short Shelf-Life, and Cell and Gene Therapy Products

    Industry guidance organizations and regulators are providing optimized methodologies for ATMP, short shelf-life, cell therapy, and gene therapy testing, such as risk-based approaches outlined in the following guidance:  

    • USP <1071>, Rapid Microbial Tests for Release of Sterile Short-Life Products: A Risk-Based Approach 
    • European Pharmacopeia Chapter 2.6.27, Microbiological Examination of Cell-based Preparations 
  • Compatible with Autologous Therapies and Allogeneic Therapies Containing Cells that Interfere with Many Test Methods (Alternative, Rapid, and Traditional)

    Traditional sterility test methods via turbidity become problematic when used for cell therapy sterility testing and gene therapy sterility testing as the product may induce turbidity upon initial preparation. Cells already containing DNA, RNA, or ATP require technology that removes the cellular debris and reduces the background while preserving microbial cells; however, many current rapid microbiological methods cannot handle this for direct inoculation and membrane filtration sterility test methods. The Celsis Adapt™ system is compatible with a wide variety of sample types and both direct inoculation and membrane filtrations for ATMP and C&GT quality control.  

  • Scalable and Adheres to CGMPs (Data Integrity, Automation, and Non-destructivity)

    Providing the fastest result possible is not enough. As an alternative and rapid microbiological test method, it must reduce human error, improve testing throughput, and lab efficiency. Celsis® systems, used in conjunction with the Celsis Adapt™ provide sound data integrity features, such as automated analysis and reporting to guarantee accurate and confident test data.  

Rapid Microbial Detection Systems for ATMP and Short Shelf-Life Therapy QC Testing 

Celsis Advance II instrument for rapid microbial detection

The Celsis Adapt™ instrument assists in the performance of QC testing for cell therapies, gene therapies, and other advanced therapies. By concentrating samples and removing cellular components that interfere with the background and ATP-bioluminescence detection signal, it allows for rapid microbial detection on Celsis® luminometers.

 

celsis advance system

We recommend combining Celsis Adapt™ sample concentrator with the Celsis Advance II™ luminometer for rapid testing of ATMPs, short shelf-life products, cell therapy, and gene therapy quality control samples. Capable of running 120 assays per hour, this instrument is best suited for high-throughput pharmaceutical bioprocessing. 

 

Celsis Accel system for rapid microbial detection

The Celsis Adapt™ sample concentrator is also compatible with the smaller Celsis Accel® luminometer. With a throughput rate of 30 assays per hour, this instrument is a smart option for contamination control for small to midsize biopharma manufacturers or for optimizing quality testing during research and commercialization of cell and gene therapies.
 

Celsis Adapt™ Product Details

  • Product Specifications
    Size (Height x Width x Depth): 13.9 in x 11.5 in x 6.2 in / 35.3 cm x 29.2 cm x 15.7 cm
    Weight: 8.8 lbs / 4.0 kg
    Electrical Requirements:

    Supply: 100-240VAC, 1.5A, 50-60 Hz
    Operating: 12VDC, 3A

    Maximum Sample Volume: 10 mL
    Software Compatibility: Operated with on-board firmware
    Pre-programmed protocols
    Celsis® Instrument Compatibility: 

    Celsis Advance II™
    Celsis Accel® 


    Celsis® Reagent Kits Available: 
    Celsis Adapt™ Cell 100 Kit

     

  • Product Codes

     

    Product Code

    Celsis Adapt™ Sample Concentrator 
    On-board firmware
    Power Supply with Type B, C, and G Regional Adapters 
    Washing Solution Adapter
    Tubing Line & Clip

    AD9000

    Celsis Adapt™ Cell 100 Kit
    Celsis Adapt™ Cell Reagents
    Celsis Adapt™ Concentrating Solution, Sterile x 3 cans
    Celsis Adapt™ Tips, 0.2 µm , Sterile x 40 tips
    Celsis Adapt™ Maintenance Tip x 1 tip

    AD1420

    Celsis Advance II™ Instrument
    Celsis® Advance II.im software
    USB-serial cable
    Power supply
    Cuvette rack
    Reagent rack

    7456004

     

  • Specificity Testing

    The Celsis Adapt™ method does not impact the specificity of the overall Celsis®  ATP-bioluminescence. As part of a rigorous development and method validation program followed by beta testing in collaboration with several pharmaceutical companies, the Celsis Adapt™ has been proven to detect the presence of the following common challenge microorganisms, but not limited to those as stated in regulatory guidance documents. 

    Compendial Challenge Organisms  Industry-Relevant and Objectionable Organisms*
    Aspergillus brasiliensis  Burkholderia cepacia  
    Bacillus subtilis   Clostridium sporogenes  
    Candida albicans   Cutibacterium acnes  
    Escherichia coli   Kocuria rhizophila  
    Pseudomonas aeruginosa   Penicillium chrysogenum  
    Staphylococcus aureus    
    *A longer list of industry-relevant and objectionable organisms can be found in the Celsis Adapt™ Sample Concentrator product sheet
  • Limit of Detection

    The limit of detection for the assay remains at 1 CFU and continues to adhere to validation parameters described in PDA TR 33, USP <1223>, and Ph. Eur. 5.1.6. This sample preparation still maintains the non-destructive benefit of Celsis® ATP-bioluminescence while utilizing a small amount of the original incubated sample.

    The biopharmaceutical industry is in a period of huge innovation and rapid changes as the paradigm shifts to personalized medicines using cell and gene therapy technology. In turn, the ability to ensure patient safety through rapid, confident quality control and contamination detection shouldn’t fall behind either.  

Frequently Asked Questions about Rapid Detection of Short Shelf-Life Products and Cell Therapies

  • What are ATMPs?

    Advanced therapy medicinal products (ATMPs) are a class of medicines that can be classified as either a somatic cell-based therapy, gene therapy, or product engineered from tissue. They fall under the broader category of medicinal product of biologics. 

  • What are short shelf-life products?

    Short shelf-life products are ATMPs which typically possess a very short shelf life (sometimes measured in hours) that must be administered to patients before the end of traditional contamination test methods. They often contain no preservatives or stabilizing components, as these components impact the nature of the therapy itself (tissue, cell, or gene based). These types of products are also often manufactured in very small batch sizes. Additionally, radiopharmaceuticals and nuclear pharmaceuticals are also considered short shelf-life products, such as those used in nuclear diagnostic imaging.  

  • What are cell and gene therapies?

    Cell therapies or cell-based therapies contain manipulated human or animal somatic cells. Cells from a donor are engineered and transferred to a recipient, where the modified cells treat a wide variety of disease such as cancers, autoimmune disorders, and skeletal or connective tissue damage.

    Gene therapies, on the other hand, involve transferring genetic material from a donor to a recipient, typically using a vector to transport in the material into the new host. 

  • How do you test for contamination in ATMPs, short shelf-life products, and cell and gene therapies?

    ATMPs and short shelf-life products can be tested using traditional sterility test methods since they are injected into the patient. However, these have been administered at risk due to the fact that the traditional sterility test requires a 14-day incubation period or longer if the sample induces turbidity.  

    When administered at risk to the patient, due to the product’s short shelf life, manufacturers of these medicinal products must monitor the sterility test and notify clinicians immediately if the product fails sterility. There are lethal consequences if patients cannot be administered antibiotics or necessary treatment as soon as possible, especially if a fungal contamination is present. Therefore, manufacturers of these therapies require the fastest testing methods possible to minimize the at-risk period for patients. 

  • What guidance exists for quality control testing of ATMP and cell therapies?

    The following resources are available that provide guidance on contamination testing of advanced therapy medicinal products, cell therapy, and gene therapy classifications: 

    • Food & Drug Administration: Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs) 
    • USP <1071>, Rapid Microbial Tests for Release of Sterile Short-Life Products: A Risk-Based Approach 
    • European Pharmacopoeia Chapter 2.6.27, Microbiological Examination of Cell-Based Preparations 
    • EudraLex: Governing Medicinal Products in the European Union. Volume 4. GMP. Guidelines on Good Manufacturing Practice Specific to Advanced Therapy Medicinal Products