Support For Your Move Toward Clinical Trials
As you consider initiating clinical trials for your cell therapy, there are many aspects of your preclinical research program to transform. Part of this exciting transition is building a robust manufacturing process that will require more extensive qualification of your raw materials.
We understand that need, and you can rely on us to provide appropriate grades of key materials – with flexibility and customization to fit your process. Our mission is to enable your therapy to reach more patients.
In the following sections, learn about how Bio-Techne’s offerings make your transition to GMP (Good Manufacturing Practice) as seamless as possible.
Why Should You Consider Animal-Free or GMP Raw Materials?
As your program moves farther along the transition from research to clinical manufacturing, it is increasingly important to document that your raw materials are compatible with manufacturing a therapeutic.
It is critical to utilize reagents that have been extensively tested and to document that the supplier’s manufacturing facility, processes, and operators are fully qualified. This is to ensure reagent integrity, batch-to-batch consistency, and traceability from starting material to final product. Thorough documentation is critical for demonstrating to regulatory agencies that raw material production meets all relevant guidelines. The additional scrutiny required to manufacture them comes at a cost but provides safeguards for patient safety as well as for your process.
Higher Grade Reagents
- More extensive QC testing
- Increased manufacturing control
- More complete documentation
Benefits for Your Process
- Improved process consistency
- Reduced risk of batch failure
- Regulatory compliance
- Time and money savings
Benefits for the Patient
- Improved safety
- Increased availability of therapy
When should you adopt GMP reagents? - Incorporation of Good Manufacturing Practice raw material grades early in your program can simplify your transition to the next stage. It is far easier to perform equivalency testing during preclinical stages than afterwards when material changes can be much more costly and time-consuming. These savings typically outweigh the additional cost of animal-free and GMP materials.
What options are there besides GMP? - For certain developmental stages, we also offer intermediate grades of proteins (Animal-Free RUO Grade) and small molecules (Ancillary Materials Grade) that are subject to more extensive testing, review, and documentation than RUO reagents, without the more costly GMP requirements. Learn more about our GMP Capabilities including certifications for each of our GMP manufacturing facilities.
Learn more about our GMP Capabilities including certifications for each of our GMP manufacturing facilities.
Case Studies
Meeting the GMP Cytokine Need for Cell Therapy Manufacturing
A cell therapy customer partnered with us for their transition to GMP cytokines and to reduce cytokine waste in a closed cell culture system.
Scaling GMP Protein Production
A customer requested the conversion of an existing RUO protein to GMP-grade as well as delivery of the GMP protein at the required scale.
What’s Important For Choosing a Raw Materials Supplier?
The relationship between a raw materials supplier and customer needs to be a partnership. It is important to evaluate potential suppliers based on how well they can support your process. Your transition from RUO to GMP can be seamless with proper communication, planning, and support from an experienced supplier. Incorporating GMP reagents into your process does not have to be a big jump.
- Ensure your supplier will have a deep understanding of quality management systems and analytical testing methods. A supplier experienced in regulatory matters will help you navigate rapidly evolving regulatory landscapes.
- Inquire about the supplier’s manufacturing processes and specifications for all available grades of raw materials. Differences in either physical or performance specifications could signal that your transition might not be straightforward.
- Audit your supplier’s production facilities. Your supplier should make virtual audits available if in-person audits are not possible.
- Request Drug Master Files (DMFs) that contain detailed information about their raw materials. These documents will assist regulatory authorities and simplify your applications for investigational new drugs (IND).
- Confirm your supplier’s capacity to deliver increased quantities of raw materials on the schedule you require.
Read Key Considerations for Cytokine Supplier Selection for Cell Therapies Article
Cytokines and Growth Factors
You can rest assured that incorporating R&D Systems™ GMP proteins into your process will not require you to perform extensive comparability testing. Our Animal-Free RUO and GMP grade proteins exhibit equivalent bioactivity and should perform the same in your process. We manufacture both grades of the corresponding proteins using the same methods and utilize the same vialing process.
Learn About Our GMP Manufacturing Facility
This consistency extends to our immunoassay platforms which are used to determine cytokine concentrations in cell culture media. Our Quantikine™ ELISAs and Simple Plex™ automated ELISAs are matched with the corresponding proteins to ensure equivalent results when moving from one grade to another.
Equivalent bioactivity with RUO, animal-free preclinical, and GMP grades of cytokines as measured in cell proliferation assays. (A) animal-free preclinical and GMP grades of human IL-2 (red and green, respectively). (B) animal-free preclinical and GMP grades of human IL-7 (red and green, respectively). (C) animal-free preclinical and GMP grades of human IL-15 (red and green, respectively).
Animal-Free RUO Proteins minimize experimental variables caused by trace animal components or mammalian pathogens. No animal-containing materials are permitted inside the production facility or in contact with the laboratory equipment.
Read our full Animal-Free Statement at R&D Systems.
Request an Animal-Free Protein Sample
GMP Proteins meet relevant guidelines to ensure their identity and safety for potential contact with patients. This includes final review and approval of batch documentation, formal validation of GMP processes, extensive safety testing of raw materials, and greater QC testing. We have filed drug master files (DMFs) with the FDA for many of our GMP proteins to simplify your investigational new drug (IND) applications.
You may need to use GMP growth factors and cytokines from different production lots which could be a source of variability in your process. To guard against this variability, each of our new lots must meet stringent quality control specifications for activity in a well-defined bioassay. We also test new lots against a master lot to control for assay variability. We provide lot-specific activity information on each product certificate of analysis (CoA) and provide lot-to-lot sample data on request.
ScaleReady™ Immune Cell Manufacturing Workflow
Our ScaleReady partnership accelerates immune cell therapy manufacturing, enabling high throughput parallel processing within a small footprint – efficiently producing more with less.
GMP Small Molecules
Transition your stem cell or regenerative medicine therapy to GMP with the right grade of small molecules at the right time. We offer RUO and GMP grades as well as an intermediate tier of small molecules (Ancillary Material Grade).
We manufacture GMP small molecules to the relevant sections of ICH Q7 guidelines to ensure consistency, traceability from start to finish, and animal-free production.
Ancillary Material Grade small molecules provide increased manufacturing control compared to research grade.
AM-grade small molecules offer enhanced QC testing, a more detailed QA review, and more extensive documentation than RUO compounds, without the more costly GMP requirements.
The synthesis of Ancillary Material Grade small molecules is based on established procedures for the equivalent RUO compounds but adhere to the ISO technical standard ISO/TS 20399 guidelines on the requirements for ancillary materials.
A comparison of RUO with Ancillary Material Grade and GMP products. Each block represents a stage in the manufacturing process, control measure, or guidelines followed to assure the quality of the final product. The size of the bar represents the relative time expended.
Non-Viral Gene Transfer With TcBuster™
Sidestep the hurdles of gene engineering with lentivirus by using a non-viral method. TcBuster is a next-generation non-viral genetic modification system with the potential to deliver therapeutic payloads to multiple cell types to address a broad range of therapeutic applications.
TcBuster can help strengthen your gene engineering process.
- Significant time savings for developing cell therapies
- Reduced cost of gene modification
- Ready availability throughout your manufacturing process
- Delivery of larger genetic cargoes for multi-gene insertions
Antibodies
Antibodies are essential in cell and gene therapy manufacturing, from cell activation and isolation to phenotypic and functional characterization. We can manufacture antibodies with enhanced specifications and documentation at gram quantities for your cell therapy process.
Our team of dedicated experts will work with you to
- Develop a GMP antibody from scratch to your exact specifications
- Convert an antibody from RUO to GMP
- Convert an existing antibody to a recombinant version
GMP Quality Compliance
Navigate through evolving regulatory guidelines and geographical differences with less time and effort. Our Quality Team includes more than 120 employees in quality and regulatory roles worldwide. We ensure compliance with all relevant guidelines from governing authorities. We can help you move into regulatory agency submissions without disrupting your process.
Our team oversees:
- Personnel training programs
- Facility maintenance and safety programs
- Validation of equipment and equipment calibration schedules
- Raw materials inspection, testing, and tracing
- Supplier qualification
- Material review board oversight of variances
Our QA team also oversees documentation covering processes and process changes, product change notifications, test methods, individual SOPs and batch records, lot-specific certificates of analysis, and certificates of origin. We perform a full QA review of all batch and bottling records before any material is shipped.
Each of our facilities is regularly audited by clients. We welcome both on-site and virtual audits.
What If Animal-Free Or GMP Materials Are Not Available? Customize!
Rapid process innovations can make it difficult to obtain suitable off-the-shelf raw materials. At Bio-Techne, a dedicated project manager from our Custom Team will work with you to provide the right quality of raw materials at the times you need them.
We will work with you to develop and deliver GMP raw materials and services that meet your unique process requirements. We can provide customized vialing by mass and activity, construct design, formulation, and quality control analysis. If particular GMP products are not available, we can develop them specifically for you. Our expert scientists, quality assurance team, and world-class technical support, will provide solutions exactly tailored to minimize comparability testing during later stages.
- Convert RUO materials to GMP
- Vialing based on activity or mass to fit your process
- Liquid bottling
- Custom labeling
- Batch reservation
- Supply and quality agreements
- Validation of specialized QC assays (such as raw material stability)
Background Information
1. Cell and gene therapy manufacturers need to bridge cytokine batches (lot-to-lot consistency, GMP testing against master lot). How can you ensure lot-to-lot consistency and reduce variability?
Cytokines and growth factors are made in biological systems and can be susceptible to variability.
They should only be released to market after successful manufacturing of many consecutive batches that have passed stringent specifications. This builds a solid foundation for future manufacturing consistency and reliability. Manufacturing processes must be controlled with rigorously documented SOPs and highly trained staff. This information should be made available during audit. It is fair to request data from several lots in order to assess a vendor’s ability to manufacture proteins reproducibly. Ideally, materials from multiple lots should be obtained so they can be tested for consistency in your system. At Bio-Techne, we maintain master control lots. Each new bulk lot is compared against the master lot prior to release to market. This reduces variability and ensures consistent product performance.
2. How do you ensure the raw materials you use in your manufacturing are appropriate to make products that can be used for ex vivo manufacturing?
We source raw materials from qualified suppliers with supplier qualification and monitoring systems in place. We also perform risk assessments for critical raw materials used in GMP processes every three years. This includes visual inspection of raw materials with documentation tracking of the Certificate of Analysis (CoA), Certificate of Origin (CoO), TSE/BSE statements, and animal-free statements, if applicable. We perform identity confirmation for some critical raw materials before accepting. For animal-derived materials, we always source from countries considered to be a negligible or controlled BSE risk.
3. What advice would you give to cell therapy developers when sourcing their raw materials?
We advise cell therapy developers to source raw materials from USP-grade or GMP-grade if possible. Our GMP-grade products are manufactured and tested according to applicable standards in United States Pharmacopeia (USP) Section 1043 Ancillary Materials for Cell, Gene, and Tissue-Engineered Products, and European Pharmacopeia (Ph. Eur.) General Chapter 5.2.12 Raw Materials of Biological Origin for the Production of Cell-based and Gene Therapy Medicinal Products. A supplier should have a certified quality management system (QMS), such as ISO 9001:2015 or ISO 13485: 2016. This means the supplier has been independently audited and has policies and processes in place designed to meet the needs of their customers. Suppliers of these raw materials should be further qualified and monitored by questionnaire, performance of on time delivery, SCARs, and other auditing activities. The Certificate of Analysis, Certificate of Origin and other related documents should be received from each supplier and kept as development and manufacturing records.
You should have early discussions about quality and supply agreements with suppliers to avoid surprises as you progress into production. A manufacturer should have the ability to scale up and meet your future needs in order to avoid late-stage changes that might require costly revalidation.
Identify secondary suppliers early as well. Raw materials may look identical on a Certificate of Analysis but could behave differently in your biological system. Do not assume that you can easily switch between suppliers for a given raw material. Validation studies are required to show equivalency between raw materials from different suppliers.
4. What are ancillary materials?
Ancillary materials (raw materials) are essential components required for the manufacture of cell and gene therapies or tissue-engineered therapies, but they are not intended to be part of the final product. This includes reagents such as small molecules and proteins as well as cell culture media. Although ancillary materials are not meant to be in the final product, they can impact the safety, purity and thus the suitability of the final cell product for clinical use.
GMP Proteins for Cell Therapy Manufacturing
Animal-Free Recombinant Proteins
GMP Small Molecules for Stem Cell Therapy Manufacturing
Culture Your Cells Serum-Free and Animal-Free
ExCellerate Serum-Free and Animal-Free Cell Expansion Media
Cell and Gene Therapy Manufacturing
Custom Services for Cell and Gene Therapy
T Cell Manufacturing for Cell Therapy
Natural Killer (NK) Cells for Cell Therapy
Induced Pluripotent Stem Cells (iPSCs)
Analytical Solutions for Cell and Gene Therapy
Professional Assay Services at ACD