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Higher Raw Material Grades To Fit Your Advancing Process
As you develop and scale your process, your requirements for raw materials will likely become more demanding. You may need to improve experimental consistency, or you may need to satisfy regulatory guidelines for clinical manufacturing. In addition, you may require increased quantities of raw materials and have confidence your suppliers can meet your needs.
We understand the need for adopting increasingly well-defined raw materials. Regardless of where your program is in this trajectory, you can rely on us to provide multiple grades of key materials – with flexibility and customization to fit your process.
Why Consider Animal-Free or GMP Raw Materials?
Higher grades of raw materials offer advantages over research use only (RUO)-grade materials. Compared to RUO, these grades are manufactured with increased process control, are more extensively tested, and are supplied with more complete documentation. This additional scrutiny comes at a cost but provides the user with improved process consistency and regulatory compliance.
Incorporation of higher grades of materials early in your program can actually simplify your transition to the next stage. If clinical applications are your goal, it is far easier to perform equivalency testing during preclinical stages than later when material changes can be much more costly and time-consuming. These savings typically outweigh the additional cost of animal-free and GMP products.
Ancillary Materials 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.
Animal-free preclinical proteins are particularly important for minimizing 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.
Animal-free GMP (good manufacturing practices) materials meet relevant guidelines to ensure the identity and safety of any raw materials that could potentially come into contact with patients. This includes final review and approval of batch documentation, formal validation of GMP processes, and extensive safety testing of raw materials. Greater QC testing stringency increases a customer’s ability to standardize manufacturing processes, leading to increased consistency at scale. This de-risks manufacturing processes by reducing the likelihood of batch failures. Learn about our GMP Capabilities.
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 whether or not they can support your process. With proper communication, planning, and support from a supplier, your process transition can be seamless. The transition from research use only (RUO) to animal-free and GMP materials does not have to be a big jump.
- An experienced supplier will have a deep understanding of quality management systems and analytical testing methods. In addition, a supplier experienced in regulatory matters will help you navigate rapidly evolving regulatory landscapes.
- A flexible supplier should be readily accessible for providing technical and regulatory support throughout the duration of your program.
- It is perfectly valid to 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.
- A supplier should welcome audits of their production facilities and should make virtual audits available if in-person audits are not possible.
- A supplier that provides Drug Master Files (DMF) with detailed information about their raw materials can assist regulatory authorities and ease applications for investigational new drugs (IND).
How We Support Your Translational Research
As you advance your research towards clinical manufacturing, you should have confidence that incorporating animal-free and GMP raw materials is efficient and does not functionally impact your process. In the following sections, learn about how Bio-Techne’s offerings make this transition as seamless as possible.
Cytokines and Growth Factors
Our animal-free preclinical and GMP proteins share the same biological activities as those produced using our standard processes. We manufacture both grades of the corresponding proteins using the same methods and are packaged with the same vialing process. This ensures the smoothest possible transition from one grade to the next.
This consistency extends to our immunoassay platforms which are used to determine cytokine concentrations during QC testing of 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) RUO, animal-free preclinical, and GMP grades of human IL-2 (black, red, green, respectively). (B) RUO, animal-free preclinical, and GMP grades of human IL-4 (black, red, and green, respectively). (C) RUO, animal-free preclinical, and GMP grades of human IL-6 (black, red, and green, respectively).
Small Molecules
To meet the rapidly increasing needs of stem cell and regenerative medicine research, we offer RUO and GMP grades as well as an intermediate tier of small molecules. The synthesis of Ancillary Material Grade small molecules is based on established procedures for the equivalent RUO products but adhere to the ISO technical standard ISO/TS 20399 guidelines on the requirements for ancillary materials. We manufacture GMP small molecules to the relevant sections of ICH Q7.
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.
Cloudz™ Cell Activation Kits
The GMP versions of our kits for immune cell activation are built with in-house, fully humanized GMP antibodies. The GMP kits meet USP 71 sterility guidelines and are packaged in larger volumes for the activation and expansion of larger batches of cells. We also offer a Cloudz Human NK Cell Expansion Kit that utilizes humanized RUO antibodies instead of mouse RUO antibodies.
Primary human CD3+ cells were activated with the RUO (1st and 3rd panels) and GMP (2nd and 4th panels) Cloudz Human T Cell Activation Kits with ExCellerate T Cell Expansion Media and Recombinant Human IL-2. By day 9 of culture, both kits induced 50-60 fold expansion of the cultures (1st and 2nd panels) and maintained 90% viability (3rd and 4th panels).
Advance your cultures with an innovative cell expansion platform that alleviates scale-up challenges. Our partners at ScaleReady offer G-Rex well plates and closed-system bioreactors that allow the same protocols to be used from early research through commercial scale up, dramatically simplifying transition to GMP manufacturing.
Antibodies
Antibodies are essential in cell and gene therapy manufacturing, from cellular activation and isolation to phenotypic and functional characterization. Our team of dedicated experts will work with you to develop a GMP antibody from scratch to your exact specifications. Alternatively, convert an antibody from RUO to GMP and have confidence in a consistent and scalable supply.
Gene Engineering
Realize the potential of genome engineering by partnering with our experts. Engineer any cell type including T cells, NK cells, and iPSC with our non-viral TcBuster™ gene delivery system. The TcBuster™ gene delivery system is the basis for our cell engineering services for everything from proof-of-concept work through process development. From the outset we will work with you to build in the flexibility needed to meet the demands of scaling to commercialization.
- TcBuster shortens the timeline and cost for engineering your cells.
- TcBuster delivers larger cargo sizes compared to virus-based methods.
Quality Compliance
Ensuring compliance with all relevant guidelines from governing authorities is time consuming considering the evolving guidelines and geographical differences. Count on our team of over 120 quality and regulatory employees to ensure that you can move into regulatory agency submissions without disrupting your process.
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.
- Converting 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)
Serum-Free and Animal-Free Cell Culture
Increase the consistency of your cell cultures as you approach translational studies for regenerative medicine and cell therapy programs. Adopting these media will
- Reduce variability in media composition
- Simplify compliance with regulatory guidelines
- Simplify comparability testing for raw material changes
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.
