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In this article, we’ve outlined a handy guideline in understanding the meanings and differences behind research use only (RUO), good manufacturing practices (GMP), as well as research and clinical grade reagent labeling. Also covered are key points to consider for effectively changing from research to clinical grade reagents, and how labs can confidently and easily transition their pre-clinical workflow to clinical grade reagents.
Human platelet lysate (hPL) is widely known as a consistent and safe protein-rich cell culture supplement, and is an important alternative to fetal bovine serum (FBS), especially for downstream therapeutic applications. Human platelet lysate is a key ingredient in cell culture media for efficient expansion of many therapeutic cell types, including mesenchymal stem cells (MSCs) and T cells.
There are many varieties of hPL available to suit different culture requirements, and it may be overwhelming to choose the right reagent for your cultures. When transitioning research workflows to GMP or clinical grade reagents, forethought and strategic planning for this change is important, and should happen well before a switch is needed in order to avoid delays and potential protocol changes to fit new quality and documentation requirements. Luckily, PLTMax® and PLTGold® hPL make the transition from research to clinical grade products simple and streamlined.
Good manufacturing practices (GMP) is a set of guidelines that ensures that a product is manufactured in a way that ensures consistent high quality and traceability. For cell culture reagents labeled as GMP, manufacturing practices are put in place with a quality system to ensure raw material sourcing, manufacturing controls, product QC testing, and documentation are all aligned and maintained for use in applications that require a higher level of quality, reproducibility, and safety in the product itself, such as development of cell-based therapies or other clinical-focused processes. Both research grade and clinical grade products can be manufactured following cGMP guidelines.
Reagents labeled RUO, meaning “for research use only”, are products that are intended to be used for research and early development, and not for final product manufacturing. Some RUO-labeled products are not produced according to GMP quality standards, and they must not to be used to produce any products for human use without full validation. Technically, RUO products can be used in clinical applications, but they require significantly more effort to verify their suitability, safety, and effectiveness for the intended use. Since this validation would require substantial costs and time, it’s better to use GMP or clinical grade materials for therapeutic applications.
Because of the added quality control and validation that goes in to the manufacture of a clinical grade reagent, these products often come with a higher price. While it would be simplest to use clinical grade reagents throughout the entire R&D and product development process, this is often cost-prohibitive and not realistic for most labs. Odds are, if you are working in the stem cell and regenerative medicine fields, you will find yourself somewhere in the middle of these two scenarios.
While there are many factors involved in this decision, in a nutshell, it’s never too early to plan the transition to clinical grade reagents for clinical applications while in research and early development stages. Delaying this planning stage or building a workflow with reagents that are not compatible with clinical transition will inevitably result in additional costs, timeline delays, and lots of frustration. Working with high quality research grade reagents that are manufactured following cGMP guidelines will significantly decrease the time and effort of the transition to clinical grade products.
In the next few sections, we’ll take a closer look at the quality attributes of PLTMax and PLTGold human platelet lysate to understand how the similarities between the research and clinical grade versions of these supplements allow for a smooth transition within a translational workflow.
Both research and clinical grades of PLTMax® and PLTGold® hPL are manufactured from expired platelets collected from healthy human donors. The platelets are obtained through accredited blood banks in the United States and were originally intended for clinical transfusion purposes. Because the platelets were already validated for patient injection, the safety of the material is managed by the US Food & Drug Administration (FDA) and the Association for the Advancement of Blood & Biotherapies (AABB), which set the safety standards for such transfusion products. By using these platelets as the raw material for human platelet lysate (hPL), the PLTMax and PLTGold hPL are safe, low-risk serum-replacement solutions for clinical translation.
All varieties of PLTMax and PLTGold hPL are manufactured and tested under a quality management system and facility that is cGMP certified to ISO 9001:2015. The manufacturing site has been audited multiple times by prominent commercial processors. The cGMP guidelines are designed following the recommendations of USP<1043> ancillary materials for cell, gene, and tissue-engineered products. The products are generally compliant with European Pharmacopoeia 5.2.12 and 5.1.7 as well.
Drug master files (DMFs) are submissions to FDA used to provide confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drug products. It contains the information on the specific reagent that the FDA will need as part of a comprehensive review of all materials that are used in a final therapeutic product, making it an important piece of documentation for potential clinical applications.
All PLTMax and PLTGold reagents (both research grade and clinical grade) are covered under a Type II Drug Master File # CBER MF 16784. This DMF can be referenced with the FDA via a Letter of Authorization request. Please contact Captivate Bio for more information.
PLTMax® is the original hPL product, launched and the clinical grade format has been used in many clinical trials worldwide. PLTMax is a completely animal serum-free supplement, though a small amount of heparin is used in the manufacturing process as an anticoagulant and is required while preparing complete media to minimize coagulation. PLTMax is available in research and clinical grades, as well as a gamma-irradiated clinical grade reagent for added safety against potential viral pathogens.
PLTGold® uses the same high-quality human platelets as PLTMax, but is a clot-free and completely xeno-free formulation, as there is no use of heparin in the manufacturing process. PLTGold has not been fibrinogen depleted. PLTGold is available as research and clinical grade, with pathogen-inactivated and gamma-irradiated treatments available for sensitive clinical applications.
The research and clinical grade PLTMax and PLTGold hPL supplements are manufactured in the same way under cGMP conditions in the same facility. The difference between research and clinical grades is that the clinical grade solutions are certified to be endotoxin-free with additional quality testing, which is documented on the products Certificate of Analysis.
While it may seem like the similarities would make it more difficult to choose a specific product, these similarities are very important. The fact that the research and clinical grade reagents hold the same high quality standards, share the same starting material and the same cGMP manufacturing processes is key for an easy clinical translation. Having the ability to easily move to the clinical grade version without needing to re-validate a workflow developed with the research grade version allows a smooth and simple transition from discovery and development to clinical applications.
Did you know that Captivate Bio is the LARGEST supplier of human platelet lysate for both research and cell therapy applications? Contact us today for more information.
Learn more about how we support researchers with cell culture products, contract manufacturing and storage services, custom reagent sourcing, as well as marketing, sales, and distribution programs for our industry partners.
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Human platelet lysate has become a gold standard supplement for cell production in cell therapy research. With the largest portfolio of HPL, request a sample from Captivate Bio today.
