Cell Therapy Systems (CTS™) FAQs
Below are commonly asked questions relating to the Cell Therapy Systems (CTS™) line of products.
Cell Therapy Systems (CTS™) FAQs
- What is Cell Therapy Systems (CTS™)?.
- Where are these products manufactured, and what is the importance of manufacturing in such facilities?
- How are CTS™ products different from RUO products, and what does the updated intended use statement mean in terms of where and how it can be used?
- What products would you recommend for clinical use, given that the proper local regulatory documentation is in place (cGMP-manufactured, RUO-labeled, serum-supplemented, reduced-serum, serum-free, xeno-free or chemically defined, IVD-labeled, CTS™-labeled, or 510(k)-cleared)?
- If I have approval from a local authority and proper regulatory documentation, can I use your cGMP-manufactured media and substrates to propagate cells ex vivo followed by transplant back into the human body?
- Are TrypLE™ Select CTS™ and Accutase of human origin? Are they clinical grade?
- Can I place a custom order for CTS™ products?
- Is the CTS™ brand of products rated for preclinical use?
- I am a US customer. What is required from me in order to use catalog products for clinical use (IVD, RUO, 510(k), CTS™)? How about international customers?
- A product has 510(k) clearance for “ex vivo expansion." Does this mean I have approval to use the product for in vitro expansion? For example, I will be doing TREG expansion with Dynabeads® and would like to use AIM V® CTS™, KnockOut™ SR, or KnockOut™ SR Xeno-Free CTS™—is this OK?
- Which product is better for clinical use: StemPro® MSC SFM or StemPro® MSC SFM Xeno-Free?
- Can I have the formulation of your products for my clinical study?
- How can we get access to your DMF?
- Where can I find technical literature such as Certificates of Analysis (COA), MSDS, and Product Manuals?
- What documents are available with CTS™ products?
- Do you have any products that can be used as excipients for cell therapy injections?
The Gibco® Cell Therapy Systems (CTS™) brand offers a wide selection of products for use in cell therapy applications, including media, reagents, growth factors, enzymes, cell selection/expansion reagents, and devices. Gibco® CTS™ products are of high quality, and are supplied with harmonized documentation such as Certificates of Analysis, Certificates of Origin, and access to authorization letters for our Drug Master Files, as appropriate. The Gibco® CTS™ product line enables you to reduce the burden in qualifying reagents during your transition from research to clinical applications.
2. Where are these products manufactured, and what is the importance of manufacturing in such facilities?
Cell culture media and reagents are manufactured in our Grand Island, New York facility. This facility is cGMP, ISO 9001, and ISO 13485 compliant. Growth factors are manufactured in our Frederick, Maryland facility, which is cGMP and ISO 13485 compliant. The DynaMAG™ CTS™ and Dynabeads® CTS™ products are manufactured in our Oslo, Norway facility, which is certified according to the quality standards of ISO 9001 and ISO 13485, and follows the requirements of cGMP when necessary. The quality system is maintained in order to meet both the ISO standard and the Medical Device Directive in Europe. By following these regulatory guidelines and manufacturing under cGMP, we provide high-quality products with lot-to-lot consistency and traceability, helping to ensure the best foundation for reproducible, reliable results.
3. How are CTS™ products different from RUO products, and what does the updated intended use statement mean in terms of where and how it can be used?
The label for CTS™ products may vary:
"For Research Use Only or Manufacturing of Cell, Gene, or Tissue-Based Products":
This label indicates the product can be used as a raw material component in the customer’s process of manufacturing cells, genes, or tissues (in addition to research or preclinical research use). The CTS™ product is considered the customer’s raw material component. Products include, for example, OpTmizer™ CTS™, TrypLE™ Select CTS™, GlutaMAX™-I CTS™, DPBS CTS™, and DynaMAG™ CTS™.
"For Research Use or Non-commercial Manufacturing of Cell-Based Products for Clinical Research":
Examples: CELLstart™ CTS™, KnockOut™ DMEM CTS™ , Dynabeads® CD3⁄CD28 CTS™, all CTS™ growth factors
"For human ex-vivo tissue & cell culture processing applications":
Examples: KnockOut™ SR XenoFree CTS™, AIM V® Medium CTS™
These products also include the standard caution statement, “CAUTION: Not Intended for Direct Administration into Humans or Animals."
4. What products would you recommend for clinical use, given that the proper local regulatory documentation is in place (cGMP-manufactured, RUO-labeled, serum-supplemented, reduced-serum, serum-free, xeno-free or chemically defined, IVD-labeled, CTS™-labeled, or 510(k)-cleared)?
If you already have regulatory approval, any of these products are good options. If you do not have approval but intend to secure it, CTS™ and 510(k)-cleared products, xeno-free, or those with a DMF on file with the FDA may be somewhat easier than those products with animal-origin components that do not have traceability or supporting documentation.
5. If I have approval from a local authority and proper regulatory documentation, can I use your cGMP-manufactured media and substrates to propagate cells ex vivo followed by transplant back into the human body?
You must have regulatory approval via an IND, IDE, or appropriate regulatory filing in the country in which the process will take place, for us to recommend products for use in ex vivo applications. AIM V® Medium (0870112) and KnockOut™ SR XenoFree (1099201) are cleared by the FDA for use in ex vivo applications.
6. Are TrypLE™ Select CTS™ and Accutase of human origin? Are they clinical grade?
TrypLE™ Select CTS™ and Accutase are not of human origin. We do not offer a clinical-grade dissociation reagent. TrypLE Select CTS™ is labeled “For Research Use Only or Manufacturing of Cell, Gene, or Tissue-Based Products.” Accutase is labeled “For Research Use Only.
7. Can I place a custom order for CTS™ products?
Yes. Whether you’d like a price inquiry or an order, call 1-800-955-6288 ext. 46501, or email firstname.lastname@example.org to discuss your request with a Life Technologies CTS™ representative.
8. Is the CTS™ brand of products rated for preclinical use?
CTS™ products can be used for preclinical use if the end user validates the component for their intended use. You must have an IND or IDE to perform a clinical trial within the US.*
9. I am a US customer. What is required from me in order to use catalog products for clinical use (IVD, RUO, 510(k), CTS™)? How about international customers?
Customers within and outside the US may use Life Technologies products in clinical trials as long as they have approved INDs or IDEs. If you require labeling for investigational devices per 21 CFR 812.5, you will need to purchase a custom product with the appropriate labeling: “Labeling for investigational devices: CAUTION – Investigational device. Limited by Federal law to investigational use.”
10. A product has 510(k) clearance for “ex vivo expansion." Does this mean I have approval to use the product for in vitro expansion? For example, I will be doing TREG expansion with Dynabeads® and would like to use AIM V® CTS™, KnockOut™ SR, or KnockOut™ SR Xeno-Free CTS™—is this OK?
The 510(k) means the product has been shown to be cleared ”for human ex vivo tissue and cell culture process applications.” It may also be used for in vitro expansion.
11. Which product is better for clinical use: StemPro® MSC SFM or StemPro® MSC SFM Xeno-Free?
Either one is an option if you have prior regulatory (FDA) approval. The xeno-free product may be easier to secure approval for, due to the lack of bovine components. Without regulatory approval, our catalog Research Use Only products can be used in research laboratories, including clinical research applications, ONLY.
12. Can I have the formulation of your products for my clinical study?
The answer to this depends on the product, the reason you need the information, and your location. If the product’s formulation is not confidential, we will provide it in full. If the formulation is confidential, we can work with you under a confidentiality agreement (CDA) to determine if the disclosure is possible. If you need detailed information to assist in a regulatory filing, we will work with you to allow you to reference an existing or new DMF (for US customers), or provide information directly to the authorities (for customers outside the US).
13. How can we get access to your DMF?
DMF request forms can be found on the CTS™ Support page on our website: http://www.invitrogen.com/gibcoctssupport
14. Where can I find technical literature such as Certificates of Analysis (COA), MSDS, and Product Manuals?
Technical information can be found on the CTS™ Support page: gibcoctssupport
15.What documents are available with CTS™ products?
Certificate of Origin, Certificate of Analysis, animal origin designation, adventitious agent testing, and Drug/Device Master File for relevant products. We also offer product reserves (lot-specific) and raw material alerts.
16. Do you have any products that can be used as excipients for cell therapy injections?
No, because they would need to be made under the pharmaceutical GMPs (21 CFR Part 210 & 211).
A 510(k) is a premarket submission made to the FDA to demonstrate that the device to be marketed is at least as safe and effective (i.e., substantially equivalent) as a legally marketed device (21 CFR 807.92(a)(3)) that is not subject to PMA. NOTE: The 510(k) indicates a specific use, and it does not cover all possible clinical uses.
Premarket approval (PMA) is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or that present a potential unreasonable risk of illness or injury.
What is the difference between a 510(k) and a PMA?
A 510(k) is a submission for premarket clearance for a Class II device that shows substantial equivalence to a predicate device. A PMA is a submission for premarket clearance for a Class III device. The PMA includes clinical and analytical data to support the safety and effectiveness of the device.
A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) by the manufacturer that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. The submission of a DMF is not required by law or FDA regulation. A DMF is submitted solely at the discretion of the holder. The information contained in the DMF may be used to support an Investigational New Drug Application (IND), a New Drug Application (NDA), an Abbreviated New Drug Application (ANDA), another DMF, an Export Application, or amendments and supplements to any of these. The customer must have one of these submissions with the agency in order for Life Technologies to provide a letter of reference to our DMF. The DMF is not provided to the requestor; instead, Life Technologies will provide a letter of authorization to the FDA providing them authorization to review our DMF on behalf of the requestor. The requestor will also receive a copy of the letter to be included in their filing with the FDA.
Investigational New Drug. Current federal law requires that a drug be the subject of an approved marketing application before it is transported or distributed across state lines. A sponsor will most likely want to ship an investigational drug to clinical investigators in many states; it must seek an exemption from that legal requirement. The IND is the means through which the sponsor obtains this exemption from the FDA.
An investigational device exemption (IDE) allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support a Premarket Approval (PMA) application or a Premarket Notification (510(k)) submission to FDA. Clinical studies are most often conducted to support a PMA. Only a small percentage of 510(k)s require clinical data to support the application. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices. All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the study is initiated.
Life Technologies Corporation (LTC) definitions
A mammal (including human), avian, or eukaryotic aquatic species.
Animal origin–free (AOF) component (primary)
A component will be considered to be animal origin–free (primary) if it has not been directly derived from animal tissue, cells, or body fluid. Products produced via bacterial or yeast recombinant processes will not be considered to be of animal origin even if the manufacturing process includes animal components in the fermentation broth or process enzymes.
Animal origin–free (AOF) component (secondary)
A component will be considered to be animal origin–free (secondary) if the component and/or the processes used during the manufacturing of the component were not derived from material produced via bacterial, yeast, or other recombinant processes where animal components were included in the fermentation broth or processing enzymes.
Xeno-free (XF) product
Gibco® XenoFree media and reagents include products that may contain discrete proteins, bulk protein fractions, or recombinant proteins of human or non-animal origin. They may also contain proteins, hydrolysates, or components of unknown composition of human or non-animal origin.
cGMP (Current Good Manufacturing Practices)
Our Gibco® cell culture media, balanced salt solutions, and animal sera are categorized under the classification of Cell and Tissue Culture Products, class I, medical devices, in vitro diagnostics (21 CFR Part 864, subpart C).