Federal State Budgetary Institution “Scientific Center on Expertise of Medical Application Products”, responsible for conducting of scientific expertise of drugs for medical use and BMCP for the purposes of state registration, published an article devoted to the description of typical operations to obtain BMCP. In addition, the article contains requirements for the content of the documentation provided by the developer of BMCP in the registration dossier. Although the article was published long before the entry into force of the FZ 180 “On biomedical cell products” and other normative acts on BMCP, it contains key information concerning the production and registration of BMCP.

According to this article, obtaining of effective and safe BMCP involves the following typical operations:

• Developing cell line with specific cell composition
• Obtaining the sufficient amount of cells of a specific cell line for therapeutic use as a part of BMCP.
• Quality control and standardization of the developed cell line

 

1. Developing cell line with specific cell composition

One of the types of cells used to develop BMCP is mesenchymal stromal cells (MSC). They are obtained from bone marrow, adipose tissue and other vascularized tissues. Then the MSC can develop into muscular, fatty, nerve cells, the cells of bone and cartilage tissue.

MSC cell line is obtained in 5 stages.

The first stage is the selection of the donor. At this stage, donor of biological material is examined to identify contraindications for obtaining biological material for the production of BMCP.

The next stage is sampling of biological material It involves the implementation of the following operations in aseptic conditions: Obtaining of donor tissues, their grinding, reception of suspension of cells and its concentration.

In the third stage it is necessary to isolate stem cells from the donor’s material.

The fourth stage is obtaining of a  standardized homogeneous population of cells. This process involves the development of sufficient number of cells to cultivate them in a special equipment-bioreactor.

In the fifth stage the passport of the cell line is prepared. Certification is a necessary procedure documenting the results of control of the composition, quality and safety of the cell line.

2. Obtaining the sufficient amount of cells of a specific cell line for therapeutic use as a part of BMCP.

Then the cells that passed the “passport control” are placed into the bioreactor with the appropriate nutrient medium. There they grow and multiply. Then they are collected and prepared for concentration. After that they are concentrated and packed.

3. Quality control and standartization of the developed cell line

According to the FZ 180 “On biomedical cell products” under the quality of BMCP it is implied the compliance of BMCP to requirements of normative documentation. Quality control is devoted to the general requirements for quality indicators that are applicable to all cellular lines, and individual ones, which are used to evaluate therapeutic drugs that have their own range of indications.

It should be noted that the process of BMCP production is a complex and laborious task. It is even more difficult to develop a single set of requirements for the normative documentation necessary for the formation of the registration dossier.

References:

1. FZ № 180 «On biomedical cell products»
2. For citation: Supotnitskiy M.V., Elapov A.A., Merkulov V.A., Borisevich I.V., Klimov V.I., Mironov A.N. Common technological processes used in manufacture of biomedical cell culture products. BIOpreparations. Prevention, Diagnosis, Treatment. 2015;(2):36-45. (In Russ.) https://doi.org/10.30895/2221-996X-2015–2-36-45 (by link in Russian – технологические процессы)