This essay will discuss about the regulation of cellular therapies. Producing of cellular therapy is researched in the division of cell and gene therapies in the center of cellular, gene therapy and tissue. This part introduce cell therapy and gene therapy. This research speak about gene and cell therapy and cell therapy products. This division has three parts that consist of laboratory researches such as check products. They conclude of the immunogenicity branch, the tumor vaccines, the gene transfer and, and the biotechnology branch, and the cellular and tissue therapy branch.

Somatic cell therapy are set as biological exist in public health services in section 351. Where that have concern about infection disease.

Human cells are set as biologics if some of the scale are met: they are minimally retouch. These cells used in way that isn’t homologous to their normal function. These cells have a systemic effect and they are dependent upon the metabolic activity for primary function in living.

These scales are sometimes as malicious factors. This meaning that FDA set a clinical development under IND or new drugs. Confirmed presale will be needed these cells meet these scales.

A dangerous factors on the previous studies recognized by FDA in 1933. Somatic cell therapy that defined in biology as allogeneic, autologous, or xenogeneic cells that used this factors as expanded, propagated, selected, pharmacologically treated and these factors can decrease symptoms of illness and cure the illness and injures.

Some samples about cell therapy products include of stem cell derived products and stem cell. For instance such as those from hematopoietic, mesenchymal, and umbilical cord blood, cancer vaccines, embryonic and immunotherapies, such as dendritic cell vaccines, monocytes, activated T or B lymphocytes, and modified or unmodified cancer cells, allogeneic pancreatic islet cells, chondrocytes for cartilage repair, keratinocytes, hepatocytes and fibroblasts.

Xenotransplantation products are also set in cell therapy. This term said by FDA. This point is that definition includes more than one cell. It’s Also includes whole organ xenotransplantation also have ex vivo contact that exist in tissue and organs. If you have embryonic stem cell and have grown on a murine feeder layer that these products defined Xenotransplantation. Recently interest in using Xenotransplantation products has been used the use porcine pancreatic islets for the cure of diabetes and porcine hepatocytes for the cure of sharp liver insufficiency. So we prognosticated this field will be increase in future.

Here are guidance evidences prepare by United States government to arrange the public health risks that associated with xenotransplantation.

The previous section covered by cell therapies. Now we explain that how cell therapy are set. Which rules apply to cell therapy?

The list of stipulations has shown on this part as 21 of the federal regulations that we called CFR that this rules uses in cell therapy products. The tissue and organs rules doing in part 1271, the biologics necessities outlined in the part 600 and 610, the investigational new drug necessities in part 312, and the medicines manufacturing necessities in parts 211 and 212. Then FDA manage a cell therapy with regulation about drugs and medicines. This method has advantages and good points but these products have a many unique features that are different from medicines.

We have some concern about unique to cellular products. First the size of producing is a lot. Just one or two doses can treat a patients. The limitations of this method is we have a limited material for testing. The most of patients shows that we must sure every person how many need? Till receive a correct count.

The second concern is the timing of produce, administration and testing. Many of the products cannot be archest and must be executed after harvest. In this items shipping, testing and administration procedures must be quick to guarantee the quality of cell therapy product.



Every patients and donors will have a biopsy, apheresis, or other cellular starting material or another different patients and donors. Also biological experiments used to describe a cell but have a lots of features. One of point is that cell therapy is not stable.

Another challenge aseptic processing is need to keep sterility.

In this term quality of control that sure us about levels of manufacturing and this rules ensure this products. This includes tissues and incoming cells. We need a confident program until improve grades and quality. We can test a process of manufacturing in time. Final product testing are required to confident self-life of the cells.

FDA needs that the donor cells for an allogeneic product meet donor competency necessaries, just the same as for human tissue donors. Although cell banks for cell therapy products are different from another cells in the cell bank that used a biologics materials and we need a same test. The cell bank may be from cells have been grown in cell culture that cells grow before a few passage. In some items you used a kind of cell to cure a couple of patients.

This method hasn’t any regulations and this method advised a 21 CFR 610 rule. Final product testing is needed by regulation. However FDA lets company to produce a drugs and medicines that is suitable.

This part show a list that biologists needs to this process. This discussion talk about potency, purity, sterility and identity. Products of cell therapy are exempt from general exam. We need the Mycoplasma for culture in a long period of time. Cells that culture in a short time exempt from Mycoplasma testing.

Sterility one of test that take time to 14 days. Most of Cell therapy products are frozen and these cells cannot stored for 14 days until receive an experiments that take time 14 days. Flexibility by allowing a cell therapy product to be understood based on process sterility testing results. For instance you might sample the cell that grew in lab plate that culture 3 days in there and final levels you inject the cells into patients. Now this essay we talk about gram stain. This experiments isn’t very sensitive assay but this experiments is fast and detect large contamination. The gram stain is usually used in cases that the results of the 14 days sterility test cannot be available before to patients. For these items the sponsor is needed to have a plane for positive result that are gave after patient administration.

The action plan should have notification of the physician of a positive result, a plan for how the patient will be cured and evaluated, and an investigation plan to evaluate the producing process to prevent future positive sterility test results. FDA encourage sponsors until utilize quickly sterility test.

All biologists needs endotoxin test. We have an impurities after that final test residual solvents, animal products or antibiotics that might use these additives in lab plate and these products may cause be sensitive and make a bad conditions for patients or maybe occur adverse events. So that FDA wants to make final product testing until remove bad result about endotoxin test.

When biologists talking about impurities also they interest in the cellular composition of the final product, including contaminating cell types. For instance T cell therapy products doing by sponsor with FDA. Unknown cells may influence in product results.

We need identify test until can recognize each products of them. This a challenge for products of cell therapy and help us to not able recognize patients-specific from one another. For these products labeling, tracking and segregation systems must to be in place and we must avoid mixed ups between patient-specific products.

Potency is meaning that one product have ability that can influence in one result. The test for potency include vitro or in vivo test that both of them designed to show them abilities and potencies. Measuring potency in cell therapy it’s so important for FDA so that FDA interested in approach to potency. Showing the biological functions and activities of the cells in vitro might not translate into the cell’s activity in vivo.

We can measure potencies and biological activities by one of method that biologists called direct ASS-ay. For instance you might use a mixed lymphocyte reaction to we can see reaction of cells against target tissue we measured activities of cells by sigh-toe-kine secretion. Also FDA has allowed to use indirect measure till we can correlate cell phenotype with a function.

For example dendritic cells can set a co-stimulatory molecule such as CD86 that it could be indirect measure of dendritic cell activation and potency. Nowadays FDA has allowed to researchers that measure a matrix approach in cells and examine potency and the test has a lots of features that these features describe cell’s ability. For instance FDA usually questions for viability testing lot understand and viability can notice you about potency. Although FDA not accept measuring as the measurement of potency.

Before than inject this product to the patients we take results about potency testing. Potency testing must be fully validated and this test must show activity product.

This subject must illustrate a measure of product consistency. Often sponsors might tell FDA that cannot test final testing because cells before giving a results to researchers will be died. FDA tried to elect every choices. Sometimes need to keep cell products that may affect these cells. FDA usually preparing endotoxin testing results. This test may take time up to two hours. In this process of testing provides important documents and for us and help us determining how to apply the lot release testing. FDA wants to try and gain as complete an understanding as is possible of the cell therapy product.

So sponsors encourage are encouraged to look beyond just the simple lot release testing, and include additional testing, such as a full panel of markers for phenotypical analysis. They also encouraged to look at protein and gene expression utilizing powerful assays such as arrays that give to us many data. Also FDA encourage sponsors to look at another parameter and feature. Oftentimes the minimum lot release testing is not really sufficient enough to tell you everything you need to know about the product. This essay show two guidance evidences that are explain cell therapy disease.


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