Like-for-Like: The Importance of Homologous Use in Stem Cell Therapy

Our products are developed with “Homologous Use” in mind, as mandated by 21 CFR 1271.10(a)(2). The cells and tissues we offer perform the same basic function in the recipient as they do in the donor. Our robust validation process guarantees that each product aligns with this principle, further reinforcing our commitment to both regulatory compliance and patient safety.

Keeping it Pure: When Stem Cells Shouldn’t Mix

In keeping with 21 CFR 1271.10(a)(3), BioCellSupply ensures that our human cells and tissues are not combined with any other articles, except as explicitly permitted. When necessary, we use only water, crystalloids, or FDA-approved sterilizing, preserving, or storage agents. This practice ensures both safety and efficacy while meeting regulatory expectations.

Autologous and Relative Use: When Stem Cells Have Systemic Effects

In alignment with 21 CFR 1271.10(a)(4), any of our products that exhibit systemic effects or are dependent on the metabolic activity of living cells are strictly designed for autologous use, allogeneic use within close relatives, or reproductive use. This meticulous approach guarantees our unwavering compliance with this particular regulatory criterion.

The Paper Trail: Must-know Record-keeping Practices in the Stem Cell Industry

BioCellSupply places great emphasis on impeccable record-keeping and transparent reporting. As dictated by 21 CFR 1271.21, we are duly registered and have listed our products with the FDA. Moreover, our quality control measures are crafted to conform to “Good Tissue Practices” as prescribed in 21 CFR 1271 Subpart D. This ensures standardized methods, facilities, and controls for manufacturing, storing, and distributing HCT/Ps.

Safety First: Donor Eligibility and Other Key Criteria

Last but not least, BioCellSupply is committed to meeting the donor eligibility criteria specified in 21 CFR 1271 Subpart C. Our rigorous screening and testing processes are designed to minimize any risk of transmission of communicable diseases, ensuring both product quality and patient safety.

Section 361 of the Public Health Service (PHS) Act (42 U.S.C. 264) is a specific legislative provision that grants the U.S. Food and Drug Administration (FDA) the authority to issue and enforce regulations to prevent the spread of communicable diseases. These regulations can apply to the control of diseases at their source and can include sanitation, quarantine, and isolation measures. In the context of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps), Section 361 allows the FDA to regulate these products to ensure they do not pose a risk for the transmission of infectious diseases.

HCT/Ps that are regulated solely under Section 361 are often termed “361 products.” These are distinct from HCT/Ps that are regulated as drugs, devices, and/or biological products under Section 351 of the PHS Act. Products that meet specific criteria, outlined in 21 CFR Part 1271, are regulated solely under Section 361 and are not subject to premarket approval. These criteria include:

1. Minimal Manipulation: The cells or tissues must be minimally manipulated.
2. Homologous Use: The cells or tissues must be intended for homologous use.
3. Not Combined with Another Article: The product should not be combined with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent.
4. No Systemic Effect or Dependent on Metabolic Activity: If the HCT/P has a systemic effect or is dependent on the metabolic activity of living cells, certain conditions must be met.

In addition, establishments that manufacture these 361 products must register and list their products with the FDA and adhere to Good Tissue Practices, which cover methods, facilities, and controls for manufacturing, storing, and distributing HCT/Ps.

By adhering to Section 361 and the relevant sections of 21 CFR Part 1271, manufacturers ensure that their HCT/Ps meet the necessary safety standards aimed at minimizing the risks of communicable disease transmission and other potential hazards.

Section 351 of the Public Health Service (PHS) Act (42 U.S.C. 262) pertains to the regulation of biological products, including Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) that do not meet the criteria to be regulated solely under Section 361. Unlike Section 361 products, which are primarily regulated to prevent the risk of communicable disease transmission, Section 351 products are subject to more stringent regulatory oversight due to their higher risk profile.

Biological products under Section 351 are regulated as drugs, devices, and/or biological products and must undergo premarket approval. This involves a rigorous review process, including the submission of an Investigational New Drug Application (IND) or a Biologics License Application (BLA), and often requires clinical trials to demonstrate safety and efficacy.

Here are some of the key aspects that distinguish Section 351 products:

Pre-Market Approval

Products regulated under Section 351 usually require pre-market approval, which can be a lengthy and expensive process. This is to ensure that the product is safe, effective, and produced using consistent quality standards.

Clinical Trials

Most Section 351 products must undergo clinical trials to demonstrate their safety and efficacy for a specific indication. These trials are closely monitored and must adhere to strict regulatory guidelines.

Good Manufacturing Practices

Manufacturers of Section 351 products must comply with Good Manufacturing Practices (GMP), which are more stringent compared to the Good Tissue Practices (GTP) required for Section 361 products.

Labeling and Marketing

Products approved under Section 351 are generally allowed more latitude in labeling and marketing, especially when it comes to making claims about the product’s effectiveness for specific indications.

Post-Market Surveillance

After approval, Section 351 products are subject to post-market surveillance to monitor for any adverse events or quality issues.

Section 351 of the PHS Act pertains to the regulatory pathway for biological products, including certain HCT/Ps, that require premarket approval by the FDA. These products are subject to more rigorous standards for safety and efficacy compared to those regulated solely under Section 361.

Both Sections 351 and 361 of the Public Health Service (PHS) Act govern the regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps), but they do so in significantly different ways, reflecting different risk profiles and intended uses of these products. Below are the key differences between Section 351 and Section 361:

Regulatory Oversight:

• Section 351: Products are regulated as biological products, drugs, and/or medical devices. They require premarket approval through mechanisms such as Investigational New Drug Applications (INDs) or Biologics License Applications (BLAs).

• Section 361: Products are regulated to primarily prevent the spread of communicable diseases and do not require premarket approval. They must adhere to specific criteria outlined in 21 CFR Part 1271 to qualify for this pathway.

Clinical Trials:

• Section 351: Typically requires clinical trials to establish the safety and efficacy of the product for its intended use.

• Section 361: Does not require clinical trials if the product meets the criteria for regulation solely under this section.

Manufacturing Standards:

• Section 351: Requires adherence to Good Manufacturing Practices (GMP), which are more stringent standards for quality control.

• Section 361: Requires adherence to Good Tissue Practices (GTP), focusing on methods, facilities, and controls for manufacturing, storing, and distributing HCT/Ps.

Intended Use:

• Section 351: Usually intended for non-homologous uses or involves more than minimal manipulation, thus requiring more rigorous scrutiny for safety and efficacy.

• Section 361: Intended for homologous use and involves minimal manipulation, thereby aligning closely with natural function and posing lower risk.

Marketing and Labeling:

• Section 351: Allows for more specific medical claims related to the product’s effectiveness for particular conditions, following FDA approval.

• Section 361: Marketing claims must be limited to the product’s homologous use and cannot include claims of treatment, cure, or mitigation of diseases.

Post-Market Surveillance:

• Section 351: Subject to post-market surveillance to monitor for any adverse events or quality issues.

• Section 361: Less stringent post-market requirements but must still adhere to record-keeping and reporting guidelines to ensure safety.

Time and Cost:

• Section 351: Usually involves more time and financial investment due to the need for clinical trials and premarket approvals.

• Section 361: Generally less time-consuming and costly, as it avoids the need for premarket approval.

By understanding these key differences, one can better appreciate the regulatory landscape surrounding HCT/Ps and how it aims to balance both safety and innovation in this fast-evolving field.

To qualify for governance under Section 361 of the Public Health Service (PHS) Act, Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) must meet specific criteria outlined in 21 CFR Part 1271. These criteria are designed to ensure that the products are safe and pose minimal risk of spreading communicable diseases. Here are the key criteria that an HCT/P must meet to be regulated solely under Section 361:

Minimal Manipulation

The HCT/P must be “minimally manipulated,” as defined in 21 CFR 1271.3(f). In simple terms, the processing should not alter the original relevant characteristics of the cells or tissues as they relate to their utility for reconstruction, repair, or replacement.

Homologous Use

The HCT/P must be intended for “homologous use,” as stipulated in 21 CFR 1271.10(a)(2). This means that the HCT/P should perform the same basic function or functions in the recipient as in the donor. For example, a skin graft should only be used to replace or repair skin.

Not Combined with Another Article

The HCT/P should not be combined with another article, such as a drug or device, except for water, crystalloids, or a sterilizing, preserving, or storage agent. This is detailed in 21 CFR 1271.10(a)(3).

No Systemic Effect or Dependent on Metabolic Activity

If the HCT/P has a systemic effect or is dependent on the metabolic activity of living cells, it should meet specific conditions outlined in 21 CFR 1271.10(a)(4). Typically, this means the HCT/P should be for autologous use (from the same individual), for use within a close relative, or for reproductive use.

Record-keeping and Reporting

Even if an HCT/P is regulated solely under Section 361, it is required that establishments manufacturing these products register and list them with the FDA. This is governed by 21 CFR 1271.21. Additionally, such establishments must adhere to Good Tissue Practices (GTP) as defined in 21 CFR 1271 Subpart D.

Additional Regulatory Requirements

The HCT/P must also meet donor eligibility criteria and other safety requirements to minimize the risk of transmission of communicable diseases. These are outlined in 21 CFR 1271 Subpart C.

If an HCT/P fails to meet any of these criteria, it will typically be regulated as a drug, device, and/or biological product under Section 351 of the PHS Act, which involves a more rigorous approval process.

No, a Human Cells, Tissues, and Cellular and Tissue-Based Product (HCT/P) that is regulated solely under Section 361 of the Public Health Service (PHS) Act does not require premarket approval from the FDA to be marketed. However, it must meet the specific criteria outlined in 21 CFR Part 1271 to qualify for regulation under Section 361. These criteria are designed to minimize the risk of communicable disease transmission and ensure general safety.

While Section 361 products do not require FDA premarket approval, establishments that manufacture these products must:

1.  Register and List Products with the FDA: As per 21 CFR 1271.21, establishments must register themselves and list their HCT/Ps with the FDA.
2.  Adhere to Good Tissue Practices (GTP): As specified in 21 CFR 1271 Subpart D, these practices cover methods, facilities, and controls for manufacturing, storing, and distributing HCT/Ps.
3.  Comply with Donor Eligibility Criteria: According to 21 CFR 1271 Subpart C, the HCT/P must meet specific donor eligibility criteria to minimize the risk of transmission of communicable diseases.
4.  Maintain Records and Report Adverse Reactions: Establishments must keep accurate records and are required to report to the FDA any adverse reactions or complaints associated with the use of their HCT/Ps.

If the FDA finds that an establishment or its HCT/Ps are not in compliance with these requirements, the agency may take regulatory actions, which could include product recalls, public health advisories, or legal sanctions.

Therefore, while Section 361 products can be marketed without premarket approval, they must still adhere to specific regulatory criteria to ensure they are safe and effective for their intended homologous use.

An RFD, or Request for Designation, is generally submitted when a product’s regulatory classification is unclear or in dispute. This often occurs for products that could be regulated as a drug, a device, a biological product, or a combination thereof. In the context of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps), an RFD may be submitted to determine whether the product should be governed under Section 351 or Section 361 of the Public Health Service (PHS) Act, or whether it falls under another regulatory pathway altogether.

Here are some situations when an RFD should be considered:

Unclear Classification

If a manufacturer is uncertain whether their HCT/P should be regulated under Section 361 as a tissue product or under Section 351 as a biological product, drug, or device, submitting an RFD can help clarify its appropriate regulatory pathway.

Dispute with FDA

If there is a disagreement between the manufacturer and the FDA regarding the classification of the product, an RFD can serve as a formal mechanism to resolve the dispute.

New or Novel Products

For new or innovative HCT/Ps where the regulatory landscape may not be fully defined, an RFD can provide much-needed clarity.

Change in Intended Use or Manufacturing Process

If there has been a significant change in the intended use or manufacturing process of an HCT/P that could potentially change its classification, an RFD may be advisable.

Marketing and Labeling Claims

If a manufacturer wishes to make specific claims about the product’s efficacy that could potentially shift its classification from one governed by Section 361 to one requiring premarket approval under Section 351, an RFD can offer guidance.

The FDA’s Office of Combination Products (OCP) is typically responsible for reviewing RFDs and providing a formal determination usually within 60 days of submission. This determination will clarify the product’s primary mode of action and the appropriate center within the FDA that will have regulatory oversight (e.g., Center for Biologics Evaluation and Research, Center for Drug Evaluation and Research, or Center for Devices and Radiological Health).

Submitting an RFD can be a critical step for manufacturers to ensure they are adhering to the correct regulatory guidelines and to expedite the product development process.

The term “minimally manipulated” refers to a specific regulatory criterion for Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) as defined by the U.S. Food and Drug Administration (FDA). According to 21 CFR 1271.3(f), minimal manipulation is described as:

“Processing that does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement.”

In simpler terms, “minimal manipulation” means that the processing of the cells or tissues should not fundamentally change the characteristics that make them useful for their natural function in the body, such as repair or replacement of tissues.

Examples of Minimal Manipulation:

1. Bone: Cutting or grinding bone may be considered minimal manipulation if those processes do not change the bone’s original relevant characteristics, like its strength and rigidity.
2. Skin: Cleaning and sizing skin grafts may be considered minimal manipulation as they do not change the skin’s original relevant characteristics, like providing a barrier to the external environment.
3. Cellular Products: For cellular products, minimal manipulation means that the processing does not change the relevant biological characteristics such as differentiation potential or function.

Importance in Regulatory Classification:

The concept of minimal manipulation is crucial for determining how an HCT/P is regulated. If a product is minimally manipulated and meets other specific criteria (homologous use, not combined with another article, etc.), it may be regulated solely under Section 361 of the Public Health Service (PHS) Act. Such products are subject to less stringent regulatory oversight compared to those that are more than minimally manipulated, which are usually regulated under Section 351 and require premarket approval.

Understanding whether an HCT/P is minimally manipulated is essential for manufacturers and healthcare providers to ensure they are following the appropriate regulatory guidelines.

The term “homologous use” refers to a specific regulatory criterion for Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) as defined by the U.S. Food and Drug Administration (FDA). According to 21 CFR 1271.10(a)(2), homologous use is defined as:

“The repair, reconstruction, replacement, or supplementation of a recipient’s cells or tissues with an HCT/P that performs the same basic function or functions in the recipient as in the donor.”

In simpler terms, “homologous use” means that the HCT/P should be used for the same basic function in the recipient as it performs in the donor. For example, bone marrow stem cells, which produce blood cells in the donor, should be used to restore blood cell production in the recipient.

Examples of Homologous Use:

1.  Bone: Using bone to repair or replace skeletal defects is considered a homologous use because the bone performs the same basic function in both the donor and the recipient.
2.  Skin: Using skin grafts to treat burns or wounds is considered a homologous use because the skin serves the same basic barrier function in both the donor and the recipient.
3.  Corneas: Transplanting corneas to restore sight in cases of corneal blindness is a homologous use because the cornea serves the same basic function of refracting light in both the donor and recipient.

Importance in Regulatory Classification:

The concept of homologous use is crucial for determining how an HCT/P is regulated. If a product is intended for homologous use and meets other specific criteria (minimal manipulation, not combined with another article, etc.), it may be regulated solely under Section 361 of the Public Health Service (PHS) Act. Such products are subject to less stringent regulatory oversight compared to those intended for non-homologous uses, which are typically regulated under Section 351 and require premarket approval.

Understanding whether an HCT/P is intended for homologous use is essential for manufacturers and healthcare providers to ensure they are following the appropriate regulatory guidelines.

Yes, different registered tissue types can have different homologous applications, reflecting their natural function in the human body. The concept of “homologous use,” as defined by the U.S. Food and Drug Administration (FDA), means that the Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) should perform the same basic function in the recipient as they do in the donor.

Here are some examples to illustrate how different tissue types can have different homologous applications:

Bone Tissue

• Homologous Use: Repair or replacement of skeletal defects.
• Natural Function: Providing structural support and facilitating movement.

Skin Tissue

• Homologous Use: Treating burns, wounds, or skin defects.
• Natural Function: Serving as a barrier to external environment and pathogens.

Corneal Tissue

• Homologous Use: Restoration of sight in cases of corneal blindness or damage.
• Natural Function: Refracting light to enable vision.

Heart Valves

• Homologous Use: Replacement of damaged or diseased heart valves.
• Natural Function: Facilitating unidirectional blood flow within the heart.

Bone Marrow Stem Cells

• Homologous Use: Restoration of blood cell production in cases of bone marrow failure.
• Natural Function: Hematopoiesis, or the production of blood cells.

Amniotic Membrane

• Homologous Use: Wound covering to support healing.
• Natural Function: Serving as a protective barrier for the fetus in utero.

Cartilage

• Homologous Use: Repair or replacement of damaged cartilage in joints.
• Natural Function: Providing cushioning and support within joints.

Because each tissue type has its own natural function, its homologous use in medical applications will differ. Understanding these different homologous uses is crucial for both healthcare providers and manufacturers to ensure that they are in compliance with regulatory guidelines, particularly those outlined in 21 CFR Part 1271 and Section 361 of the Public Health Service (PHS) Act.

Yes, for an HCT/P (Human Cells, Tissues, and Cellular and Tissue-Based Products) to be regulated solely under Section 361 of the Public Health Service (PHS) Act, it must meet specific criteria, including being “minimally manipulated.” The concept of minimal manipulation is defined in 21 CFR 1271.3(f) as:

“Processing that does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement.”

Manufacturers or establishments that produce HCT/Ps need to be able to provide evidence or documentation that demonstrates the product has undergone only minimal manipulation. This evidence could include:

1. Process Descriptions: Detailed documentation of the manufacturing and processing steps that demonstrate they do not alter the original relevant characteristics of the tissue.
2. Scientific Studies or Literature: Peer-reviewed studies or literature that support the claim that the processing methods do not alter the original relevant characteristics.
3. Comparative Analysis: Comparing the characteristics of the processed tissue with those of the original tissue to demonstrate that no fundamental alterations have been made.
4. Validation Data: Data from internal quality control tests that confirm the tissue retains its original functionality after processing.

Failure to meet the minimal manipulation criterion would mean that the HCT/P could be subject to more stringent regulations under Section 351 of the PHS Act, requiring premarket approval and adherence to more rigorous manufacturing standards.

Thus, evidence of minimal manipulation is not just advisable but often essential for establishing that an HCT/P qualifies for the less stringent regulatory pathway under Section 361. This evidence is crucial for both regulatory compliance and for ensuring the safety and efficacy of the product.

The U.S. Food and Drug Administration (FDA) provides guidance documents and regulations, notably in 21 CFR Part 1271, to outline the criteria that Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) must meet to qualify for regulation solely under Section 361 of the Public Health Service (PHS) Act. While the FDA doesn’t maintain a definitive list of tissue types that do not qualify for Section 361, certain characteristics or criteria can render an HCT/P ineligible for this regulatory pathway. These include:

More Than Minimal Manipulation

If the processing alters the original relevant characteristics of the tissue relating to its utility for reconstruction, repair, or replacement, the HCT/P would not qualify for Section 361 and would be subject to regulation under Section 351. For instance, stem cells that have been gene-modified to express a therapeutic protein would likely be considered more than minimally manipulated.

Non-Homologous Use

An HCT/P intended for a function other than what it naturally performs would not qualify for Section 361. For example, using bone marrow stem cells to treat neurological conditions might be considered non-homologous use.

Combined with Another Article

HCT/Ps combined with other articles like drugs, devices, or biologics, may not qualify for Section 361 unless the combination is with water, crystalloids, or a sterilizing, preserving, or storage agent.

Systemic Effect or Dependent on Metabolic Activity

If the HCT/P has a systemic effect or is dependent on the metabolic activity of living cells for its primary function, and it doesn’t meet additional criteria (like being for autologous use or use among close relatives), it won’t qualify for Section 361.

Failure to Meet Additional Regulatory Requirements

Failure to comply with donor eligibility criteria, Good Tissue Practices, or other requirements specified in 21 CFR Part 1271 Subparts C and D can also make an HCT/P ineligible for Section 361.

For more specific guidance, manufacturers often consult directly with the FDA or submit a Request for Designation (RFD) to clarify the regulatory status of their product. While the FDA guidance documents provide a general framework, the regulatory classification often depends on the specific characteristics and intended use of the HCT/P in question.

Yes, Section 361 products can contain live cells. The key regulatory focus for products under Section 361 of the Public Health Service (PHS) Act is primarily on minimizing the risk of communicable disease transmission and ensuring general safety, rather than on the viability of the cells within the product.

However, there are specific criteria that these products with live cells must meet to be regulated solely under Section 361, as outlined in 21 CFR Part 1271:

1. Minimal Manipulation: The cells must be minimally manipulated, meaning the processing should not alter the original relevant characteristics of the cells related to their natural function.
2. Homologous Use: The cells must be intended for homologous use, meaning they should perform the same basic function in the recipient as they do in the donor.
3. Not Combined with Another Article: The cells should not be combined with another article, such as a drug or device, unless it’s water, crystalloids, or a sterilizing, preserving, or storage agent.
4. No Systemic Effect or Dependent on Metabolic Activity: If the cells have a systemic effect or are dependent on the metabolic activity of living cells for their function, they must be intended for autologous use, allogeneic use in a first-degree or second-degree blood relative, or reproductive use.
5. Additional Regulatory Requirements: The cells must meet donor eligibility criteria and other safety requirements, including Good Tissue Practices, to minimize the risk of communicable disease transmission.

If a product with live cells meets these criteria, it can be regulated under Section 361 and does not require premarket approval from the FDA. However, it is crucial for manufacturers to provide evidence that their product complies with these criteria to avoid being subject to more stringent regulations under Section 351 of the PHS Act.

According to the U.S. Food and Drug Administration (FDA) guidelines, an HCT/P (Human Cells, Tissues, and Cellular and Tissue-Based Products) does not necessarily have to be used in the same anatomic location to be considered for “homologous use,” as long as it performs the same basic function or functions in the recipient as it does in the donor. The focus is on the basic function of the tissue or cells, not their location.

The key criterion, as outlined in 21 CFR 1271.10(a)(2), is that the HCT/P should be intended for “homologous use,” defined as:

“The repair, reconstruction, replacement, or supplementation of a recipient’s cells or tissues with an HCT/P that performs the same basic function or functions in the recipient as in the donor.”

For example:

• Bone Marrow Transplants: Bone marrow cells naturally produce blood cells. These cells can be transplanted into the bone marrow of a recipient to perform the same basic function, even if the specific bones involved are different from the donor’s.

• Skin Grafts: Skin serves as a protective barrier. A skin graft can be used in different anatomic locations in the recipient than where it was harvested from the donor, as long as it serves the same basic function of acting as a barrier.

However, it’s crucial to note that the determination of homologous use often depends on the specific claims made by the manufacturer regarding the product’s therapeutic benefits. If the manufacturer claims that the HCT/P can perform functions other than its basic, homologous functions, then the product may not qualify for the less stringent regulatory pathway under Section 361 of the Public Health Service (PHS) Act and may be subject to regulation under Section 351 instead.

In summary, the same basic function or functions must be performed by the HCT/P in both the donor and the recipient for it to be considered for homologous use, but this does not necessarily have to occur in the same anatomic location.

BioCellSupply oversees every stage of the manufacturing process following recovery, encompassing the processing, storage, labeling, packaging, and distribution of all human cell or tissue products that are manufactured and marketed by BioCellSupply.

Disassociated amniotic membrane products transformed into a flowable form do not qualify for regulation under Section 361 of the PHS Act because they undergo more than minimal manipulation. According to the FDA, the basic function of the amniotic membrane is to act as a barrier. When processed into a liquid or flowable state, the product no longer retains its primary utility as a barrier, making the processing more than minimal manipulation.

This naturally raises questions about how BioCellSupply’s Wharton’s jelly products, processed in a similar manner, meet the criteria for minimal manipulation while amniotic flowables do not. While the FDA doesn’t specify the primary functions of Wharton’s jelly, clinical literature extensively describes its roles in providing cushioning and support and protecting the umbilical vein and arteries from mechanical stress. Unlike the amniotic membrane, Wharton’s jelly maintains its capability to perform its primary functions even when processed into a flowable form.

It’s worth noting that some structural tissues may undergo processing that changes cellular or extracellular matrix components without altering their original relevant characteristics. However, the same processing methods could change the original relevant characteristics of another type of structural tissue. Therefore, when evaluating whether a processing step changes a tissue’s original relevant characteristics related to its utility for reconstruction, repair, or replacement, one should consider the impact of the processing on the properties contributing to each specific tissue type’s function in the donor.