TUESDAY, 27 FEBRUARY 2018 / PUBLISHED IN BLOG

Although they can perform surgeries, osteopathic physicians try to avoid doing so whenever possible. Because of this, PRP seems to be an excellent fit for their practice. Since Osteopathy was built on the idea of self-healing, PRP seems to be a perfect fit.

The Current State of PRP Research

A while ago, PRP research was reviewed by The Journal Of The American Osteopathic Association, which concluded that more studies and evidence are needed to make a solid statement on its efficacy. Later, a case study was filed showcasing an 18-year-old high school football player who suffered from a sports injury. The case study showed that the muscle injury healed rapidly under PRP therapy. Although PRP is not yet universally acclaimed, it doesn’t mean Osteopathic Physicians can’t learn a lot or benefit from its use in their practice.

How Osteopathic Physicians Can Benefit From PRP

It’s Holistic

Osteopathic Physicians prefer to treat the patient rather than just treating a disease or its symptoms, making PRP a great fit. PRP works by using the body’s own resources and mechanics to help it heal itself over time. Instead of merely addressing symptoms like many conventional medicines do, it tackles the problem directly.

For example, there are cases where PRP therapy has taken the place of surgery and medication. Female patients have revived their sex drive after being treated for incontinence. While PRP therapy was initially pushed by allopathic doctors, it works wonders in Osteopathic medicine and can become a key treatment method for Osteopathic physicians.

Musculoskeletal Issues

In many practices, musculoskeletal pain is a common issue for Osteopathic Physicians. PRP is quickly becoming a primary treatment for these kinds of problems. For instance, many researchers believe PRP should be the main choice for patients suffering from knee meniscus issues.

In 2016, University of Missouri Doctor Patrick Smith published an FDA-sanctioned double-blind randomized placebo-controlled clinical trial on PRP. These trials are considered the gold standard in research. The study concluded that PRP provides safe and notable benefits for people suffering from knee osteoarthritis.

The Vast Potential of PRP

The third and most important reason why all physicians, including Osteopathic Physicians, should start using PRP therapy is its wide scope. Since PRP is simple and common, it’s safe to say that if PRP works on knee joints and tendons, it likely works on other tendons, joints, bones, and muscles. PRP will soon be a commonplace treatment for nearly all musculoskeletal diseases.

This means PRP has near limitless potential. This is especially important for Osteopathic Physicians because if a patient has a wrist problem, the main issue might appear further down the arm. Multiple PRP injections in various areas can not only heal the issue but also enhance other traditional methods used. This will help restore balance to the body and give full functionality back to the patient.

Success Stories and Expert Opinions

American Academy of Regenerative Medicine Doctor Peter Lewis has administered over 100,000 PRP injections to over 12,000 patients. He claims that more than 80% of his patients who have undergone PRP therapy have had fantastic results. Even patients who were candidates for surgery have benefited from PRP.

Are PRP Treatments FDA Approved?

As of this year, PRP treatments are not yet subject to FDA approval. This is because all treatments are performed on the same day as the extraction and use only materials already inside the patient’s body. Therefore, PRP therapy falls within the scope of the FDA Code of Federal Regulation title 21, part 1270, 1271.1, making it exempt from needing approval.

TUESDAY, 30 JANUARY 2018 / PUBLISHED IN BLOG

Regenerative medicine is the exciting cutting-edge “medicine of the future” which holds the hope and promise of efficacy centered around the ability of human tissue to be repaired, replaced, and healed (regenerated) once human tissues and organs are damaged or diseased. Regenerative therapies aid and supplement the natural healing mechanisms of the body. These therapies often employ the activation of stem cells to stimulate the renewal of tissue damaged by injury, disease, or age. The rapid expansion of scientific knowledge offers great promise for continuing advances in this field of medicine, which holds vast potential to improve the quality of human life.

What are Stem Cells?

Stem cells are the basic building blocks of life. They are unspecialized cells that can produce more stem cells through mitosis or differentiate into specialized cells that carry out specific functions in the body. Stem cells are found throughout the body’s tissues, organs, and systems, although usually in small quantities in adults.

What are Hematopoietic Stem Cells?

Hematopoietic stem cells (HSCs) can give rise to all types of blood cells, including red blood cells, white blood cells, and platelets. They are particularly useful in the treatment of blood-related diseases and conditions.

What are Mesenchymal Stem Cells?

Mesenchymal Stem Cells (MSCs) are multipotent stromal cells that are non-blood-forming stem cells and can differentiate into a variety of cell types, including muscle, bone, cartilage, and fat cells.

When introduced into a patient’s body, MSCs can repair or replace damaged or degenerating tissue by communicating with the surrounding cells, causing a cellular cascade of healing (paracrine signaling).

The History and Potential of MSCs

Historically, the term MSC was coined in the late ’80s by the biomedical research authority, Dr. Arnold Caplan of Case Western Reserve. The acronym has recently been redefined by Caplan to “Medicinal Signaling Cell” since these cells secrete powerful bioactive molecules involved in cellular signaling and regeneration. Caplan now describes MSCs as a “multisite-regulatory dispensary” (Natural Drug Store).

The production of MSCs in the human body can be precipitated by bioactive placental tissues containing Growth Factors, Cytokines, and other powerful bioactive agents which trigger cell signaling.

The remarkable ability of MSCs makes them irreplaceable in medical treatments.

Accessible Sources of Stem Cells

Stem cells can be extracted from various parts of the body. They have been extracted from bone marrow and adipose tissue for a few decades. More recently, birth tissues from live births, including umbilical cord blood, cord tissue with Wharton’s Jelly, and amniotic membrane tissue, have been found to be a rich source of both HSCs and MSCs. These tissues precipitate target tissue production of MSCs through paracrine signaling. Growth Factors, Cytokines, Exosomes, and micro-RNA from birth tissues give rise to stem cells in this way. These cells, as well as MSCs contained in Wharton’s Jelly, tend to be more fit than adult stem cells.

Wharton’s Jelly

Wharton’s jelly is a gelatinous substance found in the umbilical cord, which is rich in stem cells. Studies have shown that mesenchymal stem cells (MSCs) have low immunogenicity. Human umbilical cord Wharton’s jelly provides a new source for MSCs that are highly proliferative and have multi-differentiation potential. Wharton’s Jelly Cells (WJCs) express MSC markers but low levels of human leukocyte antigen (HLA)-ABC and no HLA-DR. WJCs have low functional immunogenicity, and therefore recipient rejection has not been documented.

Advanced Regenerative Medicine

Advanced Regenerative Medicine involves the use of regenerative biomolecules, tissue engineering, and stem cells to treat diseased or injured tissues.

Exploring the Power of Platelet-Rich Plasma (PRP) in Regenerative Medicine

WEDNESDAY, 14 MARCH 2018 / PUBLISHED IN BLOG

We have been in the regenerative medicine specialty for about 8 years. Like pretty much everyone, we started by using Platelet-Rich Plasma (PRP). We learned about it, were fascinated by it, and treated our patients with it. Patients loved it, and so did we.

The Versatility of PRP

PRP, if obtained and used correctly, is a very powerful tool to implement in any medical practice. It is especially useful for treating the elderly, osteoarthritis, wear and tear of tendons and ligaments, and loss of vitality. PRP is also frequently used in plastic and reconstructive surgery for wound care, scar improvement, and overall rejuvenation of the skin.

How Does PRP Work?

We are all familiar with platelets. They have significant power and influence over tissue regeneration. By concentrating them in a blood sample, we can obtain signaling proteins, cytokines, and growth factors. Adding white blood cells to the mix creates what is called L-PRP (leukocyte-rich PRP), making that “soup” even more potent.

Activating PRP for Maximum Benefits

To harness the power of these bioactive substances, we need to coax the cells into releasing them. Normally, platelets get activated by the addition of calcium or by contact with collagen. However, several studies have demonstrated the influence of low-intensity laser on the activity of some cells. This effect is called “Photobiomodulation.”

Understanding Photobiomodulation

Photobiomodulation is a form of light therapy that uses non-ionizing light sources, like LEDs or Helium-Neon lasers, to produce photochemical events at various biological scales. It has been demonstrated that this light interacts with the enzyme Cytochrome C oxidase, which is crucial in mitochondrial processes.

The Impact of Low-Level Laser Therapy

Several scientists studied this light and its effects on cellular cultures. They found that cells proliferate more when exposed to low-level laser and showed increased viability. We compared the levels of cytokines and growth factors in irradiated and non-irradiated samples. Sure enough, some growth factors even tripled in concentration after laser exposure. The famous Interleukin 10, an anti-inflammatory protein, doubled its levels, and endorphins were released in high levels.

Benefits of Photobiomodulation

The photobiomodulation process provides extraordinary benefits in pain management, inflammation reduction, immunomodulation, and promotion of wound healing and tissue regeneration. It plays a fundamental part in our protocols.

Conclusion

Isn’t it all amazing? The potential of PRP and photobiomodulation in regenerative medicine continues to astonish us. We will see you in the next blog. Keep your cells healthy!

TUESDAY, 23 JANUARY 2018 / PUBLISHED IN BLOG

Hair loss is very common, with tens of millions, if not hundreds of millions, of people all over the world suffering from it. Hundreds of thousands of people decide to utilize hair restoration therapy and other procedures in order to try to get at least some of their former hair back. Although some treatments are effective, most of the time, they only move already existing hair from one place to another. However, with stem cell therapy, we try to help new hair grow by helping the follicles to regenerate.

The Role of Adimarket in Hair Restoration

Adimarket, alongside a few other companies, helps provide new and reliable uses for PRP and stem cell therapies. We provide the equipment and other services so that doctors and practices can offer these treatments to their patients.

Promising Advances in PRP and Stem Cell Therapies

While the main proponents of PRP and stem cell therapies are smaller companies like us, many other people, including doctors and practices, are also discussing and seeing potential in these therapies. For example, Dr. Lazaro M Garcia, a doctor from Miami, already utilizes PRP and stem cell therapy for people who suffer from hair loss and is currently conducting a study supported by the National Institutes of Health.

How the Study Works

To participate in the study, patients pay a small fee, which varies based on their study stage. Afterwards, they receive two injections of PRP and stem cells made from their own body over three months. Dr. Garcia uses the body’s own growth factors to increase the amount of blood and nutrients to the otherwise dead hair follicles. This revitalizes the dead follicles and promotes new hair growth.

How PRP is Made

To make Platelet-Rich Plasma (PRP), the patient’s own blood, which can come from either bone marrow or other fat sources, is used. The blood is then placed into a centrifuge, which concentrates the composition and allows it to be injected into the treatment site. While it is a relatively simple procedure, some training is still necessary to ensure that it is done safely.

Adimarket’s Equipment Offerings

At Adimarket, we do not perform stem cell and PRP therapies, but we do offer the equipment so that doctors and practices can do so themselves. Our offerings include amniotic tissue, stem cell and PRP kits, centrifuge devices, and more. Practices and doctors can order directly from us.

The Importance of Quality PRP Systems

It is important to note that not all PRP systems are equal. Our system uses a closed tabletop system that can process PRP in under 10 minutes. For more information, contact us or visit our website.

Conclusion

Hair loss is a serious problem, with many people suffering from it. Thanks to PRP and stem cell therapies, we no longer have to rely solely on hair replacement surgery to help patients. PRP and stem cell therapies may be the best solutions available for both your patients and your practice.

Why Adimarket Offers Both PRP Equipment and Marketing Services

TUESDAY, 23 JANUARY 2018 / PUBLISHED IN BLOG

Here at Adimarket, we sell equipment to practices that are willing and able to add PRP and stem cell therapies to their lineup. The equipment we offer is among the best, and we have helped hundreds of doctors and practices to offer PRP and stem cell therapies. However, we also provide marketing services above that as well.

The Importance of Marketing in Regenerative Medicine

Although it might seem odd that we offer both marketing services and equipment, it is not so odd once you understand why. Simply offering services and having the equipment to do so does not in itself help patients to fully know that you are offering new services. It is best practice to get the word out to as many people in the area as possible.

Why Marketing Services are Essential

While there are many reasons why we do this, here are the three main reasons:

1. Regenerative Medicine is Relatively New

Compared to many other medical practices, such as surgery and physical therapy, regenerative medicine is still fairly new. In fact, most people do not really know that PRP and stem cell therapy even exists, let alone can be used to manage chronic pain.

The fact that not many people even know about the existence of regenerative medicine, let alone what it can be used for, means that it would be difficult to get your patients to even understand what you are offering as a service. This can be addressed with marketing. Through marketing, a practice can not only let it become known that they are offering these new services, but also explain shortly what the service entails.

2. Marketing is Like Dieting

Pretty much every doctor and dietitian knows that good nutrition is vital to great health down the line. Waiting until you’re sick and deficient to discuss nutrition is not the best way to address the issue. Marketing is similar in that instance. Marketing not only can be used to keep current patients informed, but can also be used to inform new patients about what you offer. Practices that don’t market often suffer in the same way as people who don’t get good nutrition.

3. There’s a Lot of Competition

Medicine has sadly become more and more like a business in recent years. This means that even doctors and practices need to have a good business sense if they are going to continue to provide the type of services that patients need and desire. Not understanding business would only make any practice fail or at least prevent them from growing.

Because of this, private practices, as well as other medical groups, are forced to compete. Marketing is a big way to make sure that you get patients instead of your competition. If you are utilizing PRP and stem cell therapies as a way to generate more income, then great! However, you will still have to market those services to get the word out, as well as compete.

How Adimarket Supports Your Practice

We at Adimarket offer these services as a way to help the field of regenerative medicine succeed. We not only help your practice start to utilize regenerative medicine, but we also help you to promote your practice in the same way. This will help your patients know that you are using these methods, and what they are, so that you can get a leg up over the competition.

Introduction

The International Federation of Adipose Therapeutics and Sciences (IFATS) appreciates this opportunity to submit the following comments to supplement its earlier written comments and recent testimony at the September 12-13, 2016 Public Hearing on the 2014-2015 Draft HCT/P Guidances concerning: a) Minimal Manipulation; b) Same Surgical Procedure; c) Adipose Tissue; and d) Homologous Use.

IFATS Overview

International Federation of Adipose Therapeutics and Sciences (IFATS)
45 Lyme Road – Suite 304
Hanover, NH 03755 USA
Tel: 1-603-643-2325, Fax: 1-603-643-1444

Date: September 26, 2016

Addressed to:
Division of Dockets Management (HFA–305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852

Re: FDA-2014-D-1856 – Comments to 2014-2015 Draft Guidance regarding:

• Docket FDA-2014-D-1584: “Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception; Draft Guidance for Industry”
• Docket FDA-2014-D-1696: “Minimal Manipulation of Human Cells, Tissues, and Cellular and Tissue-Based Products; Draft Guidance for Industry and Food and Drug Administration Staff”
• Docket FDA-2014-D-1856: “Human Cells, Tissues, and Cellular and Tissue-Based Products from Adipose Tissue: Regulatory Considerations; Draft Guidance for Industry”
• Docket FDA-2015-D-3581: “Homologous Use of Human Cells, Tissues, and Cellular and Tissue-Based Products; Draft Guidance for Industry and FDA Staff”

Commitment to Advancing Adipose-Based Therapies

IFATS is committed to the responsible advancement of the science and translation of new adipose therapies, ensuring patient safety. Founded in 2003 by pioneering adipose stem cell biologists and clinician–scientists, IFATS aims to advance the science of adipose tissue biology and its clinical translation to therapeutic applications.

IFATS’s Global Influence and Expertise

Membership now spans 40 countries across North America, Europe, Africa, the Middle East, Asia, Australia, and Central and South America. It includes basic scientists, translational researchers, clinicians, and regulatory and biotech representatives. IFATS is aligned with prestigious journals, Stem Cells and Stem Cells Translational Medicine, and has contributed to defining adipose-derived cells in the publication Cytotherapy.

Review of FDA Draft Guidances

Drawing on this expertise, IFATS has reviewed the 4 draft guidances with great care. It respectfully requests the FDA to reconsider and modify the 4 draft HCT/P guidances as follows:

Recommendations

Recommendation #1: Cell-Based Risks

Interpret and evaluate an HCT/P’s homologous use and minimal manipulation based on its manufacturer’s intended use in the patient.

Recommendation #2: Provider-Based Risks

Reduce provider-created risks by targeting provider behavior.

Recommendation #3: Recognize Structural and Nonstructural Functions

Recognize that adipose HCT/Ps have both structural and nonstructural functions, and regulate based on its manufacturer’s intended use in the patient.

Recommendation #4: Revise Evaluation of Minimal Manipulation and Homologous Use

Revise the evaluation of minimal manipulation and homologous use as they pertain to particular applications of adipose tissue.

Conclusion

IFATS is committed to collaborating with the FDA to meet the challenges of regulating HCT/P therapies. We respectfully request a meeting with FDA representatives to discuss these issues and others related to the advancement and regulation of adipose-based therapies.

Respectfully submitted on behalf of IFATS,

Adam J. Katz, MD, FACS
Chair, IFATS Regulatory Affairs Committee & IFATS Co-Founder
University of Florida College of Medicine
Professor
Director of Plastic Surgery Research, Laboratory of BioInnovation and Translational Therapeutics
Division of Plastic Surgery, Department of Surgery

IFATS Board of Directors

• Bruce Bunnell, PhD – Tulane University / United States
• Louis Casteilla, PhD – University of Toulouse / France
• Sydney Coleman, MD – New York & Pittsburgh Universities / United States
• Julie Fradette, PhD – Lavalle University / Canada
• William Futrell, MD – Founders’ Board, University of Pittsburgh / United States
• Marco Helder, PhD – VU University Medical Center Amsterdam / The Netherlands
• Adam J. Katz, MD, FACS – Founders’ Board, University of Florida / United States
• Ramon Llull, MD, PhD – Founders’ Board, University of Barcelona / Spain
• Kacey Marra, PhD – University of Pittsburgh / United States
• Ricardo Rodriguez, MD – President (2016), Private Practice / Johns Hopkins / United States
• Peter Rubin, MD, FACS – Chair, Founders’ Board, Chairman of the Board, University of Pittsburgh / United States
• Stuart K. Williams, PhD – University of Louisville / United States

Members-at-Large

• Jeff Gimble, MD, PhD – Pennington Biomedical / United States
• Keith March, MD, PhD – Indiana University / United States

IFATS Recommendations for FDA Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products

Introduction

IFATS recognizes the FDA’s challenge in developing regulations that fulfill the agency’s dual and interrelated responsibilities of protecting patients while promoting innovation. Although these are complementary rather than competing objectives, they are often difficult to pursue simultaneously. The FDA’s 3-tiered, risk-based §§ 361 – 351 framework balances these concerns by making the degree of regulatory oversight proportionate to the degree of an HCT/P therapy’s risk.

Key Regulatory Concepts

The concepts of homologous use and minimal manipulation are key determinants of whether an HCT/P will be classified as a § 361 product (which does not need premarket approval) or a § 351 drug, device, and/or biological product (which requires formal premarket approval). The applicability of § 351’s “same surgical procedure” exception also turns on homologous use and minimal manipulation.

Challenges for Manufacturer-Clinicians

For most manufacturer-clinicians, § 351 categorization raises insurmountable obstacles due to the time and expense of obtaining premarket approval. In such cases, § 351 classification effectively prohibits access to safe and effective HCT/P therapies, even when those therapies involve a patient’s own cells and/or can deliver superior results with reduced risks. At the same time, § 351 oversight is essential for therapies that pose greater risks due to the HCT/P’s characteristics, mechanism(s) of action, and circumstances of use.

Addressing Provider Misconduct

A second type of risk involves rogue clinicians offering false promises in the form of unproven therapies performed with few safeguards and less training. Provider misconduct is not unique to HCT/P therapies; it pervades all areas of medical practice. Nevertheless, IFATS shares the FDA’s alarm over such practices in the context of HCT/Ps and is equally determined to curtail them. Effective regulation of HCT/P-related risks must recognize and respond to their multivariate causes. Put simply:

• Sections 351 and 361 appropriately attempt to regulate HCT/P therapies proportionate to the risks of unpredictable and/or unsafe cell behavior.
• However, the risks of untrained providers misusing HCT/P therapies are caused by providers misbehaving, not cells misbehaving.

Comprehensive Risk Management Strategy

Interpretive guidance that restricts the definition and application of HCT/P terminology can only go so far in restricting provider-based risks. Additionally, restrictive, inaccurate, or imprecise definitions and interpretations carry their own risks of restricting access to therapies and a patient’s right to evaluate risk through the process of informed consent. Therefore, IFATS recommends that the FDA adopt an overall two-part strategy that focuses on both categories of HCT/P risks: those relating to cell behavior and those that pertain to provider behavior.

Recommendations

Recommendation #1 – Cell-Based Risks

Interpret and evaluate an HCT/P’s homologous use and minimal manipulation based on its manufacturer’s intended use in the patient. Interpretive guidance should predicate each definition on the functions and/or characteristics of the specific composition (i.e., cell type(s) and/or matrix or other component(s)) that are involved in, and/or relevant to, the manufacturer-clinician’s intended use in the patient.

Recommendation #2 – Provider-Based Risks

To reduce provider-created risks, the FDA should target provider behavior by collaborating with IFATS and comparable organizations to draw on and supplement existing federal and state methods of certification, registration, and similar measures.

Detailed Explanation of Recommendations

Recommendation #1 – Cell-Based Risks

The four draft guidances on homologous use, minimal manipulation, same surgical procedure, and adipose tissue individually and collectively intend to “improve stakeholders’ understanding” of 21 CFR 1271 by clarifying the FDA’s interpretation of homologous use and minimal manipulation. As demonstrated by the initial round of public comments and the ensuing public hearing on September 12 and 13, 2016, the draft guidance documents have not clarified applicable regulations. They have instead compounded the difficulty of understanding and complying with them. The drafts’ introduction of new definitional inaccuracies has also amplified rather than reduced patient risk.

IFATS respectfully requests the agency to clarify the definitions and application of homologous use and minimal manipulation by interpreting each as referring to the characteristics of the specific cell type(s) and/or the matrix or other component(s) that are involved in, and/or relevant to, the manufacturer’s intended use in the patient.

Homologous Use Definition:

21 CFR 1271.3(c): Homologous use means 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.

Recommended Guidance:

As used in this section, “performs the same basic function or functions in the recipient as in the donor” shall be interpreted as referring to one or more of the functions of the specific composition of the therapeutic/product, reflecting the specific cell type(s) and/or the specific matrix or other component(s) in the donor tissue that are involved in, and/or relevant to, the manufacturer’s intended use in the patient.

Minimal Manipulation Definition:

21 CFR 1271.3(f) Minimal manipulation means:

• For structural tissue, processing that does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement;
• For cells or nonstructural tissues, processing that does not alter the relevant biological characteristics of cells.

Recommended Guidance:

As used in this section, “relevant” characteristics shall be interpreted to mean the characteristics of the specific cell type(s) and/or the specific matrix or other component(s) in the donor tissue that are involved in, and/or relevant to, the manufacturer’s intended use in the patient.

Rationale:

Incorporating and relying on the manufacturer’s intended use harmonizes the interpretation and definition of homologous use and minimal manipulation with statutory directives to predicate the regulation of drugs, devices, and biologics on the manufacturer’s intended use. Defining relevant characteristics in terms of “the characteristics of specific cell type(s) and/or the matrix or other component(s) in the donor tissue that are involved in, and/or relevant to the manufacturer’s intended use in the patient” promotes patient safety by insisting on a reasonable and scientifically supportable rationale for using an HCT/P for a particular mechanism of action. This clarification balances the FDA’s dual responsibilities of protecting patients from undue safety risks while promoting the ongoing availability and continued development of HCT/P therapies.

Example of Non-Homologous Use:

Decellularized adipose matrix used to accomplish the manufacturer’s intended use of a particular metabolic or systemic effect in the patient (e.g., reducing insulin levels in a diabetic patient) is non-homologous because decellularized matrix is not relevant to metabolic or systemic activity.

Conclusion

Adopting this two-part strategy can control risk more comprehensively—and therefore more effectively—in furtherance of the FDA’s dual and interrelated obligations of protecting patients and promoting the availability of HCT/P therapies.

Introduction to FDA Regulations and IFATS Recognition

IFATS acknowledges the FDA’s dual role in patient protection and innovation promotion within the HCT/P sector. Balancing these objectives is crucial yet challenging.

Understanding the FDA’s Risk-Based Framework

The FDA’s § 361 – § 351 framework categorizes HCT/P therapies based on risk levels, influenced by concepts like homologous use and minimal manipulation.

Impact of Regulatory Classification on Access to HCT/P Therapies

Homologous use and minimal manipulation determine whether an HCT/P falls under § 361 (no premarket approval needed) or § 351 (requires premarket approval), affecting accessibility and innovation.

Provider Misconduct Risks in HCT/P Therapies

Rogue clinicians offering unproven therapies pose significant risks. Addressing provider behavior is essential for patient safety and regulatory efficacy.

IFATS Recommendations for Risk Mitigation

Recommendation #1 – Cell-Based Risks: Interpreting Homologous Use and Minimal Manipulation

IFATS proposes clarifying homologous use and minimal manipulation definitions based on manufacturer-intended use, enhancing regulatory clarity and patient safety.

Recommendation #2 – Provider-Based Risks: Targeting Provider Behavior

Collaboration with IFATS and other bodies to enhance certification and monitoring mechanisms can mitigate risks associated with provider misconduct effectively.

Recommendation #3 – Regulatory Scope for Adipose HCT/Ps

Expanding the definition of adipose tissue to include both structural and nonstructural functions aligns with biological accuracy and regulatory intent.

Conclusion: Enhancing Patient Safety and Access to HCT/P Therapies

IFATS urges the FDA to adopt a comprehensive strategy that addresses both cell-based and provider-based risks to uphold patient safety and foster innovation in HCT/P therapies.

Regulating an HCT/P’s Risks Based on Manufacturer’s Intended Use

Regulating the risks of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) is crucially tied to their intended use and mechanisms of action in patients. This ensures effective regulatory oversight and evaluation.

Regulatory Framework: §§ 351-361

The regulatory oversight of HCT/Ps under §§ 351-361 hinges on assessing the product’s risk level. Central to this determination are the criteria of homologous use and minimal manipulation.

Homologous Use Defined (21 CFR 1271.3(c))

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 as in the donor.

Minimal Manipulation Criteria (21 CFR 1271.3(f))

Minimal manipulation of structural tissue involves processing that preserves the tissue’s original characteristics essential for its utility in repair, reconstruction, or replacement. For nonstructural tissues, it preserves relevant biological characteristics.

Impact on Adipose Tissue

The classification of adipose tissue as exclusively structural neglects its nonstructural functions, limiting evaluation under § 361 criteria and obstructing risk assessment.

Same Surgical Procedure Exception

The § 351 “same surgical procedure” exception applies only to HCT/Ps meeting homologous use and minimal manipulation criteria, impacting nonstructural adipose applications.

Recommendation #4: Revising Evaluation Criteria

IFATS urges the FDA to reconsider specific adipose tissue applications concerning homologous use and minimal manipulation criteria.

Example A: Decellularizing Adipose Tissue

Decellularization of adipose tissue for structural use should be recognized as minimal manipulation under §§ 351 and 361 guidelines.

Example B: Structural Use of Fat in Breast Surgery

Applying adipose tissue for breast augmentation should be considered homologous use due to its structural function in restoring form and shape.

Example C: Stromal Vascular Fraction (SVF) for Nonstructural Use

SVF extraction from adipose tissue retains nonstructural components crucial for nonstructural applications, meeting minimal manipulation and homologous use criteria.

Conclusion and Call to Action

IFATS requests the FDA to amend draft guidance on HCT/Ps to align with scientific understanding and clinical practices of adipose tissue applications.

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