Thomas E. Young, LLC 4/20/12
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| ||Center for Biologics Evaluation and|
1401 Rockville Pike
Rockville, MD 20852-1448
April 20, 2012
VIA FACSIMILE AND UPS
Thomas E. Young, MD.
Owner and Medical Director
Young Medical Spa
213 North Broad Street 3rd floor
Lansdale, PA 19446
Dear Dr. Young:
During an inspection of your establishments, Young Medical Spa, located at 213 North Broad Street, Lansdale, PA 19446, between December 19, 2011, and January 10, 2012, and 4025 West Hopewell Road, South Center Valley, PA 18034, between January 6 and January 10, 2012, the Food and Drug Administration (FDA) determined that your firm recovers and processes adipose tissue (aka lipoaspirate) from donors for autologous use. You formerly used (b)(4) to isolate the stem cells from the lipoaspirate. The lipoaspirate is processed (b)(4). This product is injected into specific areas of the body such as the joints, breasts, and other locations.
Your website, found at: http://www.youngmedicalspa.com, and your brochure collected during the inspection, promote intradermal stem cell injections of (b)(4) for Natural Breast Augmentation (NBA). Your website explains that, “Fat is gently removed from body areas, such as the abdomen and waist, using standard tumescent liposuction techniques. The fat is then processed in our state-of the-art lab which is the only one of its kind in the area. The lab extracts the regenerative and stem cells from the fat cells . . .. The stem cell mixture is examined for viability and is then combined with other fat cells that were removed from your body at the beginning of the procedure. This results in a stem cell enriched fat sample which is then injected into your breasts for a smooth and natural volume increase . . .. By adding stem cells to the harvested fat it helps to increase new blood vessel formation that is needed to feed the fat after transfer and helps to tighten the skin over the breast.”
These adipose derived stem cells are human cells, tissues, or cellular and tissue-based products (HCT/Ps) as defined in 21 CFR 1271.3(d). However, this cellular product is an HCT/P that does not meet all of the criteria in 21 CFR 1271.10(a) and therefore is not regulated solely under section 361 of the Public Health Service Act (PHS Act) [42 U.S.C. 264], and the regulations in 21 CFR Part 1271. Specifically, your processing alters the relevant characteristics of the adipose tissue relating to the tissue’s utility for reconstruction, repair or replacement. Therefore, the processing would not meet the definition of minimal manipulation for structural tissue such as adipose tissue. As a result, the (b)(4) product does not meet the criterion in 21 CFR 1271.10(a)(1).
In addition, some of the treatments you offer do not meet the definition of homologous use in 21 CFR 1271.3(c); for example, treatment of (b)(4) and clinical uses involving injection of (b)(4) product into the breast tissue for the purpose of breast augmentation. As a result, the (b)(4) product is a drug under section 201(g) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. 321(g)] and biological product as defined in section 351(i) of the PHS Act [42 U.S.C. 262(i)] that cannot qualify for regulation solely under section 361 of the PHS Act and 21 CFR Part 1271.
Please be advised that in order to lawfully market such a biological drug product, a valid biologics license must be in effect [21 U.S.C. 355(a); 42 U.S.C. 262(a)]. Such licenses are issued only after a showing of safety and efficacy for the product’s intended use. While in the development stage, such products may be used in humans only if the sponsor has an investigational new drug (IND) application in effect as specified by FDA regulations [21 U.S.C. 355(i); 21 CFR Part 312). The (b)(4) product is not the subject of an approved biologics license application (BLA) nor is there an IND in effect. Based on this information, we have determined that your actions have violated the FD&C Act and the PHS Act.
Additionally, during the inspection, FDA investigators documented evidence of significant deviations from current good manufacturing practice (CGMP) and current good tissue practice (CGTP) from December 2010 to January 2012, in the manufacture of the (b)(4) product. These deviations from CGMP and CGTP include the applicable requirements of Section 501(a)(2)(B) of the FD&C Act, Section 361 of the PHS Act, and Title 21, Code of Federal Regulations, (21 CFR) Parts 210, 211, and 1271.
At the close of the inspections, our investigators issued Forms FDA 483, Inspectional Observations, to both the Center Valley and Lansdale locations, which described a number of significant objectionable conditions relating to your establishments’ compliance with CGMP and CGTP requirements. (The items below refer to the Lansdale location unless otherwise noted). These include, but are not limited to the following:
1. Failure to have written procedures designed to prevent microbiological contamination of drug products purporting to be sterile. Such procedures shall include validation of all aseptic and sterilization processes [21 CFR 211.113(b)]. For example:
- You failed to validate your aseptic manufacturing process and establish written procedures to prevent microbiological contamination of your (b)(4) product.
- Your Center Valley location uses (b)(4) for sterilization but failed to validate the sterilization process for the instruments and utensils used in your aseptic manufacturing process. (b)(4)
2. Failure to ensure appropriate laboratory testing of each batch of drug product required to be free of objectionable microorganisms [21 CFR 211.165(b)]. Specifically, you failed to perform sterility testing on (b)(4) product manufactured that later was injected into the breasts, face, or joints of patients.
3. Failure to maintain laboratory controls that include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity, including a determination of conformance to written descriptions of sampling procedures and appropriate specifications for drug products [21 CFR 211.160(b)]. For example:
4. Failure to establish and follow written procedures describing the handling of all written and oral complaints regarding a drug product including review of any complaint involving the possible failure of a drug product to meet any of its specifications [21 CFR 211.198(a)]. Six of (b)(4) patients who received the (b)(4) product at your Center Valley location experienced adverse reactions. These reactions included, but were not limited to, fever, redness, soreness, cyst formation, mastitis, and infection. There were no records of any investigation into these adverse events. For example:
5. Failure to establish and follow written production and process control procedures designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess and to ensure such procedures are drafted, reviewed and approved by the appropriate organizational units [21 CFR 211.100(a)]. Specifically, you have not validated your (b)(4) manufacturing process that incorporates the use of, among other items, (b)(4). In addition, the Standard Operating Procedure (SOP) for the manufacturing process does not provide operating parameters for, or the identity of, this equipment.
6. Failure to ensure that batch production and control records are prepared for each batch of drug product produced [21 CFR 211.188].
7. Failure to establish and follow written procedures describing in sufficient detail the receipt, identification, storage, handling, sampling, testing, and approval or rejection of components and drug product containers and closures [21 CFR 211.80(a)]. Specifically, your firm has utilized (b)(4) in the manufacture of the (b)(4) product. There is no procedure in place that describes the receipt, identification, storage, handling, sampling, testing, and approval or rejection of these materials.
8. Failure to establish a quality control unit that has the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated [21 CFR 211.22(a)].
9. Failure to establish a written record of major equipment cleaning, maintenance, and use, and to include in that record the date, time, product and lot number of each batch processed [21 CFR 211.182]. For example; there are no written records of cleaning, maintenance, and use for:
10. Failure to establish and follow written procedures for cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing, or holding of a drug product, including a description in sufficient detail of the methods, equipment, and materials used in cleaning and maintenance operations [21 CFR 211.67(b)]. For example:
11. Failure to record and justify any deviations from written procedures [21 CFR 211.100(b)]. Specifically, on 12/22/11, you (b)(4)
12. Failure to ensure that each container or grouping of containers for components or drug product containers, or closures is identified with a distinctive code for each lot in each shipment received [21 CFR 211.80(d)]. Specifically, you failed to record the lot numbers of components and supplies utilized in manufacturing of the (b)(4) product including, but not limited to: (b)(4).
13. Failure to ensure buildings used in the manufacture, processing, packing, or holding of a drug product have suitable construction to facilitate cleaning, maintenance, and proper operations [21 CFR 211.42(a)]. Specifically, your manufacturing facility has an exposed brick wall and curtains that cannot be easily cleaned or sanitized.
14. Failure to label each HCT/P in accordance with the requirements in 21 CFR 1271.370. For example:
a. The following information did not appear on the (b)(4) product label: a distinct identification number in accordance with 21 CFR 1271.290(c); a description of the type of HCT/P; and an expiration date, if any.
b. The (b)(4) product, which is for autologous use, was not prominently labeled as being “For autologous use only” and “Not evaluated for infectious substances.” These warnings are required under 21 CFR 1271.90(b).
We acknowledge receipt of your written responses dated January 24, 2012, which address the inspectional observations on the Forms FDA 483 issued at the conclusion of the inspection, and we have reviewed their contents. Your responses lack sufficient detail to be properly evaluated, and only address the 483 items individually. Additionally, you did not address your overall plan to come into compliance with the applicable laws and regulations.
Neither this letter nor the observations noted on the form FDA 483, which were discussed with you at the conclusion of the inspection, are intended to be an all-inclusive list of deficiencies that may exist at your facility. It is your responsibility as management to assure that your establishment is in compliance with the provisions of the FD&C Act, the PHS Act, and all applicable federal laws and regulations. Federal agencies are advised of the issuance of all Warning Letters about biological products so that they may take this information into account when considering the award of contracts.
You should take prompt action to correct these deviations. Failure to promptly correct these deviations may result in regulatory action without further notice. Such actions include seizure and/or injunction.
For further information about IND requirements, contact Dr. Patrick Riggins, Director of Regulatory Management Staff, Office of Cellular, Tissue, and Gene Therapies, at (301) 827-5366. Please include a copy of this letter with your initial submission to CBER.
Please notify this office in writing, within 15 working days of receipt of this letter, of any additional steps you have taken or will take to correct the noted violations and to prevent their recurrence. Include any documentation necessary to show that correction has been achieved. If corrective actions cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.
Your response should be sent to the U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, HFM-600, 1401 Rockville Pike, Rockville, Maryland 20852-1448. If you have any questions regarding this letter, please contact Robert A. Sausville, Director, Division of Case Management, CBER at 301-827-6201.
Mary A. Malarkey
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research