department of health and human servlces … · nebulization. were manufactured at ... the written...

EMPLOVEE(S) SIGNATUllE OATE ISSUEO

SEE REVERSE Darla J Christopher, Investigator 7/27/2017 OF THIS PAGE Mi chele L Forster, Investigator - Team OWJ~pt.w

Bi ologics x &F.:::~~ov,.tr4

FORM FDA ~83 (09ii)8) PREVIOUS eon ION onsow rn lNSPECTIONAL OBSERVATIONS PAGE 1 OF 10 PAGES

DEPARTMENT OF HEALTH AND HUMAN SERVlCES FOOD AND DRUO ADMINISTRATION

LJSI ""'' A0011ESS ANO PHONE NUMO~R OATE(S) OI' INSPECTION

19701 Fairchild Irvine, CA 92612-2445 (949)608-2900 Fax: (949)608-4417

7/21/2017-7/27/2017* t101 .. ~lij1:1<

3013670025

NAl.11' AtlO Oll~ OF INDIVIDUAi. TO WHO/J RE.PORT ISSUEO

Judi E. Meglio , Office Manager FIRM NI.ME STREET 1\0.,.,.,SS

California Stem Ce l l Treatment Center/Cell Surgica l Network

120 S Spalding Dr, Suite 300

CITY, STATE, ZIP COut. COVllTRY TYPE CSTAlll,JGHMEHT INSPECTED

Beverly Hills, CA 90212-1800 Manufacturer

This document lisis observations made by the FDA representa tive(:;) during the inspection o f your facility. They arc lnspcctionnl observations. tmd do not represent a Jinul Agency determination regarding your compliance. If you hn\'c an objection regard ing an obscrvnlion. or hu1•e implcmcmcd, or plan 10 irnplemcm. corrective action in rcspansc to rm observn1ion. you may discuss the objec1ion or action with the f7[)A reprcscntntivc(s) during the i11i;pection or submit this information to FDA :1l the address above. If you have any questions. please contact r DA ol 1hc phone number and uddress nbove.

The observations noted in this Form FDA-483 are not an exhaustive listing of objectionable conditions. Under the law, yo11r firm is responsible for conducting internal self-audits to identify and correct any and all violations of the quality system requirements.

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:

OBSERVATION 1 There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess.

Specifically,

Your firm has failed to validate your manufacturing process for the autologous S VF product and the

I (DJ(4J lrroduct at your Beverly Hills facility.

OBSERVATION 2 Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established and followed.

Specifically,

Since July 2, 2015, your firm has manufactured approximate! batches of autologous Stromal Vascular Fraction (SVF) product. The autologous SVF product is to be administered by intravenous

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION

STlllCT l\CCRESSAMlPHONFNUMBER

19701 fairchi ld Irvine, CA 92612-2445 (949)608-2900 Fax : (949)608- 4417

Judi E. Meglio , Office Manager Ff MNAME

California Stem Cell Treatment Center/Cell Surgical Network

Bever l y Hills, CA 90212-1800

ION

7/21/2017-7/27/2017*

3013670025

STAEET AOD!l£$S


ryp· ST/\llUSHMEHT INSPECTEI)

Manufacturer

EMPLOYEE(S) SIGNATURE

SEE REVERSE Darla J Christopher, Investigator OF THIS PAGE Michele L Forster, Investigator - Team

Biologics

FORM FDA C8J (09/0~I .. REVIOUS EDITION OB~LC'lli INSPECTIONAL OBSERVATIONS

DAtE ISSUEO

7/27/2017

PAGE l OF IO !'AGES

infusion, intra-articular injection, injection into soft tissue, intra-cerebroventricular injection, or nebulization.

were manufactured at your firm. Th was prepared, at your firm by an outside affiliate under their procedures. Your firm

-~---prepared the autologous SVF product from recovered adipose tissue usin our SVF re aration procedure and deployed the mixed roduct. The product is to be administered b intravenous or intra-tu moral injection. As an example, one batch of the

...... ~__... ................... ..__~-product was manufactured in this manner and deployed at your firm on 7/19/17 .

(A) An aseptic process for manufacturing the autologous SVF product and '--~~~a...&..1 ..... 11.-~~--'

product has not been established and validated to assure that these products can be consistently manufactured in a manner that prevents microbiological contamination.

i. No evidence was rovided to show that the manufacturing of autologous SVF product and

.................... .... roduct is performed in a controlled environment. For example, no evidence was ·-~

provided to demonstrate --~

that clean area control parameters, such as pressure differentials, air flow, temperature, humidity and air particulate count, have been established for the suite used for production of these prod~cts.1 ii Ci)~ ... ,9-rf 111 p The written procedure for gowning in the suite where the autolo ous SVF roduct is prepared is

deficient. According to "Standard Operating Procedures of 1 used by your firm for preparation of the autologous SVF product, personnel are only required to wear a cap, mask, and sterile gloves. There is no requirement for personnel who prepare the SVF product to wear an appropriate gown as a barrier to protect exposed containers and materials from microbiological contamination.


DISTiii T NlORESS ANO J>HOrlE NUMBER

19701 Fairchild Irvine, CA 92612-2445 (949)608-2900 Fax : (949)608~4417

NMIE ANO Tl OF INOtVICUA~ 0 WHOM REPORT ISSUED

Judi E. Megl io , Office Manager F111M NAME SlnEET A ESS

DATE(S) Of IHP Tl<»I

7/21/2017-7/27/2017~ ~El N\JMIJER

3013670025

California Stem Cell Treatment 120 S Spalding Dr, Suite 300 Cencer/Cell Sµrgical Network

- c 1 !Y," Alll.ZI' 1 VII'! l!Sl/.OUSliMer' INSP.EcrE


EMPlOVEE(S} SIGNATURE


Biologics

FORM FDA 4SJ (09/081 PREVIOUS EI>ITION OBSOLETE INSPECTIONAL OBSERVATIONS

OllTE ISSUED

7/27/2017

PllGE J OP 10 PAOES

(B) Your firm has failed to validate th terilizationprocess used to sterilize various reusable stainless steel instruments and used for production of the autologous SVF product.

OBSERVATION 3 Each batch of drug product required to be free of objectionable microorganisms is not tested through appropriate laboratory testing.

Specifically,

Your firm has failed to perform sterility testing on approximately manufactured from July 2, 2015 to July 20, 2017 and atches o roduct manufactured from December 3, 2015 to July 19, 2017. Autologous SVF batches manufactured by your firm are administered by intravenous infusion, intra-articular in'ection, injection into soft tissue, intra-cerebroventricular injection, or nebulization. The batches manufactured by your firm are administered by intravenous or intra-tumoral injection.

OBSERVATION 4 Aseptic processing areas are deficient regarding the system for monitoring environmental conditions.

Specifically,

No environmental monitoring is performed during the manufacture of the autologous SVF product and

th-..... ~._.1 ...... ~--~---'


Dl9TRICT AOORE!>S ANI> PliUNr. "'-JMBER OATE(S) OF INSPECTION

19701 Fairchild 7/21/2017-7/27/2017* Irvine, CA 92612-2445 FEI NUMBER

(949)608-2900 Fax: (949)608-4417 3013670025

NAME /\NO f l rt.E Ol' LNDMOUAI. TO w,.,._. no.rvRT 1$$Ull0

Judi E . Meglio , Office Manager FlRM NAMt< STREET AOORESS

California Stem Cell Treatment 120 S Spalding Dr, Suite 300 Center/Cell Surgical Network OrrY, STATE, ZIP CODE, COUNTRY TYPE EST ABUSHMENT lNSPECTEO

Beverly Hills , CA 90212-1800 Manufacturer

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Darla J Christopher, Investigator 7/27/2017 OF THIS PAGE Michele L Forster, Investigator - Team .... ,J~ ....

Biologics 90,,Ckll:IJ, Cb.-W-Oplwr-$ X ~1n:tao11

FORM FDA 483 (0911J8) l'REVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 4 or 10 PAGES

(A) There is no personnel monitoring.

(B) There is no non-viable particulate monitoring.

(C) There is no active or passive air monitoring.

OBSERVATION 5 Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions.

Specifically,

(A) Your firm utilizes a checklist for cleaning of the suite where the autologous SVF product and

IDJ(4J product is prepared and deployed, but there is no written procedure established for cleaning the suite that includes assignment of responsibility and a description in sufficient detail of the methods, equipment, and materials used to perform the cleaning.

(B) Your written procedure for cleaning reusable stainless steel instruments used for the production of the autologous SVF product an (b)(4) roduct does not include sufficient detail of the methods, equipment, and materials used to perform cleaning operations.

OBSERVATION 6 The identity of each component of a drug product is not verified by conducting at least one test to verify the identity, using specific identity tests if they exist.

Specifically,


PHONE NUMBER

19701 Fairchild Irvine, CA 92612-2445 {949)608 - 2900 Fax:(949)608- 4417

Judi E. Meglio , Office Manager FIRM NAME


- crrY:S AT c:ooe, COUNTRY

Beve rly Hi l l s , CA 90212-1800

01\lE(S) 0 INSPECTION

7/21/2017-7/27/2017* FEI NUMBER

30 13670025

STREET ADDRESS

120 S Spalding Dr , Suite 300

1YP6ESTA0USllMEHT•<W£C1ED

Manufacturer

SEE REVERSE OF THIS PAGE

FORM FDA 483 (09/08)

EMPLOYEE(S) S'GNATURE

Darla J Christopher, Investigator Michele L Forster, Investigator - Team Biologics

PREVIOUS EDITIONOOSOLEiii JNSPECTIONAL OBSERVATIONS

DATE ISSUED

7/27/2017

PAGE 5OF 10 PAGES

VF

Since July 2, 2015, your firm has manufactured approximately --~~~__.__. ............... ...._~~~..... ·----~--batch es of autologous SVF product. Since December 3, 2015, your firm has manufactured batches of the product.

OBSERVATION 7 Laboratory controls do not include the establishment of scientifically sound and appropriate specifications, standards, sampling pla~1s and test procedures designed to assure that components, drug product containers, closures, in-process materials and drug products conform to appropriate standards of identity, strength, quality and purity.

Specifically,

(A) Your fi rm failed to perform an identit test for the fo llowin com onents used for the autolo ous SVF product manufacturing: in Since July 2, 2015, your firm has manufactured approximate! batches of autologous SVF product. ---(B) Your firm did not establish a written rocedure that describes the in~ recess and release criteria for the autologous SVF product. An is used to calculate the or autologous SVF product. Your firm has failed to establish written specifications for or the release of autologous SVF product. Since July 2, 2015, approximate! batches of autologous SVF product were manufactured and deployed to

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMJNISTRATJON

0 1sm1et IODRl:S:JAND PllOI<~ NUMaEJI

19701 Fairchild I rvine, CA 92612-2445 (949)608-2900 Fax : (949)608-4417

Rl issue

Judi E. Megl io , Office Manager

California Stem Cell Treat ment Center/Cell Surgical Networ k CITY. ST T6, ZIP 006, COIJWRV

Beverly Hi l l s, CA 90212-1800

7/21/2017- 7/27/2017* I 'lJMBEJI

3013670025

STREEl ADORES$

120 S Spalding Dr, Sui t e 300

TYPE ESTABLISHMENT INSPECTED

Manufacturer


FORM l'DA 4&l (O.!)IO~)

EMPl.OYEE(S) SIGNATURE

Da r la J Christopher, I nvest i gator Miche le L Forster, Investigator - Team Biol ogics

PREVJOlJS BOliJON 08SOtE1'E lNSPECTIONALOBSERVATIONS

DATE ISSUED

7 /27 /2017

PAGE 6 OF 10 PAGES

OBSERVATION 8 Batch production and control records are not prepared for each batch of drug product produced and do not include complete information relating to the production and control of each batch.

Specifical I y,

(A) Your firm has not prepared and maintained batch records for approximately

autologous SVF product since July 2, 2015 and atches of the ,__~--------~ .....

manufactured since December 3, 2015.

(B) Your firm failed to identify the specific component lots used in the manufacturing of each batch of

autologous SVF product and roduct. These components include, but are not

limited to:

..... the equipment used in the manufacture of each batch of autologous SVF ..--~--. ......... ......,. ~.:.......,

product, including, but not limited to: syringes, the

the

· (D) Your firm failed to record the start and stop times for th in the

manufacturing of each batch of autologous SVF product and roduct. ,__~--------~---

----

DEPARTMENT OF HEALTH AND HUMAN SERVICES

19701 Fairchild Irvine, CA 92612-2445 (949)608-2900 Fax : (949)608- 4417

NAlotE Mil IT Of INDCll'o(X.l,OL 1 WliOM T ~O

Judi E. Meglio , Office Manager flRMNAM


TRY

Beverly Hills, CA 90212-1800

FOOD ANO DRUO ADMINISTRATION

MBEA

3013670025

&TAUi

120 S Spalding Dr, Sui~e 300

Manufacturer


FORM 1'DA 483 (09/0I)

EMPl.OVEE(S) SIGAAlUIE

Darla J Christopher, Investigator Michele L Forster, Investigator - Team Biologics

rR£VtOUS E.DITJON OOSOLST£ INSPECTION AL OBSERVATIONS

MTEISSUED

7/27/2017

PAOS70F IOPAOSS

(E) Your finn failed to identify the personnel er ormin each significant step in the manufacturing of

each batch of autologous SVF product and ===~~!::ii"f...--.Jl'roduct, including, but not limited to the personnel preparing the and the personnel performing the ...__&.;I_~

OBSERVATION 9 Written procedures are lacking which describe in sufficient detail the receipt, identification, storage, handling, sampling, testing, approval and rejection of components.

Specifically,

Written procedures are limited in regards to the manufacturing process for autologous SVF product in that:

(A) Your firm lacks written stabili test data to suppo1t the expiration date of

one year forL---------.i11.....1L-l111--11r..---------' nd frozen fonn.

(B) Your firm lacks written procedures for monitoring the storage and temperatures of frozen in your freezer.

1--~~--;&..lm...;;.;iiL.-~---I

OBSERVATION 10 The responsibilities and procedures applicable to the quality control unit are not in writing.

Specifically,

DEPARTMENT OF HEALTH AND KUMAN SERVICES FOOD AND DRUG ADMINISTRATION

DISTRICT ADOREOGANDPl1()N1> llUMIJl;R lll\T~(S) or INSl'l'OTTON

19701 Fa i rchild 7/21 / 2017-7 /27/2017 * Irvi ne , CA 92612- 244 5 FEINVMBER

(949) 608-2900 Fax : (949) 608- 4417 3013670025

N\ME AN> Til l£ OF INOMOUAI. TO WHOM llEPORT ISSUED

Judi E. Megli o , Office Manager FIRM""""' STREET ADDRESS

California Stem Cell Treatment 120 S Spalding Dr, Suite 300 Center/Cell Surgical Network CITY, STATE, ZIP COOE, COUNTRY TYPE ESTA9L1Sf!MEl'ITINSPECTED

Beverly Hills , CA 90212-1800 Manufacturer

EMPlOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Darla J Chris t opher, Investigator 7/27/2017 OF THIS PAGE Michele L Forster, Investigator - Team OllSIJO~t

::;.:re;;·-'°"-.. Biologics x Ol••S'911ild: 11.m::on

FORM FDA 483 (09A>8) PREVIOUS EDJTION OBSOLl!lB INSPECTIONAL OBSERVATIONS PAGE 8 OF 10 PAGES

(a) No written procedures have been established for the approval or rejection of all components, in process materials, and dr~g products.

(b) No written procedures have been established for approving or rejecting all procedures impacting on the identity, strength, quality, and purity of the autologous SVF product andl OIJ (4) I ~roduct. Your firm uses written procedures that have not been reviewed and approved by the quality control unit.

OBSERVATION 11 Employees are not given training in current good manufacturing practices.

Specifically,

No training in current good manufacturing practices is provided to employees engaged in the manufacture of the autologous SVF product and I IDJ(4J !product.

OBSERVATION 12 Equipment used in the manufacture, processing, packing or holding of drug products is not of appropriate design to facilitate operations for its intended use.

Specifically,

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMrN ISTRATION

Oii RICI MS

19701 Fairchild Irvine, CA 92612-2445 (949) 608 - 2900 Fax : (949) 608-~417

Judi E. Meglio , Office Manager

California Stem Cell Treatment Center/Cell Sur ical Network Cl Y,

Beverly Hills , CA 90212-1800

o.t.TE(l)O I CTION

7/21/2017-7/27/2017* FEI~

3013670025


Manufacturer

EllPl.O\'EE(S)-TURE


Biologics

FORM FDA <8) (09/01) l'RRVIOUS EDJTION 0030!.ETil INSPECTION AL OBSERVATIONS

DAT!:ls.suEO

7/27/2017

PAGl! 901'10PAG8S

OBSERVATION 13 Written procedures describing the handling of all written and oral complaints do not include provisions for review to determine whether the complaint represents a serious and unexpected adverse drug experience which is required to be reported to the Food and Dmg Administration.

Specifically,

Your written procedure for handling adverse events does not assure that events are adequately evaluated and reported to the FDA. The following events were not investi ated or re 01ted to the FDA:

i. Patient as treated for astrocytoma with th roduct manufactured by your firm and deployed by your firm by IV drip on 12/17 /15. The patient died on 4/21/16.

ii. A patient treated for COPD with the SVF product manufactured by your firm experienced hyperventilation during the deployment procedure on 2/6/17. He passed out at the end of the procedure and was subsequently resuscitated and hospitalized. The SVF product was administered by IV and nebulization.

DISTRICT AOCRES$AND PHONE NUf,101:1'

19701 Fairchild


OAlC(S) Of lNSP~CllON

7/2 1/2017-7 /27/2017* FEJNIJMBER Irvine, CA 92612-2445

(949)608-2900 Fax: (949)608 - 4417 3013670025

NAME l\ND 1mJ: 0> INOl\llv UN. JOWl <OM •<C>'VK1 !SWED

Judi E. Meglio , Office Manager FllWNAME

California Stem Cell Treatment Center/Cell Surgical Networ k


CITY, STATE, ZIPCOOE, COUHTRY TYPE ESTABUSHMENT INSP£CTED


*DATES OF INSPECTION 7/21/2017(Fri),7/24/2017(Mon),7/25/2017(Tue),7/27/2017(Thu)


EMPLOYEE(S) SIGAATlJRE

Darla J Christopher , Investigator Michele L Forster, Investigator - Team Biologics

Qad,~(h~

x mto;,~;.t"~"

FORM FDA '83 (09/08) PAGES

PREVfOUS EDTTiON oosoc.em INSPECTION AL OBSERVATIONS

DATE CSSUEO

7/27/2017

PAGE !()OP 10

Date: September 14, 2017 Judi E. Meglio California Stem Cell Treatment Center, Inc 120 S Spalding Dr Suite 300 Beverly Hills, CA 90212-1800 Subject: System Notification Dear Judi E. Meglio, We are notifying you that due to a technical error related to a software update, the FDA Form 483 you received recently inadvertently included a sentence meant only for medical device firms. That statement says, “Under the law, your firm is responsible for conducting internal self-audits to identify and correct any and all violations of the quality system requirements.” This statement refers to quality system requirements applicable only to medical device establishments, but was inadvertently included on certain Form 483’s issued to non-device establishments for a brief period of time. Please note that the statement has no bearing on the inspection observations themselves, which remain applicable as of the date that you were issued the Form FDA 483. Should you have any questions, please send to [email protected]. Sincerely,

Lisa Creason Director, Office of Information Systems Management Office of Regulatory Affairs Food and Drug Administration

U.S. Food & Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20903 www.fda.gov

mailto:[email protected]

www.fda.gov

department of health and human servlces … · nebulization. were manufactured at ... the written...

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