of foooano orug administration - fda.gov · stale. zip code. country biloxi, ms 39532 oate(s) of...
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EMP\.OYEE(S) SJGNA TUllE EMPLOYEE(S) NANE ANO TITlE (Prl'1t or Typo) DATE ISSUED SEE
REVERSE
cf~J·B~ OF THIS Samantha J. Bradley, Drug Investigator 4/6/2018 PAGE
FORM FDA 483 (09/08) Jl'RIMOUS l!t>TlOH ~e'T!! INSPECTIONAL OBSERVATIONS Page1Of1
DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOOANO ORUG ADMINISTRATION
Cl.STRICT 1'00RECG ANO PHONii: N'UM9£R
Pharma Division II 404 BNA Drive, Building 200, Suite SOO Nashville, TN 37217 (615) 366-7801 I Email: [email protected] Indust ry Information: www.fda.gov/oc/industry
OATE(S) OF INSPECTION
03/12/2018-04/06/2018 .
FEJNIMSER
3005180755
MME AND TITLE OF INOllllOUAl TO WHOIA REPORT ISSUED
Dr. Rickey L. Chance, President & Owner FIRM NAME
Coastal Meds, LLC STREET AOOllESS
1759 Medical Park Drive, Suite C OTY. STA TE. ZIP CODE. COUNTRY
Biloxi, MS 39532
.. TYl'E ESTABUSHIEllT INSl'ECTB>
Outsourcing Facility
This document lists observations made by the FDA representative(s) during the inspection of your facility. H1ey are lnspectlonal °"
observations, and do not represent a final Agency determination regarding your compliance. If you have an objection regarding an observation, have implemented, or plan to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this information lo FDA at the address above. If you have any questions, please cootad FDA al the phone number and address above.
DURING AN INSPECTION OF YOUR FIRM (I) (WE) OBSERVED:
OBSERVATION 1
Aseptic processing areas are deficient regarding the system for monitoring environmental conditions. Specifically, environmental monitoring (EM) samples are not taken in high-risk areas or so that they represent t he conditions of the areas being monitored. For example:
a. The material pass-through box, which is used to transfer materials between the uncontrolled dispensing room and the ISO 7 clean room, is not monitored on any frequency.
b. Fingertip samples are taken ~ 6)(4) ~he pharmacist[(6) (4) ~'with sterile (6) (4} I The sample is also limited to (b)(4) :on hisKo) -(4) I
c. The surface sample taken from the[(6) (4) t eated in the ISO 7 clean room, is performed after th6(1:)) (4Jhas been sanitized with sterile'(b) (4)
d. On 3/13/2018, I noted the surface sample taken from surface of theK6) (4) I [(o) -(4) as done in an area still wet with ste rile [(6) (4) I
e. Pressure differential data is not reviewed. It is recorded on a 6) (-4) nd when anomalies occur. Data is uploaded[(6) (4) 'and printed. The electronic files are not saved and there is no review of the data. As a result, there have been no explanations for or investigations into pressure loss. For example, the following pressure differential excursions were recorded on 12/5/2017:
DEPARTMENT OF HEALTH ANO HUMAN SERVICES FOOD ANO DRUG ADMINISTRATION
ClSTRCT ADORES& HID l't<ONC NUMDCR DA TE(S) OF INSPECT\:IN
Pharma Division II 03/12/2018-04/06/2018 .. 404 BNA Drive, Building 200, Suite 500
Nashville, TN 37217 FEt NUMBER
(615) 366-7801 I Email : [email protected] 3005180755 Industry Information : www.fda.gov/oc/industry MME ANOTnU OF NOl\llDU~ TO'MIOM RE!'Olll ISSUED
Dr. Rickey L. Chance, President & Owner FIRMHAME STREET AOORESS
Coastal Meds, LLC 1759 Medical Park Drive, Suite C CITY, STATE. ZIP cooe. CDUN1RY . TYPE ESTAllUSHMENT NSPECTEO
Biloxi, MS 39532 Outsourcing Facility
ISO 7 Ante Room.to General Area ISO 7 Cleanroom to ISO 7 Ante Room
Specification:!(l5) (4) J_
E.00u9 rn ·· ' !;:;~~=:] Specification (b) ( 4) I
[=~ .~ -~~=1 (o) (~ l 0.062 r(o) (~ J. 0.026
0.004 0.002
0.008 0 .002
0.010 0 .011
0.026 0.02
0.064
0.014
0.008
0.025
0.036
0.005
0.028
0.065
EMPlOYl:E(S) SICN.\ TURE EMPlOYEE(S) NAME llNO TtllE (1'11nl or Typt) DATE ISSUED SEE
REVERSE OF THIS Sj 1?> Samantha J. Bradley, Drug Investigator 4/6/2018
PAGE
FORM FDA 483 (09/08) Pfte\'.c)US etJ(Ttott OSSOLnr. INSPECTIONAL OBSERVATIONS Paoe:> OF 7
METHYLCOBALAMIN, Lot MC/120517, was produced t he same d ay and later distributed. There is no
explanation for or investigation into this series of events.
OBSERVATION 2
Protective apparel is not worn as necessary to protect drug products from contamination. Specifically, on 3/13/2018, I observed t he aseptic attire worn in the cleanroom does not include goggles, which leaves the skin
of personnel exposed around their eyes and forehead.
* * *THIS IS A REPEATED OBSERVATION* 0
OBSERVATION 3
Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the
aseptic condit ions.
DEPARTMENT OF HEALTH ANO HUMAN SERVICES , fOOO ANO ORUG AOMINISlRATION
DSTRiCT ADOMS:S N<0 "'10NI! NUMBe~ 0AT€(C) oP INSPECTION
Pharma Division II 03/12/2018-04/06/2018.
404 BNA Drive, Building 200, Suite 500 Nashville, TN 37217 l'EI NIMOEA
{615) 366-7801 I Email: [email protected] 3005180755 Industry Information: www.fda.gov/oc/industry PM.MEAHOTTT1...f ~ NOMOVAl TO'M"f0\11 REPORT ICCUEO
Dr. Rickey l. Chance, President & Owner FlRMHAME STREET ADDRESS
Coastal Meds, LLC 1759 Medical Park Drive, Suite C CITY. STAlE, l:JPOOOE. COUNlRY
.... TYPE ESTABUSHalENl" INSPECTB>
Biloxi, MS 39532 Outsourcing Facility
SEE EMPLOVtE(S) SIGNATURE EMP\.OVEE(S) NAME AND Tffi.E (A1nt <T Typo) OATE ISSUED
REVERSE Sj'B OF THIS Samantha J. Bradley, Drug Investigator· 4/6/2018 PAGE
FOl\M FOA483 (0!tf0&) Pf<l!VIOl'3 ~CITIOH OOSOU'tE INSPECTIONAL OBSERVATIONS Page30f 7
Specifically, the pressure gauges used to monitor the differentia ls between the cleanroom, ante room, and uncontrolled areas, are not calibrated.
OBSERVATION 4
Laboratory controls do not include the establishment of scientifically sound and appropriate specifications and test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity. Specifically,
a. Visual examination of finished products is not performed under appropriate conditions to identify potential quality issues with injectable drug products. Per SOP 0 -16, Rev. 0, Testing and Release Criteria, effective 12/30/2016, visual inspectors should look for fill volume, particulate matter (PM), container seal/closure, or any other defect. It states PM should be identified using a contrasting background illuminated with [(b) (21-) )ights or brighter. .
Visual inspectors are not provided with a contrasting background and sufficient light for inspection. All products are packaged in amber vials and numerous products are light to dark red in color. On 3/13/ 2018, inspectors were not observed holding vials up to the ceiling lights, the only light source available, during their visual inspection. There is no assurance quality defects are identified during visual inspection of injectable drug products.
b. Finished product release testing does not include (o ) -( 4) 'content, the preservative used in all injectable drug products.
OBSERVATION S
Procedures designed to prevent microbiological contamination of drug products purporting to be steri le do not include adequate validation of the sterilization process. Specifically,
a. Pharmaceutical grade, sterilizing!(l5) (4 )~re[(o) (4) 'after use via a[D f{4) 'that is
not in compliance with the manufacturer's test method and has not been independently validated.
DEPARTMENT OF HEAlTHANO HUMAN SERVICES FOOD ANO DRUG ADMINISTRATION
DISTfOCT ,,tOOf\£.G.c: ANO PHOtE. H\JMOCR 04 TE(S:) OF INSPECTION
Pharma Division II 03/12/2018-04/06/2018" 404 BNA Drive, Building 200, Suite 500
Nashville, TN 37217 FEINl.MBI:~
(615) 366-7801 I Email: [email protected] 3005180755 Industry Information: www.fda.gov/oc/industry PW.IE AHO TTTU! OF NOMOUAI. TO 'MICIM REPORT ISSUED
Dr. Rickey L. Chance, President & Owner FIRM NAME STREET ADDRESS
Coastal Meds, LLC 1759 Medical Park Drive, Suite C CITY. STATE. ZIP COOE.COl.tlTRY 1"re ESTASUSH!IEHT NSPECTfO
Biloxi, MS 39532 Outsourcing Facility
SEE EIJPlOYEE(S) SIG>t\ TUAI: EMP\.OYe::(S) HA'-'E MO TTTLE (Rini OI 'TJ-P<} [)t.TEISSUEO
REVERSE SjB OF THIS Samantha J. Bradley, Drug Investigator 4/6/2018 PAGE
FORM FDA 483 (09/08) PREVIOUS EDITION 06SOLl!Tf_ INSPECTIONAL OBSERVATIONS Pago4 0~ 7
Per SOP 0 -14, Rev. 0, Validation of Sterilization Methods, effective 12/30/2016, the used~t>) (4))s ~(15)(4) to~(b)(4) '3nd (b)(4) 'to 0)(4) 'of (b )(4) Thel(b) ( 4) Jis reached whenl(b) ( 4) I
Per the manufacturer the used(t>) (4J us~fif{4) 1prior to obtaining the l(o) (4) !There is no assurance the sterilizing'(b) ( 4) esults are passing.
b. Media fill records lack significant Information. There Is no record of media preparation, the materials used (including the vials, tubing, and steril izin~(t)) (4 )1 the filling process followed, or the number of vials placed in the incubators. In the most recent revision of the media fill record, there is no record of the number of vials which were filled.
OBSERVATION 6
Buildings used in the manufacture, processing, packing, or holding of a drug product do not have the suitable construction to facilitate cleaning. Specifically, the materials used for equipment within the ISO 7 cleanroom are not appropriate for the cleaning solutions being used. On 3/13/2018, I observed rust on several HEPA return grates, the ante room door handle, and door frame.
OBSERVATION 7
There is a fai lure to thoroughly review the fai lure of a batch or any of its components to meet any of its specifications whether or not the batch has already been distributed.
Specifically, since 9/24/2015, there have been at least 23 batches found to have potency failures and 13 found to have sterility failures. Each batch was rejected, but investigations lack significant information and do not extend to other similar batches. The QRE (quality related event) investigation forms were initiated beginning in 2017 and each event was classified as " Minor".
For potency failures, thirteen (13) out of the 23 were presumed to be due to weighing errors. The others had potential root causes of incomplete dissolution, light exposure, or none listed. No evidence was provided in any case to support the conclusions. METHYL-PLEX was d iscontinued due to potency failures for three (3) consecutive batches in 2018. No other product formulation incompatibilities were considered during the investigations.
DEPARTMENT OF HEALTH ANO HUMAN SERVICES FOOD ANO DRUG ADMINISTRATION
DISTlllC'l' AOORESS MID PHONE !\'UMBER
Pharma Division II 404 BNA Drive, Building 200, Suite 500 Nashville, TN 37217 (615) 366-7801 I Email: [email protected] Industry Information: www.fda.gov/oc/industry NAME ANO TITl.E Of INOIVIOUAL TO \MiOM REPORT ISSLIEO
Dr. Rickey L. Chance, President & Owner
Coastal Meds, LLC CITY. STAlE. ZIP CODE. COUNTRY
Biloxi, MS 39532
OATE(S) Of INSPECTION
03/12/2018-04/06/2018*
FEINUMBER
3005180755
STREET ADDRESS
1759 Medical Park Drive, Suite C TYPE ESTABLISHMENT INSPECTED
Outsourcing Facility
SEE REVERSE OF THIS
PAGE
FORM FDA 483 (09/08)
EMPLOVEE(S) SIONA T\JRE
SJ~ PREVIOUS EDITION OBSOLETE
EMPt.OYEE(S) NAME AND TITLE (Print or TyP<J) DATE ISSUEO
Samantha J. Bradley, Drug Investigator 4/6/2018
INSPECTIONAL OBSERVATIONS Pago 5 OF 7
For steril!ty failures, each investigation conch .. ~des aseptic technique should be followed and hand hygiene sampling was performed. Organisms were identified in seven (7) out of the 13 events and Baciflus circulans was identified as the organism in four (4) out of the seven (7) events. Documentation was not reviewed, environmental conditions were not reviewed, EM sampling results were not reviewed, the identified organisms were not evaluated, and these events did not trigger cleaning.
In all investigations, there is a lack of historical review, trend analysis, extension to other batches, a statement regard ing product disposition, and overall quality impact assessment.
***THIS IS A REPEATED OBSERVATION***
OBSERVATION 8
Each lot of drug product containers and closures is not withheld from use until the lot has been sampled, tested, examined, and released by the quality control unit.
Specifically, sterile, depyrogenated drug product containers and closures are accepted after confirming they match the purchase order, without requiring sampling, testing, examination, or release. There is no specification for the containers and closures; there is no requirement to obtain and review the manufacturer certificate of analysis (COA) for each batch received.
OBSERVATION 9
Drug products do not bear an expiration date determined by appropriate stability data to assure they meet applicable standards of identity, strength, quality and purity at the time of use.
Specifically, stability studies have not been initiated for all injectable drug products to support their 6-month (180-day) expiration date. Since 9/24/2015, the following products have been made and distributed without stability studies being initiated/performed:
• • • •
ADENO-PLEX HYDROXOCOBALAMIN L-CARNITINE LIPO-DEN EXTREME
DEPARTMENT OF HEAL TH AND HUMAN SERVICES FOOOAND DRVG ADMINl5lRA110N
Ol&'MICT AOD"fMANO-~ oi.TE(S) OF o><SPECTIOH
Pharma Oivi~ion II 03/12/2018-04/06/2018*
404 BNA Drive, Building 200, Suite 500 Nashville, TN 37217 F£I NLMBER
(615) 366-7801 I Email: [email protected] 3005180755 Industry Information: www.fda.gov/oc/lndustry MMC ANO TnlE. OF tNCHVIOVAL. TOVvHOM REPORT lSSU£0
Dr. Rickey l. Chance, President & Owner FIRM NAME STREET ADDRESS
Coastal Meds, LLC 1759 Medical Park Drive, Suite C CITY.STATE. ZIP cooe. COUNTRY TYPE ESTABLISHMENT lNSPoCTEO
Biloxi, MS 39532 Outsourcing Facility
EMPl.O~(S) SIGNA TVRE EMPLOY!E(S) NAME AND nn.e (AW at Type) OATE ISSUED SEE
REVERSE SjE OF THIS Samantha J. Bradley, Drug Investigator 4/6/2018 PAGE
FORM FOA4U lotlll81 PREVtOUS EDITION 06SOl.ETE INSPECTIONAL OBSERVATIONS Pogo 6 01'7
• • • • • • • •
UPb-DEN MAX
LIPO-DEN PLUS
LIPO-PLEX
UPO-X
METHYLCOBALAMIN
METHYL-PLEX
PVRIDOXINE
ROD EX
* 0 THIS IS A REPEATED OBSERVATION***
OBSERVATION 10
Equipment and utensils are not maintained at appropriate intervals to prevent malfunctions that would alter the
safety, strength, quality, or purity of the drug product .
Specifically, critical equipment has not been qualified for use. Incubators and refr igerato rs are lacking
temperature mapping studies and are not monitored using calibrated thermometers. These include a
refrigerator used for media storage, a refrigerator used for bulk drug substance storage, and(t5) (4)incubators used for EM sample and media fill vial incubation.
OBSERVATION 11
The labels of your outsou rcing facility's drug pro ducts are deficient.
The labels of some of your outsourcing facility's dru g products do not include information r equired by
section 503B(a)( lO)(A) and (B).
Specifically, the following information is not found on some of your drug product labels, as required by
sect ion 503B(a)(lO)(A):
• •
The dosage strength;
The st atement , "Not for resale 11 •
DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD ANO ORUG AOMINISTRA TION
DISTRICT AOORESS ANOPHDNE NUM8ER
Pharma Division II 404 BNA Drive, Building 200, Suite 500 Nashville, TN 37217 (615) 366-7801 I Email: [email protected] Industry Information: www.fda.gov/oc/industry NAME ANO TITl.E OF INDIVIDUAL TO WHOM REPORT ISSUED
Dr. Rickey L. Chance, President & Owner FlRMNAME
Coastal Meds, LLC CHY. STATE. ZIP COCE, COUNTRY
Biloxi, MS 39532
DATE(S) OF INSPECl'ION
03/12/2018-04/06/2018*
FEINUMBER
3005180755
STREET AOORESS
1759 Medical Park Drive, Suite C 1YPE ESTABLISHMEm INSPECTED
Outsourcing Facility
FORM FOA 483 (09/08) CTIONAL OBSERVATIONS Page 7 OF 7 PREVIOUS EDITION OBSOLETE INSPE
J~ j · JS~
In addition, th.e following information is not found on yoµr drug pro.duct container labels, as described in section 503B{a)(10)(B):
• Information to facilitate adverse event reporting: www.fda.gov/medwatch and 1-800-FDA-1088 Examples of drug product labels that do not contain this information :
o o o o o o o o o o
Adeno-Plex Injectable 30 ml Cyanocobalamin injectable 30 ml Hydroxocobalamin injectable 30 ml MDV Lipo-B injectable 30 ml Lipo-Den injectable 30 ml MDV Lipo-Den Extreme injectable 30 ml MDV Lipo-Den Plus injectable 30 ml MDV Lipo-Plex injectable 30 ml MDV Methylcobalamin injectable 30 ml MDV Pyridoxine injectable 30 ml MDV
•OATES OF INSPECTION:
03/12/2018 {Mon), 03/13/2018 {Tue), 03/14/2018 {Wed), 03/15/2018 (Thu), 03/16/2018 (Fri), 03/19/2018
(Mon), 04/06/2018 {Fri)
SEE REVERSE OF THIS
PAGE
EMPl.OVEf(S) SIGNATURE EMPLOYEE(S) NAME AHO TIT\.E tprfnt ot f1pe}
Samantha J. Bradley, Drug Invest igator
0.0.TE ISSUED
4/6/2018