(JjJQQIIIIIIIIII^IIIIIIIIIIIIIIIIIIII^^ supporting exhibit ... · 7/6/2017 · 02/01 /2016 -...
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DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION DISTRICT OFFICE ADDRESS AND PH(^ NUMBER US Food & Drug Administration New England District One Montvale Avenue, 4th Floor Sloneham, MA 02180 F Industry Inforrnation; VAv^v.fda.gov/oc/induslry Phone: (781)587-7500 DATE(S) OF INSPECTION 02/01 /2016 - 02/05/2016, 02/1 1 /2D16 FEI NUMBER 3008477155 TO: Amarpreet Singii Sawhncy, President, CEO, and Chairman of the Board FIRM NAME Ocular Therapculix, Inc. CITY, STATE AND ZIP CODE Bedford, MA 01730 STREET ADDRESS 36 Crosby Drive, Suite JOl TYPE OF ESTABLISHMENT INSPECTED Sterile Drug Manufacturer THIS DOCUMENT LISTS OBSERVAnONS MADE BY THE FDA REPRESENTATIVE(S) DURING THE INSPECTION OF YOUR FACILITY. THEY ARE INSPECTIONAL OBSERVATIONS; AND DO NOT REPRESENT A FINAL AGENCY DETERMir\iATION REGARDING YOUR COMPUANCE. IF YOU HAVE AN OBJECTION REGARDING AN OBSERVATION. OR HAVE IMPLEMEI^ED. OR PLAN TO IMPLEMENT CORRECTIVE ACTION IN f^SPONSE TO AN OT ^RVATION. YOU MAY DISCUSS THE OBJECTION OR ACTION WITH THE FDA REPRESENTATI\^(S) DURING THE INSPECTION OR SUBMIT THIS INFORMATION TO FDA AT THE ADDRESS ABOVE. IF YOU HAVE ANY QUESTIONS, R.EASE CONTACT FDA AT THE PHONE NUMBER AND ADDRESS ABOVE. DURING AN INSPECTION OF YOUR FIRM (I) (WE) OBSERVED: Observation 1 Laboratory records do not include a complete record of all data secured in the course of each test, including all spectra from laboratory instrumentation, properly identified to show the lot tested and drug product tested. Specifically: A. Review ofyour firm*s source documentation for analytical data (JjJQQIIIIIIIIII^IIIIIIIIIIIIIIIIIIII^^ supporting exhibit batchejS!HQHII|I^I^^BII^^^^H^^nd that printed HPLC chromatograms and integration results for dose content uniformity and purity were discarded following and only the reprocessed data was printed and retained. For 'example: a. Review of source dose content uniformitydat^^^^^Q^HHim ncluded in the submission for T^l^y|Hreve5edthS5S5 the original printed chromatograms and integration results were discarded. b. Review of source dose content uniformity data included in the submission for l^^y^jJJvealedthat^^Q the original printed chromatograms and integration results were discarded. I, Exhibit Lot # I were reprocessed and I, Exhibit Lot # were reprocessed and SEE REVERSE OFTH/S PAGE FORM FDA ^{9fQB) PREVIOUS EDITION OBSOL EMPLOYEE(S) NAME AND TITLE {Print or Typo) Edmund F. Mrak Jr., Investigator Jonathan G. Matrisciano, Investigator Aditi Tliakur, Chemist, Vidya Pal, Reviewer Chunchun Zhang, Reviewer INSPECTIONAL OBSERVATIONS I DATE ISSUED 02/11/2016
Transcript of (JjJQQIIIIIIIIII^IIIIIIIIIIIIIIIIIIII^^ supporting exhibit ... · 7/6/2017 · 02/01 /2016 -...
DEPARTMENT OF HEALTH AND HUMAN SERVICESFOOD AND DRUG ADMINISTRATION
DISTRICT OFFICE ADDRESS AND PH(^ NUMBER
US Food & Drug AdministrationNew England DistrictOne Montvale Avenue, 4th FloorSloneham, MA 02180 F
Industry Inforrnation; VAv^v.fda.gov/oc/induslry
Phone: (781)587-7500
DATE(S) OF INSPECTION
02/01 /2016 - 02/05/2016, 02/1 1 /2D16
FEI NUMBER
3008477155
TO: Amarpreet Singii Sawhncy, President, CEO, and Chairman of the BoardFIRM NAME
Ocular Therapculix, Inc.
CITY, STATE AND ZIP CODE
Bedford, MA 01730
STREET ADDRESS
36 Crosby Drive, Suite JOl
TYPE OF ESTABLISHMENT INSPECTED
Sterile Drug Manufacturer
THIS DOCUMENT LISTS OBSERVAnONS MADE BY THE FDA REPRESENTATIVE(S) DURING THE INSPECTION OF YOUR FACILITY. THEY ARE INSPECTIONALOBSERVATIONS; AND DO NOT REPRESENT A FINAL AGENCY DETERMir\iATION REGARDING YOUR COMPUANCE. IF YOU HAVE AN OBJECTION REGARDING ANOBSERVATION. OR HAVE IMPLEMEI^ED. OR PLAN TO IMPLEMENT CORRECTIVE ACTION IN f^SPONSE TO AN OT̂ RVATION. YOU MAY DISCUSS THEOBJECTION OR ACTION WITH THE FDA REPRESENTATI\^(S) DURING THE INSPECTION OR SUBMIT THIS INFORMATION TO FDA AT THE ADDRESS ABOVE. IFYOU HAVE ANY QUESTIONS, R.EASE CONTACT FDA AT THE PHONE NUMBER AND ADDRESS ABOVE.
DURING AN INSPECTION OF YOUR FIRM (I) (WE) OBSERVED:
Observation 1
Laboratory records do not include a complete record of all data secured in the course of each test, including allspectra from laboratory instrumentation, properly identified to show the lot tested and drug product tested.
Specifically:
A. Review ofyour firm*s source documentation for analytical data(JjJQQIIIIIIIIII^IIIIIIIIIIIIIIIIIIII^^ supporting exhibit batchejS!HQHII|I^I^^BII^^^^H^^ndthat printed HPLC chromatograms and integration results for dose content uniformity and purity were discardedfollowing and only the reprocessed data was printed and retained. For'example:
a. Review of source dose content uniformitydat^^^^^Q^HHimncluded in the submission for T^l^y|Hreve5edthS5S5
the original printed chromatograms and integration results were discarded.
b. Review of source dose content uniformity data
included in the submission for l^^y^jJJvealedthat^^Qthe original printed chromatograms and integration results were discarded.
I, Exhibit Lot #I were reprocessed and
I, Exhibit Lot #were reprocessed and
SEEREVERSEOFTH/SPAGE
FORM FDA ̂{9fQB) PREVIOUS EDITION OBSOL
EMPLOYEE(S) NAME AND TITLE {Print or Typo)
Edmund F. Mrak Jr., InvestigatorJonathan G. Matrisciano, InvestigatorAditi Tliakur, Chemist, Vidya Pal, ReviewerChunchun Zhang, Reviewer
INSPECTIONAL OBSERVATIONS
I DATE ISSUED
02/11/2016
DEPARTMENT OF HEALTH AND HUMAN SERVICESFOOD AND DRUG ADMINISTRATION
DISTRICT OFFICE ADDRESS AND PHONE NUMBER ^ DATE(S) OfI US Food & Drag AdministrationNew England District 02/01 /20One Montvale Avenue, 4th Floor p-,Sloncham, MA 02180 Phone: (781) 587-7500Industry Information: www.fda.gov/oc/industry 3008477NAME AND TTTLE OF INDIVIDUAL TO WHOM REPCWT IS ISSUED
TO; Amarprcct Singh Sawhney, President, CEO, and Chairman of the BoardFIRM NAME ~~ STREET ADDRESS
Ocular Therapeutix. Inc. 36 Crosby Drive, Suite 101CITY, STATE AND ZIP CODE TYPE OF ESTABLISHMENT INSPECTED
Bedford, MA 01730 StCTile Drug Manufacturer
DATE(S) OF
|c. Review of source dose cotitentSBS^HIinciuded in the submission for [l3||I^^Hreveai^and the original printed chrornatograms and integration results were discarded.
INSPECTION
02/01 /2016 - 02/05/2016,02/11/2016
FEI NUMBER
3008477155
I, Exhibit Lot#ns were reprocessed
d. Review of source purity datathe submission for NDAjyQ^|eveaied thaflSSmchrornatograms and integration results were discarded.
In each case there was no documented explanation for B9original source data with reprocessed chrornatograms.
included in
runs were reprocessed and the original printed
to support the replacement of
I. Review of the reprocessed fur purity analysisExhibit Lot submitted inQQ^X^^^^Hveale^failure to include the area
or a typical peak of unknown impurity at a retention time the total area andcontent of unknown impurities.
Review purity analysisStability I pi imt, supporting data submitted in H^^^^BWreve^d a failure
area of approximatel}^^^^^^Bi thetotal area and conten^numiowinmpffl
C. Review of source dose content uniformity data Exhibit Lot #in the submission for ND/flSBuHfound that this analysis was performed on
SBNQIHIHHHHHBIHIII^^^HH^cview of the raw data found sets printed on different dates11/07/2013 and 11/26/2013. No documentation was provided to explain why{|2||^IHill^B^cre processedand printed on 11/26/2013 whil^^Qm||||^^^^^|^|^ere all printed on 11/07/2013 or what happened to theoriginal dala sheets printed on 11/07/20I3.
D. You do not have written procedures to clearly specify how manual integration of chromatograms is performed.
SEEREVERSEOF THISPAGE
FORM FDA 4pal9rt)8) PREVIOUS EDITION OBSOLETE
eMPLOYeE(S) NAME AND TITLE {Print or TVpeJ
Edmund F. Mrak Jr., InvcsligalorJonathan G. Motrisciano, InvestigatorAditi 'ibakur, Chemfst, Vidya Pai, ReviewerChunchun Zhang, Revicwcr
f^djCbh^rilt&U^DATE ISSUED
02/11/2016
Page 2 of 8
DEPARTMENT OF HEALTH AND HUMAN SERVICESFOOD AND DRUG ADMINISTRATION
DISTRICT OFFICE ADDRESS AND PHONE NUMBER
US Food & Drug AdministrationNew England DistrictOne Montvale Avenue, 4th FloorStoneham, MA 02180 Phone: (781) 587-7500Industry Information: www.fda.gov/oc/industryNAME AND TITLE OF INDIVIOUAL TO WHOM REPORT IS ISaiED
DATE(S) OF INSPECTION
02/01/2016 - 02/05/2016,02/11/2016
FEI NUMBER
3008477155
TO: Amarpreet Singh Sawhn^, President, CEO, and Chairman of the BoardFIRM NAME
Ocular ITicrapeutix, Inc.
STREET ADDRESS
36 Crosby Drive, Suite 101CITY, STATE AND ZIP CODE
Bedford, MA 01730
TYPE OF ESTABUSHMENT INSPECTED
Sterile Drug Manufacturer
Observation 2
Samples taken of drug products for determination of conformance to written specifications are not representative.
(b) (4)Sgecrficajly^^ours^^ plan supporting product release and stability testing!designed to assure that samples are representative of (he entire subject lot or unit to
be tested. Your procedure SOP 1004, Revision: C, Release of Drug Products, states that product sampling for LALtesting "should result in a random sampling of a finished production lof' and product sampling for performancetesting is non-specific regarding the sampling t^hnique. Your procedure does not include any explanation ofsampling techniques or samplingdistributionassure^toob^ini^^ there were nodocumented samplq records batchejjSE^M
the satnplmg di^ibutionand that sampling was representative of the complete lots to support data submitted in NDA(b)(4)(b)(4)
Observation 3
Control procedures are not established which monitor the output and validate the performance of thosemanufacturing processes that may be responsible for causing variability in the characteristics of in-processmaterial and the drug product.
Specifically:A. Control procedures fail to include adequacy of mixing to assure uniformity and homogeneity of the
) as part of the bulk preparation(b)(4)(b) (4)
(b)(4)
SEEREVERSEOF THISPAGE
EMFLOYEE(S) NAME AND TITLE (Rif/if or Type)
Edmund F. Mrak Jr., InvestigatorJonathan G. Matrisciano, InvestigatorAditi Thakur, Cliemist, Vidya Pai, ReviewerChunchun Zhang, Reviewer
DATE ISSUED
02/11/2016
FORM FDA 48X^/08} PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS Page 3 of 8
DEPARTMENT OF HEALTH AND HUMAN SERVICESFOOD AND DRUG ADMINISTRATION
DISTRICT OFFICE ADDRESS AND PHONE NUMBER " ' |OATE(S) biUS Food & Drug AdministrationNew England District 02/01^0One Montvale Avenue, 4tli Floor ppi mi macStoncham, MA 02180 Phonei (781) 587-7500Industry Information; www.fda.gov/oc/indusiry 3008477NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT IS ISSUED
TO; Amarpreet Singh Sawhney, President, CEO, and Chairman of the BoardFIRM NAME ~ ~ I STREET ADDRESS
Ocular Thcrapcutix. Inc. 36 Crosby Drive, Suite 101CITY, STATE AND ZIP CODE —— ____ TYPE OF ESTABLISHMENT INSPECTED
Bedford, MA 01730 Sterile Drug Manufacturer
OATE(S) OF INSPECTION
02/01/2016 - 02/05/2016,02/11/2016
FEI NUMBER
3008477155
m (4) dpomt Thendpoint forfOICIM
therefore may challenge adequate determination of a [laMBi
B. product does includeevaluation to terminal sterilization despite that clevatedHlB^^^^Jn the drug productmay have a detriinental effect on product quality when exposed to the^^^HI^I^HIlfjjjjjmrocess.
(4)C, Preparation used
product strands mcIudesB[Q^n|||||||||||||^^ unthat
to nlastcr batch recortflMEI^^^^^MBBi contained||QE^^^^H|||^^^|^|D^ne^^|BHHH^B^|during^QgJ||nie amount o theQllJIIIIIIIIIIIIIfis^ controlled, quantified, or optimized in relation to potential effects on the product includingdrug content uniformity or drying properties.
D. You do not characterize and trend rejects produced during inspection of dnip product using tM016lM^vstem.Hquipmentyyu|P||^^H^^^HHH||||||||||||^^|||||||||||||||^^Additionally, a form may not be accomplished therefore potentiallymissing detection of voids and other defects that may affect drug content or other quality attributes.
SEEREVERSE0F7H/SPAGE
FORM FDA 4: PREVIOUS EOmON OBSOLETE
EMFIOYEEIS) NAME AND TITLE (Prinl or Type)
Edmund F. Mrak Jr., InvcshgatorJonatlian G. Mnlrisciano, InvestigatorAditi Thokur, ChcmisL Vidyn Pal, ReviewerChunchun Zhang, Reviewer
INSPECTIONAL OBSERVATIONS
^^d,Gpht|n.ualipn||ai^^DATE ISSUED
02/11/2016
Page 4 of 8
DEPARTMENT OF HEALTH AND HUMAN SERVICESFOOD AND DRUG ADMINISTRATION
DISTRICT OFFICE ADDRESS AND PHONE NUMBER
US Food & Drug AdministrationNew England DistrictOne Montvale Avenue, 4th FloorStoneham, MA 02180 Phone: (781) 587-7500Industry Information: www.fda.gov/oc/industiyNAME AND TITLE OF II«)IVIDUAL TO WHOM REPORT IS ISSUED
DATE(S) OF INSPECTION
02/01/2016 - 02/05/2016,02/11/2016
FEI NUMBER
3008477155
TO: Amarpreet Sin^ Sawhney, President, CEO, and Chairman of Uic BoardFIRM NAME
Ocular Therapeutix, Inc.
STREETADDRESS
36 Crosby Drive, Suite 101CITY, STATE AND ZIP CODE
Bedford, MA 01730
TYPE OF ESTABUSHMENT INSPECTED
Sterile Drug Manufacturer
Observation 4
Actual yield and percentages of theoretical yield arc not determined at the conclusion of each appropriate phase ofmanufacturing of the drug product.
Speciilcally: The batch sizeunits, submittedu not conform to the formulated bulk drug quantity which thepreticaliy mayprodu(j|yy|||||[H results In a lack of accountability for the full formulated batch quantity,qualityVdti^imsneddrag yield.
Observation 5
Written production and control procedures include batches formulated with the intent to provideTcrcent of the labeled or established amount of active ingredient.
(b) (4)
(b) (4)Soecificallv:
input to drug product formulation is not calculated based on the specific lotassay value. You have not evaluated API input at the acceptable low end of the batch record specified quantityrange for input and API assay at the low end of the acceptable range for release. Also, you have not evaluated APIinput at the acceptable hi^ end of the batch record specified quantity range for input and API assay at the highend of the acceptable range for release.
SEEREVERSEOF THISPAGE
EMPLOYEE(S) NAME AND TITLE (Print or Type)
Edmund F. Mrak Jr., InvestigatorJonathan G. Matn'sciano, InvestigatorAditi Thakur, Chemist, Vidya Pai, ReviewerChunchun Zhang, Reviewer
DATE ISSUED
02/11/2016
FORM FDA ̂(9A)8) PREVIOUS EDTnON DBSOLETE INSPECTIONAL OBSERVATIONS Page 5 of8
DEPARTMENT OF HEALTH AND HUMAN SERVICESFOOD AND DRUG ADMINISTRATION
DISTRICT OFFICE ADDRESS AND PHONE NUMBER
US Food & Drug AdministrationNew England DistrictOne Montvale Avenue, 4th FloorStoneham, MA 02180 Phone: (781) 587-7500
Industry Information: www.fda,gov/oc/industry
DATE(S) OF INSPECTION
02/01/2016 - 02/05/2016,02/11/2016
FEI NUMBER
3008477155
NAME AND nTLE OF INDIVIDUAL TO WHOM REPORT IS ISSUED
TO* Amarprcet Singh Sawhney, President, CEO, and Chairman of the BoardFIRM NAME
Ocular Therapeutix, Inc.
STREET ADDRESS
36 Crosby Drive, Suite 101
CITY. STATE AND 2P CODE
Bedford, MA 01730
TYPE OF ESTABLISHMENT INSPECTED
Sterile Drug Manufacturer
Observation 6
Laboratory controls do not include the establishment of scientifically sound and appropriate test proceduresdesigned to assure that drug products conform to appropriate standards of identity, strength, quality and purity.
Specifically:A. Testing and release specifications for(b)(4)
(b)(4) scessaty to assure {
equifements and Q^i||l[||||uniformity.
g product strands do not include assessment of thecritical to achieving finished drug product
(b)(4)
(b)(4)
B.1used in|(b) (4)
|(b) (4) jhe product and
sed in the production of specific product
drug product contact operations in thpackaging components is not sampled and testethere is no system to record the lot identificatio
C. A written procedure was not available to prescribe your handling of invalid laboratory data shown to have anassignable root cause for the discrepancy.
Observation 7
Equipment for adequate control over air pressure, micro-organisms, humidity, and temperature is not providedwhen appropriate for the manufacture, processing, packing or holding of a drug product.
Specifically:A. The temperature and humidity in th^{b){4)
!{b) (4) lased to produce(b) (4)
I is not monitored to assure that conditions are appropriate for
EMPLO
SEEEEV£/?SEOF THISPAGE
EMPLOYEE(S) NAME AND TTTLE (Piint or Type)
Edmund F. Mrak Jr., InvcsUgatorJonathan G. Moirisciano, Investigator.diti Thakur. Chemist, Vidya Pal, Reviewer
Cliitnchun Zhang, Reviewer
DATE ISSUED
02/11/2016
FORM PDA^WS (9/08) PREVIOUS EOmON OBSOLETE
DEPARTMENT OF HEALTH AND HUMAN SERVICESPOOD AND DRUG ADMINISTRATION
DISTRICT OFRCE ADDRESS AND PHONE NUMBER
US Pood & Drug AdministrationNew England DistrictOne Montvale Avenue, 4th FloorStoneham, MA 02180 Phone: (781) 587-7500
Industry Information; www.fda.gov/oc/industry
DATEIS) OF INSPECTION
02/01/2016 - 02/05/2016,02/11/2016
FEI NUMBER
3008477155
NAME AND TITLE OF INDIVIDUAL TO VI/HOM REPORT IS ISSUED
TO; Amarprect Singh Sawhncg^, President, CEO, and Chairman of the BoardFIRM NAME
Ocular Therapeutix, Inc.
STREET ADDRESS
36 Crosby Drive, Suite 101
CITY, STATE AND ZIP CODE
Bedford, MA 01730
TYPE OF ESTABLISHMENT INSPECTED
Sterile Drug Manufacturer
production operations throughout the process including produci
6. The fifllEmHfcleanroom facility IHHBised to produceleanroom facilimjjjjl^
:eps.
(b) (4)
^^^^^^^^s from to the
production room iheahlng that airborne contaminants in the gowning room may be swept into the production roomwhen the door is opened for personnel and equipment entry and exit.
(b) (4)
{b)(4)
C.The(b) (4) and (b) (4) (b)(4)in the incubators used tqdrug product are not monitored at a frequency designated to assure that
appropriate conditions aire maintained throughout the operaition.(b) (4)
D.The(b)(4)
!(b) (4) 1 used toj(b)(4)
Idrug product andKb) (4) ire not monitored
at a frequency designated to assure that appropriate conditions are maintained throughout tlie operation.
Observation 8
Time limits are not established when appropriate for the completion of each production phase to assure the qualityof the drug product.
Specifically:
(b)(4)A. The maximum hold time for|to terminal sterilization has not been established or controlled.
m (4)B. There is no documentation or control of th(
time outside refrigeration during manufacturing operations.
drug product produced prior
I drug product
EMPL
SEEREMORSEOF THISPAGE
EMPLOYEE(S) NAME AND TITLE (Print or Type}
Edmund F. Mrak Jr., InvestigatorJonathan O. Matrisciano, (nvestlgatorAdili Thakur, Chemist, Vidya Pai, ReviewerCbunchun Zhang, Reviewer
DATE ISSUED
02/11/2016
FORM FD^83 (9/08) PREWOUS EDmON OBSOLETE INSPECTIONAL OBSERVATIONS Page 7 of8
DEPARTMENT OF HEALTH AND HUMAN SERVICESFOOD AND DRUG ADMINISTRATION
DISTRICT OFFICE ̂DDRESS AND PHONE NUMBERUS Food & Drug AdministrationNew England DistrictOne Montvale Avenue, 4th FloorStoneham, MA 02180 Phone: (781) 587-7500Industry Information: www.fda.gov/oc/industryNAME AND TfllE OF INDIVIOUAL TO WHOM REPORT IS ISSUED
TO; Amarprcet Singh Sawhney, President, CEO, and Chairman of the Board
DATE(S) OF INSPECTION
02/01/2016 - 02/05/2016,02/11/2016
FEI NUMBER
3008477155
HRMNAME
Ocular Thcrapeutix, Inc
CITY, STATE AND ZIP CODE
Bedford, MA 01730
STREET ADDRESS
36 Cro-sby Drive, Suite 101TYPE OF ESTABUSHMENT INSPECTED
Sterile Drug Manufacturer
Observation 9
Unauthorized personnel have access to enter areas of the buildings and facilities designated as limited access areas
Specifically:A. On 02/01/2016 we observed that your receiving / shipping bay is shared with another tenant of the building andthe door leading to production areas from the receiving bay is not locked or otherwise secured from unauthorizedaccess. At the same time we observed fiJOSSBfiver enter the production facility, unchallenged, through thereceiving bay.
3. On 02/01/2016, we observed that thecontact operations to manufactuiso that the filling port could potenTIal^ oe accesses
used in drug productas unsecured and open
y unauthorized personnel.
Observation 10
Buildings used in the manufacturing of a drug product are not maintained in a good state of repair.
Specifically: On 02/01/2016, we observed gaps up to approximately two centimeters under the receiving /shipping bay doors. We also observed numerous scrap corrugate, wood, and plastic packaging materials piled inhe receiving / shipping bay in the comer and along the walls providing potential harborage to pests.
SEEREVERSEOF THISPAGE
EMPLOYEE(S) NAME AND TITLE (Prim or Type)
Edmund F. Mrak Jr., InvcstigaiorJonathan G. Matrisciano, Investigator
diti Thakur, Chemist, Vidya Pai, ReviewerChunchun Zhang, Reviewer
DATE ISSUED
02/11/2016
FORM PDA m) PREVIOUS EOrnON OBSOLETE INSPECTIONAL OBSERVATIONS Page 8 of 8
