DEPARTMENT AND HUMAN SERVICES

DEPARTMENT OF HEAL TH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION

DISTRICT OFFICE ADDRESS ANO PHONE NUMBER

U.S. Food and Drug Administration, ORA OPQO HQ 12420 Parldawn Drive, Room #2032 Rockville, MD 20857, USA Email: [email protected] Industry Information: www.fda.gov/oc/industry

NAME ANO TITLE OF INOIV10UAL TO WHOM REPORT IS ISSUED

TO: Mr. Xiuguo Tuo, General Manager FIRM NAME

Yibin Lihao Bio-technical Co., Ltd. CITY. STATE ANO ZIP CODE

Yibin, Sichuan, China, 644104

STREET ADDRESS

OATE(S) OF INSPECTION

7 /31-8/2120l9;8/5-8/6/2019

FEINUMBER

3008846564

Qihang Xi Rd.(No.5 Binjiang Rd.), Luoloog Industrial Park TYPE OF ESTABUSHMENTINSPECTEO

Intermediate API Manufacturer

THIS DOCUMENT LISTS OBSERVATIONS MADI: BY THE FDA Rf:f'f(ESENTATIVE(~) DURING THE INSPECTION OF YOUR FACILITY. nteY AAE. INSPECTIONAL 08SERVATIONS; ANO DO NOT REPRESENT A FINAL AGENCY DETERMINATION REGARDING YOUR COMPLIANCE. IF YOU HAVE AN OBJECTION REGARDING AN OBSERVATION, OR HAVE IMPlEMENTEO, OR Pl.AN TO IMPLEMENT COAAECTIVE ACTION IN RESPONSE TO AN OBSERVATION, YOU MAY DISCUSS lHE 06JECTION OR ACTION WITH THE FDA REPRESENTATIVE($) DURING THE INSPECTION OR SUBMIT THIS INFORMATION TO FDA AT THE ADDRESS ABOVE. IF YOU HAVE ANY QUESTIONS. PLEASE CONTACT FDA AT THE PHONE NUMBER AND ADDRESS ABOVE. -

DURING AN INSPECTION OF YOUR FIRM (I) (WE) OBSERVED:

OBSERVATION 1 Batch production and cleaning records are not completed contemporaneously.

Specifically, it appears that records of crude~6}l .il) time of production and cleaning. For example,

roduction and equipment cleaning are not completed at the

A. On 07/31/2019, it was explained that the firm was not producing crude~)(if) The finn was testing equipment. During my walkthrougb of the QA office, I observed too numerous to count records on the floor, desks, cabinets, etc. of the QA office. A brief review of the records revealed that the records included what appeared to be b) (if) receiving records, batch production and equipment cleaning records. equipment qualification and calibration records, etc.

i. On 07/31/2019 (first walkthrough of the QA office):_ the Manager explained that the records observed in the QA Office were created for a government project that will allow the firm to apply for government funding. It was explained that the records observed were not production records for real products.

ii. On 08/01/2019: the QA Manager explained that the batches being manufactured in the crud Cb) <4> orkshop at the time of the inspection were not for companies that manufacture drugs. The batches being man actured in the crudet6}~('1)---ivorkshop were for testing equipment and for selling to those companies that manufacture products, otlierlff'an drugs, like cosmetic manufacturers.

o~\~j

SEE REVERSE OF THIS

PAGE

EMPLOYEE($) SIGNA TIJRE

FORM FDA 483 (9/08) PREVIOUS EDITION OBSOLETE

EMPLOYEE($) NAME ANO TITLE (Print or Type} DATE ISSUED

Marijo B. Kambere, Investigator

INSPECTIONAL OBSERVATIONS Page 1 of7

DEPARTMENT OF HEAL TH AND HUMAN SERVICES FOOD ANO DRUG ADMINISTRATION


U.S. Food and Drug Administration, ORA OPQO HQ 12420 Parklawn Drive, Room #2032 Rockville, MD 20857, USA Email: [email protected] Industry Information: www.fda.gov/oc/indusuy

NAME ANO TITLE OF INDIVIDUAL TO WHOM REPORT IS ISSUED

TO: Mr. Xiuguo Tuo, General Manager FIRM NAME STREET ADDRESS

DATE(S) OF INSPECTION

7/31-8/2/2019;8/5-8/6/2019

FEINUM8ER

3008846564

Yibin Lihao Bio-technical Co., Ltd. Qihang Xi Rd.(No.5 Binjiang Rd.), Luolong Industrial Park CITY, STATE ANO ZIP CODE

Yibin, Sidman, China, 644104

TYPE OF ESTABUS)-lMENT INSPECTED


iii. On 08/02/2019 (second walkthrough of the QA office): the QA Manager explained that some records of crude (b) (<l) aybe mixed up with records observed on 07131/2019 which are required for the government project. The Manager and QA Manager explained the finn needed time to organize the records.

B . On 07/31/2019, I during inspect· > __ _.room, I observed crud {bf(<l in the b) <4> tank #4. The equipment status card of #4 states "idle". There was no lot number 1 entlfie on the equipment status card. The batch r (b Batch Production Record ll:i>l4> was not filled.

C.On07/31/2019 lobservedth><4> o .____,.._,lot#<b><4> in'the;b><4> ~2fromappro ·

Per thetb) <4> truct1ons on e ~ (b) ~atch Production Record l Sampling, Packaging 2 a es : th .~-- (!6) ~~~ Pressure pa '(ti e maintained during the roce d record 1>}14) (<l) gauge read~~ However the batch record observ · parts: • Time: <l) Temperature (°C)~ • Time: Temperature (°C): < / {6)-(<l) When as ed about the discrepancy in ----· auge and the batch records, the crud ' produc · on su rvisor initiated the'(tif< the following: ___ ...., • Time: (b) <

4> Temperature (0 C):m Pressure

D. On 07/31/2019, during inspection of the crudet6) <4> workshop, I found what appeared to be production in-process testing records on top of the electrical wire shaft located in thel6) rf) ea. The production supervisor proceeded to grab the records from my hands.

SEE REVERSE OF THIS

PAGE

FORM FDA 483 (9/08) PREVIOUS EDITION OBSOLETE

EMPLOYEE(SJ NAME AND TITLE (Print or Type) DATEISSUED


INSPECTIONAL OBSERVATIONtS Page2 of7

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION

DISTRICT OFFICE ADDRESS AND PHONE NUMBER

U.S. Food and Drug Administration, ORA OPQO HQ 12420 Parklawn Drive, Room #2032 Rockville, MD 20857, USA Email: [email protected] Industry Information: www.fda.gov/oc/industry

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT IS ISSUED



7/31-8/2/2019;8/5-8/6/2019

FEINUMBER

3008846564

Yibin Lihao Bio-technical Co., Ltd. Qihang Xi Rd.(No.5 Binjiang Rd.), Luolong Industrial Parle CITY, STATE AND ZlP CODE


OBSERVATION 2

"TYPE OF ESTABLISHMENT INSPECTED

Intennediate API Manufacturer

Document related to the manufacturing of intermediate API and cleaning of equipment are not available for review

Specifical!y, your 9.a~h records consist of production and cleaning records. During my review of your incoming and ou~01ng crud~(!>) <4> warehouse records, R-LH-Management-022-02, I found that}~]batches of crude (l>)(.if) (lot# n>H.i!) t ~6}l4) were manufactured from 06/01/2019 to 07/30/2019. Your QA Manager ai ecfto provide the complete batch production records of: out o~~) atches when requested on 08/02/2019 .. It

was ex lained that the onl complete batch production records availab e for review were those for lot #s (b) <4> andtl>) (.if) Per your incoming and outgoin~ crud,.~1>>14> arehouse records, R-LH-Management-022-02, 52 out ofl~~{}atches of crud ~fi>l4> (lot# ,u, , .. , to ti)l.if) have been distributed.

OBSERVATION 3 Procedures to prevent unintentional or unauthorized use or distribution of intermediate APis are not established or followed

On 07/31/2019, ~ labeled in parts: .... ~? ba •••" was observed in the crud~4

) storage room. The warehouse keeper attempted to leave the crude(b) <4> storage room with ~«t6}l4) . Upon examination of the content of the drum, nyo ha s containing crud (b) <4> ot #s (b) <4> ( > <4> , m~ufacturing date 07/26/2019) and (6} (.ii) (b) (.if) , manufacturing date 07/27/2019) were found 1ns1 e the {!>> (.ilf \trum. Per the Manager and QA Staff the manufacturin and testin records of these two batches where not available for review. However, crud ~6)14> ot #sl6}l..f) and<1>>l4) were not quarantined.

EMPLOYEE(S) NAME AND TITLE (P,t,t or Type)

Marijo B. Kamberc, lnvcstigator

FORM FDA '83 (9108) PREVIOUS EOtTION OBSOLETE INSPECTIONAL OBSERVATIONS Page3of7



U.S. Food and Drug Administration, ORA OPQO HQ 12420 Parklawn Drive, Room #2032 Rockville, MD 20857, USA Email: [email protected] Industry Information: www.fda.gov/oc/industry

NAME AND Tin£ OF INDIVIDUAL TO WHOM REPORT IS ISSUED

TO: Mr. Xiuguo Tuo, General Manager FIRMNAME STREET ADDRESS

OATE(S) OF INSPECTION

7 /31-8/2/l0 l 9;8/5-8/6/2019

FEINUMBER

3008846564

Yibin Lihao Bio-technical Co., Ltd. Qihang Xi Rd.(No.S Binjiang Rd.), Luolong Industrial Park CITY, STATE ANO ZIP CODE


OBSERVATION 4

TYPE OF ESTABLISHMENT INSPECTED

lntenncdiate APl Manufacturer

The Quality Control Unit oversight over the issuance of controlled documents is deficient.

SpecificaUy, the firm uses unbound production, cleaning and testing records of crud !{6f(..f

A. During my walkthrough of the facility, crudJ(b) (..f) roduction records were observed without the QA approval stamp used for document controls. Per SOP L-H Management, 001, Document recording regulations, approval dated 05/30/2019, QA stamp is required prior to issuance of records.

B. On 07/31/2019, during my inspection of the QA office, I observed a stalk of paper containing what appeared to be crude (b) <4> manufacturing records. Per the QA staff the records were being used as scrap paper.

OBSERVATION 5 The responsibilities of the Quality Units are not in writing or fully followed

Specifically,

A. The Quality Unit failed to ensure all production deviations are reported and evaluated. For ~xample:

i. On 07/31/2019, I observed {6f(..f

(b) (:if) perator failed to maintam 1 C). No deviations was reported.

SEE REVERSE OFTHIS PAGE

EMPLOYEE($) SJGNAT E

FORM FDA '83 (9/08) PREVIOUS EOmON OBSOLETE

in the b) (..f ~2 from approximately. The L...___. .... ---.-.... uring the(b) <4> rocess (See Observation

EMPLOYEE(S) NAME AND l1TI.E (Print or Type)


INSPECTIONAL OBSERVATIONS Page 4 of7



U.S. Food and Drug Administration, ORA OPQO HQ 12420 Parldawn Drive, Room #2032 Rockville, MD 20857, USA Email: [email protected] Industry Information: www.fda.gov/ocfmdustry

NAME AND T11lE OF INDMDUAL TO WHOM REPORT IS ISSUED



7/31-8/2/2019;8/5-8/6/2019

FEINUMBER

3008846564

Yibin Lihao Bio-technical Co., Ltd. Qihang Xi Rd.(No.5 Binjiang Rd.), Luolong Industrial Parle CITY, STATE AND ZIP CODE

Yibin, Sichuan, China. 644104


Intermediate APT Manufacturer

ii. On 07/31/2019, an unidentified batch was observed in ther(6f(..f deviations was reported.

nk # 4 (Observation I B). No

iii. On 07 /3l/2019, during manufacturing of lot (fiH4> the tb) (..f) k #14 was observed to be leaking.

No deviations was reported. ----- -----B. The Quality Unit failed to ensure that corrective and preventative actions (CAPAs) described in your CAPA Response Report dated 01/10/2019, are implemented. Per our CAPA, production o~rators can only usJ(b) <4> indicator suitable for rul!fOW (~) ange. Duringlb) <4> (frudelb) <4> ot # (b) <4> I observed <~>

indicator chart fro~~f > Pe~ e productioh supervisor th~~~~ Jndicator is used for etemumng~~~ alue ~f the (bf(4) (b) (4) (

4)

C. The Quality Unit oversight over production facilities is deficient. For example, on 07/31/2019: ..

i. Pest activities was observed in the crude(b) <4> toraS.:.;oom ii. Large pools of water were observed in die cruae< -<4> _Jvorkshop iii. Decommissioned equipment in what appeared unsanitary condition was observed in the crude b) (:if

workshop

Per your QA routine check list, QA performed a routine check of the facility on 07/30/2019. No deficiencies were noted on the QA routine check list.

SEE REVERSE OF THIS PAGE

.FORM FDA 483 (9108) PREVIOUS EDITION OBSOLETE

EMPLOYEE(S) NAME AND TITLE (Print or Type)


INSPECTIONAL OBSERVATIONS

DATE ISSUED

Page5of7

DEPARTMENT OF HEAL TH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION


U.S. Food and Drug Administration, ORA OPQO HQ 12420 Parklawn Drive, Room #2032

DATE($) OF INSPECTION

7/31-8/2/2019;8/S-8/6/2019

Rockville, MD 20857, USA Email: [email protected] Industry Information: www.fda.gov/oc/industry NAME ANO OF INDIVIDUAL TO WHOM REPORT IS ISSUED

TO: Mr. Xiuauo Tuo, General Manager FIRM NAME STREET ADDRESS

FEINUMBER

3008846564

Yibin Lihao Bio-technical Co., Ltd. Qihang Xi Rd.(No.5 Binjiang Rd.), Luolong Industrial Parle CITY, STATE ANO ZIP COOE


OBSERVATION 6

lYPE OF ESTABLISHMENT INSPECTED

lntennediate API Manufacturer

Equipment is not adequately maintained to prevent potential contamination that would alter intermediate APT quality

Specifically, on 07/31/2019, during production of crude 6>l4>

following conditions:

ot # f(6f(.il) , and bf{4 I observed the

A. What appeared to be rust/corrosion on the internal surfaces ot:Cb) (.J) #1 and #2 B. What appeared to be rust/corrosion on the internal surfaces of the filter locat [1>>l4> ___ tanks #1, #2, and

#3.

OBSERVATION 7 Production utensils and tools are not adequately stored to prevent potential contamination that would alter intermediate API quality

Specifically, on 07/31/2019, during inspection of thetl>fC.il oom, I observed a<b> <4> container with what appeared to be an(b) (<l) eter a <6> (.J) ontamer, a ong handle spade, a long handle scrub brush. Per the production supervisor, eCb) 4> ontainer is used for sampling the'C6) C.J>~s and the long handle scrub brush is used for cleaning the floor.

OBSERVATION 8 Containers or Equipment are not adequately identified to prevent mix ups

Specifically, on 07/31/2019, during inspection of the crude~b}l4 workshop and crude '{6)(.J) storage room, I observed multiples unlabeled or mislabeled containers. or equipment. For example:

A. AJb) (4) drum labeled i~~)• ag" in the crud f(bf(<l torage room was observed to contained crude(b) <4> B. An"uiil~eled drum in Hie crud {l>fC torage room was observed to contained,m.Jags

SEE REVERSE OF THIS

PAGE

FORM FDA "83 (9108) PREVIOUS EDITION OBSOLETE

EMPLOYEE($) NAME ANO TITLE (Print or Type)



DATE ISSUED

Page6of7

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD ANO DRUG ADMINISTRATION


U.S. Food and Drug Administration, ORA OPQO HQ 12420 Parldawn Drive, Room #2032 Rockville, MD 20857, USA Email: [email protected] Industry Infonnatioo: www.fda.gov/oc/iodustry NAME ANO TITLE OF INDIVIDUAL TO WHOM REPORT IS ISSUED



7/31-8/2/2019;8/5-8/6/2019

FEINUMBER

3008846564

Yibin Lihao Bio-technical Co., Ltd. Qihang Xi Rd.(No.5 Binjiang Rd.), Luolong Industrial Park

CITY, STATE AND ZIP COOE




C. The equipment status card on the!{6f<.if nk #4 states "idle", h~wever the tank was observed to contained crude(6) <4> aterial at the (b) <4> process step D. The cleaning collector tank in the crude (b) <4> orkshop is not identified E. (bf(.if) • container labeled lbT('f} was described as containing water by the crude(b) <4> workshop production supemsor r. .

F. -~ 6)14) ontainer labeled (fi) (.if) olution" was described as containing'<6J < olution by the crude i(6}l4> mksho production supervisor G. A (b) <

4> container labeled "tools" was described as containing discarded materials by the crud (b) <4>

worksh.£1? production ervisor H lfif('I) 'unlabeled'.<b) (.if) ontainers were observed. Per the crud ~l>)l.if) orkshop production supervisor the containers containe'a discarded materials.

OBSERVATION 9 Training procedure is deficient

For example,_07/31/2019, during my inspection of the crud~lij (.if) orkshop th~-f.t.roduction supervisor failed to explain the(b) (4) structions on the Crude(bf(.if) atch Production Record _ (6} < > Sampling, Packa . . . Per the pr~uctlon supervisor, t6J (.if) is app 1e m ermittently durin thet6}l4> g; ess. Per the Crud ~b) <4> Batch Produftion Record n>n4> Sampling, Packaging the(b) <4> emperature 4~ <!> C) and Pressure b) <4> pa (b) (.if) pa) are mamtamed during the (b) <4> rocess for (b) <4> ours and. recorded 6)14)

SEE REVERSE OF THIS PAGE

FORM FDA ,.a, (9/08) PREVIOUS EDITION OBSOLETE

EMPLOYEE(S) NAME AND TITLE (Print or Type)

Marijo B. Karnbere, Investigator


DATE ISSUED

Page7of7

Documents

DEPARTMENT AND HUMAN SERVICES