inspection report for who...capa corrective actions and preventive actions cc change control cfu...

20, AVENUE APPIA – CH-1211 GENEVA 27 – SWITZERLAND – TEL CENTRAL +41 22 791 2111 – FAX CENTRAL +41 22 791 3111 – WWW.WHO.INT

Chengdu Institute of Biological Products, Chengdu - China : 9-13 April 2018

This public inspection report is the property of the WHO

Contact: [email protected]

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Prequalification Team Inspection services

WHO PUBLIC INSPECTION REPORT

Vaccine manufacturer

Part 1: General information

Manufacturers details

Company information

Name of

manufacturer

Chengdu Institute of Biological Products Co., Ltd.

Contact person Dr. Yonghong Ge; [email protected]

Mrs. Lingjiang Yang; [email protected] and [email protected]

Inspected site

Address of

inspected

manufacturing

site

379, 3rd

Section , Jinhua Road, Jinjiang District, Chengdu, 610023, Sichuan Province, P.

R. China

Unit / block Japanese Encephalitis Vaccine production, filling & packaging;

SPF Animal Breeding Facility 1 and Facility 2;

Quality assurance and quality control;

Culture Preparation;

Utilities;

Finished Product Warehouse;

Raw Material Warehouse;

Hazardous Raw Material Warehouse.

Inspection details

Dates of

inspection

9 to 13 April 2018

Type of

inspection

Routine inspection

Representative

from the

National

Regulatory

Authority

The national regulatory authority (NRA) of the country where the inspection took place

was informed and took part in the inspection.

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Introduction

Brief summary

and general

information

about the

manufacturing

activities of the

company

The Chengdu Institute of Biological Products Co., Ltd. (CDIBP) was founded in 1958.

The company is affiliated to Sinopharm China National Biotec Group (CNBG), one of

the six biological product institutes in China.

The major products in production are the following:

Japanese Encephalitis Vaccine, live (freeze-dried);

Diluent for 5 dose JE Vaccine

o PBS 2.5mL/vial, aseptically filled by CDIBP.

23-Valent Pneumococcal Polysaccharide Vaccine;

BCG Series of Products;

Diphtheria, Tetanus and Acellular Pertussis Combined Vaccine, Absorbed;

In addition, the company has about 20 other products not routinely manufactured,

such as Hib and typhoid vaccine.

The major products under development are as follows:

Human Papillomavirus quadrivalent Vaccine (recombinant);

Rabies Vaccine for Human Use (freeze-dried);

13-valent Pneumococcal Conjugate Vaccine;

Group A and C Meningococcal Conjugate Vaccine.

Japanese Encephalitis Vaccine (JEV), the focus of this inspection, was developed

collaboratively by CDIBP and the National Institute for Food and Drug Control

(NIFDC). The vaccine is for active immunization of healthy children older than 8

months of age, as well as children and adults who intend to enter the endemic areas from

non-endemic areas.

JE vaccine has been produced since 1989 and millions of doses have been administered

in China and to other Asian children. Since 2000, JE vaccine has been successfully

registered in a total of 11 countries; China, Korea, Sri Lanka, Nepal, India, Thailand,

Laos, Cambodia, Burma, Malaysia, and Vietnam, and has been exported to those

countries in large quantities.

History The initial on-site WHO GMP inspection took place in May 2013;

CFDA Follow-up GMP Inspection took place in February 2014;

WHO GMP inspection took place in May 2016;

Sichuan FDA inspection took place in June 2016;

CFDA inspection took place in September 2016;

Sichuan FDA follow up inspection took place in October 2016;

Indonesian FDA inspection took place in August 2017.

Brief report of inspection activities undertaken

Scope and limitations

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Areas inspected The inspection focused on the production and control of Japanese Encephalitis Vaccine

(live, attenuated). The inspection covered all the sections of the WHO GMP text,

including quality assurance, sanitization and hygiene, complaints and recalls, self-

inspection, personnel, training, personal hygiene, premises and equipment, materials,

documentation, qualification and validation, production, quality control and utilities.

Restrictions None

Out of scope Products and vaccines other than Japanese Encephalitis vaccine (live, attenuated) were

not inspected during this inspection.

Vaccines

covered by the

inspection

Japanese Encephalitis Vaccine (live, attenuated) 1 dose/vial and 5 dose/vial.

Lyophilised active component to be reconstituted with excipient diluent before use.

Two vial set (active + excipient)


0.5mL/ampoule, moist heat sterilized WFI. Purchased from Jiangsu Desano

Pharmaceutical Co., Ltd.


PBS 2.5mL/vial, aseptically filled by CDIBP.

Abbreviations AHU Air Handling Unit

ALCOA Attributable, Legible, Contemporaneous, Original and Accurate

APR Annual Product Review

APS Aseptic Process Simulation

BMR Batch Manufacturing Record

BPR Batch Production Record

CA Compressed Air

CAPA Corrective Actions and Preventive Actions

CC Change Control

CFU Colony-Forming Unit

CIP Cleaning In Place

CoA Certificate of Analysis

CpK Process capability

DQ Design Qualification

EDI Electronic DeIonization

EM Environmental Monitoring

FMEA Failure Modes and Effects Analysis

FTA Fault Tree Analysis

GMP Good Manufacturing Practices

GPT Growth Promotion Test

HEPA High Efficiency Particulate Air

HVAC Heating, Ventilation and Air Conditioning

IQ Installation Qualification

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JE Japanese Encephalitis

JEV Japanese Encephalitis Vaccine

LAF Laminar Air Flow

LIMS Laboratory Information Management System

MB Microbiology

MBL Microbiology Laboratory

MF Master Formulae

MFT Media Fill Test

MR Management Review

MRV Measles Rubella vaccine

NC Non Conformity

NCA National Control Authority

NCL National Control Laboratory

NRA National Regulatory Agency

OQ Operational Qualification

PHA Process Hazard Analysis

pH (-ve) logarithm of H+ concentration

PLC Programmable Logic Controller

PM Preventive Maintenance

PQ Performance Qualification

PQR Product Quality Review

PQS Pharmaceutical Quality System

PW Purified Water

QA Quality Assurance

QC Quality Control

QCL Quality Control Laboratory

QMS Quality Management System

QRM Quality Risk Management

RA Risk Assessment

RCA Root Cause Analysis

RO Reverse Osmosis

SH Single Harvest

SIP Sterilization In Place

SMF Site Master File

SOP Standard Operating Procedure

UN United Nations

UNICEF United Nations Children's Fund

URS User Requirements Specifications

UV Ultraviolet-Visible Spectrophotometer

VVM Vaccine Vial Monitor

WFI Water for Injection

WHO World Health Organization

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Part 2: Brief summary of the findings and comments

1. Pharmaceutical quality system

It appeared that adequate resources were made available for the management of the implemented QMS.

Quality assurance and quality control activities operate independently from the production unit.

Managerial responsibilities were specified in job-descriptions. Production and control operations were

specified in written form and GMP requirements were generally followed. Product and processes were

monitored and the results were taken into account in the batch release; regular reviews of the quality of

vaccines were conducted.

The quality risk management was deficient in the following:

Procedures for quality risk management and risk assessment were in place. FMEA and HACCP were

used. QRM examples were spot checked. This aspect of the QMS was fairly basic and this element of the

QMS required further utilization for fuller maturity and to make best use of resources. This was

adequately addressed through the CAPA provided by the company following the inspection.

Deviation management:

Procedure for the control of non-conformances (NCs) was in place. On the basis of the quality risk

assessment, NCs can be classified as critical, major and minor according to the impact on the product

quality. Timelines for reporting NCs were in place. Critical NCs were reported within 24 hours, major

and minor NCs were reported within 72 hours. NCs should be completed within 30 calendar days from

the date of first reporting event or within the timeframe decided by the Quality Compliance Forum

(QCF); if not, this should be justified before a new date is proposed. Regular trending of NCs was in

place.

Management review:

Procedure for the management review was in place. Quality management meetings were held once a year

with the attendance of high level managers, production heads and representatives from other relevant

departments. Management review was enhanced since 2016 and two reports were available. The

management review report held in 2017 was spot checked. It included the status of the implementation of

the recommendations raised in 2016 as well as new recommendations raised in 2017. In the current

practice only high level recommendations are recorded and documented. This was adequately addressed

through the CAPA provided by the company following the inspection.

Change control:

Procedure for change control management was in place. Change controls are categorized as critical, major

and minor. Critical changes have a potential critical impact on the product quality, safety and efficacy,

which are to be verified and validated and, further, need to be approved and registered by CFDA. Major

changes have a potential medium impact on the product quality, safety and efficacy and need to be

verified and validated but do not need to be approved or registered by CFDA. Minor changes have a

minor potential impact on the product quality, safety and efficacy and do not need to be approved or

registered by CFDA. Change control reports were spot checked and found adequately implemented.

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CAPA management:

Procedure for CAPA management was in place. The CAPA resulting from the last WHO inspection

carried out in April 2016 was spot checked.

CAPA regarding the implementation of the terminal sterilisation of the PBS diluent was still ongoing.

The company faced an issue related to residual amount of silicon oil from rubber stopper attached to the

vial wall after terminal sterilization. New rubber stoppers were qualified. The performance qualification

(PQ) and process validation is due by the first half of 2018.

Product quality review:

The PQR of live attenuated JE vaccine diluent (PBS) produced in 2017 was spot checked. Trends analyses

were conducted. The quality parameters of the PBS are stable and no trend could be observed.

The PQR of live attenuated JE vaccine was spot checked and covered all the lots manufactured in 2017 of

both 1-dose vials and 5-dose vials. The production of JEV live attenuated includes breeding of hamsters,

kidney collection, cell preparation, virus inoculation and culture, single virus harvest, bulk preparation,

final bulk preparation, filling and lyophilization, labeling and packaging. The PQR of live attenuated JE

vaccine included the review of all these processes except labelling and packaging as well as the steps

before kidney collection and breeding of hamsters.

Trend analysis was conducted using statistical tools such as Student’s t test or MannWhitney U test. The

quality parameters of cells, the harvest, the bulk, the final bulk, the 1-dose and the 5-dose vaccines are

generally consistent. As comparted to 2016, a slight trend toward higher titers of the single harvest and,

consequently, of the bulk, might be observed, likely due to the overall improvement of cell quality in the

production year 2017. In contrast, trend might be observed neither on the final bulk, nor on the vaccine. It

is noted that some lots of vaccine produced in 2017 displayed titers above the alert limit and even, in

some cases, the action limit. After review of the related OOT report it appeared that the lot testing is valid

and that these OOT are not linked to laboratory issues. The root cause was linked to the fact that 1) as

mentioned above, the virus titre of the harvest has slightly increased and 2) that the hold time of the single

harvest (i.e. not more 15 days 2 to 8°C) was unusually shorter for the lots that displayed these OOT. It is

worth noting that the OOT were observed only in the lots released in early 2017 and were no more

observed afterward, and that these lots still meet the acceptance criteria.

There were six lots of finished product with the residual BSA exceeding the upper alert limit. Four of

these were also exceeding the upper action limit. These observations occurred mainly in the 2nd

half of the

production year 2017. Upon review of the related OOT report, it appeared that this was likely due to the

lack of consistency of the BSA assay kit lots. This kit is provided by an external supplier. It was observed

that a same sample may display different results, depending on the kit lot which has been used. The

difference is such that a given sample remains below the alert limit when first tested with a particular kit

lot, and exceeds the action limit when retested with another kit lot. It is noted that the BSA level is well

below the regulatory limit. This inconsistency was adequately addressed by the company through the

CAPA provided following the inspection.

Change control, investigation of OOS, non-conformance, quality complaints and trend charts are reported

in the PQR. Some of these elements were spot checked.

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Documentation:

Document management system was described in the relevant procedures. SOP batch numbering

management system was spot checked. There was different batch numbering system for finish products,

bulk, intermediate, test purpose, media solution, water for injection, animals used for test.

Overall, the production activities are recorded in the form of batch manufacturing records, equipment

logbook and/or general control records. Procedures, operating conditions and specifications related to the

manufacturing processes are established. The quality control activities are recorded in the respective

documents of record including laboratory control records, equipment logbooks and general control

records. Procedures, operating conditions and specifications related to the quality control activities are

established.

Batch Release Process:

The release process was in place. The scope of this procedure covers intermediates, final product, raw

materials, etc… Samples are tested according to their specifications. Finished product results are introduced

in the intranet QC management system. If an OOS occurred, the OOS procedure should be followed. The

results are electronically reported on specific templates. Relevant information including the name of the

product, the presentation, date of the samples received, date of the report, batch number, production

department, acceptance criteria, results. Data are reviewed by the head the department (bioassays,

microbiological or physico-chemical) where the test is achieved, as well as by the head of QC who is

reviewing the whole report. The report is eventually sent to the QA department. The report is also peer

reviewed by another QA reviewer.

The Final products test and release management procedure describes how a batch will be or not submitted to

the NRA. It is an internal batch release which precedes the formal NRA batch release. One hundred percent

of the batches submitted to the NRA in 2017 passed and were actually released by the authorities. Therefore,

rejection, if any, is occurring earlier, during the internal release of intermediates.

Lot Summary Product review

Procedure for LSP with relevant information to be provided to NIFDC was implemented as agreed between

NIFDC and CDIBP.

Complaints

The provision for complaint management was in place. The list of complaints recorded in the last three

years was provided.

Two return of JEV due to VVM change of color were recorded. The corrective action consists of placing

the label on vials in a light controlled area.

Product recalls:

Procedures were available for recall. No recall was recorded.

The recall procedure should be initiated once requested by the NRA, in relation to AEFI or any complaint

due to quality compliance. As soon as a complaint is triggered, the QA section acts immediately, initiates

an investigation and further refers it to the product safety committee. If requested by the NRA, action

should be taken immediately. Should the request be issued by the CDIBP, the response would be

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classified into one out of 3 classes. Then, it should be responded within timeframe; 24h, 48 h or 72h for

class I, class II or class C respectively.

Regarding return/ replacement of product, the relevant procedure describes the scope and the conditions

of return and replacement management procedure. Returns were recorded for 2016-2017. Two returns due

to a change of VVM color and one due to wrong batch number were reported.

Pharmacovigilance:

A pharmacovigilance system was implemented for JEV. It includes a master file with all relevant SOPs

aimed at describing this system. A safety data exchange agreement with the oversea agents was made

available by November 2014.

From December 2016 till November 2017, 7,311 cases were reported, of which 7305 from china, four

from Thailand and two from Myanmar. Ninety three percent of non-serious and 5 fatal reports were

recorded. During the reporting period, 67,265,124 doses of JEV have been distributed in both the

international and the domestic markets. It is predicted that 33,574,125 persons have been vaccinated with

JEV. Out of these 7,311 case reports, 9 were received from ‘spontaneous’ source, 7,298 were received

from the ‘regulatory authority’ and 4 case reports were received from ‘literature’ source. These 7,311 case

reports encompass a total of 8,423 adverse events. Most of these (7,867 - 93.39%) were classified as non-

serious listed, 78 (0.93%) events were considered as serious unlisted, 148 (1.76%) were serious listed,

and the remaining 330 (3.92%) were non-serious unlisted.

The PSUR from December 2015 till November 2016 were spot checked. A total of 5,945 case reports

were received from various sources. Ten case reports were received from ‘spontaneous’ source, 5,933

from ‘regulatory authority’ and 2 case reports from the ‘literature’. Whereas the majority of these case

reports, i.e. 5,943, were received from China, two reports came from Thailand.

These 5,945 case reports relate to 6,805 adverse events. The majority of the events were judged as non-

serious listed 6,342 (93.20%), 72 (1.06%) events were judged as serious unlisted, 99 (1.45%) were

serious listed, and remaining 292 (4.29%) were non-serious unlisted.

The number of reported cases increased in 2017 as compared to 2016. This was due to an enhancement of

the collection reports and an improved education of health workers.

It was recommended to add conclusion about the status of all investigations in PSUR and zero reporting.

Self-inspection:

The management of GMP internal audit was in place. The procedure describes the self-inspection

process, the frequency and different type of self-inspection. The self-inspection plans for 2017 and 2018

were spot checked. The summary reports of the self-inspection conducted in 2017 and the proposed

resulting CAPAs were reviewed.

Quality audits and suppliers’ audits and approval:

Procedure for vendor qualification and verification was in place. Testing and review of the quality system

and documentation have been considered for vendor selection. The interval for re-qualification of vendors

was based on the risk assessment. The qualification of the suppliers of the primary packaging and raw

material including animal sourced material are reviewed every 2 years and for other material every 3

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years.

Contract production, analysis and other activities And Quality agreement:

There was no contract production for JEV. The manufacturing of the WFI diluent for 1 dose in ampoules

is subcontracted to a qualified vendor with GMP certified facility. Quality agreement was in place.

Nine laboratory subcontractors have been listed by CDIBP to perform various tests including testing of raw

material, water, animals and primary packaging. The contract renewal review is processed annually.

Personnel:

Organizational charts showing the relationships between different areas including quality assurance,

production and quality control, with identification by name and title of key personnel was presented.

CDIBP was considered sufficiently staffed with qualified personnel.

Training:

The Training department under human resources department is responsible for the training management

of all the employees at CDIBP. A three-level training management system has been established consisting

of company-level, the department-level and the team/group-level training. Annual training plans for

company and department level for 2017 and 2018 were spot checked.

Personal hygiene:

The human resources department was responsible for the organization of health examinations of employees

at CDIBP. All new employees are subject to the relevant health examinations before starting working in

CDIBP. JEV immunization policy based on biosafety risk assessment was described in the relevant

procedure. Staffs working in JEV vaccine were not required for vaccination as per the biosafety assessment

study conducted by the company in 2011.

2. Production system

Resources were available, including qualified and trained personnel, premises, equipment and services,

materials, containers and labels, procedures and instructions, laboratories and equipment for in-process

and other controls. Procedures for qualification and validation of equipment, manufacturing processes and

quality control testing methods were in place. Qualifications and validations were performed. Systems

were in place for handling complaints and recalling batches of product from sale or supply.

In general terms, the production of JEV at CDIBP site was considered under control through the reviewed

following items:

Virus seed lot system establishment, maintenance and testing;

Colony establishment, maintenance and testing;

Primary cell culture;

Cell-culture medium;

Production and control of a single virus harvest;

Virus inoculation and incubation;

Harvest of vaccine virus;

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Test on single harvest;

Preparation and control of virus pool or bulk material and Preparation and control of final bulk;

Batch manufacturing record review (BMR).

3. Facilities and equipment system

The manufacturing buildings for JEV are dedicated. Zone segregation principles based on cleanliness grades

were considered for premises. Production unit has individual HVAC systems, assuring the balance of

pressure difference and air exchange frequency rates. Pressure differentials between the premises with

different cleanliness grade are provided. Regular environmental monitoring is carried out. Cleaning and

disinfection of premises and equipment are considered. Regarding the bio-waste management, procedures

for discarding wastes in production area have been spot checked. Solid wastes are decontaminated via

autoclave. Liquid wastes are collected from manufacturing site to external tank which is subjected to steam

cycle before releasing the content to the main central waste site reservoir.

The company has provided an acceptable Site Master File with relevant documentation regarding the

manufacturing processes, buildings, equipment, materials and personnel flows, utilities and maintenance

plans.

The live JE vaccine workshop was completed and available for use in July 2010. The maximum production

capability is designed to be 35 million vials annually.

The manufacturing buildings dedicated to Japanese Encephalitis vaccine are of 3 floors:

1st floor contains the kidney collection area, final product packaging area, storage area and utilities.

2nd

floor is dedicated to filling, lyophilisation and capping of JEV final bulk as well as to the preparation,

filling and capping for JEV PBS diluents. Visual inspection area is performed at the 2nd

floor.

3rd

floor is dedicated to bulk production area. It contains non-classified area and clean area used for cell

preparation, virus inoculation, culture, harvest, bulk pooling and final bulk formulation. A dedicated area

of Zone D is dedicated to some testing of JE vaccine intermediate products and final product.

The JE vaccine manufacturing buildings are equipped with independent PW, WFI and compressed air

systems.

Qualification and validation:

Provisions for qualification and validation were in place and cover premises, equipment, utilities and

systems, processes and procedures at periodic intervals and when changes have been made. Preventive

maintenance programme and calibration plan were in place.

The qualification and validation of the following equipment was spot checked.

Validation of aseptic process through media simulations;

HVAC qualification;

Autoclaves;

Lyophilizers;

Depyrogenation Tunnel;

Fumigation of manufacturing facility;

Cleaning and disinfection studies;

Incubators;

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PW and WFI.

Although the premises and equipment involved and dedicated to the production of JEV at CDIBP site was

considered suitable to the operations to be carried out, deficiencies were raised and should be appropriately

addressed. For more details refer to Part 3 “Deficiencies”.

4 Laboratory control system

Quality Control is an independent department, separate from the Production. QC performs testing of

incoming raw materials, packing materials, intermediate products and final products, purified water,

water for injection, pure steam, and the environmental monitoring and stability studies for intermediate /

finished products. Animal testing is also carried out by Quality Control Department. The products at

intermediate/ final stages are tested against established specifications as per respective testing SOPs.

Physico chemical laboratory:

The Physico chemical testing group is part of the QC and is located in Building 208, 3rd

floor. The required

testing on final product and water for injection is conducted there. In general terms provisions for calibration

and validation of all equipment’s are in place at periodic intervals and when major changes have been made.

Validation and qualification were performed in accordance with written protocols and adequate written

reports on the outcome of the validation were produced. Calibration plan for 2017 and re validation master

plan 2017 and 2018 were reviewed.

The following activities were observed during the tour:

The QC area is separated from the production area which takes place on the same floor. In particular, a

dedicated lift has been build such that the QC lab has its own independent entry. Indeed, not using the

same entrance as the one of the production building was a requirement formerly requested by WHO.

Accordingly, the QC area is now completely separated from the production area.

The rooms for adventitious agent testing of cell substrates, for mycoplasma testing as well as for sterility

testing were visited. However no testing activities were ongoing during the visit. Adventitious agent

testing of cells encompasses observation of CPE and haemadsorption. The corresponding SOPs were

available. The equipment was adequately qualified.

The virus titration activity was observed during the tour.

Test method procedure:

The Virus titration procedure covered seed lots, single harvest, bulk, final bulk, finished product and

thermal stability. A national reference was used. The titre of viruses was performed by PFU determination

on BHK21 cell monolayers. For each sublot (each lyophilisation process), three samples were analysed.

Consequently, 6 samples were analysis for each batch. Serial ten times dilutions were made and used to

infect the monolayers. The tests were conducted separately (i.e. no pooling of samples). PFU titre was

determined by counting the foci in the well where these are between 10 and 1000. If the foci number is

less than 5 at one dilution, and more than 100 at the preceding 10 time dilution, then an intermediate

titration point is established at 10-4.5

.

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The SOP on mycoplasma testing by incubation method was spot checked. The scope of this SOP includes

single harvest, bulk and raw materials, MSV, WSV, Trypsin and bovine serum. Three types of

mycoplasma growth media are used.

The training protocol of QC staff for mycoplasma testing was spot checked. Upon review, a special

attention was paid to the mycoplasma testing. In particular, it was noted that recognition of positive

samples was part of the training. Indeed, it was felt important that the staff may identify positive samples

since positive outcome during routine process is expected to be quite unusual.

The SOP for the adventitious agent testing on the bulk, the seed lot and the trypsin and the SOP for the

adventitious agent testing for the cell substrate were both following the TRS recommendations.

Accordingly, 4 cell types (Vero, PHK, BHK21, MRC-5) were used for the detection of adventitious

agents. The positive control used is JE virus. Haemadsorption testing is achieved with chicken and

guinea-pig erythrocytes, using hemagglutinin as a positive control. Test samples are kept at 8°C and at

25°C and examined at 7 and 14 days and after subculture, the same is further incubated for another 14

days.

Management of OOS test results:

Handling of out of specification (OOS) results was conducted as per the relevant procedure.

Method Validation:

Validation of the virus titration method was validated for repeatability (CV ≤20%), intermediate precision

(ANOVA analysis among the results of the same sample tested by different analysts, P value should be

≥0.05), reproducibility (ANOVA analysis among the results of the same sample tested by different

laboratories, P value should be ≥0.05), robustness (different temperature and different staining time) and

range. The reviewed raw data are supportive of the conclusion drawn in the validation report. The original

validation was conducted in 2010. The method has been successfully revalidated in 2013.

Characterization of Antiserum was spot checked.

Characterization of MCB and WCB:

Not applicable since PHK cells are issued from a primary culture. Instead, most of the controls take place at

the level of the hamster flock.

Characterization of MSB and WSB was spot checked.

5 Materials system

Provisions for incoming materials, intermediates and finished products are in place for reception,

quarantine and release processes. Appropriate storage conditions are provided. Rejected and returned

material procedures were in place.

6 Packaging and labelling system

The labelling and packaging system areas were spot checked however not inspected in details during this

inspection.

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Part 3: Conclusion

Based on the areas inspected, the people met and the documents reviewed, and considering the findings of

the inspection, including the deficiencies listed in the Inspection Report, as well as the Corrective Actions

taken and planned, Chengdu Institute of Biological Products Co., Ltd. was considered to be operating at

an acceptable level of compliance with WHO GMP guidelines.

All the non-conformances observed during the inspection that were listed in the full inspection report as

well as those reflected in the WHO Public Inspection Report (WHOPIR), were addressed by the

manufacturer, to a satisfactory level, prior to the publication of the WHOPIR.

This WHOPIR will remain valid for 3 years, provided that the outcome of any inspection conducted

during this period is positive.

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