QUALIFICATION OF CONTRACT TESTING LABORATORY

QUALIFICATION OF CONTRACT TESTING LABORATORY

The purpose of this SOP is to describe the procedure for selection, approval, renewal of contract testing laboratory for testing / calibrations.

SCOPE OF CONTRACT TESTING LABORATORY:

This procedure is applicable for testing done at contract testing laboratory for raw material, intermediate, packaging material, finished product, stability, water analysis, analytical method validation, calibration etc.

RESPONSIBILITY:

Quality unit shall be responsible for:

Identifying contract testing laboratory.

Assessment of contract testing laboratory registration form and coordinate/ conduct audit of contract testing laboratory and follow up for action plans.

Generation, coordination, review and approval of Quality agreement.

Periodic audits of contract testing laboratory.

Monitoring of contract laboratory for regulatory implications.

Sending samples “Calibration standards to contract laboratory and verification of COA analytical report/ Calibration certificate with its traceability/ raw data received.

Monitoring of calibration performed by instrument vendor.

Sending of calibration standards for calibration to outside testing lab or instrument vendor whenever required.

CQC shall be responsible for management of contract laboratories through SAP.

Research and development (R&D) is responsible for:

Identifying contract testing laboratory.

DEFINITIONS:

Contract testing laboratory: Any laboratory, which is other than Own laboratory and authorized for analysis of sample & calibrations.

Quality Unit: Quality Unit is comprises of Quality Assurance and Quality Control.

Quality agreement: It is an agreement made between company and contract testing laboratory to have the predefined terms and conditions and to clearly establish the duties of each party.

Debarment certification : A certification form provided by the Department for execution by the prospective bidder or subcontractor certifying that he is not, nor has been, debarred, suspended, proposed for debarment, declared ineligible, or voluntarily excluded from certain transactions and has not been

PROCEDURE:

Identification of new contract testing laboratory

Any laboratory which has the required instrumentation and has the potential to work can be identified as a contract testing lab.

Contract testing laboratory must be approved by Local FDA and NABL, ISO or equivalent certification in case of Packing material. In case of sample testing, the laboratory shall comply with the GMP requirements of the country where the end product will be distributed.

The samples shall be sent to contract laboratory in following cases but, not limited to:

1. Inability to do a particular testing
2. Regulatory/ Customer requirement for outside testing

Evaluation of contract testing laboratory:

If the contract testing laboratory complies the basic requirement shall provide the “Site registration form” with contract testing laboratory.

The Site registration form shall be filled by the contract testing laboratory and the form can be filled during audit also.

Quality unit and/ or other required function shall conduct the audit of contract testing laboratory. The auditors shall have experience in QC or analytical laboratory and must be experienced enough to assess the laboratory.

Each audit shall be assigned a unique number.

Audit scheduler for contract testing laboratories shall be maintained and monitored through SAP / Manually.

Companies being used as contract testing laboratory shall be audited as per “Corporate quality audit” and considered as approved.

During audit, following systems needs to be covered but not limited to;

Auditor(s) shall use the basic questionnaire for reference and basic questionnaires shall be send via mail along with site registration form or can be fill during the audit.

License issued by relevant authorities (E.g. FDA).

Organogram, job description

Site master file, validation master plan

Sample management

Instrument qualification, calibration

Instrument logs

Glassware calibration, cleaning

Analyst Qualification& training.

Management of standards (weights, primary standards, working standards etc.)

Excel sheet validation (If used for calculation).

Handling of reagents

Handling of cultures & microbiological testing (In case if microbial testing is done)

Handling of OOS results/ Failure investigations

Documentation controls

Data integrity & security controls (Data back-up, 21 CFR part 11 compliance etc.)

Quality management system (Change management, deviation etc.)

Document archival system.

Maintenance and control of electronic systems

Review of sample tested and report as applicable

Additionally, collect the information on capability of the laboratory to perform various test/ calibrations for the material/ products/ items for which the testing / calibrations may be contracted in future. Maintain such information in the list of test methods and testing laboratories. The list shall be updated by site Quality periodically as per the current requirement.

Audit of contract testing laboratory shall be done as per due date from the date of audit or whenever required. Once the audit is completed, the audit report shall be shared to the contract testing laboratory. After receiving of satisfactory compliance to critical and major observations, audit can be closed and laboratory can be approved.

Auditor shall send signed audit report to the auditee within 30 working days from the date of audit.

In case there are no observations recorded during onsite audit, the auditor shall classify the site as ‘Acceptable’ and shall sign off the Audit report and close the audit.

If No observation recorded by Auditor during audit the compliance report is not required and auditor may classify the site as “Approved” while issuing the audit report.

Auditor shall request auditee to submit compliance report, for the observations classified as critical, major and minor, within 30 working days from the date of receipt of audit report.

In case compliance report is not received within 30 working days, CQC Department shall decide further course of action such as follow up with contract laboratory. Follow up shall be done via mail/Fax/Telephonically and reported.

The compliance report should contain corrective actions and preventive actions (CAPA) against each observation along with target date of completion or justification for adequacy of current practices.

Auditor shall review the compliance report for adequacy of proposed Corrective and Preventive actions or justification.

If the compliance report is adequate, the auditor shall classify the site as ‘Approved’ in the audit closer from.

If in case the compliance reported is inadequate, the auditor shall classify the site as ‘Not Approved’ in the Audit closer form.

If the contract testing laboratory is approved, then initiate Quality agreement with the contract testing laboratory.

Validity period of audit of contract testing laboratory shall be 5 years from date of audit unless any situation arises to reject/ cancellation of the contract services. If the work to be continued at contract testing laboratory beyond this period, re-audit shall be conducted.

If any audit could not be conducted with in the acceptable timeframe i.e. within ± 3 Months of scheduled date due to unavoidable circumstances e.g. non availability of the dates, etc. then it can be further rescheduled within next 3 months supported by adequate Justification.

In case there is no business forecast with approved contract testing laboratories, scheduled re-audit can be postponed and same shall be performed before sending any sample.

If re-audit is done before 5 years in that case, new quality agreement shall be prepared and validity of quality agreement shall be considered for 5 years from the date of new agreement after re-audit.

Quality agreement

Prior to start work with contract testing laboratory, Quality agreement shall be initiated.

Each quality agreement shall be assigned a unique number.

Quality agreement shall include but not limited to following clauses

1. a) Purpose & scope of agreement
2. b) Qualification and validations
3. c) Testing instruction and specification
4. d) Inspection and audits
5. e) Subcontracting
6. f) Change management and approval
7. g) Deviation, out of specification and out of calibration results and failure investigation
8. h) Reference standards
9. i) Test samples and storage
10. j) Testing of products
11. k) Reporting of results
12. I) Stability testing
13. m) Archiving and retention of documentation
14. n) Term and expiration of quality agreement

Contract acceptor shall not use any other subcontractor or facility of subcontractor for any service without prior approval from Company.

Contract acceptor shall intimate and obtain approval from company.

Changes in the test methods, specifications and other contractual requirements wherever applicable shall not be made unless the changes are approved by company.

Quality agreement shall be signed by Head Quality/ designee from site Quality assurance or CQC and representative from contract testing laboratory.

Any testing activity shall be allotted to contract testing laboratory only after Quality agreement is in place.

Monitoring of Contract testing laboratory:

Management and monitoring of contract testing laboratories along with status approved/ not approved shall be performed by corporate quality compliance (CQC) in electronically through SAP/Manual.

List of contract testing laboratory shall be exported / printed through SAP/manual by authorized personnel.

Approved contract testing laboratory shall be applicable for applicable for all the sites of company.

Contract testing laboratory shall provide documents like debarment certificate, cGMP certificate. Wherever the method transfer/ verification is required, shall be performed as mutually agreed.

Contract testing laboratory shall inform company in case of any cGMP non-conformances observed at the testing site by regulatory agency (e.g. USFDA, TGA, MHRA etc.).

Quality unit shall evaluate the non-conformances and shall take the corrective and preventive action/ decision based on the evaluation. Risk based approach shall be followed.

The site approving the testing laboratory shall share the audit and compliance report and relevant documents such as certificates etc. with other location QA/ CQC for their reference.

Handing of calibration standards/ samples or other items to contract testing laboratory:

Ensure that valid technical agreement with the contract testing laboratory is available prior to sending samples or calibration standards (e.g. standard weight .box)/ other items (e.g. scale, micro meter, Vernier caliper etc.)

On receipt of specification/ method of analysis for a material, QC/analytical development laboratory shall review the same. List out any such test not possible to be carried out in the QC/ analytical development laboratory.

The analyst shall refer to details recorded for the information of the analytical lab which is approved for that particular test.

Unless otherwise specified, sufficient quantity of samples shall be packed in double polythene bag/ glass bottles with proper label bearing the details of the samples. Additional precaution shall be taken during packing if the sample is temperature/ humidity/ light sensitive.

Head QC shall ensure method transfer or Method Validation or Method Verification has been completed as appropriate, (based on requirement), prior to sending the sample for analysis. Other items as mentioned above shall be securely packed before sending for calibration.

The Analyst shall generate the outside laboratory testing request and a returnable/ non- returnable gate pass as the case may be by mentioning the details of tests to be performed at the contract testing laboratory.

Analyst shall enter ANDA /DMF Number in remark provide (as applicable) and shall be ensure that, contract testing lab where sample/s are going for testing is file in ANDA/ DMF (Yes /No) and duly approved by Head QC. If Lab is not filed, in ANDA/ DMF then such case shall be handle through Change control procedure.

If re-print required for outside laboratory testing request due to any specific reason (e.g. request not physically printed on printer, printer error, smudged printing etc.) then approval shall be taken from authorized person.”.

The Analyst shall generate the Sample / Material Label for outside laboratory testing.

If re-print required for Sample / Material Label due to any specific reason (e.g. label not physically printed on printer, printer error, smudged printing etc.) then approval shall be taken from authorized person.

The analyst shall label the sample with name of the product/ material/Item name, Identity number, Batch number, manufacturer’s name, pharmacopeia status if applicable, quantity of sample, mfg. date, expiry/retest date, storage condition etc. suitably packed so that integrity of the sample/item is not affected.

In case of calibration standards, the weight box or instrument shall be securely packed and labelled before sending.

In case of SAP is down (planned or unplanned shut down) or Non-SAP managed batches, then Sample / Material Label shall be affixed and outside laboratory testing request.

System default electronic log of all outside laboratory testing request printed / re-printed shall be available in SAP.

Note: For SAP managed batches, SAP Inspection lot shall be considered as A.R. Number. Whereas, for Non-SAP managed batches,

A.R. Number shall be allocated.

While sending samples of commercial batches samples / Materials to the external laboratory/contract testing lab, QC shall ensure as per below procedure

• The selected lab must be part of approved lab list.
• For commercial sample, the same lab, which was in filled in ANDA /DMF should be selected for commercial samples.

Note: For tracking of the same (ANDA/DMF filed Labs).

The samples shall be transported as per recommended storage condition to outside testing laboratory. Other items/ calibration standards should be transported to outside Lab securely as per recommendation. If sample is received in bad condition like sample wetting, open condition etc. by the contract testing laboratory, then the contract testing laboratory shall be informed to Company immediately.

Outside laboratory testing request number shall be generated automatically. In case SAP is down (planned or unplanned shutdown) or Non-SAP managed batches, then reference number in the Print outside testing request shall be numbered.

In case any Out of specification or unexpected result observed during the analysis of any sample at contract testing laboratory, the same should be brought to the notice of the concerned personnel of company and the closure report for such incidents should be approved by an authorized person of company as applicable.

Upon completion of analysis, the contract testing laboratory shall send the COA/ test report to company. Copies of chromatograms/ spectrum/ raw data duly signed shall be sent whenever required by company.

The COA/ calibration certificates and other analytical documents or raw data received from contract testing laboratory shall then be reviewed by concerned person in site QC department. Affix green coloured stamp of “Reviewed and accepted with sign and date” on each page of the document at the bottom.

Attach the documents received from the contract testing laboratory for a particular test of the material along with the analytical record of company.

After receipt of Result/ COA from outside laboratory testing, Laboratory testing report number shall be updated in SAP.

In case of SAP is down (planned or unplanned shut down), then QC shall update the register meant for analysis in contract testing laboratory.

Result of a test from contract laboratory shall be communicated in writing either through electronic system or hard copy. No verbal communication shall be entertained in this regard.

Instrument calibration is done in-house by external vendor.

In case of calibration done in-house by outsourced vendor/ Agency, an agreement shall be established between the vendor and company before allowing the vendor for calibration

ABBREVIATIONS:

COA: Certificate of analysis

e.g.: For example

EIR: Establishment inspection report

etc.: Etcetera

FDA: Food and drug administration

NABL: National Accreditation Board for Testing and calibration laboratories

ANDA: Abbreviated New Drug Application

DMF: Drug master file

CTL: Contract testing laboratory

CQC: Corporate Quality compliance

SAP: Systems, Applications & Products in Data Processing

BASIC QUESTIONNAIRE FOR EVALUATION OF CONTRACT TESTING LABORATORY

The present Questionnaire is part of our approval procedure and it is a prerequisite for future process. It should be filled in as completely as possible.

Please answer the questions with respect to a specific site. If the work is divided and done at different sites, please fill it in separate questionnaires.

Also answer the questions with respective to the activities with clear defined scope of the activities.

We kindly request you to complete and return this questionnaire within the next two weeks.

Note:

Sections to be filled out as applicable. If particular section is “Not applicable”, mention NA.

Wherever Yes or No option given specify “tick mark (✓) in the space provided under -Yes or No.

1.GENERAL INFORMATION

Analytical Testing service: Chemical/Microbiology/Stability/Packaging material/Others (Specify)

Name of the Company:

Address: ———

City/ State/ Country/ Pin: ————-

Tele phone/ Fax: ________________________ _

Number of personnel: Total: ________ Quality: ________ _

How long the company has been in this business?

Does the laboratory is having necessary licenses and permissions

Is there a published Quality Manual?

If yes, to which international norm (e.g.: IS09001, GMP, ICH) is your quality system related?

If yes, to which international norm (e.g. IS09001, GMP, and ICH) is your quality system related?

Is your system certified by other institutions?

Please, attach copy of your certificate(s).

Is your site inspected by National Health Authorities or FDA?

If yes, indicate the most recent inspection and the outcome?

2.PERSONNEL

Is there an employee training program, including records of training completed for all personnel?

Are people trained when new methods are used?

Are people trained on GMP regularly?

Are your personnel aware that the analytical service you provide is used for the release and qualification of drug substance, drug products etc.

How is this demonstrated?

3.AUDIT & INSPECTIONS

Is there a formal program for internal quality audit?

Would your company be receptive to an audit by a representative of company?

4.PREMISES AND FACILITIES

Are the premises designed or adapted-for the present use?

Does the design prevent Chemical contamination?

Does the design prevent Physical contamination?

Does the design prevent Microbial contamination?

Are laboratories clean, uncluttered, and of sufficient size?

Are there separate areas for handling of samples?

Are there separate areas for storage of samples?

Are there separate areas for microbial testing?

Are there separate areas for sterility testing?

Are your working-rooms air-conditioned?

Are your working-rooms supplied with security and fire protection measurements?

Are your working-rooms utilized with control access, where appropriate?

5.LABORATORY EQUIPMENT/ COMPUTERIZED SYSTEMS

Is there a list of all equipment used in the laboratory?

Do you have an SOP for qualification of laboratory equipment?

Are there user requirements and functional specifications for each equipment?

Within qualification of equipment, is there a protocol and report for Installation, operational and performance Qualification with test cases, acceptance criteria and test results?

Do you have an SOP for maintenance (calibration of laboratory equipment?

Is there logbooks of main usage/ maintenance of equipment?

Are analytical instruments periodically calibrated/ tested by qualified people (including records)? Do you have a VMP? Please summarize:

Is any laboratory equipment software controlled (e.g. LIMS, acquisition data software?)

If yes:

Is the software validated?

Are modifications of software implemented by qualified laboratory personnel?

Do you have an SOP for back-up and Recovery?

Do you have an SOP for security management? (Access control of laboratory, equipment, data archival system etc.)

Do you maintain data integrity in lab?

6.TEST METHODES AND PROCEDURES

Does your general method comply with relevant compendia (e.g. EP, USP, JP, etc.)?

What is your approach to verification of pharmacopoeia methods and methods received from customer?

Do you have an SOP for analytical method validation?

If yes, how are analytical methods validate?

Are methods periodically qL1alified1after their initial validation?

Are non-Compendia! Methods validated?

Is System Suitability Testing part of your routine analytical method?

Do you have an SOP for “Out of Specifications” test results management?

How are OOS test results used in your laboratory?

Do you have an SOP for sample handling?

Do you have a sample tracking system?

Do you have an SOP for reference standards management?

How are samples and reference standards stored?

Do you have an SOP for reagent management?

How do you manage retain sample control?

Are third parties involved in the services, you offer?

If yes, please specify tasks and responsibilities:

Provide the list of your analytical

7.DOCUMENTATION, DATA & REPORTING

How do you manage your documentation (SOPs, notebooks, analytical test records, electronic records)?

Is your documentation approved by QA?

Do you have an Index of general SOPs (please, attach)?

Do you have an SOP for change control, deviation?

How do you verify and approve laboratory data/ release of results (e.g. second person who checks of all QC data, etc.)? Please explain:

How do you manage your documentation retention/ archiving?

Do the provided reports are adequate, complete and contain thorough information?

Explain how the data is acquired, secured, analyzed and finally reported back to the client organization?

Explain how the data is acquired, secured, analyzed and finally reported back to the client organization?

How do you conduct the validation of methods to your organization?

8.SAFETY, HEALTH AND ENVIRONMENT (If Applicable)

Do you have an operational management system for EHS?

Is this system:

Based on an international standard OH SAS 18001?

Certified?

Do you have a dedicated organization for SHE?

How many people are employed in this organization?

Do you have a structured SHE program, which is regularly monitored and updated?

Is your personnel instructed on the handling of any kind of hazardous materials that you use and on how to act in case unwanted events?

Do you have an adequate emergency response plan?

Do you run SHE audits?

Please enclose with this questionnaire a List of SOPs, List of Equipment’s and List of Software’s and a copy of the organogram.

9. Additional comments (If any):

We certify that the information provided in response to the questions posed are true, accurate and complete.

Issued for:

Signed, for:

(Contract testing laboratory)

QUALITY AGREEMENT FOR CONTRACT TESTING LABORATORY

I.WHEREAS, Contract testing lab ————————is well-established .and reputed for Industrial Research engaged in the business of Testing and method validation.

II.AND WHEREAS, company is a global pharmaceutical company, inter-alia engaged in the research and development, manufacturing, distribution and marketing of a wide broad range of healthcare and pharmaceutical products in India and abroad.

Ill. AND WHEREAS, Contract testing lab —————- has represented to company that the owns the testing facilities and has an expertise,  experience, facility, qualifications and personnel along with all regulatory licenses, permissions, approvals to test the Samples.

IV.AND WHEREAS, Company and Contract testing lab ——————- for Industrial Research, by this Agreement, wish to define the individual responsibilities of the quality aspects of testing of Product to ensure compliance with the approved Product specification and/or company requirements.

This Quality Agreement details the activities associated with testing of Product. Unless otherwise indicated, responsibility for each activity is assigned to either Contract testing lab ——————- for testing /validation or company, or is assigned to both Contract testing lab —— and company. 

QUALITY AGREEMENT

BETWEEN

Company Name and address 

AND Laboratory

Name & Address: ————–Hereinafter

Referred to as “————– 

This Quality Agreement (“Agreement”) is executed as of dated——– between company and Laboratory Name: -·——has agreed to testing, the samples specified below:

1. PURPOSE
2. SCOPE
3. COMMUNICATION/SITE CONTACTS
4. TERM & TERMINATION
5. CONTRACT LABORATORY:
6. TEST SAMPLE AND STORAGE
7. DOCUMENTATION MANAGEMENT
8. REVIEW AND STORAGE OF RAW DATA AND REPORTS
9. QUALITY ASSURANCE
10. NON-CONFORMANCES
11. FAILURE INVESTIGATIONS
12. CHANGE CONTROL
13. REGULATORY CONTACTS/ INSPECTIONS/ GMP COMPLIANCE
14. REFERENCE/ WORKING STANDARDS
15. HANDLING OF WASTE MATERIALS
16. VALIDATION/QUALIFICATION
17. SUB-CONTRACTING
18. QUALIFICATIONS AND TRAINING
19. FINAL REPORTS
20. RESULT TRANSFER
21. CONFIDENTIALITY
22. ASSIGNMENT
23. RESOLUTION OF QUALITY ISSUES
24. DEBARMENT
25. MISCELLANEOUS

Also read – SOP on Good Laboratory Practices (GLP)