SOP for approval of contract testing laboratory in pharmaceuticals
1.0 OBJECTIVE:
The objective of this procedure is to lay down the process for selection and approval of contract testing laboratory for testing the Raw Material, Packing Material, Intermediate, Finished Products and stability sample testing.
2.0 SCOPE:
The scope of this SOP is applicable to all samples of Raw Material (RM), Packing Material (PM), intermediates, Finished Product (FP) and stability samples to be analysed in the contract laboratory sent by quality control division of [company name] as and when required due to non-availability of instrument, urgency or any emergency situation.
3.0 RESPONSIBILITY:
Head QC: Follow the procedure as per SOP for handling of sample sent to the contract Laboratory. Auditing of the contract Laboratory.
Head QA: Shall be responsible for selection, auditing and approval of the contract laboratory and compliance to the system.
4.0 PROCEDURE:
4.1 Select a contract testing laboratory based on market survey, internet or a quality control laboratory of [company name]’s other manufacturing site.
4.2 For all Raw Material, intermediate, Finished Product & stability samples the contract laboratory must be approved by FDA of Government of India and preferably accepted by applicable regulatory agencies i.e. MHRA, USFDA, EU, etc.
4.3 Carry out audit of the respective contract laboratory facility as per checklist in Annexure-I to assess their technical and analytical capability.
4.4 Head QA/ Designee will audit the contract Laboratory along with Head Quality control/ Designee. The auditors should at least have five year’s relevant experience. Total audit hours should be of minimum 10 hours.
4.5 Send the audit report to the auditee with a target date for compliance.
4.6 Approve the contract laboratory based on audit. Carry out compliance audit in case critical nonconformance is observed and approve / reject the same based on re-audit.
4.7 Review the performance of the contract laboratory every year within ± one month of the due month as per the audit planner as mentioned in Annexure-II. Recertification of the contract laboratory shall be made based on the audit observation and compliance status.
4.8 A technical agreement with the contract laboratory shall be made duly authorized by Head of contract laboratory, Site Head QA, [company name] and Unit Head, [company name]. The technical agreement will include the following but not limited to:
4.8.1 Consent letter duly signed by authorized signatories of both contract laboratory and [company name].
4.8.2 Name, Address, Phone number and e-mail ID of contact personnel.
4.8.3 The laboratory shall procure reagents / materials from their approved vendors. In critical issue [company name] can assist for the same.
4.8.4 The laboratory shall maintain reference standards / working standards as per pharmacopoeia / [company name]’s specification, if provided by [company name].
4.8.5 Analysis of the materials shall be carried out as per the specification and the method of analysis forwarded by [company name].
4.8.6 Cancellation of approval from regulatory authorities of the contract laboratory shall immediately be notified to [company name] by the contract laboratory.
4.8.7 Any deviation from the specification & method of analysis provided by [company name] shall require to be authorized by site Head QA of [company name] prior to carrying out the deviation.
4.8.8 Any Out of Specification (OOS) reported during analysis of the materials forwarded by [company name] shall immediately be intimated to Head QC at [company name] along with the raw data.
4.8.9 OOS observed at contract laboratory can be handled according to their procedure of handling OOS.
4.8.10 All specification, method of analysis and related documents provided by [company name] shall be treated as confidential. No photocopy shall be made and given to third party without authorization by Head QA of [company name]. Technical assistance can be provided by [company name] on need base.
4.8.11 The necessary analysis reports, raw data, chromatogram etc. shall be maintained by the contract laboratory. The entire document shall be reproduced as & when required by [company name]. However a photocopy of the spectrum / chromatogram shall be forwarded with every analytical report by the contract laboratory.
4.8.12 The COA shall be forwarded to [company name] duly approved by the authorized signatories of the contract laboratory preferably within 20 days of receipt of the sample.
4.8.13 The contract laboratory shall allow [company name] representative to audit the facilities as & when required in addition to yearly audit plan.
4.8.14 The contract laboratory shall not pass any of [company name] ’s samples to other outside laboratory for analysis.
4.8.15 The laboratory shall maintain all quality standards as per CGMP and will be auditable by any regulatory authority with respect to analysis of materials sent by [company name] with or without any prior notice. In the event of any complaint / product quality problem all investigation records to assess the quality of product shall be accessible to [company name] .
4.8.16 All information supplied by either party must be kept confidential and will not be disclosed to any other party without express permission of the counter party.
4.8.17 The agreement shall be valid for minimum of one year and require to be reviewed on last month of agreement due after compliance audit carried out by [company name] .
4.8.18 Any change in site of testing, instrument (used for analysis of [company name] ’s materials) or renovation shall be notified by the contract laboratory immediately. Decision to re-audit the facility shall be the discretion of Site Head QA.
4.9 Site Head QA shall be responsible for renewal, updation and cancellation of technical agreement.
4.10 Handling of samples to contract laboratory
4.10.1 Ensure that the updated technical agreement with the contract laboratory is available.
4.10.2 On receipt of specification / method of analysis for a material review the same by QC. List out any such test not possible to be carried out in the QC. In case of urgency, a sample can be sent to the contract laboratory on approval by Head QC.
4.10.3 The analyst shall label the sample with name of product/material, Batch Number, Batch size, manufacturer’s name, pharmacopoial status if applicable, quantity of sample, mfg. date, exp. date, storage condition etc. suitably packed so that the integrity of the sample is not effected.
4.10.4 The analyst shall prepare the analysis requisition slip as per Annexure-III
and non returnable gate pass mentioning the test details to be performed at the contract laboratory duly approved by Head QC.
4.10.5 Send the sample to the contract laboratory.
4.10.6 Enter the sample details sent to contract laboratory for analysis in the register as per Annexure-IV.
The Ref. No. in the analysis requisition slip shall the numbered as follows:
i.e. AAAA/YY where in,
AAAA: Serial Number. The serial number shall be continued irrespective of any specific contract laboratory.
YY: Last two digits of the current year.
4.10.7 On analysis the contract laboratory shall send the COA to [company name] with copies of chromatograms / spectrum duly signed.
4.10.8 The COA & chromatograms / spectrums received from the contract laboratory shall then be reviewed by site Head QC/ designee Stamp the COA as reviewed by QC at the bottom as per Annexure –V in violet colour and sign with date.
4.10.9 Attach COA and all other supporting documents received from the contract laboratory for a particular test of the material along with [company name] ’s COA of the material.
4.10.10 Update the register by QC meant for analysis in contract laboratory as per Annexure-IV.
4.10.11 Result of a test from contract laboratory shall be communicated in writing.No verbal communication shall be entertained in this regard.
4.10.12 Scan copy or Fax copy can be accepted in place of original one, duly signed by QC Head.
5 ANNEXURE (S)
Annexure – I: Audit Checklist (Contract Laboratory)
Annexure – II: Audit Planner for Contract Laboratory
Annexure – III: Analysis Requisition Slip
Annexure – IV: Details of Sample Sent to Contract Laboratory
Annexure – V: Sample Stamp
Annexure – I: Audit Checklist (Contract Laboratory)
Name and Address of Contract Laboratory
Any brochure available / not
Contact Person
Audit Date
Total Audit Hours
Audited By
Personnel of Contract Laboratory Involved during the Audit
Total No. of Analysts on site
Volume of analysis carried out each month (Average)
Name of some other clients, if available
Audit Observation:
Conclusion:
Comments / Explanation:
AUDIT CHECKLIST
1. Updated SOP List
2. List of latest compendia
3. List of Technical Persons
4. List of Instruments
5. List of Updated Specification / GTP / MOA
6. Organogram
7. Job Responsibilities of Key Personnel (Check for one / two persons randomly)
8. SOP on Training of personnel Check Training record of one analyst each in Chemical & Instrumental section.
9. Is the laboratory maintained in a good state of repair?
10. Is the laboratory neat and orderly with sufficient space for instruments & operation?
11. Is there an evidence of good housekeeping?
12. SOP of Out of Specification Investigation check record of OOS of [company name] materials.
13. Are all reagents and solutions clearly labeled with name, date of receipt, date of opening, use before date?
14. Are prepared solution labeled?
15. Is there an approved annual preventive maintenance (APM) program for all instruments available in the lab?
16. Is the person / agency carrying out APM qualified to do so?
17. Check for APM of major instruments in the laboratory e.g.
HPLC: ID No.
GC: ID No.
IR Spectrophotometer: ID No.
Dissolution Apparatus: ID No.
Any other:
18. Are calibration / APM methods / Processes defined? Does it provide for external calibration?
19. Is there any approved calibration schedule for all instruments? Check compliance. Is the frequency adequate?
20. Are standards used during calibration certified by an international / national recognized entity?
21. Are standard certificates available?
22. Is there a valid calibration sticker on each instrument?
23. Check SOP on operations, calibration and calibration record for major instruments in the lab e.g.
HPLC: ID No.
GC: ID No.
IR Spectrophotometer: ID No.
Dissolution Apparatus: ID No.
Any other:
24. Is there an SOP on corrective action in the event of OOC?
25. If any instrument is required to be sent outside for calibration / APM is any established procedure followed?
26. Is history card maintained for each instrument?
27. Is any control form used to include equipment in to the calibration / APM system to change frequency and to remove instrument from calibration / APM system?
28. Policy on glassware calibration
29. Cleaning verification of glassware
30. Check SOP on Glassware cleaning
31. Is there an SOP on sample management including receipt, recording, issuance for analysis, storage and destruction after analysis.
32. Is there an SOP on backup of electronic data acquisition e.g. HPLC etc. and its compliance
33. Check for 21 CFR Part II compliance for electronic data in case of HPLC etc. validation & security of computerized / automated processes
34. Whether instruments are in network & its security access
35. Validation of excel spreadsheet.
36. Check SOP on “Reference standard / working standard” management program
detailing sourcing, purity and assay, preparation of WS, qualification, storage and stability record for period of maximum storage. Check for current Lot No. of USP reference standard & storage condition.
37. Is there any SOP on CAPA?
38. Check analytical data for one RM & FP for the following:
• Tractability of all instruments used, calibration status, weight details.
• Adherence to written MOA
• Reference for preparation of mobile phase ( for HPLC analysis)
• Tractability of name of manufacturer, Lot No. & use before (if applicable) for all standards used in the analysis
• Reporting of results upto significant figure.
• System suitability checks on chromatographic system (e.g. GC / HPLC)
• Audit Trail
39. Temperature mapping of refrigerator including open / close door recovery study.
40. Storage of standards in case of malfunctioning of refrigerator
41. Check SOP and record for internal audit
42. Check SOP on “Reporting of Analytical results” & its compliance. (e.g. Rounding off, reporting up to significant no. etc.)
43. Check SOP on “Correction of Documentation error” & its compliance
44. Check SOP on “Documentation & Data Control” & its compliance (e.g. issue and control of updated approved worksheets)
45. Policy on storage & retrieval of analytical documents.
46. Are there persons designated to review and approve document changes / new documents?
47. SOP on Change Control, its compliance & closing. Check for records of last 6 months.
48. SOP on deviation / incidents & its compliance & closing. Check for records for last 6 months.
49. Documentation on reserve samples.
50. Procedure on qualification of instruments. Check IQ / OQ / of two major instruments.
Instrument ID No.
51. Adequate safety procedures available / not and its compliance.
52. Check availability and working of fume hoods, safety shower etc including periodic checks
53. Check storage condition for chemicals and its issue.
54. Other observation if any:
Annexure – II Audit Planner for Contract Laboratory
Frequency: Once in a year
Year: Month
Sr. No.
Name of Approved Contract Laboratory
Reviewed by:
Note: Audit of the respective contract laboratory shall require to be carried out within ± one month of the due month of audit.
Annexure – III Analysis requisition Slip
To,
Ref. No.
M/s.
Date
Please receive the samples for analysis as mentioned below:
Name of Sample:
Batch No:
A.R No.:
Batch Size :
Storage Condition :
Mfg. Date:
Exp. Date:
Manufacture /Supplier:
Quantity Of Sample:
Tests to be carried out:
Ref. Specification:
Ref. Method of Analysis:
Remark if any:
Prepared By:
Approved By:
Sample Received By/ Date(Contract Laboratory):
Annexure – IV QC Department
Details of Samples Sent to Contract Laboratory
Ref. No. of Sample / Date
Name of Sample
A. R. No.
Batch No.
Sample Sent to
Quantity of Sample
Test required to be carried out
Sign/Date by QC
Contract Laboratory Report No. / Date
Status (Approved / Rejected)
Head QC/ Designee
Sign / Date
Annexure – V: Sample Stamp
[Not provided here]