SOP for API Vendor Qualification

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It describes the (Standard Operating procedure) SOP for API Vendor Qualification

SOP for API Vendor Qualification

I. Purpose & Scope:

  • To provide a general methodology to be followed for API vendor Qualification
  • Applicable to all personnel who are working in Production, Quality control and quality Assurance Department

II. Responsibilities:

• Head- Operation, Head- Quality control ,Head-Purchase shall be responsible to follow and implement this SOP.

III : Introduction and Procedural Part :

IV. Selection of Vendors :

  • Head – Operation or Purchase shall be responsible for initiating the need for new vendors.
  • Head-Operation shall intimate Head-Purchase in coordination with QA to identify the vendors for required material, certification and specifications if applicable.
  • Head-Operation in consultation with Head-QA shall identify one or more prospective vendors of interest.
  • Head-Purchase shall request pre-purchase samples prospective vendors.
  • All the specifications of materials shall be provided to vendor by the purchase officer of materials department.

V. Evaluation of pre-purchase sample:

  • For APIs to be used in the manufacturing of finished product following procedure shall be employed:
  • Based on the requirement of grade of material, the vendor shall arrange to forward pre-purchase 03 independent batches samples to Purchase department along with their certificates of analysis.
  • Purchase shall send the Pre-purchase sample to QC along with Certificate of Analysis for complete evaluation. The samples should be accompanied by Standard Test Procedure (STP) or Working Standard etc., where applicable.
  • QC shall analyze the sample as per specification and convey the findings of analysis results to Head- QA. If sample does not meet the specification, stop the further qualification of vendor and inform to purchase.
  • Head-QA shall ensure that a unique code is assigned to these grades of APIs which reflects the uniqueness of the API, the materials grade, the supplier code.

 VI. Vendor Audit :

1.Head-QA in co-ordination with purchase shall plan and carry out the vendor audit wherever applicable to confirm the compliance level of GMP.

2.API Vendor audits are mandatory and not a choice for API for EU market

3.Selection criteria of vendors for audit :

  • Vendors who are having any of the accreditation from MOH (Ministry of health) such as Member Countries of EU, MHRA and USFDA also not more than two consignments rejected and CAPA closed with CAPA closure time frame for same material from last inspection, a minimum of one day audit shall suffice.
  • Vendors who are having any of the accreditation from MOH (Ministry of health) such as Member Countries of EU, MHRA and USFDA and there is rejection of more than two consignments from last inspection, a minimum of two days audit is mandatory.
  • Vendor who does not have any of the accreditation from MOH (Ministry of health) such as Member Countries of EU, MHRA and USFDA and having WHO, also not more than two consignments rejected and CAPA closed with CAPA closure time frame for same material from last inspection, a minimum of one day audit shall suffice .
  • Vendors who does not have any of the accreditation, there is rejection of more than two consignments from last inspection, a minimum of two days audit is mandatory.
  • If Vendor having multiple plants for different products at same site, a minimum of two days audit or two auditors for one day is mandatory.

4 .Head – QA or the designated person shall conduct the GMP audit prior to executing the validation batches as per the “Vendor Audit questionnaire”, but not limited to the same. Reference Format No.01.

5.The audit checklist, “Manufacturer assessment questionnaire for active pharmaceutical ingredients/ Excipients” shall be completed during site inspection. The checklist should reflect for what was checked, done and seen during the vendor audit such as Document number /SOP No. & its Version/Revision, Description of Current activity, Document review detail and its remark/conclusion etc. and same shall be recorded in the audit report to ensure that its full reflection & evaluation of site  which has been inspected.

6.It should be ensured that all the questionnaire is accompanied by, TSE (Transmissible Spongiform Encephalopathy), BSE (Bovine Spongiform Encephalopathy) and GMO (Genetically Modified Organism) , Genotoxic, Residual solvent statement, Residue Of Elemental Impurities and Nitrosamine’s Certification as per declaration deemed accepted in the vendor format.

7.After audit, Auditor will prepare audit report based on the ranking of audit observation, classify the observed deficiencies as critical, major and minor or comment. After classification of audit finding, Overall rating shall be finalized as Approved, Conditionally approved or not approved.

8.Wherever compliance report from the vendor is required, the same shall be intimated to the vendor and such report should be received preferably within 30 days from the receipt of audit report.

9.For APIs to be used in the manufacturing of other markets (Non-License products) i.e. markets wherein specific commitments on the particular manufacturer have not been made as a part of filing/registration commitment, the supplier shall be qualified on the basis of evaluation of data of pre-Purchase samples and/or successful evaluation of the supplier GMP questionnaire. Upon receipt of the completed vendor approval questionnaire, Head-QA shall review the questionnaire and based on their overall technical capabilities and quality system.

10.After receipt of audit compliance report, auditor in consultation with QA head shall take the decision for approval or rejection on the basis of vendor audit compliance report by entering CAPA evaluation details Satisfactory/require additional clarification in the remarks column of Audit report.

11.Vendor shall be considered as Approved if received CAPA compliance report is adequate. QA officer/Executive shall include the approved vendor’s details in specified format, “Addendum to Approved Vendor List for raw Materials” with following details,

  • Materials code and materials Name
  • Vendor code, Vendor Name and manufacturing site address
  • Supplier code, Supplier Name and Supplier address
  • Vendor included date
  • Included by (Sign/Date)

12.If CAPA compliance report require additional clarification, sent additional clarification details to vendor and ask for it clarification within 30 days through email. After receipt of clarification over sent requirement, if found satisfactory, follow procedure as mentioned for addition of vendor.

13.If the compliance report is adequate, the auditor shall classify the site as ‘Approved’ in the audit report and close the same. QA shall approve the vendor and update the Addendum to Approved Vendor’s List for Raw Materials.

14.If in case the compliance reported is inadequate, the auditor shall classify the site as ‘Not Approved’ in the report. QA shall be temporarily block the vendor as per procedure. However, a follow-up audit may also be planned based on review of the compliance report before taking the final decision on vendor.

15.A communication to this effect shall be given to the Purchase Department, Warehouse and Quality Control through email.

16.Approved API’s manufacturer shall be re-audited (Not more than six months from the audit due date) based on risk assessment, “Risk Assessment for API’s to determine re-inspection frequency”.

17.Audit frequency: Three years or determined re-inspection frequency.

18.Approved vendor in Addendum list shall be updated into “Approved Vendor List” once in a year or when required.

19.A current “Approved Vendor’s List” shall be maintained with Purchase, Warehouse and Quality assurance Departments.

20.Validity of GMP certificates shall be maintained in template as per specified format,Validity expired certificates shall be asked from manufacturer.

21.Approved vendor list of the API separately approved for “EU Market” and for “other market”

22.APIs from Vendor who are part of the “Approved Vendor list for “EU markets” can be approved for use in manufacturing of finished product for other markets. No deviation or change control for the same is required.

23.API from Vendor who is part of the “Approved Vendor list for other markets” cannot be approved for use in manufacturing of finished product for “EU market”.

VII. Vendor performance review

  • Approved vendors shall be re-evaluated annually.
  • Criteria to evaluate Vander based on rating and finding of observation like Vander shall be approved if.
                Classification Total No. of Finding (Observation) Evaluation
    Critical 02 Vander shall be approved and qualified
    Major 05
    Minor 10

               

                                                                                                                             

Format I

 

MANUFACTURER ASSESSMENT QUESTIONNAIRE FOR ACTIVE PHARMACEUTICAL INGREDIENTS/ EXCIPIENTS

 


GENERAL

1

 Company Name :  

2

 Company’s Detail Address/ Telephone Number / Fax Number / Email Address/ website Registered Office :  

 

3

 Company  Detail Address/Telephone Number / Fax Number / Email Address/ Website –   Works :  

 

 

        4

 Buildings, Facility and Surrounding :  

5

 How old is the facility and when was the last renovation? :  

6

 Persons responsible at manufacturer’s site    Names, designations

(For business / Quality )

 :  

7

 Material supplied/Synonym/Grade :  

8

 Date on which questionnaire is filled :  

         9

 Total number of employees (Total, Production, QC, QA etc) :  

10

 Does the company have other manufacturing facility? If yes, give the details of the same. :  
 11 Is Good Manufacturing practices (GMP) accreditation available for API? :  

 

 

 
 12 Does the manufacturer have a well-staffed quality organization and a quality control programme? :  
13 Does the manufacturer maintain adequate reserve stock to safeguard interruptions in the supply of materials? :  
14 Whether the material is TSE / BSE free and is certificate available? :  
15 Is the testing facility adequate? :  

     16

 Are job descriptions available? :  

17

 Health and hygienic requirement for personnel :  

18

 Is an organization chart available? :  

     19

 Range of products manufactured at this site.

 

 

 :  

 

 

 

 

PRODUCTS
     1 Short description of manufacturing process (flow chart) :  
     2 Is Drug Master File available (wherever applicable)? :  
     3 Is there a possibility of contamination of products/ intermediates due to: :  
o   Herbicides/ pesticides. :  
o   Environmental influences. :  
o   Ethylene oxide/ dioxane. :  
o   Aflatoxins / micotoxins. :  
o   Residual solvents. :  
o   Radioactivity. :  
o   Heavy metals :  
o   Antioxidants / preservatives. :  
o   Antibiotics. :  
o   Hormones. :  
o   Others :  
     4 Regarding possible contamination, have relevant investigations been performed? :  
     5 Container closure used for final packaging? :  
     6 What shelf life is recommended? :  
     7 Are there any special storage instructions? :  
     8 Is documentation available for stability in the chosen packing? :  
     9 Assessment of polymorphism based on literature and experimental evidence if polymorphs exist provides standards, methods and specifications. :  
 10 Particle size and bulk density specifications :  
 11 Material safety Data sheet of the product. :  
 12 Status of Synthesis (Pilot, Scale up, validation). :  
 13 From the receipt of order what is the typical lead time to supply? :
 14 Which element is the major factor in the overall lead-time? :
STORES
     1 Do you maintain Warehouse Procedures? :  
     2 Are there pest control program available? :  
     3 Are there access restrictions? :  
     4 System for receipt of material and allocated location :  
     5 When starting materials are received, are the labels on the containers compared with delivery notes? :  
     6 Do you accept vendor certificate of analysis with each receipt of incoming starting materials? :  
     7 System for Material Storage and Handling including quarantine. :  
     8 Is FIFO or FEFO been followed? :  
     9 System for labeling of Consignment :  
 10 System for Dispensing of material :  
 11 Method & recording of Balance Calibration? :  
 12 Is there a documented stock control system for all raw materials? :  
 13 Brief description on Segregation and Stacking norms :  
 14 Do you maintain Temperature, Humidity and Cleaning Logs :  
 15 Do you maintain Rejected Material Storage / Control under lock and key? :  
 16 Do you maintain Sampling areas and container sealing under lock and key? :  
PRODUCTION
    1 Are the following available:

(a)     AHU / Air conditioning

(b)     Access restrictions

  

:

:

 

  
    2 Single or multipurpose facility? :

 

  
    3 For Multipurpose facility:

(a)   Which classes of substances are

Produced?  (Attach a list, if

necessary)

(b)  Any highly active classes of

Substances are produced?

(c)  Do the production documents

contain information about the

previous product?

 :

 

:

 

:

 

:

 

  
    4 Can the manufacturer plant and machinery produce material at the required rate ? :

 

  
    5 Is Line Clearance for Product change over followed? :  
    6 How product is defined, lot / batch number? :
    7 How is Cross contamination avoided? :
8 How are lubricants and other non production materials properly controlled to prevent product contamination? :
    9 Are there written specification and sampling plans to control in process materials? :
10 Are the results of in process controls and of preliminary analysis recorded? :
11 If in process material is rejected, is there documentation of the action taken? :
12 Does the manufacturing record contained the following particulars :

(a)  Name of product.

(b)   Batch number, Batch size and yield

(c)    Equipment used and place of

manufacturing.

(d)   Name and signature of directly responsible supervisor and operator

(e)    List of Raw Materials

(f)    Description of work carried out.

(g)   Reference to actual manufacturing procedure

(h)   Results of in process control

(i)     Signature to confirm accuracy and completeness of record.

  

 

:

:

 

:

 

:

 

 

:

:

:

 

:

:

 
13 Are log books kept for critical equipments? :
14 Is Labeling of material and equipment at various stages of manufacture practiced? :
15 Is Qualification of key production equipment performed periodically? :
16 Are your Utilities – Service line coded with indication of direction? :
17 Is your areas properly segregated to prevent cross-contamination? :
18 Is yield limit at each stage of manufacturing steps are specified? What action do you take in case of out of limit? :
19 Do you have a plan to monitor water quality? What is the frequency for monitoring water quality? :
20 How do you handle disposal of residues and waste? :
21 Procedures for cleaning of equipment for same batch/product / change of products        and records for cleaning?  
22 Does your facility designed with Controlled ventilation systems for final stages of manufacturing? If yes, filter rating? :  

 

 
23 Are rejected materials investigated and subjected to reprocessing by viable methods? :
24 Do you follow any special dress coding for manufacturing areas, testing areas and warehouse area? :
25 Are key gauges and process equipment calibrated? :
26 Are the final inspection / test results recorded for each production batch/lot? :
27 Segregation of non-conforming final product from other materials. :
28 Are the shipping containers sufficiently marked to identify the contents or items with shelf life? :
29 Retest period recommendation of formal stability data. :
30 Are procedures for preventive maintenance of manufacturing equipment available? :
31 Does there an emergency plan exist? :
32 Are the manufacturing personnel suitably trained in Good Manufacturing Practices? :
QUALITY CONTROL
1. Is adequate area for laboratory provided? :
2. Are Quality Control procedures available? :
3. List down the instruments available in the laboratory? :
4. Do you maintain Adequate Specifications / Pharmacopoeias / Reference books? :
5. Whether Adequate Staff / Qualifications / Experience is available? :
6. Whether Adequate Staff Training is available? :
7. Is Quality Control Independent of Production for decision making :
8. Are there written instructions for sampling? :
9. Are the following starting materials analyzed:

(a) Raw material

(b)   Packing material

(c)    Solvents

(d)   Catalysts,

(e)   Filtration aids e.g.: Charcoal,    Celite

(f)   Water

 :
10. Reference standard/ working standard with full characteristic report (Certificate of analysis, UV, IR, NMR mass spectra etc) :
11. Do you maintain stock card of Reference Standards/ Working Standards? :
12. Do you validate the Working standards with reference to Reference Standards?  
13. What is the frequency for Calibration of instruments / equipments? Is it done by In-house Engineering or by contract vendor? :
14. Does all apparatus bear a status label with details for calibration? :
15. Incase the calibration perform by external services, is there an external review / approval of data? :
16. Validation programs for methods/ instruments/ personnel? :
17. Reagent control with respect to labeling / expiration / signature/date? :
18. Are COAs issued by Quality Control? Are they signed by Quality Control person? Who is authorized person? :
19. Is microbial monitoring performed on a regular basis?

(a)   Starting materials?

(b)   Products?

(c)   Air , floor, walls, machines /

Equipment?

(d)        Water

(e)        Personnel

 :
20. Does your company has own laboratory for microbial testing? :
21. Brief on Stability program :
22. Documentation of results of analysis (Report checking done by second person) :
23. Do you perform full qualitative – quantitative testing of raw materials prior to release use in production. :
24. Whether products are tested in own laboratory or tested in public testing laboratories, if so copies of test reports of 3 batches to be submitted :
25. Is there any written microbial monitoring program for sterile or non-sterile products :
26. Do you have an Out Of Specification (OOS) procedure? Whether it is followed? :
27. Residual solvents :

Solvents used in manufacturing apart from Organic volatile impurities (OVI)  are estimated and comply with the limits

 :
28. Data integrity :
QUALITY ASSURANCE
1. Have you implemented a Quality Assurance system in your firm?

 

 :
2. Are there Internal GMP audits / Self Inspection program available? What is the frequency of internal audit?

If “yes” are the audits recorded?

Is the internal auditor independent of the area being audited?

 

 :
3. Is there Quality Assurance manual available? :
4. Who is responsible for Batch release? Is procedure available? :
5. Is document and data control adequate? :
6. Do you have a procedure for Handling of Out of Standard / Non Compliance /Deviation? Is it notified to the customers? :
7. Do you have procedure for Review of product failure, if any? Is it reported to the customers? :
8. Is there any procedure for handling of product complaints? :
9. Are there documented crisis management (e.g. product recall) procedures? :
10. Is there any Master validation plan available? :
11. Have all the manufacturing processes been validated to address the following

(a)  Demonstrated that the product        specification, acceptance requirements can be consistently        satisfied?

 :
12. Do you have Change control procedure? How do you notify the changes to the customer? :
13. How do you track Training of new / existing technical staff? :
14. How do you approve a manufacturer? :
15. How long and where the batch documents kept including manufacturing instructions, records and test instructions, records? :
16. Does the factory have a formal product risk assessment procedure?   If “yes” is there a written assessment for all product types? :
17. System of information to customers on critical changes before implementation

 

 :

 

OTHER OBSERVATION
 

 

 

 

 

 

 

 

 
SUMMARY OF AUDIT:
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
RECOMMENDATIONS / ACTION REQUIRED:
 

 

 

 

 

 

 

 

 

 

 
Follow up CAPA Required :       □    Yes          □    No

Suggested Time-frame: ……………………………………………………………
Auditor (Designation/Sign/Date) Approval of Audit report (QA head sign/Date)
 

 

 

 

 

 

QUALITY EVALUATION: This section to be completed by “Auditor Company Quality Assurance. Based on the information provided in this evaluation, QA recommends

 

[   ] Supplier site acceptable.  No site audit or follow-up necessary.
[   ] Conditional approval only.  Additional follow-up required (see comments below)
[   ] Site audit recommended.  (See comments below)
[   ] Use not authorized.
Corrective Action And Preventive Action Tracking (For Auditor company QA only)
Observation report

sent on

 CAPA received

on

 Verified by

(Sign and Date)

 Remarks
Auditor (Designation/Sign/Date) Approval of Audit report (QA head sign/Date)

                     Format II 

              VENDOR’S AUDIT FORMAT

 

  VENDOR
  Name & Address:

 

 

 

 
 
  • Manufacturer
  • Dosage Form
  • API
  • Excipients
 Packer

………………………………….

………………………………….

………………………………….

 Other (please specify)

…………………………………………

…………………………………………

………………………………………….
  MANUFACTURING LOCATION (if different from other)
  Audit Dates :
  Nature of Audit Prospective Source / Current source / Identified Complaint Investigation Audit  / Routine Audit:
  Identified Complaint Investigation Audit :  State nature of problem(S):

 
  Audited by (Name & Designation) :
  Auditor Contact Details E-mail:

Mobile Tel No:
  MATERIALS / COMPONENTS OR SERVICE SUPPLIED BY VENDOR:
   

………………………………………………………………………………………………………….
  DMF / UK-MHRA / EDQM / US FDA / TGA  / WHO ETC ACCREDITATION No:

 

………………………………………………………………………………………………………….
  OTHER MATERIALS MANUFACTURED AT THE SITE:
   

………………………………………………………………………………………………………….
  Approximate percentage of business for the pharmaceutical industry  
  Total number of personnel on site  
  PERSONNEL INVOLVED DURING AUDIT (NAMES & POSITION)
   

(1)  …………………………………………………………              ………………………………….

(2)  …………………………………………………………              ………………………………….

(3)  …………………………………………………………              …………………………………

(4)  …………………………………………………………              ………………………………….
  ADDITIONAL COMMENTS/NOTES (if any):
   

………………………………………………………………………………………………………………..

…………………………………………………………………………………………………….……..…..

………………………………………………………………………………………………………….……

 
WAREHOUSING  
□  Raw Materials  □   Finished Goods   □   Sampling   □   Temperature Monitoring / Storage □  Quarantine    □Solvents  □   Reject   □ Pest control   □    Transport Validation   □  Handling Rejected Materials  
Observations:

…………………………………………………………………………………………….……………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

…………………………………………………………………………………………………………………

…………………………………………………………………………………………………………………

 

(Signature/Date) ……………………………………………………

  
 
QUALITY ASSURANCE		  
  □   Training  □    Personnel  □   Complaints  □  Quality Systems  □   Vendor Approval Process

□   Change Control  □  Risk Assessment  □  Validation  □ Qualification □ Self Inspection

  
  Observations:

…………………………………………………………………………………………….……………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

(Signature/Date) ……………………….………………………………………………………

  
 
PRODUCTION		  
  □   Entry-exit or Gowning   □   Process   □   Housekeeping   □  Environment Monitoring   □  Segregation

□   Documentation (BMR/BPR)  □   Cleaning   □   Equipment   □  Material Flow

  
  Observations:

…………………………………………………………………………………………….……………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

(Signature/Date) ……………………….………………………………………………………

  
  QUALITY CONTROL  
  □   Equipment □   Facilities   □   Validation   □  Calibration   □   Reference Standards

□   Stability  □   Certificate of Analysis   □    Retained Samples   □     Documentation e.g. Specifications and Methods  □   Product Release Criteria   □ Microbiology  □   AQL

□   Rejection   □    Quality Review

  
  Observations:

…………………………………………………………………………………………….……………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

(Signature/Date) ……………………….………………………………………………………

  
 
FACILITY		  
  □   HVAC System   □    Water System  □   Vacuum  □  Compressed Air  □   Gases □   HSE  
  Observations:

…………………………………………………………………………………………….……………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

(Signature/Date) ……………………….………………………………………………………

  
  MISCELLANEOUS  
  Observations:

…………………………………………………………………………………………….……………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

………………………………………………………………………………………………………………..

(Signature/Date) ……………………….………………………………………………………

  
  SUMMARY OF AUDIT  
  Summary:

……………………………………………………………………………………………………………….

……………………………………………………………………………………………………….………

……………………………………………………………………………………………………………….

……………………………………………………………………………………………………………….

……………………………………………………………………………………………………………….

……………………………………………………………………………………………………………….

  
  Recommendations / Action Required (if any):

……………………………………………………………………………………………………………….

……………………………………………………………………………………………………………….

……………………………………………………………………………………………………………….

……………………………………………………………………………………………………………….

  
  CAPA Follow up Audit Required :       □    Yes                 □     No

Suggested Time-frame:

…………………………………………………………………………………

  
   

 

Auditor’s Name: ………………………………………………….

Signature: …………………………………

Date: ………………………………………

  

 

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