Vendor Audit & Qualification Management Procedure

Vendor Audit is an evaluation of vendor’s manufacturing site, for product of interest(s), for the understanding and application of the cGMP. Successful evaluation of Vendor’s ability and capability in meeting the company’s quality system requirements in relation to the criteria established for the material being sourced.

Vendor Audit and Qualification Guideline

1.0   Objective :

• • To lay down a procedure for vendor selection, audit / evaluation, Qualification, Disqualification and Requalification of raw materials.

2.0   Scope :

• • This SOP is applicable for qualification & evaluation of vendors of raw materials to be used in the Drug Products manufacturing.

3.0   Responsibility – Vendor Audit & Management:

Head Purchase / Designee –	:	Identification of potential vendors in co-ordination with the Product Development Laboratory. Responsible for arrangement of pre-purchase samples from the prospective vendors of raw materials. To coordinate with vendor for vendor approval activity. To provide specification to the manufacturer or supplier Scheduling of vendor audit date and compliance report from vendors. To coordinate with vendor for investigation / CAPA for on-line rejection. To forward vendor questionnaire to the vendor. Shall organize Vendor audit based on the need identified by the quality assurance department.
Production	:	To assist purchase department in the identification process of the prospective vendors.
Head R&D/Head QC / Designee	:	To Evaluate the pre-purchase samples from prospective vendor and making decision whether to recommend the vendor or not based on the sample evaluation. Preparation of Analytical test Report and submitting results to QA as per VSR. Preparation of specifications and testing procedures.
Head QA / Designee	:	To forward Vendor Questionnaire to the vendor through purchase or direct and evaluate the completed one. Evaluate / audit the vendor for cGMP compliance. To create item code in ECOM if not available. To qualify vendor and to maintain approved vendor list. Preparation and distribution of vendor audit schedule to purchase.

4.0   Procedure – Vendor Audit & Qualification:

• • Definitions:

• • Vendor Audit:

• • A vendor qualification process involve in the site inspection to evaluate the capability of vendor to produce quality products.

• • Critical Observation:

• • Observation / deficiency, which has produced or lead to a significant risk of producing a product, which is harmful to the patient.

• • Major Observation:

• • A non-critical observation/deficiency that may produce a drug not meeting to the marketing authorization or any observation that could have an indirect potential impact on the safety, purity, or efficacy of the drug substance/product.

• • Minor observations:

• • Observations that cannot be classified as either critical or major but which indicates a departure from GMP.

• • Manufacturer:

• • Manufacturer is a producer of materials at his manufacturing site and supplies it either directly or through supplier.

• • Supplier:

• • Supplier is a trader, supplying materials in original manufacturer pack.

• • Vendor:

• • A terminology used to represent both manufacturer as well as supplier to handle overall material management process.

• • Vendor Qualification:

• • A process of screening to identified vendors for their evaluation and approval after verification of their capability to produce and supply quality materials.

• • Vendor Management:

• • A process to control overall material management, which includes manufacturer as well as supplier and material performance to meet marketing authorization/ regulatory commitments.

• • Vendor Audit Schedule:

• • A calendar to plan vendor audit which to be performed throughout a year.

• • Approved Vendor List:

• • A list of qualified vendor with material code, Pharmacopoeial status, manufacturer code, vendor code and storage condition.

• • Blocking:

• • It is a temporary deactivation of vendor for material procurement in software with reason.

• • Unblocking:

• • It is reactivation of vendor for material procurement.

• • Delisting:

• • It is removal of vendor from vendor list.

• • Relisting:

• • It is re-inclusion of vendor in vendor list.

• Vendor Qualification:

• • New material from new Vendor / an existing Vendor.

• • Existing material from new Vendor

• • Change in manufacturing site of Vendor

• • Routine (periodic) requalification of Vendor

• • Resumption of supplies after a gap of 3 years or more

• • To re-evaluate delisted Vendors.

• Selection of Vendor:

• • All existing Vendors who have already been approved shall continue as Approved Vendors.

• • Production in co-ordination with Head QA shall be responsible for initiating the need for new vendors.

• • Production in co-ordination with Purchase shall identify the vendors for required material, certification and specifications if applicable.

• • Purchase shall provide the information on prospective vendors to Product Development Laboratory meeting the requirements.

• • Production in consultation with Head / Designee -QA shall identify one or more prospective vendors of interest and Production shall send specification to prospective vendor.

• Assessment of Pre-purchase samples:

• • Based on the agreed specification and technical discussion, the vendor shall arrange to forward pre-purchase samples (3 independent lots), to purchase department along with their certificates of analysis.

• • Purchase department shall forward the sample to R&D/QC.

• • Samples can be evaluated by manufacturing site QC.
  • The samples shall be accompanied by Standard Test procedure or Working Standard etc., where applicable.

• • R&D/QC shall analyze the sample as per specification.

• • If any clarification is needed, then they may contact the vendor for further details.

• • Head R&D/Head/Designee QC, based on the COA, shall finally evaluate sample performance.

• • When the material meets / does not meet the requirements, R&D/QC shall convey the findings to
    Head QA /Designee through Vendor Suitability Report.

• • If vendor is suitable, Purchase / QA shall send the “Vendor Evaluation Questionnaire (Manufacturer)” to the vendor directly.

• • In case a Vendor have their own Broachers / Standard template (self assessment report) having similar information (equivalent to) Annexure I, can be accepted.

• • Upon receipt of the completed “Vendor Evaluation Questionnaire (Manufacturer)”, Head/ Designee
    QA shall review the questionnaire based on their overall technical capabilities and quality system.

• • It shall be ensured that all questionnaires are accompanied by TSE (Transmissible Spongiform
    Encephalopathy) and BSE (Bovine Spongiform Encephalopathy) statement.

• • All the materials shall be free from TSE/BSE risk.

• • In specific situation, such as suitability through stability evaluation or trial is foreseen then, the
    vendors shall be approved as provisional vendor.

• • If Sample evaluation report and adequacy in GMP Questionnaire found as per the standard of Concept then Vendor shall be approved and added in Approved Vendor List.

• • In case there is inadequacy in either Sample evaluation or in the quality standard as stated in Vendor Questionnaire then Vendor shall be rejected by Head/Designee QA.

• • DMF shall be requested for regulated markets if applicable.

• • If the sample of three batches are not provided by the vendor, COA of three batches shall be reviewed.

• Active Pharmaceutical Ingredients (API):

• • Based on the evaluation of sample, completed Vendor Questionnaire ( Manufacturer ), their overall technical capabilities and quality system, Head/Designee-QA shall recommend the vendor as follows:

• • Class A:

• • The API manufacturer having CEP, US DMF or EU DMF and/or have an approval from regulatory bodies (EU, MHRA, USFDA, TGA, MCC, TPD) of their manufacturing facilities, the manufacturer to be incorporated into “Approved Vendor List” for domestic market by QA.

• • Class B:

• • The API manufacturers do not have the approval from the Regulatory bodies, but have the satisfactory vendor questionnaire and technical documents.

• • These Vendors shall be added in approved vendor list for domestic market.

• • Based on the risk assessment vendor audit may be planned for these manufacturer before commercialization of the batch.

• • Class C:

• • Vendor not found acceptable based on the response of the questionnaire and thus rejected.

• • Any waiver from the requirements as explained above shall be taken only after prior approval from Head/Designee- QA and the reason for that shall be documented on completed vendor questionnaire or a separate deviation report needs to be filled.

• • Narcotics, controlled APIs or APIs appearing in restricted schedule shall qualify for the waiver of this kind.

• • Selection of Vendor for Excipients:

• • Upon receipt of the completed “Vendor Evaluation Questionnaire (Manufacturer)”, Head QA/Designee shall review the questionnaire.

• • Based on overall technical capabilities and quality system, the vendors shall be added in Approved Vendor list.

• • It shall be ensured that all the questionnaire is accompanied by, TSE (Transmissible Spongiform Encephalopathy) & BSE (Bovine Spongiform Encephalopathy) and GMO (Genetically Modified Organism) statement.

• • Excipients Vendor shall be audited based on following criteria

• • • Rejection due to non-compliance at receipt stage.

• • • Risk based vendor audit e.g. Microbiological Risk or TSE/BSE Risk.

• • • Any other quality problems.

• • • Low quality scoring

• • Selection of Vendors:

• • Purchase shall forward the Vendor Evaluation Questionnaire (Supplier).

• • After receipt, purchase department shall forward these questionnaires to QA for evaluation.

• • Head QA/Designee shall review the questionnaire and based on their overall technical capabilities and quality system, Head QA/Designee shall approve the supplier.

• • It shall be ensured that all the questionnaire is accompanied by, TSE (Transmissible Spongiform Encephalopathy) & BSE (Bovine Spongiform Encephalopathy) certificates.

• • In case of contract manufacturing, the responsibility of vendor approval will be lying with contract giver unless it is clearly mentioned in the contract / technical / Quality agreement.

• • Contract giver shall submit a declaration about their Vendor approval status and a copy of TSE/BSE declarations.

• Vendor Audit Criteria:

• • A Vendor which is certified by contract giver shall be exempted from site inspection or the terms & conditions of signed contract agreement shall be followed.

• • Where a re-qualification of Vendor is due and the drug product (filled Dossier/ANDA) is under approval shall be audited after receipt of regulatory approval and before commencing of commercial /exhibit / submission batches.

• • Suspended/ disqualified Vendors shall be re-qualified only after submission of previous compliance and commitment from the management of Vendor.

• • Quality audit (vendor) of excipients manufacturer shall be based on the low quality scoring.

• • Vendor those not ready to accept the audit for site, the undertaking shall be taken from respective vendors.

• • Vendors, those are not getting frequent order shall be approved based on the vendor questionnaire.

• Vendor audit Plan:

• • Purchase department shall schedule for inspection date in coordination with manufacturer/ supplier and inform to QA.

• • If an audit (vendor) is not feasible by location QA, QA may assign it to other location’s head QA / designee or may outsource a reputed / competent agency for it.

• • Technical competencies and capability of outsourced agency shall be evaluated in accordance with procedure” Handling of external agencies”.

• • If any deviations from the above systems identified shall be recorded and justification shall be documented.

• • These documents shall be put in respective Vendor files.

• • Types of Vendor Audits :

• • Vendor audits are classified in three categories i.e. Planned, Prospective and Cause Based Audit.

• • Vendor audit shall be conducted by authorized and qualified auditors.

• • Planned  Vendor Audit:

• • A planned vendor audit is applicable to re-qualification of existing qualified Vendors as per planned audit schedule.

• • Prospective Vendor Audit:

• • A prospective audit is applicable to new qualification of Vendors either for a new materials or alternate Vendor.

• • Cause based Vendor Audit :

• • An audit triggered based on certain reasons / assumption about material or product to investigate any failure or a repeat audit if recommended in planned / prospective vendor audit as remediation verification.

• • Planned Vendor Audit schedule:

• • Planed vendor audit schedule shall be prepared/approved by QA for re-qualification of approved Vendors.

• • A schedule shall be prepared and updated .

• • Addendum shall be enclosed along with vendor audit schedule for new introduction.

• • Planned audit schedule shall have version controlled and be approved  by QA

• • Any deviation (+90 days) from the approved annual vendor audit schedule shall be addressed through deviation.

• • Copy of planned vendor audit schedule shall be issued to purchase department.

• • Other needs base vendor audits (Prospective / cause based) shall be documented for records.

• • Auditor’s qualification:

• • An auditors should posses a minimum qualification up to graduate level with one of subject as chemistry, pharmacy, microbiology, biochemistry, chemical engineering, pharmaceutical engineering, and pharmaceutics having experience of more than 8 years.

• • An Auditor shall be trained by qualified auditors on practical aspect of audit of API manufactures and certified by senior auditor / Head QA to conduct independent audit.

• • List of qualified auditors shall be maintained.

• • Disqualification of qualified auditor:

• • An auditor shall be disqualified if:

• • • Change in responsibilities

• • • Incompetency in auditing

• • • Fraudulent behavior

• • Vendor audit procedure and approval:

• • Auditor shall inspect the Vendor site to evaluate GMP compliance level.

• • A general step are listed below (But not limited to):

• • • Opening meeting with Vendor’s management team

• • • Discussion on scope of vendor audit

• • • Facility tour

• • • Quality management review (man, material, procedure, facility, equipment, laboratory controls, production / packaging / labeling engineering control etc).

• • • Discussion on vendor audit deficiencies and closing meetings.

• • • Guidance document for Vendor audit shall be referred during audit.

• • • Compliance to TSE/BSE free declaration and probability of other contamination shall be verified.

• • • Scope of vendor audit to be determined as per applicable regulatory requirement of Country.

• • • ICH Q7 shall be referred for Vendor audit.

• • • Vendor Audit deficiencies (non-compliance) shall be classified as critical, major and minor and recommendations.

• • • In the audit, if any critical deficiency is noticed, shall be immediately notified to the senior management (Quality / Purchase Heads) and vendor and vendor shall be disqualified.

• • • Vendor shall submit an immediate (within 1 to 7 days based on severity) CAPA on critical deficiency.

• • • A risk shall be assessed for the material used in product or available unused stock of material at manufacturing sites either to use further or recall of products or to reject available quantity in stock.

• • • A detailed vendor audit report shall be prepared mentioning area audited i.e. general information of vendor, observations (deficiencies) recorded, product, summary, recommendation etc. and send within 30 calendar days to vendor.

• • • A timelines for response shall be assigned in the report.

• • • Unless, no critical observations are classified, a compliance report shall be asked within 30 calendar days.

• • • Vendor Audit report shall be forwarded to vendor and purchase department.

• • • Purchase department / QA shall ensure that compliance to the vendor audit report shall be submitted by the vendor within stipulated timelines.

• • • If compliance report is not been received within stipulated timeline a vendor may be blocked in software.

• • • Upon receipt of compliance report from vendor, shall be evaluated either by auditor or designee and take the decision for approval or rejection of vendor based on facts / compliance response.

• • • An auditor may recommend approval of vendor, if there is no Critical and Major deficiencies are cited.

• • Upon satisfactory compliance of deficiencies, “Vendor Approval / Rejection Certificate” shall be issued to purchase and store and vendor audit closure report shall be forwarded to the Vendor.

• • Purchase department shall forward current specifications of materials to vendor in advance or with Purchase order.

Note: Incase material received at plant location with vendor’s corporate address instead of actual manufacturing site address, a declaration shall be taken from the vendor with the reason/justification for the same and shall be filed in QA.

• • Overseas vendors shall be evaluated on Questionnaire basis, if evaluation found satisfactory same shall be approved.

• Provisional Vendors:

• • A provisional vendor may be restricted either for a total quantity of or for specific time or both.

• • The system will not allow either to generate a purchase order or to make a “goods received notes” for more than quantity or consignment restricted in the system.

• • Details of provisional vendors shall be kept along with vendor list and shall be reviewed by QA.

• Approved Vendor List:

  • Based on the evaluation of vendor questionnaire and audit (if done) and its compliance, a provisional vendor shall be qualified as “Approved vendor” and same to include in “Approved vendor list” through change control system.

• • Existing vendor, where vendor audit is not necessary, based on risk assessment vendor shall be re-qualified after completion of documentary compliance (Vendor questionnaire and subsequent document evaluation) and the same shall be included in “Approved vendor list”.

• • The approved vendor list shall be updated at-least once in a six month, if there any change, or whenever required.

• • If there is any addition of new vendor within six months, the store and purchase shall be informed through annexure V and shall be kept along with approved vendor list.

• • Approved Vendor List can be visualized in software.

• Existing vendor with New Material:

• • If existing qualified vendor is offering new material, then they may be exempted from vendor audit incase the manufacturing stream (site and block) is already approved by plant.

• • After evaluation of material suitability w.r.t. to product and such new material shall route through new material introduction.
  • Vendor shall submit a Self – assessment report/ Vendor questionnaire along with necessary documentation for GMP certification, shelf life declaration or Stability data, Residual Solvents certification, Gluten free certificate (where applicable), impurity profile data, DMF/technical dossier shall be requested from the vendor.

• • QA shall review the material related documents and on satisfactory finding of the review, material can be part of approved vendor list based on the justification.

• • This new material shall be covered in the next planned vendor audit schedule.

• Re- qualification of a Vendor:

• • The frequency of Vendor re-qualification shall be decided based on risk assessment of individual vendor i.e. based on the previous history of vendor audits etc.

• • Vendors shall be re-qualified periodically i.e. every 3 years ± 3 Months.

• • TSE/BSE certificates shall be reviewed every three years.

• • Re- audit shall be completed before the due date or as per agreed date given by vendor; Requalification of vendor shall be done as mentioned below.

• • • Either through an on-site inspection or, on submission of recent quality systems certification by an officially accredited body; or

• • • Through self-assessment report submitted by the vendor with a declaration for no change in the manufacturing process, key starting material and its source, solvent profile etc.

• • Blocking of Vendor:

• • Head QA / Designee shall block the disqualified vendors or any vendor in software so that PO cannot be issued to the vendor.

• • Disqualification of a Vendor

• • Disqualification of vendor shall be performed through change control under the following circumstances.

• • • If material rejected on any quality aspect three times a year.

• • • Supply of contaminated materials, which cause adverse impact on product quality.

• • • Inability of a vendor to comply with the gaps identified during vendor audit and frequent rejections which have serious impact on the product quality.

• • • The information regarding disqualification shall be communicated to the vendor, Purchase department, relevant QP, Production & Product Development Laboratory.

• Re-qualification of disqualified vendor:

• • A disqualified vendor shall be re-qualified by satisfactory evaluation of vendor questionnaire followed by vendor audit and satisfactory evaluation of compliances.

• • The re-qualification process shall be routed through a change control system.

• • Re-qualification shall be done after change control approval.

• • Re-qualification of disqualified vendor shall be communicated to relevant QP.

Remark: If USR is prepared by manufacturing site than USR shall be approved and Renewed by Head QA.

5.0   Reference (S)

ICH Guidelines	:	Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
WHO TRS 908	:	Annex- 4 ,Good Manufacturing Practices for pharmaceutical products: main principles
PIC/S	:	Guide To Good Manufacturing Practice For Medicinal Products PART  I & II    (PE 009-11 )

6.0   Glossary

SOP	:	Standard Operating procedure
CAPA	:	Corrective and Preventive Action
cGMP	:	Current Good Manufacturing Practices
DMF	:	Drug Master File
VSR	:	Vendor Suitability Report
ANDA	:	Abbreviated New Drug Application
CTD	:	Common Technical Document
API	:	Active pharmaceutical Ingredient
CEP	:	Certificate of Suitability
QP	:	Qualified Person
ICH	:	International Conference on Harmonization
WHO	:	World Health Organization
TSE	:	Transmissible Spongiform Encepahalopathy
BSE	:	Bovine Spongiform Encepahlopathy
R & D	:	Research & Development
QC	:	Quality Control
COA	:	Certificate of Analysis
PO	:	Purchase Order
QP	:	Qualified Person
MOA	:	Method of Analysis
AVL	:	Approved Vendor List
QA	:	Quality Assurance
US	:	United state
USFDA	:	United States Food and Drug Administration
MHRA	:	Medicines and Healthcare Products Regulatory Agency
MCC	:	Medicine Control Council
TPD	:	Therapeutic Products Directorate
COS	:	Certificates of Suitability
GMO	:	Genetically Modified Organism
TGA	:	Therapeutic Goods Administration
PIC/S	:	Pharmaceutical Inspection Co-operation Scheme

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