This article outlines the process involved in the qualification of vendor
1.0 Introduction
Manufacturing of drug substances involve good manufacturing practices so that the patients are confident in terms of safety, efficacy and quality of the medicines. Thus Vendor qualification ensures that drug being supplied is according to the specifications in terms of identity, strength, purity, quality and consistent from batch to batch. It ensures that drug substance is in compliance with GMP and within acceptable limits for impurities and contaminants. Many cases of supply of improper goods have created the need to select a supplier who can deliver the intended product in accordance with the specifications.
The guidelines given are for the materials which are classified as follows
Critical & Non critical raw materials
Intermediates
APIs
1.1 Management of Vendors or suppliers
Best Practice for management of vendors or suppliers can be done by the following steps
Supplier selection
Due diligence
Assessment of quality among the suppliers
Assessment of change control
Management of security in the supply chain
Monitoring and evaluation
1.1.1 Supplier selection
Initially when a supplier is selected then the following details are to be taken
Product name with formulae & CAS
Specification of materials
Required quantity
i) Questionnaire designed for the supplier should include the following information:
Specifications and details of manufacturing or packaging or labeling
Safety data sheet of materials
Logistics information
Certificates of quality system and residual solvents
Analytical test methods
BSE or TSE method
ii) For the Critical & Non critical raw materials, registered Intermediates and APIs the following should be assessed:
Supply assurance
Suppling in compliance with quality & regulatory aspects
Procurement and cost
Innovation or technical aspects
Communication and responsiveness capability
The data collected for the Critical raw materials, Intermediates and APIs should be assessed by team personnel from various departments.
Quality assessment of non-critical raw materials is determined by the suitability of the supplier. A positive outcome indicates the supplier selection is completed
1.1.2 Due diligence
This step in not applicable for non-critical raw materials
Due diligence for Critical raw materials, Intermediates and APIs is done in accordance with ICH Q9 guidelines based on risk assessment
Documented evidence will decide the result as to go or no go decision process
Here the long term relationship with the supplier will be evaluated
i) Based on the following criteria the assessment is done
Process, equipment, facility containment, utilities quality, availability of analytical equipment with stability chambers
Ability to prepare regulatory submissions
Analytical method validation and development
ii) Personnel
The team for evaluation should include personnel from various departments like procurement, quality, project management, engineering, and safety, regulatory and technical experts
iii) Areas to consider
a) Information
General material information should be available on purity profiles, quality and supply chain aspects
b) Quality systems
For intermediates and APIs ICH Q7 guidelines should be followed and for critical raw materials and APIs guidelines for ICH Q9 should be followed
c) Organization or plant tour
Here the ability and willingness of management to support equipment, facility, maintenance and prevention of contamination is evaluated during the plant tour
d) Documentation
Review of documents like BPR, lab records and master records should reflect the organisation ability to produce the products in compliance with ICH Q7 guidelines and quality specifications
e) Process
Process and availability of the equipment should be in compliance with ICH Q7 guidelines and quality specifications like chemical and Bio chemical synthesis, manufacturing process – Biological & Chemical processes
f) Physical properties
Physical properties like particle size, solubility profile, degrades and polymorphism should be evaluated for the product which eases the evaluation of materials that are manufactured in further processes
Other considerations
g) Stability & Analytics
h) Regulatory
i) Economics
j) Patents
k) Safety and environmental aspects
iv)Conclusion
Report on various factors is evaluated by the team personnel from various departments. If any discrepancies are identified and no proper action is initiated then it should be reported to senior management. Based on it go or no go decision is made
1.1.3 Quality assessment
Based on the guidelines the quality of Critical & Non critical raw materials, registered Intermediates and APIs the following is assessed.
Quality unit assess and decision to go or not to go is given.
The auditor in lead should be with sufficient experience or certified in the relevant field
During audit manufacturer who follow procedures other than cGMP should be checked so quality system followed by manufacture should be considered before assessing.
APIC auditing guide can be taken as guidance on how to go about supplier audit
Depending on the country and the regulations the audit should be done
Audit report should encompass the critical and major deficiencies
1.1.4 Change control
Change control management is done according to the following steps
a) Change initiation
Any changes made that alter the product quality should be notified and agreed by the firm & supplier. The changes may be relating to quality, technical, regulatory, safety, stability and environmental aspects
Mechanism
A temporary change request is initiated with proper justification and it should include the following
Tracking number
Change description
Specifications as per the user requirements
Number of batches impacted by change
Products that are affected
Reason for change
Acceptance criteria
Any other supporting documents like analytical test results
b) Execution
After receiving the temporary change request is made the process change is executed by new material which may be controlled and segregated to ensure compliance
c) Evaluation
The evaluation of material products is done by testing the materials for all materials and further the tests are used to produce final products for APIs and critical materials
Extra testing is needed to evaluate the materials so they are within the acceptable limits
A complete validation report is drafted with approval as per the site procedure
d) Closure
Closure memo is prepared which ensures that request is processed and verified. It should include the following
Evaluation of materials received and products by testing
Approval of validation report and conforming that all requirements are met
e) Monitoring
To monitor and evaluate the material & suppliers, key performance indicators should be given by the firm
Following are the examples of some KPIs in a firm
Number of observations due to agency inspections and investigations without significance
Number of batches rejected in a year
Percentage of audit observations and corrective actions completed on time
Number of customer complaints
1.1.5 Supply chain security
The supply chain components like storage, transportation, material traceability should be assessed from quality perspective in accordance with the guidelines
Data loggers can be used for humidity and temperature sensitive products which provides documented evidence
Tamper resistant packaging closure and unique seals should be used to increase supply chain security.
Label should be evaluated and should match the manufacture reference label in compliance with ICH Q7 9.42 / 43 for registered intermediates and APIs.
Labels should indicate manufacturer name & address, transport and storage conditions, identification code, batch number and quantity of the product
Assessment of CoA
1.1.6 Monitoring and Evaluation
After approval of new supplier evaluation is done by the quality unit
a) Elements to be monitored
The following criteria should be monitored according to the defined criteria
Specifications
Statistical tools to identify trends
Packaging and sealing
Labelling
Certificates and any other related documents
Quantities and delivery dates
b) Evaluation
The following data should be evaluated
Quality
Testing of materials
Complaint status
SPC or SQC analysis
Change in critical materials, APIs and intermediates
Response and reaction time
Regulatory issues
Predefined KPIs
c) Rating
After evaluating the suppliers are rated in accordance with their performance and satisfaction into following categories
Complete satisfaction – Approved
Mainly satisfied – Limited approval/ ongoing supply
Partially satisfied – Conditional approval/ no supply until corrective actions are taken
Not satisfied – disqualified supplier
d) Review
After monitoring the results and initiation of corrective actions the supplier should be informed so that relation with the supplier is maintained. It can be in person or in written form.
Vendor qualification, critical raw materials,non critical raw materials, intermediates, apis, supplier, supply chain
