A) Nature of Complaint- Critical Complaint

• Product mix-up (including different strengths of same product)
• Mislabeling (incorrect label, incorrect lot number/expiry, unreadable critical data)
• Missing label on bottle / smudged or unreadable coding detail on bottle label / blister/ strip
• Missing coding details on bottle label / primary pack/ blister/ strip
• Missing information on label / blister/strip/package insert
• Microbial contamination or any significant chemical, physical or other change or deterioration in the drug product
• Failure in one or more quality parameters of drug product to meet the specification established for it in the application.
• Foreign substance/matter embedded on the tablet
• Metallic/Glass Contamination
• Foreign matter inside bottle
• Presence of insect
• Missing dose in therapeutic life saving drug

B) Nature of Complaint- Major Complaint

• Tablet Discoloration
• Intact elimination of tablets/granules (Ghost tablet/granules) / Drug ineffective
• Spot on tablet (Black/Blue/Brown/Red/Other)
• Quick disintegration of tablet in mouth
• Broken Tablets
• Tablet capping / Lamination / edge damage / chipped tablet / coating defect / half tablet / twin tablet
• Missing imprinting on tablet
• Loose hair in bottle / pack
• Breaking / crumbling of tablets in blister / strip/ bottle
• High / Low fill in sachet
• Soft Tablets
• Difficulty in swallowing the product (Suspension/ Tablet)
• Organoleptic (Bad Taste / Odor)
• Bottle with Burnt seal / Broken seal / Partial seal / Improper sealing
• Empty sealed bottle  / sachet
• Loose caps of bottles
• Shortage of units in the bottle
• Broken desiccant (canister / sachet)
• Damaged / Dented bottles
• Double printing on label / carton
• Cosmetic defect on Carton / Product Information Leaflet (PIL)
• Empty carton / Carton with Product Information Leaflet (PIL) only
• Improper sealing of sachet
• Wrong Product Information Leaflet (PIL)
• Braille error in carton
• Temperature Excursion during shipment

C) Nature of Complaint- Minor Complaint

• 2D Data-Matrix grade on carton found outside the acceptable grade
• Shortage of unit packs in shipper
• Shortage of blister(s) / strip(s) in carton
• Missing component in carton
• Shipper/carton Damage

Step 1: Evaluation of risk: To determine/identify the potential presence of nitrosamine impurities in drug products.

Step 2: Confirmatory Testing:  To perform confirmatory testing on the products identified to be at risk of N-nitrosamine formation or (cross-) contamination and report confirmed presence of nitrosamine

Step 3: Implementation of changes:  To notify changes required to be implemented in the process to mitigate the nitrosamine impurities, if impurities are detected, to regulatory bodies.

Refer SOP Reporting of Nitrosamine Impurities for More details 

Tablets:

• Once granulation starts, operation must be completed within 3 days.
• Compression must be completed within 30 days after release of bulk sample.
• After compression, inspection and coating [if required] to be done should be finished within 30 days.
• After inspection and QA release, packing must be completed within 30 days.

Liquids:

• Once manufacturing starts, operation must be completed within 5 days.
• After bulk release [whenever applicable] filling and packing activity must be completed within 7 days.

Capsules:

• Once blending starts, operation must be completed within 7 days.
• Encapsulation of blend after release must be completed within 15 days.
• After filling is completed, inspection and packing must be completed within 30 days.

Dry Syrups:

• Once blending starts, operation must be completed within 5 days.
• After QC approval of blend, filling and packing must be completed within 7 days.

Powder Blend:

• Once blending starts, operation must be completed within 3 days.
• After QC release of blend, filling and packing must be completed within 7 days.

Support this by carryout hold time study at different stages of Manufacturing Process

The purpose of this Procedure is to lay down the instruction for all activities performed by Research & development during technology transfer and to ensure that required information, data and technology about the product, manufacturing process and analytical methods are transferred to the manufacturing plant so that quality and integrity are maintained

The receiving site (manufacturing site) is defined as the production site that is the recipient of the product, process, packaging and analytical methodology.

The transferring site (R&D department) is the site that develops the formulation, pilot manufacturing process, packaging configurations and analytical methodology.

The optimizations, evaluation of exhibit batches are considered as Transfer batch

Step 1- The basic elements of the technology transfer process are the

• Planning Phase

• Execution Phase

• Post-Transfer Phase.

Step 2- During the planning phase, the transferring site and receiving site discuss the product design, manufacturing process and overall strategy of the project.

Step 3- Before the execution phase, the Technology Transfer Package shall be approved by QA and Regulatory Affair.

Step 3- A change control shall be initiated to assess the impact to transfer of new product to manufacturing site according to change control management procedure.

Step 4- During the execution phase, the actual manufacturing, packaging, testing and release of the transfer batch shall take place. This execution phase is carried out by both the transferring site (R&D-ADL) and receiving site (Mfg. & QC). The execution phase ends when the transfer batch has been fully tested and released and the execution batch documentation has been approved.

Step 5- During the post-transfer phase, the bioequivalence / clinical trials will be taken care by project head in co-ordination with manufacturing site and BE center (as applicable for the product), also stability will be performed. The final product specifications are established and the proposed commercial manufacturing process is established.

Step 6- All applicable standard operating procedures at the receiving site are to be followed when a new product is being transferred from transferring as per existing SOPs. In an event significant change in applicable standard operating procedures shall be explained and justified and approved by both the sites.

Step 7- Analytical Method validation shall be completed as per the procedure prior to transfer.

for More details Refer SOP for Technology Transfers 

Periodic Review of System Audit Trails

System  data audit trails shall be reviewed by designated QA reviewer on quarterly (once in three months) basis or as and when required.  After completion of three months, review of system audit trails shall be completed within 30 days.

1.0 For equipment as per listed Annexure-I “List of equipment generating Audit Trail" shall be Maintained by user department, reviewed by Engineering department and approved by QA. Whenever any new system or equipment is added or removed, Annexure –I shall be updated by user department.

2.0 Designated QA person shall be granted review privileges of system audit trails.

3.0 QA shall prepare system and data audit trail review schedule yearly. The schedule shall be prepared before start (before 30 Days) of next year. New system shall be added in audit trail review schedule once it is validated and released for use. The schedule shall be version controlled and shall be revised when any new system is implemented post completion of validation.

4.0 QA shall record all the details of system and data audit trail review in Observation Sheet.

5.0 QA shall verify the system and data audit trails for its availability, accuracy and integrity of the data. The system and data audit trail shall be reviewed for the following points but not limited to:

1. User creation/modification/activation/deactivation/deletion.
2. Configuration of Role Based Privilege Right Matrix (change in User Group)
3. System policies and system configurations like password policy, system lock out duration, number of failed login attempt, administration changes, database setting, change of data storage location etc.
4. Any login-logout events via generic ID if any.
5. Verification of change in report template or rename of batch report if any.
6. Any data deletion of audit trail, history logs or file in the system if any.
7. Verify original data saved in designated folder or path and consistency in file name. (This point is application where end user manually save data at designated folder or path).
8. Verify data base or flat file randomly review to discover omitted/orphan data like data generated with file name like ABC, XYZ etc, aborted data or duplicate data generated for same batch number etc.
9. Verify superseded or obsoleted recipe is not access to operator/supervisor.
   1. QA shall verify that Data Storage Drives (C: and D: Drive for Example) are not accessible to operator and supervisor.
   2. QA shall verify that data backup shall be performed as per backup procedure.
   3. Reviewer shall record the observation of System Audit Trail of equipment during review in the format for Review checklist for System Audit Trail And Update the log.
   4. Any discrepancy if identified during audit trails review shall be investigated as per SOP Handling of Deviation. In case of any Major breakdown or access to software by OEM, user department has to intimate QA for audit trail review and activity shall be recorded in observation sheet.
   5. Any discrepancy observed during the review of system audit trails shall be reported in observation sheet and deviation shall be logged as per SOP “Handling of Deviation”.

​For Complete SOP (JSA/SOP/QA/050)- Click on Read more and Download

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Good Laboratory Practices (GLP)

To Evaluate and Documented your Good Laboratory Practices (GLP) to ensure the consistency, reliability and integrity of pharmaceuticals, chemicals, and biotechnology product analysis laboratory, here are some parameters that are must be included in your evaluation protocol (but not limited to:-

1.0 Documentation Practices for Issuance and Controls

2.0 Analyst Qualification and Personnel Training

3.0 Impurity and Assay Standards Management

4.0 Volumetric Solution Handling and Management

5.0 Stability Program effectiveness

6.0 Standard Operating Procedures (SOPs) all laboratory procedures

7.0 Instrument Calibration and Maintenance

8.0 Quality Control (QC) /Quality Assurance (QA) audit teams

9.0 Facility and Equipment suitability for the intended purpose

10.0 Raw, in-process, Finished, Stability study Sample Management for the proper handling, storage, and disposal.

11.0 Data Integrity and secure storage and backup provisions

12.0 Personnel Health and Safety of laboratory personnel

13.0 Quality Management System (OOS/OOT/Lab Incident/OOC)

14.0 Records Archiving:

Vial washing machine PQ Parameters

Vial washing machine is the one of critical Equipment in the aseptic manufacturing process which plays a crucial role in preparing containers for aseptic filling. To meet regulatory requirements, it is essential to conduct a thorough qualification of the vial washing machine. This article aims to provide a comprehensive guide for the qualification vial washing machine, covering all key concepts, processes, and regulatory considerations.

Understanding Vial Washing Machine Principle:

Vial Washing Machine are two type liner and rotatory type. In both type the vials are cleaned in below mentioned Steps:-

1st Step: External/Internal Wash with recirculated water

2nd Step: External/Internal Compressed Air Blow

3rd Step: Internal Wash with Purified water

4th Step: External/Internal Compressed Air Blow

5th Step External/Internal wash with Water for injection

6th Step External/Internal Compressed Air Blow

Performance Qualification (PQ) and Requalification:

Performance of the vial washing machine evaluated in simulated production environment.

Challenge Test Planned for Vial Washing Machine

1.0  Spiked Vial with Riboflavin dye challenge for Proper cleaning and florescence observed after cleaning under the UV cabinet. Use can use the concentration between 0.08g/L to 0.22g/L

2.0  Spiked Vials with Charcoal Slurry for determination of Visible and sub visible black particle after washing of vial. Vials Challenged in the white background for Visible Particles and for sub visible analysed through Liquid Born particle analyser.

3.0   Spiked Vials with Talcum powder for determination of Visible and sub visible white particle after washing of vial. Vials Challenged in the black background for Visible Particles and for sub visible analysed through Liquid Born particle analyser.

4.0  Spiked Vials with glass particles for determination of Visible glass particle after washing of vial. Vials Challenged in the black and white background for Visible glass Particles

5.0  Spiked Vials with NaCl Solution for determination of chemical contamination after washing of vial. Cleaned Vials are test in QC for any NaCl residue contamination.

6.0  Residual water content after blowing of compressed air inside and outside of vial to assure the vial having less than 0.4g so that it will evaporate during dehydrogenation tunnel

7.0  Endotoxin Spiked vial challenge for 1 log reduction after washing.

Before Starting the challenge test 100 ml Sample for liquid born particle count analysis shall be collected for Recirculated Water, Purified Water, WFI purge with Compressed Air.