In-Process Quality Assurance

What is quality?

Number of definitions are available in each guidelines

QUALITY SHALL BE DEFINED AS CONSUMER NEED

When we call a medicine as quality medicine?

QUALITY

TABLET MANUFACTURING PROCESS PLM OPEN ENVIRONMENT MULTI MILL COMPRESSION MACHINE COATING MACHINE INSPECTION MACHINE PACKING MACHINE

RMG FBD COMPRESSION MACHINE COATING MACHINE INSPECTION MACHINE PACKING MACHINE CLOSED SYSTEM

BOTH ARE SENT TO QUALITY LABORATORY & GOT APPROVED?

DO YOU FEEL ANY DIFFERENCE BETWEEN THESE TWO PRODUCTS?

QUALITY IS SOMETHING APART FROM TESTING AND

APPROVING OF MEDICINES

QUALITY

QUALITY

QUALITY NOT TO BE TESTED

TO BE BUILT DURING THE PROCESS.

QUALITY

100 % testing of medicines are not done. Most of the testing are destructive

testing. All impurities are not detected /analysed. What to do? Quality to be built during the process.

HOW?

QUALITY

By means of Following GMP thorough out the process. Control over input materials. Process control. Various checks during the process (IPC). Doier and checker system (cross checking) . Control over product release.

IPQA

FAULT FINDING ?

To guide the operator / supervisor regarding any deviation observed during the process.

To assure products are consistently produced as

per quality standards and predefined specifications

IPQA

Schedule M

CFR 211Sec. 211.110 Sampling and testing of in-process materials

and drug products. (a) To assure batch uniformity and integrity of drug products, written procedures shall be established and followed that describe the in-process controls, and tests, or examinations to be conducted on appropriate samples of in-process materials of each batch. Such control procedures shall be established to monitor the output and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product. Such control procedures shall include, but are not limited to, the following, where appropriate:

(1) Tablet or capsule weight variation; (2) Disintegration time; (3) Adequacy of mixing to assure uniformity and homogeneity; (4) Dissolution time and rate; (5) Clarity, completeness, or pH of solutions.

CFR 211(b) Valid in-process specifications for such characteristics

shall be consistent with drug product final specifications and shall be derived from previous acceptable process average and process variability estimates where possible and determined by the application of suitable statistical procedures where appropriate. Examination and testing of samples shall assure that the drug product and in-process material conform to specifications.

(c) In-process materials shall be tested for identity, strength, quality, and purity as appropriate, and approved or rejected by the quality control unit, during the production process, e.g., at commencement or completion of significant phases or after storage for long periods.

(d) Rejected in-process materials shall be identified and controlled under a quarantine system designed to prevent their use in manufacturing or processing operations for which they are unsuitable.

ICH Q7

EU Guideline

LINE CLEARANCE

To assure that no traces of previous product

inside the module.

To assure that correct materials brought for processing / packing.

Objective

GENERAL CHECKSArea and equipment cleanlinessArea and equipment log cardsClean primary and secondary

gowningFilter cleaningStatus labelingOnline documentationAvailability of gloves & nose masksAvailability of disinfectant solution

WAREHOUSE DISPENSING AREA Area and equipment cleanliness Area and equipment log cards Clean primary and secondary gowning Filter cleaning Status labeling Online documentation Availability of gloves & nose masks Availability of disinfectant solution Proper storage of actives and execipients. Material status. Handling of materials Dispensing Tools cleaning Labeling details. Balance calibration (log books). Dispensing activity (log books). Dispensed material staging area.

PRODUCTION PROCESS

Check all manufacturing activities are being performed as per batch processing record.

Process rate / time against specifications mentioned in BMR.

SIFTING Check for :

Right equipment in process as per BMR. Correctness of mesh /screen size. Black particles / foreign particles. Quantity retains over the mesh. Sieve integrity before and after sieving. Abnormal noise from the sifter.

GRANULATION Check for :

Right equipment in process as per BMR. Amount of granulation fluid added. Time of granulation. Amperage/torque, if applicable. Formation of good granules.

DRYING Check for :

Right equipment in process as per BMR. Filter bag integrity. Inlet / outlet temperature. Bed / Product temperature. Racking in tray drier / FBD. Proper fluidization in FBD. Formation of any lumps. Moisture content (Sampling).

BLENDING: Check for :

Right equipment in process as per BMR.

Blender speed. Blending time. Content uniformity. Bulk density. Particle size analysis. Moisture content. Compressibility index

COMPRESSION Check for : Right equipment in process as per BMR. Appearance of tablets (Correct punch ) Average weight Uniformity of weight Thickness Hardness Friability DT Machine speed

COATING Check for

Spray pattern Spray rate Inlet /out let/ product temperature RPM of coating pan Amount of coating solution % Weight gain Color / shade variation (different

lots) Mottling Chipping Orange peel effect

PACKING Check for Forming

temperature Sealing temperature Appearance of

blister Speed of machine Pack specification Leak test

Check for

Cleanliness of container / closure.

Number of tablets / container

Integrity of line.

Closing /opening torque.

Challenge test for sensors.

Correctness of label

Check for correctness manufacturing and expiry dates

YIELD RECONCILIATIONManufacturing yield at all stages to be checked.

Any out of specification/ out of trend to be investigated.

Printed packing material yield.

BMR /BPR to be reviewed at the time of sampling

IPQA

Will reduce the batch rejections Will reduce the reprocessing

BY ADOPTING VARIOUS CONTROLS OVER BY ADOPTING VARIOUS CONTROLS OVER THE PROCESS, THE PRODUCT WILL BE OF THE PROCESS, THE PRODUCT WILL BE OF

QUALITY ONEQUALITY ONE

BUILDING QUALITY DURING THE PROCESS, THERE BY GETTING THE

QUALITY PRODUCT.

Common GMP Deficiencies

Common GMP Deficiencies

Common GMP Deficiencies

Common GMP Deficiencies

Common GMP Deficiencies

Common GMP Deficiencies