Quality Assurance Handbook.pdf

QA HAND BOOK A Compendium of Guidelines and Related Materials EDITION I PHARMACEUTICAL FORMULATIONS 2022 Ajay Thakur QA HAND BOOK Page 2 of 534 INDEX S No QUALITY ASSURANCE BASIC PAGE NO 1 QUALITY ASS[.]

2022 QA HAND BOOK A Compendium of Guidelines and Related Materials EDITION - I PHARMACEUTICAL FORMULATIONS Ajay Thakur QA HAND BOOK INDEX S.No 10 11 12 13 14 15 16 17 18 QUALITY ASSURANCE BASIC QUALITY ASSURANCE STANDARD OPERATING PROCEDURE SITE MASTER FILE DRUG MASTER FILE PROCESS VALIDATION VALIDATION MASTER PLAN CHANGE CONTROL DEVIATION CORRECTIVE AND PREVENTIVE ACTION COMPLAINTS AND RECALLS CLEANING VALIDATION ANNUAL PRODUCT QUALITY REVIEW QUALITY RISK MANAGEMENT DOCUMENT & DATA COLLECTION, RECORD, CONTROL & MANAGEMENT VENDOR MANAGEMENT QUALITY / FACILITY AUDITS OOS/ OOT PHARMACOPOEIA PAGE NO 63 to 64 65 to 65 66 to 66 66 to 66 66 to 68 69 to 69 70 to 74 75 to 81 82 to 85 86 to 93 94 to 100 101 to 105 106 to 116 117 to 122 123 to 130 131 to 141 142 to 154 151 to 161 TABLET’S MANUFACTURING UNIT OPERATION 19 20 21 22 23 24 25 26 27 IPQA WAREHOUSE GRANULATION COMPRESSION COATING PACKING CALIBRATION SAMPLING GUIDELINES BASIC CONCEPTS & THEIR QUESTIONS & ANSWERS Page of 534 164 to 164 165 to 176 177 to 227 228 to 302 302 to 349 349 to 404 404 to 422 423 to 434 435 to 491 QA HAND BOOK DEFINITIONS A Accelerated Testing Studies designed to increase the rate of chemical degradation or physical change of a drug substance or drug product by using exaggerated storage conditions as part of the formal stability studies Data from these studies, in addition to long term stability studies, can be used to assess longer term chemical effects at non-accelerated conditions and to evaluate the effect of short term excursions outside the label storage conditions such as might occur during shipping Results from accelerated testing studies are not always predictive of physical changes Acceptance Criteria Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical procedures Accuracy The accuracy of an analytical procedure expresses the closeness of agreement between the value which is accepted either as a conventional true value or an accepted reference value and the value found This is sometimes terms trueness Active Ingredient An active pharmaceutical ingredient (API) is the chemical substance contained in a pharmaceutical dosage form, which is responsible for its therapeutic effect Adverse Reaction (Adverse Drug Reaction), ADR An adverse drug reaction is a response to a medicinal product which is noxious and unintended and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease or for the restoration, correction or modification of physiological function Page of 534 QA HAND BOOK the incorporation of binders to improve compatibility The granulation step and the drying step may be performed consecutively (typically using high shear granulation and fluid bed drying) or concurrently (typically using fluid bed granulation) Continuous wet granulation is increasingly being used to aid throughput in pharmaceutical processing factories X There are no terms under “X” Y Yield, Expected The quantity of material or the percentage of theoretical yield anticipated at any appropriate phase of production based on previous laboratory, pilot scale, or manufacturing data Yield, Theoretical The quantity that would be produced at any appropriate phase of production, based upon the quantity of material to be used, in the absence of any loss or error in actual production Z Z-Value The number of degrees of temperature change necessary to change the D-value by factor of 10 Page 61 of 534 QA HAND BOOK QUALITY ASSURANCE BASIC Page 62 of 534 QA HAND BOOK Why Companies Have Difficulties Analyze Verify Review Implement Identify Why? Incorrect Root Cause Identified Analyze: Not done Verify: Problem recurrence Review: Preventive Action does not work Implement: Corrective Action wrong Identify: Problem but not root cause Page 85 of 534 QA HAND BOOK CLEANING VALIDATION It is a document act of demonstrating that cleaning procedure for the equipment used in the fabrication/packaging will reduce to an acceptable level of all residues the (product & cleaning agent) and to demonstrating that routine cleaning & storage of equipment does not allow microbial proliferation Importance of Cleaning Validation • “Particular attention should be accorded to the validation of … cleaning procedures” (WHO) • “Cleaning validation should be performed in order to confirm the effectiveness of a cleaning procedure” (PIC/s) • “The data should support a conclusion that residues to an acceptable level” (FDA) Cleaning validation Studies Following cleaning validation related studies shall be carried out: Cleaned Equipment Hold Time Study (CEHT) Hold time study shall be carried out to ensure the suitability of cleaned equipment, stored in its prescribed storage conditions, and does not increase the microbial contamination level more than the limit for freshly cleaned equipment Dirty Equipment Hold Time Study (DEHT) The dirty equipment hold time studies shall be carried out to ensure the microbial proliferation over a period of time and the same shall be possible to clean Sampling Techniques Direct Surface sampling (Swab method) Rinse Samples (Indirect method) Page 94 of 534 QA HAND BOOK Repository The Life-cycle of a regulated document Document Control Each manufacturer shall establish and maintain procedures to control all documents that are required The procedure shall provide for the following: Document Approval and Distribution Each manufacturer shall designate and individuals(s) to review for adequacy and approve prior to issuance all documents established to meet the requirements of this part The approval, including the date and signature of the individuals approving the document, shall be documented Documents established to meet the requirement of regulatory agency shall be available at all locations for which they designated, used, or otherwise necessary, and all obsolete documents shall be promptly removed from all points of use or otherwise prevented from unintended use Page 118 of 534 QA HAND BOOK Audit Report Agreement and • API: years from date of the audit Technical NA • KRM/KE/Primary and Printed PM: years from the date of audit Table B: Documents/ Activities require for qualification of New Vendor Documents/Activities required for Qualification of New vendor S.No Requirement √ = Mandatory ● = Desirable □ = NA Vendor Information (VIF) Process Flow Diagram TSE/BSE Declaration/ TSE / BSE risk evaluation questionnaire (if applicable) Residual solvent declaration Stability Data / Shelf Life Declaration / Retest or Reevaluation Period Declaration Regulatory / CGMP Certificate Audit of Vendor Manufacturing Site Prior to Commercialization Page 126 of 534 API √ Input Material Raw Material Packaging Material KRM Excipie RM other Primary Printed nt other than than KE KRM √ √ √ √ √ ● √ ● √ ● √ ● √ ● √ ● √ √ √ √ ● □ □ ● ● ● ● ● ● √ √ √ □ √ √ √ ● □ □ √ √ QA HAND BOOK Table D: Documents / Activities required for Qualification of existing Vendor for New Vendor Documents/Activities required for Qualification of Existing Vendor for New vendor S.No Requirement √ = Mandatory ● = Desirable □ = NA Vendor Information (VIF) GMP Certificate Technical Agreement Stability data/ Shelf life declaration/ Retest or Reevaluation period Declaration Process Flow Diagram Residual solvent Declaration TSE / BSE Declaration / TSE / BSE risk Evaluation questionnaire (if applicable) API KRM Input Material Raw Material KE Excipient RM other than other KE than KRM Packaging Material Primary Printed Ensure the Validity ● ● ● ● ● ● ● ● √ ● √ ● √ ● √ ● ● ● □ √ √ √ √ √ ● □ √ □ Audit of Suppliers Based on the questionnaire evaluation, if any Supplier is performing repacking activity, audit of such Supplier shall be a part of approval procedure Corporate QA shall prepare a supplier audit schedule at the beginning of each calendar year for those suppliers who perform the repacking activity Page 129 of 534 ...QA HAND BOOK INDEX S.No 10 11 12 13 14 15 16 17 18 QUALITY ASSURANCE BASIC QUALITY ASSURANCE STANDARD OPERATING PROCEDURE SITE MASTER FILE DRUG MASTER FILE PROCESS... RECALLS CLEANING VALIDATION ANNUAL PRODUCT QUALITY REVIEW QUALITY RISK MANAGEMENT DOCUMENT & DATA COLLECTION, RECORD, CONTROL & MANAGEMENT VENDOR MANAGEMENT QUALITY / FACILITY AUDITS OOS/ OOT PHARMACOPOEIA... meet the established standards An audit will evaluate the strengths and weaknesses of Quality control & Quality Assurance processes, the results of which will help us to improve processes and build