cGMP and Regulatory Updates

OBJECTIVE Test for Total Microbial Count is provided to determine compliance with the requirements given in individual monograph / specifications. PRINCIPLE Total microbial count is the estimation of the number of viable aerobic micro-organisms present in the pharmaceutical articles of all kinds, from raw materials to the finished forms. BUFFERS AND MEDIA 1. pH 7.2 Phosphate Buffer Stock Solution Dissolve 34 g of Monobasic Potassium Phosphate in about 500 mL of water contained in a 1000 mL volumetric flask. Adjust to pH 7.2 ± 0.1 by the addition of 4 % w/v aqueous solution of Sodium Hydroxide (about 175 mL), add water to volume, and mix. Dispense and sterilize. Store under refrigeration. For use, dilute the Stock Solution with water in the ration of 1 to 800 , and sterilize in an autoclave at 121 OC , 15 lb pressure for about 15 min. 2. Fluid Soyabean Casein Digest Medium Pancreatic Digest of Casein 17.0 g Papacy Digest of Soybean Meal 3.0 g Sodium Chloride 5.0 g Dibasic Potassium Phos...

OBJECTIVE The test for Abnormal / Undue Toxicity / Safety test is provided to determine compliance with the requirements given in individual monograph / specifications. PRINCIPLE This test is intended to detect any unexpected, unacceptable, biological reactivity in a substance. This is an invitro test designed for safety assessment of biologics and biotechnology derived products. ANIMAL QUARTERS 1. Keep the animals individually in a quiet area with an appropriate uniform temperature allowing a variation of ± 2 OC and uniform humidity and free from disturbance. 2. Carry out the test in a quiet room where there is no risk of disturbance which can excite the animals and in which the room temperature is within 3 OC of that of their living quarters or in which the animals have been kept for at least 18 h before the test. 3. Withhold food from the animals overnight and until the test is completed , with hold water only during the test. TEST FOR UNDUE TOXICITY ( As...

OBJECTIVE The test for Staphylococcus aureus is provided to determine compliance with the requirements given in individual monograph/specifications,. PRINCIPLE Identification of Staphylococcus aureus is the detection of a pathogenic bacteria which causes infection in human body. It can be identified by using specific, differential media which support growth of only Staphylococcus aureus. REAGENT AND MEDIA Fluid Soybean - Casein Digest Medium Pancreatic digest of Casein 17.0 g Papai digest of Soybean meal 3.0 g Sodium Chloride 5.0 g Dibasic Potassium Phosphate 2.5 g Dextrose (C6H12O6.H2O) 2.5 g Distilled Water 1000 mL Final pH after sterilization 7.3 ± 0.2 Dissolve the solids in the water, warming slightly to effect solution. Cool to room temperature and add, if necessary, sufficient 0.1 N Sodium Hydroxide to give a final pH after sterilization of between 7.1 and 7.5. Filter, if necessary, to clarify. Distribute into suitable containers and sterilize in an autoclave at 121 OC for about ...

1.0 OBJECTIVE The test for Anti-microbial preservative - Effectiveness is provided to determine compliance with the requirements given in individual monograph / specifications. 2.0 PRINCIPLE Preservative efficacy test is basically a challenge test in which the function of a preservative in pharmaceutical preparation use to be checked by challenging it with different microorganisms (bacteria, fungi and yeast.) Test Organisms Aspergillus niger IMI 147 007 (ATCC 16404, IP 1431.83) Candida albicans NCPE 3179 (ATCC 10231, IP 48.72) Pseudomonas aeruginosa NCIMB 8626 (ATCC 9027, CIP 82.118) Staphylococcus aureus NCTC 10788 (NCIMB 9518, ATCC 6538, CIP 4.13) . Single-strain challenges are used and the designated micro-organisms are supplemented by other strains or species that may represent likely contaminants to the preparation. For example, Escherichia coli [NCIMB 8545 (ATCC 8739, CIP 53.126)] is used for all oral preparations and Zygosaccharomyces Rouxii[NCYC 381 (IP 2021.92)] for oral prepa...

The test for Pyrogens is provided to determine compliance with the requirements given in individual monograph / specifications. PRINCIPLE Pyrogen test is the measurement of the rise in body temperature of rabbits following the intravenous injection of a sterile solution of a substance being examined. It is designed for products that can be tolerated by the test rabbits in a dose not to exceed 10.0 mL per kg. Weight injected intravenously within a period of to more than 10 min. SELECTION OF ANIMALS 1. Use healthy, adult rabbits of either sex, weighing not less than 1.5 kg, fed a complete and balanced diet not containing antibiotics and showing no loss of body weight during the week preceding the test. 2. The rabbits must not have been used in a similar test : a. during the preceding 3 days (as per BP) or 2 days (as per USP and IP) b. during the preceding 3 weeks (as per BP) or 2 weeks (as per USP and IP) unless the material being examined passed the test Rabbits used in a test for Pyrog...

1.0 OBJECTIVE To lay down a procedure for washing and sterilization of glass apparatus. 2.0 SCOPE This SOP covers the procedure for washing and sterilization of glass apparatus is applicable to Quality Control Department Formulation Units 3.0 RESPONSIBILITY Microbiologist. 4.0 ACCOUNTABILITY Department Head. 5.0 PROCEDURE 5.1 Wash the glassware thoroughly using soap solution (Extran 1.0%) followed by potable water rinses to remove all the traces of the residues. Finally rinse with purified water. 5.2 Dry the washed glassware at 105°C in oven. 5.3 Cover the open ends of glass apparatus with a caps / cotton plugs and wrap with aluminum foil. 5.4 Sterilize in the autoclave at 15 psi, 121 OC for 20 min. 5.5 Keep the sterilized material in separate and labeled area to avoid mix up with unsterilized material. 5.6 Record the details. 5.7 For new glassware follow the following procedure 5.7.1 Treat the glasswa...

1.0 OBJECTIVE To lay down a procedure for receiving HPLC columns registering and its usage. 2.0 SCOPE This SOP is applicable to Quality Control Department. 3.0 RESPONSIBILITY Quality Control Executive / Officer. 4.0 ACCOUNTABILITY Department Head. 5.0 PROCEDURE 5.1 On receipt of a new column, enter the following details in the HPLC column register. A. Name of the column. B. Make C. Dimension and its particle size D. Date of receipt E. Mfr. Certificate : Received / Not received F. Application G. Manufacturers column number H. Column number allotted I. Usage with effective from (w.e.f.) [date] 5.3 All new columns in the lab should be numbered at the time of receipt. 5.4 Q.C Executive/Officer will be responsible to allot the number on receipt of the column. 5.5 All new columns / spare columns should be kept p...

1.0 OBJECTIVE To lay down a procedure for preparation of volumetric solutions / reagents / mobile phase & standardization of volumetric solution used for chemical analysis 2.0 SCOPE This SOP is applicable to Quality Control Department 3.0 RESPONSIBILITY Quality Control Chemist. 4.0 ACCOUNTABILITY Department Head. 5.0 GENERAL INSTRUCTIONS 5.1 All chemicals / solvents used for preparation of volumetric solutions and reagents shall be LR Grade / AR Grade / GR Grade. 5.2 All volumetric solutions / reagent shall be prepared in purified water unless otherwise the use of carbon-dioxide-free water is specified. 5.3 Volumetric Solutions : 5.3.1 All volumetric solutions / reagent shall be freshly prepared once in every three months or whenever the solution shows any fungal growth or sedimentation or deviation of the strength [Molarity / Normality] from the desired value by more than ± 10%. 5.3.2 The restandardization date shall be one month for all volumetric solutions 5.3.3 Records will be ...

1.0 OBJECTIVE To lay down a procedure for retesting of active ingredients and excipients. 2.0 SCOPE This SOP covers procedure for Retesting of Raw materials and this sop is applicable for Quality control department. 3.0 RESPONSIBILITY Quality Control Chemist. 4.0 ACCOUNTABILITY Department head. 5.0 PROCEDURE 5.1 The retesting schedule shall comprise of the list of raw materials, retesting should be carried out for each material during retesting period. 5.2 Warehouse shall take a print out of Raw Materials which are due for retesting in the next month and issue the list to Quality Control Department in the first week of the month. 5.3 Quality Control will plan the Sampling and Testing of the materials in such a way that the testing is completed before the date mentioned in the Retesting Schedule. 5.4 Sample the materials as per the SOP on “Sampling of Raw Materials”. Enter the details in Raw Materials Inward Register and allot a new...

1.0 OBJECTIVE To lay down a procedure for testing and release of in process materials and finished products for the manufacturing and release of Products. 2.0 SCOPE This SOP Covers the procedure for Approval / Rejection of In process material / Finished Product.and this is applicable to Quality Control Department. 3.0 RESPONSIBILITY Quality Control Chemist. 4.0 ACCOUNTABILITY Department head 5.0 PROCEDURE 5.1 Sample the in-process material / finished product as per the SOP on “Sampling of in-process material / finished products” SOP No. xxxxx 5.2 On receipt of in-process material / finished product samples in Quality Control Department along with analysis request sheet, Chemist shall check the following : 5.2.1 Label details on the samples to match with those on the analysis request sheet. 5.2.2 In case of any discrepancies, clarify with Department head. 5.2.3 Ensure that the samples and documents are placed properly in trays meant for the...

1.0 OBJECTIVE To lay down a Procedure for Material receipts at factory gate - Security Inward. 2.0 SCOPE 2.1.0 Areas 2.1.1 Security Office and Co-ordination centre 3.0 RESPONSIBILITY Security Supervisor 4.0 ACCOUNTABILITY Executive - Security. 5.0 PROCEDURE : 5.1.0 Whenever the material comes from the Supplier / Manufacturer the Security Supervisor has to do the following: 5.1.1 Check the unit address on Delivery Challan / Invoice for which it belongs. 5.1.2 If our factory address on the Delivery Challan confirms, the Security Supervisor has to forward the person(s) with documents to the Executive - Warehouse for clearance to inward. 5.1.3 If material is not cleared for Inward do not allow the vehicle and material inside the premises. 5.1.4 Enter the details of receipt into the Inward register and allow the Vehicle Inside. 5.1.5 Security to check if the vehicle is having any other material not pertaining to our unit, with proper documents or not, before...

1.0 OBJECTIVE To lay down a procedure for testing and release of Packaging Materials. 2.0 SCOPE This SOP covers the procedure for Approval/ Rejection of Packing material and this is applicable to Quality Control Department. 3.0 RESPONSIBILITY Quality Control Chemist. 4.0 ACCOUNTABILITY Department Head. 5.0 PROCEDURE 5.1 Sample the Packaging Material as per the SOP on “Sampling of Packaging Materials” SOP No. xxxxxx 5.2 Check the compliance of the material with SAP system through Inspection time Analysis .Now, note down the description of the material given in the SAP system. Verify the item code, Goods Receipt Note, inhouse B. No, generated A.R.No in Packing material Inward Register. In case of any discrepancy, inform to Department head and Warehouse incharge for taking corrective action. 5.3 Perform all the tests mentioned in the respective Specifications of the Packaging Material. Record all the observations on the Analytical Report Sheet. 5.4 Attach the respective sample of all prin...

1.0 OBJECTIVE To lay down a procedure for testing and release of raw materials for the manufacturing of Products. 2.0 SCOPE This SOP covers the procedure for Approval/ Rejection of Raw material and this is applicable to Quality Control Department 3.0 RESPONSIBILITY Quality Control Chemist. 4.0 ACCOUNTABILITY Department head 5.0 PROCEDURE 5.1 Sample the raw materials as per the SOP on “Sampling of Raw Materials” SOP No. xxxxx 5.2 On receipt of raw material samples in Quality Control Department along with GRN, COA of supplier (if available) and Sampler’s remarks sheet, the Chemist shall check the following : 5.2.1 Label details on the samples to match with those on GRN and COA of supplier (if available) 5.2.2 Sampler’s remarks Sheet 5.2.3 In case of any discrepancies, clarify with Department head 5.3. Ensure that the samples and documents are placed properly in trays meant for the purpose 5.4 The Chemist shall take up...

1.0 OBJECTIVE To lay down a procedure for sampling of packaging materials so as to get the representative sample of the whole lot. 2.0 SCOPE This SOP Covers the procedure for sampling of packing material and this is applicable to Quality Control Department 3.0 RESPONSIBILITY Quality Control Chemist/ Executive. 4.0 ACCOUNTABILITY Department Head. 5.0 PROCEDURE 5.1 GRN (Goods Received Note) Receipt procedure: 5.1.1 Switch on the computer and double click on SAP(ERP) log on. And double click on server name on the Desktop. 5.1.2 SAP initial screen will appear. Type user name and password and press enter. 5.1.3 Main menu screen will appear. To proceed further, follow the transaction: Via Menus User menu for F12QCPM – Quality - Customized Reports - UNDER TEST STATEMENT LIST Via Transaction Code Y_DRD_18000045 Date Date at which lot created Click the field, click [down arrow] key & select the ‘date’ and click on ‘choose’ button. ...

1.0 OBJECTIVE To lay down a procedure for sampling of non sterile raw materials so as to get a representative sample of the whole lot for Analysis. 2.0 SCOPE This SOP covers Sampling procedure of Raw material and this is applicable to Quality Control Department. 3.0 RESPONSIBILITY Quality control chemist/ Executive. 4.0 ACCOUNTABILITY Department Head 5.0 PROCEDURE 5.1 GRN (Goods Received Note) Receipt procedure: 5.1.1 Switch on the computer and double click on SAP(ERP) log on. And double click on server name on the Desktop. 5.1.2 SAP initial screen will appear. Type user name and password and press enter. 5.1.3 Main menu screen will appear. To proceed further, follow the transaction: Via Menus User menu for F11QCRM – Quality - Customized Reports - UNDER TEST STATEMENT LIST Via Transaction Code Y_DRD_113000032 Plant Plant at which lot created Click the field, click [down arrow] select the Place required and double click. Date Date at which lot created Click the field, click [down arrow...

1.0 OBJECTIVE To lay down guidelines for codification of validation documents in microbiology. 2.0 SCOPE This SOP is applicable to Quality Control Department, Formulations Units 3.0 RESPONSIBILITY Quality Control chemist / Executive 4.0 ACCOUNTABILITY Departmental Head 5.0 PROCEDURE 5.1 Codification System consists of eleven characters AXXMBYYAAZ and are as follows 5.1.1 A character represents the location , specified as – Numeric follows 1 - For Formulation Unit 1 2 - For Formulation Unit 2 3 - For Formulation Unit 3 5.1.2 XX character represents the category specified as under : Alphabetical VP : Validation Protocol ST : Sterility testing BT : Bacterial endotoxin test MT : Microbial limit test 5.1.3 MB stands for microbiology. 5.1.4 YY character represents the protocol number, specified as – Numeric follows 01,02 and so on 5.1.5 Z character represents the Revision Number, specified as – Alphabetical Follows - first time any format is prepared, the revision number shall be ‘A’. The ne...

1.0 OBJECTIVE To lay down a procedure for handling of raw materials Samples and Finished Products out-of-specifications test results in microbiology. 2.0 SCOPE This SOP is applicable to Quality control Department, Formulations Units 3.0 RESPONSIBILITY Executive 4.0 ACCOUNTABILITY Departmental Head 5.0 PROCEDURE 5.1 Any out-of-specification test result shall be investigated and documented. The investigation report shall include, 5.1.1 Errors in sampling, handling and storage of sample. 5.1.2 Error in Analysis. 5.2 In case investigation reveals that sampling is one of the reason for out of specification result, the repeat analysis shall be done on re-sample. 5.3 In case investigation reveals that out-of-specification results is solely due to analytical error, the repeat analysis shall be performed on same sample. 5.4 If repeat analysis result is found within specification, following step 5.2 or 5.3 then the sample shall be approved. If the analysis result is found out of specification, t...

1.0 OBJECTIVE To lay down a procedure for handling of “ Samples for Analysis ” of formulation / raw materials. 2.0 SCOPE This SOP is applicable to Quality Control Department, Formulations Units 3.0 RESPONSIBILITY Quality Control Chemist / Executive 4.0 ACCOUNTABILITY Department Head 5.0 PROCEDURE 5.1 Formulations 5.1.1 The QC chemist shall receive the samples along with the sample request form and he shall ensure intactness of the samples by visual checking of the seal. 5.1.2 The entries of the sample shall be made in the respective register by the QC chemist 5.1.3 Samples shall be kept in the tray labeled as ‘Under Test ’ till those are taken for analysis. 5.1.4 The samples shall be handled carefully to avoid cross contamination. 5.1.5 When the samples shall be taken for the analysis by the QC Chemist, the relevant details and shall be mentioned in the respective registers. 5.1.6 The excess samples shall be destroyed as after com...