Master Formula Record
Amoxycillin and Potassium Clavulanate Oral Suspension IP
|Sr. No.||Particulars||Page No.|
|6||Process Flow Material Dispensing Process.||05|
|7||Process Flow Chart of Filling Process.||06|
|8||Process Flow Chart of In Process Control.||07|
|9||Process Flow Chart of Packing Process.||08|
|10||List of Equipment||09|
|11||Bill of Raw Material||10|
|13||Statement of The Expected Final Yield With Acceptable Limits And Relevant Intermediate Yields||11|
|14||Reference Methods For Preparing Critical Equipments Including Cleaning Assembling and Calibration||12|
|15||Instructions For Line Clearance And In process Control||12|
|16||Instructions For Line Clearance and In process Control During Blending||13|
|17||Detailed Stepwise Processing Instructions For Homogeneity Or Uniformity In Blender Mixing||13-14|
|18||Dispensing of Active Material.||15|
|20||Instructions For In-Process Controls With their Limits||15-16|
|21||Any Special Precautions To Be Observed||17|
|22||Water activity test to be performed at the following stages||17|
|23||Packing Details and Specimen Labels Relating To The Product||17|
|27||Final Reconciliation of Batch||20|
|29||Batch History|| |
|30||Release Order and Finished Goods Store Transfer Record||18|
To provide instructions for the preparation of Master formula Record for Amoxycillin Trihydrate and Potassium Clavulanate 228.5mg Oral Suspension.
To provide a documented procedure for the preparation of Master formula record is that standard manufacturing/packing record which gives complete details of materials used along with their quantities, standard process flow, Area & equipment used, yield and reconciliation, Instruction & precautions or any other information relate to Amoxycillin Trihydrate and Potassium Clavulanate 228.5mg Oral Suspension.
This procedure is applicable for the preparation of Master formula Record for Amoxycillin Trihydrate and Potassium Clavulanate 228.5mg Oral Suspension.
Follow up: QA Executive
Overall responsibility: QA Head
5.0 Product Details:
|Generic Name:-||Amoxycillin Trihydrate and Potassium Clavulanate Oral Suspension IP (228.5mg)|
|Composition:-||Each 5ml of reconstituted suspension contains:|
Amoxycillin Trihydrate IP
Equ. to Amoxycillin Anhydrous 200mg
Potassium Clavulanate IP
Equ. to Clavulanic Acid 28.5mg
|Shelf life||18 Months|
6.0 LIST OF EQUIPMENT’S:
|Sr. No.||Name of the Equipment||Equipment No.||Location/ Section|
|1.||Electronic Weighing Balance.|
|2.||Pulvelizer for Crushing the sugar.|
|3.||SS Tray drier double door.|
|6.||Air Jet Bottle Washing Machine (Hot-air)|
|7.||Empty Bottle checking Belt.|
|8.||Automatic powder filling and Screw placing machine (Mono block) With NO2 Purging.|
|10.||Automatic Induction Sealing Machine.|
|11.||Induction bottle seal checking machine.|
|12||Filled bottle checking table.|
|13||Sticker labeling machine.|
|17||Ink Jet Printing Machine|
7.0 BILL OF MATERIALS:
equivalent to Amoxycillin
|2||Potassium Clavuanate Diluted IP|
equivalent to Clavulanic Acid
|2||Sylloid AL-1 FP||IP||2.600||Kg||2.600|
|5||Mix fruit flavour||IP||1.000||Kg||1.000|
|10||Titanium Di oxide||IP||0.200||Kg||0.200|
|1||Bottles 30 ML||10,200||No.||10,200|
|2||Labels 30 ML||10,200||No.||10,200|
8.0. Quantity of Amoxycillin and Potassium Clavulanate to be issued by multiplying the standard weight with the factor evaluated after calculating by incorporating the Assay value on as is basis, water content/ loss on drying value and appropriate conversion factors.
. Quantity to be dispensed for Amoxycillin Trihydrate:
Assay Value (on as Anhydrous basis) 101 (overages of ………%)
……..Kg X …………………………………………………..X…………………
(Std Qnty.) 100- % of water content 100
. Quantity to be dispensed for Potassium Clavulanate:
……….kg X 1.191 X ………………………………………….X…………………………………..
(Std Qnty.) Potency of diluted Pot. Clav. 100-% of water content
(Conversion Factor- 1.191 mg of Pot. Clav contains 1 mg of Clavulanic Acid
9.0 PRODUCT SPECIFICATION
Description:- An off-White colored powder , fill in transparent glass bottle & White colored
cap, Sealed with aluminum foil, with paper label.
Identification;- UV spectrum of sample corresponds with in UV spectrum of working stander
.Shows absorption maxima at about 227 nm Amoxicillin and 393 nm. Potassium Clavulanate.
Weight per ml : 1.02 gm/ml. -1.9 gm/ml (After reconstitution)
Average fill NLT 4.5 gm/30 ml bottle
Uniformity of fill 4.5 gm/30 ml bottle ±9%
Assay:- Each 5 ml of reconstituted
Assay : Each 5 ml of reconstituted suspension contains:
Amoxicillin Trihydrate NLT 90 % and NMT 120% stated amount (Limit NLT 98 % and NMT 110%stated amount IH)
Clavulanic Acid: NLT 90% and NMT 125 %stated amount (NLT 98 % and NMT 110% stated amount IH)
10.0 STATEMENT OF THE EXPECTED FINAL YIELD WITH ACCEPTABLE LIMITS AND RELEVANT INTERMEDIATE YIELDS:
|Dispensed Material||100 %|
|After mixing including in-process and QC samples||NLT 99 % of the dispensed Material|
|Final Yield :|
After packing after QC sample for testing and Control Sample
|NLT 98.0 % of the dispensed Material in terms of number of Bottle|
For any deviation min the final yield of the
The yields specified in the intermediate stage is only to monitor
11.0 REFERENCE METHODS FOR PREPARING CRITICAL EQUIPMENTS INCLUCDING CLEANING ASSEMBLING AND CALIBRATION:
Specific SOP’s to be strictly followed for:
The corresponding equipment’s for Cleaning, Assembling, disassembling and stagnant period of the usage of equipment after cleaning.
For activities related to Area cleanliness, Pest control activities, Fumigation, Bio burden estimation, Air Change Controls, Pressure differentials.
All the in-process instruments are calibrated and records are available.
Accessory instrument installed on the manufacturing equipment and standards for calibration of in-process instruments to be confirmed to ensure calibration from external lab Accredited with NABL. With the availability of calibration certificates with traceability.
12.0 INSTRUCTIONS FOR LINE CLEARANCE AND INPROCESS CONTROL:
Check to ensure that the manufacturing area is free from previous product residues and materials, containers, labels and records.
Ensure to check that all the records pertaining to area cleaning viz floors, walls, doors, ventilators, glass panels, are recorded, signed and counter signed to confirm the cleanliness of the area.
Supporting records and raw data’s pertaining to fumigation, sanitation and bio burden are recorded, signed and counter signed.
Ensure that the pressure differentials, humidity and temperature of the blending area is monitored within the predetermined limits and records are available.
If required send the swab and rinse solvent samples of the manufacturing equipment collected by QA department.
Check to ensure that updated Batch manufacturing record with appropriate signatures and counter checks by QA department for initial checks and in-process checks are available
Ensure that only personals including operators, manufacturing chemists and qualified for the appropriate jobs are assigned to perform the respective activities and records of qualification are available.
Ensure that personals involved in the manufacturing activities viz. Production Chemists, IPQA and operators are wearing protective apparels, Nose masks, Hand gloves, Head gears & goggles.
Note: In addition to the In-process instructions described above under general, in process instructions for specific areas as under requires to be followed.
13.0 INSTRUCTIONS FOR LINE CLEARANCE AND INPROCESS CONTROL
Check for the area cleanliness of the granulation area and the blending area, where the drying and blending activities takes place.
Ensure to confirm that the exterior surface of the Tray drier, Bin Blender, and Sifter are cleaned.
Ensure to confirm the cleanliness of the inner surface that comes in contact with the material and other inaccessible critical areas.
Check to ensure that the correct materials are dispensed with appropriate quantity are available for process.
14.0 DETAILED STEP WISE PROCESSING INSTRUCTIONS FOR HOMOGENITY OR UNIFORMITY IN BLENDER MIXING
Sifting and blending activities to be done under controlled conditions of Temperature and Relative humidity of 15▫ C ±2▫C & 15%±2%RH.
Sift the manitol through #40 then Dry manitol for one hour in a tray drier at 500C and record the temperature.
Ensure for the sieve integrity of sieve of mesh size #60.
Sift the Excipient sod. Benzoate, aspartame, Xanthum gum and sylloid AL-1 FP, Talcum and aerocil , mix fruit flavour and Titanium dioxide through sieve of 60 #.
Collect the sifted material into a common double lined LLDPE bag.
Sifting of Active Ingredients
Check for the Sieve integrity of the sieve of mesh number #60.
Sift separately Amoxicillin Trihydrate, and Diluted Potassium Clavulanate through sieve of mesh no
Collect the sifted Amoxicillin Trihydrate and Diluted Potassium Clavulanate into separate double lined poly bags.
Transfer the total sifted contents completely into a octagonal blender.
Ensure for the closure of the octagonal blender with the lid , air tight.
Set the RPM at 4 and time interval of 30 minutes.
Switch on the octagonal blender, and mix the contents for 30 minutes.
TRF (Raise Test Request Form) and send to QA department for sampling to be tested by QC department of release.
The water activity is performed at the specified temperature and humidity of 15▫C±2▫C & 15%±2% RH.
Dispensing of Active Materials.
Owing to the sensitivity of the active ingredients. The active materials Amoxycillin Trihydrate and Potassium Clavulanate are dispensed in the same area immediately before sifting.
The temperature and humidity are monitored at temperature of 15ºC ± 2ºC & Humidity of 15%±2%RH, 30 minutes prior to weighing and the same condition maintained until the completion of weighing of the active material and followed by sifting, serial dilution and blending.
Recording of the temperature and humidity parameters recorded and plotted against time for trend analysis.
Inlet and outlet of the AHU’s
Dust collector bags.
Area Line Clearance:
Ensure for the absence of:
Residues of the previous products
Labels and containers of the previous products.
BMR of the previous product.
Check that the updated BMR of the running batch updated to the previous stage
15.0 INSTRUCTIONS FOR IN-PROCESS CONTROLS WITH THEIR LIMITS:
REQUIREMENTS FOR STORAGE CONDITIONS OF THE PRODUCTS, INCLUDING THE CONTAINER, LABELLING AND SPECIAL STORAGE CONDITIONS WHEREVER APPLICABLE:
During the different stages of manufacturing and packing, viz. Blending filling and primary packing. Following to be considered:
Should be stored in double lined LDPE bags of appropriate size.
The mouth of the LLDPE bags should be firmly tied with nylon threads.
The LLPE bags further placed in HDPE containers.
The Net weight of the Semi bulk product to be recorded after weighing the tare weights of the double poly lined bags and the empty drum weights.
The Gross, Tare and Net weights of the individual containers to be recorded in the BMR and LOG book.
The same to be counter checked by QA department with appropriate signatures.
Sufficient number of Silica gel bags should be distributed on the LLDPE bags
Containing the Bulk product.
Ensure that the Silica gels are effective retaining blue color.
The Lids of the containers to be close air tight stored and monitored at a temperature 15 ▫C±2▫C and a Relative humidity of 15% ±5%.
As far as possible a minimum time interval to be maintained during each stage.
Containers processing the semi bulk products viz. should be fixed with labels with the following contents:
Name of the Product (in generic name)
Stage of Process:
Signature of the Chemist & Date:
The above contents remain the same except *Container No. & **Stage of Process.
The Environmental monitoring of temperature, relative humidity and the stagnant time of storage of the semi bulk product after each processing stage to be recorded in Log book.
containers are relabeled with the following contents
Name of the Product (in Brand name)
Batch Number (Alphanumeric code of the Brand Name)
Batch Size: (As per the Plan)
Stage: Filling and sealing.
Signature of the Chemist & Date:
16.0 ANY SPECIAL PRECAUTIONS TO BE OBSERVED
Ensure that cleaning of area of done as per SOP before start of operation.
Mixing, filling should be done as per SOP.
All the equipment and accessories used for manufacturing and filling area should be cleaned as per SOP.
Manufacturing & filling area enter procedure should be strictly followed as per SOP.
Packed quality should be checked every half hour interval.
Leakages of the field bottle should be checked as per SOP.
Individual bottles are subjected for visual inspection by trained personnel as per SOP.
Prior to packing : Overprinting of strips and boxes should be done as per SOP.
Packing should be done in packing area as per SOP.
Activities like dispensing , Blending , filling and packing to be carried out at control temperature and relative humidity of 15▫C ± 20C and 15 %±2% RH respectively.
Active ingredients Amoxycillin Trihydrate and Potassium Clavulanate to be dispensed immediately before blending at the controlled temperature and relative humidity of 15▫C ± 20C and 15 %±2% RH respectively.
Actives to be sifted through #60 before blending, Temp.15 ▫C±20C and a Relative humidity of 15% ±2%.
17.0 Water activity test to be performed at the following stages:
Excipients flavours, Xanthan Gum, Sweating Agents, after drying.
Blending and before starting the filling of bottles.
After, filling and labeling.
The water activity should NMT 0.2%
The Bulk finished product after different stages .of process should be stored in double lined LLDPE Bags further stored in Drums with sufficient number of dried Silica gel bags and the drums of the lid closed air tight.
During the entire stagnant time the environment to be monitored at controlled temperature and relative humidity of
18.0 PACKING DETAILS AND SPECIOMEN LABELS RELATING TO THE PRODUCT
Each outer carton contain 30m, 60ml,botte with WFR.
Configuration of Tertiary packing depends on the carton dimension used, and dimension of the Shipper-which is different for different customers
19.0 REFERENCE DOCUMENTS
BMR & BPR
Log Books and Records
Calibration records and approved labels
Chemists and operator qualification records for specific jobs
QA = Quality Assurance Department
SOP = Standard Operating Procedures
OPI = Over printing Instruction
21.0 COPIES TO DISTRIBUTION SITES
|1.0||Quality Assurance||Master Copy|
|Document Cell Owner-QA Ex.QA Head|
|2.0||Production Department||Control Copy||Head Production|
22.0 MATERIAL RECONCILIATION
|ITEM DESCRIPTION||Bottle||Label||WFR||CARTON||SHIPPER||SHRINK WRAP||BOPP TAPE||CELLO TAPE|
|C||Extra Qty. Taken|
|D||Total Qty. ( B + C)|
|E||Rejection During Overprinting|
|F||Rejection during Packing|
|G||Total Qty. Rejected|
( E + F )
|PACKED QUANTITY DETAILS|
|H||Qty. Returned To Stores in Numbers.|
|I||Total qty. used|
D – (G+H)
Done By :Production
|Reconciliation Checked By: IPQA|
23.0 FINAL RECONCILIATION OF PRODUCT.
(Details to be entered after completion of batch packing)
Note: Write “NA” whenever is Not Applicable.
|Sr. No.||Description||In Nos.|
|A||Batch Size ( In no. of Bottles)|
|B||Actual Batch size for packing|
|C||Tablets transferred from manufacturing to packing In kg :____________|
|D||Quantity transferred to Finished Goods Stores (In No. of Blisters)|
|E||Total sample qty|
|F||Total quantity packed (D+E)|
|G||Inspection Loss of defoiled tabs|
Batch Yield = (F/B x 100) = _____________ % (Limit =98.0 to 102%)
Reconciliation Done By: ____________ Checked By: ___________ Verified By: ___________
(Production Officer/Executive) (Department Head) (IPQA Officer/Executive)
Note: – Give justification for % Yield Limit Variation, if any & take approval from QA Head.
Justify by (Head Production) _________________
Sign/Date (QA Head) _____________________
|24.0 RECONCILIATION OF DOCUMENTS|
|Sr. No.||Document Title||Observation||Checked By (QA)|
|1.||Environment Control Record.|
|3.||Packaging Order (Primary).|
|4.||Raw. Material Tags Card sheet.|
|5.||Area/Equipment Clearance Tags Card Sheet.|
|4.||Wash Water Analysis Report.|
|6.||Manufacturing and compression Operation Card.|
|7.||Bulk Analysis Request And Report.|
|10||Packaging Line Clearance Operation & Inspection Record.|
|11||Weighing Sheet Corrugated Box.|
|12||Printed Packaging Coding & Accountability Record.|
|13||Certificate of Analysis – Finished Products.|
|14||NCR if any.|
|15||Finished Good transfer Slip.|
|16||Terminal Inspection Report.|
|17||Additional material requirement form.|
|18||Washing of Containers, Equipment and Accessories Record.|
25.0 BATCH HISTORY
Record Deviation / Incident/NCR:-
|Sr. No.||Page No.||Detail of NCR||Corrective Action||Preventive Action||Done by||Verified by|
Production Officer/Executive IPQA Officer/Executive
Sign & Date Sign & Date
26 .0 RELEASE ORDER AND FINISHED GOODS STORES TRANSFER RECORD
We have verified the batch records of the following product and release and batch quantity given against if for Sale and distribution. The batch number given below has been produced and controlled in accordance with the requirement of the tablets claim and all other relevant provision required for production of this.
Sign. Manager-Prod. Sign. Manager-QA
27.0 QUANTITY PER SHIPPER: _____________
|Date of Finished Goods Stores transfer||Pack Size|
|Nos. of Box|
|Nos. of shipper Packed||Finish Goods Transfer Note|
|Executed Batch Packing Record Reviewed By|