Amoxycillin and Potassium Clavulanate Oral Suspension IP

Master Formula Record

Amoxycillin and Potassium Clavulanate Oral Suspension IP

  INDEX

 1.0 Purpose:

To provide instructions for the preparation of Master formula Record for Amoxycillin Trihydrate and Potassium Clavulanate 228.5mg Oral Suspension. 

2.0 Objective:

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.

3.0 Scope:

This procedure is applicable for the preparation of Master formula Record for Amoxycillin Trihydrate and Potassium Clavulanate 228.5mg Oral Suspension.

4.0 Responsibility:

Follow up: QA Executive

Overall responsibility: QA Head 

5.0 Product Details:   

6.0 LIST OF EQUIPMENT’S: 

7.0 BILL OF MATERIALS:

  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

=…………………Kg

. Quantity to be dispensed for Potassium Clavulanate:

100                                                     100

……….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

=………………..Kg

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)

  Ph                                         3.8-6.6 

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: 

 Note:

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:

IN GENERAL:

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

DURING BLENDING

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.

Sifting

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

#60.

Collect the sifted Amoxicillin Trihydrate and Diluted Potassium Clavulanate  into separate double lined poly bags.

Blending

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.

Area Cleanliness

Floor

Walls

Top Ceilings

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:

Container Number:

Name of the Product (in generic name)

Batch Number

Batch Size

Mfg. Date

Expiry date

Gross weight

Tare Weight

Net Weight

Stage of Process:

Signature of the Chemist & Date:

Storage Condition:

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)

Mfg. Date

Expiry date

Gross weight

Tare Weight

Net Weight

Stage: Filling and sealing.

Signature of the Chemist & Date:

Storage Condition:

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

Label.

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

Relevant SOP’s

Log Books and Records

Specifications

Calibration records and approved labels

Chemists and operator qualification records for specific jobs 

20.0 ABBREVIATIONS:

QA  = Quality Assurance Department

 SOP = Standard Operating Procedures

  OPI  = Over printing Instruction 

21.0 COPIES TO DISTRIBUTION SITES  

 22.0 MATERIAL RECONCILIATION

23.0 FINAL RECONCILIATION OF PRODUCT.

(Details to be entered after completion of batch packing) 

 Note:    Write “NA” whenever is Not Applicable.

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)

Sign/Date (QA Head) _____________________

25.0 BATCH HISTORY

       Record Deviation / Incident/NCR:-

                 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.

      Checked by     

                                                                                                                                            Released By

          Sign. Manager-Prod.                                                                                         Sign. Manager-QA

27.0 QUANTITY PER SHIPPER: _____________