SOPs

Artwork Management Procedure

Artwork Management , Purpose:

Artwork Management , To lay down the general guideline about preparation, approval and preservation of artwork, printed specimen and approved color and design standard of printed packaging materials that are required to develop packaging materials for products.

Artwork Management , Scope:

This SOP is applicable for art work development of new as well as existing products of both General and Sterile Block in XX pharmaceuticals limited.

Definition/Abbreviation:

[][]PD : Product Development
[][]PMD : Product Management Department
[][]QC : Quality Control
[][]QA : Quality Assurance
[][]SCM : Supply Chain Management
[][]XX : Current Version

Responsibilities:

[][]The roles and responsibility are as follows:

Marketing Department

[][]Preparation and checking of text for the packing materials.
[][]Raise a change control in case of any change in the existing art work.
[][]Prepare the final art work for regulatory submission.
[][]Design of all art work as per dimension and text.

Product Development Department

[][]Checking the draft art work for dimension and texts.
[][]Checking dummy carton and machine proof sample and shade card.

Quality Control

[][]Generation of packing specification according to approved artwork and shade card.

Quality Assurance

[][]Checking the text of draft, dummy and machine proof sample.
[][]Preparation and timely review of the SOP.

Head of Marketing

[][]Check and review of all Art works.

Head of Plant Operation

[][]Review of all art work.

Head of Quality Assurance

[][]Approval of all art works as per XX specification.
[][]Approval of the SOP.

Procedure:

[][]After receiving product proposal report from PMD, PD will generate Artwork Technical specification according to Annexure–I and send to PMD. PD will also preserve a copy in the product master file.
[][]PMD will generate the artwork as per Artwork Technical specification (Annexure-I) and send two copies artwork to Quality Assurance. PMD will also generate material code in ERP.
[][]Each artwork will contain the respective material code and version no. with signature of PMD personnel.
[][]Quality Assurance will check the artwork and will take comment from PD regarding label claim, pack size, primary packaging information, and width of foil etc. for any new product and new width of foil or new dimension of carton for existing products. For any correction Quality Assurance will forward the artwork copy to PMD department for further action.

[][]After all reviewing, Quality Assurance & PD will sign the artwork and then forward to Head of Plant Operation for checking.
In the meantime, size and shape (dimension) of the Packaging materials will be confirmed by machine trial or by operation with dummy samples. After receiving dummy samples from PMD, PD and Production will work jointly to finalize the size and shape.
[][]PD will provide samples of required size strips/blisters to PMD for preparation of dummy carton when requested.

[][]Head of Plant Operation will review the artwork and send to Head of Quality Assurance for final approval.
[][]Quality Assurance will send one copy of approved artwork to PMD and preserve another copy at QA.

[][]For new product, PMD will raise commercial requisition after getting three month stability declaration from PD. After commercial requisition Supply Chain will find out the source for preparation of shade card.

Selection of Color:

[][]PMD will suggest the color of Printed components by considering the following:
[][]Preferably color shall be dissimilar in different strengths of same product.
[][]Color shall be stable and not fade on storage or during any operation of the material.
[][]Suggested color shall be forwarded to PD and Quality Assurance for comment.
[][]In case of any major anomaly in color selection, final decision shall be taken jointly by PMD and PD.

Approved Color and Design Standard of Printed Packaging material:

[][]PMD will then send 5 standards of packaging materials to Quality Assurance. Quality Assurance will check the text of printed components against approved artwork and give comments. These standards are for:
=>PMD Copy
=>Quality Control Copy
=>Quality Assurance Copy
=>Supply Chain Copy
=>Supplier Copy
[][]Quality Assurance will send one copy of approved shade card along with artwork to QC for preparation of specification.
[][]After approval of specification, QA will send controlled copy of specification along with shade card to QC, PMD, Supply Chain and the Supplier.
[][]For supplier approval / alternate source development, Supply Chain will send source approval document to QC through PMD. Source approval documents are:
=>Duly filled Vendor Questionnaire
=>Vendor Approval Form
=>Certificate of Analysis/ Conformation
=>Supplied list of material

Change Control:

[][]Any change in the printed components like foil/ carton/ leaflet/ label shall be processed following SOP.
[][]Any change in pack size or brand name of the product shall require approval of local Drugs Authority/Regulatory Authority.
[][]When any change in packaging components, PMD and Supply Chain should ensure that following documents will be collected from the supplier through Obsolete Form of Artwork/ Supplier (Annexure-II). Documents are:
=>Previous version of Artwork
=>Previous version of Shade card
=>Previous version of Plate positive
=>When any supplier will be rejected from approved vendor list, Supply Chain will be proceed through Obsolete Form of Artwork/ Supplier (Annexure-II).

Annexure:

Annexure – I: Artwork Technical Specification
Annexure – II: Obsolete Form of Artwork/ Supplier

Artwork Management Procedure Read More »

Line Clearance Procedure

Job Solution, Quality Assurance, SOPs

Line Clearance Procedure, Purpose :

Line Clearance Procedure, To ensure that the area and equipment to be used for the dispensing, manufacturing and packing of products are free from remnants of previous product/batch.

Line Clearance Procedure, Scope :

This procedure is applicable for clearance of dispensing, manufacturing, packing area & equipments at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]N/A

Responsibilities:

[][]The roles and responsibility is as follows:

Quality Assurance Personnel

[][]Responsible to perform the activities as per SOP.

Concerned department

[][]To maintain procedure as described in SOP

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Procedure:

Dispensing:

[][]Before start of dispensing of raw material/coating material Production Executive shall check the following and keep record in BMR.
[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Equipment cleanliness
[][]Removal of material of previous batch/product from dispensing area
[][]Balance calibration records, daily accuracy check/ function check of balance
[][]Entry in Log book
[][]Status label of material/ component
[][]Cleanliness of container of material to be dispensed.
[][]Quality Assurance Executive shall monitor and then provide counter check/ signature to ensure that line clearance checking has been performed properly by dispensing people and all above stated parameters are satisfactory.

Manufacturing:

[][]For Granulation/ Compression/ Blending of Powder or Pellets/Coating
[][]Before start of any manufacturing operation concerned Production Executive shall check the following parameters and keep the records in BMR.
[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Equipment/ machinery cleanliness
[][]Removal of material of previous batch/product from granulation/ compression/ blending/ coating area.
[][]Balance calibration records, daily accuracy check/ function check of balance
[][]Room Temperature and % Relative Humidity of the granulation/ compression/ blending/ coating area (if applicable)
[][]Entry in Log book
[][]Room display/ Product display

For Powder for Suspension/ Encapsulation:

[][]Before start of any manufacturing operation concerned Production Executive shall check the following parameters and keep the records in BMR.
[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Equipment/ machinery cleanliness
[][]Removal of material of previous batch/product from area
[][]Balance calibration records, daily accuracy check/ function check of balance
[][]Room Temperature and % Relative Humidity of the manufacturing area (if applicable)
[][]Entry in Log book
[][]Room display/ Product display

Packaging:

[][]Before start of any packaging operation concerned Production Executive shall check the following parameters and keep the records in BPR.
[][]Printing Line Clearance
[][]Name of the previous product (to be recorded)
[][]Batch No. of previous product (to be recorded)
[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Entry in Log book
[][]Room display/ Product display

Packaging Area Equipment Clearance:

[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Equipment/ machinery cleanliness
[][]Removal of material of previous batch/product in packaging line
[][]Room Temperature and % Relative Humidity of the packaging area (if applicable)
[][]Entry in Log book
[][]Room display/ Product display

Annexure:

N/A

Line Clearance Procedure Read More »

Batch Release Procedure

Quality Assurance, SOPs

Batch Release, Purpose:

Batch Release, This procedure defines the correct procedures for the release and distribution of finished products to ensure Assurance with the requirements of GMP and includes details of the responsibility of the Authorized Persons.

Batch Release, Scope:

This SOP is applied to storage, release and distribution of finished products and it’s supporting activities at XX Pharmaceuticals Limited (Both General & Sterile).

Definitions / Abbreviation:

[][]QA : Quality Assurance
[][]SOP : Standard Operating Procedure
[][]FIFO : First In First Out
[][]COA : Certificate of Analysis

Responsibilities:

[][]The roles and responsibility is as follows:

Production Executive

[][]Check the quantity of the product before transfer into the ware house.
[][]Transfer the finished goods to warehouse.
[][]Issue Transfer Note accordingly

Warehouse Executive

[][]Receive finished goods from the production floor after proper checking.
[][]Keep the finished product into the ware house accordingly.
[][]Transfer the finished goods to central warehouse after getting release note from QA.

Quality Assurance Executive

[][]Check the quantity of the product before transfer into the ware house.
[][]Compilation of Batch Production Record.
[][]Follow the overall batch release procedure.
[][]Quality Control Executive/ Microbiologist
[][]To provide analytical support for various samples drawn for batch release.
[][]Prepare Certificate of Analysis (COA).

Head Of Quality Assurance

[][]Give approval to release the finished goods into the market.
[][]To ensure Assurance of the SOP.
[][]Approval the SOP.

Annexure:

Annexure-I: Checklist for Batch Documentation
Annexure-II: Finished Product Release Note
Annexure-III: Final Inspection Sheet

Procedure:

[][]After completion of packaging operation, finished packed shipper cartons will be stored at the Quarantine area of packaging hall. Production Executive will raise the Finished Goods Transfer Note to Quality Assurance Department for final inspection mentioning product name, batch number, quantity, master carton number.

[][]The finished product will be transferred to warehouse after physical checking by Quality Assurance Executive according to final inspection sheet (Annexure- III).
[][]Warehouse Executive will check the product name, batch number, quantity, pack size, and label of finished product(s) against the transfer note during receiving.
[][]If all information (Product name, batch number, quantity, pack size, label) of finished product transfer note is matched with transferred quantity, then Warehouse Executive will receive & store the product in QUARANTINE AREA (for finished product) of warehouse maintaining storage condition as per attached product label on the shipping carton.
[][]After completion of full batch packaging, Production Executive will submit the Batch Packaging Record to Quality Assurance Department mentioning the transferred quantity in the BPR for release of the product.
[][]Quality Assurance personnel will review all the documents / parameters according to checklist . If all parameters are found complies, then he/she will compile the full batch production record (BMR, BPR) along with all related documents.
[][]After compilation of the batch documents, QA Executive will entry in the ERP of release note verification and Head of QA will approve the release in the software.
[][]Quality Assurance will attach the Approved Label in every pallet containing released product. (One labels per pallet).
[][]During reviewing the documents according to the check list, following matters need to be considered.
[][]Batch Manufacturing Record (BMR)
[][]Evaluate all the in-process result are within limit, cleaned/partially cleaned label are available, dispensing weights are accurate & dispensing slip along with print out is available, all manufacturing part has been done as per instruction, all the responsible persons have signed in respective operation stages in BMR.
[][]If any deviation/change control was raised, reference number is recorded in the respective place of BMR.
[][]Review the reconciliation steps are correctly calculated and loss result is justified.
[][]Review the line clearance in each steps of manufacturing and Packaging stages are signed by responsible person.
[][]Review the related Deviation/Change Control is closed and the reference number of this documents are recorded in the respective area of the BMR.
[][]Review the completed BMR is approved by Quality Assurance and Production after completion of operation.
[][]Review the associated documents such as all relevant labels, IPC record, particle count record (If any) is correct and signed. Review all the results are within limit or not. If any results are found out of limit, then related Out of Specification (OOS) is attached with the document.
[][]Review the completed BMR is approved by Head of Production or his/her designate and Head of Quality Assurance or his/her designate after completion of operation.

Certificate of Analysis (COA)

[][]Review the Certificate of Analysis (Chemical and Microbial) is signed and approve by responsible person. Review all the results are within the specification. Review all the print out of QC analysis result attached with COA.

Batch Packaging Record /BPR (Primary and Secondary)

[][]Review all the packaging materials are correctly dispensed and authentication information for packaging start up is correct.
[][]Review the in process checks are routinely performed.
[][]Review the reconciliation steps are correctly calculated and Yield & loss result is justified.
[][]Review the line clearance in each step (i.e. primary packing, secondary packing), inspection and labeling are signed by responsible person.
[][]Review the related Deviation/Change Control is closed check the presence of the Deviation/Change Control reference number into the respective place of BPR.
[][]Review the completed BPR is approved by Head of Production or his/her designate and Head of Quality Assurance or his/her designate after completion of operation.

Review the quantity of the packs and presence of all signatures accordingly.

[][]Head of QA/Designee shall verify the Batch Production Record as per checklist (Annexure-I) for correct entries, reconciliation of quantity, yield, change control, deviation, out of specification (OSS), (if any), in-process checking records analytical test results etc. After reviewing if all the parameters found satisfactory then the Manager, /designee shall release the product for dispatch.
[][]For dispatch of finished product, Quality Assurance personnel will issue the Finished Product Release Note (Annexure-II) for getting approval from Head of Quality Assurance. Finish Product Release Note is a self carbonated pre-printed copy as per the original approved copy of Annexure-II
[][]Which contains three different colors Then one carbonated (Yellow colored) copy of the finished product release note will send to central warehouse for distribution. The original blue colored copy will be attached with the batch document.
[][]In case of release of any optimization or validation batch before completion of process validation report, & risk analysis report must be conducted before release. All the documents are approved accordingly by Head of Quality Assurance or his/her designate.
[][]Full batch will be released at a time after completion of the total packaging operation of the batch.
[][]After QA release, Warehouse Executive will store the released product orderly in separated passed area maintaining storage condition. FIFO must be maintained by warehouse executive during dispatch of the released product for distribution.
[][]Quality Assurance Executive will compile all the batch records and kept in the respective Batch Production Record archive area after keeping record in the document archiving log book.
[][]Batch history which must be kept for one year after expiry of the batch.
[][]Fraction batch quantity can only be released with same batch number (while the batch is fractioned as Commercial, Trial Aid or Export) after approval of Head of Quality Assurance.

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Room Numbering System

Quality Assurance, SOPs

Room Numbering , Purpose:

Room Numbering , To provide guidelines for numbering system to all rooms of General Block and Sterile Block in XX Pharmaceuticals Limited.

Room Numbering , Scope:

This procedure is applicable for assigning sequential identification number to all rooms located on each floor of the production, PD/QC/Microbiology area and other area related to Plant operations such as warehouse, plant room, utility area etc are also included in room numbering system.

Definition / Abbreviation:

[][]None

Responsibilities:

[][]The roles and responsibility are as follows:

Executive / Sr. Executive, Engineering

[][]He / she shall be responsible for assigning the sequential identification number to all rooms.

Quality Assurance personnel

[][]He/she shall be responsible for effective implementation and monitoring of procedure.

Quality Assurance Head or Designee

[][]To ensure implementation of SOP.

Procedure:

[][]Numbering for Room
[][]Each room shall be assigned a unique identification number.
[][]Engineering department shall assign floor wise alpha numeric sequential identification Number to all rooms in a logical order on lay out and record the numbering details in Annexure –I.
[][]Do not repeat the same number to another room.
[][]The room numbering shall be a floor wise sequential number having 6 characters as shown below.
=>e.g. GPRXXX
where
=>(G) is the code for General Block
=>(PR) is the working area code for production
=>(XXX) is the first sequential number of room start from 001 to 999
=>Next room shall be numbered GPR002 ……….& so on.

[][]The Building code for each building is given below.

Building name/ Code

=>General Block/G
=>Sterile Block/C
[][]The Working area code for each area is given below.

Area/ Code

=>Production/PR
=>Packaging/PK
=>Warehouse/ WH
=>Product Development/ PD
=>Quality Control/QC
=>Microbiology/MB
=>Mezzanine /ME
=>Roof Top/RT
=>Engineering/EN

Annexure:

Annexure – I: List of rooms

Room Numbering System Read More »

In Process Check (IPC) Procedure

GMP, Quality Assurance, SOPs

In Process Check, Purpose :

In Process Check, To set up a general guideline for in-process checking that will be followed during the course of manufacturing. This SOP also includes handling of IPC parameters failure during production.

In Process Check, Scope :

This procedure is applicable to all Production activities such as Manufacturing, Packing and warehouse department at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QA: Quality Assurance

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Assurance

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure: In Process Check

General Instruction:

[][]Check the general environment in the department
[][]Ensure proper gowning by the personnel in concerned work area.
[][]Check for the daily calibration of balance.
[][]Check the calibration status label of machines.
[][]Ensure that the line clearance is obtained before starting the next step.
[][]Ensure the destruction of all In-process, rejects, excess overprinted packing material after packing.
[][]Ensure that the every stage of process, appropriate status label is affixed on equipment /machines and containers.
[][]Non Assurance shall be reported immediately to concerned department Head.
[][]Ensure the completion of documentation at the end of each processing stage.

Warehouse Raw Material: In Process Check

=>Ensure line clearance before commencement of dispensing activity.
=>Ensure all the material having properly labeled.
=>Ensure that only “Quarantine” material is stored in quarantine area.
=>Ensure the transfer of Approved material in “Approved Area”.
=>Ensure that storage conditions of raw material are met.

Ensure the following points on Approved Quality Control labels.

=>Analytical Report Number.
=>Re-test date.
=>Ensure that the loose containers are properly closed after dispensing.
=>Ensure that the material is issued on FIFO basis.
=>Ensure that the environmental conditions are maintained in the respective areas.
=>Ensure that the details on dispensed material, material issues slip/dispensing slip are matching with Material Issuance form.

Warehouse Packaging Material:

[][]Ensure proper segregation of materials.
[][]Ensure proper disposal of the rejected items.
[][]Ensure that the material is issued on First In First Out (FIFO) basis.

Warehouse Finished (Drug) Product:

[][]Ensure that the products are dispatched only after QA release.
[][]Ensure the proper storage of goods.
[][]Ensure that “Quarantine” drug product are stored in quarantine area of Warehouse drug product

Parameter for In-process checking during Dispensing:

[][]Area cleanliness, absence of irrelevant/ foreign material.
[][]Equipment cleanliness.
[][]Cleaning record.
[][]Removal of material of previous batch/product from dispensing area.
[][]Balance calibration records, daily accuracy check/ function check of balance.
[][]Status label checking of raw materials prior to weigh.
[][]Weight checking of materials.
[][]Room temperature and Relative Humidity of Dispensing area.

Parameter for In-process checking during Manufacturing:

[][]Generally following parameters shall be checked during manufacturing of tablet/ capsule/ dry powder
[][]Area cleanliness, absence of irrelevant/ foreign material.
[][]Equipment/ machinery cleanliness.
[][]Cleaning record.
[][]Removal of material of previous batch/product from granulation/ compression/ blending/ encapsulation/filling area.
[][]Balance calibration records, daily accuracy check/ function check of balance.
[][]Room temperature and Relative Humidity of the granulation/ compression area (if applicable).
[][]Room display/ product display.

For Tablets:

[][]In Granulation Stage:
[][]Moisture
[][]Temperature (if applicable)
[][]Relative Humidity (if applicable)

In Compression Stage: In Process Check

[][]Appearance (Shape, Surface texture, Physical flaws, Consistency, Identification marking etc.)
[][]Average weight
[][]Uniformity of weight
[][]Relative Standard Deviation
[][]Hardness
[][]Thickness
[][]Diameter
[][]Friability
[][]Room temperature
[][]Relative Humidity (if applicable)
[][]Disintegration time
[][]Machine speed
[][]Organoleptic test (if applicable)

In Coating Stage:

[][]Appearance (Physical flaws)
[][]Average weight
[][]Disintegration time
[][]Weight gain/ coating loss

For Capsules:

[][]In Encapsulation Stage:

[][]Appearance (Color, Size, Identification marking)
[][]Average fill weight
[][]Uniformity of weight
[][]Disintegration time
[][]Relative Humidity of encapsulation room/ area
[][]Temperature of encapsulation room/ area
[][]Locking of capsule

For Powder for Suspension or Syrup:

[][]In Blending Stage:
[][]Relative Humidity of blending/ manufacturing area.
[][]Temperature of blending/ manufacturing area.

In Filling Stage:

[][]Appearance
[][]Relative Humidity of filling room/ area
[][]Temperature of filling room/ area

[][]For Kidney Dialysis Fluid
=>In Manufacturing Stage:
=>Relative Humidity of manufacturing area
=>Temperature of manufacturing area.
[][]In Filling Stage:
=>Uniformity of filling weight
=>pH of solution
=>Conductivity of solution

Checking procedure for IPC during manufacturing:

[][]Room Temperature and Relative Humidity:
[][]Room Temperature and Relative Humidity shall be checked by using Digital Hygrometer and the result shall be recorded in the Batch Manufacturing Record (BMR) in mentioned stage. Room Temperature and Relative Humidity shall be checked as per frequency specified in BMR/BPR.

Moisture:

[][]Moisture shall be checked by using Mettler Toledo balance following corresponding SOP and the result shall be recorded in the Batch Manufacturing Record (BMR) in mentioned stage.

Appearance:

[][]Parameters (as applicable for dosage form type) as mentioned below shall be checked during start-up and in every fifteen (15) minutes interval. About 500 coated tablets from each part shall be checked after completion of coating. Physical flaws of coated tablets shall be recorded in Coated Tablet Visual Inspection Record Sheet.
[][]Color/ Clarity
[][]Shape of tablet
[][]Identification marking
[][]Physical flows in case of capsule

Physical Flaws/ Acceptable Quality Level

[][]Uncoated Tablet
=>Critical Defects (Cracking, Capping/Lamination)/ 0.025%
=>Major Defects (Erosion, Picking/ Sticking)/ 0.25%
=>Minor Defects (Roughness, Illegible logo, Peeling)/ 1.5%
[][]Coated Tablet
=>Critical Defects (Cracking) / 0.025%
=>Major Defects (Blocking, Color Variation, Erosion, Picking/ Sticking) / 0.25%
=>Minor Defects (Twinning, Roughness, Peeling, Core Erosion, Loss of Logo Definition, Logo Bridging ) / 1.5%

The acceptable quality level of physical flaws of coated/ uncoated tablet are as follows:

[][]Weight:

Tablet:

[][]Weight of 05 composite samples, each of which consists of 10/20 tablets shall be checked during start-up and in every fifteen (15) minutes and the result shall comply with the specification as mentioned below:
=>If theoretical tablet weight is ≤80 mg then composite weight shall be in between ±4.0% of theoretical tablet weight.
=>If theoretical tablet weight is >80 mg or <250 mg then composite weight shall be in between ±3.0% of theoretical tablet weight.
=>If the theoretical tablet weight is >250 mg then composite weight shall be in between ±2.5% of theoretical tablet weight.

Capsule:

[][]Composite Fill weight of 10/20 capsules shall be checked during start-up and in every fifteen (15) minutes and the result shall comply with the specification as mentioned below:
=>If fill weight is ≤300 mg then composite fill weight shall be in between ±5.0% of fill weight.
=>If fill weight is >300 mg then composite fill weight shall be in between ±3.0% of fill weight.

Dry powder:

[][]Empty bottle/ plastic container shall be weighted and then tare button of Mettler Toledo balance shall be recorded.
=>After filling with dry powder the filled bottle/ plastic container shall be weighted again to determine the fill weight.
=>Fill weight shall be checked from each filling nozzle. In case of single filling nozzle at least five fill weight shall be checked.
=>The fill weight shall be within the range as specified in BMR. Fill weight shall be checked during start-up and in every thirty (30) minutes interval.

Uniformity of weight: In Process Check

Uniformity weight for tablet and capsule shall be checked during start-up and in every two (2) hours interval.

Tablet:

[][]A number of tablets shall be weighted individually as per the number of punch (if no. of punch is less than 20, then uniformity of weight shall be checked with minimum 20 tablets) of the compression machine. The printed record of statistical data shall be taken and the result of average tablet weight, range of individual weight and % RSD shall be recorded in BMR. The result shall comply with the specification as mentioned below:
[][]Observed average weight shall be within the range calculated with ±2.5 of theoretical tablet weight.
[][]Relative Standard Deviation (RSD) shall be NMT 6.0%.
=>Observed individual tablet weight shall comply with the specification as mentioned below:
=>If tablet weight is ≤80 mg then NMT two tablets shall be outside ±10.0% and none shall be outside ±20.0% range of theoretical tablet weight.
=>If tablet weight is >80 mg or <250 mg then NMT two tablets shall be outside ±7.5% and none shall be outside ±15.0% range of theoretical tablet weight.
=>If tablet weight is ≥250 mg then NMT two tablets shall be outside ±5.0% and none shall be outside ±10.0% range of theoretical tablet weight.

Capsule:

[][]The uniformity of capsule’s fill weight shall be checked by weighing 20 capsules individually. Then the printed record of statistical data shall be taken and the result of average capsule weight shall be recorded in BMR. The result shall comply with the specification as mentioned below:
[][]Observed average capsule fill weight shall be within the range calculated with ±3.0 of theoretical capsule fill weight.
[][]Specification of Relative Standard Deviation (RSD) shall be NMT 6.0%.
Observed individual capsule fill weight shall comply with the specification as described below:
=>If capsule fill weight is ≥300 mg then NMT two shall be outside ±7.5% and none shall be outside ±15.0% range of theoretical capsule fill weight.
=>If capsule fill weight is <300 mg then NMT two shall be outside ±10.0% and none shall be outside ±20.0% range of theoretical capsule fill weight.

Hardness, Thickness and Diameter:

Tablet:

=>Hardness, thickness and diameter of randomly taken 10 tablets shall be checked by ERWEKA TBH 125 machine and a print of found data with statistical evaluation shall be taken and the result shall be recorded in BMR. Hardness, thickness and diameter shall comply with the limit as specified in BMR. Hardness and =>thickness shall be checked during start-up in every one hour interval and diameter shall be checked during start-up.

Disintegration Time: In Process Check

[][]Randomly selected 6 tablets/ capsule shall be placed in 6 different glass tubes of Electrolab ED2 disintegration tester with/without disc (as applicable). The time by which each tablet/ capsule is disintegrated into smaller particles or granules expressed in minutes shall be recorded in BMR. DT of tablet/capsule shall be checked during start-up and every five hours if the batch runs for more than five hours. General guideline for DT of different forms of tablet/ capsule is as follows:
=>Uncoated/ core tablet : NMT. 15 minutes
=>Film coated tablet : NMT. 30 minutes
=>Effervescent tablet : NMT. 5 minutes
=>Hard capsule : NMT. 30 minutes
=>Soft capsule : NMT. 30 minutes
=>Gastro-resistant capsule : 1-2 or 3 hours in acid medium and NMT. 1 hour in buffer medium.

Friability:

[][]Randomly 20 tablets/ 6.5 gm of tablets (for average weight ≤650 mg) or 10 tablets (for average weight >650 mg) shall be selected for friability test. Initially weight of tablets (W1) shall be taken and then be placed in the Friabilator.
[][]The Friabilator shall be run for four minutes at 25 rpm and then tablets of this machine shall be reweighted (W2).Friability of tablets shall be calculated with following formula:

% Friability =W1–W2/ W1×100

[][]A Maximum weight loss NMT 1.0% is considered acceptable for most of the products. Friability of effervescent tablets and chewable tablets may have different specifications.
[][]In case of hygroscopic tablets, an appropriate humidity-controlled environment is required for friability.
[][]Friability shall be checked during start-up and in every two (2) hours interval and be recorded in BMR.

Reconstituted volume for dry powder:

[][]Glassware required for doing the test is 50 ml or 100 ml graduated cylinder.
[][]Water (quantity) shall be taken as specified for the product with a graduated cylinder.
[][]Water shall be poured to the filled bottle and syrup/ suspension shall be made as specified in Leaflet/ Inner carton of the product.
[][]Any observed anomaly (e.g. color, odor, consistency etc.) and the volume with the same cylinder shall be checked.

Parameter for In-Process Checking during packaging:

[][]In case of export besides the following some additional parameters (where applicable) shall be checked like registration no. on foil/label/carton, Text of foil (English/ Bengali), Security overprint on blister/strip etc.

Area:

[][]Room cleanliness
[][]Machine cleanliness
[][]Temperature (0C) [if applicable] [][]% Relative Humidity (if applicable)

Bulk Product:

[][]Product name and strength
[][]Appearance of bulk
[][]Strip/ Blister packing:
[][]General appearance of bulk
[][]Cutting/ perforation
[][]Pocket formation, empty or ruptured pocket
[][]Broken tablets in pocket
[][]Print and color of foils
[][]Color and cleanliness of film (if applicable)
[][]Printing/embossing of Batch No., Mfg. Date and Expiry Date on blister/strip (as applicable)
[][]Improper or inadequate knurling
[][]Sealing (Leak Test)
[][]Camera challenge test (If available on blister machine)

Glass Bottle/ Plastic Container Filling & Packing (Tablets & Capsule):

[][]Appearance of bulk
[][]Quantity per bottle/ container
[][]Cap sealing/ Leak test (as applicable)
[][]Relative Humidity (RH) and Temperature in filling area
[][]Product name with strength on label
[][]Coding Batch no./ Mfg Date/ Exp. Date/ MRP on label (as applicable)
[][]Print and color of label
[][]Security overprint (if applicable)

Inner Cartoning:

[][]Product name and strength
[][]Coding Batch no./ Mfg. Date/ Exp. Date/ MRP (overprinting)
[][]Presence of Leaflet/ Dropper/ Spoon/ Cup/ Cylinder (if applicable)
[][]Adaptability
[][]No. of strip/ blister per pack
[][]Placing of Holographic sticker (if applicable)

Shipping Carton:

[][]Product name and strength
[][]Coding Batch no./ Mfg. Date/ Exp. Date (as applicable)
[][]No. of inner cartons
[][]Serial no.
[][]Size no. and adaptability
[][]Date of cartoning
[][]Signature of the person closing the shipping carton

Checking procedure for IPC during Packaging:

Room Temperature and Relative Humidity:

Room temperature and relative humidity shall be checked as stated above

Leak Test:

[][]At least one sample of conventional strip/ blister/ bottle/ plastic container from each delivery/ cutting channel of the machine shall be picked up from packaging line except sealing machine of one delivery/ cutting channel where two samples shall be collected and checked for integrity following corresponding SOP.
Frequency of Leak test shall be as per following table:

Sample/ Frequency

=>Blister/ Start-up and every hour
=>Empty sealed glass bottles/Start-up and in every hour

[][]If color solution enters into any of the pocket of the strip(s)/blister, into bottle(s)/ plastic container(s) it indicates the leakage.
[][]Calculate the percentage of leakage and record in Leak Test Record Sheet.

Tablet/ Capsule Counting Procedure:

[][]Tablet/ capsule counting procedure shall be performed during start-up and in every 30 minutes.

Annexure: In Process Check

Annexure-I: Coated Tablet Visual Inspection Record Sheet
Annexure-I: Leak Test Record Sheet

In Process Check (IPC) Procedure Read More »

Recall Procedure

Product Complaints, Product Defects, Product Recalls, Quality Assurance, SOPs

Recall, Purpose :

Recall, To ensure recall of products that are known or suspected to be defective or hazardous in accordance with a pre-determined plan promptly and effectively from the market

Recall, Scope :

This procedure is applicable for all products manufactured and distributed from XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Recall: A process for withdrawing or removing a pharmaceutical product from the pharmaceutical distribution chain because of defects in the product, complaints of serious adverse reactions to the product and/ or concerns that the product is or may be counterfeit. The recall might be initiated by the manufacturer, wholesale dealer, license holder, or Department of Health.
[][]Market Withdrawal: Market Withdrawal means a firm’s removal or correction of a distributed product which involves a minor violation that would not be subjected to legal action by the Drugs Administration or which involves no violation, e.g., normal stock rotation practices, routine equipment adjustments and repairs etc.
[][]PMD: Product Management Department
[][]QA: Quality Assurance

Responsibilities:

The roles and responsibility is as follows:

Head of PMD

[][]Responsible for determining the intensity of recall to be taken by consultation with Head of QA and taking necessary action.
[][]When product is distributed in domestic/ overseas market, Head of PMD or his authorized nominee shall inform Head of QA for the action to be taken for recall.
[][]Coordinate the recall after obtaining approval from Managing Director.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Classification of Recall:

[][]Recalls are classified according to the following system
Class I recalls: Occur when products are potentially life-threatening or could cause a serious risk to health.

Examples of Class I Defects

[][]Wrong Product (label and contents are different products)
[][]Correct product but wrong strength, with serious medical consequences
[][]Microbial contamination of sterile injection or ophthalmic product
[][]Chemical contamination with serious medical consequences
[][]Mix up of some products (‘rogues’) with more than one container involved.
[][]Wrong active ingredient in a multi-component product with serious medical consequences

Class II recalls: Occur when product defects could cause illness or mistreatment, but are not Class I.

Examples of Class II Defects

[][]Mislabeling e.g. wrong or missing text or figures
[][]Missing or incorrect information- leaflets or inserts
[][]Microbial contamination of non-injectable, non-ophthalmic sterile product with medical consequences
[][]Chemical/ physical contamination (significant impurities, cross contamination, particulates)
[][]Mix up of products in containers (“rogues”)
[][]Non-Assurance with specification (e.g. assay, stability, fill/ weight or dissolution)
[][]Insecure closure with serious medical consequences (e.g. cytotoxics, child resistant containers, potent products)
Class III recalls: occur when product defects may not pose a significant hazard to health, but withdraw may be initiated for other reasons.

Examples of Class III Defects

[][]Faulty packaging e.g. wrong or missing batch number or expiry date
[][]Faulty closure
[][]Contamination- microbial spoilage, dirt or detritus, particulate matter
[][]Recall system shall be followed in case of Instructions from Regulatory authorities or Voluntary recall by XX authority.

Reason:

=>Reports of adverse reaction.
=>Non-conforming result of on-going stability study.
=>Formulation problem/ Mix-up/ contamination.
=>Labeling errors.
=>Any other reasons.
[][]Head of Quality Assurance shall advise to carry out proper investigation for confirmation of reported defects either jointly or independently by QC, PD, Production & Quality Assurance. PMD personnel can also participate in investigation.
[][]After confirmation and justification of reported defects, Head of Quality Assurance shall discuss with Head of Production and Head of PMD.
[][]Once it is agreed to recall the product(s), Head of Quality Assurance shall seek permission for it from Managing Director (Annexure-III). A Recall Reference no. shall be given on this form as follows:

PR/XX/001
=>Where, ‘PR’ represents Product Recall.
=>‘XX’ represents the last two digits of the year 20XX
=>‘001’ represents for serial number

Recall Panel:

=>Managing Director (MD)
=>Head of Quality Assurance
=>Head of Production
=>Head of PMD
=>Head of Sales
=>Head of Distribution
=>Head of Quality Assurance shall furnish the batch details for recall notification in Annexure-IV. This shall be then forwarded to Head of PMD and Head of sales.

Recall notification shall include:

=>Products name including brand name, its strength and pack size and other details like,
=>Product License (D.A number) if applicable.
=>Batch or Lot number, Batch size, Mfg. date, Exp. date.
=>Nature of defect and reason.
=>Action to be taken (urgent within time frame/ immediate quarantining of stock /return stock) with labeling instruments & specific precautions.
=>Date of withdrawal.

[][]The Head of PMD through Distribution shall send a product recall circular, immediately upon receiving the product recall decision, to all concerned persons requesting them to return all stock of the batch under question to the depots and informing them that a credit note for the stocks returned shall be issued to them at the earliest.
[][]All product recall requests shall be given top priority unless otherwise indicated by recall coordinator.
[][]The Head of PMD along with Distribution shall immediately arrange to freeze all stocks of the batch lying with distributors, agents and customers. He shall also instruct the entire sales force to freeze further sales of batch at every distribution, sales point (stockiest, chemists, doctors, hospitals etc). This shall also include goods under transit.

[][]In case of recall as per directives of competent or Regulatory Authorities, the information shall be forwarded to them (To include Regulatory Authorities of other Countries to which the batch has been distributed). The decision of disposal of recalled batch shall be as per their directives and the destruction or disposal shall be done under notification and the Drugs Inspector’s supervision.
[][]Quality Assurance Department will record the receipt, origin & quantity of any recalled product received & holds the recalled product in a secure place to avoid mix up with other materials.
[][]The progress should be reviewed at regular, frequent intervals to monitor its effectiveness and ultimately to decide that the recall is completed.
[][]Completion will normally be reached when:
=>All the acknowledgement forms issued are returned.
=>The material listed in the acknowledgement forms has been returned.
=>There have been no further returns or further adverse reports concerning the product for a period of 2 weeks.
[][]After thorough investigation, Head of Quality Assurance will issue instructions for safe disposal of the recalled stock in due course and a disposal record will be maintained. An investigation into the root cause analysis of any product defect which led to a recall must be carried out and CAPAs to be prepared to prevent if happing again.
[][]Details of recalls shall be added to the batch dossier for all the batches concerned.
[][]Detailed records of all product returned as part of a recall must be kept.
[][]In case of recall when initiated by company (Voluntarily) this shall be informed to the Regulatory Authority.
[][]In case of voluntary recall, product when received back from market to our depots shall be identified and stored separately in a secured area while awaiting a decision on its disposal. The product shall be written off and destroyed as per the standard procedure.

Documentation:

[][]The decisions, activities and actions including progress of recall shall be documented and duly authorized.
[][]On completion of recall procedure, summary report shall be prepared which shall include the following (Annexure V).
[][]Reason for recall of a product (with Batch No. and other details about the product).
[][]Effectiveness of recall.
[][]Corrective action to prevent reason for recall.
[][]Appropriate training to concern as applicable.

[][]This summary report shall be prepared by Head of Quality Assurance and be circulated to all concerned departments (PD, Production, Accounts, Sales, PMD) and Managing Director.
[][]Distribution records should be readily made available to the person(s) responsible for recall and contain sufficient information of wholesalers, retailers, stockiest and customers/agents for prompt and effective it. (Examples: Addresses, Telephone numbers, inside or outside office working hours, batch number and its quantity with them for both domestic and exported products).

Recall Simulation:

[][]The recall procedure shall be regularly reviewed to ensure that it is up-to-date and shall be simulated ‘in house’ to ensure its effectiveness and familiarity to all key personnel.

[][]The required time limit for simulation exercise (from initiation of simulation to completion) will be not more than 15 days.

Annexure:

Annexure-I: Product Recall Flowchart
Annexure-II: Product Recall Log Book
Annexure-III: Product Recall Form
Annexure-IV: Recall Notification Form
Annexure-V: Summary Report of Recall

Recall Procedure Read More »

Floor Inspection by QA Inspector

Quality Assurance, Quality Management, SOPs

Floor Inspection, Purpose :

Floor Inspection, The purpose of this SOP is to describe the roles, responsibilities and activities of production and QC floor inspection and IPCs check by QA personnel and to ensure Assurance with cGMP requirements.

Floor Inspection, Scope :

This procedure is applicable for cGMP observations of production and QC floor at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]IPC : In Process Check
[][]QA : Quality Assurance
[][]QC : Quality Control
[][]OOS : Out Of Specification
[][]DT : Disintegration Time

Responsibilities:

[][]The roles and responsibility is as follows:

Quality Assurance Personnel

[][]Responsible for inspection of Production and QC floor to find out any cGMP observations.

Manager, Quality Assurance

[][]To ensure implementation of the procedure

Head of Quality Assurance

[][]Approval of SOP

Procedure:

[][]To assure Assurance with specification throughout a production process, Production Department will conduct the IPC checks following the In-process checks procedure.
[][]IPC inspectors of QA will verify the IPC data independently.
[][]The IPC specification will be mentioned in the relevant product specification and BMR & BPR.
[][]All OOS results will be investigated as per OOS results procedure.
[][]IPC inspector will verify the IPC data based on the frequency described in Annexure–I.
[][]During manufacturing of a batch, production personnel will check the IPC parameters.
[][]If a IPC data goes outside specification, production IPC checking personnel and QA IPC inspector will inform to production Executive for corrective measures.
[][]If QA IPC inspector observes that there is frequent failure of the IPC results then QA IPC inspector will notify the issue to Departmental Manager and Manager, Quality Assurance.

All IPCs will be performed by trained and certified QCOM and Production personnel. Inspection of

=>Adherence to Line clearance
=>Environmental conditions
=>Log books
=>General house keeping
=>Labelling status
=>Sampling
=>Reconciliation
=>Calibration status
=>Deviation
=>Pest controls
=>Cleaning & Contamination
=>Change Control
=>Document management
=>Adherence to maintenance schedule

Inspect GMP compliance in

=>Storage of Raw/Packaging materials/Finished packs
=>Manufacturing/packaging/cleaning operations
=>Dispensing of materials
=>Compliance with SOPs
=>Daily balance monitoring records
QA inspectors will visit the production floor daily. The inspection applies to all operations, specially The following:
=>If any unusual observation comes to the notice of area QA inspector, he will immediately communicate to the Departmental Executive. This report will be recorded in Daily IPC report format (Annexure-II).
=>This inspection report will be forwarded to Manager, Quality Assurance for further action.
=>QA inspectors will collect retention samples of finished packs from the running Secondary packaging line belts & record sampling date and quantity sampled in BPR with sign & date as per Sampling SOP.

In-Process Controls Check:

[][]QA Inspectors will independently conduct all In-process checks in addition to that done by production personnel as Procedure for In-Process Checks.
[][]QA inspectors will conduct the following IPC checks as per frequency described in Annexure–I and as a minimum at least once from every batch of product. This should be done at the start of every batch:

[][]Product: Tablets/Capsule

=>Manufacturing Stage: Encapsulation/ Compression/Coating
=>IPC Checks: Appearance, Average weight, Uniformity of weight, Hardness, Thickness, DT, RH & Temperature
=>Manufacturing Stage: Blister Packing
=>IPC Checks: Leak test, Overprinting, Cutting, RH, Temperature, Product name, Strength, Product code, Mfg & Expiry date, Price and Status label etc.

[][]Product: Powder for Suspension

=>Manufacturing Stage: Manufacturing, Filling & Packing
=>IPC Checks: Appearance, Uniformity of weight, Leak Test, RH, Temperature, Product code, Mfg & Expiry date, Overprinting, Price and Status label etc.

[][]Product: Sterile (Capsules/ Tablets)

=>Manufacturing Stage: Encapsulation/ Compression/Coating
=>IPC Checks: Appearance, Average weight, Uniformity of weight, Hardness, Thickness, DT, RH & Temperature.
=>Manufacturing Stage: Blister Packing
=>IPC Checks: Leak Test, Overprinting, Cutting, RH, Temperature, Product code, Mfg & Expiry date, Price and Status label etc.

[][]Product: Sterile (Powder for Suspension )

=>Manufacturing Stage: Manufacturing, Filling & Packing
=>IPC Checks: Appearance, Uniformity of weight, Leak Test, RH, Temperature, Product code, Mfg. & Expiry date, Overprinting, Price and Status Label etc.

[][]Product: Dialysis Fluid

=>Manufacturing Stage: Manufacturing, Filling & Packing
=>IPC Checks: A Appearance, pH, Weight, Induction Sealing, Cap Sealing, Leak Test, Temperature, Pressure

[][]QA inspectors will verify the IPC results as per specification.
[][]If any batch is completed before inspection of QA IPC inspector, then again QA IPC inspectors will verify the some critical parameters.
[][]In-process test failures must be brought to the attention of the Departmental Executive/ Manager & also Manager, Quality Assurance and appropriate action shall be taken and recorded.
[][]Any problem identified at production floor during printing or in-process checking during packaging, Problem observer immediately inform it, to his/her supervisor and if required Online Problem Notification Form (Annexure-III) to be raised by production through QA.
[][]Reference No. for Online Problem Notification will be as
PN-001/02/XX
Where-
=>PN represents Problem Notification
=>001 represents sequential number
=>02 represent Month of February
=>XX represents year of 20XX

[][]If any receiving quantity of packaging material requires replacement to run production smoothly, it shall be raised by production with Material Replacement Form (Annexure-IV) to warehouse through QA with justified reason for replacement.
[][]Reference No. for Material Replacement will be as
MR-001/02/XX
Where-
=>MR represents Material Replacement
=>001 represents sequential number
=>02 represent Month of February
=>XX represents year of 20XX
[][]The copy of raised Online Problem Notification Form should be sent to Manager, Supply Chain & Management with recommendation of Head of Quality Assurance if required.

QC Floor Inspection:

[][]QA IPC Inspector will also visit the Quality Control laboratory once daily for GLP in place and in use check.

Annexure:

Annexure-I: In-Process Checks
Annexure-II: Daily IPC Finding and Observation Report Sheet
Annexure-III: Online Problem Notification Form
Annexure-IV: Material Replacement Form

Floor Inspection by QA Inspector Read More »

Market Complaint Handling

Product Complaints, Product Defects, Quality Assurance, SOPs

Market Complaint , Purpose :

Market Complaint , To provide a system for timely response to a product complaint and to make relevant investigation and recommendation with proper documentation.

Market Complaint , Scope :

This procedure is applicable to all types of market complaints received from the market, related to quality, packing and shortage of the products manufactured at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Market Complaint: A written or verbal report originating from customer, retailers, physicians, field supervisor, regional sales coordinator, medical representative, hospitals, regulatory agency and our employees which relates to the inadequacy of the quality, i.e. non Assurance with standards or customer requirements and includes any packaging and labeling requirements, any query regarding specifications, analytical procedure, incomplete text and non conformance with customer requirements should be treated as complaint.
[][]Customer: The person or institution making the complaint.
[][]PMD: Product Management Department.

Responsibilities:

[][]The roles and responsibility is as follows:

Executive/ Manager, PMD

[][]Send the complaints with appropriate details & samples to Manager, Quality Assurance.

Quality Assurance Manager/ designee

[][]Responsible for registering, carrying out the investigation and taking necessary corrective actions, providing necessary technical response to PMD in consultation with General Manager, Plant and Manager, Quality Assurance, generation of the complaint report and closure of the complaint.

Manager, Quality Control

[][]Responsible for carrying out the analysis of samples as per requirement.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Procedure:

Classification of Complaints:

[][]Market complaints to be classified as minor, major and critical.
[][]Minor: Complaints related to physical appearance of packaging of the product.
[][]Major: Complaints related to physical appearance of the products (e.g. broken tablets, fading, spots etc), packaging quantity (e.g. empty blister, empty bottles, empty content etc), label missing, batch printing missing etc.
[][]Critical: Chemical property complaints related to any chemical test failure of a product, e.g. low purity, change in the impurity level and degradation and shall also include the complaints arising due to stability failure. In the event that a batch is considered to be actually or potentially harmful to user, thereby requiring a recall, following relevant SOP.

Raising of Product Complaint:

[][]Any market complaint received or to be raised by PMD / Sales team shall be filled up in the market complaint form (Annexure-III) along with complaint details (Attach original complaint document to this Annexure if applicable). If the details of the complain are not available in the document then the details of the chemist shop or recipient from where the complaint has been received will be recorded in the market complaint form.
[][]Customer complaints which are received by PMD or complaint raised by PMD will be forwarded to Manager, Quality Assurance with appropriate details in the market complaint form (Annexure- III).
[][]Head of Quality Assurance shall send the complaints along with complaint sample, if received, to Manager, Quality Assurance.
Manager, Quality Assurance shall arrange the investigation and generate a comprehensive report on the market complaints investigation form (Annexure–I).

Investigation of complaints:

[][]Manager, Quality Assurance shall record the complaint in a market compliant logbook (Annexure–II). This detail should include a complaint number, name of the product, batch No., Mfg. date, Expiry date, nature of the complaint, name & address of complainant and date of receipt at the investigating site.
[][]Quality Assurance shall assign a distinct control number to every complaint as follows:
MC/XX/001
Where,
MC – Market Complaint.
‘XX’ represents the last two digits of the year 20XX
‘001’ represents for serial number of the market compliant on continuous basis starting from
001 for the calendar year.
[][]If complaint sample is received along with the market complaint, the investigator shall record the quantity of sample received in the market complaint investigation form (Annexure–I).
[][]If no complaint sample is received along with the complaint, the investigator shall record the relevant details disclosed in the complaint form.
[][]Quality Assurance Manager shall carry out the detailed investigation of the market complaint under the supervision of Head of Quality Assurance to find out the root cause of the complaint and to generate corrective & preventive actions. In his/her absence, Head of Quality Assurance shall nominate any other person to carryout activities in this regard.
[][]Investigator shall carefully inspect and record the physical appearance of the sample, seal etc. and compare the details of the references available in documents of the same batch number. Chemical analysis shall be done on the sample at this point of time.
[][]The investigator in consultation with Head of Quality Assurance shall arrange to carry out chemical and / or microbiological analysis of the reference sample (along with the complaint sample, if available). The investigator must also scrutinize the analytical report of the product under reference.
[][]The investigator shall then discuss the results of the analysis with General Manager, Plant for the investigation at production end.
[][]General Manager, Plant along with the respective departmental manager shall investigate the complaint in details.
[][]The investigation should include scrutiny of batch production records for any manufacturing and/or packing problems encountered during the production of the batch.
[][]Any equipment breakdowns recorded during production of the batch and any material quality problems faced during manufacturing and packing of the batch also must be studied.
[][]In case of following nature of the market complaints, AGM, Quality Assurance in consultation with Managing Director may decide to recall the product / batch as per Recall procedure.
[][]Product mix up and label mix up
[][]Failure to meet regulatory specification (i.e. Assay, impurity)
[][]Adverse drug reaction due to product defect.
[][]Contamination due to foreign matter. (e.g. Glass pieces, metal pieces, black particles, particulate matter, microbial growth etc.)

[][]The closure of complaints along with redressal should be completed within 1(one) month period after the receipt of the complaints. Any delays shall be justified.

Product Complaint Redressal:

[][]Head of Strategic Marketing and Communication after consultation with Managing Director shall appraise the customer on the corrective actions taken and on the redressal actions, wherever necessary and a copy of such shall be forwarded to Head of Quality Assurance for his/her reference.
[][]Management Reviews of Complaints:
[][]The product complaint report, the trends, effectiveness of the corrective actions etc. shall be summarized and reviewed in management review meeting.

Annexure:

Annexure-I: Market Complaint Investigation Form
Annexure-II: Market Complaint Log Book
Annexure-III: Market Complaint Form
Annexure-IV: Flow Diagram For Handling of Market Complaints

Market Complaint Handling Read More »

Leak Test Apparatus Operation, Calibration and Cleaning

Quality Assurance, SOPs

Leak Test Apparatus , Purpose :

Leak Test Apparatus , The purpose of this SOP (Standard Operating Procedure) is to describe the operation, calibration and cleaning of leak test apparatus.

Leak Test Apparatus , Scope :

This procedure is applicable for leak test apparatus (Model: Electrolab, LT-101P ) used in the In Process Check of General Block at XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Asst. Manager, Quality Assurance

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Laboratory coat must be worn while handling the instrument.
[][]Disconnect the power supply before moving or cleaning of the instrument.
[][]Prior to use, user must ensure that equipment is calibrated.
[][]Preparation of Rhodamine B Dye Solution:
[][]Prepare a 2 liters solution of Rhodamine B dye by dissolving 0.5 gm of the dye in water. Take 800 ml water in a 1000 ml beaker and make it colored by adding about 5 ml of the dye solution.

Operating Procedure:

[][]Place the sample in the desiccators which is filled with Rodamin solution to the desired level.
[][]Connect the vacuum tubing between desiccators and the Vacuum Inlet Nozzle provided on the back panel of the instrument.
[][]Switch ON the power switch, then LCD screen displays LEAK TEST APPARATUS followed by SERIAL NUMBER of the instrument and changes over to Vacuum in mm, Hg and Time.
[][]Press the SET key to change to vacuum and input required data by using UP, DOWN and SHIFT keys.
[][]To change HOLD TIME press the SET key and input required data by using UP, DOWN and SHIFT keys.

[][]To show USER ID on screen, press SET key. To setup USER ID press UP or DOWN key.
[][]To change SAMPLE ID press the SET key and input required data by using UP, DOWN and SHIFT keys.
[][]To change No. of samples press the SET key and input required data by using UP, DOWN and SHIFT keys
[][]To change BATCH NO. press the SET key and input required data by using UP, DOWN and SHIFT keys.
[][]After all the data is entered, press the ENTER key and then press the RUN key to run the program which is set for required test. Then vacuum release takes place for three seconds and the pump starts and the vacuum built up which is displayed on the LCD screen. If no vacuum builds up then press desiccator top lid for a few seconds.
[][]When vacuum release reaches zero place automatically then press the print key to get full details of the test.
[][]Leak test parameters

Type of product/Pressure/Time

[][]Tablet, Capsule, Vial/450 mm-hg/5 minutes
[][]Powder for Suspension/450 mm-hg/2 minutes

Procedure for setup time, date and serial number:

[][]Switch ON the instrument and press up arrow key until hear a buzzer sound, then shows password.
[][]Enter password.
[][]The password is four digit 8824 and press enter key.
[][]Date format is 2013 02 16 (Year Month Day) and Time format is 12:15(Hours, Minutes).
[][]Input necessary data by using up, down and right shift key, Date and time can be changed.
[][]To show Serial No. on screen press Enter key
[][]Input necessary data by using up, down and right shift key, Serial No. can be changed.
[][]When all data is entered completing then press Enter key.
[][]Switch OFF the instrument.
[][]Switch ON the instrument after few minutes and check the above recorded data and verify.

Calibration procedure:

[][]Calibrated stopwatch and start timer of leak test apparatus and stop watch simultaneously.
[][]Note the reading at intervals of 60 seconds, 180 seconds and 300 seconds respectively.
[][]Acceptance criteria: 10 seconds for each interval.
[][]Vacuum gauge calibration done by external party.
[][]Frequency of calibration: Twelve months (for timer, vacuum gauge and vacuum holding capacity).

Cleaning procedure:

[][]After completion of the testing, switch off the instrument.
[][]Cleaning of leak test apparatus by using purified water and clean outer and inner surface with the help of lint free cloth.
[][]Place the apparatus for dryness for half an hour.
[][]Change the desiccator Rodamin solution twice in a week or as per required.

Annexure:

Annexure-I: Log Book of Leak Test Apparatus.

Leak Test Apparatus Operation, Calibration and Cleaning Read More »

Training Procedure

Quality Assurance, SOPs

Training Procedure, Purpose:

Training Procedure, To lay down guidelines for training of new entrants and periodic retraining of technical staff.

Training Procedure, Scope:

[][]This procedure is applicable for all employees of General block and Sterile block at XX Pharmaceuticals Ltd. for
[][]On the job training (OJT)
[][]Class room training (CT)
[][]External training
[][]Basic GMP training

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, HR & Admin.

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.
[][]To check the records of training filled by trainee.
[][]To maintain employ training record.
[][]To prepare list of training given to the employees.
[][]To file all records of training in their individual training file.
[][]Training is given in all departments as per the induction form.

Manager, Human Resources

[][]To preserve all training record
[][]To co-ordinate in all training program

General Manager, Plant

[][]To ensure that this procedure is kept up to date.
[][]To ensure implementation of the training as per SOP.
[][]To assess the training requirement.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]The manufacturer should provide training for all the personnel whose duties take them into production areas or into the control laboratories (including the technical, maintenance and cleaning personnel) and for other personnel whose activities could affect the quality of the product.

New Entrants:

New entrants to the organization shall be given induction training and brief cGMP/GLP training by Head of Quality assurance or Quality Assurance within 10 days of joining.
[][]New entrants should be given technical training (need based) by the departmental manager depending upon the nature of job for one month.
[][]New entrant should be instructed to observe the activity in the recruited department for one month after the initial induction program.
[][]A written feedback is collected from new entrants after the training to ascertain his/her competence in both technical and cGMP skills.
[][]Quality Assurance shall prepare a regular annual schedule for training/retraining of technical staff.
[][]The Qualified trainer who has conducted the training should review and assess the feedback.
[][]Based on the assessment, trainer shall identify training retraining needs.
[][]Individual Training record should be maintained for each new entrant along with their feedback.
[][]Once the induction is over the new employees hand over induction training format duly filled with all required signatures to HR & Admin. Department.

Classroom training:

[][]Prepare the training schedule and circulate to all Department Heads for information.
[][]Upon finalization of training schedule, intimate to participants.
[][]Prepare required training aids and conduct the training program.
[][]On completion of the training, evaluate the training imparted by giving a questionnaire. Trainer is required to set the questionnaire.
[][]Trainer evaluates the answer & ranks them as Excellent (>90%), Very good (>80-90%), Good (>60-80%), Poor (<50%).
[][]Poor performers are retrained and re-examined.
[][]After training, trainer provides “Individual Training Record” to the trainee for getting feedback.

[][]All trainees fill the same immediately after the program gets over & submit it to the trainer.
[][]Trainer notes the contents, signs each reports & forward the same to HR & Admin. Department who keep all training related records.
[][]Maintain the training record in training file and update the Employee training card.

On-the-job training:

[][]On need base a competent person organizes on job training to concerned persons either individually or in small group preferably of 5 to 7.
[][]Trainer first explains the theoretical aspects making use of writing boards/printed literature diagram etc.
[][]Explain or demonstrate the actual operation or system to participant.
[][]Training record is maintained in the form as explained above.

External training:

[][]Upon information from various agencies nominate the person on consultation with department head.
[][]Make the necessary arrangement like tickets, hotel arrangement etc. to attend the external training.
[][]After training, trainee will submit the report in the prescribed format as per Annexure- V, to HR & Admin. Department through Department Head. Brief [][]information about the program need to be enclosed with the report.
[][]Maintain the training record in training file and update the Employee training card of concerned employees who have undergone external training as per SOP.
[][]Trainee shares the literature & knowledge gained in the program with all this colleagues.
[][]Department Head may ask the concerned employee to make a presentation on the topic concerned for the benefit of all those concerned who were not sent for training.

Training on basic GMP practice:

[][]Department Head training the new comer on following points:

Production :

[][]Importance of good manufacturing practices and requirements.
[][]Systems related to manufacturing.
[][]System related to packaging (printed and unprinted component code etc).
[][]Documentation.

Warehouse:

[][]General warehousing procedure.
[][]Function carried out by Warehouse.
[][]Document related to warehouse.

Engineering:

[][]Facilities and services
[][]Brief working of the services
[][]Documentation

Quality Assurance:

[][]General information on SOP, GMP Documentation.
[][]Activities of Quality Assurance, Product Development, Microbiology & Quality Control.
[][]Product information.
[][]Other specific activity related to the employees department.

Training schedule:

[][]New entrant: General factory rules and cGMP –10days
[][]Regular training for staff and operators
[][]cGMP – Once in 6 months
[][]GLP – Once in 6 months
[][]Technical training – Once in 3 months
[][]A training session by an External Agency shall be conducted as and need/opportunity arises.
[][]Apart from the schedule, training/retraining sessions will be conducted as and when need arises.

Annexure:

Annexure-I: Individual Training Record.
Annexure-II: Training Log.
Annexure-II: Induction Training Format.
Annexure-IV: Employee Training Card.
Annexure-V: Training Program Report.

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