Padma rao

The Quality Assurance department plays a major role in the pharmaceutical industry. This department assuring every stage of manufacturing of the drug substance or drug product and also monitoring each processing stage and maintain all manufacturing related documentation as per Standard Operating Procedures and Vendor qualifications

Quality Assurance department follows their Standard Operating Procedures(SOP). There are also prepared SOPs with the help of each department persons.

In-process quality assurance(IPQA):

Many times samples send to QC in-between process monitoring the quality of products.IPQA persons monitoring the process and control.This is the most important activity for in-process manufacturing and critical process checks.

Ex: clean condition and proper of manufacturing area, temperature probes, Pressure, steam, RT water, brine, Personal Protective Equipment(PPE).

Customer complaints and product recalls:

Whenever any market complaints came for a product or any document by received official email from customer maintained a registered as per SOP.Type complaint based QA responsible action for the decision taken HODs as per SOPs.Change control (CCF): Any changes based on minor or major process and validation applied required change control form which department finally reviewed and approved by QA within timelines.Deviation: it is the observation of any process-related information that deviates from the standard process or Protocol. these are two types based on action. 1) Major deviation 2) Minor deviation

Out of Specifications and Out of Trend results:

In case of any out of results from testing given Standard testing procedure or method of analysis QA department investigate to find the root cause of results,

These are two types of investigations. Phase-1: Laboratory investigation (Quality Control) Phase-2: Full-scale investigation (Manufacturing or Process side)Find out the root cause of results decision to taken corrective and preventive action for these are not repeated in future.Out of trend(OOT), the results are within the specification limits but do not follow the previous batch trend results and also near to the specification limits.it indicates the process out of control or something process not properly follows.Mainly trend of the stability data varies in different conditions.OOT also investigated as per Out of Specification SOP.

Audits:

Internal audits: QA conducts internal audits frequently as per their SOPs.to check all departments follow as per their SOPs.

External Audits: to conduct an audit by QA their contract manufacturing units or APIs to check to follow as per their SOPs, guidelines and policies.

Management review meetings:

Every month or weekly conduct management review meeting with HODs of departments to discuss with quality of the product, production targets, equipment, new projects.

Monthly conducts two hours of training oral or verbal or PPT for departments in pharma guidelines and important topics of the industry. After completed training conducts a written examination for participants persons and also evaluate it.

Ex: 1) cGMP (Current Good Manufacturing Practice) 

2)ICH guidelines (International Council of Harmonisation for Pharmaceuticals Human use) 

Annual Product Quality Review:

Des: Original or a true copy, an accurate data lifecycle and all the employees shall not do any unethical practices with respect to data integrity.

DATA INTEGRITY POLICIES

The activities that who performed on Manufacturing, Analysis, Maintenance, Training, Calibrations, Packing, Cleaning, and Dispatches etc. shall be Documented the data in paper or electronic form, online and real time.

The documented data demonstrates that Complete, Consistent, Attributable, Legible, Contemporaneously, recorded, Original or a true copy, an accurate data lifecycle and all the employees shall not do any unethical practices with respect to data integrity.

Attributable

Legible Contemporaneous

Original

Accurate

Attributable

It should be possible to identify the individual who performed the recorded task. The need to document who the task / function, is in part to demonstrate that the function was Performed by trained and qualified personnel This applies to changes made to records as well corrections, deletions, Changes etc. Legible

All records must be legible, the information must be readable for it to of any use. This applies to all information that would require considering Complete, including all Originals records or entries. Where the 'dynamic' nature of electronic data (the ability to search, query, trend, etc) is important to the content and meaning of the record, the ability to interact with the data using a suitable application is important to the 'availability' f the record.

Contemporaneous:

The evidence of actions, events or decisions should be Original, accurately recorded as they take place. This documentation should serve as an accurate attestation of what was done, or what was decided and why, i.e. what influenced the decision at that time.

Original

The original record can be the first capture of information, whether recorded on paper statically or electronically (Usually dynamic, depending on the complexity of the system). Information that is originally captured in a dynamic state should remain available in that state.

Accurate

Ensuring results and records are accurate is achieved through many elements of a robust Pharmaceutical Quality management System, equipment related factors such as qualification, calibration, Maintenance and computer validation.

Policies and procedures to control actions and behaviours, including data review procedures to verify adherence to procedural requirements deviation management including root cause analysis, impact assessments and CAPA.

 Trained and qualified personnel who understand the importance of following established procedures and document their actions and decisions.

Together, these elements aim to ensure the accuracy of information, including scientific data that is used to make critical decisions about the quality products.

All information that would be critical to recreating an event is important when trying to understand the event. The level of detail required for information set to be considered complete would depend on the criticality of the information. A complete record of data generated electronically including relevant metadata.

Consistent

Good Documentation Practices should be applied throughout any process, without exception, including deviations that may occur during the process. This includes capturing all changes made to data.

Enduring

All part of ensuring records are available is making sure they exist for the entire period during which they might be needed. This means they need to remain intact and accessible as an Indelible/durable record.

Available

Records must be available for review at any time during the required retention period, accessible in a readable format to all applicable personnel who are responsible for their review whether for routine

release decisions, investigations, trending, annual reports, audits or instrutions.

META DATA: Metadata is the contextual information required to understand data. A data value is by itself meaningless without additional information about the data.

Metadata is often as data about data. Metadata is structured information that describes, explains, or otherwise makes it easier to retrieve, use, or manage data.

Data should be maintained throughout the record's retention period with all associated metadata required to reconstruct the CGMP activity.The relationships between data and their metadata should preserved in a secure and traceable manner.

AUDIT TRAIL: Audit Trail refers to a secure, computer-generated, time-stamped electronic record that enables the reconstruction of the course of events related to the creation, modification, or deletion of an electronic record.

An audit trail is a chronology of the "who, what, why and when " of a record.

For example, the audit trail for a high performance liquid chromatography (HPLC) run could include the user name, date/time of the run, the integration parameters used, and details ofa reprocessing, if any, including change justification for the reprocessing.

 CALIBRATION of HPLC

Title: Calibration of HPLC SOP NO.:QC00X-01 EffectiveDate: DD/MM/YYYY Company Logo Supersedes: NA P.No.:01 of X Dept: QC Review Date: DD/MM/YYYY  I           OBJECTIVE 

To provide a procedure for calibration of the HPLC (High-Performance Liquid Chromatography).          

II         SCOPE

 This procedure applies to the HPLC series, used in the Quality Control department of ABC Ltd, Location. 

III        RESPONSIBILITY 

 All the QC personnel involved in the analysis using the system are responsible for this.    

IV        DOCUMENT REFERENCE(s)

 SOPs   :  Policy on calibration (Current version of QA 0XX)

Forms    : S.No Details Format No.(Current version)

1 Calibration of the HPLC system QC0XX/F0X-XX

V         SCHEDULE:

  Calibration shall be carried out once every 6 months.

VI        PROCEDURE  

1.0       Calibration Procedure

1.1       To Perform the Calibration of HPLC as follows.

1.2       Calibration shall be carried out with the below parameters.

1.2.1    Pump flow calibration

1.2.2    Wavelength accuracy

1.2.3    System precision

1.2.4    Carryover

1.2.5    Detector linearity

1.2.6    Injector linearity

1.2.7    Temperature verification for oven and sample cooler.

1.2.8    Gradient Performance Check

1.2.9    Signal Noise and Drift

1.3       Enter the calibration details in the tag and appear the same to the respective instrument

1.4      Calibration procedure shall be carried out as follows

            Conditions:

   Column  : Zorbax SB-C8 150mm x 4.6mm, 3.5u or equivalent

            Wavelength                 : 273 nm

            Flow Rate                   : 1.0ml/minutes

            Injection Volume        : 20 μl

            Runtime                      : 10 min

            Temperature                : Ambient temperature

1.5       Mobile Phase Preparation

A filtered and degassed mixture of Methanol and Water in the ratio of 60:40V/V.

1.6       Preparation of Caffeine stock solutions

Weigh accurately 100 mg of Caffeine into 100 volumetric flasks and make up to the mark with the mobile phase.

1.7       Sample Solutions Preparation:

1.7.1   Sample solution-1 (0.02mg/ml concentration) preparation: Take 2.0 ml of Caffeine stock solution in a 100 ml volumetric flask and make it to the mark with the mobile phase.

1.7.2   Sample solution-2 (0.04mg/ml concentration) preparation: Take 4.0 ml of Caffeine stock solution in 100ml volumetric flask and make it to the mark with the mobile phase

1.7.3   Sample solution-3 (0.06mg/ml concentration) preparation: Take 6.0ml of Caffeine stock solution in a 100 ml volumetric flask and make it to the mark with the mobile phase.

1.7.4     Sample solution-4 (0.08mg/ml concentration) preparation: Take 8.0ml of Caffeine stock solution in a 100 ml volumetric flask and make it up to the mark with the mobile phase.

1.7.5     Sample solution-5 (0.1mg/ml concentration) preparation: Take 10.0ml of Caffeine stock solution in a 100 ml volumetric flask and make it to the mark with the mobile phase.

1.8       Pump flow rate calibration

1.8.1    Measure the flow rate ua sing 10 and ml, 25 ml volumetric flask, and calibrate the ted stop clock. Measure the flow rates of 1.0ml/min, 1.5 ml/min, 2.0 ml/min, and 2.5 m/min.                                                           Volume in ml  X 60

         Flow Rate     =  ___________________________________                                                   

                                 Actual time taken to collect the volume in seconds

1.8.2    Acceptance Criteria    :  ± 2.0%.

1.9       Wavelength Accuracy

1.9.1    Chromatographic conditions  Column  : Zorbax SB-C8 150mm x 4.6mm, 3.5 micron or equivalent

 Flow rate                 :   1.0 ml/min.

 Injection volume     :   20 ml

 Run time                 :   10 min

1.9.2  Preparation of Mobile phase: Prepare a filtered and degassed mixture of methanol and water in the ratio of 60:40 v/v.

1.9.3 Prepare 0.1 mg/ml caffeine solution in the Mobile phase. Inject caffeine solution at each length rise from 200nm – 210nm, from 239nm – 249nm, and from 268nm-278nm (increment of   1nm), record the details in HPLC calibration format record as per format No: QC0XX/F0X-0X

1.9.4   Acceptance Criteria

 Maximum peak response must be at wavelength: 205 ± 2 nm for200 nm-210 nm 

 Maximum peak response must be at wavelength: 273 ± 2   nm for 268 nm-278 nm

Minimum peak response must be at wavelength: 245 ± 2 nm for 239nm-249nm               

1.10   Detector Linearity

1.10.1  Inject Sample solution-1 to Sample solution-5 into the chromatographic system.

1.10.2  Record the area of Caffeine in each sample solution and calculate the Correlation coefficient. Draw the linearity graph with area vs. concentration.

1.10.3    Acceptance Criteria: The Correlation coefficient should be not less than 0.99.

1.11     System Precision:

1.11.1  Inject 5 times sample solution-5 into the Chromatographic system and calculate the           %RSD for Retention time and %RSD for Areas of the sample solution in 5 injections.

1.11.2  Acceptance Criteria: %RSD for Area and Retentions times should be less than 2.0.

1.12     Carryover:

1.12.1  Applies only if carry-over is run immediately after precision.

1.12.2  Inject diluent as a blank. And record the chromatogram.

1.12.3  Calculate the carryover percent using the fifth injection area of precision.

                                                                Blank area/height

                            Carryover (%) =      ------------------------    x 100

                                                               Sample area/height

1.12.4   Acceptance Criteria: NMT 0.2 % for the area and NMT 0.4 % for height. 

1.13     Temperature verification for Oven and Sample cooler:

1.13.1  Check the oven temperature at different set temperatures at 30°C, 40°C, 50°C, 60°C using calibrated Digital thermometer.

1.13.2 Check the Sample cooler temperature at 5°C and 10°C

1.13.3 Acceptance Criteria: ±1°C

1.14     Injector Linearity:    

1.14.1  Inject Sample solution-5. 10µl, 20µl, 30µl, 40µl, 50µl into    Chromatographic system.

1.14.2  Record areas of Caffeine in each injection and draw the linearity graph with area vs injection volume.

1.14.3  Calculate correlation coefficient.

1.14.4  Acceptance Criteria: The correlation Coefficient should not be less than 0.99. 

1.15    Gradient performance check:( GPV Test)

1.15.1 Preparing the Instrument:

1.15.2 Connect with union 

1.15.3 Filter and degas methanol, 0.5% acetone in methanol

1.15.4 Method Parameters:

1.15.5 Detector wavelength of 254 nm

1.15.6 Binary gradient with a total flow of 2.0 ml/min

1.15.7 Gradient table as per below table for pumps A and B.    

1.15.8 Running the Gradient proportionate Valve test:                                                             1.15.9    Purge all the pumps with a flow rate of 2 to 5 ml/min for about 2 to 5 minutes.

1.15.10  Set the total flow rate at 2.0ml/min and wait until the baseline is stable.

1.15.11  Set the gradient profile for Pumps A and B.

1.15.12  Record the height of peaks.

1.15.13 Consider height at B conc. At 100% 100 calculate the other peaks' heights.

1.15.14 For Quaternary systems, repeat the study for other channels of C and D.

1.15.15  Consider height at D conc. At 100% 100 calculate the peak heights.

 Calculation:

                                          Height of B/D peak at different concentration

 Height % of Peak B/D = ----------------------------------------------------------  X100

                                         Height of full-scale peak (100% B/D peak height)

1.15.16 Acceptance criteria: The difference in the proportion of B or D concentration should be no more than ± 1.5% for the set concentration.

1.15.17 then select the Setup Detector signal option enter the required values and click OK.

1.15.18 to her that if already method already was saved we have to open it, and if it any necessary to modify the method we can change it.

1.15.19 now run the sample, the sampler will pick the sample after the sample is picked the needle is washed from the additional vial kept for purposes 5.20 Check the flow on running and we can get the result.

1.15.21 here select printer and press OK. Again select the Report/print option. The report is printed and filed.

1.16.0   Signal noise and Drift:

1.16.1   Fix the union as a column.

             Mobile phase: Water.

             Flow rate        : 1.0 ml/min

             Wavelength    : 254 nm

             Run Time       : 24 min

             Start Time      : 03 min, End Time: 20 min

1.16.2    Run the chromatogram and record the data.

1.16.3    Evaluation of the noise and drift between 3 min to 20 min.

1.16.4    Determine the noise and drift using software.

1.16.5    Acceptance criteria: Should be less than 40µV for noise and Should be less than 500µV/Hz 8.3µV/min.            

2.0     CARE AND MAINTENANCE:

2.1 Ensure the details are documented in the column usage log after the analysis & washing activity are completed

2.2   Use 85:15 Acetonitrile and water for the plunger wash.

2.3   Use mobile phase/diluent vial for syringe needle wash.

2.4 Verify the performance of the system as per the schedule/after a major breakdown of the instrument.

2.5    Replace the inlet filters based on their performance.

2.6    Enter the breakdown details & spares utilized in the Instrument malfunction record. 

* All mobile phase solutions shall be prepared as per the analysis requirement. However mobile phase solutions stored beyond 48 hrs shall not be used. And document the details in the mobile phase and mobile phase log

REFERENCE:

*  Instrument Manual of  HPLC

REVISION HISTORY

Version Effective Date Summary of Revision

0.0 DD/MM/YYYY New SOP

END O F THE DOCUMENT                                 

                               Prepared By           Checked By             Approved By

Sign & Date

OPERATION AND CALIBRATION OF KARL FISCHER APPARATUS

SOP NO.: EffectiveDate: Review Date: QC00X-01 DD/MM/YYYY DD/MM/YYYY

Supersedes Page No.: Department: NA 01 of end Quality Control

I           OBJECTIVE 

            To describe the Operation and Calibration Procedure for the Karl Fischer Apparatus.

II          SCOPE

            This Procedure applies to the operation and calibration of the Karl Fischer Apparatus in the QC Department of ABC Ltd, Location.

III        RESPONSIBILITY 

            1. The analyst, who operates the instrument, is responsible for following the procedure.

            2. The QC Manager / Designee is responsible for implementing the procedure.

IV        DOCUMENT REFERENCE(s)

   SOPs:   a) Policy on calibration (Current version of QA 0XX)

                 b) Operation and calibration of Analytical Balance (Current version of QC00X)

                 c) Maintenance of desiccants (Current version of QC0XX)

Forms

S.No Detail Format No 1 KF Standardization Calibration Record QC00X/F01

V        SCHEDULE:

1.0      External Calibration shall be carried out once every 3 months.

2.0      Internal calibration:   Daily  

VI        PROCEDURE  

1.0       Precautions:

1.1       Keep the lid of the KF vessel tightly closed to protect against atmospheric moisture.

1.2       Care should be taken while transferring the test sample to the KF vessel so that the test sample does not fall on the wall of the KF vessel.  

1.3       Ensure that the KF tube is free from any air bubbles.

1.4       Ensure that the Silica gel is good in condition.

2.0       Operating Procedure:

2.1       Transfer about 50 to 60 ml of fresh methanol into the clean and dried titration vessel Fill the 25 ml burette with KF Reagent up to the mark.

2.2       Switch on the instrument and observe the END LED glow.

2.3       Press the start button to start the addition of KF reagent to the titration vessel.             Observe ADDLED glows.

2.4       Wait until methanol is neutralized and fill the burette to the mark.

2.5       Now add a small quantity of sample into the titration vessel.

2.6       Again press the start button to start the KF reagent addition.

2.7       Wait until the END LED glows and note down the KF consumed.

2.8       Finally calculate the moisture content of the sample using the formula given below and document the details in the equipment log.                                      Volume of KFR consumed X KFR factor X 100           Calculaton      =  ______________________________________                                   (Volume /weight) of the sample X 1000                                                                                                

3.0       Calibration Procedure    :

3.1       Fill the KF reagent in the reagent bottle.

3.2       Switch on the instrument.

3.3       Remove the mixture of KF reagent and sample solution from the titration vessel.

3.4       Wash the titration vessel with 10 ml of methanol.

3.5       Place about 50 to 60 ml of methanol into the titration vessel.

3.6       Neutralize with KF reagent to an electronic endpoint.

3.7       Weigh accurately about 0.1 to 0.15 gm of Disodium tartrate (DST) and transfer it to the titration vessel.

3.8       Stir to dissolve and titrate with KF reagent.

3.9       After completion of titration, note down the burette reading (TV) and calculate as follows:

                                             Weight of DST X 15.66 X 100              Calculaton      =  ________________________________                                                               T.V X 100                                                                       

3.10    Repeat the same from step No. 3.7 to 3.9 and take the average value of the KF factor.     

3.11    The tolerance limit for two trials should not be more than 0.15. If doesn’t comply repeat the same.

3.12     If the Karl Fischer Reagent factor is less than 4.8 mg of H2O/mL discard the Karl Fischer Reagent solution and take fresh reagent.

3.13     Ensure the details are documented in the calibration log.

3.14     Enter the breakdown details & spares utilized in the Equipment History Card.

 REFERENCE:

*  Instrument Manual of KFR Auto Titrator.  

REVISION HISTORY Version Effective Summary of Revision

0.0 DD/MM/YYYY New SOP

END O F THE DOCUMENT                                   

                                Prepared By           Checked By             Approved By

Sign & Date

How to write an SOP for Pharmaceuticals and what should be the content of an effective Pharmaceutical SOP including header, body, and footer and numbering system of SOP.

OBJECTIVE

To lay down a procedure for preparing, approving, authorizing, controlling, and revising Standard Operating Procedures.

SCOPE

This SOP describes the basic principles, defines the responsibilities and lays down the procedure for preparing SOPs. This SOP shall be applicable SOPs.

RESPONSIBILITY

Preparation & Execution: Executive and above

Approval: Asst. Manager and above

Authorization: Asst. General Manager and above

 ACCOUNTABILITY

Head of the Concerned Department

PROCEDURE

Prepare the SOP in the approved format on A-4 size paper.

Prepare the SOPs to describe the operating procedures and steps.

Write all the SOPs in clear, unambiguous language that is easy to understand and follow

Write the SOPs under the following sub-headings:

OBJECTIVE, SCOPE, RESPONSIBILITY, ACCOUNTABILITY,PROCEDURE, REFERENCES, ANNEXURES, ABBREVIATIONS

OBJECTIVE

Write here the reason for preparing the SOP in one sentence or a maximum of two sentences starting with the letter ‘To’.

 SCOPE

This Section defines the applicability of the SOP and also specifies departments, areas or sections to which this SOP shall be applicable.

RESPONSIBILITY

Write here the designation of the person/persons who are directly responsible for the operations mentioned in the ‘Objective’ of the SOP.

ACCOUNTABILITY

Write here the Head of the Department who is accountable for the compliance with the SOP.

PROCEDURE

Write the procedure/method in short sentences. Do not write the instructions in long paragraphs.

Mention all the checks to be carried out, records to be maintained, frequency of various operations, checks and special precautions if any.

Enclose all the Annexures with SOP if applicable.

REFERENCES

Mention a list of references or any other guidance documents based on which the SOP has been prepared. If there is no reference for the SOP, me

‘Not Applicable’ under this subheading.

ANNEXURES

Mention a list of all Annexures enclosed in the SOP. If there is no Annexure in the SOP, mention ‘Not Applicable’ under this subheading.

ABBREVIATIONS

Mention a list of all abbreviations & their full forms/descriptions used in the SOP. If there is no Abbreviation in the SOP, mention ‘Not Applicable’ under the subheading.

Write the SOP in English (If required, some of the SOPs shall be written in the local language i.e. Hindi in India, French in France, English in England, and The USA).

 FORMAT REQUIREMENTS

The type of font for the contents in SOPs shall be ‘Times New Roman’. The font size to be used for the contents of SOPs shall be as follows:

Content of SOP Size of Font

Header

“STANDARD OPERATING PROCEDURE” & “TITLE” 12 Bold in Upper Case

Logo on the right-hand corner 30 mm (L) x 6 mm(H)

“COMPANY NAME” ( on top left corner ) 14 Bold in Upper Case

“Pharmaceutical Ltd.” “Restricted Circulation” “Location”, “Dept.”, “Area”, “Page”, “SOP No.”, “RevisionNo.” “Effective Date”, “Supersedes”, “Review Date”, “Initiated By”, “Approved By”, “Authorized By”, “Name”, “Signature & Date”

10 Bold in Title Case

Actual Title ( detailed heading ) of SOP 12 Bold in Upper Case

Body

Subheadings 12 Bold in Upper Case

Write up of SOP 12 in Sentence Case

Footer

Format No.” 10 in Title Case

Actual format number 10 in Upper Case

THE NUMBERING SYSTEM OF THE SOP

Each SOP shall have a unique numbering system. 

Once the number is allocated to any SOP, the same number shall not be repeated to other SOP.

Each SOP No. Consists of seven alphanumeric characters. For example first SOP prepared in the QA department shall be numbered XQA-001st alpha character indicates the location code whereas ‘X’ indicates plant location. 2nd alpha character indicates the department code and 3rd alpha character indicates the subsection/area code for the departments mentioned in the. For departments other than point no.& 3rd alpha characters indicate department code as mentioned 4th character is the dash’-‘ for separator.5th, 6th & 7th numerical characters indicate a serial number of that particular department code. ‘001’ indicates the first SOP prepared under part.

Department code

Department-wise Code for an SOP Numbering System for Manufacturing and Quality Control:

Department Code General Operational 

Calibration

Cleaning Code for SOP No

Mfg. & Packing  

API, Capsules, Liquid Orals, Packing, Tablets, Other Departments, Engineering,  Safety, Health & Environment, Ware House( RM, PM, FG Quarantine )

Department-wise Code for an SOP Numbering system for other departments:

Department Code for SOP No.

Accounts, AC

Administration, Admin

Human Resources & Development,  HR

Information Technology IT

Production Planning & Supply Chain, PP

Purchase, PU

Quality Assurance QA

For example, the first General SOP of the Tablet department shall be numbered as XTG-001.

CONTENTS OF HEADER

Location: The name of the location of the plant for which SOP is applicable.

Department: The name of the Department for which SOP is applicable.

Area: The area / sub-section of the Department shall be mentioned wherever applicable.

Title: Detailed heading of the SOP.

SOP No.: Unique SOP No. as per procedures

Revision No. : Revision No. Consists of two numerical characters that start with ‘00’ with an increment of one digit after each revision. ‘00’ indicates the first issuance of that particular SOP.

Effective Date: The effective date shall be stamped by Q.A. after final authorization before circulating the SOPs.

Supersedes: For the first issuance, ‘New introduction’ shall be mentioned in this column, otherwise the effective date of obsolete.

Review Date: The normal review period will be 2 years from the effective date of the SOP. For example, if any SOP has an effective date “00 2025”, its review date will be “01-12-2025”.

SOPs shall be revised on a need basis with proper justification. All SOPs shall be mandatory reviewed and revised once in two years.

Upon the first revision of an SOP, the details of the revision shall be recorded on the revision page of the respective SOP.

 Page: The page number shall be mentioned in ‘xx of yy’ format.

Signatures: The Header comprises three columns, Initiated By, Approved by & Authorized By.

Each of the three columns consists of 3 rows i.e. Name of the person who signs the SOP in full signature and the date on which the person signs the SOP.

Initiated by designated person, who has initiated the SOP shall write their name clearly with signature & date in blue ink in the column “In By”.

Approved by: Two persons shall approve the SOP after review. One of them shall be the concerned Department Head.

Quality Assurance. They shall write names clearly with signatures and dates in blue ink. In the case of QA SOPs, first approval shall be done by Asst. Manager.

Above and second approval shall be done by the Manager and the Quality Assurance Department.

Authorized the person finally authorizing the SOP, shall sign here. The authorization shall be done by the Location Head, who shall write clearly with signature and date in blue ink. In the case of QA SOPs, the Location QA Head shall authorize all the SOPs except SOP No. XQA

(Preparation, Approval, Authorization, Control, and Revision of SOPs). This SOP shall be authorized by– Corporate QA.

CONTENTS OF FOOTER

Format No.: This is a unique number assigned to the format used for the preparation of all SOPs as described in point no. Example: Formats of QA shall have format no. FQA-001.

GENERATION OF NEW SOPs

User dept. shall prepare the draft SOP as per the procedure draft copy shall be identified by a stamp or watermark on each page.

A draft copy shall be circulated to the responsible persons for its review. The responsible persons may recommend any changes in the text.

Based on the recommendation, the user dept. shall correct the draft SOP and take the final printout for approval and authorization along with the Change History Log.

The Quality Control department major important role participates in the Pharmaceutical industry.

The main role of the Quality control department in the Pharma industry is to check the quality of the various products like raw materials, Inprocess samples and Finish products.

Their main agenda to analyse and control the quality of the products at all stages of the manufacturing of API or Drug Products.

In QC done by the Qualitative and Quantitative analysis of specific materials as per Stanard Testing Procedures(STP) or Method of Analysis.

Generally, the QC department divided into four sections. These are

Raw materials

In-process

Finished products

Stability studies

Raw materials:

The materials come from outside industries or suppliers and road tankers to check the quality of the materials as per in-house specifications or Standard testing procedures. These are categories into four parts.

General Raw materials:

These are some chemical analyses like titrimetry and chemical methods of analysis like organic and inorganic acids, bases, salts, etc… Ex: Hydrochloric acid(HCl), Sulphuric acid(H2SO4), Nitric acid(HNO3), Caustic soda(NaOH), Sodium carbonate(Na2CO3), Methanol, Toluene, Acetone, Dichloromethane etc…

Key Starting materials:

These are building blocks of drug intermediates or used for the structure formation of compounds or API or Drug substances. The sampling method is different from general raw materials. These are analyzed of both chemical and instrumental analysis. Ex: Fine Chemicals, Drug Intermediates

Packing materials:

These are used for Products/Compounds materials is stored Ex: Fibre drums, HDPE, LDPE drums, Polyethelene bags, etc…

Hazardous materials:

These are harmful or affect on body raw materials to handling in careful safety precautions and as per its Material Safety Data Sheets(MSDS) so vendors or suppliers give a certificate of analysis based on these are approved as per customer COAs. Ex: Sodium Hydride(NaH), Sodium Amide(NaNH2),Sodium Cyanide(NaCN),Vitride etc… Some catalysts are also approved as per customer COAs Ex: Raney-Nikel, Palladium/carbon(Pd/C) used for Hydrogenation reaction.

In-Process samples:

online chemical and instrumental methods analysis as per in-house specification & STPs carried out samples coming from the manufacturing blocks or production department to time to gives results after the process continuously.

Finished Products:

Completly analysis carried out as per customer or In-house or Pharmacopia specification and Standard Testing Procedures of the final products. The analysis carried out in the Quality control department divided into two parts. 

1.Chemical analysis or Wet analysis Laboratory

Volumetric analysis:

These are five types of titrations

Acid-Base Titration Ex: Hydrochloric acid(HCl), Sodium Hydroxide(NaOH)

Argentometric titration Ex: Sodium Chloride(NaCl), Aluminum chloride(AlCl3)

Redox Titration Ex: Sodium thiosulphate, Potassium permanganate

Complexometric titration Ex: Calcium chloride(Cacl2), Magnesium (Mg)Metal

Non-aqueous titration for Drug intermediates and APIs Ex: 2-Amino Pyridine, Isonipotic acid etc..

Gravimetric analysis:

Gravimetric analysis is the mass of an ion in a compound and determined to find out the mass per cent of the same ion in a known quantity of a compound.

Ex: 1) The amount of sulphate as barium sulphate(BaSO4) from sodium sulphate(NaSO4).

2) Content of Nickle in Raney-Nickle catalyst and Palladium in Pd/C catalyst.

Wet laboratory, some important chemical analysis followed that are

Ex: Water content(WC), Loss on drying(LOD), Residue on ignition(ROI), Specific Optical Rotation(SOR), Wt per mL, Thin Layer Chromatography(TLC) etc..

Water Analysis:

Softener water: this water used for boiler purpose to generate steam. Demineralized or Deionised water: This water used for chemical analysis and process Purified water: This water used for the process Three samples are collected to analyse to their specification and Standard testing procedures as per scheduled

2.Instrumental methods of Chemical analysis

Instrumental analysis to analyse quantitative and qualitative investigates analytes using the help of scientific instruments. There is main two instrumental analysis carried out of Quality Control in Pharmaceutical industries.

1) Chromatography:

This technique separates and identifies the mixture of the compounds based on their relative affinity amounts of each compound distributed between a moving mobile phase, and stationary phase. Mostly used instruments of Quality Control in the Pharmaceutical industry 1) High-Performance Liquid Chromatography(HPLC) 2) Gas Chromatography(GC)

2) Spectrophotometry:

Spectroscopic techniques are to pass a beam of electromagnetic radiation onto an unknown sample, observes to find out the difference between energy levels with reference. Most commonly used spectrophotometers of Quality Control in the Pharmaceutical industry. There are 1) Ultra-Violet Spectrophotometer(UVS) 2)Fourier-transform infrared spectrometer(FTIR) 3) Atomic Absorbtion Spectrometer(AAS)

These are main used Research development for Analytical development departments 1) Nuclear Magnetic resonance Spectrometer(NMR) 2) Mass Spectrometer(MS)

Stability Studies:

Stability studies conduct for a re-test or expiry or a shelf life period for the drug substance or the drug product and recommended storage conditions. These are analysed as per protocol or stability STP based on schedule 1)Holdtime stability studies 2)Long-term, Accelerated, intermediate condition stability studies

Quality Control department follows Proper online documentation, Logbooks, Registers, Good Laboratory Practice(GLP) and Good Documentation Practices.

After complete analysis, documented respective analysis signed and checked authorised persons to prepare the certificate of analysis approved by Head of the department or Manager.

Backup Electronic Data:

A substance used for cure, treatment, or prevent diseases. Technical name a drug or medicine for medical purposes.

Pharmaceuticals are generally classified by they add the body (pharmacological effect) and by therapeutic use.

Pharmaceuticals are classified in various origin on the idea of pharmacological properties, mode of action and pharmacological activity, chemical properties, biological system affected, or therapeutic effects. The most widely used arrangement is that the Anatomical Therapeutic Chemical arrangement.

The World Health Organization keeps an inventory of essential medicines

A sampling of classes of drugs includes:                                         

Antipyretics: Reducing fever Paracetamol                                                    

Analgesics: Reducing pain, Aceclofenac, Diclofenac and Tramadol Hcl

Antimalarial drugs: Treating malaria, Hydroxychloroquine              

Antibiotics: Inhibiting germ growth, Cefixime, and Cefroflexine

Antihypertensive: Control of blood pressure, Amlodipine, and atenolol

Antidiabetic: Control of blood glucose, Metformine and Gliclazide

Antipsychotic: Treatment of psychological problems, Olanzapine

Statins: Lovastatin, Pravastatin, and Simvastatin

Drug nomenclature

The drug is the systematic naming of medicine, especially pharmaceutical drugs. The majority of medicine have three sorts of names: Chemical, Generic, and Brand names.

The most important of which is that the IUPAC name; generic or nonproprietary names,

The most important of the International Nonproprietary Names trade names and brand names

Generic names for drugs have classified the drugs into different categories and also separate drugs within categories.

A marketed drug may additionally have an Organization code or compound code.

Different drug names

Chemical Name                                                 Generic Name       Brand name

N-acetyl-p-aminophenol                                        Paracetamol               Crocin

(RS)-2-(4-(2methylpropyl)phenyl)propanoic acid  Ibuprofen                    Nuprin

2-Acetoxy carboxylic acid                                      aspirin                        Aspirin

Generics could also be manufactured by less prominent companies or manufactured on an equivalent assembly line as branded products.

Generic brand products are of comparable quality as a branded product but are commonly made up of lower-grade ingredients, or less attention to appearance or flavor.

A generic brand may be a consumer product without a widely known name or logo because it typically is not advertised.

Generic brands are known for their very basic packaging and labels, and lower prices.

A drug or pharmaceutical brand could also be created when the patent of a reputation brand drug expires.

Drug considerations

A drug or pharmaceutical could also be created when a name-brand drug's patent expires. In the United States for most drug patents, the patent term about 20 years. There is also an exclusivity period-the length of which depends on the drug type and its use. Once a patent ends satisfied, manufacturers are permitted to supply a generic, chemically identical version of the proprietary drug. At the top of the generic's period of exclusivity, the other manufacturer which will prove that it can do an equivalent drug efficacy may make a generic version of that drug.

Some manufacturers may even create a generic version of their proprietary drug, either by manufacturing it themselves or contracting it bent another manufacturer. This strategy is sensible because insurance firm policy often dictates that a generic, when available, must be prescribed. Generics are sold at a reduction from name drugs, often about 80% less. Due to competition, margins on generic drugs are often very thin.

Most pharmaceuticals utilized in made in nations like China and India, or use ingredients that come from those countries.

Defense department purchases 80% of the active pharmaceutical ingredients (APIs) wont to make drugs within us are said to return from China and other countries like India

The United States of America is the world leader in producing new medicines or drugs.

An active pharmaceutical ingredient or drug substance used to pharmacological activity or diagnosis, treatment to affect the function of the body.

Drug Substance:

A drug substance or API  used to cure or prevention of disease in the body. An API is manufactured intermediates used in the synthesis of substances.

APIs added some excipients are to dosage form like tablets, Capsules, Pellets, Injectables in formulation development, the are chosen that the active ingredient can reach the target in the body.

Examples:

Crocin tablet contains Paracetamol is an active pharmaceutical ingredient

Olafine or Movapine tablets contains Olanzapine is an API or Drug substance

Amilokind tablet contains Amlodipine is a drug substance

Drug Product:

The drug product is a drug substance and excipients, dosage form which are the ingredients of the tablet, Capsules, Orals or the liquid in the active agent is suspended or pharmaceutical inactive.

A finished dosage form like a tablet, capsule or oral that contains an active pharmaceutical ingredient, generally, in association with inactive ingredients.

Examples:

OfloxOZ tablets is a drug product dosage form that contains Titanium oxide color agent, Ofloxacin and Ornidazole are drug substances or active pharma ingredients.

Pharma excipients are substances that are contained in a pharma dosage form, no direct used therapy action for the manufacturing process, to protect, support for bioavailability.

Excipients:

Antiadherents, Binders, Coatings, Colours, Disintegrants, Flavours, and lubricants.

The difference between the API (DS)and Finished form(DP)is the drug substance is the active pharmaceutical ingredient that is used to make the drug product, a pure material which pharmacological action on the body.

The drug product is the combination of a drug substance or two or more drug substances or excipients. Tablets, capsules or injections are known as drug product while the active part which exerts action on the body which is present in tablets, capsules or injections are known as drug substances.

API Starting Material or Key raw material:

A Key raw material or API starting materials are used in the production of intermediates or an API

API starting materials are a significant structural fragment into the structure of the API. An API Starting Materials are a material purchased from one or more approved vendors under contract manufacturing units or commercial agreement suppliers or produced in-house.

Formulations:

Top 10 pharmaceutical companies in the world

These are ranked by revenue and market capitalization:

1. Pfizer — $51.8 billion 2. Roche  — $50.1 billion 3. Novartis  — $47.45 billion                                                                                    4. Merck  — $46.9 billion 5. GlaxoSmithKline (GSK) — $43.6 billion 6. Johnson & Johnson (J&J) — $42.2 billion 7. AbbVie — $33.3 billion 8. Sanofi — $27.8 billion 9. Bristol-Myers Squibb — $26.2billion 10. AstraZeneca — $23.6 billion

1.Pfizer

Pfizer is an American multinational pharmaceutical corporation, headquartered in Manhattan. It develops and produces medicines and vaccines for a wide range including oncology, cardiology, neurology, immunology, and endocrinolog

2.Roche

Hoffmann-Roche AG is a Swiss multinational pharmaceutical company headquarters located in Basel, Switzerland.it operates two divisions: Pharmaceuticals and Diagnostics.

3.Novartis

Novartis AG is a Switzerland multinational pharmaceutical company headquarters located in Basel. It manufactures drugs clozapine, diclofenac, carbamazepine, valsartan, terbinafine, and others.

4.Merck

Merck & Co. is a German multinational pharmaceutical company incorporated in Jersey, United States of America.

5. GlaxoSmithKline ( GSK)

GlaxoSmithKline (GSK) is a British multinational pharmaceutical company headquartered in Brantford, England in 2000.

6. Johnson & Johnson (J&J)

Johnson & Johnson (J&J) is an American multinational company headquartered, New Jersey in 1886. It develops medical devices, pharmaceuticals, and consumer goods.

7. AbbVie

AbbVie is an American multinational corporation biopharmaceutical company founded in 2013. It operates as research-based pharmaceutical products, medical devices, diagnostic equipment, and nutrition products

8. Sanofi

Sanofi S.A. is a French multinational pharmaceutical company headquartered in Paris, France, founded in 2013. It operates in the R&D, manufacturing, and pharmaceutical drugs' major therapeutic areas are the cardiovascular, central nervous system, diabetes, internal medicine, oncology, and vaccines.

9. Bristol-Myers Squibb

Bristol Myers Squibb is an American multinational pharmaceutical company, located in New York City. It manufactures pharmaceuticals, biologics, therapeutics, oncology, HIV, cardiovascular, diabetes, hepatitis, arthritis, and psychiatric diseases.

10. AstraZeneca 

AstraZeneca, is a Britain-Swedan multinational biopharmaceutical company, headquarters in England. It has manufactured major disease areas cancer, cardiovascular, respiratory, and inflammation. In 1999. they merged Swedish Astra AB and the British Zeneca Group.

Top 10 pharmaceutical companies in India

The top 10 pharmaceutical companies in India ranked by revenue and market capitalization:

Rank    Industry                        $Billions        ₹Crores

1           Sun Pharma                   10.3              75326.63

2           Dr. Reddy’s                      7.4               54,223.62

3           Divi’s                                6.2               45,023.67

4          Cipla                                 5.3               38,875.43

5          Aurobindo                         4.9               35,641.85

6          Torrent                              4.4               32054.46

7          Lupin                                 4.2               30362.52

8          Zydus Cadila                     3.5               25325.64

9          Abbott India                       3.1               22624.21

10        Alkem                                2.5                18584.54

India is the largest provider of generic medicines, holding a market share of 25% to worldwide supply by volume and meets 61% of the vaccine requirement around the world. Indian pharmaceutical companies also supply 81% of antiretroviral medications (HIV/AIDS) in the worldwide markets.

The international pharmaceutical market is anticipated to surpass USD 1.2Trillion by 2022. India is one most suitable states in this worldwide pharma market. India provides more than 55% of the worldwide purpose for different vaccines and 45% of the demand for generic medicines in the United States. India’s pharmaceuticals demanded to expand at 11% CAGR during 2023 to reach 33 Billion US dollars.

1. Sun Pharmaceutical Industries Ltd

Sun Pharmaceutical Industries Ltd is an Indian multinational pharmaceutical company founder Dilip Shanghvi in 1983, Vapi, Headquarters Goregaon, Mumbai, India, And Subsidiaries Ranbaxy Laboratories, etc...It produces and sells pharmaceutical formulations and active pharmaceutical ingredients (APIs) in India also the United States. Sun Pharma provides formulations in psychiatry, cardiology, dialectology, neurology, and gastroenterology. The company supplies APIs such as etodolac, clorazepate, carbamazepine, warfarin, and anti-cancer drugs, peptides, steroids, sex hormones, etc. Sun supplies more than 2000 formulations and also exports in various other countries. The main features of Sun Pharmaceuticals are research and development facilities and its own API’s

2. Dr. Reddy’s Laboratories Ltd

Dr. Reddy’s Laboratories Ltd is an Indian multinational pharmaceutical company founder Kallam Anji Reddy in 1984, Hyderabad, India. The company produces pharmaceutical formulations and active pharmaceutical ingredients (APIs) in India and other countries and more than 195 drugs, 65 APIs for drug, biotechnology products. DRL has six APIs(CTO)and four Formulations(FTO)manufacturing plants across India. Its main focus research and development centers are Integrated product development Organization(IPDO) and Custom Pharmaceutical Services(CPS) located in Hyderabad, India.

3.Divi’s Laboratories Ltd

Divis Laboratories Ltd is an Indian pharmaceutical company founder Murali Divi in 1990, Hyderabad, India. It manufactures APIs, Intermediates, and Nutraceutical ingredients. Divis Labs have three manufacturing units located at Chouttal, Hyderabad, Chippada, A. Andhra Pradesh, and 3 Research and development centers. The Company exports the products to the USA, Europe, Japan, South Africa, Australia, and the Philippines.

4. Cipla Ltd

Cipla is an Indian multinational pharmaceutical company founder Khwaja Abdul Hamied in 1935, Headquarters Mumbai, India, And supplies top-quality generic medicines in India The company supplies a wide range of medicines. It has got a prominent position in the Indian market ad global market and more than 150 countries. The company provides quality products worldwide received approvals from major regulatory agencies and more than 2000 formulations cover areas like neurology and nephrology. Cipla has a global focus on the important markets of India, the US, and South Africa.

5.Aurobindo Pharma Ltd

Aurobindo Pharma is an Indian pharmaceutical company founder Nityananda Reddy started operations in 1988 with a single unit manufacturing Synthetic Penicillin at Pondicherry after became a public company in 1992 headquartered in HITEC City, Hyderabad, India. the company has provided key therapeutics like cardiovascular, antiretrovirals, antibiotics, gastroenterology, anti-diabetics, anti-Allergics. The company exports products to more than 160 nations in the world. Aurobindo pharma has production, research, and development and Subsidiaries units are Novagen Pharma, AuroZymes Ltd, etc

6. Torrent Pharmaceuticals Ltd

Torrent Pharma an Indian pharmaceutical company founder Uttambhai NathalalMehta in 1959 Headquarters Ahmedabad, India. started as Trinity Laboratories Ltd, and renamed Torrent Pharmaceuticals Ltd. nowadays, it is ranked leaders in the therapeutic sector of the women’s health care, cardiovascular, CNS, gastrointestinal, diabetology, oncology, gynecology, and anti-infective. They have first-class manufacturing units, R & D facilities, and a prevalent international presence in more than 50 nations. The company had procured the Elder Pharma’s Indian company, Zyg Pharma, the API plant of Glochem Industries, Unichem’s Sikkim Plant, Bio-Pharm Inc, generic pharmaceuticals, etc.

7. Lupin Ltd

Lupin is a multinational pharmaceutical company founder Desh Bandhu Gupta in 1968 Mumbai, India a large range of products like Branded & Generic Formulations, Biotechnology Products, APIs, and manufacturing centers are across India, Japan, Brazil, Mexico, and the United States. Subsidiaries are Novel Laboratories, Polynova Industries, and GAVIS Pharmaceuticals. The company is in treatment areas of Non-Steroidal Anti-Inflammatory Drugs, Cardiovascular, Gynaecology, Asthma, Paediatric, Diabetology, Gastro-Intestinal, and Anti-Infective drugs, Anti-TB and Cephalosporins sectors. The company is moved around more than 100 countries. It supplies top quality medications.

8.Zydus Cadila Healthcare Ltd

Zydus Cadila is a Zydus Cadila, is a fully integrated Indian Pharmaceutical company founded by Ramanbhai B. Patel in 1952 in Ahmedabad, Gujarat India. It provides active pharmaceutical ingredients, formulations, and animal healthcare products to wellness products. The company’s research and development facilities are in Gujarat, Maharashtra, Goa, Himachal, and Sikkim also research units in the US and Brazil. It has 1400 researchers across 20 sites, working on medicines and exploring various ideas from NCEs to vaccines, bio-similar products. The company’s global business has regulated markets of the United States, Europe, South Africa, Latin America, and also 30 other national markets in the world.

9. Abbott Pharma India Ltd

Abbott India Limited is a Pharmaceutical company founder Dr. Wallace Calvin Abbott in 1944, Mumbai, India, and a subsidiary of Abbott Laboratories United States. It manufactures pharmaceutical drugs, therapeutics Women’s Health, Neurology, Thyroid, Gastroenterology, Anti-Infective, Diabetes, Urology, Pain, Vitamins, etc., and a plant at Verna, Goa. Abbott has to produce high-quality formulations, branded generic pharmaceuticals, diagnostics, medical devices, and nutrition.

10. Alkem Laboratories Ltd