Month: February 2019

Line Clearance Procedure in Pharmaceuticals

Line Clearance

What is Line Clearance :

Line clearance is a process which provides a high degree of confidence or assurance that the said line or area is free from any unwanted residue or left over of previous processing’s before proceeding for next process. Quality assurance has to provide Line clearance before the start of any activity whether it is batch to batch change over and Product to product change over

Criteria of Batch to batch change over :

Change over from one batch to another batch of same product and same Strength or increasing in strength provided the excipients is same.

Cleaning between batches of same product but in ascending or increasing strength.

Criteria of Product to Product change over :

  1. Change over from one product to another product.
  2. Change over form one product to same product with descending or decreasing strength.
  3. Change over between batches / product with different colour/ Flavour / Excipients.
  4. Change over after post maintenance or when the next product is not known (as applicable).  
  5. Continuously running of one batch for a longer period of time.
  6. Area or Equipment is kept ideal for more period of time.

Line clearance should be carried out at change over by Manufacturing, Packaging, Raw Material Store, Packing Material Store etc independently for the stages where final dosage form & intermediates are formed, handled and processed.

Line clearance for all area should be given as per following points (but not limited to) :

  1. On request from concerned area for line clearance, QA will Check all the points/line & shall ensure the type of cleaning (Product to Product or Batch to Batch). If the machine/Area having Product to Product cleaning, then ensure the machine is in dismantling condition and check for absence of previous product/material in each dismantled parts of the machine.
  2. After complete verification of equipment at dismantled condition from IPQA checklist as well as respective documents like batch records to be signed, then production person shall go for assembling of equipment as per the plan.
  3. Once the equipment line clearance is done, the equipment can be used up to its cleaning validity only, if it crosses the validity date, then re-line clearance of equipment shall be done
  4. Check and ensure that the previous product/ batch materials and status labels are removed from the area.
  5. Ensure that dustbins in the area are emptied out and do not carry debris of previous product / batch.
  6. Check the ceiling, floor, walls, windows and door frames and electrical panels in the area are clean and free from visible traces of previous product/ batch. (Where ever applicable).
  7. Ensure cleanliness of Drain point provided in the area
  8. Ensure cleanliness of pendants, dust extraction hose are cleaned
  9. Ensure cleanliness of Weighing balance platform and Display of balance
  10. Ensure that the cleaning record for the area is updated.
  11. Ensure calibration status of all pressure gauges, balances and timers are updated
  12. Check that the documents pertaining to the previous product are removed from the area.
  13. Check that the equipment log sheets of all machines in the area are complete as on date with cleaning details.
  14. Ensure that environment conditions (Temperature & RH) record is updated.
  15. Ensure that the Batch Manufacturing Record is complete in all respects up to the stage.
  16. Line clearance for all equipments should be given as per check points mentioned in checklists and for specific areas / Parts of machine shall be verified accordingly the photographs available in checklist as well as in respective Operation and cleaning SOP’s of manufacturing equipments.
  17. Ensure that, the rejects of previous product are destroyed.
  18. Ensure that the area and equipments are appropriately labelled for status
  19. Ensure Batch manufacturing record & Batch Packing record are completed up to the executed activity and verified.
  20. Check that the machines have been cleaned as per respective SOP of respective department for the removal of previous batch/ product.
  21. The checking during line clearance should include all machine places where the product/ packaging material may get trapped. Use Additional flash light or compressed air if required to ensure adequacy of cleanliness at critical parts/areas. 
  22.  All excess / rejected packing materials of previous product shall be removed from the line.
  23.   All used hand gloves, dusters of previous product shall be removed from the line
  24. All stereos of the previous product shall be removed/ destroyed by cutting into pieces (as applicable).
  25. During line clearance of primary packing line and secondary packing line Quality Assurance personnel shall checks the complete deletion of Pharmacode / Barcode of previous product on PLC/HMI of Machine.
  26. Check conveyor belt and area below the belt for absence of previous product.
  27. Tools box checked for absence of previous product and Sorting tray checked for absence of previous product.
  28. Verify and ensure correctness of next product/ batch for label, Integrity, storage & other appropriate parameters.
  29. Individual line clearance checklist shall be done and checked by production for respective equipments which shall be verified by Quality Assurance.
  30. Production and Quality Assurance shall check & verify the specimen of Aluminium foil,PVC, Carton, label etc before start of packing activity.
  31. In case of dispensing of Raw & Packing material Quality assurance shall verify the release of the same from Quality Control.
  32. Potency Calculation of Raw material shall be checked by production & verify by Quality Assurance.
  33. Individual line clearance checklist shall be done and checked by production for respective equipment which shall be verified by Quality Assurance.

Note : Any non-compliance observed during line clearance should be investigated and documented as per the respective SOP if required deviation shall be raised.

Conclusion :

  1. Types of Line clearance terminology may vary from Organization to Organization like Type A, Type B & Type C . In most case Type A shall be considered for Batch to Batch cleaning & Type B & C for Product to product cleaning.
  2. Type A Cleaning shall be done with the help of Vacuum Cleaner & Lint free cloth. Water is not used
  3. Type B & Type C cleaning with the help of Potable and Purified water. 70 % IPA can be used in case of Beta Lactam Facility.
  4. Every organization should follow line clearance procedure & the observation made by Quality Assurance shall be compiled before starting of activity.
  5. It is a control over the entire system.
  6. Doers can make mistake so somebody has to check or verify the same

Standard Operating Procedure (SOP) of Standard Operating Procedure (SOP)

What is Standard Operating Procedure :

It is an authorized written document which describes the step by step instructions requirements for Quality system, performing operations, non specific to any product, process or material. It provides detailed procedure about systems applicable to various operation e.g. Equipment’s / Instrument’s / System’s Operation / Cleaning / Maintenance.

Everybody working in organization has to follow the instruction which are written in SOP and perform their activities accordingly.

Importance of SOP :

It is important for all industry as it explains about the Practices & procedures which are to be followed by each department before doing any activity. It plays a major role in every business of a organization & it is the backbone of all industries and integral part of Quality Assurance

Parameters of SOP :

Paper Size, ( A4 size) Paper Colour required, (White) Header, (with company logo & site name with Font Size 11 Arial Bold) SOP text (Arial with Font Size of 11) & Footer (Arial with Font Size of 11 & Footer format number Arial 10) which may vary organization to Organization.

Each SOP will have a header (in bold letters) with the following details :

Title: Mention the title of SOP for which being prepared, starting with word “Procedure for”.

Department: Mention respective department for which SOP is being written.

SOP No. : Mention a unique number to each SOP.

Supersedes: Mention previous version of SOP number with revision number. Write “Nil”, in case of the new SOP is written

Page No. : Mention the current page number followed by the total page numbers

Effective Date: Mention the date, month and year (DD/MM/YYYY) or (DD/MM/YY)

Review Before: Mention the “Review Before” date, Two years from the Effective Date.

Each SOP will have a Footer (in bold letters) with the following details :

Prepared By: Signature, date, name of person and designation shall be put who has written the procedure.

Reviewed By: Signature, date, name of person and designation shall be put who has reviewed the procedure.

Approved By: Signature, date, name of person and designation shall be put who has approved the procedure.

Format No. : All pages will have unique format number on the bottom right hand side corner outside the border.

Each SOP will have a middle portion (body) with the following subheadings :

Objective: State the aim for writing the SOP & restrict the purpose to one sentence or maximum two sentences statement, starting with the word “To”. This elaborates the usefulness of the SOP (elaborates on “What / Why”).

Scope: State the scope for which the SOP will be applicable. The scope may be applicable for processes / equipment / policies.

Responsibility: State the designation of the person(s) who is / are responsible for activity (competent enough / operating personnel / executing personnel).

Definition(s): Write the definition of the key / important words used in the SOP

Procedure: Write the procedure stepwise, short, unambiguous instructive sentences of the operating procedure, all checks to be done, record to be maintained, frequency of various operations, etc. Give special precautions (Operation / Cleaning / Calibration / Safety related), if any.

Distribution: Mention the Department name in which SOP is to be distributed.

Annex(es): Mention the title(s) of Annex(es) with Annex No. related to SOP

Reference(s): Mention the Reference(s) of SOPs which are linked with written SOP (existing).

Abbreviations: Mention the full form or full word or phrase for short forms used in the SOP

SOP Revision History Record: Mention the SOP Revision Number, Details for Revision(s) with Change Control No. and Effective Date (Sign./ Date).

Approval and Distribution of SOP :

All the SOP used in the organization shall be Approved by Quality Assurance & Approved copy shall be given to the concerned department for the training purpose.

Department Head / Designee shall give training to concerned personnel and SOP made effective within 30 calender days from from date of Approval.

Quality Assurance shall put Master stamp in the SOP & take the photocopy & issue the same to the concerned department by putting controlled or Display copy stamp.

All the approved SOPs master copy shall be kept in QA custody.

Revision of SOP  :

Revision of SOP shall be done at any time within the two years of the issue date but must necessary be reviewed at the end of two years.

Modification/change/ revision shall be done in SOP’s with the help of change control system.

Old SOP copy shall made obsolete & new SOP shall be issued to respective department.

Cancellation or withdrawal of SOP :

In case SOP / Annex are no longer required, the concerned department will raise the change control for cancellation / withdrawal.

On completion of assessment SOP / Annex, shall be cancelled / withdrawn by QA Department.

The SOP No. allocated to the Cancelled / Withdrawn SOP shall not be allocated to any other new SOP.

Destruction of SOP  :

Retrieved copies of SOP shall be destroyed by QA Department by any one of the following methods.

  1. Manual Tearing 2. Paper Shredding (through machine)

Destruction details shall be maintained by QA Department with proper documentation.

Conclusion :

  1. SOP Training is important for all the employee working in the organization irrespective of freshers and experience personnel so every employee shall taken SOP training according to the Training scheduled.
  2. Current SOP copy shall be available in the respective department or workplace.
  3. SOP shall be displayed near to the instrument, equipment’s or in the particular area or work place where activity is going on.
  4. During cleaning activities in manufacturing area the concern personnel shall ensure that it should not come in contact with water.
  5. Everybody shall follow the SOP and do what is written in the SOP.
  6. Give appropriate training and evaluate prior to make effective to any SOP.
  7. It serves as a training document for teaching users about the process for which it was written.
  8. It provides guideline for accurate and timely data collection.
  9. To provide people with all safety, Health, environmental and operational information necessary to perform the job properly.

Pl find below the Template of SOP (Annex 1) .

Difference between Fumigation and Fogging in Pharmaceuticals and other Areas

Fumigation and fogging are two methods which are commonly used in pharmaceutical (Both Sterile & Non sterile) companies to control the microbial contamination in controlled area. But now a day’s fumigation with formaldehyde solution and potassium permanganate is banned by different regulatory agencies in pharmaceutical companies.

The Photo of Fogger Instrument……….fogger

What is Fumigation :

Fumigation is a method in which we use formaldehyde and potassium permanganate chemical in a predefined ratio and by adding potassium permanganate in formaldehyde a reaction takes place and it generate fumes which effectively kill bacteria, fungus, viruses and their spores. This  is very effective method to control the contamination in controlled area.

Drawback of  formaldehyde and potassium permanganate Chemical : 

1. Different regulatory agencies banned fumigation with formaldehyde solution and potassium permanganate as formaldehyde is carcinogenic  (Cancer causing) in nature and there is risk of cancer associate with this to the personnel who is handling formaldehyde.

2. It is not safe for the personnel & there are also other drawbacks like fumigation with formaldehyde causes irritation to the eyes and nose.

3. After fumigation with formaldehyde there is requirement for de-fumigation of area in which AHU (Air Handling Unit) has to be continuously run for few hours without any activity to remove the residues from the air and cleaning and moping of equipments and area is also required.

What is Fogging :

Now a day’s fogging is used in most of the pharmaceuticals to control the microbial contamination in controlled areas and for fogging we require fogger machine and fogging solutions. Different disinfectant are also used for fogging  which can effectively control the area but hydrogen peroxide and silver Nitrate solution commonly used for fogging purpose.Virosil which contains Hydrogen peroxide 10 % and silver Nitrate 0.01 % is  commonly used for Fogging.

Advantages of Fogging with Hydrogen Peroxide and silver Nitrate solution :

1. By the fogger machines solution is sprayed in the area in form of aerosol.

2. The small particles of disinfectant solution suspend in the air for long time  and kill all the air borne bacteria, fungus and their spores.

3. This is also very effective way to control the contamination.

4. It is safe for the personnel as it does not causes irritation to the eyes and nose.

5. There is no requirement of de-fogging and cleaning of equipments and area to remove the residues as it is Hydrogen peroxide based which decomposes into water and Hydrgen.

6. It is also very effective in disinfection of all critical surfaces that comes in contact with pharma products, instruments, bottles and caps can be easily disinfected using a 5% solution.

7. Time can be saved as after fogging no ectra work related to cleaning is required

Area of Application of Foggers :

1. It can be used in Pharmaceuticals with the concentration of 20 % for 1000 cu ft of area.

2.As a surface disinfection with the concentration of 5 %  in floors, walls, table and linen.

3. As a instruments disinfection with the concentration of 10 %

4. Used to eliminate complete microbial load present in storage tanks, raw/process water,pipelines, filters and membranes of the system.

5. It can be also used in Hospitals and Operation Theatre also.

Precautions taken during Fogging :

Use nose mask, safety goggles and Hand gloves during preparation and usage of disinfectant solutions.

Before Fogging AHU (Air Handling Unit) should be OFF & after fogging area should be kept ideal & after 24 hours AHU (Air Handling Unit) should  be continuously run.