How to Identify Swab Sampling Locations for Cleaning Validation

RIBOFLAVIN CHALLENGE STUDY  

Contact parts of the equipment, used for the manufacturing of any product may have risk to carry the residue of product over to next product if not cleaned properly. So, suitable cleaning procedure applies to remove the residues of previous product form all surfaces of equipment. So for ensure the efficiency of cleaning procedure validation of the same is required to be carried out.

During collection of samples for Cleaning Validation it is not possible to take samples from entire surface of the equipment, hence representative samples are collected from the some locations only. Often selection of such sampling location are based on the experience and visually observed hard to clean area.

Once the cleaning validation sample passed for such location it is considered that the entire equipment is passing in cleaning validation. But as this locations are considered based on the experience or visual observation, there may be chances that if due to error any hard to clean area is not identified it may leads to cross contamination in the product. 

So to overcome this problem Riboflavin Challenge Study can be performed to identify the hard to clean area which is an accurate method rather than experience or visual selection. 

RATIONALE OF RIBOFLAVIN CHALLENGE  

Riboflavin is a highly fluorescent molecule and when exposed to ultra violet (UV) light, it produce fluorescence. This helps is detection of any traces remaining after cleaning of surface previously exposed with Riboflavin. To increase the adherence of Riboflavin to the equipment surface, Carboxymethylecellulose (CMC) is added in the Riboflavin Solution which makes the solution sticky and help to increase the adherence of Riboflavin. 

The places where Riboflavin traces are detected after cleaning are to be considered as hard to clean parts for cleaning and should be incorporated in cleaning validation for swab sample collection points. 

PROCEDURE 

Precautions while using UV Light

• Wear UV protected safety eye glasses and do not look directly into the UV Light.
• Do not let the skin or any body part come directly in the contact of UV Light.

Preparation of Riboflavin Solution  

• Add slowly  10 gm of Carboxymethylecellulose to hot 1 litre of purified water with vigorous stirring to make liquid slurry. 
• Add slowly 2 gm of Riboflavin to this slurry and mix thoroughly. 

Application of Riboflavin Solution to the Equipment

• Spray the Riboflavin solution evenly to the entire product contact surface area of the equipment, dismantle parts and let the spray to be dry for at least 4 hours.
• Verify the uniformity of the Riboflavin by using the UV light and take photographs.

Cleaning of the Riboflavin Solution

• Wash the equipment and dismantle parts as per respective Standard Operating Procedure by using Half Cycle Method (Half time of the washing period mentioned in the SOP).

Identification of Hard to Clean Parts

• Verify the presence of Riboflavin on the surface of equipment and dismantle parts by using the UV Light and take photographs. 
• Areas of equipment and dismantle parts which are having more Riboflavin stains shall be identified as hard to clan areas. Such areas shall be considered for locations for swab samples during Cleaning Validation. 

Conclusion 

So based on the Riboflavin challenge study we can identify hard to clean areas for the location to collect the swabs for cleaning validation with more accuracy and scientific method rather than experience or visual observations. 

So friends that all for the day, Thanks for reading and please share if you have liked this blog. Please do let me know in comment if you have any query...

How to Make User Requirement Specifications (URS)

             User Requirement Specifications also known as URS is a document, which describe the basic requirement of any Equipment, Instrument, System or Facility in terms of Make, Model, capacity, Process, Control System and other cGMP requirements. 

Basic flow for preparation of the URS is as below:

• Generally URS is prepared by the Person from the user department. 
• After preparation of the URS it will be reviewed by user department, engineering department, Quality Assurance. If required it can be reviewed by other cross functional department also. 
• After review by cross functional department, it will be sent to QA Head for approval. 
• Once the URS is approved it will be sent to Vendor for approval. Once approved by vendor Purchase order shall be raised. 
• In some cases where equipment is commercially available, URS may not required to be prepared. For such equipment technical & functional specification from vendor can be considered as URS. For example in-process testing instruments like Hardness Tester, etc. 

Basic content of the URS with the details and template (it can be changed according the requirements) of URS is mentioned below: 

		USER REQUIREMENT SPECIFICATION
		URS No.				Department
		1.	Equipment Details
		1.1	Name of Equipment		Name of equipment to be mentioned
		1.2	Preferred Make		Name of the manufacturer/s
		1.3	Preferred Model		Model type if known
		1.4	Capacity		Minimum required output, speed, range should be mentioned here
		1.5	Usage of Equipment		Mention the minimum working hour of equipment.
		2.	General Requirements
		2.1	Dimension and Environmental Condition		Dimension & environmental condition in which equipment can be run based on the room where equipment will be installed.
		2.2	Process Requirements		A brief detail of the process of the equipment with connectivity of other area and equipment if required
		2.3	Technical Requirements		If any specific technical requirement regarding the process of the equipment
		2.4	Other		Specify if any other requirement
		3.	Components Details
		3.1	Name of Major Component/s		Preferred Make, Model, Capacity, Range, etc.
		3.2	Name of Minor Component/s		Preferred Make, Model, Capacity, Range, etc.
		4.	Control Systems
		4.1	MMI		Preferred Make, Type, Model, etc.
		4.2	Data Security		Audit trail
		4.3	PLC		Make, Model, Type
		4.4	User Interface		Mention if required to be  compatible with   SCADA or DCS
		4.5	Interface to other		Mention if required interface with other Equipment / System / Instrument
		4.6	Data storage Capacity		Minimum Storage Capacity
		4.7	Password Protection		If required
		4.8	Software specifications		Preferred Make, Type, Version, etc.
		4.9	Hardware specifications		Preferred Make, Type, Model, etc.
		4.10	Others		Specify if any other object is required
		5.	Alarms, Interlock & Safety Features
		5.1	Alarms		Mention the all required alarms in equipment
		5.2	Interlock		Mention all required interlocks in equipment
		5.3	Safety Features		Mention Safety features like emergency switch, earthing, power failure, noise level, flame proof / non flame proof, IP Rating etc.
		5.4	Other		If any other safety precaution is required please specify
		6.	Documentation
		6.1	Certificates		Mentioned the requirements of certificates like Material of Construction, Components Test Certificates, Calibration Certificates, Performance Test Certificate etc.
		6.2	Drawings		Mentioned deferent type of drawing required like GA, P&ID, Electrical, etc.
		6.3	Manual		Mention the requirement of the Operation & Maintenance Manual
		6.4	Qualification Documents		Design, Installation, Operational & Performance Qualification
		6.5	Backup		Mention if backup of software is required
		6.6	FAT / SAT		Mention if Factory Acceptance Test or Site Acceptance Test is required
		6.7	Validation By Vendor		Mention the details if validation needs to be carried out by vendor
		6.8	Others		Please specify if any other document is required
		7.	URS Approval
		7.1	Prepared By		Name, sign & date of person who has prepared URS
		7.2	Reviewed By		Name, sign & date of person who has reviewed URS
		7.3	Approved By		Name, sign & date of person who has approved URS
		8.	URS Acceptance By Vendor
		8.1	Accepted By		Name, sign & date of vendor who has accepted URS

How to Make Validation Master Plan for New Facility

Validation Master Plan

The Validation Master Plan also known as VMP is a documented plan to outlines the principles involved for qualification of a facility or part of a facility that defines the layout of the operation, the associated utilities and systems, equipment, and the processes to be validated and provides a written program for achieving and maintaining a qualified facility.

Validation Master Plan also provides information as to the extent of the qualification and validation (Installation Qualification, Operational Qualification & Performance Qualification) required documentation, SOP, acceptance criteria and responsibilities.

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Contents of Validation Master Plan

Following are the basic content of the Validation Master Plan:

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1.  The first page contains Title of the Document and details of facility, address and types of products being manufactured in the facility.

2.    Next page contains revision history from initial to latest version including details of each revision.

3.  Next page contains details like name, department, designation with sign date personnel who have approved, reviewed and approved the VMP. Each section shall have the information as mentioned below:

         a)  Prepared By    :   Signature of the person who has prepared the VMP. 

         b)    Review By      :   Signature of the person who has prepared the VMP.

              c)   Approved By  :   Signature of the person who has prepared the VMP.

4.    Table of contents: This section contains a table of all contents with page no.

5.  Objective: This section describes the intent of the Validation Master Plan with respect to the facility for which this is made..

6.   Scope: It describe the extent of the facility (includes its details) to which Validation Master Plan is applicable.

7.  Responsibilities: This contains the role and responsibility of cross functional department including the service provider such as who will do what. 

8.  Validation Policy: This section describes about the firm’s overall approach and intention of all qualification & validation activities to be performed.

9.  Facilities, Systems, Equipment & Process: This section contains the brief summary of particulars which are to be validated. Generally this includes Facility, Equipment, Instruments, Computer, System, Utilities (HVAC / AHU, Water, Air, etc), Validation (Method, Process, Cleaning, Etc.)

10. Plan and Schedule: This section contains the time line of planning of validation and schedule including initial and routine. 

11.  Acceptance Criteria: This section contains the rationale for developing acceptance criteria for each qualification and validation.

12. Change Control and Deviation Management: This section describes the actions to be taken if a change is proposed and how to address if any deviation occurs during the implementation of the VMP or execution of Qualification & Validation.

13. Re-validation & Re-qualification: This section describe the reason, frequency and extent of the Re-validation & Re-qualification of each activity like equipment, utility qualification, Process, Cleaning Validation. 

14. Documents: This section stats about the requirement of related documents like Standard operating procedure, Calibration, Preventive Maintenance and Training, etc.

15. References: This section describes about the reference documents, SOP, Guideline related to the qualification & validation activity which are the base to prepare the VMP.

16.  Abbreviations: Full form of all abbreviations which are mentioned in VMP.

17.  Annexure: List the annexure, which are enclosed to VMP. Generally this include the various qualification & validation schedules. If requires template of the Installation, Operational and Performance Qualification Protocol & Report can also be included to the VMP.

Review and Revision of Validation Master Plan

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The Validation Master Plan should be reviewed at defined frequency (generally once in two year) or whenever there is a modification, expansion or addition in the existing facility.

Template of Validation Master Plan

Validation Master Plan can be prepared as per following template but can be modified as per the requirements: 

VALIDATION MASTER PLAN
VMP No.		Effective Date
Page No.: x of y