Hold Time Study of Cleaned Equipments

1. OBJECTIVE

The objective of this protocol is to lay down a procedure for carrying clean Equipment Hold time study and to establish the stabilization period for hold time for cleaned equipment or vessel of Liquid Oral facility.

2. SCOPE

This protocol is applicable to the worst case considered in cleaning validation for cleaned Equipment Hold Time Study of the equipment used in the manufacturing of various products in Liquid orals facility, This protocol shall also define the responsibility, equipment details, sampling method, sampling plan and acceptance criteria for equipment hold time study.

3. PURPOSE OF STUDY

The purpose of this protocol shall be extended to establish hold time for a Type A & Type B cleaned equipment by:
A. Studying the Microbial Load after holding it uncleaned for the specified time period. This study is applicable only to manufacturing equipment which is Type A cleaned.
B. Type ‘B’ cleaning shall be carried out immediately after the completion of specified hold time period and chemical and microbial analysis data shall be collected for the same. Evaluate results of above study for both Chemical & Microbial contamination against cleaned (Type B cleaning) equipment to understand the level of contamination to decide effective cleaning methodology.

4. RESPONSIBILITY

The validation group comprising of representatives from each of the following departments shall be responsible for the overall compliance with this protocol

QA shall be responsible for:

1. Preparation and review of the protocol
2. Execution as per the protocol after approval.
3. Swab sampling (co-ordination with manufacturing for the collection of the samples as specified in protocol)
4. Compilation of the all test data
5. Preparation and review of the final report
6. Approval of the Protocol and final report.

QC shall be responsible for:

1. Review of the protocol.
2. Microbial sampling
3. Analyzing the samples withdrawn during the execution of the protocol
4. Preparation of raw data of analysis.
5. Submission of data to QA and review of the final report.

PRODUCTION shall be responsible for:

1. Review of the protocol.
2. Cleaning of equipment & control on equipment during hold time study.
3. Provide support to QA for carrying out the sampling activity during hold time study.
4. Review of final report

5. CRITERIA FOR THE SELECTION OF EQUIPMENT FOR CLEANED EQUIPMENT HOLD TIME

As the Filter press is the most critical equipment (Hard to Clean) in the equipment matrix chain in Oral liquid Manufacturing procedures. Hence Filter press shall be considered for the Cleaned Equipment hold time study.
Filter Press, which is to be held for the specified period will be the representative of all the equipment in Liquid Orals preparation area and the results of which will be applicable for all equipment in Oral Liquid preparation facility for Type A & Type B Cleaned Equipment Hold Time Study.

6. EXPERIMENTAL PLAN

A) HOLD TIME FOR CLEANED EQUIPMENT AFTER TYPE A CLEANING

1. The study for “Hold time Study of Type A cleaned Equipment” shall be extended for 24 Hrs.
2. The study shall be conducted for Microbiological analysis as per plan (Table-I) after holding equipment unclean for 0 Hrs., 8 Hrs., 12 Hrs., 16 Hrs. and 24 Hrs.

TABLE-I

SAMPLING PLAN(Type A Cleaned Equipment)
Sl. No.	Hold Time Study	Sampling Time	Test to be Performed	Acceptance Criteria
01.	0 Hrs.	Sampling to be done immediately after use.	Microbial	To monitor & Establish Limit for Microbial counts.
02.	8 Hrs.	Sampling to be done immediately after 8 Hrs. of use.	Microbial
03.	12 Hrs.	Sampling to be done immediately after 12 Hrs. of use.	Microbial
				Chemical- NMT 10 (ppm./ 4 inch2.)
04.	16 Hrs.	Sampling to be done immediately after 16 Hrs. of use.	Microbial
05.	24 Hrs.	Sampling to be done immediately after 24 Hrs. of use	Microbial
06.	After Type -B Cleaning	Sampling to be done immediately after Type B Cleaning for  Chemical	Chemical

B) HOLD TIME FOR CLEANEDEQUIPMENT AFTER TYPE B CLEANING:

1. The study for “Hold time Study of Cleaned Equipment” shall be extended for 24 Hrs.

2. Study shall be conducted for Microbiological analysis as per plan  (Table-I) after holding equipment Cleaned (Type B) for1^st day (Immediate after Cleaning), 2^nd day, 3^rd day,5^th day & 7^th day every interval of 24 hours.

A. Immediately after completion of the activity. (On 1^st day)

B. On 2^nd day, approximately after 24 hrs. of activity completion.

C. On 3^rd day, approximately after 48 hrs. of activity completion.

D. On 5^th day, approximately after 96 hrs. of activity completion.

E. On 7^th day, approximately after 144 hrs. of activity completion.

TABLE-II 

SAMPLING PLAN (Type B Cleaned Equipment)
Sl. No.	Hold Time Study	Sampling Time	Test to be Performed	Acceptance Criteria
A	1st Day	Sampling to be done immediately after Cleaning (Type B)	Microbial & Chemical	Microbiological- NMT 25 cfu/ Swab. (4 inch2) Total Fungal Count (yeasts & molds) shall be Nil per swab. (4 inch2)
B	2nd Day.	Sampling to be done Approx. after 24 hours of holding.	Microbial
C	3rd Day.	Sampling to be done Approx. after 48 hours of holding.	Microbial
				Chemical- NMT 10 (ppm./ 4 inch2.)
D	5th Day.	Sampling to be done Approx. after 96 hours of holding.	Microbial
E	7th Day.	Sampling to be done Approx. after144 hours of holding.	Microbial

7. STORAGE

The Cleaned Equipment shall be stored properly in the area dedicated to the storage of Type A cleaned equipment.

8. SWAB SAMPLING

Swab samples shall be taken as per the standard operating procedure, after the final cleaning of the equipment once the equipment qualifies the visual inspection test.
Collected swab samples shall be transferred to QC for further Microbial & Chemical analysis
SWAB sampling (for CHEMICAL ANALYSIS)
Swab samples shall be taken as per the standard operating procedure and should be analyzed within 4 hours of sampling.

9. ACCEPTANCE CRITERIA

FOR CLEANED EQUIPMENT HOLD TIME

i) MICROBIAL DETERMINATION

During the specified holding period, the Total Bacterial Count shall be monitor & establish per swab and Total Fungal Count (yeasts & moulds) shall be Nil per swab.

ii) CHEMICAL DETERMINATION

The residue content detected in each swab collected shall be below the acceptance limits derived, for type B cleaning.
Acceptance Limit for chemical determination: Not more than 10 PPM / Swab.

10. DEVIATION / INCIDENT

Any Deviation from the protocol, related to cleaning procedure, sampling, equipment used shall be authorized and documented in the equipment hold time study report.

11. EVALUATION OF RESULTS

Results shall be documented in Test Data Sheets and photocopy of test data sheets shall be attached to the final report. Evaluation of results shall be carried out to derive a time limit for the Cleaned Equipment Hold Time Study.
Type A & Type B cleaned Equipment Hold Time Study will be the base to establish hold time of Type A& Type B cleaned Equipment intended to be Cleaned.
All test results shall be documented in the summary report and attached with the Protocol.

12. CONCLUSION

On the basis of the evaluated results, a conclusion shall be drawn to state Type A & Type B cleaned Equipment holding time-based on the result obtained for the various studies carried out as per the methodology is given in this protocol.

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