OBJECTIVE:
The objective of this SOP is to define the mandatory requirements for conducting method suitability study for microbiological procedures.
SCOPE:
This SOP is applicable to Microbiological test methods used in the analysis of sterile and non sterile drug substances and drug products Test/bioburden test for specified microorganisms and Preservative Efficacy-Test performed in Microbiological control laboratories supporting manufacture of non-sterile drug products. Sterility test, Bacteriological endotoxin test performed in Microbiological Control Laboratories supporting manufacture of sterile drug substances and drug products and requirements of suitability test, number of batches, and strength selection and verification criteria of the suitability test. Instrument/equipment qualifications, process validations and hold time studies performed in Microbiological Control laboratories at {Company Name} {Location}.
RESPONSIBILITY:
In charge-Microbiology/ Head-Quality Control: for review and approval of SOP.
Microbiologist- to follow the procedure as per SOP.
ACCOUNTABILITY:
QA Head shall be Accountable for implementation of SOP.
PROCEDURE:
Suitability study: A recovery study performed using small number of microorganisms or standards in presence of product. The study demonstrates the ability of test method to detect bioload or endo load present in the drug product/substance.
DEFINITION: The definitions listed here apply in the context of this Policy and may or may not be applicable in all other usages.
Principle:
Microbiological methods given in compendia are in generalized form.
Therefore, the method to be instituted for testing of particular drug product should be evaluated for its suitability before using the method for analysis.
Due to wide range, category, nature, strength and properties of the drug products, a product specific validation approach shall be employed in the method suitability test.
Method suitability test shall be performed by challenging with known quantity of microbiological culture or control standards as applicable.
Several factors such as product nature, interfering factors, challenged microorganisms, preparation of inoculums, specific conditions for the recovery, pH, solubility, filterability, preservative content, antimicrobial property of product effects on the performance of test.
Therefore, these factors should be considered during the method suitability study of all test methods to be established.
Requirements For Method Suitability Studies:
The Suitability study shall be performed on three independent manufacturing batches of the product.
In case of unavailability of three batches, activity shall be initiated with available batches and an interim report shall be prepared. The final summary report shall be prepared only after execution of suitability on three batches.
In case of Multi strength products, the suitability study shall be performed for maximum strength with rationale and if required for minimum strength where appropriate.
The method suitability test may be performed simultaneously along with the product testing.
Method suitability shall be re-performed under following conditions:
- Whenever there is change in the product formulation such as strength, ingredient, preservatives etc.
- Whenever there is change in the vendor or in the process of the manufacture of API.
- Whenever there is change in experimental conditions such as change in lysate, canister manufacturer, change in membrane filter, diluents, neutralizer, rinsing quantity, etc.
The suitability of the test method shall be established preferably at the product developmental stage.
The microorganisms used in the recovery study should be as specified in the compendia method. In house micro-floras shall be incorporated in the suitability study, as applicable.
The microbial culture used in the recovery studies should not be more than 5 passages.
The microbial culture preparation and standardization shall be done as per the standard operating procedures in order to get not more than 100 cfu cell population.
Microbiological media to be used in the suitability study should meet the growth promotion test requirements.
In case of suitability test performed for microbial recovery studies, the shortest time period of incubation shall be considered in the recovery study.
Pre-suitability trials shall be performed for elimination of interfering factors wherever required.
Finding of trials runs and modifications done during study should be documented with appropriate rationale and conclusion.
In case of Bacterial endotoxin test method suitability, the LAL reagent to be used should be confirmed for the labeled lysate sensitivity.
All instruments/equipments to be used in the study should be calibrated/validated for their defined set parameters.
Training should be imparted to all concerned personnel involved in the activity.
The microbiologist involved in the suitability activity must be qualified for the test.
Method Suitability Study:
Pre-suitability trials/runs for Microbial challenged recovery studies:
The main objective of pre-suitability trials/runs should be elimination or neutralization of interfering factors there by establishing the required pH, diluent, quantity of neutralizer, number of rinsing/washing cycles to be employed for suitability study.
In pre-suitability trials, neutralizer should be evaluated for its toxicity and efficacy.
The neutralizer toxicity and efficacy study shall be performed in triplicate using either pour plate or by membrane filtration method.
The acceptance criteria for the percentage recovery should be at least 70% of the challenged cell population of microorganisms.
Based on the outcome of the pre-suitability trials, a method suitability study shall be designed.
If no neutralizing method is found suitable to neutralize the antimicrobial property of the product, then it shall be considered that the failure to isolate the inoculated organism is attributable to the microbiocidal activity of the product.
Pre-suitability trials/runs may not be required in case of products having no interfering factors.
Pre-suitability trials/runs for Bacterial endotoxin test method suitability:
Pre-suitability trails for bacterial endotoxin test should be performed to eliminate various interfering factors such as pH, solubility, endotoxin extraction present in the product, rinsing, etc. using different methods along with combination of suitable buffering systems.
Pre-suitability trials/runs may not be required in case of products having no interfering factors.
Suitability test:
The method suitability test should be designed as per the conclusion derived from pre suitability trials/runs.
Methods of analysis should be clearly mentioned in the protocol along with instructions, calculations, wherever necessary and the acceptance criteria for each event of test.
Details about reference documents, instruments, and other consumables to be used should be incorporated in the protocol.
The activity should be performed as per the instructions and methodology given in the protocol.
All observations and findings shall be documented and evaluated against acceptance criteria given in the protocol.
In microbial recovery studies, acceptance criteria for the quantitative percentage recovery should be in the range of 50- 200 % of the challenged cell population of microorganisms.
Acceptance criteria for the qualitative recovery should be in terms of clearly visible growth of microorganisms comparable to that in the control vessel without product.
In the case of suitability study for specified organisms test, the growth shall be confirmed by suitable identification test.
In case of Bacterial endotoxin test suitability study, the acceptance criteria should defined as per the product test requirement.
Based on the outcome of the study, a summary report shall be prepared.
In summary report the observations and finding shall be detailed and evaluated against the acceptance criteria given in the protocol for that particular event of suitability study.
Based on the summary and conclusion of the data, the recommendation for the routine testing shall be established for compliance to the compendia method.
REFERENCES:
Not Applicable
ANNEXURES:
Not Applicable
ENCLOSURES: SOP Training Record.
DISTRIBUTION:
Master Copy : Quality Assurance Department
Controlled Copy No. 01 : Head Quality Assurance
Controlled Copy No. 02 : Head QC (Micro)
ABBREVIATIONS:
| QC | : | Quality control |
| No. | : | Number |
| SOP | : | Standard Operating Procedure |
| EM | : | Environment Monitoring |
REVISION HISTORY:
CHANGE HISTORY LOG
| Revision No. | Details of Changes | Reason for Change | Effective Date |
| 00 | New SOP | Not Applicable | To Be Written Manual |