seminar injectable dosage form

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Analysis of injectable dosage form:

Analysis of injectable dosage form Presented By: Vineeta V. Kanani M.Pharm . (Q.A.) Semester-II

Content::

Content: Raw Material Testing Validation Of Analytical Procedure Stability Indicating Methods Method Transfer Cleaning Method Validation Admixture Studies Microbiological Testing Of Parenteral Formulations

Raw Material Testing:

Raw Material Testing It can be carried out by following methods: HPLC TLC Titration method GC NIR

Raw Material Testing:

Raw Material Testing 1. HPLC: Assay and ordinary impurity determinations. Capable of separating the active ingredient from in-process impurities and be able to detect and quantitate low levels of impurities (0.05%). When the same method is used for the release and stability testing of the drug product, the in-process impurity peaks must be labelled as such to avoid their being calculated as degradation products.

Raw Material Testing:

Raw Material Testing The impurity method consists of sufficiently high concentration of the test sample such that the impurities at 0.05% levels will have sufficient signal-to-noise ratios and give reproducible peak areas. At such concentrations, the area and shape of the active peak are not suitable for assay determination. ( lower concentration of the sample must be used)

Raw Material Testing:

Raw Material Testing When impurity reference standards are available only in limited quantities, relative response factors (RRFs) to the active ingredient can be used to quantitate impurity concentrations. 2. Titration Method: When a reference standard for the active ingredient is not available, assay by titration is the method of choice.

Raw Material Testing:

Raw Material Testing 3. Thin Layer Chromatography: Determination of in-process impurities in drug substances Semi quantitative, when usual comparison of size & intensity of spot is performed. Quantitative measurements are possible by means of densitometry or fluorescence measurements.

Raw Material Testing:

Raw Material Testing 4. Gas Chromatography: Residual solvent analysis Tests for organic volatile impurities such as benzene, chloroform, 1,4-dioxane, methylene chloride and trichloroethylene along with any other specific organic solvents used in the synthesis process must be performed.

Raw Material Testing:

Raw Material Testing 5. Near Infrared Spectroscopy: Analysis is usually performed within a minute or less. Samples can be analyzed in their original containers without the need for sample preparation. Improved method precision over chromatographic methods while equivalent accuracy is maintained.

Validation Of Analytical Procedure:

Validation Of Analytical Procedure Definition: Validation is a process used to prove through scientific study that the analytical method is suitable for its intended use. Contents: ► Accuracy ► LOD ► Precision ► LOQ ► Linearity ► Ruggedness ► Specificity ► Robustness

Validation Of Analytical Procedure:

Validation Of Analytical Procedure Accuracy :Exactness of the analytical method to the true value. Determination: By spiking known amounts of analyte into placebo matrix & analyzing it. The analyte should be spiked into the placebo matrix at concentration values ranging from 50, 75, 100, 125 & 150% of the expected range. Accuracy is calculated as the percent recovery of the amount determined to the amount spiked.

Validation Of Analytical Procedure:

Validation Of Analytical Procedure Precision: Degree of repeatability of the analytical method when it is performed on multiple samples obtained from a homogeneous mixture and is expressed as the relative standard deviation. Linearity: Determined by using linear regression analysis to deduce the relationship between instrument response and known concentrations of the analyte (usually 50–150% of the expected concentration).

Validation Of Analytical Procedure:

Validation Of Analytical Procedure Specificity Ability of the analytical method to measure the analyte in the presence of other components that are expected to be present. Determination: samples are prepared by spiking possible interfering agents (impurities, degradation products, excipients, etc.) or by using forced degraded samples. Recovery of the analyte from the spiked sample is compared to that from the unspiked sample and a percent agreement is calculated.

Validation Of Analytical Procedure:

Validation Of Analytical Procedure Limit Of Detection (LOD): lowest concentration of the analyte in a sample that can be detected, but not quantitated. Limit Of Quantitation (LOQ): lowest concentration of the analyte in a sample that can be determined with acceptable precision.

Validation Of Analytical Procedure:

Validation Of Analytical Procedure Ruggedness: It is evaluated by having a second analyst independently repeat the accuracy, precision, and linearity measurements. The ability of the second analyst to reproduce the validation results of the primary analyst is taken as a proof of the ruggedness of the assay method. Robustness: Robustness is the ability of the method to withstand small, deliberate changes in the method parameters.

STABILITY-INDICATING METHODS:

STABILITY-INDICATING METHODS Quantitative analytical procedure. Detects a decrease in the amount of the active pharmaceutical ingredient (API) present due to degradation. According to FDA guidelines, a SIM is defined as a validated analytical procedure that accurately and precisely measures active ingredients (drug substance or drug product) free from potential interferences like degradation products, process impurities, excipients, or other potential impurities.

STABILITY-INDICATING METHODS:

STABILITY-INDICATING METHODS SIM includes following steps: 1. Generate the Sample 2. Developing the LC Method: Manipulating selectivity during method development Evaluating specificity during method development New technology for method development 3. Validate the Method

METHOD TRANSFER:

METHOD TRANSFER Methods are routinely transferred to QC/contract laboratories after development and validation. Before method transfer, the method, validation report, and transfer validation protocols must be documented. The written method should include system suitability requirements and acceptance criteria, details for the chromatographic parameters, column, mobile phase preparation, standard and sample preparation, and all calculations.

METHOD TRANSFER:

METHOD TRANSFER Method transfer can be via: Comparative testing : Most commonly used method where resulting data are compared with a set of predetermined acceptance criteria Co-validation between two labs: Both labs generate a matrix of data that summarizes the suitability of the testing site, analyst,date of analysis, and instrumentation. Complete or partial method validation: A repeat of method validation either completely or partially. Transfer waiver (omission of formal validation): Needs justification as to why method transfer was not needed. For example, lab is already testing the product.

METHOD TRANSFER:

METHOD TRANSFER Required Elements: Preapproved Test Plan/SOP: Protocol should describe the general transfer process and specific acceptance criteria. The document should define the responsibilities and scope of the transferring and receiving labs. Selection of materials and samples should be detailed. The identity and lot numbers of specific batches should be specified. COAs for all reference standards and samples should be provided as well. All instrumentation and associated parameters should be noted.

METHOD TRANSFER:

METHOD TRANSFER Description of Test Methods: Include records of all methods used during the transfer. Any validation data should be provided to the receiving laboratory. Description of Test Requirements: The number of lots, replicates, and injections should be summarized. In the case of dissolution testing, the number of individual units should be stipulated too.

METHOD TRANSFER:

METHOD TRANSFER Rationale for Test Requirements: Provide a rationale for the parameters chosen and overall impact on success of method transfer. Description should include any system suitability requirements. Acceptance Criteria: Transfer protocol should include suitable acceptance criteria. Documentation of Results: Results should be documented in a report that summarizes all the data.

CLEANING METHOD VALIDATION:

CLEANING METHOD VALIDATION Verify the effectiveness of the cleaning procedure for removal of product residues, degradation products, preservatives, excipients, and/or cleaning agents as well as the control of potential microbial contaminants. In addition one needs to ensure there is no risk associated with cross-contamination of active ingredients.

CLEANING METHOD VALIDATION:

CLEANING METHOD VALIDATION Validation of Cleaning Processes 2. Microbiological Considerations: Whether or not CIP systems are used for cleaning of processing equipment, microbiological aspects of equipment cleaning should be considered. This consists largely of preventive measures rather than removal of contamination once it has occurred.

CLEANING METHOD VALIDATION:

CLEANING METHOD VALIDATION Analytical Methods :The analytical methods used to detect residuals or contaminants should be specific for the substance or the class of substances to be assayed (e.g., product residue, detergent residue, and/or endotoxin) and be validated before the cleaning validation study is carried out. Sampling: Direct Surface Sampling: Establishing a level of contamination or residue per given surface area. Additionally, residues that are "dried out" or are insoluble can be sampled by physical removal.

CLEANING METHOD VALIDATION:

CLEANING METHOD VALIDATION Rinse Samples: Rinse samples allow sampling of a large surface area and of inaccessible systems or ones that cannot be routinely disassembled. Detergent: When detergents are used in the cleaning process, their composition should be known to the user and their removal should be demonstrated. The possibility of detergent breakdown should also be considered when validating cleaning procedures.

CLEANING METHOD VALIDATION:

CLEANING METHOD VALIDATION Last Rinse: Water for injection should be used as the last rinse for product-contact equipment to be utilized in the fabrication of sterile products. Establishment of Limits: The fabricator's rationale for selecting limits for product residues should be logical and based on the materials involved and their therapeutic dose. Change Control/Revalidation: To ensure that all changes that might impact the cleaning process are assessed and documented.

ADMIXTURE STUDIES:

ADMIXTURE STUDIES During infusion, the drugs are normally given as an admixture with an intravenous fluid such as 0.9% saline, 5% dextrose, or Ringer’s solution. Parenteral drugs are also used in combination with other drugs, and compatibility data for such admixture solutions are critical. Studies are performed by preparing admixtures of the drug product with various diluents in an appropriate type of flexible intravenous bag.

ADMIXTURE STUDIES:

ADMIXTURE STUDIES Initial samples are taken for analysis before the bags are stored in temperature-controlled stability chambers. Subsequent samples may be pulled at 6-, 12-, 24-, 48-, and 72-h time points. The analytical tests commonly performed include: visual appearance: Indicate formation of any particulate matter. pH & HPLC assay: indicate the chemical stability of the admixture.

MICROBIOLOGICAL TESTING OF PARENTERAL FORMULATIONS:

MICROBIOLOGICAL TESTING OF PARENTERAL FORMULATIONS Qualify and assure the continued upkeep of an aseptic environment. The simulation uses liquid microbiological growth media in place of product solution filled into the dosage units as the ultimate test of the robustness of the microbial control measures in the aseptic processing area, as well as the validation of heating, ventilation, and air condition/air systems, personnel training, and gowning.

MICROBIOLOGICAL TESTING OF PARENTERAL FORMULATIONS:

MICROBIOLOGICAL TESTING OF PARENTERAL FORMULATIONS Microbiological testing with biological indicators is also used to validate manufacturing equipment such as steam autoclaves/sterilizers, depyrogenation ovens or tunnels, component-washing machines, and isolation units. Other tests, such as microbial challenge tests of sterilizing grade filter membrane material or sterile closures, are also necessary.

Reference::

Reference: Handbook of modern pharmaceutical analysis By Satinder Ahuja & Stephen Scypinski Pharmaceutical Inspection Convention, Recommendations on Validation Master Plan, Installation and Operational Qualification, Non-Sterile Process Validation and Cleaning Validation, 2004. FDA, Guide to Inspections of Validation of Cleaning Processes, 1993. www.ich.org

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