QA and Pharmacopieal assays Flashcards
What is the purpose of pharmaceutical quality assurance?
The purpose of pharmaceutical quality assurance is to:
- Ensure that the medication being manufactured will provide the desired effect to the patient
- Quality assurance also guarantees that there are no contaminants present and that the medications will meet quality requirements and all relevant regulations
Why is Pharmaceutical Quality Assurance important? (objectives)
- Ensure public’s safety
- Protect against negative publicity
- Increase production efficiency
- Guarantee compliance
Compare QA and QC:
QA processes include:
- documentation
- audits
- supplier management
- personnel training
- change control
- investigation procedures
- good manufacturing practice
QC procedures include:
- batch inspection
- product sampling
- validation testing
- lab testing
- software testing
- good laboratory practice
- QA is proactive while QC is reactive - QC uncovers quality issues
- QA is process oriented and focuses on preventing quality issues from arising, while QC is product oriented and focusses on the quality of the manufactured products
- QA controls overall method and procedures at the system level; QC controls the parts in the processes that manufacture the products
- QA activities is a roadmap for creating high quality products; QC involves verification of the pdts in post-manufacture stage
- QA involves the entire team; QC is conducted by dedicated technical personnel
5 key components of good manufacturing practice (GMP): 5Ps
- Primary materials and products must be pure - based on monograph purity specifications
- Premises and equipment used for manufacturing must be maintained for operational readiness - clean, no introduction of impurities
- People involved in manufacturing process must be trained to competent level
- Procedures for manufacturing must use the latest technology and science
- Processes must be documented to show compliance
Who overlooks the quality for medicines?
International Conference on Harmonisation of Technical Requirements For Registration of Pharmaceuticals for Human Use (ICH)
Standardizes the requirements for medicines regulation throughout the world
Standardizes the validation of analytic procedures and indicates that validation is required for:
- Identification tests
- Quantitative tests for impurities
- Limits tests for the control of impurities
- Quantitative tests of the active pharmaceutical ingredients, drug products, and selected components in the drug product
List the sources of impurities exposed to pharmaceutical manufacturing
- Raw materials
- Method of manufacture
- reagents employed
- reagents added to remove other impurities (e.g., chloroform)
- solvents
- reaction vessels (e.g., detergent residual)
- Atmospheric contaminants
- dust in the air
- carbon dioxide dissolve in water => corbonic acid (dcr pH)
- Manufacturing Hazards
- Particulate contamination
- Process errors
- Cross-contaminations
- Microbial contaminations
- Packing errors
- Inadequate storage
- filth
- chemical instability
- reaction w container materials
- physical changes
- temperature effects => hydrolysis
- degradation during storage
[Limit test]
What is limit test?
Limit test are quantitative or semi-quantitative tests designed to identify and control small quantities of impurity which may be present in the drug substance
[Limit test]
Semi-quantitative test:
Comparison method (compare test solution with a standard solution containing the impurity)
- Standard containing a definite amount of impurity is set up at the same time and same conditions as the test experiment
- The official limit (based on pharmacopeia) for chlorides, sulphates, iron, and heavy metals such as lead and mercury, are based on this principles
Test solution should not have precipitate or turbidity more than the standard => if so, test solution is below the allowable limit and has passed the limit test
[Limit test]
Quantitative test for impurities:
Types of quantitative limit tests:
- Limits of insoluble matter
- Limits of soluble matter
- Limits of moisture, volatile matters, and residual solvents
- Limits of non-volatile matter
- Loss on ignition (limits of residue on ignition, ash values)
- Precipitation methods
Total ash method:
- measure of total remaining ash after incineration - high ash value indicates contamination in the crude drugs; indicates presence of inorganic salts of carbonates, phosphates, silicates of sodium, potassium, calcium, magnesium constituents of residues
- E.g., Fentanyl citrate - residue on ignition not more than 0.5%
[Identification tests]
Identification tests in Acetaminophen USP:
- Infrared absorption
- Compare the IR spectrum of the test sample and the USP reference standard to seek evidence for identity
- IR absorption relates to stretching and bending of bonds in different functional groups to the structure of the analyte
- Fingerprint region (600-1400 cm-1) of the IR spectrum
- Ultraviolent absorption
- Over 200-400nm
- Compare the UV spectra of the test and standard solution: determine the absorptivities and/or absorbance ratios as indicated in the monograph
- Requirements are met if UV absorption spectra of the test and standard solutions exhibit maxima and minima at the same wavelength and the absorptivities and/or absorbance ratios are within specified limits
- Thin layer chromatographic identification test
- E.g., use silica gel chromatographic plate, with solvent chloroform, methanol, water (180:15:1), unless otherwise specified in the monograph
- Rf value (dist traveled by component/dist traveled by solvent) of test solution vs standard solution
Note that these do not quantify
Note that pharmacological activity cannot be used to identify a chemical drug substance
[Titrimetric analysis for pharmaceuticals]
Principle:
Application:
Principle:
Amount of a standard reagent of precisely known concentration is used to react chemically with an analyte => estimate purity of the analyte
Application:
Used in pharmacopeial assays to determine purity of API, content of API in a dosage form, purity of raw materials
(Quantitative tests of the active pharmaceutical ingredients, drug products, and selected components in the drug product)
[Titrimetric analysis for pharmaceuticals]
Advantages
- High degree of precision and accuracy
- Methods are generally robust
- Analyses can be automated and cheap to perform
[Titrimetric analysis for pharmaceuticals]
Limitations
- Method may not be selective
- Time-consuming
- Require large amounts of sample and reagents
[Titrimetric analysis for pharmaceuticals]
Types
- Direct acid/base titration in aq phase
- Indirect titration in aq phase
- Argentometric titration
[Titrimetric analysis for pharmaceuticals]
Primary standards
Primary standards are stable chemical compounds that are available in high purity and that can be used to standardize the standard solutions used in titrations
E.g., Sodium hydroxide standard solution may be standardized against potassium hydrogen phthalate, which is available in high purity (NaOH is the secondary standard, potassium hydrogen phthalate is the primary standard)
