QC basics Flashcards
UV looking for
wavelengths
What do you compare TLC to?
a standard
What are you looking for in uniformity of mass
deviation
What are the key components of a HPLC?
Main High-Performance Liquid Chromatography (HPLC) Components. The HPLC system mainly consists of an infusion pump, a sampler, a chromatographic column, a detector, and a data recording and processing device. Among them, the infusion pump, the chromatographic column, and the detector are key components
What types of issues would you expect from a HPLC and how would you identify them?
One of the most common peak problems in HPLC is peak splitting or broadening. This can be caused by a variety of factors, including column overload, poor column packing, or improper mobile phase composition. In some cases, peak splitting can also be caused by sample matrix effects or poor sample preparation techniques
One common error in HPLC is poor peak shape. This can be caused by a number of factors, including an improper choice of stationary phase, an incorrect flow rate, or a faulty column. To fix this issue, the first step is to identify the cause of the problem.
Variable peak heights, split peaks, and broad peaks can be caused by incompletely filled sample loops, incompatibility of the injection solvent with the mobile phase, or poor sample solubility. Whenever possible, dissolve and inject samples in mobile phase
How would you validation a HPLC system?
Change control, IQ, OQ, PQ, Method Validation.
Validation of HPLC method gives information about various stages and parameters like accuracy, precision, linearity, Limit of detection, Limit of quantification, specificity and robustness. Validation should be done as per regulatory guidelines such as ICH guidelines.
In case of an HPLC method, it is assured by complete separation of peak(s) of analyte(s) from other peaks originated from the sample matrix. Specificity evaluation was done by injecting separately 20 µl solution of standard, sample, placebo, and blank into the chromatographic system.
What do you understand by Dissolution (Type 1 and 2)?
basket type (apparatus I) and paddle type (apparatus II) are most commonly used for oral solid dosage forms but many different product types, from capsules to creams, can be testing using the apparatus defined in the USP
Can you describe a dissolution bath and the important aspects wrt to setup and key parameters?
Usually consists of 6 containers each containing a solvent and basket or paddle. The solvent should be set to a specific temperature (approx. 37) and be a specific volume (approx. 1000mL) and the paddle or basket should be set at a specific speed.
How would you calibrate a dissolution bath?
Change control, URS, IQ, OQ, PQ including: Rotation per minute by using Digital Tachometer, Vessel temperature calibration by Digital Thermometer, Paddle/ basket wobble test by using Wobble Centering Gauge, Distance between the bottom edge of basket/paddle to the lowest inner surface of vessel by using Depth Gauge.
The study should include a measurement of the speed of the shaft rotation for each vessel contained within the dissolution apparatus. Speed should be measured using a photo tachometer for 30 minutes or the time specified in the individual monograph, whichever is greater.
What reference tablets do you use for dissolution testing?
Prednisone Tablets with the Paddle Method and Salicylic Acid Tablets with the Basket Method
in dissolution what is the meaning of the Q value?
Q represents the targeted amount of active substance, expressed as a percentage of the label claim, which should be dissolved within a certain time. The ‘Q value’ should be seen as a “reference value” to which the dissolution results are compared.
Wrt sample methods i.e. swabs and rinse waters what are their respective pros and cons?
Swabbing and rinsing are the two most common techniques used for sampling of cleaned surfaces). Swabbing is a direct surface sampling method, while rinsing is an indirect method. In practice, physical access to surfaces and parts of equipment to be cleaned tends to drive the choice of sampling method.
Two advantages of using rinse samples are that a larger surface area may be sampled, and inaccessible systems or ones that cannot be routinely disassembled can be sampled and evaluated
A disadvantage of rinse samples is that the residue or contaminant may not be soluble or may be physically occluded in the equipment
The swab test offers the advantage that sampling can be carried out directly at the critical points and even sparingly soluble residues can be collected. The disadvantages are the high demands on analytical method development and the problem of reproducibility.
The disadvantages of swab tests are mainly that the testing protocol needs to be more rigorous, in order to get consistent results. It is hard to know exactly what surface has been sampled (the contact between the swab tip and the surface depends on the swab angle), and how much pressure was applied.
Validation of an analytical method. What standard would you use and where would you find it. What are the factors to be validated.
Follow ICH Q2 guidance. Factors could include accuracy and precision, specificity, LOD, LOQ, Range, Robustness and repeatability
How would you deal with an OOS analytical result?
Is it a true result? Follow MHRA guidance on OOS investigation - phase 1a, phase 1b, hypothesis testing, Phase 2, deviation investigation
What is a system suitability test and what is it looking for?
“System Suitability Tests are an integral part of gas and liquid chromatographic methods. They are used to verify that the resolution and reproducibility of the chromato- graphic system are adequate for the analysis to be done.
Where would you find information on system suitability tests?
Pharmacopeia and ICH
Explain the BP uniformity of weight test?
Weigh individually 20 units taken at random or, for single-dose preparations presented in individual containers, the contents of 20 units, and determine the average mass - not more than 2 deviate from the average weight by a percentage greater than that specified
Explain the BP content of uniformity test?
The test for uniformity of content of single-dose preparations is based on the assay of the individual contents of active ingredient of a number of single-dose units to determine whether the individual contents are within limits set with reference to the average content of the sample.
Tell me about antibiotic assays e.g. pros and cons of bioassays as opposed to HPLC?
An antibiotic assay tests enable the serum concentrations of certain antibiotics to be monitored. This helps to ensure adequate dosing for efficacy, and to avoid risks associated with potentially toxic levels.
Two kinds of assays are usually referred: dilution and diffusion. In the former, the antibiotic is presented to the test organism at one concentration. The concentration is uniform throughout the medium. The medium may be liquid as in tube methods or solidified by agar as in a plate dilution method.
What is Bio-assay.
A bioassay is an analytical method to determine the potency or effect of a substance by its effect on living animals or plants, or on living cells or tissues.
Bioassays provide valuable information concerning the potency of biological products. This is essential for evaluating batch-to-batch consistency and stability. Bioassay data are crucial at all stages in the development of biological products, from early research work to final quality control of finished products
Advantages: Quick and simple with more precision than a matching assay. There is a possibility of using certain statistical procedures although not with much confidence. Disadvantages: still an inherent lack of precision, no accuracy, need for specific organisms and potential limitations in detecting certain contaminants
Parametric release. What does this mean?
Parametric release is a system of release that gives the assurance that terminally sterilised product is of the intended quality based on information collected during the manufacturing process and on the compliance with specific GMP requirements related to Parametric Release
There is no performance of a sterility test, so no waiting for results and no additional delays due to investigations of common “false” sterility test positive results. Another benefit may be financial savings from the absence of expenses related to sterility testing and product holding.
Sterilisation out of specification, test product, sterility test OK what then?
Batch is still in the bin, if we have a failed sterilisation cycle the batch cannot be released - this will be one of the release checks therefore no impact to product on the market
What information would you expect on a CofA and CofMc?
A Certificate of Analysis (COA) is a document that communicates the results of a scientific test done on a product such as food or drugs. The COA also lists the chemicals used in the product’s manufacturing and testing and is created to ensure all important regulations are met and complied with.
-the name and address of the laboratory issuing the CoA;
–the identification number of the CoA and on each page an identification, the page number and the total number of pages to ensure that every page is recognized as a part of the certificate;
–the name, address and contact person representing the originator of the request for analysis;
–the number assigned to the sample by the laboratory during registration upon receipt;
–the date on which the sample was received in the laboratory and the quantity of sample (number of units or packages);
–the name, description (for example, active ingredient, dosage form, strength, package size in the case of FPPs; grade in the case of starting materials; type and material of the primary packaging), batch number (used by the original manufacturer and repacker or trader) of the sample for which the certificate is issued, the expiry date (or retest date, where applicable) and date of manufacture (if available);
–the name and address of the original manufacturer; in addition, if supplied by repackers or traders, the certificate should show the name and address of the repacker or trader;
–specifications for testing and a reference to the test procedure(s) used, including the acceptance criteria (limits);
–the results of all tests performed on the sample for which the certificate is issued (in numerical form, where applicable) and a comparison with the established acceptance criteria (limits); results of tests performed by subcontractors should be identified as such;
–any comments, observations or information on specific test conditions, where these are necessary for the interpretation of the results;
–a conclusion as to whether or not the sample was found to be within the limits of the specification;
–the date and signature of the head of the laboratory or other authorized person approving the certificate.
What statistics do you use in comparing 2 sets of results from two separate laboratories?
A t-test is a statistical hypothesis test used to test whether the difference between the response of two groups is statistically significant or not. It is any statistical hypothesis test in which the test statistic follows a Student’s t-distribution under the null hypothesis.
T-tests are used when the data sets follow a normal distribution
(1) one-sample t-test; (2) two-sample t-test; and (3) two-sample paired t-test.
The Student’s t test is used to compare the means between two groups, whereas ANOVA is used to compare the means among three or more groups.
Describe the contents of a typical monograph.
Monographs articulate the quality expectations for a medicine including for its identity, strength, purity, and performance. They also describe the tests to validate that a medicine and its ingredients meet these criteria.
A pharmacopeial monograph provides detailed parameters that are used to determine whether a medicine meets key quality attributes and can be marketed legally in any given country
a monograph contains detailed instructions for identification, purity tests and other specific tests to limit the amount of undesirable impurities, all of which may be used to verify common requirements by manufacturers and formulators concerned with the quality of their ingredients and products.
Contents: Action and use, definition, content of drug, Identification, Tests (e.g. dissolution - test conditions, procedure, determination of content, related substances, test conditions etc), Assay (method, conditions, system suitability, determination of content), labelling, impurities
What is the difference between British Pharmacopoeia and European Pharmacopoeia?
The BP is the only comprehensive collection of authoritative official standards for UK pharmaceutical substances and medicinal products. It contains all texts and monographs of the European Pharmacopoeia (signposted with a chaplet of stars), as well as the national standards developed by the BP.
