BTEC 3320 Exam 2 QUESTIONS & ANSWERS 2022 UPDATE 100% correct

Quiz 6 Which of these changes to protein purification using an AKTA would most likely be classified as minor change? The flow rate was increased 25% higher. The buffer that is used in the mobile phase was replaced with a different weak acid The set number of times the column can be washed and reused is changed from 20 to 25 reuses. The tempeature setting for the column was decrease 25% from the earlier settings. The detector was replaced with a newer model that is more sensitive in detecting lower amounts of impurities Info from slide Minor change ● Minimal impact/risk to product QuIPS ● Require a summary of the change in their annual report to the FDA ● Documentation required to support this change would include technical study reports and possible re-validation ● Includes tightening of acceptance criteria, alternative analytical SOPs What is the first step in a document change control process? Originator drafts the proposed change. 1 The revised document is distributed to users. 5 QA assigns an effective date. 4 A document number is assigned by the QA. 2 Users are trained on the execution of the revised SOP 6 The proposed changes are circulated for review. 3 Info from slides The change control process starts with an author, i.e., the person making the change If it’s a new document, this person writes it up For changes or obsoletions, the author makes the appropriate changes with a red pen directly on to the document There is an intermediate approval by key people that will be affected by the document, then it formally enters the QA Document System QA assigns a document number, if it’s new, the document is circulated for review The document is evaluated and approved The effective date is assigned QA then distributes the document to authorized personnel who are then trained. Master copy is retained Document now effective What is not part of the change control process? Older SOPs are rendered obsolete The draft of the revised document is circulated for review Users are trained prior to the document becoming effective A master copy of the approved document is retained within the QA document system Older SOPs are retained by users A company's change control board is made mainly of members of the quality assurance and quality control groups TRUE FALSE Info from slide Include QA, QC, Regulatory, Production, Product/Process Development, Research The intent of change control system is to determine the need for actions that would ensure that the system is maintained in a ________________ state. Innovative Balanced Validated Advance Modern Small changes to a process can over time can add up and lead to a product that is no longer what was promised in the New Drug Application. The result is what is referred to as product ______________. Creep Recall Validation Failure Specification Malfunction Info from slide Creep- changes to documentation, big and small, over time can add up and incrementally lead to this To prevent creep, documentation must be controlled Some changes would not require approval by the FDA before the drug product that was manufactured using the changed process can be distributed. TRUE FALSE What can be a repercussion from an inadequate response to the violations listed by the FDA to Wockhardt? Forceful ending of sponsorships and partnerships the firm may have with similar companies Reporting only passing test results in laboratory notebooks Withholding approval of any new applications listing the firm as a drug product manufacturer Jail time of a period no less than 5 years for the laboratory manager and the expulsion of all quality control unit workers A public media statement by the FDA not recommending the product to consumers "The SOPs that a company uses to manufacture their product are included in the chemistry, manufacturing, and controls (CMC) section of the ____________________________________ that the company submits to the FDA at the conclusion of successful Phase III clinical trials." New Drug Application Investigational New Drug Application Establishment Inspection Report Active Pharmaceutical Ingredient Summary Deviation reports Master Batch Record A description of the change is to be included in the annual report to the FDA only if the change is classified as moderate or major. FALSE TRUE Info from slide Require a summary of the change in their annual report to the FDA The level of effort and formality of change management is highest during manufacturing a drug product for: Product discontinuation Phase I human trials Commercial distribution Phase II clinical trials in humans Technology transfer from small to commercial scale manufacturing Pre-clinical animal testing "In the Immunomedics warning letter, there were three deviations that were not closed by the due date. Deviations should not remain open unless an _____________ was requested." invalidation obsoletion exemption excuse Extension Quiz 7 What is not a main job responsibility of the QC group? Make the final decision on disposition of materials Testing and release of finished drug products Environmental monitoring for viables and non-viables "Testing of containers, closures, packaging and labels" "Developing, validating, and performing assays in support of production" Info from slide Quality Control ● Developing, validating, and performing assays ● Testing of materials and finished products ● Providing analytical support for process validation ● Environmental monitoring "18 drums of bulk raw material were delivered to your manufacturing company. As the QC analyst assigned to handle the delivered material, what is the minimum number of drums that you should sample and test for attributes like identity, appearance, impurities or water content? 9 drums 6 drums 4 drums 5 drums 11 drums "What is not a source of information on acceptable sampling sizes, like the table shown in front?" American Society for Quality International Organization for Sampling Design International Organization for Standardization American National Standards Institute Military standard "____________________ testing is where samples obtained from all drums of delivered raw materials from the same lot are pooled in a single container, mixed, and analyzed as one sample for different attributes." Composite Multiplex Simultaneous Representative Conformance Info from slide Composite testing- samples obtained from all drums are pooled in a single container, mixed, analyzed as one sample for different attributes. Done for attributes other than identity. What does not apply to reference materials that are used by QC in tests? of the highest quality (identity and purity) for its use available from independent suppliers or vendors always produced internally by drug manufacturers "used as standards in assay, identity, or purity tests" stored at sufficient quantities for later comparability and equivalence studies many are purchased from pharmacopeias Info from slides Reference materials- used as standards in assay, identity, or purity tests- of the highest quality for its use The development and maintenance of an analytical method totally depends on internal or external reference standards Internal reference materials are produced initially during process development using material from the first batches produced according to the protocol Later, when material is manufactured in the pilot plant, reference material will be taken from this bulk Enough quantities of reference material should be stored to enable later comparability and equivalence studies possible "There are two types of risks involved when a company samples a small number products for testing, instead of testing every single one of the products. In a type of sampling risk classified as producer's risk:" Lot is marketed Consumer's health is not put at risk. Manufacturer's revenue is not affected Lot is bad and rejected and not released for marketing Lot is accepted Info from slide Lot is accepted, Impact if Lot is Good= Correct Decision, Impact if Lot is bad= Incorrect Decision is a Type II risk or “Consumer Risk” Lot is rejected, Impact if Lot is Good=Incorrect Decision a type I risk or producer’s risk, Impact if Lot is Bad=Correct Decision For sampling and testing of API received by the drug manufacturer: A minimum of two identity test is required Samples from different lots can be combined and tested as pooled samples Full testing against CofA should be performed for each lot Only one identity test is necessary for each lot of API Testing against CofA is optional Info from slide Certificates of analysis (CofA) should be received for each lot of raw material ● Full testing against CofA for all API lots ● Identity tests for other raw materials (excipients) "During bioprocess, to measure the amount of recombinant protein produced during increasing duration of bacterial growth, you can withdraw a sample from a port and measure enzymatic activity. This type of measurement is considered:" In-line measurement Non-invasive measurement At-line measurement On-line measurement Out-of-line measurement Info from slide Non-invasive: sensor is not in contact with the material Online measurements- system is connected to the process via a diverted sample stream, material may be returned Inline measurements: in contact with process stream (i.e. probe), real time offline/ atline measurements: sampling in production area->lab->analyze What is not always a requirement for cGMP-compliant sampling? Samples obtained must be properly identified and handled Samples must be an accurate representatiion of the material or drug product batch Sampling plans must be based on appropriate statistical criteria >50% of a drug product lot should be tested "Sampling plans and methods must be written, defined, and pre-approved" Info from slides 4 themes in cGMP sampling requirements 1. Sampling plans and methods must be written and defined 2. Samples must be representative of the population 3. Sampling plans must be based on appropriate statistical criteria 4. Samples must be properly identified and handled Quiz 8 What is not a product release test for biologics? amino acid sequencing of biologic mg antibody per vial of drug product tests for potency test for endotoxins sequence of recombinant gene in production host What is not considered as in-process tests for typical coated tablets? Tablet capping Fill accuracy Blend uniformity Water content Particle size distribution It is acceptable for QA to periodically monitor the end product in place of working to prevent contamination. FALSE TRUE Analytical tests are performed on: Stability samples All are correct Active pharmaceutical ingredients In-process materials Final drug products Raw materials "Friability tests are performed on tablets using a ""hamster wheel"" to measure:" API release profile inside the patient's blood stream "Resistance to chipping, crumbling, or breaking when shaken in containers" Uniformity of API concentration in the average tablet Uniformity of API concentration in blended in-process materials Breaking of the drug product into smaller pieces inside the GI tract What is not one of the three components of sampling? Dilutions None of the other choices Method of sampling Specifications Sample size "In the production of biotherapeutic protein using Chinese Hamster Ovary cells as expression hosts, which of these impurities is a process-related impurity, that is, not considered a product-related impurity?" Degradation products Aggregates Mismatched disulfide bridges Hyperglycosylated protein CHO proteins Info from slides Product-related impurities ● Precursor molecules ● Degradation products ● Aggregates ● Glycosylation products, deamidated, isomerized, mismatched S-S linked, oxidized or altered conjugated forms What is not used as a potency assay for antibodies? Peptide mapping Cell-based killing Activation of a reporter gene in cells "In vitro binding assays, like ELISA" Testing activity In animal models Info from slide ● Enzymes-enzyme activity ● Inhibitors- inhibition of enzyme activity ● Antibodies ○ Cell based assay demonstrating inhibition or activation ○ Assay demonstrating the antibody binds the specific antigen (ELISA, FACS, or BIAcore) ● Cytokines- inhibition or activation in a cell based assay ● Some proteins require an animal model to measure potency (FSH) ● In vitro binding assays (ELISA or BiaCore) What is not true about RSD? RSD stands for relative standard deviation Reflects deviation of individual samples from the mean The RSD is independent of the number of samples obtained RSD is often expressed as a percentage "The lower the RSD value, the better" Quiz 9 Environmental monitoring in an aseptic manufacturing facility does not include: Measuring the levels of safe carbon monoxide Measuring the levels of dust that could be generated from growth media Measuring the levels of dust that could be from equipment Measuring the levels of bacterial spores in the air Measuring the levels of fungi on equipment surfaces Info from slides ● Viable- bacteria, spores ● Non-viable ○ Dust particles ○ Environment-related ○ Equipment-related ○ From materials "To confirm a media sterilization SOP using an autoclave, what are placed inside the autoclave during the sterilization run to demonstrate the effectiveness of the sterilization process?" Biological indicator strips RODAC plates Sabouraud agar plates LB Agar plates TSA contact strips Info from slide Biological Indicator Strips ● Placed inside autoclave or bioreactor (for stream-in-place/SIP) and sterilization process is run ● QC microbiologists then inoculate strips into solid media, then quantify growth The drug filling area is a specially vulnerable area to contamination thus requiring Class A (Class 100) air quality. How many microbes are allowable per meter cube in an area which is class 100? Less than 1 CFU per cu. m. Less than 10 CFU per cu. m Less than 100 CFU per cu. M 1 or less CFU per cu. m Less than 200 CFU CFU per cu. M Info from slide Pharmacopeial specifications consists of each of the following except: Volume of nitrogenous liquids Sterility tests Microbial limits Uniformity of dosage units There are pharmacopeial specifications for all the other choices "Endotoxins are lipopolysaccharides found on the outer membrane of Gram negative, but not in Gram positive bacteria. What is not used to test for the presence of endotoxins in drug products?" Hybridization assay Rabbit Pyrogen Test LAL gel clot assay Chromogenic LAL Assay Pyrogene Recombinant Factor C assay Mycoplasma is a common contaminant of cell cultures and can adversely affect virus propagation for vaccines and recombinant protein quality. Which immediate corrective action could be taken when one detects Mycoplasma in their cell cultures? Throwing the contaminated cell cultures away Implementing additional decontamination and cleaning techniques Incorporating additional filtration techniques Additional personnel training Identifying a better source of quality materials Info from slides ● Throw it away (most conservative path) ● Treat with mycoplasma specific antibiotics such as ciprofloxacin Mycoplasma is a common contaminant of cell cultures and can adversely affect virus propagation for vaccines and recombinant protein quality. What is not used as a test for Mycoplasma? Gram staining Hoechst fluorescent stain Microscopy Polymerase chain reaction Fried egg-shaped colonies on plates Quiz 10 What does the phrase "testing into compliance" mean? A non-conforming batch is reprocessed and retested until it passes specs Test results from a non-conforming batch is manipulated by a second analyst until the numbers are within specs A non-conforming batch is resampled and retested until results obtained meet acceptance criteria A non-conforming batch is rejected after non-conforming test results A non-conforming material is tested using a different SOP to see if it passes specs What is an unacceptable disposition for a drug product batch which is confirmed OOS for a critical quality attribute? Batch is discarded Company recalls the marketed drug Batch is reprocessed for some drug products Batch is rejected All the other answers are possible dispositions QA releases batch for marketing In what instance might a drug product be considered out of specifications? The quality attribute measurement is the exact value as the pre-written acceptance criteria The obtained test results are below the upper limit of the acceptance criteria range The obtained test results are above the lower limit of the acceptance criteria range The obtained test results exceeded the upper limit of the acceptance criteria range The obtained test results are in the middle of the range of acceptable values "In the event of non-assignable cause for OOS, what would be part of the Phase II of the OOS investigation?" The analyst who generated the OOS result redoes the test in triplicate A second analyst does one retest of the same samples that were tested by the first analyst Evaluation of the overall manufacturing process sequences that may have caused the problem A second analyst redoes the test using the solutions originally used by the first analyst The original analyst redoes the test using the original prepared solutions Info from the slide PhII: In the event of non-assignable causes: ● Evaluate the overall manufacturing process that may have caused the problem ○ Production, process development, research, QA/QC ● Review of batch production records, if applicable ● Review of other batches and products possibly affected "For stability samples, a product lot will be recalled once a second analyst performs retests of the first analyst's solutions and obtains OOS results also." TRUE FALSE "For tablets, in which of these activities will test results outside of the specified criteria be considered OOS?" API content measured in blend samples fail the uniformity criteria Results from process development tests which are out of pre-specified criteria Results of method validation which are out of pre-specified criteria Moisture content of in-process blend is above acceptance criteria after 30 mins of a 60 min maximum specified drying time Results of API content testing of drug product release samples are out of the prespecified passing range Info from slide: OOS Does not apply to: ● Process development work ● In-process checks, if process can be adjusted ○ Moisture, blend uniformity ● instrument/method qualification or calibration, or validation of methods ● Method transfers What is not out of compliance with FDA expectations on OOS investigations? Failure to investigate promptly Failed to follow OOS investigation protocol Failure to investigate OOS within 30 business days Risks to other batches were not assessed Failed to investigate before the OOS actually happened What does not apply to specifications? Inclusion and exclusion of tests for critical quality attributes for drug product release should be justified Drug product specifications are not required in New Drug Applications submitted by companies for marketing approval Specifications includes acceptance criteria for drug product release prior to distribution Justification for specifications are based on lots manufactured for pre-clinical and clinical testing Specifications include a series of tests and instructions on performing the tests Info from slide Specifications- consist of a series of test procedures with established acceptance criteria to which the DS/DP must conform prior to release Justification for specifications ● Rationale for and against inclusion of tests for CQA ● Data-based ○ From pre-clinical or clinical lots ○ Validation lots for demonstration of process/product consistency ○ Stability studies ● Required section in NDA/CTD The Ishikawa diagram is a useful tool for root cause investigation of an OOS. The root cause of OOS results can be traced to any one of the 5M inputs in the drug manufacturing process. Which is not one of the 5Ms? Man Environment Material Machine Methods Money Info from slide ● Manpower ● Materials ● Environment ● Methods ● Machines What is not considered an assignable cause for an OOS event? An analytical method for a different component was used The wrong weight was plugged into the equation used for calculations Analyst made a mistake in weighing one of the components The analytical balance was calibrated prior to its use There were undissolved crystals found in one of the solutions Info from slide