Pharmaceutical Quality Control and Assurance, Exams of Biochemistry

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QA-QC EXAM 2 Latest Questions with Correct

Answers.

Q1. What is not always a requirement for cGMP compliant sampling? - Correct Answers Samples must be stored at low temperatures. Q1. What is always a requirement for cGMP compliant sampling? - Correct Answers - Sampling plans and methods must be written, defined, and pre-approved.

• Samples must accurately portray the quality attributes of a drug product lot.
• Sampling plans must be based on appropriate statistical criteria
• Samples obtained must be properly identified and handled. Q1. Which is not an In-process control test used to monitor the progress of protein production during fermentation? - Correct Answers Gene copy number Q1. Which is an In-process control test used to monitor the progress of protein production during fermentation? - Correct Answers - Concentration of biologic
• Presence of misfolded proteins
• Presence of chemicals used to clean the bioreactor
• Endotoxin levels Q1. In the sampling table shown in slide 35, for a lot size of 660, __________ units should be obtained and tested for conformance to specifications. - Correct Answers 32 Units Q1. During bioprocess, the temperature sensors (probes) are dipped in the fermentation culture inside the bioreactor, signal from the sensors read by a computer, and the temperature of the heating blanket gets automatically adjusted. The temperature measurement by the sensor is an example of... - Correct Answers In-line measurement Q1. What is not a main job responsibility of the QC's group? - Correct Answers Checking the adherence of process technician to batch record SOPs. Q1. What is a main job responsibility of the QC's group? - Correct Answers - Analytical testing of raw materials against specifications before use by the production group.
• Testing of drug products against specifications before release.
• Provide analytical support for process validation and in-process test.
• Environmental monitoring for viables and non-viables. Q1. What does not apply to raw materials or raw material testing? - Correct Answers Full testing against the CofA should be conducted on all raw materials. Q1. What does apply to raw materials or raw material testing? - Correct Answers - Criticality of materials and tests differ for different raw materials depending on their intended use.

• Raw materials must be identified, quarantined, their identity tested by specific assays, and released by QC and QA.
• Quality requirements for raw materials are met somewhat differently in production of pre- clinical, clinical batches, and manufacturing of licensed products.
• If the raw material is microbiologically sensitive, it may be prudent to sample every container regardless of lot size.
• Certificates of analysis should accompany every lot of delivered raw material. Q1. What is not a process control variable in the downstream cell harvesting processes that could impact product quality and yield? - Correct Answers Bioreactor cleaning reagents. Q1. What is a process control variable in the downstream cell harvesting processes that could impact product quality and yield? - Correct Answers - Filtration backpressure.
• Filtration temperature.
• pH of chromatography mobile phase.
• Centrifugation speed. Q1. 45 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 impurities or water content? - Correct Answers 8 drums √n + 1 Q1. In the manufacturing of small molecule drugs, what would be considered as an impurity rather than a contaminant? - Correct Answers incompletely synthesized API Q1. In the manufacturing of small molecule drugs, what would not be considered as an impurity rather than a contaminant? - Correct Answers - equipment lubricants
• microbes
• endotoxins
• dust particles
• an inorganic catalyst. Q1. What does not apply to specifications for release of finish drug products? - Correct Answers Acceptance criteria should be changed if test results don't conform to specifications. Q1. What does apply to specifications for release of finish drug products? - Correct Answers - Many analytical procedures that are part of specifications are found in the US Pharmacopeia.
• Specifications consist of test procedures.
• Release specifications are approved by regulatory agency as conditions for marketing approval.
• Specifications include rejection criteria for certain attributes.

Q1. In the Genzyme video on producing biotherapeutics using mammalian cells... What is the correct sequence of manufacturing activities in the 90 - day production flow? - Correct Answers Thaw frozen cell bank → small-scale growth → large-scale growth → harvesting → filtration → chromatographic purification → fill and finish Q1. What is not a source of information on acceptable sampling sizes, like the table shown below? - Correct Answers American Institute for Sampling Compliance Q1. What is a source of information on acceptable sampling sizes, like the table shown below? - Correct Answers - American National Standards Institute

• American Society for Quality
• Military standard
• International Organization for Standardization Q2. What is an acceptable quantity of each sample that should be obtained when sampling in-process material for blend uniformity using a sample theif, if the final drug product is a 300 mg tablet containing 30 mg API? - Correct Answers 500 mg Q2. Procedures and Acceptance Criteria for release testing of tablet dosage forms are found in __________, while those for biotechnological or Biological Products are found in ICH Q6B. - Correct Answers ICH Q Q2. In the production of biotherapeutic protein using Chinese Hamster Ovary cells as expression hosts, which of these impurities is a product-related impurity, that is not considered a process-related impurity? - Correct Answers Recombinant product missing the first 10 amino acids. Q2. In the production of biotherapeutic protein using Chinese Hamster Ovary cells as expression hosts, which of these impurities is a product-related impurity, that is also considered a process-related impurity? - Correct Answers - Detergents used to clean bioreactors.
• Host cell proteins.
• Lysozyme used to break cell open.
• Media components. Q2. Stability testing of biologics with shelf life 1 year or less is performed on at least 3 lots ______. - Correct Answers at 0, 1, 2, 3, 6, 9, 12th month. Q2. For blend uniformity, a typical API acceptance range is _________% of target API amount. - Correct Answers 90 - 110% Q2. Dissolution tests are performed on tablets or capsules to predict: - Correct Answers There's no correct answer.

Q2. Dissolution tests are not performed to predict: - Correct Answers - API release profile inside the patient's blood stream.

• Uniformity of API concentration in the average tablet.
• Resistance to chipping, crumbling, or breaking when shaken in containers.
• Breaking of the drug product into smaller pieces inside the GI tract. Q2. Stability tests look at the change in quality attributes over time. For biologics, what quality tests are not performed as part of stability studies because the results are not expected to change much from time zero? - Correct Answers Amount of host cell protein Q2. Stability tests look at the change in quality attributes over time. For biologics, what quality tests are performed as part of stability studies because the results are not expected to change much from time zero? - Correct Answers - Quantity
• Product potency
• Percent purity
• Peptide mapping Q2. What is not used as a potency assay for antibodies? - Correct Answers NMR - Nuclear Magnetic Resonance Q2. What is used as a potency assay for antibodies? - Correct Answers - Cell-based killing.
• In-vitro binding. assays, like ELISA.
• Activation of a reporter gene in cells.
• Testing activity in animal models. Q2. What is not a product release test for biologics? - Correct Answers Identity test for the cell substrate. Q2. What is a product release test for biologics? - Correct Answers - amino acid sequencing of biologic.
• PCR for viral contaminants.
• mg antibody per vial of drug product.
• tests for potency. Q2. For determining uniformity of API in blends; an acceptable sample size for a non- validated manufacturing process would be 30, while for a validated process it would be _______. - Correct Answers 10 units. Q2. Blend uniformity is tested on ______, while content uniformity is tested on_______. - Correct Answers In-process material & Drug Product Q2. What is not true about RSD - Correct Answers The higher the RSD value, the better. Q2. What is true about RSD - Correct Answers - RSD is often expressed as a percentage.
• RSD is a statistical measure of process variability.

• RSD stands for Relative Standard Deviation.
• RAD value reflects deviation of individual samples from the mean. Q3. The Ibis T5000 Universal Biosensor: - Correct Answers Identifies a bacterial contaminant present in a raw material. Q3. What is not true about endotoxins? - Correct Answers Belong to a class of molecules called lipoproteins. Q3. What is true about endotoxins? - Correct Answers - are molecules found on the outer membrane of Gram-negative, but not in Gram-positive bacteria.
• Bacterial Endotoxin Tests are found in ICH Q4B
• Are chemical substances that cause fever in humans in drugs that are administered intravenously.
• In mammalian cell production hosts, endotoxins are considered contaminants rather than process impurities. Q3. In the video on autoclaving, what is not mentioned as having an effect on the effectiveness of the sterilization process? - Correct Answers Effectiveness can be affected by racks which are coated with non-tick Teflon Q3. In the video on autoclaving, what is mentioned as having an effect on the effectiveness of the sterilization process? - Correct Answers - Efficiency of sterilization using an autoclave can be affected by temperature.
• Autoclaving is most effective in sterilization when moist heat is used.
• Efficiency of sterilization using an autoclave can be affected by the amount of media loaded in the autoclave.
• The duration of the autoclaving cycle can affect the efficiency of sterilization process. Q3. To investigate a possible source of microbial contamination of a parenteral drug product, QC might test samples from: - Correct Answers - Walls of the manufacturing suite.
• In-process materials.
• Personnel surfaces.
• Finished product. Q3. In an aseptic manufacturing suite with class A (class 100) air quality, < 1 CFU is allowed to grow on sampling plates per meter cube of sampled air. What does CFU stand for? - Correct Answers Colony Forming Units Q3. Mycoplasma is a common contaminant of cell cultures and can adversely affect virus propagation for vaccines and recombinant protein quality. Which corrective or preventive action taken whenever Mycoplasma contamination is detected will lead the most to producer's revenue loss? - Correct Answers Throwing the contaminated cell cultures away.

Q3. Mycoplasma is a common contaminant of cell cultures and can adversely affect virus propagation for vaccines and recombinant protein quality. Which corrective or preventive action taken whenever Mycoplasma contamination is detected will least lead to producer's revenue loss? - Correct Answers Treating the cultures with the antibiotic, ciprofloxacin Q3. In the video on sterilization of Biosafety Cabinets (BSC), for sterility testing of a 4 - ft BSC, what was not done to the settling plates. - Correct Answers Place plates upright in the incubator. Q3. In the video on sterilization of Biosafety Cabinets (BSC), for sterility testing of a 4 - ft BSC, what was done to the settling plates. - Correct Answers - Write date, start and end times on petri dishes.

• Use 4 settling plates for a 4 ft BSC
• Leave settling plates uncovered for 30 min in the BSC
• Wipe petri dishes with 70% ethanol prior to putting in BSC. Q3. Of the locations given, which one is supposed to be a Class 100 area? - Correct Answers Biosafety Cabinet (BSC) with blower on. Q3. The BACT-ALERT 3D system is not, or does not: - Correct Answers Promote growth of recombinant E. coli used in biotherapeutic protein production. Q3. The BACT-ALERT 3D system is, and only is: - Correct Answers - Useful for drug products with short shelf lives, like cellular products.
• Compliant with FDA's initiative on process analytical technologies (PAT).
• A much faster alternative to compendial tests for bacteria which can take 14 days.
• Detects carbon dioxide produced by respring microbes. Q3. The endotoxins found on the surface of Gram-negative bacteria are lipopolysaccharides that cause fevers when injected into the bloodstream of animals. What is not a type of bacterial endotoxin tests? - Correct Answers Calorigenic Q3. The endotoxins found on the surface of Gram-negative bacteria are lipopolysaccharides that cause fevers when injected into the bloodstream of animals. What is a type of bacterial endotoxin tests? - Correct Answers - Pyrogene
• Chromogenic LAL test
• Turbidimetric LAL test
• Gel clot Q3. Environmental monitoring in an aseptic manufacturing facility does not include: - Correct Answers Measuring the number of tryptic soy agar plates that were used. Q3. Environmental monitoring in an aseptic manufacturing facility does include: - Correct Answers - Measuring the levels of dust that could be generated from growth media.
• Measuring the levels of fungi on equipment surfaces.

• Measuring the levels of bacterial spores in the air.
• Measuring the levels of dust that could be from equipment. Q3. Growth promotion tests are not performed to: - Correct Answers Demonstrate that antibiotics are not destroyed by autoclaving. Q3. Growth promotion tests are performed to: - Correct Answers - Demonstrate that colonies growing on test plates came from test samples and not from the media itself.
• Demonstrate that microbiological plates were sterile prior to use.
• Demonstrate that the media can actually support growth of microbe.
• Demonstrate that colonies growing on test plates came from environmental samples and not from the media itself. Q4. What is an unacceptable disposition for a drug product batch which is confirmed OOS for a critical quality attribute? - Correct Answers QA releases batch for marketing Q4. What is an acceptable disposition for a drug product batch which is confirmed OOS for a critical quality attribute? - Correct Answers - Company recalls the marketed drug.
• Batch is discarded.
• Batch is rejected. Q4. In certain analytical tests, like that using an HPLC, what is run together with the samples for similarity with the retention times of the test samples? - Correct Answers Reference standard Q4. In certain analytical tests, like that using an HPLC, what is not run together with the samples for similarity with the retention times of the test samples? - Correct Answers - Alcohol
• Representative sample
• Buffer
• Acid or Base Q4. What does the phrase "testing into compliance" mean? - Correct Answers A non- conforming batch is resampled and retested until passing results are obtained. Q4. For tablets, in which of these activities will test results outside of the specified criteria be considered OOS? - Correct Answers Moisture content of in-process blend is above acceptance criteria after a 60 min maximum specified drying time in SOP. Q4. For tablets, in which of these activities will test results outside of the specified criteria not be considered OOS? - Correct Answers - 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 from process development tests which are out of pre-specified criteria.
• API content measured in blend samples fail the uniformity criteria.

Q4. Which drug product quality attribute is expected to be higher in stability samples than in the release test results (time = 0)? - Correct Answers Impurities Q4. Which drug product quality attribute is not expected to be higher in stability samples than in the release test results (time = 0)? - Correct Answers - Assay

• Content uniformity
• Dissolution rates
• Appearance Q4. In specification sheets, the abbreviation NMT stands for: - Correct Answers Not More Than Q4. In the event of non-assignable cause for OOS, what would be part of the Phase II of the OOS investigation? - Correct Answers Re-sampling if the original samples were not representative of the batch. Q4. In the event of non-assignable cause for OOS, what would not be part of the Phase II of the OOS investigation? - Correct Answers - The original analyst redoes the test using the original prepared solutions.
• A second analyst redoes the test using the solutions originally used by the first analyst.
• 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. Q4. In what instance might a drug product be considered out of specifications? - Correct Answers The specification sheet requires white crystals while the material is cream- colored powder Q4. In what instance might a drug product not be considered out of specifications? - Correct Answers - The obtained test results are above the lower limit of the acceptance criteria range.
• The obtained test results are below the upper limit of the acceptance criteria range.
• The quality attributes matches that of the pre-written acceptance criteria.
• The obtained test results are in the middle of the range of acceptable values. Q4. What is not considered an assignable cause for an OOS event? - Correct Answers The analyst has been trained 3 times on the SOP. Q4. What is considered an assignable cause for an OOS event? - Correct Answers - There was an error found in the volume of a reagent specified in a method for quantifying an impurity.
• A retired method for quantifying the API was used.
• There were undissolved crystals found in one of the unused solutions.
• The analyst plugged in the wrong value in the formula for calculating the % API.

Q4. What is not an acceptable practice with regards to OOS? - Correct Answers Only data that conform with specifications should be recorded in lab notebooks. Q4. What is an acceptable practice with regards to OOS? - Correct Answers - Retest other batches that were analyzed by the same analyst who generated OOS results in another batch.

• Non-conforming drug product should not be released for distribution.
• OOS should be investigated whether or not the batch has been distributed.
• A Field Alert Report should be filed with the FDA within 3 days for marketed drug products that got OOS stability results. Q4. What does not always apply to both deviations and OOS? - Correct Answers Deviations and OOS both involve not following an instruction as written in the Master Batch Record Q4. What always apply to both deviations and OOS? - Correct Answers - Deviations, just like OOS should be accurately documented.
• Both deviations and OOS need to be investigated thoroughly and root cause determined.
• The risk to drug products should be assessed for both deviations or OOS.
• FDA expected companies to come up with corrective and preventative actions for both deviations and OOS. Q4. What does not apply to specifications? - Correct Answers Specifications need to have quantitative values. Q4. What does apply to specifications? - Correct Answers - Drug product specifications are required under cGMP regulations.
• Drug product specifications are proposed and approved as part of BLAs or NDAs.
• OOS results can result from deficiencies in the manufacturing process or in the tests performed by the QC group.
• OOS results can arise from errors in tests performed by the QC group. Q5. What is not a performance aspect that needs to be validated for holding tanks for biologics? - Correct Answers Need to validate pumps for feeding nutrients to the growing cells. Q5. What is a performance aspect that needs to be validated for holding tanks for biologics? - Correct Answers - Need to assure that tanks are connected to a working back- up generator.
• Need to validate the ability of the holding tank to maintain low temperatures.
• Need to validate effectiveness of cleaning process in getting rid of detergents.
• Need to validate holding time effects on aseptic conditions. Q5. When manufacturing of the anti-inflammatory drug, Remicade, was transferred from the Netherlands site to Pennsylvania and scaled up, what was the unanticipated consequence of processing the resulting increased product yield which led to a need to

revalidate processes. - Correct Answers A significant portion of the product do not bind to the chromatography column and just goes through the column. Q5. Which of the steps in bioreactor qualification documents whether the bioreactor to be purchased will meet the minimum functional requirements of the user? - Correct Answers Deign Qualification Q5. In method validation, which method attribute pertains to the ability to obtain instrument readings, say absorbance, which are directly proportional to the concentration (amount) of analyte in the sample. - Correct Answers Linearity Q5. Which of the steps in equipment qualification is where it is determined first whether the detector is able to produce a signal when reference standards are injected in an HPLC or a protein chromatography set up? - Correct Answers Operational Qualification Q5. A different kind of baffle was installed in the bioreactor to improve gas and nutrient exchange. Which test may not need to be performed to check the effect of the change on product quality attributes? - Correct Answers Testing for adventitious viruses Q5. A different kind of baffle was installed in the bioreactor to improve gas and nutrient exchange. Which test may need to be performed to check the effect of the change on product quality attributes? - Correct Answers - Examining 3D structure by NMR.

• Testing for product degradation.
• Testing for activity of the protein product.
• Immunological tests including Western blots. Q5. Sensitivity in method validation - Correct Answers Pertains to the ability of the method to detect very low levels of an impurity in a drug product Q5. Validation is expensive. What is not a way by which validation saves the company money in the long run? - Correct Answers Improved process consistency eliminates the need for raw material testing. Q5. Validation is expensive. What is a way by which validation saves the company money in the long run? - Correct Answers - Improved process efficiency means lower utility and raw material costs.
• Increased throughput or productivity due to a reduction in rejects and reworks.
• Better product quality can translate to enhanced customer preference and market share.
• Fewer product complaints that need to be addressed or investigated and less product returns or recalls. Q5. The Cutter Incident led to regulations on the need for process validation. What is not related to the Cutter Incident? - Correct Answers Autoclaving process change

Q5. The Cutter Incident led to regulations on the need for process validation. What is related to the Cutter Incident? - Correct Answers - Unsafe polio vaccine

• Paralysis
• Formaldehyde
• Virus inactivation Q5. What will not need to be established in the process validation for production of a biologic drug? - Correct Answers Cell transformation efficiency Q5. What will need to be established in the process validation for production of a biologic drug? - Correct Answers - Holding of the supernatant or filtrate.
• Removal of host cell proteins.
• Endotoxin control.
• Virus removal. Q5. Being a zealous manufacturing supervisor, you noticed that your autoclave loading plan leaves room for additional material which can be loaded. Realizing that increasing that amount of material in the autoclave will shorten the turn around time for the production line you considered increasing the amount of material loaded into the autoclave than specified by the loading plan. Despite the change in loading amount, design and installation qualification will not need to be redone. - Correct Answers True Q5. In method validation, say for a PCR, which method attribute pertains to the lowest amount of DNA in a given sample that can be measured accurately? - Correct Answers Limit of quantification