Quality control

Question 1

Definition of quality - subjective

Answer 1

Attribute, characteristic, or property of a thing or phenomenon that can be observed and interpreted, and may be quantified but cannot be measured e.g. beauty, feel, flavour, taste.

Question 2

Objective definition of quality

Answer 2

Measurable and verifiable aspect of a thing or phenomenon, expressed in numbers or quantities, such as lightness or heaviness, thickness or thinness, softness or hardness.

Question 3

Manufacturing definition of quality

Answer 3

Strict and consistent adherence to measurable and verifiable standards to achieve uniformity of output that satisfies specific customer or user requirements.

Question 4

ISO definition of quality

Answer 4

the totality of features and characteristics of a product or service that bears its ability to satisfy stated or implied needs.

Question 5

Definition of pharmaceutical quality

Answer 5

“ The term quality control refers to the procedures undertaken to ensure the identity and purity of a particular pharmaceutical. Such procedures may range from simple chemical experiments e.g. screening for the presence of particular pharmaceutical substance, to more complicated requirements of pharmacopoeial monographs.

Question 6

Quality managements

elements and explanation of the elements

Answer 6

Quality Assurance - Wide range concept covering all matters that influence the quality of a product

Good manufacturing process: ensures that products are produced and controlled to meet appropriate quality standards

Quality control: is a process dedicated to sample, test and specify materials at each end level of manufacturing, determining if they meet the requirements

Question 7

Pharmaceutical quality

list of aspects

Answer 7

Identity: existence of API(s) indicated on the label;
Purity: no harmful contaminants, no cross-contamination;
Strength or potency: API(s) content range [90-110], ensuring long shelf life;
Uniformity of the dosage form in: consistency, colour, shape, size of tablets/capsules, etc.;
Bioavailability: speed and completeness with which the pharmaceutical enter the bloodstream;
Stability: the medicine should retain its properties until the expiration date.

Question 8

examples of poor quality

Answer 8

-A poor quality medicine may contain toxic substances that have been added unintentionally.

A medicine that contains little or none of the claimed active ingredient will not have the intended therapeutic effect.

Question 9

Anti-counterfeit packaging

Answer 9

Counterfeit is a problem of product security!
Counterfeiting products, packaging or product-pack means producing replica of the originals, products which are not controlled as authentic ones.
With reference to packaging, counterfeit can act as:
Duplication: copying labels, packaging, products, instructions and usage information;
Substitution: placing products of low (or not controlled) quality in authentic or reused packaging;
Tampering: by altering packages/labels and using not controlled products in place as real;

Question 10

anti-counterfeit - medicines

Answer 10

problem of poor quality control
Counterfeit medicine is fake medicine. It may be contaminated or contain the wrong or no active ingredient. They couldhave the right active ingredient but at the wrong dose. Counterfeit drugs are illegal and may be harmful to your health.
FDA takes all reports of suspect counterfeits seriously and, in order to combat counterfeit medicines, is working with other agencies and the private sector to help protect the nation’s drug supply from the threat of counterfeits.[1]

Question 11

Counterfeit medicines can act as

Answer 11

With reference to medicines, counterfeit can act as:
May contain no API(s)
May contain the wrong API(s), e.g. cheap vs expensive
May contain an incorrect quantity of the API(s), e.g. low
May be included in a low-quality packaging
May be manufactured using low-quality API(s) or excipients
May be manufactured under poor standards of good manufacturing practice (GMP) compliance

Question 12

Importance of quality control

list

Answer 12

-correct and dosed ingredients
-Labels: instructions, expiration date, storage and ingredients
-number of items per pack
-packaging requirements
etc

Question 13

Quality control in medicines

Answer 13

Quality is tested by the manufacturer’s Quality Control department,
Quality of products must be checked also by other authorities e.g. British Pharmacopoeia
Product specifications are assessed by the government regulatory agency
Monographs can be used to provide information about the quality of the medicinal product.

Question 14

Where is quality control performed at?

Answer 14

Quality Control is performed at:
Suppliers (materials)
Manufacturing levels (production)

Question 15

Quality control department -examples of things checked

Answer 15

Raw materials are examined to make sure they meet the appropriate specifications;
Partially completed products are also analysed (correct production processes);
Finished pharmaceutical products are tested to determine if the requirements are met.
Suitable packaging specifications are issued (pack-product requirements);
Stability tests are performed to determine product’s shelf-life and storage conditions.

Question 16

Drug development process

Answer 16

Synthesis
Biological testing
Chemical development
Product development
Process development
Package development
Stability
Clinical trials
Drug approval 
Manufacture: large scale production

Question 17

Chemical development

Answer 17

Design the synthesis method for the drug as raw material, with the most economical and safest large scale production.
Identity:
infrared spectroscopy, ultraviolet spectroscopy, nuclear magnetic resonance spectroscopy, mass spectroscopy
Strength:
assay, iodine value, saponification value
Quality:
pH, optical rotation, specific gravity, viscosity, and refractive index
Purity:
solubility, melting point, boiling point, loss on drying, residue on ignition, readily carbonisable substances, congealing range, sulfate, chloride, heavy metals, arsenic, lead, foreign matter, and known impurities
Physical Properties:
colour, taste, texture, crystallinity, description

Question 18

Define accuracy

Answer 18

the sense of trueness and precision.

Question 19

Define specificity

Answer 19

the ability to register only the desired analyte, while all other components in the formulation do not influence the results.

Question 20

Define sensitivity

Answer 20

the smallest absolute amount of change in analyse that can be detected by a measurement.

Question 21

Questions to answer when accuracy testing

Answer 21

Questions to answer:
Is a substance present or not?
In which range of concentration is the substance present?
Does the concentration lie far from a verifiable threshold limit?
Has the threshold limit been exceeded?
In what concentration, ± confidence interval, is the substance in question present in the sample?

Question 22

QC at prototyping level

Answer 22

From its discovery, the new drug is produced in a variety of dosage forms, e.g. tablet, capsule, cream, liquid syrup, injectable solution, etc.
In its dosage form, the drug substance is usually mixed with excipients, e.g. filler, binder, lubricant, disintegrant, etc.

Quality Control tests designed to test the purity of materials in small batches

Question 23

QC at small-scale production

Answer 23

Quality Control tests designed to optimise and validate the production

Review of formulation for the new equipments used.
Review of validation methods for large scale production.
Evaluation of the process in which materials are compounded into dosage form(s) is complex and efficient: all quality requirements are here considered.

Question 24

QC of drug metabolism/pharmacokinetics

Answer 24

Develop analytical techniques for measuring compound and metabolite concentrations in tissues
Determine major metabolites in relevant test species
Determine PK parameters in test species

Question 25

QC safety assessment

Answer 25

Safety pharmacology
In vitro toxicology
Short- and Long-term animal tests

Question 26

QC clinical development

Answer 26

Phase I: assessment of PK characteristics and side effects in normal volunteers
Phase II: dose-finding and efficacy tests in small groups of patients
Phase III: definitive trials of efficacy in large groups of patients

Question 27

3 main QC steps and what they are

Answer 27

• sampling
• testing
• documentation

Question 28

Sampling SPC method

Answer 28

Statistical Process Control (SPC) methods:
extend the use of descriptive statistics to monitor the quality of the product and process.
are used to make sure production stays within this normal range.
quickly detect the occurrence of identifiable causes of quality variation in the production process.

Control charts are the most commonly used tool for monitoring a production process, showing whether a sample can be classified within the required range of variation.
By collecting data from samples at different points within the process, process variations that may affect the quality of the finished product can be detected and corrected, thus reducing waste (and costs) as well as customer’s risks.

Question 29

Acceptance sampling

Answer 29

Acceptance sampling is a form of Statistical Quality Control that involves random testing of samples from lots or batches either before ore after a manufacturing process.
Note: The test is always performed against standards.
Acceptance Sampling plans: single, double or sequential sampling plan;
Acceptance/Rejection criteria are based on: the size of the lot, the number of tested samples and the level of confidence to attain (requirements);
The operating characteristic (OC) curve is used to determine the probability of accepting a lot given various proportions of defects in a lot.

Question 30

Testing quality of finished product

Answer 30

Assay the API(s) and other ingredient(s), if appropriate, to match Quality Standards.
Medicine homogeneity e.g. uniformity of content in tablets and capsules of ingredient(s).
Release of the active ingredient from the formulation (to match with bioavailability requirements).
Microbiological tests e.g. sterility tests for injectable and ophthalmic products.

Question 31

Documentation of QC

Answer 31

Registration number of the sample (batch number)
Date of receipt
Name and address of the laboratory testing the sample
Name and address of the originator of the request for analysis
Name, description, and batch number of the sample (where appropriate)
Name and address of the original manufacturer
Reference to the specification used for testing the sample
Results of all tests performed (mean and standard deviation, if applicable) with the prescribed limits
Conclusion as whether or not the sample was found to be within the limits of the specification
Expiry date or retest date, if applicable
Date on which the test(s) was (were) completed
Signature of the head of laboratory or other authorised person