Pharm 125 Post Midterm Content

QA & QC, sterile, ophthalmic/nasal, radiopharmaceuticals, biotech drugs, pulmonary dosage forms

QA and QC

What is quality assurance (QA)?

department that ensures all quality related activities are performed properly

What is quality control (QC)?

part of GMP, focused on testing/sampling/documentation to ensure high-quality products

What are the main responsibilities of QA?

• main contact for regulatory agencies

• final authority on product accept/rejection

• ensure proper performance on all quality related activities

• identify/prep SOPs

• audit systems, facilities and procedures

What does QC do?

• sampling, specifications and testing

• documentation and release procedures

• ensure only approved items are used/sold

• embed quality checks into all decisions/stages

What are the 3 main areas of QC?

1. raw material

2. in process checks

3. finished product testing

Why is QA important?

prevent defects, ensure consistency, support compliance

Why is QC important?

detect problems early, ensure safe/effective products

What is cGMP?

regulations for safe and consistent drug production

ex: cleanliness, training, record keeping

What is the purpose of cGMP?

• ensure consistent product quality

• cover all (premises → record keeping)

• protect patient

What is the Pharmaceutical Quality System (PQS)?

integrate QA, QC, GMP, and risk management through product’s life

Why are QA/QC/cGMP/PQS important?

• protect patient

• meet legal standards

• ensure consistent quality

• build trust in product/company

What are the key Canadian GMP guidelines and who issues them?

GMP guidelines (GUI-00001) by Health Canada

What are some key areas covered by GUI-00001?

• premises and equipment

• personnel training

• sanitation

• raw material testing

• in process and finished product controls

• documentation

What does NAPRA provide standards for?

facility design

personnel training and competency

QA programs

documentation and traceability

environmental and hazardous substance control

What is USP <1163> focused on?

QA in pharmaceutical compounding

What does USP <1163> ensure?

compounded product meets strength, purity and quality standards

What is ICH Q10?

international guidelines for pharmaceutical quality systems

Does ICH Q10 cover the entire product life cycle?

yes

What does ICH Q10 emphasize?

risk management, continuous improvement, harmonization

Sterile Dosage Forms

What are parenteral products?

sterile preps, injections/infusion/implantation, bypass GI tract

Why must parenteral product be sterile?

prevent microbial contamination that can cause systemic infection since it bypasses the body’s natural defense

Why must parenterals be pyrogen free?

prevent febrile rxn caused by bacterial endotoxins (harmful or fatal)

What is the significance of having no visible particular matter in parenterals?

prevent embolism or vein irritation

Why is stability important in parenteral products?

ensure drug remains effective through shelf life

What does isotonicity mean and why is it important for parenterals?

isotonicity: similar osmolarity to body fluids

prevent pain or cell damage at site of injection

SHOULD be isotonic BUT not requirement

What is the ideal pH for parenterals to ensure tissue compatibility?

7.4

What are the most common parenteral routes?

IV, IM, subcutaneous, intrathecal, epidural

What dosage form should you be weary of?

epidural, bypasses more layers (spinal fluid), pass BBB

What packaging characteristics are required for parenterals?

maintain sterility, tamper proof, protect from light/air, allow visual inspection

How does osmolarity affect parenteral solutions?

impermeable solutes (Na+, glucose) can cause osmotic gradients that shift body fluids

What is the primary advantage of IV routes?

fastest onset of action, 100% bioavailability

What are some disadvantages of IV admin?

risk of infection, phlebitis, infiltration

requires skill

more expensive

What is the typical volume limit for IM injection?

up to 3mL

What are advantages to IM admin?

faster absorption than SC or rectal

sustained release

good for vax or long-acting meds

What are disadvantages of IM admin?

painful, risk nerve damage, limited to small volumes

What is the main advantage of subcutaneous (SC) injection?

easy self admin, steady absorption, good for insulin

What are disadvantages of SC injection?

slow onset, not suitable for irritating drugs, 3mL limit

What is the purpose of intradermal (ID) admin?

diagnostic testing (ex: TB, allergy test)

What are limitations of intradermal injections?

very small volume

technique sensitive

What is intrathecal (IT) admin used for?

deliver drug directly to CNS (Ex: chemo, anesthesia)

What is the risk of intrathecal admin?

fatal if wrong drug used

What is the difference between epidural and intrathecal routes?

epidural: into epidural space

intrathecal: into subarachnoid space

When is a central catheter preferred over a peripheral IV line?

long-term therapy, irritating drugs or poor peripheral access

What are advantages of central IV access?

large volumes, high osmolarity, long term use

What are disadvantages of central IV access?

higher infection, thrombosis, more complex insertion

What are examples of less common parenteral routes?

intraarterial

intracardiac

intraarticular

intraperitoneal

intraocular

What is the purpose of sterile production areas in parenteral manufacturing?

minimize contamination, ensure sterility/safety of injectables

What is the critical site?

any area that comes in contact with sterile drug

What are the 4 cleanroom classifications under ISO standards?

ISO class 5, 7, 8 and controlled/unclassified areas

What ISO class is required for direct compounding areas?

ISO class 5

What is the role of the Primary Engineering Control (PEC)?

provide ISO class 5 environment

use HEPA-filtered unidirectional airflow

What are the common types of PECs?

laminar airflow workbenches (LAFW)

biological safety cabinets (BSC)

compounding aseptic isolators (CAI)

What ISO class is the buffer area (cleanroom) outside the PEC?

ISO class 7

What ISO class is the anteroom for handwashing and garbing?

ISO class 8

(ISO class 7 for hazardous compounding area)

What is the purpose of HEPA filters in sterile areas?

remove >=99.97% particles >= 0.3 microns

maintain air cleanliness

T/F laminar airflow workbench (LAFW) protects the user and is used for both nonhazardous and hazardous compounding

F, no protect user, only nonhazardous compounding

What is the difference between vertical and horizontal laminar airflow?

differ in origin of first air

horizontal: back → front (towards user)

vertical: top → bottom, better for hazardous drugs

How many classes do biological safety cabinets have? Which one is most common?

3 (I, II, III)

II, protects user, can be used for hazardous

What is BSC Class II similar to?

vertical laminar airflow, HEPA filter at top

BUT air goes ½ to front ½ to back with a dead zone in the middle

What environmental conditions must be controlled in sterile compounding areas?

temp, humidity, air pressure, particulate count, microbial contaminaton

What is the frequency for environmental monitoring of PECs?

daily - surface cleaning

monthly - air/surface sampling

What does “first air” mean in PEC?

HEPA-filtered air that is unobstructed and directly contacts critical surfaces

cleanest

What should never obstruct “first air”?

hands, packaging, supplies

What is the BUD in a segregated compounding area?

12h

What is the required airflow velocity in a laminar flow good?

90 +/- 20 feet/min (USP)

How long must PECs run before use if turned off?

at least 30 mins before compounding

T/F the anteroom AKA ISO class 8 or better is 10x cleaner than the cleanroom

F, 10x dirtier

What is required for hazardous drug compounding areas?

ISO 7 attached to anteroom (ISO 8)

- pressure for buffer → ante, + pressure ante → non controlled

What is sterilization?

process that destroys or eliminates microbial life, including spores

What is the sterility assurance level?

probability that single unit that has been sterilized remains non-sterile

What is the gold standard for sterility assurance level (SAL)?

10^-6 by GMP

What are the 5 main methods of sterilization used for parenterals?

1. steam (moist heat)

2. dry heat

3. filtration

4. gas (ethylene oxide)

5. radiation

What is the most common and preferred sterilization method for aq parenterals?

steam (autoclaving)

What are the standard conditions for steam sterilization?

121*C, 15psi, 15-20 mins

What is the main mechanism of action of steam sterilization?

coagulation and denaturation of microbial proteins

What types of products can be sterilized by dry heat?

powders, heat stable items

What are the standard conditions for dry heat sterilization?

200-250*C, 30-60 mins

How does dry heat sterilization work?

oxidative, destroy microorganisms and pyrogens

What is filtration sterilization used for?

thermolabile (heat-sensitive) drugs (proteins, vax, antibiotics)

What are the limitations of filtration sterilization?

does not remove pyrogens or viruses

When is gas (ethylene oxide) used?

heat and moisture sensitive products

What is a major concern with ethylene oxide sterilization?

toxic residue

What are 2 types of radiation used in sterilization?

gamma rays and e- beams

How is sterility of a batch typically verified?

biological indicators (ex: spores), sterility testing, validation protocols

What are large volume parenterals?

>100mL, used to replace fluid, admin with pump

What are small volume parenterals?

<=100mL, IV and syringes

What is sterile water for injection (SWFI) used for?

IV (mix drug API + SWFI)

T/F for partial drug doses, you must take into account powder volume

T

What is normal saline?

0.9% NaCl, isotonic

What is 5% dextrose in water (D5W)?

isotonic, use for calories, common for IV

What is lactated ringer’s?

isotonic, isotonic hydration (electrolytes)

What is Ringer’s injection?

isotonic, electrolyte replacement

What is 0.45% NaCl?

hypotonic (1/2 of normal saline amount), move fluids INTO cells

be careful with burn patients, may increase cranial pressure

What is 3% NaCl and 10% dextrose in water?

hypertonic, hyponatremia, can cause high BP

T/F you should only add necessary excipients and they need to be able to be sterilized

T

T/F antimicrobial agents are required for single and multi dose

F, only req for multi

Many hospitals use single dose vials multiple times, is this okay?

No!

What is the purpose of aseptic technique in drug prep?

prevent contamination of sterile products