Ch3-Lec 3- Good Manufacturing and Compounding Practices Flashcards
Standards for good cGMPs
•Regulations are established by the FDA
–Purpose: to set minimum standards for product quality
–Kefauver-Harris inspired the first set of GMP regulations
–Establish requirements for all aspects of pharmaceutical manufacture
–No distinction in how regulations are applied to domestic and foreign suppliers and manufacturers
cGMP for Finished Pharmaceuticals- 1
•Batch
•Batchwise control
•Certification
•Compliance
•Component
•Drug Product
•Inactive ingredient
•Lot
•Lot number
•Master record
Study Definitions on page 67 of textbook
cGMP for Finished Pharmaceuticals- 2
Quality assurance
•Quality audit
•Quality control
•Quality control unit
•Quarantine
•Representative sample
•Reprocessing
•Strength
•Verified
•Validation
Study Definitions on Page 67-68 of textbook
**Quality control unit: **
Any person or organizational element designated by the firm to be responsible for the duties relating to quality control
**Theoretical Yield: **
Quantity that would be produced at any appropriate phase of manufacture, in the absence of any loss of error
Actual Yield:
Quantity that is actually produced at any appropriate phase of manufacture.
What is the name of the regulatory process through which industry measures quality performance, and compares to standards?
_ (A) Quality assurance
–(B) Quality audit
–(C) Quality control
–(D) Quality control unit
Organization and Personnel:
–This division is responsible for
•Quality control and employees
–Responsibilities are,
•Assess product components and reject if necessary
•Assess product specifications, finished products, standards of packaging and labeling
•Adequate education and training is a must
Buildings and Facilities:
–Must be designed to enable thorough cleaning, inspection, safe & effective use for performance operations and evaluations
•Weighing and measuring rooms
•Sterile areas
•Flammable storage areas
•Material storage areas
•All must be consistent with Occupational safety & Health Administration Regulations
Equipment
•Exact to the specifications
–The type of equipment
–Where the equipment is located
–Parts of equipment must not interfere with development of drug products
–Filter materials must not mix with injectable drug products. This must be prevented.
Control of components, containers, and closures
•Bulk chemical ingredients of drug products must meet all specifications at time of ordering
•When ingredients are received they must be officially logged in.
•Purchase order number
•Date of receipt
•Control number
•Quantity received
• Raw materials are quarantined quality verified. Materials that don’t meet specifications are rejected
Production and process controls
–Written documentation is required to make sure that each drug product has the
•Correct identity
•Correct strength
•Correct quality
•Correct purity
–All automated equipment is evaluated
–Batches are evaluated from time to time to check on batch-batch consistency
•Production personnel
•Quality control laboratory
Packaging and Labeling Control
•Written documentation is required for
•Receipt, storage, handling, sampling and testing of products
•All outdated labels must be destroyed
•When drug products need further investigation by quality control unit the problems must be identified and resolved
•When drug products are approved by quality control visual and/or electronic inspection is performed
•This prevents mislabeling of products
•Check for expiration date
•Tamper-evident packaging required
Records and Reports
•Production information must be maintained on file for at least 1 year following expiration date of batch
•Control records must include
–Name and Strength of product dosage form
–Components and dosage units
–Control procedures
–Equipment used
–In-process controls
–Results of analysis
–Calibration of instruments
Returned and Salvaged Drug Products
•What do you do when products come back from the marketplace?
•If the products happen to meet all product specifications they may be used again.
•If the products have not been stored under appropriate condition these should never see marketplace again
•Exact reason for product return must be documented and dated
Additional cGMP Regulatory Requirements
•Pharmaceutical excipients must be produced according to cGMP specifications.
NO FDA APPROVAL SYSTEM FOR PHARMACEUTICAL EXCIPIENTS
Clinical Trial Materials
•Pharmaceutical product are continuously being characterized and optimized for human treatment from phase 1 to phase 2.
•All regulatory requirements must be met by phase 3 and reported to the FDA
•For i.e., production of 100,000 capsules
•Placebos must be prepared by this stage
Current Good Compounding Practices
•Patient-specific medications, Why?
–Dosages are not commercially available
–Certain dosage forms are not available
–Patients are allergic to certain excipients
–Children have different needs
–Some medicines require frequent dispensing
–Some medicines not yet available by manufacturer
–Physicians have different needs
–Veterinary products not always available
–Home health care pharmacies: Sterile preparations
–Hospice care: new approaches to pain management
_____________________________________________________
See page 77 of textbook for more detailed descriptions
FDA recognizes importance of compounding: Under section 127 of Public Law 105-115
•FDA modernization Act of 1997
–Ensured patients’ access to compounded products
–Prevented unnecessary FDA regulation of health professional (pharmacy) practice, but did not exempt the drug manufacturing company
Packaging, Labeling, and Storage of Pharmaceuticals
•Containers:
–Must meet specifications for clinical trials
–Specifications vary according to container type, I.e.,
–Parenterals and non-parenterals
–Pressurized
–Glass, plastic and metal
Plastic vs. Glass containers
•Plastic containers have advantage over glass containers,
–Lightness in terms of weight
–Greater flexibility in terms of design and appearance
–Plastic squeeze bottle
•Autoclavable Plastic:
–Methyl groups to every other carbon atom of polyethylene will produce polypropylene (autoclavable)
–Polyvinyl chloride (PVC): strong and rigid material useful for packaging capsules and tablets
What are the problems with plastic containers over glass?
•Permeability of containers
•Leaching of constituents of container
•Absorption of drug to container
•Transmission of light through container
•Change in container material overtime
Child-resistant and Adult-Senior use packaging:
•Why?
–To prevent accidental poisoning
•Child-resistant container is one that is difficult to open by children under 5 years of age
•Designs used to prevent children from opening containers are,
•Align arrows,
•press down and turn
•Squeeze and turn
•Latch top
Certain drugs are exempt due to practical considerations, sublingual tablets, cardiac drugs due to immediate access.
Compliance Packaging
•Labeling
•Prescription Label
•OTC Labeling
•Storage
Labeling
•Must meet Code of Federal Regulations
•Labeling includes immediate container, packaging, inserts, company literature, brochures, and any mailings
•Benefit to risks factors must be indicated in the packaging inserts….. Full Disclosure
Prescription Label
•Pharmacist must include the following when filling a prescription
•Name and address of pharmacy
•Serial number of prescription
•Date of prescription
•Name of the prescriber
•Name of patient
•Directions for use
_______________________________________________
See what additional information State laws may require, page 89
OTC Labeling in 1997
•FDA developed standard procedure for labeling OTC drug products due to inconsistent practices
•FDA called for simple headings and subheadings for easy understanding
•OTC package labeling must contain warning statements if misuse can lead to serious complications
OTC labeling: What is required on the label?
- Name and address of the manufacturer, packer, or distributer
•Product name
•Net quantity of contents
–This includes all ingredients
•Must indicate pharmacologic category
•Cautions and warnings to protect consumer
•Sodium content (for oral products) when necessary
•5 mg or more per single dose
•140 mg or more in maximum dose
•Storage conditions
–Must include storage in safe place out of the reach of children
–Lot number and expiration date
- Any anticipating side effects
OTC warnings
•Medication may lead to serious complications
•Ex: Laxatives may cause additional pain during an appendicitis. For this reason,
•“Warning: Do no use when abdominal pain, nausea, or vomiting is present. Frequent or prolonged use of this preparation may result in dependence on laxatives”
OTC warnings 2
•Medications can mask as serious condition requiring medical attention
•Ex: how serious is a cough?
•“Warning: A persistent cough may be a sign of a serious condition. If cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash, or persistent headache, consult a doctor ”
Dietary Supplement Labeling
Figure 3.8; See Ansel’s Textbook pg. 88
•Claims must be accurate and truthful
•No disease claims allowed
•For ex, those that infer “drug can be used to prevent, treat cure, mitigate, or diagnose a disease.”
Storage
•To ensure stability of pharmaceutical preparation
•The following are conditions defined by USP
•Cold: 8 ºC (46 ºF)
•Cool: Between 8 ºC and 15 ºC
•Room Temp: 20 ºC to 25 ºC
•Warm: Between 30 and 40 ºC
•Excessive Heat: Above 40 ºC
Transportation
•Must maintain appropriate conditions of temperature and humidity during shipment
•Special consideration may be needed
manufacturer
wholesale
Pharmacy
Patient
•Regulations are established by the FDA
–Purpose: to set minimum standards for product quality
–Kefauver-Harris inspired the first set of GMP regulations
–Establish requirements for all aspects of pharmaceutical manufacture
–No distinction in how regulations are applied to domestic and foreign suppliers and manufacturers
Standards for good cGMPs
•Batch
•Batchwise control
•Certification
•Compliance
•Component
•Drug Product
•Inactive ingredient
•Lot
•Lot number
•Master record
Study Definitions on page 67 of textbook
cGMP for Finished Pharmaceuticals- 1
Quality assurance
•Quality audit
•Quality control
•Quality control unit
•Quarantine
•Representative sample
•Reprocessing
•Strength
•Verified
•Validation
Study Definitions on Page 67-68 of textbook
cGMP for Finished Pharmaceuticals- 2
Any person or organizational element designated by the firm to be responsible for the duties relating to quality control
**Quality control unit: **
Quantity that would be produced at any appropriate phase of manufacture, in the absence of any loss of error
**Theoretical Yield: **
Quantity that is actually produced at any appropriate phase of manufacture.
Actual Yield:
_ (A) Quality assurance
–(B) Quality audit
–(C) Quality control
–(D) Quality control unit
What is the name of the regulatory process through which industry measures quality performance, and compares to standards?
–This division is responsible for
•Quality control and employees
–Responsibilities are,
•Assess product components and reject if necessary
•Assess product specifications, finished products, standards of packaging and labeling
•Adequate education and training is a must
Organization and Personnel:
–Must be designed to enable thorough cleaning, inspection, safe & effective use for performance operations and evaluations
•Weighing and measuring rooms
•Sterile areas
•Flammable storage areas
•Material storage areas
•All must be consistent with Occupational safety & Health Administration Regulations
Buildings and Facilities:
•Exact to the specifications
–The type of equipment
–Where the equipment is located
–Parts of equipment must not interfere with development of drug products
–Filter materials must not mix with injectable drug products. This must be prevented.
Equipment
•Bulk chemical ingredients of drug products must meet all specifications at time of ordering
•When ingredients are received they must be officially logged in.
•Purchase order number
•Date of receipt
•Control number
•Quantity received
• Raw materials are quarantined quality verified. Materials that don’t meet specifications are rejected
Control of components, containers, and closures
–Written documentation is required to make sure that each drug product has the
•Correct identity
•Correct strength
•Correct quality
•Correct purity
–All automated equipment is evaluated
–Batches are evaluated from time to time to check on batch-batch consistency
•Production personnel
•Quality control laboratory
Production and process controls
•Written documentation is required for
•Receipt, storage, handling, sampling and testing of products
•All outdated labels must be destroyed
•When drug products need further investigation by quality control unit the problems must be identified and resolved
•When drug products are approved by quality control visual and/or electronic inspection is performed
•This prevents mislabeling of products
•Check for expiration date
•Tamper-evident packaging required
Packaging and Labeling Control
•Production information must be maintained on file for at least 1 year following expiration date of batch
•Control records must include
–Name and Strength of product dosage form
–Components and dosage units
–Control procedures
–Equipment used
–In-process controls
–Results of analysis
–Calibration of instruments
Records and Reports
•If the products happen to meet all product specifications they may be used again.
•If the products have not been stored under appropriate condition these should never see marketplace again
•Exact reason for product return must be documented and dated
Returned and Salvaged Drug Products
•What do you do when products come back from the marketplace?
•Pharmaceutical excipients must be produced according to cGMP specifications.
NO FDA APPROVAL SYSTEM FOR PHARMACEUTICAL EXCIPIENTS
Additional cGMP Regulatory Requirements
•Pharmaceutical product are continuously being characterized and optimized for human treatment from phase 1 to phase 2.
•All regulatory requirements must be met by phase 3 and reported to the FDA
•For i.e., production of 100,000 capsules
•Placebos must be prepared by this stage
Clinical Trial Materials
–Dosages are not commercially available
–Certain dosage forms are not available
–Patients are allergic to certain excipients
–Children have different needs
–Some medicines require frequent dispensing
–Some medicines not yet available by manufacturer
–Physicians have different needs
–Veterinary products not always available
–Home health care pharmacies: Sterile preparations
–Hospice care: new approaches to pain management
_____________________________________________________
See page 77 of textbook for more detailed descriptions
Current Good Compounding Practices
•Patient-specific medications, Why?
–Ensured patients’ access to compounded products
–Prevented unnecessary FDA regulation of health professional (pharmacy) practice, but did not exempt the drug manufacturing company
FDA recognizes importance of compounding: Under section 127 of Public Law 105-115
•FDA modernization Act of 1997
•Containers:
–Must meet specifications for clinical trials
–Specifications vary according to container type, I.e.,
–Parenterals and non-parenterals
–Pressurized
–Glass, plastic and metal
Packaging, Labeling, and Storage of Pharmaceuticals
•Plastic containers have advantage over glass containers,
–Lightness in terms of weight
–Greater flexibility in terms of design and appearance
–Plastic squeeze bottle
•Autoclavable Plastic:
–Methyl groups to every other carbon atom of polyethylene will produce polypropylene (autoclavable)
–Polyvinyl chloride (PVC): strong and rigid material useful for packaging capsules and tablets
Plastic vs. Glass containers
•Permeability of containers
•Leaching of constituents of container
•Absorption of drug to container
•Transmission of light through container
•Change in container material overtime
What are the problems with plastic containers over glass?
–To prevent accidental poisoning
•Child-resistant container is one that is difficult to open by children under 5 years of age
•Designs used to prevent children from opening containers are,
•Align arrows,
•press down and turn
•Squeeze and turn
•Latch top
Certain drugs are exempt due to practical considerations, sublingual tablets, cardiac drugs due to immediate access.
Child-resistant and Adult-Senior use packaging:
•Why?
•Labeling
•Prescription Label
•OTC Labeling
•Storage
Compliance Packaging
•Must meet Code of Federal Regulations
•Labeling includes immediate container, packaging, inserts, company literature, brochures, and any mailings
•Benefit to risks factors must be indicated in the packaging inserts….. Full Disclosure
Labeling
•Name and address of pharmacy
•Serial number of prescription
•Date of prescription
•Name of the prescriber
•Name of patient
•Directions for use
_______________________________________________
See what additional information State laws may require, page 89
Prescription Label
•Pharmacist must include the following when filling a prescription
•FDA developed standard procedure for labeling OTC drug products due to inconsistent practices
•FDA called for simple headings and subheadings for easy understanding
•OTC package labeling must contain warning statements if misuse can lead to serious complications
OTC Labeling in 1997
•Product name
•Net quantity of contents
–This includes all ingredients
•Must indicate pharmacologic category
•Cautions and warnings to protect consumer
•Sodium content (for oral products) when necessary
•5 mg or more per single dose
•140 mg or more in maximum dose
•Storage conditions
–Must include storage in safe place out of the reach of children
–Lot number and expiration date
OTC labeling: What is required on the label?
•Medication may lead to serious complications
•Ex: Laxatives may cause additional pain during an appendicitis. For this reason,
•“Warning: Do no use when abdominal pain, nausea, or vomiting is present. Frequent or prolonged use of this preparation may result in dependence on laxatives”
OTC warnings
•Medications can mask as serious condition requiring medical attention
•Ex: how serious is a cough?
•“Warning: A persistent cough may be a sign of a serious condition. If cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash, or persistent headache, consult a doctor ”
OTC warnings 2
•Claims must be accurate and truthful
•No disease claims allowed
•For ex, those that infer “drug can be used to prevent, treat cure, mitigate, or diagnose a disease.”
Dietary Supplement Labeling
Figure 3.8; See Ansel’s Textbook pg. 88
•To ensure stability of pharmaceutical preparation
•The following are conditions defined by USP
•Cold: 8 ºC (46 ºF)
•Cool: Between 8 ºC and 15 ºC
•Room Temp: 20 ºC to 25 ºC
•Warm: Between 30 and 40 ºC
•Excessive Heat: Above 40 ºC
Storage
•Must maintain appropriate conditions of temperature and humidity during shipment
•Special consideration may be needed
manufacturer
wholesale
Pharmacy
Patient
Transportation
