Pharmaceutical GMP Professional (PGP)

A. Global regulatory framework

Identify the acts, statutes, directives, etc., that apply to pharmaceuticals. (Understand)
B. Regulations and guidances 
Interpret frequently used regulations and guidelines/guidances, including those published or administered by the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Cooperation Scheme (PIC/S), Health Canada, the World Health Organization (WHO), the International Conference on Harmonization (ICH), the European Medicines Agency (EMEA), the Food & Drug Administration (FDA), the Therapeutic Goods Administration (TGA), USDA 9CFR, USDA Veterinary Service Memoranda and the International Pharmaceutical Excipients Council (IPEC). (Understand)
C. Mutual recognition agreements
Interpret requirements that govern product registration, import or export of raw material or finished product, the sharing of inspection findings, etc. (Understand)
D. Regulatory inspections 
Define and describe various types of inspections (pre-approval (PAI), system-based, for-cause, license renewal, etc.), including what triggers them, their frequency, and the inspection process used. (Understand)
E. Enforcement actions
Define and describe various enforcement actions and consequences (e.g., FDA 483s, warning letters, license withdrawals, product seizure). (Understand)
F. Regulatory agency reporting
1. Post-marketing changes 

Describe how post-marketing changes to specifications, processes, methods, etc. are assessed for impact to determine the appropriate reporting method. (Understand)
2. Regulatory reporting requirements 
Describe reporting requirements, including supplements, NDA Field Alerts, Biological Product Deviation Reports, annual reports, variations to dossiers and applications, etc. (Understand)
G. Site master file (SMF) and drug master file (DMF)
Describe the purpose and content of these files. (Understand)
A. Quality management system (QMS)
1. QMS elements

Describe key elements of the structure of a QMS, identify their interrelationships, and develop and describe their hierarchical positions. (Create)
2. QMS requirements 
Apply requirements related to QMS development and operations, as defined in ICH Q10, EU GMP, and other guidances. (Apply)
B. Quality unit (site) management 
Describe quality management elements for individual sites or units, including responsibilities for company management, qualified persons, batch release requirements, the need for quality units to be independent from operations, etc. (Understand)
C. Risk management 
Use various methods to apply risk management principles, as described in ICH Q9 and other guidance or regulatory documents. (Apply)
D. Training and personnel qualification
1. Needs analysis

Identify the requirements for determining the type of training needed by quality staff members, operations personnel and related functions. (Understand)
2. Staff development requirements 
Determine proof of proficiency based on regulations, guidances, and directives and including documented evidence (job titles, job descriptions, etc.). (Apply)
E. Change control and management
1. Pre-change analysis

Assess the impact that proposed changes will have on products, processes, facilities, utilities, etc., to ensure risk minimization and ongoing regulatory compliance. (Analyze)
2. Post-change analysis
Analyze data and other inputs to determine the results of a change, and evaluate any new risk factors created by the change. (Analyze)
F. Investigations and corrective and preventive action (CAPA)
1. Trigger events 

Identify trigger events that necessitate investigation and the implications of the event elsewhere, and determine the underlying cause for the event. (Evaluate)
2. Response actions
Define immediate action, corrective action, and preventive action, and explain their importance in terms of management responsibility, methods of implementing them, etc. (Evaluate)
3. CAPA feedback and trending 
Describe how trending is used in relation to CAPA data. Use investigation feedback and CAPA results to modify appropriate quality system elements. (Create)
G. Audits and self-inspections
1. Audits processes and results

Differentiate between various audit types (systems, product, process) and analyze audit results to assess conformance to requirements. (Analyze)
2. Audit follow-up
Use various methods to evaluate and verify the adequacy of corrective actions taken. (Evaluate)
3. Ineffective corrective actions
Determine appropriate strategies to use when corrective actions are not implemented or are not effective. (Evaluate)
H. Documents and records management
1. GMP document system
Examine the GMP document system, including corporate standards, master plans, procedures, manufacturing and test instructions, etc., to determine compliance to regulatory requirements. (Analyze)
2. GMP compliance records
Review various records (log books, tags, training evidence, etc.) to confirm compliance to requirements. (Analyze)
3. Record retention
Identify regulatory requirements for GMP compliance in record retention. (Understand)
I. Product quality complaints vs. adverse event reports
1. Quality complaints 

Describe and distinguish between product complaints and adverse events, and evaluate complaint-handling processes. (Evaluate)
2. Adverse events and pharmacovigilance
Describe adverse events and identify the regulatory reports for these events and pharmacovigilance. (Understand)
3. Problem response
Evaluate the level of action that needs to be taken in response to these types of events, including corrections, product removal, etc. (Evaluate)
J. Product trend requirements
Describe and distinguish between components of the US annual product review (APR) and the European product quality review (PQR) with regard to data trends and other required review methods. (Understand)
K. Supplier and contractor quality management
1. Supplier quality systems
Identify and interpret standards and regulations (e.g., ISO 17025) related to monitoring supplier and contractor quality management systems. (Analyze)
2. Supplier controls
Assess the adequacy of controls over procurement and receipt of raw materials, components, and contract services. Determine the need for formal contracts. (Evaluate)
3. Supplier evaluation
Assess the quality systems of suppliers and contractors using various methodologies, including supplier qualification, certification, evaluation, audit, as well as supplied product or service performance trending. (Evaluate)
A. Compendia (US, Europe, and Japan)
1. Required vs. informational compendia

Describe and distinguish between required and informational (“general”) compendial chapters. (Apply)
2. Marketing requirements vs. compendia
Distinguish among the US Pharmacopoeia (USP), European Pharmacopoeia (PhEur or EP) and Japanese Pharmacopoeia (JP) in terms of requirements for marketing authorization. (Understand)
3. Compendial methods review
Review compendial methods to ensure that they are verified as suitable for use in the testing lab. (Evaluate)
4. Compendial requirements review
Review test methods, qualifications, and validations against required compendial general chapters as well as against informational general compendial chapters whenever more specific tests are not prescribed in the product compendial monograph. (Analyze)
5. Biological, microbiological, chemical, and physical test methods
Identify and interpret results from compendia identification tests, quantitative analysis, qualitative analysis, and other tests or studies for biological, microbiological, and chemical, and physical tests. (Apply)
B. Laboratory investigations of aberrant results
1. Test data
Describe and distinguish among biological, microbiological, and chemical test data, and develop procedures for investigating each type. (Analyze)
2. Aberrant results
Identify, analyze, and interpret data on processes or products that are out-of-specification (“no test” in USDA) or out-of-trend, and determine the outcome of the laboratory portion of the investigation and the criteria for further investigation. (Evaluate)
C. Instrument control and record-keeping
1. Instrument control

Examine operating procedures for instrument identification, classification (e.g., GMP, for-information-only), and calibration, to meet requirements. (Apply)
2. Instrument calibration
Determine whether instruments are calibrated within the specified range of operation, and whether they are accurate and precise. (Apply)
[Note: Calibration of facilities equipment is covered in IV.E.]
D. Specifications
1. Types of specifications

Determine whether approved specifications exist for raw materials, intermediates, packaging components, finished products, etc. (Analyze)
2. Test data and specifications
Compare test data with specifications to determine whether raw materials, intermediates, packaging, or products meet requirements. (Analyze)
3. Specifications revision 
Review and update specifications when methods are revised or compendia are changed. (Evaluate)
E. Laboratory record-keeping and data requirements
1. Record review

Review laboratory records to detect errors or falsification and to prevent loss of data. (Apply)
2. Record-keeping requirements 
Identify and review record-keeping requirements for data acquisition systems. (Apply)
3. Certificates of analysis (COAs) 
Review COAs to ensure they are complete, internally reviewed, and appropriately retained. (Apply)
F. Laboratory handling controls
1. Sample identification 

Determine whether samples are identified and handled in accordance with requirements, including name, sample identification, chains of custody, etc. (Apply)
2. Reagents, solutions, and standards identification 
Determine whether reagents, solutions, and standards are identified and labeled in accordance with requirements, including opened-on, expiry, (validated) use-by, or recertify-by dates. (Apply)
3. Storage requirements 
Describe and use procedures to store samples, reagents, solutions, and standards in appropriate environmental conditions (e.g., temperature, humidity, light exposure, absence of oxygen, etc.) to maintain the material’s characteristics for testing. (Apply)
G. Stability programs
1. Release tests vs. stability-indicating tests
Define and distinguish between these two types of tests. (Apply)
2. Stability test data
Review stability data and identify trends that can support or challenge an expiry date. (Evaluate)
3. Stability-point failure
Identify the stability-point failure of a product or material, and evaluate the implications for regulatory compliance. (Evaluate)
H. Reserve samples and retains 
Describe the various regulatory requirements for retains and reserve samples. (Apply)
A. Facilities
1. Buildings

Determine requirements for appropriate size and construction of buildings and areas as well as location of control systems.  Ensure that construction and location facilitate proper operation and minimize the risk of error and cross contamination. (Apply)
2. Manufacture and storage environment
Identify requirements for appropriate lighting, ventilation, and drainage to avoid adversely affecting product (either directly or indirectly) during manufacture and storage. (Apply)
3. Facilities change control
Use various methods to verify that change control practices are in use to maintain the qualified state of the facilities. (Apply)
B. Utilities
1. Water supply systems

Identify and interpret regulatory requirements for design of water supply systems, including various unit operations (e.g., dechlorination, reverse osmosis, deionization, distillation, etc.), delivery lines, back-flow or back-siphonage prevention, and drainage systems, as appropriate for the type of water (potable, purified, water for injection, etc.) needed in various processing steps. (Apply)
2. Compressed air and gas systems
Identify and apply regulatory requirements related to compressed air and gas systems, including storage, flow regulation, filtration, venting and purging, etc. (Apply)
3. Utility design for production 
Identify and select utility designs related to production steps (e.g., washing, sterilizing, depyrogenation, etc.) for use with specific materials and processes. (Apply)
4. Utilities design specifications 
Review operations of utilities to ensure that they meet design specifications. (Apply)
5. Utilities change control
Use various methods to verify that change control practices are in use to maintain the qualified state of affected utilities. (Apply)
C. Equipment
1. Equipment planning 

Review equipment location, design, construction, installation, and maintenance based on the operations to be conducted. (Apply)
2. Equipment layout
Determine the layout of equipment to minimize the risk of errors, to facilitate effective cleaning and maintenance, and to avoid contamination or any other undesired effect on product quality. (Apply)
3. Equipment cleaning and maintenance
Review procedures and schedules for equipment cleaning, maintenance, and, where necessary, sanitization to ensure that they meet requirements. (Apply)
4. Equipment cleaning validation or verification
Evaluate the need and methodology for product-contact cleaning validation, verification, or both. (Evaluate)
5. Equipment change control 
Use various methods to verify that change control has maintained the qualified state of equipment. (Apply)
D. Qualification and validation 
Verify that the qualifications and validations of facilities, equipment, and utilities are conducted in accordance with various requirements, including factory and site acceptance testing (FAT/SAT), installation, operational, and performance qualification (IQ/OQ/PQ) prior to process validation. (Analyze)
E. Maintenance and metrology systems
1. Maintenance procedures 
Verify that procedures are in use for routine and non-routine maintenance of heating, ventilation, air conditioning (HVAC) systems, air and water filters, and other GMP equipment and utilities, etc. (Analyze)
2. Metrology change control 
Verify that appropriate calibration and engineering/equipment change control procedures are in use, and that a metrology program exists for the calibration of instruments that control manufacturing facilities, utilities, and equipment. (Analyze) [Note: Calibration of instrumentation is covered in III.D.3.]
F. Cleaning, sanitization, and sterilization systems
1. Washing facilities

Verify that washing facilities are adequate and properly located. (Apply)
2. Cleaning procedures
Review cleaning procedures in accordance with prior cleaning validation, whenever validation is required and performed. (Apply)
3. Sanitization procedures
Review sanitization procedures for facilities and equipment, including details on cleaning schedules, methods, equipment, materials, etc., and verify that sanitizers, disinfectants, sporicides, and sterilants are used in accordance with marketing authorization and any required validation studies. (Apply)
4. Pest control 
Review and verify that a pest control program is in place and that it uses authorized rodenticides, insecticides, fungicides, fumigating agents, and appropriate traps for pest elimination, etc. (Apply)
5. Sterilization processes
Verify that appropriate sterilization processes are in place. (Apply)
G. Automated or computerized systems
1. Validation procedures

Review procedures for validation of these systems, including building maintenance systems, utilities and equipment. Verify that critical parameters for their operation and maintenance are controlled and monitored. (Evaluate)
2. Open and closed computerized systems
Distinguish between open and closed computerized systems. (Apply)
3. Configuration control
Verify that version control and configuration are maintained and monitored. (Evaluate)
4. Security requirements 
Evaluate computerized systems to ensure they meet regulatory and guidance requirements for key elements, such as access control, data protection, change control, data archiving, maintenance, transcription, audit trail, periodic system monitoring, etc. (Evaluate)
H. Business continuity and disaster recovery planning
1. Supply chain impact
Review plans and verify procedures for disaster recovery and business continuity that will guard operations from interruption to the supply chain. (Evaluate)
2. Contingency plan
Verify the testing and effectiveness of contingency plans as required or proceduralized. (Apply)
A. Receipt of materials
1. Incoming materials

Describe and use processes to receive and store incoming materials, including raw materials, tank farm liquid chemicals or solvents, components, labels, etc., and take appropriate action on deviations, such as damaged materials, materials from unapproved suppliers, missing documentation, etc. (Apply)
2. Inventory transactions
Describe and use procedures for documenting inventory transactions, such as material selection and “stop shipments” for quality holds. (Apply)
B. Sampling processes
1. Sampling plans

Review sampling plans for representative sampling, appropriate sample size, and test or inspection criteria. (Apply)
2. Sampling environment 
Differentiate and apply the requirements for sampling environment and utensils to the type of the material being sampled. (Apply)
3. Cleaning 
Ensure that the sampling environment is appropriately cleaned and monitored and that sampling utensils are appropriately cleaned or are single-use. (Apply)
C. Material storage, identification, and rotation
1. Storage suitability

Confirm that the storage environment is suitable, controlled, and monitored as required for the type of materials. (Analyze)
2. Storage labels 
Confirm that the identification label for stored materials contains the required information. (Analyze)
3. Stock rotation
Define and use stock rotation requirements, such as first-in/first-out (FIFO) and first-expired/first out (FEFO). (Apply)
4. Retest dates vs. expiration dates
Describe the difference between retest dates and expiration dates. (Understand)
5. Mix-up risk
Describe potential sources of mix-up and identify methods to minimize their risk, including material segregation, labeling, special storage for rejects, control of material returns, lot-control methods, special process for materials with similar names, etc. (Analyze)
D. Shipping and distribution
1. Temperature-sensitive requirements 

Identify special requirements for temperature-sensitive products, including tertiary packaging design, monitoring devices, etc. (Analyze)
2. Special requirements
Determine specific product requirements and apply them to routine shipping processes. (Apply)
3. Report requirements
Analyze shipping reports and transportation requirements in accordance with good distribution practices. (Analyze)
4. Supply chain security
Identify and apply the various means to secure the supply chain, including tamper-evident seals, shipping manifests, verification of documentation, barcoding, radio frequency identification (RFID), etc. (Apply)
E. Traceability and sourcing
1. Traceability requirements 

Define and differentiate the requirements for traceability of incoming materials, intermediates, and finished drugs. (Apply)
2. Biological agent requirements
Identify and apply the requirements related to biological agents such as bovine and transmissible spongiform encephalopathy (BSE and TSE). (Apply)
3. Pedigree and sourcing requirements
Identify and apply requirements for maintaining pedigree and sourcing details for active pharmaceutical ingredients (APIs), biological starting materials, excipients, intermediates, finished products, etc., and document the supply chain, from raw materials through wholesale or retail to end user. (Apply)
F. Salvaged/returned goods and destruction
1. Disposition 

Review salvaged and returned goods and evaluate them for disposition. (Evaluate)
2. Destruction facilities and processes
Determine whether qualified facilities and processes need to be used to destroy materials. (Apply)
A. Master batch and completed batch records
1. Required elements 

Review batch records for required elements, including proper issuance, sections on yields, critical manufacturing step verification, processing instructions, hold times, etc. (Apply)
2. Record processing requirements
Confirm that batch records meet requirements for execution, review and disposition decisions. (Analyze)
B. Production operations
1. Application factors

Describe and differentiate the requirements for manufacturing processes according to their application: human or veterinary drugs or biologics. (Apply)
2. Utility requirements 
Identify the facility and utility requirements that are appropriate for different production environments and product types, including sterile vs. nonsterile manufacturing, solid and semisolid dosage forms, liquids, creams, ointments, combination products, etc. (Analyze)
3. Sanitization and protection 
Identify various production operations that require gowning, sanitization, hygiene, and other product-protective steps. (Apply)
C. In-process controls
1. In-process testing 

Identify appropriate tests for each step in the manufacturing process and review results. (Analyze)
2. Critical process parameters (CPPs)
Identify and select appropriate CPPs. (Analyze)
3. Process capability studies
Review process capability studies, and calculate Cp and Cpk. (Apply)
4. Specification limits
Assess specification limits in relation to registration or compendial requirements. (Evaluate)
D. Dispensing and weighing controls
1. Staging areas

Review product dispensing and after-dispensing staging areas to determine whether they meet requirements. (Analyze)
2. Dispensing materials
Identify the requirements for using weighing equipment and handling utensils for dispensing raw materials or intermediates, including proper cleaning, labeling, and environmental controls, based on the type of material and manufacturing process being used. (Apply)
E. Requirements for critical unit processes
1. Parameters for sterilization

Identify required CPPs for such unit processes as sterilization or sterilizing filtration, aseptic filling, depyrogenation, lyophilization, other drying processes, tablet granulation and compression, terminal sterilization, cream or ointment emulsification, etc. (Analyze)
2. Validation studies
Explain and evaluate the validation studies, specifically the methodologies and acceptance criteria–required before implementing critical unit processes. Explain and evaluate validation studies required for aseptic processes including process simulations (“media fills”).(Evaluate)
3. Unit processes
Assess unit processes or their validations for deviations requiring investigation. (Analyze)
4. Operating procedures
Review qualification and validation results and confirm that they are reflected in operating procedures. (Analyze)
5. Reevaluation and revalidation
Determine appropriate criteria and frequency for reevaluation and revalidation of unit processes. (Evaluate)
6. Environmental monitoring requirements
Differentiate between environmental monitoring requirements for different manufacturing area classifications. (Apply)
7. Monitoring tools
Describe and use various monitoring tools to measure viable and nonviable particulates, pressure differentials, temperature, humidity, etc. (Apply)
F. Contamination and cross-contamination
1. Sources 

Identify potential sources for these events. (Apply)
2. Risk mitigation
Describe and apply various techniques for mitigating the risk of these events, including cleaning, facility and equipment design, qualified disinfectants, operator training, validation, monitoring, etc. (Apply)
G. Reprocessed and reworked materials
1. Disposition process

Distinguish reprocessing from reworking and apply appropriate documentation, approval, and disposition methods for these materials. (Apply)
2. Storage 
Describe and apply requirements for segregation and secure storage of these materials. (Apply)
A. Filling operations and controls
1. Materials control

Develop and review procedures to ensure the identity, strength, and purity of specified materials (e.g., liquids, powders, ointments, tablets, capsules, suspensions, etc.) and to prevent them from being altered. (Create)
2. Filling equipment control 
Analyze the controls needed for various types of production equipment and processes and ensure that the appropriate controls are in place to verify filling criteria. (Analyze)
3. Contamination controls
Identify controls to prevent microbial and other contamination at all stages of filling. (Apply)
4. Staged materials
Review staged materials and confirm that they are approved for use. (Apply)
5. Status labeling
Identify and apply proper status labeling throughout the process. (Apply)
B. Environmental monitoring 
Use various monitoring techniques (active air sampling, settle plates, nonviable particle counting, contact plates for surfaces and people, etc.) to determine that appropriate environmental conditions are maintained in various operations. (Apply)
C. In-process and finished goods inspections
1. Finished goods inspections 

Develop criteria for in-process and finished goods inspections of filled and packaged materials, including seal tests, torque testing, bottle rejection systems, etc. (Create)
2. Vision and detection systems
Ensure that vision and detection systems are qualified, calibrated, and challenged as required for the system. (Apply)
3. Defect characterizations
Ensure that defect characterizations are identified for each product and can be detected by inspection or test. (Apply)
4. Equipment failure detection
Confirm by inspection or test that equipment failures can be detected. (Apply)
D. Parenteral product inspection
1. Staff evaluation

Ensure that staff who perform manual inspections are properly trained and that their inspections meet reproducibility requirements. (Apply)
2. Automated inspection processes
Ensure that automated inspection processes are validated. (Apply)
3. Defect library
Ensure that a defect library is available to confirm proper manual and automated inspection processes. (Apply)
4. Inspector requirements
Establish requirements for inspectors to have periodic eye examinations. Confirm and document that they take frequent breaks from inspection. (Apply)
E. Packaging operations and controls
1. Content protection 

Develop and apply procedures to prevent the environment or events from altering the identity, strength, and purity of the package content. (Create)
2. Qualification and maintenance of equipment
Ensure that equipment used in packaging operations is qualified and maintained. (Apply)
3. Line clearance operations
Determine that line clearance is performed and documented. (Apply)
4. Quality check criteria
Identify and apply specified criteria when quality checks are performed. (Apply)
5. Cut-label procedures
Apply appropriate procedures for cut labels, splices, etc. (Apply)
6. Hand-applied label procedures
Ensure that hand-applied labels are 100% inspected. (Apply)
7. Production process controls 
Distinguish between controls needed for different types of production processes. (Analyze)
8. Contamination controls
Identify controls to prevent microbial and other contamination at all stages of packaging. (Apply)
9. Tamper-evident packaging
Ensure that tamper-evident and child-proof packaging requirements are in place for required products. (Apply)
F. Labeling operations and controls
1. Label printing in packaging

Confirm and document that any printing done separately or in the course of packaging is performed correctly. (Apply)
2. Quality of print used
Ensure that any type of print information (engraved, embossed, etc.) on packaging materials is clear and resistant to fading, smudging, or erasure. (Apply)
3. Label reconciliation
Confirm that label reconciliation is performed. (Apply)
4. Label changes
Determine whether regulatory notification and approval is required for proposed label changes. (Apply)
5. Unused labels
Confirm that procedures are in place and in use for destroying unused labels and labeling materials. (Apply)
G. Filling and packaging records
1. Terms
Define terms related to these records, including evidence of line clearance, printed material reconciliation, yields, etc. (Understand)
2. Setup instructions
Ensure that packaging line setup instructions are appropriate for all components. (Apply)
H. Artwork development and controls
1. Terms

Define terms related to artwork/graphics, offline printing, roll label splicing, gang printing, secure storage and destruction, etc. (Understand)
2. Access control
Ensure that controls are in place for the creation and use of artwork. (Apply)
A. Quality by design concepts
1. Critical quality attributes (CQAs) and critical process parameters (CPPs)

Identify CQAs for products and CPPs for processes. (Understand)
2. Design space
Define the concept of design space as it is used throughout the product lifecycle. (Understand)
3. Process analytical technology (PAT) tools 
Identify PAT tools, including multivariate data analysis, process analyzers, process and endpoint controls, etc., and describe their use in supporting the manufacture of quality products. (Remember)
B. Phase-appropriate GMP requirements
1. ICH Q8 

Identify recommendations contained in the ICH Q8 guidance for pharmaceutical development. (Understand)
2. Development phases
Identify recommendations and requirements in relation to phases of development, including method qualification/validation, comparability protocols, adoption of critical process parameters and specifications, etc. (Understand)
3. Combination products

Identify various studies required for combination drug-device or drug-delivery products. (Understand)
4. Clinical trials material
Describe and apply requirements for packaging of clinical trials material/IMPs. (Apply)
C. Raw materials, packaging, and infrastructure for product development 
Select appropriate development studies for raw material selection and evaluate the results to determine their critical quality attributes . (Analyze)
D. New product development studies and reports
Analyze studies and reports, including stability reports, material compatibility, method development, development reports, etc., to support product development and submissions. (Analyze)
E. Scale-up and transfer activities
1. Development and validation reports
Identify and distinguish development and validation studies. (Understand)
2. Technology transfer types
Define different types of technology transfer, including, manufacturing site change, analytical laboratory site change, etc., and analyze inter-site comparison of results. (Analyze)
3. Transfer efficiency
Define various studies, including ranging, capability, in-process control, hold times, shipping, etc., to improve transfer efficiency between development and commercial processes. (Apply)