10.6 Quality Assurance & Quality Control Programs
Key Takeaways
USP <797> Section 18 requires formal, written QA and QC programs that ensure every part of CSP preparation meets the chapter and the law, with the roles, duties and training of QA staff described in the SOPs.
The designated person must ensure the program establishes a system of adherence to procedures, prevention and detection of errors and quality problems, evaluation of complaints and adverse events, and appropriate investigations and corrective actions.
USP's FAQ lists nine integrated QA components: training, SOPs, documentation, verification, testing, cleaning and safety, containers and labeling and storage, outsourcing (if used), and responsible personnel.
Quality control is the set of specific checks and tests (component checks, release inspection, sterility and endotoxin tests, environmental and personnel monitoring, equipment verification); quality assurance is the system that plans, reviews and improves them.
Outsourced CSPs are part of the program. A 503B supplier is qualified by its FDA registration, inspection and recall history, product testing and expiration data, and a written quality agreement.
10.6 Quality Assurance & Quality Control Programs
Every requirement in USP <797> produces data: fingertip plates, pressure logs, visual inspection results, sterility tests, complaints. A quality program turns those data into decisions. The BCSCP outline lists quality control programs (task 3A4) under quality management.
QA versus QC
| Quality assurance (QA) | Quality control (QC) | |
|---|---|---|
| Focus | The system: planning, procedures, review, improvement | The checks and tests on products, processes and environment |
| Timing | Continuous, forward-looking | At defined points (in process, at release, on a schedule) |
| Examples | SOP program, training program, trend review, CAPA, supplier qualification | ACD accuracy check, visual inspection, sterility test, GFT, surface sampling |
| Question it answers | "Will our process keep producing acceptable CSPs?" | "Does this CSP, room or person meet specification right now?" |
USP <797> Section 18 requirements
- The facility's QA and QC programs must be formally established and documented in its SOPs. They must make sure that every part of CSP preparation meets USP <797> and the laws of the jurisdiction.
- The designated person must make sure there are formal, written QA and QC programs that establish a system of:
- Adherence to procedures
- Prevention and detection of errors and other quality problems
- Evaluation of complaints and adverse events
- Appropriate investigations and corrective actions
- The SOPs must describe the roles, duties and training of the people responsible for each part of the QA program.
- Sections 18.1 to 18.3 add recall of out-of-specification CSPs, complaint handling and adverse event reporting (see 12.2).
USP's FAQ adds that a QA program should include nine integrated components: (1) training, (2) SOPs, (3) documentation, (4) verification, (5) testing, (6) cleaning, disinfecting and safety, (7) containers, packaging, repackaging, labeling and storage, (8) outsourcing, if used, and (9) responsible personnel.
QC activity map
| QC activity | Minimum frequency or trigger | Reference |
|---|---|---|
| Order and component verification; calculation checks | Every CSP | USP <797> 9.3, 11 |
| Visual inspection, label check, closure integrity check | Every CSP before release; again before release if not dispensed the same day | USP <797> 12.1 |
| Sterility testing | Category 2 CSPs that need it for their BUD; every Category 3 batch | USP <797> 12.2 |
| Bacterial endotoxin testing | Injectables from nonsterile components when the BUD requires sterility testing; all Category 3 injectables from nonsterile components | USP <797> 12.3 |
| Viable air sampling | At least every 6 months (Category 1 and 2); monthly (Category 3) | USP <797> 6.2 |
| Surface sampling | At least monthly (Category 1 and 2); weekly plus after each batch (Category 3) | USP <797> 6.3 |
| Certification and particle counts | At least every 6 months | USP <797> 5 |
| Pressure differentials | Continuous monitoring; documented daily review | USP <797> 4.2.5 |
| GFT and media fill | 3 initial garbing evaluations; every 6 months (Category 1 and 2) or 3 months (Category 3) | USP <797> 2.2, 2.3 |
| ACD accuracy | Before first use and each day of use | USP <797> 9.1 |
| Storage temperatures | Daily or continuous | USP <797> 9.3.4, 19.1 |
| Cleaning documentation | Each activity, per Table 10 | USP <797> 7 |
Quality metrics and trend review
Collecting data is not enough; USP <797> requires regular review for trends, and it requires environmental data to be looked at together with personnel data. A practical quality dashboard reviewed monthly by a quality committee might track:
- Environmental results by site, with alert and action excursions and the organisms recovered
- GFT and media-fill pass rates by person and by shift
- Errors and near misses caught by workflow technology, per 1,000 CSPs
- Sterility or endotoxin test failures and OOS investigations
- Complaints, adverse events and recalls
- Certification findings and pressure excursions
- On-time completion of SOP reviews and training
Use statistical process control (trend charts) to spot drift before an action level is breached, and feed the findings into CAPA (see 12.1). The plan-do-check-act cycle gives the structure: plan a change, test it, check the data, then standardize or adjust.
Outsourcing oversight
When a facility buys CSPs from a 503B outsourcing facility, those products are still part of its quality program. Qualify the supplier before first purchase and review it periodically:
- FDA registration as an outsourcing facility, and the products it reports making
- Inspection history: Forms 483, Warning Letters, recalls and import alerts
- Quality agreement covering specifications, testing, expiration dating, change notification, complaints and recalls
- Certificates of analysis or test summaries for each lot, and confirmation that labels meet 503B requirements
- Receiving checks: shipping temperature, label, lot and expiration, physical inspection
- Performance data: complaints, delivery problems, shortages
State rules may add their own licensing requirements for out-of-state suppliers.
Common audit findings
- Monitoring data collected but never reviewed or trended
- Excursions without a documented investigation or proof that the fix worked
- QA roles not defined in SOPs, or no deputy for the designated person
- Outsourced CSPs received with no supplier qualification file
Under USP <797> Section 18, the designated person must ensure the facility's written QA and QC programs establish a system of which elements?
Adherence to procedures; prevention and detection of errors and quality problems; evaluation of complaints and adverse events; and appropriate investigations and corrective actions
Only annual certification of the cleanroom
Marketing of CSPs to prescribers
Pricing and billing accuracy
Which of these is a quality control activity rather than a quality assurance activity?
Writing the facility's training program
Qualifying a new 503B supplier and signing a quality agreement
Performing the daily gravimetric accuracy check on the automated compounding device
Leading the monthly quality committee's trend review
A hospital plans to start buying premixed syringes from a 503B outsourcing facility. Which step best qualifies the supplier?
Choose the lowest-priced supplier and inspect the first delivery
Ask the supplier to follow the hospital's USP <797> BUD tables
Rely on the supplier's marketing brochure
Confirm FDA outsourcing facility registration, review FDA inspection history (Forms 483, Warning Letters, recalls), get a quality agreement covering testing, expiration dating, change notification and recalls, and set receiving checks
Sections you finish are checked off in the contents.