GMP Compliance Training (Day 1)

I attended a GMP training course entitled “GMP Compliance Training: Implementing Regulatory and GMP Requirements into the Operations of Pharmaceutical Companies” which was organized by SGS from 14th to 16th December 2009. The course was designed for individuals from all levels within pharmaceutical manufacturing organizations focusing on QA, QC, Production and Management. I would like to summarize some contents for sharing.

Day 1 (14 Dec 2009)
Ms. Cherry Lau (Sr. Technical Executive) was the trainer who presented the four sessions in day 1, including “General principle of GMP”, “Personnel; training; sanitization & cleaning”, “Premises & equipment; qualification & validation” and “Complaints; deviations; returns; recalls; contract production & testing; self inspections; quality audit”.

The following figure showed the GxP in different pharmaceutical legislative cycle. It is a very useful to overview the whole picture of GLP/GCP/GMP.


GMP applies to “Critical” processes, which means any process that directly or indirectly may have a negative impact on safety, quality or efficacy of the product are concerned. It ensures quality, safety and efficacy of drugs delivered to patients.

The GMP manufacturing site diagram

Quality Relationships:
Quality Management > Quality Assurance > GMP > Quality Control and Manufacturing

In ISO 9000:2005, the definition of audit and inspection are given in following:
Audit: systematic, independent and documented process for obtaining audit evidence and evaluating it objectively to determine the extent to which audit criteria are fulfilled.
Inspection: conformity evaluation by observation and judgment accompanied as appropriate by measurement, testing or gauging.

It has some different interpretation in GMP below.
Inspections are carried out by government agencies (also called the Competent Authorities).
Audits are preformed by drug companies (also called the Marketing Authorization Holder), including:
- Internal self-inspections
- External audits of suppliers and contractors

Personnel requirements were also introduced. Individuals must receive training in GMP:
- initial training
- continuing training, including hygiene standards

Heads of Production and Quality Control should be independent of each other but they may share some responsibilities depending on the national regulations such as authorization of written procedures (SOPs) and other documents, environmental monitoring and control, process validation and calibration, training, etc.

For Sanitation and Hygiene requirements, all aspects of manufacturing should be considered including personnel, premises, equipment, apparatus, production materials and container, and all potential sources of cross-contamination.

The following factors should be considered to prevent cross-contamination.
- Segregated areas for production
- Ventilation systems and airlocks
- Clothing
- Closed processing systems
- Cleaning and decontamination

The manufacturing environment is critical for product quality, such as light, temperature, humidity, air movement, microbial contamination, particulate contamination, etc.

The different classifications of cleanroom were shown.

The validation requirements of cGMP were shown in the following sequence.
i) User Requirement Specification (URS)
ii) Impact assessment
iii) Design Review (DR) or Design Qualification (DQ)
iv) Commissioning / Qualification
v) Installation Qualification (IQ)
vi) Operational Qualification (OQ)
vii) Performance Qualification (PQ)
viii) Cleaning Validation (CV)
ix) Process Validation (PV)

One of the most important documents for GMP inspection is Validation Master Plan (VMP) which should contain at least:
i) Validation policy
ii) Organization structure
iii) Summary of facilities, systems, equipment, processes to be validated
iv) Documentation format for protocols and reports
v) Planning and scheduling
vi) Change control
vii) Training requirement

Reference:
USA 21 CFR on Food and Drugs, parts 210 and 211.
US GMP: http://www.gpoaccess.gov/cfr/index.html

EU Commission Directive 2003/94/EC; for human drugs
EU Commission Directive 91/412/EEC; for veterinary drugs
EU GMP: http://www.ec.europa.eu/enterprise/pharmaceuticals/eudralex/index.htm