• Self-inspection should be carried out in order to verify compliance by the enterprise with the requirements of these Rules and suggest the necessary corrective actions.
• Issues related to personnel, as well as facilities, equipment, documentation, process control, quality control, drug sales, complaints and reviews activities and self-inspection activities should be regularly reviewed in accordance with a pre-approved program on a specific schedule for checking their compliance with the principles of quality assurance.
• Self-inspection should be carried out independently and carefully by specially appointed qualified (s) person (s), who are (them) in the state of the enterprise. If necessary, an independent audit by third-party experts can be carried out.
• Self-inspection results should be documented. The reports should include all the observations made during the audit, and, where applicable, suggestions for corrective actions. Actions taken as a result of self-inspections should also be documented.
Self Inspection requirements are mentioned in the EU GMP.
Inspection procedures Inspectors
Organisation of inspections
Inspection of contract manufacturers
Inspection of suppliers
Questionnaire for preparing GMP-inspections
Guidance for Industry. Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical CGMP.
Why do inspectors already look at an organisation’s QMS and QRM programmes during inspections?
Looking at how companies react when things go wrong or are changing and are under pressure is a major diagnostic indicator of the robustness of the scientific and organisational integrity of a company’s operations
– Do they investigate to improve knowledge or simply build arguments for release of product
– Quality of investigations- appropriateness of depth of investigation
– Reactive rather than proactive usage of knowledge
– Quality is everyone’s responsibility – Is this true when things go wrong?
– Is the company a learning organisation? And where is it on the learning curve?
Risk Classification of Good Manufacturing Practices (GMP) Observations (GUI-0023)
Summary report of the Drug Good Manufacturing Practices (GMP) Inspection Program - April 1, 2006 to March 31, 2011
Comply with good manufacturing practice (GMP) and good distribution practice (GDP), and prepare for an inspection
Compilation of Community Procedures on Inspections and Exchange of Information EMA/385898/2013 Rev 16
Good Manufacturing Practice: An analysis of regulatory inspection findings in the centralised procedure EMEA/INS/GMP/23022/2007
Examples of critical and major observations from GMP inspections
Collaborative procedure between World Health Organization Prequalification of Medicines Programme (WHO-PQ) and selected National Medicines Regulatory Authorities (NMRAs) in inspection activities
A recommended model for risk-based inspection planning in the GMP environment PIC/S PI 037-1
Guidance on classification of GMP deficiencies PIC/S PI 040-1
Inspections of utilities
ACTIVE PHARMACEUTICAL INGREDIENTS COMMITTEE (APIC)
WHO Classification of observations
Critical Deficiency – an observation that has produced, or may result in a significant risk of producing a product which is
harmful to the user.
Major Deficiency – a non-critical deficiency which either:
- has produced or may produce a product which does not comply with its prequalification application (including variations); and/or
- indicates a major deviation from the GMP guide; and/or
-indicates a failure to carry out satisfactory procedures for release of batches; and/or
-indicates a failure of the person responsible for QA/QC to fulfill his/her duties; and/or
-consists of several other deficiencies, none of which on its own may be major, but which may together represent a major deficiency and should be explained and reported as such.
- An observation that cannot be classified as either critical or major, but indicates a departure from good manufacturing practice.
- A deficiency may be “other” either because it is judged as minor, or because there is insufficient information to classify it as major or critical.
EMEA Classification of observations
Critical GMP observations
- failure occurs when a practice could give rise to a product which could or would be harmful to the patient or animal, or which has produced a harmful product.
- a combination of major deficiencies, which indicates a serious system failure, may also be classified as a critical deficiency.
A deficiency may be classified as major for the following reasons:
- A non-critical deficiency which has produced or may produce a product, which does not comply with its marketing authorisation; or
- A non-critical deficiency which indicates a major deviation from EU GMP; or (within EU) A non-critical deficiency which indicates a major deviation from the terms of
the manufacturing authorisation; or
- A non-critical deficiency which indicates a failure to carry out satisfactory procedures for
release of batches or (within EU) a failure of the Qualified Person to fulfill his legal duties;
- A combination of several “other” deficiencies, none of which on their own may be major, but which may together represent a major deficiency and should be explained and reported as such.
Deficiencies which are classified as “other” represent deficiencies which cannot be classified as critical or major, possibly because of lack of information, but which nevertheless indicate departures from GMP. They are not necessarily of a minor nature and are essentially unclassified.
- A deficiency which has produced or significantly risks producing a product which is harmful to humans or veterinary patients or which could result in a harmful residue in a food-producing animal.
- Any departure from good distribution practice that results in a significant risk to patients. This includes an activity which increases the risk of counterfeit medicines reaching patients.
Major deficiency a non-critical deficiency which:
- has or may produce a product that doesn’t comply with its marketing authorisation
- indicates a major deviation from GMP or GDP or from the terms of the manufacturer licence or wholesale licence
- indicates a failure to carry out satisfactory batch release procedures or (within EU) a failure of the Qualified Person or Responsible Person to fulfil their legal duties
- a combination of several ‘other’ deficiencies which on their own may not be major but together may represent a major deficiency and should be explained and reported as such
A deficiency which cannot be classified as either critical or major or there is not enough information to classify it as critical or major but which indicates a departure from good manufacturing and distribution practice.
Critical observation (Risk 1) : Observation describing a situation that is likely to result in a non-compliant product or a situation that may result in an immediate or latent health risk and any observation that involves fraud, misrepresentation or falsification of products or data.
Major observation (Risk 2) : Observation that may result in the production of a drug not consistently meeting its marketing authorization. Certain Risk 2 observations may be upgraded to Risk 1
Other observation (Risk 3) : Observation that is neither critical nor major but is a departure from the GMP.