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9. The RP’s Duties and GDP Inspections
Hilton Olympia, London 12th February 2013
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Calcott Consulting consultant to the pharmaceutical & biotechnology industry
Presenter’s note
• Please note, the slides contained herein, along with the narrative, are of a generic nature. These have been created in order to promote the general understanding of the principles of EU Good Distribution Practice for Medicinal Products.
• The author and presenter does not accept any liability for any inappropriate action taken or misinterpretation of legislation.
© Copyright inglasia pharma solutions Ltd /
Calcott Consulting LLC. 2012
LEARNING OBJECTIVES
• What are the Roles and Responsibilities of the Responsible Person or Qualified Person in The Distribution of Medicinal Products?
• The Regulatory Authority Inspection
• What would the Inspectors Expect to See?
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
What Are The Main Responsibilities of the RP/QP in
Distribution?
• Safeguarding against potential hazards
• Ensure wholesale dealer’s licence conditions are met
• Ensure compliance to Good Distribution Practice
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Qualification of The Responsible
Person
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
• Education – Pharmacy Degree or suitable qualification
• Working Experience – Competency, knowledge and on going GDP training
• Audits – Performed internal and externals
audits
The RP Job Description
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
• So what areas should typically be addressed in the Job Description as a minimum for the provisions of GDP? Ensure compliance with the general conditions of the authorisation Ensure compliance with the requirements of GDP guidelines Ensure that all aspects of the quality system are implemented and
maintained Involved in the approval of controlled documents Involved in self inspections Ensure that all relevant staff members are trained in the duties assigned to
them Review temperature records on a regular defined basis Approve for return to saleable stock any medicinal product returned by a
customer. Involved in any decision to quarantine or dispose of returned, rejected,
recalled or counterfeit products Approval of contracted services and their ongoing evaluation Involved in the approval of suppliers and customers To fulfil their responsibilities personally.
The RP Should Have…
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
• a clear reporting line to the license holder or Managing Director;
• personal knowledge of the products traded under the license and the conditions necessary for their safe storage and distribution;
• access to all areas, sites, stores and records which relate to the licensable activities and regularly review and monitor all such areas, etc. and the standards achieved
• Experience with hosting or being involved in regulatory authority inspections
Affiliate Office RP (MA Holder in that Country)
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
• Procure and sell medicinal products; • Outsource warehousing and storage to
outside business partner; • Outsource any rework of product (secondary
packaging/labelling) to outside business partner;
• Outsource despatch of product to outside courier service.
GDP Inspections - what to
expect before, during and after • The inspector will:
– Assess compliance with the principles and
guidelines of Good Distribution Practice; – Assess compliance with the provisions of the
wholesale dealer’s license; – Conduct ‘for cause’ inspections, as necessary.
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Inspection Process
• Four parts of an inspection:
– Opening Meeting; – Facilities/security/storage areas (if applicable); – Review of records/documentation; – Close-out Meeting
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Opening Meeting
• What the inspector wants from you; • What you can expect of the inspector; • Company background/personnel (who does
what); • Staff/staff training; • Anti-counterfeit awareness/strategy/bona fides
check; • Returns policy and management; • Quality Agreement; • Transportation management; • Recall management.
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Site Inspection
• The premises – physical walk around; • Inspection of all storage areas; • Inspection of special storage areas (e.g. returns,
quarantine, disposal); • Pest control/housekeeping; • Stock and stock management; • Goods in (receipt and check-in of deliveries); • Temperature monitoring and recording (location
and suitability of temperature recorders, etc.); • Temperature monitoring equipment/calibration; • Goods out
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Review of Documents and Deficiencies
• Review of quality system (SOPs); • Review of temperature records; • Review of training records; • Review of purchase and sales documentation; • Review evidence of bona fide checks; • Review any other documentation as required; • Review and categorisation of any deficiencies
found
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Close Out Meeting
• Clarification of any inspection deficiencies; • Discussion of any remedial proposals.
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Post Inspection Letter
• Written confirmation of any inspection deficiencies; – Any deficiencies found will be itemised and
categorised; – Deficiencies are rated as Critical, Major or Other
dependent on the impact to public health
• Letter will advise that response is required within 28 days.
© Copyright inglasia pharma solutions Ltd /
Calcott Consulting LLC. 2012
Definition of Deficiencies Categories (1)
• Critical Deficiency – Deficiency which has caused or leads to a
significant risk of causing either a product to be harmful to the patient; or
– A combination of a number of major deficiencies that indicates a serious systems failure.
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Definition of Deficiencies Categories (2)
• Major Deficiency – A non-critical deficiency which
• has caused or may cause a product not to comply with its marketing authorisation;
• indicates a major deviation from EU Good Distribution Practices;
• indicates a major deviation from the terms and provisions of the wholesale dealers license;
• indicates a failure to carry out satisfactory procedures for distribution of medicines or a failure of the Responsible Person to fulfil his legal duties;
• a combination of several ‘other’ deficiencies, none of which on their own may be major but which together represent a major deficiency and should be explained and reported as such.
© Copyright inglasia pharma solutions Ltd /
Calcott Consulting LLC. 2012
Definition of Deficiencies Categories (3)
• Other (minor) deficiency – A deficiency which cannot be classified as either critical
or major, but which indicates a departure from good distribution practice.
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Follow-up, Close-out and Sanctions
• Response will be reviewed by the Inspector;
• If the response is acceptable, the inspection will be closed out by letter;
• If unacceptable it will be escalated to an internal advisory group in the event of a critical deficiencies or un actioned deficiencies. © Copyright inglasia pharma solutions Ltd /
Calcott Consulting LLC. 2012
Most common deficiencies (UK data for 2005/2006)
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Description of deficiency Incidence (%) General storage – temperature control & monitoring
16.7
Unauthorised activity 9.6 Lack or inadequate written procedures 8.8 Supplier status 7.9 Cold storage – temperature control & monitoring
7.9
Premises, equipment & calibration 7.0 Cold chain transportation 7.0 Quality system & duties of RP 5.3 Segregation of unsaleable stock 3.5 Returns 3.5
Top 5 deficiencies (UK data for April 2008-March 2009)
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Description of deficiency # of times reported
Lack of, or inadequate written procedures 30
General storage - temperature control and monitoring
24
Un-authorised activity 19
Quality system and duties of the Responsible Person
18
Cold storage - temperature control and monitoring 13
General Storage – Temperature Control and Monitoring
• Medicinal products are stored inappropriately. Products stored on mezzanine levels where temperatures in the summer are regularly above 25ºC. At inspection temperature display was 28ºC with a maximum recorded of 37ºC;
• Monitoring & control of temperature records was inadequate: – Temperature ranges have not been properly kept with
frequent gaps in the record; – Temperature records were not available for 2005/2006 at
inspection; – Where temperatures in excess of 25ºC were recorded
there was no record of corrective action; – Temperature monitoring system in warehouse was broken.
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
What The Inspector Expects to See?
• Temperature map of the warehouse; • Storage area temperatures recorded
daily; • Temperature records reviewed on a
regular basis with any excursions noted and corrective actions taken recorded;
• SOPs in place covering systems for temperature monitoring and excursion handling. © Copyright inglasia pharma solutions Ltd /
Calcott Consulting LLC. 2012
Unauthorised Activity
• License holder has failed to inform the licensing authority of changes required to the license in that medicinal products have been stored at unlicensed premises not named on the wholesale dealers license. © Copyright inglasia pharma solutions Ltd /
Calcott Consulting LLC. 2012
What The Inspector Would Expect to See
• All procurement, storage, and distribution activities involving medicinal products undertaken by the license holder must be performed in accordance with the WL;
• Competent Authority approval must be
obtained prior to commencing any procurement, storage, & distribution activities involving medicinal products.
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Supplier Status
• Control of purchasing of pharmaceuticals is unacceptable:
– UK packs of X and Y product had been
purchased from ABC company in Dubai. Company is outside of the EU and no bona fides of this company have been obtained; Shipment of 507 X tablets have been received from ABC company with no supporting paperwork available.
© Copyright inglasia pharma solutions Ltd /
Calcott Consulting LLC. 2012
What The Inspectors Expect to See
• Medicinal products should only be purchased from licensed wholesalers and manufacturers;
• Bona fides of each supplier should be
checked to ensure they are licensed to supply medicinal products. These checks should be documented and the status of each supplier should be assessed at regular intervals. © Copyright inglasia pharma solutions Ltd /
Calcott Consulting LLC. 2012
Premises, Equipment and Calibration
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
What The Inspectors Expect to See
• Receiving bays should protect deliveries from bad weather during unloading;
• Reception areas should be separate from storage areas;
• Building should be proofed against the elements; • Storage facilities should be clean and free from
litter, dust, and pests. Adequate precautions should be taken against spillage or breakage, attack by micro-organisms, and cross contamination;
• Temperature monitoring devices should be of the required accuracy and calibrated on an annual basis.
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Quality Systems and Duties of The RP
• RP has failed to ensure the conditions of the WL are met and that the guidelines on GDP have been complied with;
• Products have been purchased from
companies where bona fides have not been established contrary to the company SOPs.
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
What The Inspectors Expect to See
• Roles and responsibilities of the RP should be clearly defined; where services of a contract RP are used a Quality Agreement between the company and the RP should be in place;
• Conduct of annual self inspections to demonstrate compliance with the conditions of the WL and GDP;
• Clear documentation of all decisions relating to GDP.
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Returns
• Return of products to stock was not subject to sufficient control: – Products that have been outside the
control of the warehouse for a period of time in excess of the company SOP were being returned to stock.
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
What The Inspectors Expect to See
• Segregation of returned medicinal products from saleable stock to prevent redistribution until a decision has been reached;
• For products which have left the care of the wholesaler, these should be returned to saleable stock if: – Goods are in their original unopened containers and in
good condition; – It is known that the goods have been stored and handled
under the proper conditions; – The remaining shelf life period is acceptable
• Records of returns received and formal release by the RP of goods back into stock.
© Copyright inglasia pharma solutions Ltd /
Calcott Consulting LLC. 2012
The RP, a summary
Responsible Person – who qualifies?
Sufficient experience
No Academic Pre-requisites.
Detailed knowledge of pharmaceutical directives and guidelines of local region.
Detailed knowledge of the following: 1. Law and Admin 2. Role and Responsibilities
of an RP 3. Storage and Distribution
requirements 4. Aspects of GMP
requirements applicable to GDP
© Copyright inglasia pharma solutions Ltd / Calcott Consulting LLC. 2012
Calcott Consulting consultant to the pharmaceutical & biotechnology industry
Q&A